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Management of Type 1 Diabetes With a Very Low–Carbohydrate Diet
Pediatrics
Abstract
Objectives:
To evaluate glycemic control among children and adults with type 1 diabetes mellitus (T1DM) who consume a very low-carbohydrate diet (VLCD).
Methods:
We conducted an online survey of an international social media group for people with T1DM who follow a VLCD. Respondents included adults and parents of children with T1DM. We assessed current hemoglobin A1c (HbA1c) (primary measure), change in HbA1c after the self-reported beginning of the VLCD, total daily insulin dose, and adverse events. We obtained confirmatory data from diabetes care providers and medical records.
Results:
Of 316 respondents, 131 (42%) were parents of children with T1DM, and 57% were of female sex. Suggestive evidence of T1DM (based on a 3-tier scoring system in which researchers took into consideration age and weight at diagnosis, pancreatic autoimmunity, insulin requirement, and clinical presentation) was obtained for 273 (86%) respondents. The mean age at diagnosis was 16 ± 14 years, the duration of diabetes was 11 ± 13 years, and the time following a VLCD was 2.2 ± 3.9 years. Participants had a mean daily carbohydrate intake of 36 ± 15 g. Reported mean HbA1c was 5.67% ± 0.66%. Only 7 (2%) respondents reported diabetes-related hospitalizations in the past year, including 4 (1%) for ketoacidosis and 2 (1%) for hypoglycemia.
Conclusions:
Exceptional glycemic control of T1DM with low rates of adverse events was reported by a community of children and adults who consume a VLCD. The generalizability of these findings requires further studies, including high-quality randomized controlled trials.
... One study in particular demonstrated 'exceptional glycaemic control' and yielded promising results. 31 In this observational study, over 300 subjects with T1DM voluntarily adhered to a VLCD, resulting in exceptional glycaemic control and low adverse event rates. 31 Their mean haemoglobin A1c was 5.67%, with a mean daily insulin dose of 0.4 U/kg, and an average diet duration of 2.2 years ± 3.9 years. ...
... 31 In this observational study, over 300 subjects with T1DM voluntarily adhered to a VLCD, resulting in exceptional glycaemic control and low adverse event rates. 31 Their mean haemoglobin A1c was 5.67%, with a mean daily insulin dose of 0.4 U/kg, and an average diet duration of 2.2 years ± 3.9 years. These findings underscore the effectiveness of a very low-carbohydrate (VLC) TCR eating pattern not only for improving glycaemia but also for achieving normoglycaemia in T1DM management, warranting further exploration and consideration among clinicians and patients. ...
... Findings from research trials and clinical case studies have suggested no incidence of or elevated risk of DKA compared with prevailing rates. 29,31,35,38,39,41 However, it's important to note that all individuals with T1DM, regardless of dietary patterns, are susceptible to DKA and more systematic studies are needed. All individuals with T1DM should have a sick day management plan in place for times when they may be more vulnerable to DKA. ...
This article presents the position of the Society of Metabolic Health Practitioners (SMHP) regarding therapeutic carbohydrate reduction (TCR) nutrition interventions for type 1 diabetes mellitus (T1DM). A modified Delphi methodology was used to arrive at a consensus consisting of several focus groups, multiple rounds, and an anonymous survey. The field of endocrinology has seen many new advances for the treatment of T1DM including hybrid closed-loop insulin delivery systems and continuous glucose monitors for better glycaemic control, monoclonal antibodies to delay the onset of disease and increased access to paediatric endocrinologists, among many other noteworthy achievements. Despite these advancements, standard of care approaches to T1DM result in higher than acceptable morbidity and mortality, with a high prevalence of microvascular and macrovascular complications. Insulin resistance in type 1 diabetes is an independent risk factor for adverse outcomes even in well controlled type 1 diabetes. In 2021, only 21% of adults with T1DM in the United States achieved the American Diabetes Association’s (ADA’s) target haemoglobin A1C goal of 7.0%, while data in the paediatric and adolescent population have demonstrated worse glycaemic control. Supported by observational and interventional evidence, the SMHP advocates for the reevaluation of the prevailing nutritional therapy for T1DM with more broad consideration for TCR. The SMHP recommends open access and clinical support for TCR nutrition interventions for individuals with T1DM of all ages and calls upon the medical community to help foster more attention and research on TCR for T1DM.
... Various guidelines have proposed that the ideal diet for cardiovascular (CV) risk reduction is a low-fat diet (7-10%); hence, prescribing low-fat diets with nearly 60% of calories obtained from CHO is a standard for CV patients [86,87]. Consuming fat-rich diets has been believed to adversely affect cardiovascular outcomes, and saturated fats mainly increase low-density-lipoprotein cholesterol LDL-C, thus promoting intravascular fat deposition [86]. ...
... Given the well-explained role of the KD in improving insulin sensitivity, it provided an excellent opportunity for glycemic control and the treatment of IR-associated conditions. By lowering the glycemic response generated by CHO and improving IR, the KD can improve both insulin-dependent diabetes mellitus (IDDM/T1DM) and T2DM [27,41,42,87]. When the effects of CHO-restricted KD were assessed in various studies, and among those with T2DM and non-diabetics with different degrees of obesity, the KD was able to lower fasting plasma glucose, improve insulin sensitivity, and improve glycemic control as observed by hemoglobin A1c levels [158][159][160]. ...
... LCD had significantly lower average daily blood glucose levels, euglycemia, less glycemic variability, and a lower need for daily doses of insulin [161]. Other studies on T1DM patients following the KD have also reported good glucose control with a nearly normal HbA1C level (5.3-5.7%), a low rate of severe adverse events, and a higher satisfaction [27,87]. However, many patients have also reported frequent hypoglycemic episodes [27], which indicates that close blood glucose monitoring in those patients is essential. ...
Insulin resistance (IR) plays a role in the pathogenesis of many diseases, such as type 2 diabetes mellitus, cardiovascular disease, non-alcoholic fatty liver disease, obesity, and neurodegenerative diseases, including Alzheimer’s disease. The ketogenic diet (KD) is a low-carbohydrate/high-fat diet that arose in the 1920s as an effective treatment for seizure control. Since then, the KD has been studied as a therapeutic approach for various IR-related disorders with successful results. To date, the use of the KD is still debatable regarding its safety. Some studies have acknowledged its usefulness, while others do not recommend its long-term implementation. In this review, we applied a SWOC (Strengths, Weaknesses, Opportunities, and Challenges) analysis that revealed the positive, constructive strengths of the KD, its potential complications, different conditions that can make used for it, and the challenges faced by both physicians and subjects throughout a KD. This SWOC analysis showed that the KD works on the pathophysiological mechanism of IR-related disorders such as chronic inflammation, oxidative stress and mitochondrial stress. Furthermore, the implementation of the KD as a potential adjuvant therapy for many diseases, including cancer, neurodegenerative disorders, polycystic ovary syndrome, and pain management was proven. On the other hand, the short and long-term possible undesirable KD-related effects, including nutritional deficiencies, growth retardation and nephrolithiasis, should be considered and strictly monitored. Conclusively, this review provides a context for decision-makers, physicians, researchers, and the general population to focus on this dietary intervention in preventing and treating diseases. Moreover, it draws the attention of scientists and physicians towards the opportunities and challenges associated with the KD that requires attention before KD initiation.
... Det å optimalisere HbA1c-nivåer står sentralt i DM1-behandling for å redusere risikoen for mikro-og makrovaskulaere komplikasjoner (7). I senere tid har dietter med lite karbohydrater («lavkarbo») fått økt oppmerksomhet, og har nylig blitt foreslått for barn og unge med DM1 på grunn av muligheter for et mer stabilt blodsukker og lavere HbA1cnivåer (bedre glykemisk kontroll) (8). En «lavkarbo»-diett har ingen offisiell definisjon, men kjennetegnes av lavere mengde karbohydrat relativt til fett og protein i kostholdet (9). ...
... Studier på voksne ble også ekskludert. Etter eksklusjon ble 11 artikler inkludert (tabell 1) (8,(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). ...
... Resultatene på glykemisk kontroll på lavkarbodietter for barn med DM1 er vist i Tabell 1 (8,(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). ...
Background: Diabetes type 1 is a chronic disease where the body does not produce the hormone insulin. Dietary intervention has been the cornerstone in the treatment of type 1 diabetes in children since before the discovery of insulin. Insulin treatment has enabled a carbohydrate-rich diet, with the risk of suboptimal glycemic control. Low-carbohydrate diets have thus become more popular recently, but little research is available on low-carbohydrate diets as treatment for type 1 diabetes in children. The aim of this study was to systematically summarize the studies on low-carbohydrate diets and glycemic control for type 1 diabetes in children, in addition to identifying potential negative outcomes. Method: We searched the PubMed database until April 20 th 2022. Results: A total of eleven articles were included. Most studies included single cases but indicated an achievement of HbA1c <53 mmol/mol (<7.0%) for 7 out of12 children on low-carbohydrate diets. Two studies were online questionnaires (n = 131 and n = 622) that reported achieved HbA1c of 39 (5.7%) and 48 (6.5%) on low-carbohydrate diets. Two studies were cross-over interventions using continuous glucose measurements and reported lower blood glucose variations and total insulin dosage throughout the day on low-carbohydrate diets. However, the studies also reported impaired growth, less physical activity, dyslipidemia, reduced bone health, and psychiatric symptoms in some children. Conclusion:Low-carbohydrate diets may improve glycemic control for children with type 1 diabetes, but may also result in serious endocrine, metabolic and psychiatric side effects.
... Cases of patients treated with insulin and low carbohydrate diets (LCD) have been reported since the 1970s [20] but traditionally, these diets have been contraindicated for patients with DM 1 because of the risk of the onset of diabetic ketoacidosis or hypoglycemia related to the reduced carbohydrate intake [21,22]. Moreover, the long-term outcomes of very low carbohydrate diets in people with DM 1 are unknown, and there is still debate about the safety and tolerability [23]. ...
... Recently, however, several scientific studies have been published highlighting the safety and efficacy of low carb diets in the management of DM 1, showing better glycemic control and reductions in insulin requirement, hypoglycemia rates, and reductions in the incidence of diabetic ketoacidosis [21][22][23][24]. ...
... Carbohydrate restriction required a concomitant reduction in the absolute number of insulin units, especially rapid insulin, which is more involved in the management of postprandial hyperglycemia; the low carbohydrate intake also led to a reduction in postprandial glycemic peaks, reducing the glycemic average, glycemic variability, and the insulinogenic stimulus at the level of residual beta cells. This has been shown to be in line with other studies on the subject [21,23]. ...
A eucaloric very low carbohydrate diet (EVLCD) is a diet with a daily caloric intake equal to the total daily energy expenditure (TDEE) with a carbohydrate content of <50 g/day. The literature on very low carbohydrate diets (VLCD) in type 1 diabetes (DM 1) is limited, although recently published scientific studies have highlighted their safety and efficacy in managing DM 1. In this retrospective analysis, we report the clinical data of 33 patients affected by DM 1 carrying out insulin therapy who switched voluntarily from their usual diet (high carb, low fat) to an EVLCD. Our aim is to evaluate the glycemic control, the amount of insulin needed in order to maintain glycemic control and safety of EVLCD. The switch improved glycemic control (mean glycated hemoglobin decreased from 8.3% to 6.8% (p < 0.01). The number of patients who reached a glycated hemoglobin value of <7% increased statistically from 12% to 57% (p < 0.01), and there was a statistically significant decrease (p < 0.01) in the units of daily insulin (from 36.7± 14.9 IU to 28.9 ±9.1 IU) A reduction from 54% to 24% in clinical level 2 hypoglycemia episodes was reported. No cases of severe hypoglycemia or ketoacidosis were observed. The results of the study support that EVLCD in DM 1 seems safe and effective when adopted under tight medical supervision.
... The time in range at baseline was 47% (34-55) for the LC diet and 52% (38-60) for the MED diet group (p = 0.211) ( Table 2). The delta time in range at three months compared to baseline was higher for the LC diet than the MED diet group: 22 (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31) ...
... The lower daily average insulin levels in our LC diet group are consistent with other studies, and likely resulted from reduced carbohydrate intake and BMI. 18,21 Concurrently, the mean daily insulin dose decreased after three months in the LC diet group, whereas it increased in the MED diet group. This difference is probably due to the accuracy of counting carbohydrates that were supervised throughout the intervention. ...
Aim
Low‐carbohydrate (LC) diets have gained popularity. We compared glycaemic and metabolic parameters following an LC versus a Mediterranean (MED) diet in adolescents and youths with type 1 diabetes.
Methods
In a six‐month, open‐label, randomised trial, 40 individuals were assigned to either diet. Glycaemic outcomes, based on continuous glucose monitoring, included per cent time of blood glucose in the range [3.9–10.0 mmol/L (70–180 mg/dL)] and haemoglobin A1c (HbA1c).
Results
Twenty‐eight (70%) were females. The median age was 18 years. After 6 months, the median time in range increased from 47% to 58% in the LC and from 52% to 64% in the MED diet group ( p = 0.98). The delta values for the time in range were 16% and 7% for the respective groups ( p = 0.09). The percentage of time >13.9 mmol/L (>250 mg/dL) improved more in the LC diet than in the MED diet group: −10% vs. −2% ( p = 0.005). The percentage of time <3.0 mmol/L (<54 mg/dL) was comparable. The delta HbA1c improved in both groups: −0.7% vs. −0.1% ( p = 0.02). Changes in BMI Z‐score and lipid levels were similar.
Conclusion
Both diets improved glycaemic outcomes in adolescents and youths with type 1 diabetes, without increasing hypoglycaemia or cardiovascular risk factors, indicating comparable safety and efficacy.
... Regarding growth, the largest study of TCR in people with Type 1 diabetes showed no associated growth reduction. 15 The AAP report correctly points out that insulin is required for proper growth and development but omits the fact that people with T1D following TCR must use exogenous insulin to cover protein. Thus, TCR does not fully alleviate the requirement of exogenous insulin for people with T1D, and it is in the context of protein and insulin that growth occurs normally and normoglycaemia is possible. ...
... Thus, TCR does not fully alleviate the requirement of exogenous insulin for people with T1D, and it is in the context of protein and insulin that growth occurs normally and normoglycaemia is possible. 15 It is also worth noting the unprecedented efficacy with an average a1c of 5.67% in the participants who adopted TCR. We know from numerous studies that elevated A1cs that are typical of children with T1D following the standard carbohydrate emphasised diet are responsible for stunting growth and causing damage to a child's developing brain. ...
Recent reviews of using therapeutic carbohydrate reduction to treat metabolic disease in paediatric patients have consistently made errors in the form of bias against recommending this nutrient-dense eating pattern despite strong evidence for its use in adults and emerging evidence in paediatric patients. The purpose of this perspective is to review these errors, which include conflating 4:1 ketogenic diets with well-formulated ketogenic diets and the needless medicalisation of using therapeutic carbohydrate reduction in paediatric populations.
... 31 A survey study was conducted with an international social media-based group of adults with type 1 diabetes and parents of youth with type 1 diabetes who choose to use low-or very low-carbohydrate diets as adjunct treatment. 32 Respondents reported excellent glycemic control but poor relationships with diabetes care providers associated with distrust and feeling judged about their diabetes management decisions. 32 Results of this survey suggest that health care provider-patient relationships would benefit from meeting families where they are, keeping in mind that there are a number of physiologic and psychological reasons to use caution with this approach in growing children and adolescents, and multidisciplinary surveillance is recommended (Table 1). ...
... 32 Respondents reported excellent glycemic control but poor relationships with diabetes care providers associated with distrust and feeling judged about their diabetes management decisions. 32 Results of this survey suggest that health care provider-patient relationships would benefit from meeting families where they are, keeping in mind that there are a number of physiologic and psychological reasons to use caution with this approach in growing children and adolescents, and multidisciplinary surveillance is recommended (Table 1). 30,[33][34][35][36][37][38][39][40][41] Research is lacking to evaluate the mental health or behavioral outcomes associated with using carbohydrate-restricted diets in youth with type 1 diabetes. ...
Carbohydrate restriction is increasingly popular as a weight loss strategy and for achieving better glycemic control in people with diabetes, including type 1 and type 2 diabetes. However, evidence to support low-carbohydrate diets in youth (children and adolescents 2–18 years of age) with obesity or diabetes is limited. There are no guidelines for restricting dietary carbohydrate consumption to reduce risk for diabetes or improve diabetes outcomes in youth. Thus, there is a need to provide practical recommendations for pediatricians regarding the use of low-carbohydrate diets in patients who elect to follow these diets, including those with type 1 diabetes and for patients with obesity, prediabetes, and type 2 diabetes.
This clinical report will:Provide background on current dietary patterns in youth, describe how moderate-, low-, and very low-carbohydrate diets differ, and review safety concerns associated with the use of these dietary patternsReview the physiologic rationale for carbohydrate reduction in youth with type 1 diabetes and for youth with obesity, prediabetes, and type 2 diabetesReview the evidence for low-carbohydrate diets in the management of youth with type 1 diabetesReview the evidence for low-carbohydrate diets in the management of youth with obesity, prediabetes, and type 2 diabetesProvide practical information for pediatricians counseling families and youth on carbohydrate recommendations for type 1 diabetes and for obesity, prediabetes, and type 2 diabetes
... Dr Richard K Bernstein, who is a type 1 diabetic himself, advocates a low-carbohydrate diet for both type 1 and type 2 diabetes. In the publication that he co-authored with Lennerz et al. (9), the glycemic control in type 1 diabetes following this dietary approach was evaluated. Reported mean HbA1c was 5.67% ± 0.66%. ...
... Only 7 (2%) respondents reported diabetes-related hospitalizations in the past year, including 4 (1%) for ketoacidosis and 2 (1%) for hypoglycemia. Exceptional glycemic control of T1DM with low rates of adverse events was reported by a community of children and adults who consume a VLCD (9). This was better than T1D patients adhering to a standard, carbohydrate-focused diet. ...
Traditional guidelines for type 1 diabetics do not restrict carbohydrates to improve clinical outcomes for patients. This paper highlights the favorable blood glucose control outcomes when a type 1 diabetic focuses on caloric intake from protein and healthy fats instead of the traditional carbohydrate-focused meals. We followed a male type 1 diabetic in his 20s adopting a ketogenic diet through a process of slowly lowering total daily carbohydrate intake. Diabetes-related biomarkers were measured throughout the process. Diabetes-related biomarkers saw massive improvements and ended up in the official non-diabetic range. Total daily insulin requirements dropped by 70%. The patient also experienced great improvements in his quality of life. This study demonstrates the possibility of improving diabetes-related biomarkers through dietary changes, which have positive effects on health outcomes in patients living with this disease.
Learning points:
The adaptation of a ketogenic diet improved diabetes-related biomarkers in this patient. Diabetes-related biomarkers, such as HbA1c, are the main risk factors for developing complications in diabetics. The ketogenic diet is a feasible approach to minimizing the risk of developing complications in diabetics. Total daily insulin requirements dropped by 67% adapting a ketogenic diet. The patient experienced enormous changes in the quality of life after adapting to the new diet. The safe and physiological state of ketosis might be associated with additional benefits for the patient.
... The evidence in the literature is currently insufficient to support the use of low-carbohydrate diets (LCD) as an adjunctive treatment for T1DM. However, given the difficulty of matching carbohydrate intake with insulin dose, reducing dietary carbohydrate consumption among people with diabetes has become a common dietary pattern [4,5]. ...
... Baseline median percentages of micronutrients were calculated according to DRI values as follows: fiber 115% (97. 5 , and vitamin C 359% (200; 471). After 6 months of the LCD intervention, the median intakes of several macronutrients and micronutrients were significantly different than at baseline ( Table 1). ...
Objective:
The aim of this study was to evaluate the macronutrient and micronutrient intake and status in youth with type 1 diabetes mellitus (T1DM) following the consumption of a low-carbohydrate diet (LCD).
Research methods and procedures:
In a prospective intervention clinical trial, adolescents with T1DM using a continuous glucose monitoring device were enrolled. Following a cooking workshop, each participant received a personalized diet regime based on LCD (50-80 g carbohydrate/day). A Food Frequency Questionnaire was administered, and laboratory tests were taken before and 6 months following the intervention. Twenty participants were enrolled.
Results:
The median age was 17 years (15; 19), and the median diabetes duration was 10 years (8; 12). During the six-months intervention, carbohydrate intake decreased from 266 g (204; 316) to 87 g (68; 95) (p = 0.004). Energy intake, the energy percent from ultra-processed food, and fiber intake decreased (p = 0.001, p = 0.024, and p < 0.0001, respectively). These changes were accompanied by declines in BMI z-score (p = 0.019) and waist-circumference percentile (p = 0.007). Improvement was observed in the median HbA1c from 8.1% (7.5; 9.4) to 7.7% (6.9; 8.2) (p = 0.021). Significant declines below the DRI were shown in median intake levels of iron, calcium, vitamin B1, and folate.
Conclusions:
The LCD lowered ultra-processed food consumption, BMI z-scores and the indices of central obesity. However, LCDs require close nutritional monitoring due to the possibility of nutrient deficiencies.
... De Bock et al. published a case series showing that carbohydrate restriction in children with diabetes may cause growth and developmental retardation and increase the cardiovascular disease risk profile due to increased fat intake (11). Lennerz et al. reported that the height z-score of 34 children who were on a low-carbohydrate diet for an average of 2.3 years, which was 0.41 at diagnosis, decreased to 0.2 after a low-carbohydrate diet (12). Fransechi et al. detected growth and developmental retardation in two children who continued to be fed with a low-carbohydrate diet (12% and 17% of total energy) after the honeymoon period (13). ...
... The GL takes into account both the GI and serving size of a carbohydrate-containing food. The GL of the meal can be classified low (0-10), medium (11)(12)(13)(14)(15)(16)(17)(18)(19), and high (≥20) depending on the portion of consumed foods. GI and GL should be evaluated together in achieving good metabolic control. ...
Medical nutrition therapy is a cornerstone in type 1 diabetes management and is based on the principles of healthy eating and the recommendations presented are valid for all children and their families. Although carbohydrates are the main nutrient that affects postprandial blood glucose in individuals with type 1 diabetes, intake of carbohydrates (type and amount), protein and fat content of the meal, and glycemic index affect the postprandial glycemic response. In recent years, the relative increase in studies on Ramadan fasting for individuals with type 1 diabetes has required health professionals to be informed about this issue. The difficulties in the nutrition management of preschool children should be solved with a professional approach. The increasing frequency of celiac disease in people with type 1 diabetes and an increasing interest in a gluten-free diet for non-celiac reasons (popular diet trends for weight loss or healthy eating) make diabetes management difficult. This review provides evidence-based approaches to frequently encountered problems on medical nutrition therapy in children and adolescents with type 1 diabetes.
... 7 In another report, a social media group surveyed pediatric and adult T1DM patients who consumed a very low-carbohydrate diet (VLCD) and found glycemic control was excellent with a reported mean HbA1c of 5.7%. 8 Despite the excellent glycemia, some investigators expressed concern regarding selection bias, noting that respondents who were self-selected followers of the VLCD were also likely to possess other beneficial attributes that contribute to optimal glycemia (e.g., close adherence to glucose monitoring and insulin administration). 9 While the limited number of studies provide some suggestion that LCDs may modestly improve glycemia, to date no randomized, prospective study has pragmatically quantified this benefit. ...
... 10,11 Small studies have reported associations between LCDs and detrimental lipid changes, such as increases in total low-density lipoprotein cholesterol (LDL-C). 8,12 Conversely, advanced measures of lipoprotein profiles using nuclear magnetic resonance (NMR) suggest LCDs are associated with lower risk LDL particles that are larger and less dense. 13 have enumerated additional potential negative impacts of LCDs, including the psychosocial burden of carbohydrate restriction leading to social isolation and adding sources of conflict within the family. ...
Aims:
Despite enthusiasm for low carbohydrate diets (LCDs) among patients with type 1 diabetes (T1DM), no prospective study has investigated outcomes in adolescent T1DM. We aimed to quantify a pragmatic LCD intervention's impact on glycemia, lipidemia, and quality of life (QOL) in adolescents with T1DM.
Methods:
At an academic center, we randomized 39 patients with T1DM aged 13-21 years to one of three 12-week interventions: an LCD, an isocaloric standard carbohydrate diet (SCD), or general diabetes education without a prescriptive diet. Glycemic outcomes included glycosylated hemoglobin (HbA1c) and continuous glucose monitoring.
Results:
There were no significant differences in glycemic, lipidemic, or QOL parameters between groups at any timepoint. Median HbA1c was similar at baseline between groups and did not change appreciably (7.9% to 8.4% in LCDs, 7.9% to 7.9% in SCDs, and 8.2% to 7.8% in controls). Change in carbohydrate consumption was minimal with only one participant reaching target carbohydrate intake.
Conclusions:
This pragmatic LCD intervention did not alter carbohydrate consumption or glycemia. Although this study was unable to evaluate a highly controlled LCD, it indicates that adolescents are unlikely to implement an educational LCD intervention in routine clinic settings. Thus, this approach is unlikely to effectively mitigate hyperglycemia in adolescents. This article is protected by copyright. All rights reserved.
... Nevertheless, the collective evidence demonstrated promising results, including improvements in HbA1c, total daily insulin and frequency of severe hypoglycaemia in T1D adults [12]. A recent observational study of individuals with T1D (n=316) showed that exceptional HbA1c levels of ~5.7% (39mmol/mol) can be obtained with adherence to a very LC diet (~35g/day) [13]. Until prospective clinical trials with sufficient sample sizes are conducted to conclusively determine the effect(s) of RC diets in adults with T1D, small-scale studies exploring the use and feasibility of RC diets in real-world clinical practice settings are useful to help practitioners better understand the role of RC diets for T1D management [9,12]. ...
... It has been previously reported that individuals with T1D following RC diets experience difficulties in seeking professional support. An online survey of 316 people with T1D self-engaging in a VLCKD reported high levels of overall health and satisfaction with their diabetes management but not with their professional diabetes care team, with only 49% of respondents agreeing or strongly agreeing that their diabetes care providers were supportive of their dietary choices [13]. In the current study, 85% of participants presented to the community-based diabetes centre specifically seeking support with a LC dietary approach for T1D management. ...
Background: The aim of this study was to explore the clinical application of reduced-carbohydrate (RC) diets for type 1 diabetes (T1D) management at a community-based diabetes centre. Methods: To be included in this retrospective case series, adults with T1D must have attended at least two appointments with a Credentialled Diabetes Educator and Accredited Practising Dietitian (CDE/APD) for advice regarding: (a) advanced carbohydrate counting, (b) carbohydrate reduction, and/or (b) low-carbohydrate diet support. Data regarding specific dietary recommendations and clinical outcomes was extracted from patient records stored at the center. A semi-structured interview with the CDE/APD was conducted to collect additional information about the design and delivery of the RC diets. Thematic analysis was used to identify core components of the RC diets, and descriptive statistics were used to assess pre-post changes in clinical T1D outcomes. Results: 26 adults with T1D were eligible and included (77% female). The RC diets represented a patient-led approach involving adjustments to energy and macronutrient intakes, glucose self-monitoring, and insulin management. 22/26 participants attended the center seeking low-carbohydrate diet support, and the average carbohydrate prescription was 63g/day (22-253g/day) which translated to a 37% reduction from baseline. HbA1c reduced from 9.0% (75mmol/mol) to 7.0% (53mmol/mol) (-5.7 to -0.1%), with an average follow-up of 55weeks (n=8). Estimated A1c reduced from 7.1% (54mmol/mol) to 6.3% (45mmol/mol) (-2.9 to+0.6%) over 21 weeks (n=19). Mean total daily insulin reduced from 44 to 31 U/day (-46 to+6 U/day), with an average follow-up of 17 weeks (n=15). Conclusions: This study provides real-world insights into the clinical application of RC diets in the management of adults with T1D at a community-based diabetes centre. Prospective clinical trials are needed to conclusively determine the effects of RC diets on clinical T1D outcomes.
... Our findings are consistent with recommendations by the American Diabetes Association to reduce carbohydrates in the diet as a strategy to maintain glycemic control. In line with this recommendation, studies using low-carbohydrate diets have shown promise in diabetes [39]. In addition, high-protein diets provide greater satiety [40], thus offering a potential opportunity to control overconsumption of calories and thus glycemia by simultaneously reducing carbohydrates while increasing protein intake. ...
Glucocorticoid-induced diabetes is the most common form of drug-induced hyperglycemia. In addition, chronic exposure to glucocorticoids promotes lean mass loss and fat mass accumulation. In this study, we hypothesized that a high-protein diet (60% kcal; HPD) would help to offset sarcopenia during oral administration of corticosterone to C57BL/6J mice. Carbohydrates were reduced in the HPD to ensure it was isocaloric with the normal-protein diet (20% kcal; NPD). We found that the HPD prevented fat mass accumulation but did not protect against reductions in lean mass in both male and female mice. Mice consuming a HPD did not develop hyperglycemia, while mice given the NPD developed hyperglycemia within two weeks. The HPD diet did not improve insulin sensitivity in response to glucocorticoids but did alter gene expression patterns in adipose tissue and liver measured by RNA sequencing. We conclude that a HPD diet may be beneficial to limit rises in blood glucose and adipose tissue accrual during glucocorticoid therapy.
... Studies of various designs show that a low-carbohydrate diet (under about 100 g/day) lowers HbA1c, even approaching the prediabetic values of <48 mmol/mol (<6.5%), reduces glucose variability, and time spent in hypoglycemia without reducing quality of life (19)(20)(21)(22)(23). The ketogenic diet (about 20-50 g/day of carbohydrates) appears even more beneficial, with HbA1c levels approaching non-diabetic values <42 mmol/mol (<6.0%) and normalize weigh (24)(25)(26)(27)(28)(29)(30)(31)(32). In addition, nutritional ketosis protects against the potentially detrimental effects of insulin resistance, high levels of insulin, and high/variable levels of glucose, thereby probably preventing and even treating symptoms of psychiatric disease and neurodegeneration (33). ...
Differentiating between an irrational versus a rational fear of hypoglycemia has treatment implications and presents significant challenge for clinicians facing patients with type 1 diabetes, illustrated in this case. A 39-year-old woman with autoimmune-positive insulin-dependent diabetes sought help to alleviate severe diabetes distress, and symptoms of depression and anxiety, associated with unpredictable drastic blood glucose drops. After exhausting conventional methods, she adopted a ketogenic diet (KD). Her glucose values decreased from around 20 mmol/L to 12 mmol/L (360 mg/dL to 216 mg/dL) in the first days. Then, by combining a KD with an insulin pump, her time in optimal glucose range increased from 8 to 51% after 2 months, reducing her HbA1c with 25 mmol/mol (2.2%). This reduced biological and psychological stress, immediately improving her mental health and renewing her hope for the future. The main concerns regarding KD in patients with comorbid type 1 diabetes is the assumed increased risk of ketoacidosis, theoretical depletion of glycogen stores, and a potential adverse effect of saturated fat on cardiovascular risk factors. These concerns are evaluated against existing empirical evidence, suggesting instead that a KD may protect against acidosis, hypoglycemia, and cardiovascular risk. The present case, together with available data, indicate that patients with type 1 diabetes experiencing high levels of biological and psychological stress should be informed of the expected benefits and possible risks associated with a KD, to ensure their right to take informed decisions regarding their diabetes management.
... Even in adults, a minimum of 130 g of carbohydrates should be ensured per day to provide sufficient glucose as fuel for the brain. [11] Lennerz et al. in 2018 [27] conducted an online survey using a social media platform to evaluate glycemic control among adults and parents of children with T1D reported a mean daily carbohydrate intake of 36 ± 15 g, with excellent glycemic control (mean HbA1c was 5.67 ± 0.66%) with low rates of adverse events or severe hypoglycemia. However, the authors also mentioned that additional research is needed to determine the degree of carbohydrate restriction to achieve the mentioned benefits. ...
Nutritional guidelines are of importance in directing food choices of T1D patients. The objective is to summarise existing nutritional recommendations and examine its adherence by T1D patients. Literature was searched on dietary guidelines in T1D using electronic databases PubMed, Science Direct, Scopus, Google Scholar, in English and 29 papers were selected. As per ADA, EASD, ISPAD, and ICMR guidelines, energy recommendations for T1D are based on ideal body weight to prevent overweight and obesity. The safe amounts of carbohydrates, protein and fat includes 50–55%, 15–20% and 25–30% of total energy respectively with fiber intake recommended at 20–30 g/day. Vitamin and mineral supplementation are beneficial in the presence of deficiency. Adherence to nutritional recommendations was suboptimal but better in those who were frequently consulting a dietician. As suboptimal dietary adherence leads to poor glycaemic control, nutritional guidelines must be followed to manage T1D and prevent or delay diabetic complications.
... Despite advances in modern medicine with various treatment options for T1D, KD remains an effective method for blood glucose control (65). Numerous studies have shown that KD not only helps reduce blood glucose fluctuations but also lowers HbA1c levels (66,67). However, maintaining a KD long-term presents a significant challenge for many patients, as most find it difficult to adhere to this diet over time (68). ...
Objective
The ketogenic diet (KD) has been explored for diabetes management; however, a quantitative synthesis of its specific effects on diabetes has not yet been conducted. This study aims to examine the current status and research hotspots of KD in diabetes management from 2005 to 2024, providing a reference for future research.
Methods
We retrieved articles published between 2005 and 2024 from the Web of Science database and analyzed them using R software, VOSviewer, and CiteSpace.
Results
This study includes 432 relevant publications. From 2005 to 2024, the volume of literature in this field has shown a steady upward trend, with a notable increase from 2017 to 2021, and a slight decline observed from 2021 to 2023. The United States is the leading country in terms of the number of publications, followed by China, Australia, and Canada. The United States not only leads in publication volume but also maintains a broader international collaboration network. Nutrients and the American Journal of Clinical Nutrition are the most frequently published and cited journals. Current research hotspots primarily focus on the impact of KD on blood glucose control, insulin resistance, and lipid metabolism in diabetic patients. Mechanistic studies on KD in diabetes management concentrate on aspects such as the “regulation of genes by β-hydroxybutyrate,” “anti-inflammatory effects,” and “oxidative stress.” The role of the gut microbiome is also emerging as an important research area. Currently, exploring the application of KD in managing different age groups and types of diabetes has become a significant research trend.
Conclusion
As an emerging dietary intervention, KD is gradually attracting widespread attention from researchers around the world and is expected to become a major research focus in the future for diabetes management and control. This paper provides a systematic review and analysis of the current research status and hotspots of KD in diabetes management, offering important references and insights for future research in related fields.
... Notably, HDL levels remained within the recommended range (57). Similarly, an online survey of over 300 adults and children with T1D who followed KD for ∼2 years on average, reported a mean HbA1C = 5.67 ± 0.66% with negligible number of adverse events (58). This again, is astonishing, considering the large sample size and that this HbA1C value is similar to that of individuals with no diabetes. ...
Ketogenic diet (KD) is a high-fat, low-carbohydrate (CHO) diet, designed to induce a metabolic state of ketosis in which the body metabolizes primarily lipids for energy production. Various forms of KD are being promoted as promising treatments for numerous health conditions from chronic headaches to weight-loss and even different forms of cancer and are becoming increasingly more popular. KD appears to be an efficacious approach for weight-loss, and maintenance, improved glycemia, cognitive function and cancer prognosis. However, there is a controversy regarding the safety of KD, and the potential health risks that might be associated with long-term exposure to KD. There is a gap between the acceptance and utilization of KD in individuals with health conditions and the criticism and negative attitudes toward KD by some clinicians. Many individuals choose to follow KD and are encouraged by the positive results they experience. Although the medical establishment does not endorse KD as a first line of treatment, clinicians need to be informed about KD, and offer support and medical supervision for patients who self-select to follow KD. This can ensure that within the boundaries of KD, patients will make good and healthy dietary choices and prevent clinical disengagement in extreme cases. To that end, there is an urgent need for good quality research to address the issues of long-term safety of KD in different clinical populations and for standardization of KD both in research and in the clinic.
... We refer the reader to reviews that examine other pathologic conditions that may benefit from low-carbohydrate dietary patterns, especially ketogenic interventions, as a standalone or an adjunct to conventional therapies. These conditions include but are not limited to type 1 diabetes [204], cancer [205], epilepsy [206], Alzheimer's [207], Parkinson's [208], multiple sclerosis [209], traumatic brain injury [210], rheumatologic arthritis [211], spinal cord injury [212], and psychiatric disorder [213]. ...
Purpose of Review
Considering the high prevalence of obesity and related metabolic impairments in the population, the unique role nutrition has in weight loss, reversing metabolic disorders, and maintaining health cannot be overstated. Normal weight and well-being are compatible with varying dietary patterns, but for the last half century there has been a strong emphasis on low-fat, low-saturated fat, high-carbohydrate based approaches. Whereas low-fat dietary patterns can be effective for a subset of individuals, we now have a population where the vast majority of adults have excess adiposity and some degree of metabolic impairment. We are also entering a new era with greater access to bariatric surgery and approval of anti-obesity medications (glucagon-like peptide-1 analogues) that produce substantial weight loss for many people, but there are concerns about disproportionate loss of lean mass and nutritional deficiencies.
Recent Findings
No matter the approach used to achieve major weight loss, careful attention to nutritional considerations is necessary. Here, we examine the recent findings regarding the importance of adequate protein to maintain lean mass, the rationale and evidence supporting low-carbohydrate and ketogenic dietary patterns, and the potential benefits of including exercise training in the context of major weight loss.
Summary
While losing and sustaining weight loss has proven challenging, we are optimistic that application of emerging nutrition science, particularly personalized well-formulated low-carbohydrate dietary patterns that contain adequate protein (1.2 to 2.0 g per kilogram reference weight) and achieve the beneficial metabolic state of euketonemia (circulating ketones 0.5 to 5 mM), is a promising path for many individuals with excess adiposity.
Graphical Abstract
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... Diabetes is a major risk factor for heart disease, dementia, kidney failure, blindness, amputation, and other serious complications, but the trajectory of progression to disability could be altered by adopting a healthy whole-food diet that is lower in carbohydrate and higher in healthy fat. Long-term studies of people with type 2 diabetes, prediabetes, and metabolic syndrome have shown that consuming low-carbohydrate higher-fat diets is safe and can significantly reduce fasting blood glucose, fasting insulin levels, and hemoglobin A1C, reduce the requirement for insulin and other diabetes medications, promote weight loss, reduce systolic and diastolic blood pressure, and improve biomarkers of cardiovascular disease without adverse effects [148][149][150][151]. Lowcarbohydrate diets have also been shown to improve glucose control and reduce the insulin requirement in people with type 1 diabetes, and low-carbohydrate diets were often used to treat diabetes prior to the discovery of insulin [152,153]. ...
In response to a perceived epidemic of coronary heart disease, Ancel Keys introduced the lipid–heart hypothesis in 1953 which asserted that high intakes of total fat, saturated fat, and cholesterol lead to atherosclerosis and that consuming less fat and cholesterol, and replacing saturated fat with polyunsaturated fat, would reduce serum cholesterol and consequently the risk of heart disease. Keys proposed an equation that would predict the concentration of serum cholesterol (ΔChol.) from the consumption of saturated fat (ΔS), polyunsaturated fat (ΔP), and cholesterol (ΔZ): ΔChol. = 1.2(2ΔS − ΔP) + 1.5ΔZ. However, the Keys equation conflated natural saturated fat and industrial trans-fat into a single parameter and considered only linoleic acid as the polyunsaturated fat. This ignored the widespread consumption of trans-fat and its effects on serum cholesterol and promoted an imbalance of omega-6 to omega-3 fatty acids in the diet. Numerous observational, epidemiological, interventional, and autopsy studies have failed to validate the Keys equation and the lipid–heart hypothesis. Nevertheless, these have been the cornerstone of national and international dietary guidelines which have focused disproportionately on heart disease and much less so on cancer and metabolic disorders, which have steadily increased since the adoption of this hypothesis.
... Well-intentioned doctors can thus malign patients' dietary choices, believing, for example, that it is dangerous for a child with type 1 diabetes to use a low-carb diet (A. Martin, personal communication), despite evidence that it can improve glycemic control [54,55]. Gluten-free diets are becoming increasingly common, and can lead to micronutrient deficiencies, as gluten-free alternatives typically lack the fortification of wheat products [56]. ...
Effective nutrition training is fundamental to medical education. Current training is inadequate and can cause harm to students and patients alike; it leaves physicians unprepared to counsel on nutrition, places undue focus on weight and body mass index (BMI), can exacerbate anti-obesity bias, and increase risk for development of eating disorders, while neglecting social determinants of health and communication skills. Physicians and educators hold positions of influence in society; what we say and how we say it matters. We propose actionable approaches to improve nutrition education to minimize harm and pursue evidence-based, effective, and equitable healthcare.
... En el estudio publicado en Pediatrics, Lennerz, Barton y Bernstein nos presentan datos recolectados de una comunidad online de pacientes con diabetes tipo 1 y concluyen que con dietas con muy baja cantidad de hidratos de carbono, es posible lograr un control metabólico excepcionalmente bueno, disminuir los requerimientos de insulina y no aumentar el riesgo de efectos adversos 1 Marzo 2020 insulínicos y la variabilidad glucémica? Obviamente no. ...
Destacados 63 RESUMEN El presente es el comentario de un estudio cuyo objetivo fue evaluar el control glucémico en niños y adolescentes con diabetes mellitus tipo 1 que con-sumen una dieta baja en carbohidratos. Para llevarlo a cabo, se realizó una encuesta en línea a un grupo internacional de redes sociales para personas con diabetes que siguen una dieta muy baja en carbo-hidratos. Los encuestados fueron adultos con la en-fermedad y padres de niños con diabetes tipo 1. Se evaluó la hemoglobina A1C actual como variable de resultado primaria, y el cambio en HbA1C después del inicio autoinformado de la dieta, la dosis total de insulina y los eventos adversos como variables de resultado secundarias. Además, se obtuvieron datos confirmatorios del equipo médico tratante y los registros médicos. De 316 encuestados, 131 (42%) fueron padres de niños con diabetes tipo 1 y el 57% fueron de sexo femenino. Para confirmar el tipo de diabetes se obtuvieron pruebas denominadas sugestivas, basadas en un sistema de puntuación de 3 niveles, en el que los investigadores tomaron en cuenta la edad y el peso en el momento del diagnóstico, la autoinmunidad pancreática si estaba disponible el dato, el reque-rimiento de insulina y la presentación clínica, en el 86% de los encuestados. La edad media en el momento del diagnóstico fue de 16 ± 14 años, la duración de la diabetes fue de 11 ± 13 años y el tiempo de la restricción de hidratos fue de 2.2 ± 3.9 años. Los participantes tuvieron una ingesta media diaria de carbohidratos de 36 ± 15 g. La HbA1C media informada fue de 5.67% ± 0.66. Sólo 7 (2%) de los encuestados informaron hos-pitalizaciones relacionadas con la diabetes en el último año, incluyendo 4 por cetoacidosis y 2 por hipoglucemia. Los autores concluyen que en una comunidad de niños y adultos que consumieron una dieta muy baja en carbohidratos, se informó un control glucé-mico excepcional para pacientes con diabetes tipo 1, con bajas tasas de eventos adversos. Aclaran, sin embargo, que la generalización de estos hallazgos requiere más estudios, incluidos ensayos controla-dos aleatorios de alta calidad. Comentario En el estudio publicado en Pediatrics, Lennerz, Barton y Bernstein nos presentan datos recolec-tados de una comunidad online de pacientes con diabetes tipo 1 y concluyen que con dietas con muy baja cantidad de hidratos de carbono, es posible lograr un control metabólico excepcionalmente bue-no, disminuir los requerimientos de insulina y no aumentar el riesgo de efectos adversos 1. ¿Resulta original pensar que una menor carga de hidratos de carbono disminuye los requerimientos COMENTARIOS BIBLIOGRAFICOS MANEJO DE LA DIABETES TIPO 1 CON UNA DIETA MUY BAJA EN CARBOHIDRATOS.
... Approximately 400 000 people have been diagnosed with T1DM in the UK, accounting for around 10% of people living with diabetes (1). Historically, carbohydrate reduction was one of the few effective treatments for T1DM in the pre-insulin era (2,3). Currently, with the availability of insulin replacement therapy, the strategy has been to match insulin doses to carbohydrate (CHO) intake. ...
The use of a low-carbohydrate diet (LCD) reduces insulin requirements in insulinopenic states such as type 1 diabetes mellitus (T1DM). However, the use of potentially ketogenic diets in this clinical setting is contentious and the mechanisms underlying their impact on glycaemic control are poorly understood. We report a case of a patient with a late-onset classic presentation of T1DM who adopted a very low-carbohydrate diet and completely avoided insulin therapy for 18 months, followed by tight glycaemic control on minimal insulin doses. The observations suggest that adherence to an LCD in T1DM, implemented soon after diagnosis, can facilitate an improved and less variable glycaemic profile in conjunction with temporary remission in some individuals. Importantly, these changes occurred in a manner that did not lead to a significant increase in blood ketone (beta-hydroxybutyrate) concentrations. This case highlights the need for further research in the form of randomised controlled trials to assess the long-term safety and sustainability of carbohydrate-reduced diets in T1DM.
Learning points
This case highlights the potential of low-carbohydrate diets (LCDs) in type 1 diabetes mellitus (T1DM) to mediate improved diabetes control and possible remission soon after diagnosis.
Could carbohydrate-reduced diets implemented early in the course of T1DM delay the decline in endogenous insulin production?
Adherence to an LCD in T1DM can facilitate an improved and less variable glycaemic profile.
This case suggests that LCDs in T1DM may not be associated with a concerning supraphysiological ketonaemia.
... Moreover, diets limiting the supply of carbohydrates may increase the risk of hypoglycemia or potentially weaken the effect of glucagon in the treatment of severe hypoglycemia [12]. Long-term studies on the use of low-carbohydrate diets in the treatment of diabetes are still lacking [4,13]. Regardless of the amount of carbohydrates in the diet, effort needs to be made to minimize postprandial increase in glycemia, which is mainly caused by carbohydrates, through an appropriate time of insulin administration, moderate amount of protein and increased amount of dietary fiber in the meal, and the use of products with a low glycemic index [3][4][5]. ...
... Additionally, circulating βHB is typically below 0.5 mM, but can increase in response to fasting, exercise, or in untreated diabetes, where it has been measured to reach up to 10 mM in blood and 6 mM in CSF (Ohman et al., 1994;Robinson & Williamson, 1980). In a ketogenic diet, which has attracted interest for its role in treatment of intractable epilepsy or diabetes (Lennerz et al., 2018;Ułamek-Kozioł et al., 2019), the level of circulating ketone bodies is elevated to around 1-4 mM, but can reach concentrations higher than 10 mM in extreme ketoacidosis (Laffel, 1999;van Delft et al., 2010). ...
The metabolic demands of neuronal activity are both temporally and spatially dynamic, and neurons are particularly sensitive to disruptions in fuel and oxygen supply. Glucose is considered an obligate fuel for supporting brain metabolism. Although alternative fuels are often available, the extent of their contribution to central carbon metabolism remains debated. Differential fuel metabolism likely depends on cell type, location, and activity state, complicating its study. While biosensors provide excellent spatial and temporal information, they are limited to observations of only a few metabolites. On the other hand, mass spectrometry is rich in chemical information, but traditionally relies on cell culture or homogenized tissue samples. Here, we use mass spectrometry imaging (MALDI‐MSI) to focus on the fuel metabolism of the dentate granule cell (DGC) layer in murine hippocampal slices. Using stable isotopes, we explore labeling dynamics at baseline, as well as in response to brief stimulation or fuel competition. We find that at rest, glucose is the predominant fuel metabolized through glycolysis, with little to no measurable contribution from glycerol or fructose. However, lactate/pyruvate, β‐hydroxybutyrate (βHB), octanoate, and glutamine can contribute to TCA metabolism to varying degrees. In response to brief depolarization with 50 mM KCl, glucose metabolism was preferentially increased relative to the metabolism of alternative fuels. With an increased supply of alternative fuels, both lactate/pyruvate and βHB can outcompete glucose for TCA cycle entry. While lactate/pyruvate modestly reduced glucose contribution to glycolysis, βHB caused little change in glycolysis. This approach achieves broad metabolite coverage from a spatially defined region of physiological tissue, in which metabolic states are rapidly preserved following experimental manipulation. Using this powerful methodology, we investigated metabolism within the dentate gyrus not only at rest, but also in response to the energetic demand of activation, and in states of fuel competition. image
... Dietary changes can reduce T1DM's chronic consequences. Although the level of glucose restriction (along with other dietary considerations) required to achieve these effects is consistent with the ideal insulin regimen for T1DM (particularly to prevent severe hypoglycemia), safety and efficacy (in randomized controlled trials) vary in individual T1DM patients [19]. ...
... However, the long-term effects and safety of a carbohydrate-restricted diet, especially in the pediatric population, are still unknown. Indeed, this type of diet is discouraged in children due to the potential risk of DKA, dyslipidemia, inappropriate caloric intake, adverse effects on growth and pubertal development and a patient's poor diet adherence [70]. Lejk et al. also evaluated the impact of specific LCD (30% of daily caloric intake compared to 50%) on glycemic control in a small population of Polish children with T1D and continuous blood glucose monitoring (CGM). ...
In children with type 1 diabetes, a healthy lifestyle is important to control postprandial glycemia and to avoid hyperglycemic peaks that worsen the inflammatory state of vessels and tissues. Glycemic index and glycemic load are two important indexes which assess the quality and quantity of foods consumed during meals. The main macronutrients of the diet have a different effect on postprandial blood glucose levels, so it is important that diabetic children consume foods which determine a slower and steadier glycemic peak. In this review, we present the results of the most recent studies carried out in the pediatric population with T1D, whose aim was to analyze the effects of low-glycemic-index foods on glycemic control. The results are promising and demonstrate that diets promoting low-glycemic-index foods guarantee a greater glycemic stability with a reduction in postprandial hyperglycemic peaks. However, one of the main limitations is represented by the poor adherence of children to a healthy diet. In order to obtain satisfactory results, a possibility might be to ensure a balanced intake of low-, moderate- and high-glycemic-index foods, preferring those with a low glycemic index and limiting the consumption of the high- and moderate-glycemic-index types.
... 1 However, there is little data about the ketoacidosis risk with LCD/VLCDs 2 and self-selected groups of people with T1D following these diets report that ketoacidosis is rare. 3 Furthermore, the level of nutritional ketosis observed in individuals with T1D following an LCD/VLCD is poorly described, with inconsistent measurements of ketone concentrations at infrequent time points. [4][5][6][7][8] To better define the diurnal changes in nutritional ketosis in T1D, we performed a real-world observational study in a single tertiary diabetes centre in England, comparing ketone levels in those following an LCD/ VLCD to those following an unrestricted carbohydrate counting diet. ...
Aims:
Adopting a low- or very low-carbohydrate (LCD or VLCD) diet in type 1 diabetes mellitus (T1D) is a controversial intervention. The main fear is that these diets may increase the risk of diabetic ketoacidosis. However, there is little data about the ketoacidosis risk and the level of physiological nutritional ketosis in individuals following these diets. We aimed to define the level of ketosis in those with T1D following carbohydrate restricted diets in a real-world observational study.
Methods:
Patients with T1D who had self-selected dietary carbohydrate restriction were enrolled from local clinics and were compared to those following an unrestricted regular carbohydrate control diet (RCCD). Participants completed a 3-day diary, documenting food intake, ketones, and blood/interstitial glucose concentrations.
Results:
Participants were divided into three groups according to mean carbohydrate intake: VLCD (<50 g carbohydrates/day) n = 6, LCD (50-130 g carbohydrates/day) n = 6, and RCCD (>130 g carbohydrates/day) n = 3. Mean beta-hydroxybutyrate (BOHB) concentrations were 1.2 mmol/l (SD 0.14), 0.3 mmol/l (SD 0.12) and 0.1mmol/l (SD 0.05) in the VLCD, LCD and RCCD groups, respectively (p = 0.02). Post hoc Dunn test demonstrated this reached statistical significance between the VLCD and RCCD groups (p = 0.02).
Conclusion:
Carbohydrate restricted diets, in particular VLCDs, are associated with a higher BOHB level. However, the degree of ketosis seen is much lower than we expected, and significantly lower than the level typically associated with diabetic ketoacidosis. This may suggest the risk of ketoacidosis is lower than feared, although safety will need to be evaluated further in large scale randomised trials.
... Additionally, some participants experienced difficulties managing conflicting dietary advice from other healthcare professionals. An online survey of 316 individuals with T1D reported that the majority of participants did not feel supported by their healthcare team to follow a very LC diet [88]. A previous systematic review of adults with T2D showed that effective LC diet studies included moderate to high frequency of follow-up with medical professionals [31], that may also be an integral feature of other successful dietary interventions [89,90]. ...
Public interest in low-carbohydrate (LC) diets for type 1 diabetes (T1D) management has increased. This study compared the effects of a healthcare professional delivered LC diet compared to habitual diets higher in carbohydrates on clinical outcomes in adults with T1D. Twenty adults (18–70 yrs) with T1D (≥6 months duration) with suboptimal glycaemic control (HbA1c>7.0% or >53 mmol/mol) participated in a 16-week single arm within-participant, controlled intervention study involving a 4-week control period following their habitual diets (>150 g/day of carbohydrates) and a 12-week intervention period following a LC diet (25–75 g/day of carbohydrates) delivered remotely by a registered dietitian. Glycated haemoglobin (HbA1c –primary outcome), time in range (blood glucose: 3.5–10.0 mmol/L), frequency of hypoglycaemia (<3.5 mmol/L), total daily insulin, and quality of life were assessed before and after the control and intervention periods. Sixteen participants completed the study. During the intervention period, there were reductions in total dietary carbohydrate intake (214 to 63 g/day; P<0.001), HbA1c (7.7 to 7.1% or 61 to 54 mmol/mol; P = 0.003) and total daily insulin use (65 to 49 U/day; P<0.001), increased time spent in range (59 to 74%; P<0.001), and improved quality of life (P = 0.015), with no significant changes observed during the control period. Frequency of hypoglycaemia episodes did not differ across timepoints, and no episodes of ketoacidosis or other adverse events were reported during the intervention period. These preliminary findings suggest that a professionally supported LC diet may lead to improvements in markers of blood glucose control and quality of life with reduced exogenous insulin requirements and no evidence of increased hypoglycaemia or ketoacidosis risk in adults with T1D. Given the potential benefits of this intervention, larger, longer-term randomised controlled trials are warranted to confirm these findings.
Trial Registration: https://www.anzctr.org.au/ACTRN12621000764831.aspx
... Only seven patients gave a history of diabetes-related hospitalizations in the last year: four were due to ketoacidosis, and only two were due to hypoglycemia. The authors concluded that a ketogenic diet affected glycemia control in type 1 diabetes, with a low rate of adverse effects, in both adults and children on a very low-carbohydrate diet (the mean value of 36 g of carbohydrates meets one criterion of a ketogenic diet) [65]. One case study described a 37-year-old male with type 1 diabetes who, in 20 days, had covered a distance of 4011 km on a bicycle in Australia, while being on a ketogenic diet. ...
The exponentially growing frequency of diagnosing diabetes mellitus means that a verification of the previous dietetic approach to treating the disease seems justified. The simultaneous growth of interest in the ketogenic diet and the development of knowledge in this field have contributed to the increasingly frequent application of the ketogenic diet in diabetes treatment. This paper also deals with that issue; its aim includes an extensive analysis of the influence of the ketogenic diet on the prophylaxis and treatment of diabetes. The paper has been prepared based on a wide, meticulous analysis of the available literature on the subject. Among other findings, a favorable effect of that nutrition model has been demonstrated on the values of glycated hemoglobin, glucose, insulin, or other metabolic parameters in diabetes patients. The effect of the ketogenic diet on the pharmacotherapy of type 1 and type 2 diabetes has been presented and compared with the standard nutritional management plan recommended for that disease. Further research is needed in this field, especially studies with a long follow-up period. The discussed articles report interesting therapeutic advantages to the ketogenic diet in comparison with standard diets.
... In recent years, ketogenic diets re-emerged as popular weightloss regimens in the general population, with some evidence of positive effects on glycemia, HbA1c and blood lipid profile in people with type 2 diabetes [4]. There are mounting case reports and small-scale studies describing the benefits of the ketogenic diet in patients with type 1 diabetes, particularly related to improvements in glycemic control and variability, and reduction in insulin requirements [5][6][7]. However, there are potential risks associated with ketogenic diet consumption by type 1 diabetes patients, such as incidents of severe hypoglycemia and ketoacidosis, which are reported [7,8], but remain less investigated. ...
Hypoglycemia-associated autonomic failure (HAAF) is a serious, life-threatening complication of intensive insulin therapy, particularly in people with type 1 diabetes. The ketogenic diet is reported to beneficially affect glycemic control in people with type 1 diabetes, however its effects on the neurohormonal counterregulatory response to recurrent hypoglycemia and HAAF development are understudied. In this study we used Sprague Dawley rats to establish a HAAF model under non-diabetic and streptozotocin (STZ)-induced diabetic conditions and determined how nutritional ketosis affected the neurohormonal counterregulation and the activity of energy-sensing orexin (OX) neurons. We found that antecedent hypoglycemia diminished the sympathoexcitatory epinephrine response to subsequent hypoglycemia in chow-fed non-diabetic rats, but this did not occur in STZ-diabetic animals. In all cases a ketogenic diet preserved the epinephrine response. Contrary to expectations, STZ-diabetic keto-fed rats showed reduced OX activity in the recurrent hypoglycemia group, which did not occur in any other group. It is possible that the reduced activation of OX neurons is an adaptation aimed at energy conservation accompanied by diminished arousal and exploratory behaviour. Our data suggests that while a ketogenic diet has beneficial effects on glycemia, and epinephrine response, the reduced activation of OX neurons could be detrimental and warrants further investigation.
... 6 Obesity is a state of excess adipose tissue mass. However, in the presence of nutritional abundance and a sedentary lifestyle, and influenced importantly by genetic endowment, this system increases adipose energy stores and produces adverse health consequences [7,8] . ...
... It is therefore vital to understand the nutrient status of diets that contain fewer carbohydrates and whether they can be appropriate for younger people. While LCHF approaches have been explored in children and adolescents to manage obesity and diabetes, one recent study considered low-carbohydrate diets for obese adolescents [14], and another considered LCHF diets in the context of glycaemic control in children with type 1 diabetes, for example [15]-an assessment of the nutritional adequacy of LCHF diets intended for healthy children of normal weight has not yet been done. ...
There is well-established evidence for low-carbohydrate, high-fat (LCHF) diets in the management of chronic health conditions in adults. The natural next step is to understand the potential risks and benefits of LCHF diets for children, where they may have useful applications for general health and a variety of chronic health conditions. It is vital that any diet delivers sufficient micronutrients and energy to ensure health, wellbeing, and growth. This descriptive study assesses the nutrient and energy status of LCHF sample meal plans for children. We designed four meal plans for hypothetical weight-stable male and female children (11 years) and adolescents (16 years). Carbohydrates were limited to ≤80 g, protein was set at 15-25% of the total energy, and fat supplied the remaining calories. Using FoodWorks dietary analysis software, data were assessed against the national Australian/New Zealand nutrient reference value (NRV) thresholds for children and adolescents. All meal plans exceeded the minimum NRV thresholds for all micronutrients; protein slightly exceeded the AMDR recommendations by up to three percentage points. This study demonstrates that LCHF meal plans can be energy-, protein-, and micronutrient-replete for children and adolescents. As with any dietary approach, well-formulated meals and careful planning are key to achieving the optimal nutrient status.
In this chapter, our focus is to illuminate the multifaceted landscape of type 1 diabetes (T1D), addressing its challenges, innovations, and clinical manifestations. We begin with a thorough overview, delving into the causes and associated risk factors, as well as demographic trends and prevalence figures. We focus on the daily challenges that people with T1D encounter and dive into the complexities of management, emphasising the critical role of insulin therapy. Furthermore, we explore technological developments that have transformed treatment paradigms, providing new perspectives that help in improving quality of life. Keeping up with the most recent research and development developments, we highlight continuing initiatives to improve T1D understanding and treatment options. Finally, we examine the often-overlooked psychosocial aspects of living with this chronic condition, hoping to raise understanding and empathy among healthcare professionals and the general public. This chapter aims to provide new insights into T1D, promoting a nuanced understanding of its complexities and manifestations.
The ketogenic diet (KD) has recently gained increasing popularity. This high-fat, adequate-protein, and carbohydrate-poor eating pattern leads to nutritional ketosis. The KD has long been known for its antidiabetic and antiepileptic effects and has been used therapeutically in these contexts. Recently, the KD, due to its effectiveness in inducing weight loss, has also been proposed as a possible approach to treat obesity. Likewise, a KD is currently explored as a supporting element in the treatment of obesity-associated metabolic disorders and certain forms of cancer. Here, we discuss the metabolic and biochemical mechanisms at play during the shift of metabolism to fatty acids and fatty acid–derived ketone bodies as main fuel molecules, in the substitution of carbohydrates, in ketogenic nutrition. Different sources of ketone bodies and KDs as alternatives to glucose and carbohydrates as main energy substrates are discussed, together with an attempt to weigh the benefits and risks posed by the chronic use of a KD in the context of weight loss, and also considering the molecular effects that ketone bodies exert on metabolism and on the endocrine system.
Referencial Teórico: O Diabetes Mellitus tipo I é uma doença que afeta as células beta no pâncreas, inibindo a síntese de insulina. Tendo em mente os graves danos sistêmicos, variadas intervenções são sugeridas, tais como a dieta cetogênica, que limita rigorosamente a quantidade de carboidratos, e a contagem de carboidratos, que possibilita liberdade na alimentação por meio da aplicação de inúmeras injeções. Objetivo: Comparar os tratamentos de Diabetes Mellitus Tipo I por dieta cetogênica e contagem de carboidratos em estudos científicos na literatura. Metodologia: Foi realizada uma revisão sistemática a fim de analisar ensaios clínicos que comparam dois tratamentos para o Diabetes Mellitus Tipo I: a dieta cetogênica e a contagem de carboidratos.
Adults with type 1 diabetes (T1D) have an elevated risk for cardiovascular disease (CVD) compared with the general population. HbA1c is the primary modifiable risk factor for CVD in T1D. Fewer than 1% of patients achieve euglycemia (<5.7%HbA1c). Ketogenic diets (KD; ≤50g carbohydrate/day) may improve glycemia and downstream vascular dysfunction in T1D by reducing HbA1c and insulin load. However, there are concerns regarding the long-term CVD risk from a KD. Therefore, we compared data collected in a 60-day window in an adult with T1D on exogenous insulin who consumed a KD for 10 years versus normative values in those with T1D (T1D norms). The participant achieved euglycemia with an HbA1c of 5.5%, mean glucose of 98[5]mg/dL(median[IQR]), and 90[11]%time-in-range 70-180mg/dL (T1D norms: 1 st percentile for all); and low insulin requirements of 0.38±0.03IU/kg/day (T1D norms: 8 th percentile). Seated systolic blood pressure (SBP) was 113mmHg (T1D norms: 18 th percentile) while ambulatory awake SBP was 132±15mmHg (T1D target: <130mmHg), blood triglycerides were 69mg/dL (T1D norms: 34 th percentile), low-density lipoprotein was 129mg/dL (T1D norms: 60 th percentile), heart rate was 56bpm (T1D norms: >1SD below the mean), carotid-femoral pulse wave velocity was 7.17m/s (T1D norms: lowest quartile of risk), flow-mediated dilation was 12.8% (T1D norms: >1SD above mean), and cardiac vagal baroreflex gain was 23.5ms/mmHg (T1D norms: >1SD above mean). Finally, there was no indication of left ventricular diastolic dysfunction from echocardiography. Overall, these data demonstrate below-average CVD risk relative to T1D norms despite concerns regarding the long-term impact of a KD on CVD risk.
Carbohydrate restriction is not typically recommended for children with type 1 diabetes mellitus (T1DM) because of concerns regarding growth retardation, ketoacidosis, severe hypoglycemia, and dyslipidemia. There is no consensus regarding the effects of carbohydrate restriction on the growth of children with T1DM. However, some previously reported cases of T1DM exhibited growth retardation during carbohydrate restriction, whereas others showed no obvious impairment. A female child with T1DM exhibited severe height growth velocity impairment during carbohydrate restriction in early childhood. Her height standard deviation score (SDS) was 1.12 at the initial T1DM diagnosis (2 yr and 11 mo of age) and –1.33 at 4 yr and 8 mo of age. Her height velocity was only 1.7 cm/yr (SDS –7.02). Discontinuing carbohydrate restriction substantially improved her height growth velocity. Implementing a carbohydrate-restricted diet in children with T1DM can negatively affect height growth velocity.
Type 1 diabetes mellitus (T1DM) is a chronic metabolic disease that results from the autoimmune destruction of pancreatic β-cells, leading to insulin deficiency and hyperglycemia. It is a common chronic disease in childhood, with a prevalence of 1 in 300 children in the United States and an increasing incidence of 2-5% annually, worldwide. Managing T1DM requires regular insulin administration, adjustment of food intake and exercise, and a comprehensive understanding of nutrition. This review aims to explore the relationship between dietary factors, physical activity, obesity, genetics, and glycemic control in children and adolescents with T1DM. To conduct this review, we conducted a thorough search of publications from December 2004 through April 2022 using PubMed, ScienceDirect, and Embase databases. Key topics included obesity, children, adolescents, nutrients, carbohydrates, proteins, fat, water-soluble vitamins, fat-soluble vitamins, dietary patterns, fruits and vegetables, physical activity, genetics, food habits, carbohydrate count and environmental factors.
We examined relations among permissive parenting, mealtime behaviors, nutrition, and HbA1c in pediatric type 1 diabetes (T1D). Sixty-three children (Mage = 10.3, SD = 1.9) with T1D and caregivers completed surveys. Permissive parenting significantly negatively correlated with vegetable consumption (r=-0.27, p = .03). It was positively correlated with child resistance to eating (r = 0.48, p < .01), parent aversion to mealtime (r = 0.51, p < .01) and mealtime disturbance (r = 0.48, p < .01). Child resistance to eating did not mediate the relation between permissive parenting and HbA1c or permissive parenting and vegetable consumption. Because permissive parenting relates to eating behaviors, parent-child interventions promoting healthy eating and more effective parenting in T1D should be explored.
Purpose of review:
Interest in the use of calorie restriction with low-carbohydrate diets for patients with type 1 diabetes appears to be increasing despite physicians' discomfort about its longer term outcomes. A divergence in opinion regarding the balance of benefits and safety may lead to patient disengagement from conventional medical supervision. This review describes the current evidence regarding the benefits and risks of these diets and suggests a way forward to addressing this potential misalignment between the aims of patients and their physicians.
Recent findings:
Benefits on glycaemia are observed in many studies, with improved HbA1c, time within target range and reduced glycaemic variability. A characteristic lipid profile with high LDL cholesterol is observed in many patients, but association with future cardiovascular events is undefined. A negative impact on growth has been identified in the paediatric population, and impact on mental health and disordered eating is of theoretical concern, without measurement in clinical studies.
Summary:
Patients will continue to trial and, with immediate glycaemic benefits, potentially remain on lower carbohydrate diets irrespective of concern by treating physicians about potential longer term risks. A supportive multidisciplinary approach with greater nutritional supervision and more research is required, to allow these patients to achieve their desired glycaemic outcomes without compromising longer term safety.
Objetivo: identificar as ações de autocuidado de adolescentes com Diabetes Mellitus Tipo 1. Método: estudo qualitativo, realizado entre 2019 a 2020, com utilização da dinâmica de criatividade e sensibilidade corpo-saber no ambulatório de endocrinologia pediátrica de um hospital universitário do Distrito Federal. Os dados foram transcritos e submetidos à análise temática. Resultados: participaram 12 adolescentes, sendo que 10 eram do sexo masculino, sete tinham 15 anos, seis cursavam o ensino fundamental e cinco o ensino médio. Das hospitalizações, cinco delas ocorreram apenas uma vez e cinco entre duas e cinco vezes. Seis categorias temáticas foram identificadas: (Des)Cuidado com a Alimentação; (Des)Controle dos níveis glicêmicos; (Des)Conhecimento dos sinais e sintomas da glicemia alterada e estratégias para controle; Cuidado medicamentoso; Atividade física; e Autocuidado no contexto escolar. Conclusão: os adolescentes com Diabetes Mellitus 1 possuíam conhecimento adequado sobre o autocuidado, porém mostraram dificuldades em realizar o tratamento. O papel do(a) enfermeiro(a) é fundamental, não apenas nas ações de educação em saúde, mas também na escuta qualificada, levando-se em consideração a individualidade e o momento de cada adolescente.
Résumé
Chez les patients atteints de diabète de type 1 (DT1), les régimes restreints en glucides, initialement employés avant la découverte de l’insuline, sont de plus en plus souvent utilisés afin de réduire la variabilité glycémique, les hyperglycémies post-prandiales, et pour améliorer le taux d’HbA1c. Contrairement au diabète de type 2, la littérature est pauvre concernant la balance bénéfices/risques des diètes cétogènes dans le DT1. Il est important de superviser et d’accompagner les patients pour réduire les risques d’acidocétose et d’hypoglycémie. Malgré une amélioration de l’équilibre glycémique, l’adhérence à long terme de ce type de régime semble limitée. Des essais cliniques sont nécessaires pour comprendre comment cette diététique peut aider les patients dans la gestion du DT1. En attendant ces essais, les diètes cétogènes peuvent éventuellement être envisagées pour des patients sélectionnés après discussion des risques encourus et sous supervision médicale stricte.
A significantly large body of experimental, epidemiological, and clinical evidence has demonstrated a link between diet and adverse health outcomes. While bad nutritional practices and poor diets have a negative impact on health, specific dietary interventions are considered as important components of any nutrition-based approaches for disease treatment and prevention. Thus, there is not only an increase in public interest in human nutrition for health, but also scientific investigation into establishing dietary approaches that can be undertaken for the prevention and treatment has markedly increased. Accordingly, this article will briefly discuss recent advances in the investigation into the role of four major dietary components: carbohydrates, fats, protein hydrolysates, and bioactive peptides and prebiotics in human health and disease.KeywordsHuman nutritionCarbohydratesDietary fatsProtein hydrolysatesBioactive peptidesPrebioticsResistant starchHealth and disease
\textbf{Objectives}\textbf{Methods}\textbf{Results}\textbf{Conclusion}$: Fewer correction boluses are delivered during closed-loop period. The size of snacks appears to worsen glucose control possibly because of carbohydrate-rich content of snacks. Modifiable behavioral patterns may be important determinants of glucose control.
Objectives:
We evaluated patterns of meal intake, insulin bolus delivery, and fingerstick glucose measurements during hybrid closed-loop and sensor-augmented pump (SAP) therapy, including associations with glucose control.
Methods:
Data were retrospectively analyzed from pump-treated adults with type 1 diabetes who underwent, in random order, 12 weeks free-living closed-loop (n = 32) and 12 weeks SAP (n = 33) periods. We quantified daily patterns of main meals, snacks, prandial insulin boluses, correction boluses, and fingerstick glucose measurements by analyzing data recorded on the study glucometer and on study insulin pump.
Results:
We analyzed 1942 closed-loop days and 2530 SAP days. The total number of insulin boluses was reduced during closed-loop versus SAP periods by mean 1.0 per day (95% confidence interval 0.6-1.4, P < 0.001) mainly because of a reduced number of correction boluses by mean 0.7 per day (0.4-1.0, P < 0.001). Other behavioral patterns were unchanged. The carbohydrate content of snacks but not the number of snacks was positively correlated with (1) glycemic variability as measured by standard deviation of sensor glucose (closed-loop P < 0.05; SAP P < 0.01), (2) mean sensor glucose (P < 0.05), and (3) postintervention HbA1c (P < 0.05). Behavioral patterns explained 47% of between-subject variance in glucose variability during SAP period and 30%-33% of variance of means sensor glucose and postintervention HbA1c.
Conclusion:
Fewer correction boluses are delivered during closed-loop period. The size of snacks appears to worsen glucose control possibly because of carbohydrate-rich content of snacks. Modifiable behavioral patterns may be important determinants of glucose control.
Objective:
To examine the association between glycated hemoglobin (HbA1c) and severe hypoglycemia rates in patients with type 1 diabetes receiving usual care, by analysing data from the US Type 1 Diabetes Exchange (T1DX), German/Austrian Diabetes Patienten Verlaufsdokumenation (DPV), and Western Australian Children Diabetes Database (WACDD) diabetes registries.
Methods:
Data for patients with type 1 diabetes, aged <18 years with a minimum duration of diabetes of 2 years, were extracted from each registry for a 12-month observation period between 2011 and 2012 (7,102 T1DX, 18,887 DPV, and 865 WACDD). Rates of severe hypoglycemia (self-reported loss of consciousness/convulsion) were estimated per 100 patient-years and analyzed by HbA1c, source registry, treatment regimen, and age group.
Results:
Overall, the severe hypoglycemia rate per 100 patient years was 7.1, 3.3, and 6.7 in T1DX, DPV, and WACDD patients, respectively. Lower HbA1c was not associated with an increased rate of severe hypoglycemia when examined by source registry, treatment regimen, or age group.
Conclusion:
An inverse relationship between mean HbA1c and risk of severe hypoglycemia was not observed in this study of 3, independent cohorts of children and adolescents with type 1 diabetes. Investigation in other large, longitudinal cohorts is recommended to further characterize the contemporary relationship between glycemic control and risk of severe hypoglycemia rates in pediatric patients with type 1 diabetes.
Diabetes is a syndrome defined by higher than normal blood glucose levels. Those higher blood glucose levels are associated with the development of physical abnormalities termed complications. Those abnormalities are found in small blood vessels and cause pathology termed retinopathy and nephropathy. Small-vessel abnormalities are part of cardiovascular and peripheral nerve pathology as well. Larger–blood vessel abnormalities are manifest as atherosclerotic plaques that stiffen and reduce blood flow while causing embolic occlusions. This results in ischemic hearts, lungs, and brains, causing life-devastating and -ending events. High glucose levels have been associated with nonvascular damage to the lens of the eye, peripheral nerve, myelin sheath, and nonmyelinated autonomic nerves. These abnormalities cause cataracts, loss of sensation, and proprioception, as well as dysregulation of autonomic function. Autonomic dysfunction compromises normal blood flow, gastric motility, temperature regulation, and sexual function. Preventing these issues has made lowering blood glucose a major goal in the management of diabetes.
There has been little concern about the influence of hyperglycemia on the structure or function of the central nervous system (CNS). The major CNS concern related to diabetes is the opposite issue, hypoglycemia. The symptoms of hypoglycemia are very dramatic, involving intoxicated behavior and mentation, seizures, and loss of consciousness. On occasion, hypoglycemia-induced hemiparesis will result in an extensive medical evaluation and rehabilitation. Generally, these abnormalities are transient …
Introduction: Type 1 diabetes mellitus (T1DM) patients are usually instructed to follow a low fat/high carbohydrate diet. A few studies in literature, however, reported metabolic benefits and sustainability of carbohydrate restricted diets. Case Report: Herein, we present a case of a 19-year-old male with newly diagnosed T1DM. The patient was first put on an insulin regime. Twenty days later, he shifted towards the paleolithic ketogenic diet and was able to discontinue insulin. Strict adherence to the diet resulted in normal glucose levels and a more than three-fold elevation of C-peptide level indicating restored insulin production. Currently, the patient is on the paleolithic ketogenic diet for 6.5 months. He is free of complaints, and no side effects emerged. Conclusion: We conclude that the paleolithic ketogenic diet was effective and safe in the management of this case of newly diagnosed T1DM. Marked increase in C peptide level within two months indicates that the paleolithic ketogenic diet may halt or reverse autoimmune processes destructing pancreatic beta cell function in T1DM.
The inability of current recommendations to control the epidemic of diabetes, the specific failure of the prevailing low-fat diets to improve obesity, cardiovascular risk, or general health and the persistent reports of some serious side effects of commonly prescribed diabetic medications, in combination with the continued success of low-carbohydrate diets in the treatment of diabetes and metabolic syndrome without significant side effects, point to the need for a reappraisal of dietary guidelines. The benefits of carbohydrate restriction in diabetes are immediate and well documented. Concerns about the efficacy and safety are long term and conjectural rather than data driven. Dietary carbohydrate restriction reliably reduces high blood glucose, does not require weight loss (although is still best for weight loss), and leads to the reduction or elimination of medication. It has never shown side effects comparable with those seen in many drugs. Here we present 12 points of evidence supporting the use of low-carbohydrate diets as the first approach to treating type 2 diabetes and as the most effective adjunct to pharmacology in type 1. They represent the best-documented, least controversial results. The insistence on long-term randomized controlled trials as the only kind of data that will be accepted is without precedent in science. The seriousness of diabetes requires that we evaluate all of the evidence that is available. The 12 points are sufficiently compelling that we feel that the burden of proof rests with those who are opposed. (C) 2015 The Authors. Published by Elsevier Inc.
The selection of a glycemic goal in a person with diabetes is a compromise between the documented upside of glycemic control-the partial prevention or delay of microvascular complications-and the documented downside of glycemic control-the recurrent morbidity and potential mortality of iatrogenic hypoglycemia. The latter is not an issue if glycemic control is accomplished with drugs that do not cause hypoglycemia or with substantial weight loss. However, hypoglycemia becomes an issue if glycemic control is accomplished with a sulfonylurea, a glinide, or insulin, particularly in the setting of absolute endogenous insulin deficiency with loss of the normal decrease in circulating insulin and increase in glucagon secretion and attenuation of the sympathoadrenal response as plasma glucose concentrations fall. Then the selection of a glycemic goal should be linked to the risk of hypoglycemia. A reasonable individualized glycemic goal is the lowest A1C that does not cause severe hypoglycemia and preserves awareness of hypoglycemia, preferably with little or no symptomatic or even asymptomatic hypoglycemia, at a given stage in the evolution of the individual's diabetes.
Growth parameters are important indicators of a child's overall health, and they are influenced by factors like blood glucose control in diabetic children. Data on growth parameters of Indian diabetic children is scarce. This retrospective, cross-sectional, case control study was conducted at diabetes clinic for children at a tertiary care center at Pune, to study growth parameters of diabetic children in comparison with age-gender matched healthy controls and evaluate effect of different insulin regimes and age at diagnosis of diabetes on growth.
ONE TWENTY FIVE DIABETIC CHILDREN (BOYS: 50) and age gender matched healthy controls were enrolled. All subjects underwent anthropometric measurements (standing height and weight). Mean height (HAZ), weight (WAZ) and body mass index (BAZ) for age Z scores were calculated. Diabetes control was evaluated by measuring glycosylated hemoglobin (HbA1C). Statistical analysis was done by SPSS version 12.
Mean age of diabetic children and age gender matched controls was 9.7 ± 4.4 years. Diabetic children were shorter (128.3 ± 24.3 cm vs. 133.6 ± 24.7 cm) and lighter (29.2 kg ± 15.3 vs. 31.3 ± 15.4 kg). HAZ (-1.1 ± 1.2 vs. -0.2 ± 0.8) and WAZ (-1.2 ± 1.3 vs. -0.7 ± 1.3) were significantly lower in diabetic children (P < 0.05). Children on both insulin regimes (intensive and conventional) were shorter than controls (HAZ-intensive -1.0 ± 1.0, conventional -1.3 ± 1.3, control -0.2 ± 0.8, P < 0.05). HAZ of children who were diagnosed at <3 years of age was the least (-1.6 ± 1) amongst all diabetic children while those diagnosed after puberty (>14 years) were comparable to healthy controls.
Growth was compromised in diabetic children in comparison to controls. Children diagnosed at younger age need more attention to optimize growth.
Very-low-carbohydrate diets or ketogenic diets have been in use since the 1920s as a therapy for epilepsy and can, in some cases, completely remove the need for medication. From the 1960s onwards they have become widely known as one of the most common methods for obesity treatment. Recent work over the last decade or so has provided evidence of the therapeutic potential of ketogenic diets in many pathological conditions, such as diabetes, polycystic ovary syndrome, acne, neurological diseases, cancer and the amelioration of respiratory and cardiovascular disease risk factors. The possibility that modifying food intake can be useful for reducing or eliminating pharmaceutical methods of treatment, which are often lifelong with significant side effects, calls for serious investigation. This review revisits the meaning of physiological ketosis in the light of this evidence and considers possible mechanisms for the therapeutic actions of the ketogenic diet on different diseases. The present review also questions whether there are still some preconceived ideas about ketogenic diets, which may be presenting unnecessary barriers to their use as therapeutic tools in the physician's hand.European Journal of Clinical Nutrition advance online publication, 26 June 2013; doi:10.1038/ejcn.2013.116.
Background
Reduction of dietary carbohydrates and corresponding insulin doses stabilizes and lowers mean blood glucose in individuals with type 1 diabetes within days. The long-term adherence for persons who have learned this technique is unknown. To assess adherence over 4 years in such a group the present audit was done retrospectively by record analysis for individuals who have attended an educational course. Adherence was assessed from HbA1c changes and individuals’ own reports.
Findings
Altogether 48 persons with diabetes duration of 24 ± 12 years and HbA1c > = 6.1% (Mono-S; DCCT = 7.1%) attended the course. Mean HbA1c for all attendees was at start, at 3 months and 4 years 7.6% ± 1.0%, 6.3 ± 0.7%, 6.9 ± 1.0% respectively. The number of non-adherent persons was 25 (52%). HbA1c in this group was at start, at 3 months and 4 years: 7.5 ±1.1%, 6.5 ± 0.8%, 7.4 ± 0.9%. In the group of 23 (48%) adherent persons mean HbA1c was at start, at 3 months and 4 years 7.7 ± 1.0%, 6.4 ± 0.9%, 6.4 ± 0.8%.
Conclusion
Attending an educational course on dietary carbohydrate reduction and corresponding insulin reduction in type 1 diabetes gave lasting improvement. About half of the individuals adhered to the program after 4 years. The method may be useful in informed and motivated persons with type 1 diabetes. The number needed to treat to have lasting effect in 1 was 2.
Regulation of blood glucose to achieve near-normal levels is a primary goal in the management of diabetes, and, thus, dietary techniques that limit hyperglycemia following a meal are likely important in limiting the complications of diabetes. Low-carbohydrate diets are not recommended in the management of diabetes. Although dietary carbohydrate is the major contributor to postprandial glucose concentration, it is an important source of energy, water-soluble vitamins and minerals, and fiber. Thus, in agreement with the National Academy of Sciences-Food and Nutrition Board, a recommended range of carbohydrate intake is 45-65% of total calories. In addition, because the brain and central nervous system have an absolute requirement for glucose as an energy source, restricting total carbohydrate to < 130 g/day is not recommended. Both the amount (grams) of carbohydrate as well as the type of carbohydrate in a food influence blood glucose level. The total amount of carbohydrate consumed is a strong predictor of glycemic response, and, thus, monitoring total grams of carbohydrate, whether by use of exchanges or carbohydrate counting, remains a key strategy in achieving glycemic control. A recent analysis of the randomized controlled trials that have examined the efficacy of the glycemic index on overall blood glucose control indicates that the use of this technique can provide an additional benefit over that observed when total carbohydrate is considered alone. Although this statement has focused primarily on the role of carbohydrate in the diet, the importance of achieving/ maintaining a healthy body weight (particularly in type 2 diabetes) in the management of diabetes should not be ignored. Moderate weight loss in overweight/obese individuals with type 2 diabetes results in improved control of hyperglycemia as well as in a reduction in risk factors for cardiovascular disease. Because much of the risk of developing type 2 diabetes is attributable to obesity, maintenance of a healthy body weight is strongly recommended as a means of preventing this disease. The relationship between glycemic index and glycemic load and the development of type 2 diabetes remains unclear at this time.
The persistence of an epidemic of obesity and type 2 diabetes suggests that new nutritional strategies are needed if the epidemic is to be overcome. A promising nutritional approach suggested by this thematic review is carbohydrate restriction. Recent studies show that, under conditions of carbohydrate restriction, fuel sources shift from glucose and fatty acids to fatty acids and ketones, and that ad libitum-fed carbohydrate-restricted diets lead to appetite reduction, weight loss, and improvement in surrogate markers of cardiovascular disease.
Patients with type 1 diabetes are known to have a higher hospital admission rate than the underlying population and may also be admitted for procedures that would normally be carried out on a day surgery basis for non-diabetics. Emergency admission rates have sometimes been used as indicators of quality of diabetes care. In preparation for a study of hospital admissions, a systematic review was carried out on hospital admissions for children diagnosed with type 1 diabetes, whilst under the age of 15. The main thrust of this review was to ascertain where there were gaps in the literature for studies investigating post-diagnosis hospitalisations, rather than to try to draw conclusions from the disparate data sets.
A systematic search of the electronic databases PubMed, Cochrane LibrarMEDLINE and EMBASE was conducted for the period 1986 to 2006, to identify publications relating to hospital admissions subsequent to the diagnosis of type 1 diabetes under the age of 15.
Thirty-two publications met all inclusion criteria, 16 in Northern America, 11 in Europe and 5 in Australasia. Most of the studies selected were focussed on diabetic ketoacidosis (DKA) or diabetes-related hospital admissions and only four studies included data on all admissions. Admission rates with DKA as primary diagnosis varied widely between 0.01 to 0.18 per patient-year as did those for other diabetes-related co-morbidity ranging from 0.05 to 0.38 per patient year, making it difficult to interpret data from different study designs. However, people with Type 1 diabetes are three times more likely to be hospitalised than the non-diabetic populations and stay in hospital twice as long.
Few studies report on all admissions to hospital in patients diagnosed with type 1 diabetes whilst under the age of 15 years. Health care costs for type 1 patients are higher than those for the general population and information on associated patterns of hospitalisation might help to target interventions to reduce the cost of hospital admissions.
Low carbohydrate diets for the management of type 1 diabetes have been popularised by social media. The promotion of a low carbohydrate diet in lay media is in contrast to published pediatric diabetes guidelines that endorse a balanced diet from a variety of foods for optimal growth and development in children with type 1 diabetes. This can be a source of conflict in clinical practice. We describe a series of 6 cases where adoption of a low carbohydrate diet in children impacted growth and cardiovascular risk factors with potential long-term sequelae. These cases support current clinical guidelines for children with diabetes that promote a diet where total energy intake is derived from balanced macronutrient sources.
The objective was to compare effects of high carbohydrate diet (HCD) versus low carbohydrate diet (LCD) on glycaemic parameters and cardiovascular risk markers in patients with type 1 diabetes. Ten patients (4 women, insulin pump-treated, median?SD age: 48???10?years, HbA1c: 53???6?mmol/mol (7.0???0.6%)) followed one week of isocaloric HCD (?250?g/day) and one week of isocaloric LCD (?50?g/day) in random order. After each week, we downloaded pump and sensor data and collected fasting blood and urine samples. Diet compliance was high (225???30 vs 47???10?g carbohydrates/day, p?<?0.0001). Mean sensor glucose levels were similar between diets (7.3???1.1 vs 7.4???0.6?mmol/l, p?=?0.99). LCD resulted in more time in 3.9-10.0?mmol/l (83???9 vs 72???11%, p?=?0.02), less time ?3.9?mmol/l (3.3???2.8 vs 8.0???6.3%, p?=?0.03), and less glucose variability (SD 1.9???0.4 vs 2.6???0.4?mmol/l, p?=?0.02) than HCD. Cardiovascular markers were unaffected, while fasting glucagon, ketone and free fatty acid levels were higher at end of the LCD-week than the HCD-week. In conclusion, LCD resulted in more time in euglycaemia, less time in hypoglycaemia and less glucose variability than HCD without altering mean glucose levels.
Objective
To study longitudinal growth in children with type 1 diabetes mellitus. Methods
Anthropometry, disease duration, insulin regimens and HbA1C recorded from patients with diabetes enrolled in a specialty clinic. Results160 children (75 boys; mean (SD) age 9.4 (3.3) y) were enrolled. 35% children had low (<25th centile) height velocity. Disease duration and HbA1C affected height velocity (adjusted for puberty). Children on basal-bolus had higher height velocity Z scores than those on a split mix regimen [(0.5(1.6) vs. -0.3(1.4), P<0.05)]. Children diagnosed before 5 years of age had lowest height velocity. Of the children who reached final height, 53% remained below target height. Conclusion
Children with type 1 diabetes mellitus have lower height velocity compared to healthy children; those diagnosed at younger age were at higher risk for growth failure.
Diets that boost ketone production are increasingly used for treating several neurological disorders. Elevation in ketones in most cases is considered favorable, as they provide energy and are efficient in fueling the body's energy needs. Despite all the benefits from ketones, the above normal elevation in the concentration of ketones in the circulation tend to illicit various pathological complications by activating injurious pathways leading to cellular damage. Recent literature demonstrates a plausible link between elevated levels of circulating ketones and oxidative stress, linking hyperketonemia to innumerable morbid conditions. Ketone bodies are produced by the oxidation of fatty acids in the liver as a source of alternative energy that generally occurs in glucose limiting conditions. Regulation of ketogenesis and ketolysis plays an important role in dictating ketone concentrations in the blood. Hyperketonemia is a condition with elevated blood levels of acetoacetate (AA), 3-β-hydroxybutyrate (BHB), and acetone. Several physiological and pathological triggers, such as fasting, ketogenic diet, and diabetes cause an accumulation and elevation of circulating ketones. Complications of the brain, kidney, liver, and microvasculature were found to be elevated in diabetic patients who had elevated ketones compared to those diabetics with normal ketone levels. This review summarizes the mechanisms by which hyperketonemia and ketoacidosis cause an increase in redox imbalance and thereby increasing the risk of morbidity and mortality in patients.
Risk factors for CVD are well-established in type 2 but not type 1 diabetes (T1DM). We assessed risk factors in the long-term (mean 27 years) follow-up of the Diabetes Control and Complications Trial (DCCT) T1DM cohort. Cox proportional hazards multivariate models assessed the association of traditional and novel risk factors, including HbA1c, with major atherosclerotic cardiovascular events (MACE: fatal or non-fatal myocardial infarction or stroke) and any-CVD (MACE plus confirmed angina, silent MI, revascularization or congestive heart failure). Age and mean HbA1c were strongly associated with any-CVD and with MACE. For each percentage point increase in mean HbA1c, the risk for any-CVD and for MACE increased by 31% and 42%, respectively. CVD and MACE were associated with seven other conventional factors such as blood pressure, lipids and lack of ACE-inhibitor use, but not with gender. The areas under the receiver operating characteristics curves for the association of age and HbA1c taken together with any-CVD and for MACE were 0.70 and 0.77, respectively, and for the final models, including all significant risk factors, were 0.75 and 0.82. Although many conventional CVD risk factors apply in T1DM, hyperglycemia is an important risk factor second only to age.
The effects of low-carbohydrate (LC) diets on body weight and cardiovascular risk are unclear, and previous studies have found varying results. Our aim was to conduct a meta-analysis of randomised controlled trials (RCT), assessing the effects of LC diets
v
. low-fat (LF) diets on weight loss and risk factors of CVD. Studies were identified by searching MEDLINE, Embase and Cochrane Trials. Studies had to fulfil the following criteria: a RCT; the LC diet was defined in accordance with the Atkins diet, or carbohydrate intake of <20 % of total energy intake; twenty subjects or more per group; the subjects were previously healthy; and the dietary intervention had a duration of 6 months or longer. Results from individual studies were pooled as weighted mean difference (WMD) using a random effect model. In all, eleven RCT with 1369 participants met all the set eligibility criteria. Compared with participants on LF diets, participants on LC diets experienced a greater reduction in body weight (WMD –2·17 kg; 95 % CI –3·36, –0·99) and TAG (WMD –0·26 mmol/l; 95 % CI –0·37, –0·15), but a greater increase in HDL-cholesterol (WMD 0·14 mmol/l; 95 % CI 0·09, 0·19) and LDL-cholesterol (WMD 0·16 mmol/l; 95 % CI 0·003, 0·33). This meta-analysis demonstrates opposite change in two important cardiovascular risk factors on LC diets – greater weight loss and increased LDL-cholesterol. Our findings suggest that the beneficial changes of LC diets must be weighed against the possible detrimental effects of increased LDL-cholesterol.
Early-onset type 1 diabetes may affect the developing brain during a critical window of rapid brain maturation. Structural magnetic resonance imaging was performed on 141 children with diabetes (ages 4-10 years at study entry) and 69 age-matched controls at two time points spaced 18 months apart. For the children with diabetes, HbA1c was 7.9±0.9% (63±9.8 mmol/mol)(mean±SD) at both time points. Relative to controls, children with diabetes had significantly less growth of cortical gray matter volume and cortical surface area, and significantly less growth of white matter volume throughout the cortex and cerebellum. For the diabetic population, the change across longitudinal time points of the blood glucose level at the time of scan was negatively correlated with the change in gray and white matter volumes, suggesting that fluctuating glucose levels in children with diabetes may be associated with corresponding fluctuations in brain volume. In addition, measures of hyperglycemia and glycemic variation were significantly negatively correlated with development of surface curvature. These results demonstrate that early-onset type 1 diabetes has widespread effects on the growth of gray and white matter for children whose blood glucose levels are well within the current treatment guidelines for management of diabetes.
Purpose:
The present study describes the epidemiology of severe hypoglycemia and identifies patient characteristics or behaviors associated with severe hypoglycemia in patients with insulin-dependent diabetes mellitus (IDDM) participating in the Diabetes Control and Complications Trial (DCCT).
Patients and methods:
The DCCT is a multicenter randomized clinical trial designed to compare the benefits and risks of intensive therapy with those of conventional management of IDDM. The DCCT's feasibility phase demonstrated that intensive therapy, with the aim of achieving glucose levels as close to the non-diabetic range as possible, was accompanied by a threefold increase in severe hypoglycemia compared with conventional therapy. This report is based on the first 817 subjects who entered the DCCT, with a mean follow-up of 21 months.
Results:
Two hundred sixteen subjects reported 714 episodes of severe hypoglycemia; 549 (77%) occurred in intensively treated subjects. The incidence of severe hypoglycemia in the intensive treatment group ranged from two to six times that observed with conventional treatment. Severe hypoglycemia occurred more often during sleep (55%); 43% of all episodes occurred between midnight and 8 AM. Of episodes that occurred while subjects were awake, 36% were not accompanied by warning symptoms. In intensively treated subjects, predictors of severe hypoglycemia included history of severe hypoglycemia, longer duration of IDDM, higher baseline glycosylated hemoglobin (HbA1c) levels, and a lower recent HbA1c. Multivariate analyses failed to yield predictive models with high sensitivity.
Conclusions:
In the DCCT, intensive treatment of IDDM increased the frequency of severe hypoglycemia relative to conventional therapy. Intensive treatment may cause even more frequent severe hypoglycemia when applied to less selected and less motivated populations in the clinical practice setting. These findings underscore the importance of determining the benefit-risk ratio of intensive and standard therapy of IDDM.
Background: High levels of the triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio are associated with obesity, metabolic syndrome, and insulin resistance.
Objectives: We evaluated variability in the remaining lipid profile, especially remnant lipoprotein particle cholesterol (RLP-C) and its components (very low-density lipoprotein cholesterol subfraction 3 and intermediate-density lipoprotein cholesterol), with variability in the TG/HDL-C ratio in a very large study cohort representative of the general U.S. population.
Methods: We examined data from 1,350,908 US individuals who were clinically referred for lipoprotein cholesterol ultracentrifugation (Atherotech, Birmingham, AL) from 2009 to 2011. Demographic information other than age and sex was not available. Changes to the remaining lipid profile across percentiles of the TG/HDL-C ratio were quantified, as well as by three TG/HDL-C cut-off points previously proposed in the literature: 2.5 (male) and 2 (female), 3.75 (male) and 3 (female), and 3.5 (male and female).
Results: The mean age of our study population was 58.7 years, and 48% were men. The median TG/HDL-C ratio was 2.2. Across increasing TG/HDL-C ratios, we found steadily increasing levels of RLP-C, non-HDL-C and LDL density. Among the lipid parameters studied, RLP-C and LDL density had the highest relative increase when comparing individuals with elevated TG/HDL-C levels to those with lower TG/HDL-C levels using established cut-off points. Approximately 47% of TG/HDL-C ratio variance was attributable to RLP-C.
Conclusions: In the present analysis, a higher TG/HDL-C ratio was associated with an increasingly atherogenic lipid phenotype, characterized by higher RLP-C along with higher non-HDL-C and LDL density.
Keywords: triglycerides; high-density lipoprotein cholesterol; TG/HDL-C ratio; lipids; cut-off points; remnant lipoprotein particle cholesterol
To examine the overall state of metabolic control and current use of advanced diabetes technologies in the U.S., we report recent data collected on individuals with type 1 diabetes participating in the T1D Exchange clinic registry. Data from 16,061 participants updated between 1 September 2013 and 1 December 2014 were compared with registry enrollment data collected from 1 September 2010 to 1 August 2012. Mean hemoglobin A1c (HbA1c) was assessed by year of age from <4 to >75 years. The overall average HbA1c was 8.2% (66 mmol/mol) at enrollment and 8.4% (68 mmol/mol) at the most recent update. During childhood, mean HbA1c decreased from 8.3% (67 mmol/mol) in 2-4-year-olds to 8.1% (65 mmol/mol) at 7 years of age, followed by an increase to 9.2% (77 mmol/mol) in 19-year-olds. Subsequently, mean HbA1c values decline gradually until ∼30 years of age, plateauing at 7.5-7.8% (58-62 mmol/mol) beyond age 30 until a modest drop in HbA1c below 7.5% (58 mmol/mol) in those 65 years of age. Severe hypoglycemia (SH) and diabetic ketoacidosis (DKA) remain all too common complications of treatment, especially in older (SH) and younger patients (DKA). Insulin pump use increased slightly from enrollment (58-62%), and use of continuous glucose monitoring (CGM) did not change (7%). Although the T1D Exchange registry findings are not population based and could be biased, it is clear that there remains considerable room for improving outcomes of treatment of type 1 diabetes across all age-groups. Barriers to more effective use of current treatments need to be addressed and new therapies are needed to achieve optimal metabolic control in people with type 1 diabetes.
© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
BACKGROUND
Long-term microvascular and neurologic complications cause major morbidity and mortality in patients with insulin-dependent diabetes mellitus (IDDM). We examined whether intensive treatment with the goal of maintaining blood glucose concentrations close to the normal range could decrease the frequency and severity of these complications.
METHODS
A total of 1441 patients with IDDM -- 726 with no retinopathy at base line (the primary-prevention cohort) and 715 with mild retinopathy (the secondary-intervention cohort) were randomly assigned to intensive therapy administered either with an external insulin pump or by three or more daily insulin injections and guided by frequent blood glucose monitoring or to conventional therapy with one or two daily insulin injections. The patients were followed for a mean of 6.5 years, and the appearance and progression of retinopathy and other complications were assessed regularly.
RESULTS
In the primary-prevention cohort, intensive therapy reduced the adjusted mean risk for the development of retinopathy by 76 percent (95 percent confidence interval, 62 to 85 percent), as compared with conventional therapy. In the secondary-intervention cohort, intensive therapy slowed the progression of retinopathy by 54 percent (95 percent confidence interval, 39 to 66 percent) and reduced the development of proliferative or severe nonproliferative retinopathy by 47 percent (95 percent confidence interval, 14 to 67 percent). In the two cohorts combined, intensive therapy reduced the occurrence of microalbuminuria (urinary albumin excretion of ≥ 40 mg per 24 hours) by 39 percent (95 percent confidence interval, 21 to 52 percent), that of albuminuria (urinary albumin excretion of ≥ 300 mg per 24 hours) by 54 percent (95 percent confidence interval, 19 to 74 percent), and that of clinical neuropathy by 60 percent (95 percent confidence interval, 38 to 74 percent). The chief adverse event associated with intensive therapy was a two-to-threefold increase in severe hypoglycemia.
CONCLUSIONS
Intensive therapy effectively delays the onset and slows the progression of diabetic retinopathy, nephropathy, and neuropathy in patients with IDDM.
Context:
Few studies have assessed factors associated with severe hypoglycemia (SH) and diabetic ketoacidosis (DKA) in adults with type 1 diabetes (T1D).
Objective:
Our objective was to determine frequency of and factors associated with the occurrence of SH and DKA in adults with T1D.
Design and setting:
We conducted a cross-sectional analysis from the T1D Exchange clinic registry at 70 U.S. endocrinology centers.
Patients:
Analysis included 7012 participants in the T1D Exchange clinic registry aged 26 to 93 years old with T1D for ≥2 years.
Results:
Higher frequencies of SH and DKA were associated with lower socioeconomic status (P < .001). SH was strongly associated with diabetes duration (P < .001), with 18.6% of those with diabetes ≥40 years having an event in the past 12 months. SH frequency was lowest in those with hemoglobin A1c (HbA1c) levels of 7.0% (53 mmol/mol) to 7.5% (58 mmol/mol), being higher in those with HbA1c levels <7.0% (<53 mmol/mol) or >7.5% (>58 mmol/mol). DKA frequency increased with higher HbA1c levels (P < .001), with 21.0% of those with HbA1c ≥10.0% (≥86 mmol/mol) having an event in the past 12 months.
Conclusions:
SH and DKA are more common in those with lower socioeconomic status. DKA, most common in those with HbA1c ≥10.0% (≥86 mmol/mol), should be largely preventable. In contrast, SH, most frequent with diabetes ≥40 years duration, cannot be abolished given the limitation of current therapies. To reduce SH in adults with longstanding diabetes, consideration should be given to modifying HbA1c goals, particularly in patients with very low HbA1c levels.
Most clinical laboratories directly measure serum triglyceride, total cholesterol, and high- density lipoprotein cholesterol. They indirectly calculate low-density lipoprotein cholesterol value using the Friedewald equation. Although high serum triglyceride (>400 mg/dL or 4.52 mmol/L) devaluates low-density lipoprotein cholesterol calculation by using this formula, effects of low serum triglyceride (<100 mg/dL or 1.13 mmol/L) on its accuracy is less defined.Two hundred thirty serum samples were assayed during a one-year period. In 115 samples, the triglyceride level was below 100 mg/dL and in 115 samples from age- and sex-matched patients the triglyceride level was 150 - 350 mg/dL (1.69 - 3.95 mmol/L). In both groups total cholesterol was above 250 mg/dL (6.46 mmol/L). On each sample, total cholesterol, high-density lipoprotein cholesterol, and triglyceride were directly measured in duplicate and low-density lipoprotein cholesterol measured directly and calculated with Friedewald equation as well. Statistical analysis showed that when triglyceride is <100 mg/dL, calculated low- density lipoprotein cholesterol is significantly overestimated (average :12.17 mg/dL or 0.31 mmol/L), where as when triglyceride is between 150 and 300 mg/dL no significant difference between calculated and measured low-density lipoprotein cholesterol is observed. In patients with low serum triglyceride and undesirably high total cholesterol levels, Friedewald equation may overestimate low-density lipoprotein cholesterol concentration and it should be either directly assayed or be calculated by a modified Friedewald equation. Using linear regression modeling, we propose a modified equation.
Background:
Clinical guidelines differ regarding their recommended blood glucose targets for patients with type 1 diabetes and recent studies on patients with type 2 diabetes suggest that aiming at very low targets can increase the risk of mortality.
Objectives:
To assess the effects of intensive versus conventional glycaemic targets in patients with type 1 diabetes in terms of long-term complications and determine whether very low, near normoglycaemic values are of additional benefit.
Search methods:
A systematic literature search was performed in the databases The Cochrane Library, MEDLINE and EMBASE. The date of the last search was December 2012 for all databases.
Selection criteria:
We included all randomised controlled trials (RCTs) that had defined different glycaemic targets in the treatment arms, studied patients with type 1 diabetes, and had a follow-up duration of at least one year.
Data collection and analysis:
Two review authors independently extracted data, assessed studies for risk of bias, with differences resolved by consensus. Overall study quality was evaluated by the 'Grading of Recommendations Assessment, Development, and Evaluation' (GRADE) system. Random-effects models were used for the main analyses and the results are presented as risk ratios (RR) with 95% confidence intervals (CI) for dichotomous outcomes.
Main results:
We identified 12 trials that fulfilled the inclusion criteria, including a total of 2230 patients. The patient populations varied widely across studies with one study only including children, one study only including patients after a kidney transplant, one study with newly diagnosed adult patients, and several studies where patients had retinopathy or microalbuminuria at baseline. The mean follow-up duration across studies varied between one and 6.5 years. The majority of the studies were carried out in the 1980s and all trials took place in Europe or North America. Due to the nature of the intervention, none of the studies could be carried out in a blinded fashion so that the risk of performance bias, especially for subjective outcomes such as hypoglycaemia, was present in all of the studies. Fifty per cent of the studies were judged to have a high risk of bias in at least one other category.Under intensive glucose control, the risk of developing microvascular complications was reduced compared to conventional treatment for a) retinopathy: 23/371 (6.2%) versus 92/397 (23.2%); RR 0.27 (95% CI 0.18 to 0.42); P < 0.00001; 768 participants; 2 trials; high quality evidence; b) nephropathy: 119/732 (16.3%) versus 211/743 (28.4%); RR 0.56 (95% CI 0.46 to 0.68); P < 0.00001; 1475 participants; 3 trials; moderate quality evidence; c) neuropathy: 29/586 (4.9%) versus 86/617 (13.9%); RR 0.35 (95% CI 0.23 to 0.53); P < 0.00001; 1203 participants; 3 trials; high quality evidence. Regarding the progression of these complications after manifestation, the effect was weaker (retinopathy) or possibly not existent (nephropathy: RR 0.79 (95% CI 0.37 to 1.70); P = 0.55; 179 participants with microalbuminuria; 3 trials; very low quality evidence); no adequate data were available regarding the progression of neuropathy. For retinopathy, intensive glucose control reduced the risk of progression in studies with a follow-up duration of at least two years (85/366 (23.2%) versus 154/398 (38.7%); RR 0.61 (95% CI 0.49 to 0.76); P < 0.0001; 764 participants; 2 trials; moderate quality evidence), while we found evidence for an initial worsening of retinopathy after only one year of intensive glucose control (17/49 (34.7%) versus 7/47 (14.9%); RR 2.32 (95% CI 1.16 to 4.63); P = 0.02; 96 participants; 2 trials; low quality evidence).Major macrovascular outcomes (stroke and myocardial infarction) occurred very rarely, and no firm evidence could be established regarding these outcome measures (low quality evidence).We found that intensive glucose control increased the risk for severe hypoglycaemia, however the results were heterogeneous and only the 'Diabetes Complications Clinical Trial' (DCCT) showed a clear increase in severe hypoglycaemic episodes under intensive treatment. A subgroup analysis according to the baseline haemoglobin A1c (HbA1c) of participants in the trials (low quality evidence) suggests that the risk of hypoglycaemia is possibly only increased for patients who started with relatively low HbA1c values (< 9.0%). Several of the included studies also showed a greater weight gain under intensive glucose control, and the risk of ketoacidosis was only increased in studies using insulin pumps in the intensive treatment group (very low quality evidence).Overall, all-cause mortality was very low in all studies (moderate quality evidence) except in one study investigating renal allograft as treatment for end-stage diabetic nephropathy. Health-related quality of life was only reported in the DCCT trial, showing no statistically significant differences between the intervention and comparator groups (moderate quality evidence). In addition, only the DCCT published data on costs, indicating that intensive glucose therapy control was highly cost-effective considering the reduction of potential diabetes complications (moderate quality evidence).
Authors' conclusions:
Tight blood sugar control reduces the risk of developing microvascular diabetes complications. The evidence of benefit is mainly from studies in younger patients at early stages of the disease. Benefits need to be weighed against risks including severe hypoglycaemia, and patient training is an important aspect in practice. The effects of tight blood sugar control seem to become weaker once complications have been manifested. However, further research is needed on this issue. Furthermore, there is a lack of evidence from RCTs on the effects of tight blood sugar control in older patient populations or patients with macrovascular disease. There is no firm evidence for specific blood glucose targets and treatment goals need to be individualised taking into account age, disease progression, macrovascular risk, as well as the patient's lifestyle and disease management capabilities.
Objective:
Severe hypoglycemia (SH) and diabetic ketoacidosis (DKA) are common serious acute complications of type 1 diabetes (T1D). The aim of this study was to determine the frequency of SH and DKA and identify factors related to their occurrence in the T1D Exchange pediatric and young adult cohort.
Research design and methods:
The analysis included 13 487 participants in the T1D Exchange clinic registry aged 2 to <26 yr with T1D ≥2 yr. Separate logistic regression models were used to evaluate the association of baseline demographic and clinical factors with the occurrence of SH or DKA in the prior 12 months.
Results:
Non-White race, no private health insurance, and lower household income were associated with higher frequencies of both SH and DKA (p < 0.001). SH frequency was highest in children <6 yr old (p = 0.005), but across the age range, SH was not associated with hemoglobin A1c (HbA1c) levels after controlling for other factors (p = 0.72). DKA frequency was highest in adolescents (p < 0.001) and associated with higher HbA1c (p < 0.001).
Conclusions:
Our data show that poor glycemic control increases the risk of DKA but does not protect against SH in youth and young adults with type 1 diabetes. The high frequencies of SH and DKA observed in disadvantaged minorities with T1D highlight the need for targeted interventions and new treatment paradigms for patients in these high risk groups.
Context:
The T1D Exchange includes a clinic-based registry, a patient-centric web site called Glu, and a biobank.
Objective:
The aim of the study was to describe the T1D Exchange clinic registry and provide an overview of participant characteristics.
Design:
Data obtained through participant completion of a questionnaire and chart extraction include diabetes history, management, and monitoring; general health; lifestyle; family history; socioeconomic factors; medications; acute and chronic diabetic complications; other medical conditions; and laboratory results.
Setting:
Data were collected from 67 endocrinology centers throughout the United States.
Patients:
We studied 25,833 adults and children with presumed autoimmune type 1 diabetes (T1D).
Results:
Participants ranged in age from less than 1 to 93 yr, 50% were female, 82% were Caucasian, 50% used an insulin pump, 6% used continuous glucose monitoring, and 16% had a first-degree family member with T1D. Glycosylated hemoglobin at enrollment averaged 8.3% and was highest in 13 to 25 yr olds. The prevalence of renal disease was ≤4% until T1D was present for at least 10 yr, and retinopathy treatment was ≤2% until T1D was present for at least 20 yr. A severe hypoglycemic event (seizure or coma) in the prior 12 months was reported by 7% of participants and diabetic ketoacidosis in the prior 12 months by 8%.
Conclusions:
The T1D Exchange clinic registry provides a database of important information on individuals with T1D in the United States. The rich dataset of the registry provides an opportunity to address numerous issues of relevance to clinicians and patients, including assessments of associations between patient characteristics and diabetes management factors with outcomes.
To investigate the effect of type 1 diabetes on growth and adult height.
Data from 22 651 children (10 494 females) with type 1 diabetes documented at onset of the disease from specialized centers in Germany and Austria were analyzed. Patients of non-German and non-Austrian origin and patients with celiac disease were excluded from the analysis. Near-adult height data were available in 1685 patients.
At the time of diagnosis of type 1 diabetes, the mean age of the 22 651 children was 8.8 ± 4.2 years, with a mean height SDS of 0.22 ± 1.0. The 1685 patients with diabetes onset before age 11 years reached a mean adult height of -0.16 ± 1.0 SDS. Mean adult height was was 167.1 ± 6.2 cm (-0.16 ± 0.97 SDS) in females (n = 846) and 179.6 ± 7.1 cm (-0.17 ± 1.0 SDS) in males (n = 839). Mean duration of diabetes was 9.1 ± 2.6 years, and mean Hemoglobin A1c concentration was 7.9% ± 1.2% (63 ± 10 mmol/mol). In a multivariate regression model, adult height was positively correlated with height at onset of diabetes (P < .0001) and negatively with mean Hemoglobin A1c (P < .0001) and duration of diabetes (P = .0015).
Height at the time of diagnosis of type 1 diabetes is above average. Even with intensive insulin therapy, growth and adult height remain indicators of metabolic diabetes control in the 21st century.
To evaluate the influence of biopsy-proven celiac disease (BPCD) on somatic development and metabolic parameters in children with type 1 diabetes mellitus (T1DM) in a multicenter survey.
Within the Diabetes Patienten Verlaufsdokumentationssystem-Wiss project, data of 41 951 patients with T1DM, aged <20 years (52% males, mean age 13.9 years; mean duration of diabetes 5.5 years) were collected in 297 centers in Germany and Austria from 1995 to 2009.
The number of BPCD (0.6% in 1995; 1.3% in 2008) has increased over time. Patients with BPCD were significantly younger at diabetes onset (5.9 vs 8.3 years), had a significantly lower weight standard deviation score (SDS); (0.20 vs 0.43) and height SDS (-0.28 vs -0.03) (P < .001, each) compared with patients without celiac disease. No differences were found in hemoglobin A1c or numbers of severe hypoglycemia. In a subgroup of 9805 patients (183 with BPCD) significantly lower height and weight SDS (P < .001) were still found after a 5-year follow-up.
Screening for celiac disease is important in children with T1DM to prevent persistent growth failure.
Diabetes type 1 seems to be more prevalent in epilepsy, and low-carbohydrate diets improve glycemic control in diabetes type 2, but data on the use of the classic ketogenic diet (KD) in epilepsy and diabetes are scarce. We present 15 months of follow-up of a 3 years and 6 months old girl with diabetes type 1 (on the KD), right-sided hemiparesis, and focal epilepsy due to a malformation of cortical development. Although epileptiform activity on electroencephalography (EEG) persisted (especially during sleep), clinically overt seizures have not been reported since the KD. An improved activity level and significant developmental achievements were noticed. Glycosylated hemoglobin (HbA1c) levels improved, and glycemic control was excellent, without severe side effects. Our experience indicates that diabetes does not preclude the use of the KD.
Research electronic data capture (REDCap) is a novel workflow methodology and software solution designed for rapid development and deployment of electronic data capture tools to support clinical and translational research. We present: (1) a brief description of the REDCap metadata-driven software toolset; (2) detail concerning the capture and use of study-related metadata from scientific research teams; (3) measures of impact for REDCap; (4) details concerning a consortium network of domestic and international institutions collaborating on the project; and (5) strengths and limitations of the REDCap system. REDCap is currently supporting 286 translational research projects in a growing collaborative network including 27 active partner institutions.
To define the relationship between HbA(1c) and plasma glucose (PG) levels in patients with type 1 diabetes using data from the Diabetes Control and Complications Trial (DCCT).
The DCCT was a multicenter, randomized clinical trial designed to compare intensive and conventional therapies and their relative effects on the development and progression of diabetic complications in patients with type 1 diabetes. Quarterly HbA(1c) and corresponding seven-point capillary blood glucose profiles (premeal, postmeal, and bedtime) obtained in the DCCT were analyzed to define the relationship between HbA(1c) and PG. Only data from complete profiles with corresponding HbA(1c) were used (n = 26,056). Of the 1,441 subjects who participated in the study, 2 were excluded due to missing data. Mean plasma glucose (MPG) was estimated by multiplying capillary blood glucose by 1.11. Linear regression analysis weighted by the number of observations per subject was used to correlate MPG and HbA(1c).
Linear regression analysis, using MPG and HbA(1c) summarized by patient (n = 1,439), produced a relationship of MPG (mmol/l) = (1.98 . HbA(1c)) - 4.29 or MPG (mg/dl) = (35.6 . HbA(1c)) - 77.3, r = 0.82). Among individual time points, afternoon and evening PG (postlunch, predinner, postdinner, and bedtime) showed higher correlations with HbA(1c) than the morning time points (prebreakfast, postbreakfast, and prelunch).
We have defined the relationship between HbA(1c) and PG as assessed in the DCCT. Knowing this relationship can help patients with diabetes and their healthcare providers set day-to-day targets for PG to achieve specific HbA(1c) goals.
The use of diets with low glycemic index (GI) in the management of diabetes is controversial, with contrasting recommendations around the world. We performed a meta-analysis of randomized controlled trials to determine whether low-GI diets, compared with conventional or high-GI diets, improved overall glycemic control in individuals with diabetes, as assessed by reduced HbA(1c) or fructosamine levels.
Literature searches identified 14 studies, comprising 356 subjects, that met strict inclusion criteria. All were randomized crossover or parallel experimental design of 12 days' to 12 months' duration (mean 10 weeks) with modification of at least two meals per day. Only 10 studies documented differences in postprandial glycemia on the two types of diet.
Low-GI diets reduced HbA(1c) by 0.43% points (CI 0.72-0.13) over and above that produced by high-GI diets. Taking both HbA(1c) and fructosamine data together and adjusting for baseline differences, glycated proteins were reduced 7.4% (8.8-6.0) more on the low-GI diet than on the high-GI diet. This result was stable and changed little if the data were unadjusted for baseline levels or excluded studies of short duration. Systematically taking out each study from the meta-analysis did not change the CIs.
Choosing low-GI foods in place of conventional or high-GI foods has a small but clinically useful effect on medium-term glycemic control in patients with diabetes. The incremental benefit is similar to that offered by pharmacological agents that also target postprandial hyperglycemia.
Context:
The Atkins diet books have sold more than 45 million copies over 40 years, and in the obesity epidemic this diet and accompanying Atkins food products are popular. The diet claims to be effective at producing weight loss despite ad-libitum consumption of fatty meat, butter, and other high-fat dairy products, restricting only the intake of carbohydrates to under 30 g a day. Low-carbohydrate diets have been regarded as fad diets, but recent research questions this view.
Starting point:
A systematic review of low-carbohydrate diets found that the weight loss achieved is associated with the duration of the diet and restriction of energy intake, but not with restriction of carbohydrates. Two groups have reported longer-term randomised studies that compared instruction in the low-carbohydrate diet with a low-fat calorie-reduced diet in obese patients (N Engl J Med 2003; 348: 2082-90; Ann Intern Med 2004; 140: 778-85). Both trials showed better weight loss on the low-carbohydrate diet after 6 months, but no difference after 12 months. WHERE NEXT?: The apparent paradox that ad-libitum intake of high-fat foods produces weight loss might be due to severe restriction of carbohydrate depleting glycogen stores, leading to excretion of bound water, the ketogenic nature of the diet being appetite suppressing, the high protein-content being highly satiating and reducing spontaneous food intake, or limited food choices leading to decreased energy intake. Long-term studies are needed to measure changes in nutritional status and body composition during the low-carbohydrate diet, and to assess fasting and postprandial cardiovascular risk factors and adverse effects. Without that information, low-carbohydrate diets cannot be recommended.
Atherosclerotic disease accounts for much of the increased mortality and morbidity associated with type 2 diabetes. Epidemiological studies support the potential of improved glycemic control to reduce cardiovascular complications. An association between glycosylated hemoglobin (HbA(1c)) level and the risk for cardiovascular complications has frequently been reported. Most epidemiological data implicate postprandial hyperglycemia in the development of cardiovascular disease, whereas the link between fasting glycemia and diabetic complications is inconclusive. Moreover, in many studies, postprandial glycemia is a better predictor of cardiovascular risk than HbA(1c) level. Postprandial glucose may have a direct toxic effect on the vascular endothelium, mediated by oxidative stress that is independent of other cardiovascular risk factors such as hyperlipidemia. Postprandial hyperglycemia also may exert its effects through its substantial contribution to total glycemic exposure. The present review examines the hypothesis that controlling postprandial glucose level is an important strategy in the prevention of cardiovascular complications associated with diabetes.
Due to failure to achieve control twenty-two patients with type 1 diabetes with symptomatic fluctuating blood glucose started on a diet limited to 70-90 g carbohydrates per day and were taught to match the insulin doses accordingly. The caloric requirements were covered by an increased intake of protein and fat. The purpose was to reduce the blood glucose fluctuations, the rate of hypoglycaemia and to improve HbA1c. After three and 12 months the rate of hypoglycaemia was significantly lowered from 2.9 +/- 2.0 to 0.2 +/- 0.3 and 0.5 +/- 0.5 episodes per week respectively. The HbAlc level was significantly lowered from 7.5 +/- 0.9% to 6.4 +/- 0.7% after three months and was still after 12 months 6.4 +/- 0.8%. The meal insulin requirements were reduced from 21.1 +/- 6.7 I.U./day to 12.7 +/- 3.5 I.U./day and 12.4 +/- 2.6 I.U./day after three and 12 months respectively. Furthermore the triglyceride level was significantly lowered whereas the levels for total cholesterol and HDL-cholesterol were unchanged. The present report shows that a 70-90 g carbohydrate diet is a feasible long-term alternative in the treatment of type 1 diabetes and leads to improved glycaemic control.
In response to the emerging epidemic of obesity in the United States, a renewal of interest in alternative diets has occurred, especially in diets that limit carbohydrate intake. Recent research has demonstrated that low-carbohydrate ketogenic diets can lead to weight loss and favorable changes in serum triglycerides and high-density lipoprotein cholesterol. This review summarizes the physiology and recent clinical studies regarding this type of diet.
The Diabetes Complications and Control Trial (DCCT) established that diabetic complications could be reduced by improvement in glycemic control. The ideal diabetes treatment protocol would maintain blood glucose levels in normal ranges without resulting in frequent hypoglycemia. Because several studies suggest an inverse relationship between carbohydrate consumption and the level of glycemic control, the effects of an intensive treatment program, which included dietary carbohydrate restriction, are examined in this paper. A chart review was performed of 30 patients who self-reported the consumption of 30 g of carbohydrate daily, followed a strict insulin regimen, monitored blood glucose levels at least four times daily, and had follow-up clinical visits or phone calls with their physician. For both type I and type II diabetics, there were significant improvements in glycemic control and mean fasting lipid profiles at follow-up. The mean hemoglobin A1c decreased by 27.8% from 7.9 to 5.7 (p < 0.001). The LDL cholesterol decreased by 16.5%, from 155.4 to 129.7 mg/dL (p = 0.004). The triglycerides decreased by 31.1%, from 106.8 to 73.6 mg/dL (p = 0.005). The HDL cholesterol increased by 43.3%, from 50.4 to 72.2 mg/dL (p < 0.001). The cholesterol/HDL ratio decreased by 31.5%, from 4.99 to 3.42 (p < 0.001). A carbohydrate-restricted regimen improved glycemic control and lipid profiles in selected motivated patients. Therefore, further investigation of the effects of this protocol on treating diabetes mellitus should be considered. Additionally, the reduction of insulin afforded by this diet could theoretically lead to a reduction in hypoglycemic events.
- Iatrogenic Hypoglycemia
iatrogenic hypoglycemia. Diabetes.
2014;63(7):2188-2195
Bernstein's Diabetes Solution: The Complete Guide to Achieving Normal Blood Sugars
- R K Bernstein
- Dr
Bernstein RK. Dr. Bernstein's Diabetes
Solution: The Complete Guide to
Achieving Normal Blood Sugars. 4th ed.
Boston, MA: Little, Brown & Company;
2011