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Restricting carbohydrates at breakfast is sufficient to reduce 24-hour exposure to postprandial hyperglycemia and improve glycemic variability

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Background The breakfast meal often results in the largest postprandial hyperglycemic excursion in people with type 2 diabetes. Objective Our purpose was to investigate whether restricting carbohydrates at breakfast would be a simple and feasible strategy to reduce daily exposure to postprandial hyperglycemia. Design Adults with physician-diagnosed type 2 diabetes [n = 23; mean ± SD age: 59 ± 11 y; glycated hemoglobin: 6.7% ± 0.6%; body mass index (kg/m2): 31 ± 7] completed two 24-h isocaloric intervention periods in a random order. Participants consumed one of the following breakfasts: 1) a very-low-carbohydrate high-fat breakfast (LCBF; <10% of energy from carbohydrate, 85% of energy from fat, 15% of energy from protein) or 2) a breakfast with dietary guidelines–recommended nutrient profile (GLBF; 55% of energy from carbohydrate, 30% of energy from fat, 15% of energy from protein), with the same lunch and dinner provided. Continuous glucose monitoring was used to assess postprandial glucose responses over 24 h, and visual analog scales were used to assess ratings of hunger and fullness. Results The LCBF significantly reduced postprandial hyperglycemia after breakfast (P < 0.01) and did not adversely affect glycemia after lunch or dinner. As such, overall postprandial hyperglycemia (24-h incremental area under the glucose curve) and glycemic variability (mean amplitude of glycemic excursions) were reduced with the LCBF (24-h incremental area under the glucose curve: −173 ± 361 mmol/L; P = 0.03; mean amplitude of glycemic excursions: −0.4 ± 0.8 mmol/L · 24 h; P = 0.03) compared with the GLBF. Premeal hunger was lower before dinner with the LCBF than with the GLBF (P-interaction = 0.03). Conclusions A very-low-carbohydrate high-fat breakfast lowers postbreakfast glucose excursions. The effects of this simple strategy appear to be sufficient to lower overall exposure to postprandial hyperglycemia and improve glycemic variability. Longer-term interventions are warranted. This trial was registered at clinicaltrials.gov as NCT02982330.

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... Lunch and dinner were the same for the two conditions. In this study, breakfast carb reduction led to significantly reduced 24-h iAUC for glucose and 24-h mean amplitude of glycemic excursions as measured with CGM [59]. The reported effect was of a similar magnitude to that observed with the use of acarbose [60]. ...
... For all other patients who wish to eat more frequently, substitution of carb with protein could also be a way to achieve tighter glycemic control and reduced postprandial insulin responses [78]. Regarding the effect of breakfast skipping in glycemia control in T2DM, no study has found an adverse effect of breakfast consumption, and all available evidence suggests that breakfast should be regularly consumed by T2DM patients [47][48][49][50][51]. Apart from and in addition to the evidence in favor of breakfast consumption, there is also evidence showing the importance of breakfast macronutrient composition in glycemia management [57][58][59]63]. Large carb-loaded breakfasts do not seem to be the best option for T2DM patients, and a reduced proportion of carb at breakfast [57], replacement of breakfast carb with either protein [58] or fat [64], or total omission of carb from breakfast [63] have a favorable impact on glycemia both in the short term (following breakfast or lunch) [57,58,63] and in the longer term (whole-day glycemic response) [59]. ...
... Regarding the effect of breakfast skipping in glycemia control in T2DM, no study has found an adverse effect of breakfast consumption, and all available evidence suggests that breakfast should be regularly consumed by T2DM patients [47][48][49][50][51]. Apart from and in addition to the evidence in favor of breakfast consumption, there is also evidence showing the importance of breakfast macronutrient composition in glycemia management [57][58][59]63]. Large carb-loaded breakfasts do not seem to be the best option for T2DM patients, and a reduced proportion of carb at breakfast [57], replacement of breakfast carb with either protein [58] or fat [64], or total omission of carb from breakfast [63] have a favorable impact on glycemia both in the short term (following breakfast or lunch) [57,58,63] and in the longer term (whole-day glycemic response) [59]. Other authors have also suggested that replacing rapidly available carbohydrates with non-refined carb from whole grains and cereal fibers, proteins, and unsaturated fatty acids at breakfast may be a useful strategy for achieving favorable metabolic outcomes [79]. ...
Article
A variety of eating patterns are recommended by international guidelines to help people with type 2 diabetes mellitus (T2DM) achieve general health and glycemia goals. Apart from eating patterns, there is evidence that other approaches related to the everyday application of dietary advice, such as meal frequency, breakfast consumption, daily carbohydrate distribution, and order of food consumption during meals, have significant effects on glycemia management. The aims of this review were to examine published diabetes nutrition guidelines concerning specific recommendations with regard to the above approaches, as well as to review evidence from studies that have investigated their effect on glycemia in T2DM. The data suggest that eating breakfast regularly, consuming most carbohydrates at lunch, avoiding large dinners late at night, and applying the carbohydrate-last meal pattern are effective practices towards better nutritional management of T2DM.
... Four studies included in the analysis compared reduced carbohydrate content with higher carbohydrate content meals and showed that reducing the amount of carbohydrates of a meal results in a lower GL of that meal, and therefore better glycemic control [24][25][26][27]. ...
... In a more recent randomized crossover trial, Chang et al. [25] investigated the effect of altered nutrient breakfasts on postprandial glucose response, but instead of altering GI through replacement of high-GI foods with low-GI ones, they altered GL by reducing the total amount of carbohydrate, resulting in a low-carbohydrate breakfast (LCBF). In the LCBF, carbohydrates provided approximately 10% of energy. ...
... Chang et al. [25] (i) A low-CHO, high-fat breakfast where energy from CHO accounted for less than 10% energy lowered postprandial glucose excursions (p < 0.01); (ii) overall postprandial hyperglycemia and glycemic variability decreased with the low-carbohydrate diet (p < 0.03) (i) Short duration of the intervention (ii) Research design did not include measurements of insulin excursions 6. ...
Article
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The increasing prevalence of type 2 diabetes (T2D) worldwide calls for effective approaches to its management. Strategies for diabetes have generally focused on optimizing overall glycemic control as assessed by glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG) values. However, since 2001, the American Diabetes Association has established postprandial glucose (PPG) as an independent contributor to both HbA1c and diabetes complications, and increasing evidence suggests that all three glycemic parameters of HbA1c, FPG, and postprandial glucose (PPG) are independently important. Objectives: The objective of this review was to comprehensively summarize the literature on the effects of nutritional strategies incorporating glycemic index (GI)/glycemic load (GL) on the postprandial hyperglycemia in people with T2D, as well as to provide recommendations for effective dietary strategies addressing both the dietary glycemic index and load in clinical practice. Design: An advanced Pubmed search was conducted. A total of 10 randomized controlled studies met the inclusion criteria. Six studies compared low-GI with higher GI meals, three included studies that compared reduced carbohydrate content with higher carbohydrate content, and one study compared meals of low-GI (with high or low fiber) with meals of higher GI (with high or low fiber). Results: Most of the clinical trials resulted in significant improvement (p < 0.05) of postprandial hyperglycemia. Conclusions: Either reducing the amount of carbohydrate in a meal or increasing consumption of soluble fiber has a favorable effect on postprandial glucose excursions.
... Insulin and certain oral hypoglycemic medications reduce glycemic variability 15,16 . Multiple studies have shown improvements in glycemic control from bariatric surgery, low-calorie diets, or carbohydrate restriction 2,[17][18][19] . However, adverse events and high cost can limit the use of bariatric surgery 2 . ...
... Low-calorie diets (e.g. less than 800 kcal/day) to manage diabetes may be difficult to maintain over the long term 1 . Low carbohydrate studies showed improved glycemic control, but often were only small short-term trials, excluded subjects taking insulin, or were limited to morbidly obese patients 1,[18][19][20][21][22][23][24] . None of the studies so far have combined long-term continuous glucose monitoring (CGM), artificial intelligence methods, and precision nutrition for long-term management of glycemic variability. ...
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The objective of this retrospective observational cohort study was to measure glycemic variability and reductions in body mass index (BMI), blood pressure (BP), and use of antihypertensive medications in type 2 diabetes (T2D) patients participating in the digital twin-enabled Twin Precision Treatment (TPT) Program. Study participants included 19 females and 45 males with T2D who chose to participate in the TPT Program and adhered to program protocols. Nine additional enrollees were excluded due to major program non-adherence. Enrollees were required to have adequate hepatic and renal function, no myocardial infarction, stroke, or angina ≤ 90 days before enrollment, and no history of ketoacidosis or major psychiatric disorders. The TPT program uses Digital Twin technology, machine learning algorithms, and precision nutrition to aid treatment of patients with T2D. Each study participant had ≥ 3 months of follow-up. Outcome measures included glucose percentage coefficient of variation (%CV), low blood glucose index (LBGI), high blood glucose index (HBGI), systolic and diastolic BP, number of antihypertensive medications, and BMI. Sixty-four patients participated in the program. Mean (± standard deviation) %CV, LBGI, and HBGI values were low (17.34 ± 4.35, 1.37 ± 1.37, and 2.13 ± 2.79, respectively) throughout the 90-day program. BMI decreased from 29.23 ± 5.83 at baseline to 27.43 ± 5.25 kg/m². Systolic BP fell from 134.72 ± 17.73 to 124.58 ± 11.62 mm Hg. Diastolic BP decreased from 83.95 ± 10.20 to 80.33 ± 7.04 mm Hg. The percent of patients taking antihypertensive medications decreased from 35.9% at baseline to 4.7% at 90 days. During 90 days of the TPT Program, patients achieved low glycemic variability and significant reductions in BMI and BP. Antihypertensive medication use was eliminated in nearly all patients. Future research will focus on randomized case–control comparisons.
... Patients with type 1 diabetes CGM Reduced GV and improved protection against hypoglycemia [87][88][89] Insulin analogues degludec Minimized morning GV [91] Canagliflozin Improved indices of GV [92] Dapagliflozin over 24 weeks Improved GV without increasing the time spent in the range indicating hypoglycemia [93] Empagliflozin as adjunct to insulin Decreased glucose exposure and variability and increased time in glucose target range [103] Combination of basal insulin with ipragliflozin or dapagliflozin Improved TIR and the mean glucose level [104] Low carbohydrate diet Resulted in more time in euglycemia, less time in hypoglycemia [108][109][110] Patients with type 2 diabetes Dapagliflozin on 24-h Improved measures of GV [94] Once-weekly trelagliptin and once-daily alogliptin Improved glycemic control and reduced GV without inducing hypoglycemia [95] Combination of basal insulin with a GLP-1 RA Lowered GV and hypoglycemia [96] Exenatide once weekly Improved daily glucose control and reduced GV [97] Lixisenatide added to basal insulin Reduced GV and PPG excursions without increasing the risk of hypoglycemia [98] Liraglutide Lower mean time in hyperglycemia [99] Combination of metformin and gemigliptin or sitagliptin Significantly reduced GV [100] Vildagliptin or pioglitazone Significantly reduced MAGE, glycated hemoglobin and mean plasma glucose levels [101] Combination of metformin and vildagliptin or glimepiride Improved glucose level with a significantly greater reduction in GV and hypoglycemia [102] Intensive insulin therapy combined with metformin Reduced both glucose fluctuation and nocturnal hypoglycemic risk [105] Low-carbohydrate high-fat diet Reduced glycemic fluctuation [106,107,111] Sequence of food ingestion Associated with lower post-lunch glucose excursions and lower glucose coefficients of variation [115] Aerobic and combined exercise sessions Reduced glucose levels and GV [116][117][118] Short-term exercise training Improved glycemic control and GV but unaffected oxidative stress [119,121] Frequent interruptions of prolonged sitting Improved fasting glucose and night-time glycemic variability [120] Others Low glycemic index foods Reduced the glycemic response and variability and promoted fat oxidation. [112,113] Food order Reduced glycemic excursions [114] Exercise in the fasted and postprandial state Exercise in the postprandial state after breakfast, but not in the fasted state, decreased glucose excursions [122] Aerobic and eccentric exercise Reduced all the indices of GV [123] Immediate post-breakfast physical activity Improved mean, CV and AUC glucose [124] RA) with basal insulin observed the lowest GV and hypoglycemia in type 2 diabetes [96]. ...
... Furthermore, low carbohydrate diet contributed to more time in euglycemia, less GV than high carbohydrate diet [108][109][110]. Particularly, a very-low-carbohydrate high-fat breakfast appeared to be sufficient to reduce postprandial hyperglycemia and improve glucose excursions [111]. Low glycemic index foods can minimize blood glucose fluctuations and have been advocated to use in diabetic patients. ...
Article
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Abstract Glycemic variability (GV), defined as an integral component of glucose homoeostasis, is emerging as an important metric to consider when assessing glycemic control in clinical practice. Although it remains yet no consensus, accumulating evidence has suggested that GV, representing either short-term (with-day and between-day variability) or long-term GV, was associated with an increased risk of diabetic macrovascular and microvascular complications, hypoglycemia, mortality rates and other adverse clinical outcomes. In this review, we summarize the adverse clinical outcomes of GV and discuss the beneficial measures, including continuous glucose monitoring, drugs, dietary interventions and exercise training, to improve it, aiming at better addressing the challenging aspect of blood glucose management.
... Consistent timing of all meals and snacks is likely to be of value to prevent both hypoglycaemia and hyperglycaemia in pregnant women with type 1 diabetes [61]. Blood glucose levels often increase to high levels after breakfast, whereas a low-carbohydrate breakfast may lower postprandial glucose excursions after breakfast [76]. We therefore recommend a relatively low amount of carbohydrates in the breakfast [61]. ...
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In women with type 1 diabetes, the risk of adverse pregnancy outcomes, including congenital anomalies, preeclampsia, preterm delivery, foetal overgrowth and perinatal death is 2–4-fold increased compared to the background population. This review provides the present evidence supporting recommendations for the diet during pregnancy and breastfeeding in women with type 1 diabetes. The amount of carbohydrate consumed in a meal is the main dietary factor affecting the postprandial glucose response. Excessive gestational weight gain is emerging as another important risk factor for foetal overgrowth. Dietary advice to promote optimized glycaemic control and appropriate gestational weight gain is therefore important for normal foetal growth and pregnancy outcome. Dietary management should include advice to secure sufficient intake of micro- and macronutrients with a focus on limiting postprandial glucose excursions, preventing hypoglycaemia and promoting appropriate gestational weight gain and weight loss after delivery. Irrespective of pre-pregnancy BMI, a total daily intake of a minimum of 175 g of carbohydrate, mainly from low-glycaemic-index sources such as bread, whole grain, fruits, rice, potatoes, dairy products and pasta, is recommended during pregnancy. These food items are often available at a lower cost than ultra-processed foods, so this dietary advice is likely to be feasible also in women with low socioeconomic status. Individual counselling aiming at consistent timing of three main meals and 2–4 snacks daily, with focus on carbohydrate amount with pragmatic carbohydrate counting, is probably of value to prevent both hypoglycaemia and hyperglycaemia. The recommended gestational weight gain is dependent on maternal pre-pregnancy BMI and is lower when BMI is above 25 kg/m2. Daily folic acid supplementation should be initiated before conception and taken during the first 12 gestational weeks to minimize the risk of foetal malformations. Women with type 1 diabetes are encouraged to breastfeed. A total daily intake of a minimum of 210 g of carbohydrate is recommended in the breastfeeding period for all women irrespective of pre-pregnancy BMI to maintain acceptable glycaemic control while avoiding ketoacidosis and hypoglycaemia. During breastfeeding insulin requirements are reported approximately 20% lower than before pregnancy. Women should be encouraged to avoid weight retention after pregnancy in order to reduce the risk of overweight and obesity later in life. In conclusion, pregnant women with type 1 diabetes are recommended to follow the general dietary recommendations for pregnant and breastfeeding women with special emphasis on using carbohydrate counting to secure sufficient intake of carbohydrates and to avoid excessive gestational weight gain and weight retention after pregnancy.
... Big breakfasts also resulted in greater improvement in glucose tolerance than big dinners in combination with metformin therapy, despite equal total caloric intake [57]. Another study suggests that lowcarbohydrate, high-fat breakfast lowered glucose levels and glucose variability in patients with type 2 diabetes [58]. In summary, the current evidence suggests that consuming a significant proportion of calories, particularly carbohydrates, in breakfast is beneficial for the chronic management of obesity and its associated metabolic syndrome compared to consuming the same amount of calories or carbohydrates at dinner. ...
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The central circadian clock in the brain controls the time-of-the-day variations in acute meal responses, with a low glycemic response but a high satiety/thermogenic response to meals consumed at waking compared to other time points. Consistently, studies show that consuming a significant proportion of calories, particularly carbohydrates, in breakfast is beneficial for the chronic management of obesity and its associated metabolic syndrome, compared to consuming identical meals at dinner. Conversely, breakfast skipping or/and late dinner can have unfavorable metabolic outcomes. It remains controversial how meal frequency affects metabolic health. In contrast, irregular meals, especially irregular breakfasts, show consistent adverse metabolic consequences. Time-restricted feeding (TRF), with all calories consumed within less than 12-h per day, can improve metabolism and extend lifespan. A major component of TRF in humans is caloric restriction, which contributes significantly to the beneficial effects of TRF in humans. By comparison, TRF effects in rodents can be independent of caloric restriction and show day/night phase specificity. TRF could alleviate metabolic abnormalities due to circadian disruption, but its effects appear independent of the circadian clock in rodents. Understanding neuroendocrine mechanisms underlying clock-mediated metabolic regulation will shed light on the metabolic effects of temporal meal patterns.
... The postprandial blood glucose results are consistent with those of a study published by Chang, Francois, & Little who found similar results in a study population of adults with type 2 diabetes. 28 In another study of adults with type 1 diabetes, a crossover design study revealed that a 40% protein/20% carbohydrate diet resulted in lower glycemic variability and shorter times in hypoglycemia than both a 50% carbohydrate and a Mediterranean diet with 40% carbohydrate. 29 The ADA consensus report, ''Nutrition Therapy for Adults with Diabetes or Prediabetes'' (2019) provides recommendations for eating patterns that were supported by research evidence to improve overall health, but does not specify advice for women with GDM. 30 While there are differing etiologies for the different types of diabetes, one factor that is common to all forms of diabetes is the need to ingest food to survive and the subsequent need to regulate blood glucose. ...
Article
Introduction: There is an urgent need to establish an evidence base for recommendations regarding proportions of macronutrients for optimized nutritional management of gestational diabetes mellitus (GDM). Our study compared isocaloric diets in women with GDM that differed in protein and carbohydrate content with fats held constant. We hypothesized that the glucose area under the curve (AUC) would be lower with the higher protein/lower carbohydrate diet. Research design and methods: This study used a random order crossover design within a controlled research unit environment. Nineteen women were randomized to treatment, with 12 participants completing both arms of the study. Blood sampling occurred preprandially and at t = 30, 60, 120, and 180" relative to meals. Inclusion criteria were confirmed diet-controlled GDMA1, singleton gestation, and with no pre-existing medical comorbidities. Mean gestational age at entrance to study = 32 (±1.76) weeks. Mean prepregnant body mass index of participants = 28.7 (±5.3) kg/m2 Participants were randomly assigned initially to either an increased protein/low carbohydrate (iPRO30%/CHO35%) diet or a lower protein/higher carbohydrate (LPRO15%/CHO50%) diet for a 36 hour inpatient stay on the research unit. All meals and snacks were prepared in a metabolic kitchen. After a 3-7 day washout period, participants were randomized to the opposite treatment. Results: On day 2 (with confirmed overnight fasting), the average 3-hour pre- through postprandial glucose AUC was lower in iPRO30%/CHO35% treatment arm (17395.20 ± 2493.47 vs. 19172.47 ± 3484.31, p = 0.01). Conclusion: This study is the first to demonstrate that a higher protein, lower carbohydrate meal, especially at breakfast, can result in lower postprandial blood glucose values in women with gestational diabetes. A lack of statistically significant differences at other collection time points could have been due to several factors, but most likely due to small sample size. Longer term outcomes of a higher protein diet, including maternal glycemic control, nitrogen balance, and impact on fetal growth outcomes, are needed.
... For example, nutritional interventions targeting breakfast using food low in carbohydrates have reported improved glycemic responses in individuals with T2D. 10,16 The timing and macronutrient content of breakfast also appear to influence the risk of progression of T2D. 25 Previous studies have suggested an association between consuming a regular breakfast with a decreased risk of T2D progression compared with breakfast skipping or infrequent breakfast consumption. 26,27 The macronutrient content of breakfast can also influence subsequent glucose and insulin responses. ...
Article
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Background There is minimal experience in continuous glucose monitoring (CGM) among underserved racial/ethnic minority populations with or at risk of type 2 diabetes (T2D), and therefore a lack of CGM-driven insight for these individuals. We analyzed breakfast-related CGM profiles of free-living, predominantly Hispanic/Latino individuals at-risk of T2D, with pre-T2D, or with non-insulin treated T2D. Methods Starting February 2019, 119 participants in Santa Barbara, CA, USA, (93 female, 87% Hispanic/Latino [predominantly Mexican-American], age 54·4 [±12·1] years), stratified by HbA1c levels into (i) at-risk of T2D, (ii) with pre-T2D, and (iii) with non-insulin treated T2D, wore blinded CGMs for two weeks. We compared valid CGM profiles from 106 of these participants representing glucose response to breakfast using four parameters. Findings A “northeast drift” was observed in breakfast glucose responses comparing at-risk to pre-T2D to T2D participants. T2D participants had a significantly higher pre-breakfast glucose level, glucose rise, glucose incremental area under the curve (all p < 0·0001), and time to glucose peak (p < 0·05) compared to pre-T2D and at-risk participants. After adjusting for demographic and clinical covariates, pre-breakfast glucose and time to peak (p < 0·0001) were significantly associated with HbA1c. The model predicted HbA1c within (0·55±0·67)% of true laboratory HbA1c values. Interpretation For predominantly Hispanic/Latino adults, the average two-week breakfast glucose response shows a progression of dysglycemia from at-risk of T2D to pre-T2D to T2D. CGM-based breakfast metrics have the potential to predict HbA1c levels and monitor diabetes progression. Funding US Department of Agriculture (Grant #2018–33800–28404), a seed grant from the industry board fees of the NSF Engineering Research Center for Precise Advanced Technologies and Health Systems for Underserved Populations (PATHS-UP) (Award #1648451), and the Elsevier foundation.
... In people with T2D, glycemic variability has been tied to a higher risk of renal disease, macrovascular events, ulceration/gangrene, cardiovascular disease, and mortality [98]. Given the primary effect of carbohydrate on insulin secretion, it is not surprising that very low-carbohydrate diets are related to lower glycemic variability in people with type 1 diabetes [99,100] and T2D [64,74,93,101], which at a basic level enables many of the positive responses observed in clinical trials. ...
Article
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The decades-long dietary experiment embodied in the Dietary Guidelines for Americans (DGA) focused on limiting fat, especially saturated fat, and higher carbohydrate intake has coincided with rapidly escalating epidemics of obesity and type 2 diabetes (T2D) that are contributing to the progression of cardiovascular disease (CVD) and other diet-related chronic diseases. Moreover, the lack of flexibility in the DGA as it pertains to low carbohydrate approaches does not align with the contemporary trend toward precision nutrition. We argue that personalizing the level of dietary carbohydrate should be a high priority based on evidence that Americans have a wide spectrum of metabolic variability in their tolerance to high carbohydrate loads. Obesity, metabolic syndrome, and T2D are conditions strongly associated with insulin resistance, a condition exacerbated by increased dietary carbohydrate and improved by restricting carbohydrate. Low-carbohydrate diets are grounded across the time-span of human evolution, have well-established biochemical principles, and are now supported by multiple clinical trials in humans that demonstrate consistent improvements in multiple established risk factors associated with insulin resistance and cardiovascular disease. The American Diabetes Association (ADA) recently recognized a low carbohydrate eating pattern as an effective approach for patients with diabetes. Despite this evidence base, low-carbohydrate diets are not reflected in the DGA. As the DGA Dietary Patterns have not been demonstrated to be universally effective in addressing the needs of many Americans and recognizing the lack of widely available treatments for obesity, metabolic syndrome, and T2D that are safe, effective, and sustainable, the argument for an alternative, low-carbohydrate Dietary Pattern is all the more compelling.
... Human studies have demonstrated that postprandial hyperglycaemia and hyperlipidaemia are positively correlated with oxidant production [27]. The dietary carbohydrate intake is one of the primary determinants of postprandial hyperglycemia and it remains a cause of concern for those subject with type 2 diabetes [28,29]. Green tea consumption reduces the level of postprandial glucose. ...
... Another non-pharmacological strategy is dietary interventions. Low carbohydrate diet appeared to be sufficient to reduce postprandial hyperglycemia and improve glucose fluctuation, resulting in more time in euglycemia, less time in hypoglycemia and less GV [110][111][112][113]. ...
Article
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Diabetes mellitus is the major risk factor for the development of macrovascular and microvascular complications. It is increasingly recognized that glycemic variability (GV), referring to oscillations in blood glucose levels and representing either short-term or long-term GV, is involved in the pathogenesis of diabetic complications and has emerged as a possible independent risk factor for them. In this review, we summarize the metrics and measurement of GV in clinical practice, as well as comprehensively elaborate the role and related mechanisms of GV in diabetic macrovascular and microvascular complications, aiming to provide the mechanism-based therapeutic strategies for clinicians to manage diabetes mellitus.
... 18 19 As observed in our study, the morning glucose excursion also corresponds to the largest glycemic peak across the day. Controlled feeding studies [18][19][20][21] have reported that lowering postbreakfast glycemic responses improves glucose variability, suggesting that the early glucose peak is critical to the overall dysglycemia across the day. In free-living people with T2D, glycemic responses are superimposed on numerous internal (ie, chronobiological mechanisms) and external (eg, habitual diet quality, medications, physical activity, social, and emotional) factors which influence glucose levels and variability. ...
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Introduction This pilot study evaluated the impact of a diabetes-specific nutritional shake (DSNS) used twice daily by people with type 2 diabetes (T2D) on glycemic response assessed by continuous glucose monitoring (CGM). Research design and methods Adults (n=81) with T2D managed by oral medications were studied in a randomized, open-label, three-group parallel study design. The study was conducted in two phases over 14 days: Baseline (days 1–6), during which study participants consumed their habitual self-selected diets (SSD), followed by the Intervention (days 7–14), during which participants were randomized as follows: (1) SSD group received no study product (n=32); (2) DSNS breakfast/afternoon snack (Bkfst/AS) group consumed one DSNS as a breakfast meal replacement and a second to replace their mid-afternoon snack (n=24); (3) DSNS breakfast/prebed snack (Bkfst/PBS) group consumed one DSNS as a breakfast meal replacement and added a second as a prebed snack (n=25). Glucose was assessed by CGM throughout the study. Additionally, participants were asked about snacking behaviors, cravings, and other questions related to the use of DSNS as meal replacements and snacks. Results All groups reduced their postprandial glycemic response (positive area under the curve (pAUC, mg/min*dL ⁻¹ )) and adjusted peak value (mg/dL) when compared with the baseline phase. Participants consuming DSNS in place of their usual breakfast showed greater reductions in pAUC compared with the SSD group (p=0.008) for the DSNS Bkfst/AS group with a trend (p=0.069) for the DSNS Bkfst/PBS group. Adjusted peak value showed greater reductions in both DSNS groups as compared with the SSD group (p=0.002 for DSNS Bkfst/AS and p=0.010 for DSNS Bkfst/PBS). Nocturnal glucose variability was significantly decreased during the intervention phase compared with baseline phase in the DSNS Bkfst/AS group (p=0.020), with no significant differences between groups. After intervention, the DSNS Bkfst/AS group had a significantly lower percentage of participants (17%) reporting cravings for starchy meals/sides compared with before the study (33%) (p=0.046). This group also reported a significant increase in confidence in choosing foods to control their diabetes (from 58.3% to 91.7%, preintervention vs postintervention, respectively, p=0.005). Conclusions Use of DSNS to replace breakfast and as an afternoon snack improves both glycemic control and behavioral factors related to dietary management of diabetes. Trail registration number NCT04230889 .
... As shown in Figures 2A and 2B, breakfast PPG and daily mean glucose are better when breakfast is split into two meals. This finding is in agreement with a recent study showing that a low-carbohydrate, balanced breakfast improves the glucose profile throughout the day (71,82). Also, moderating breakfast PPG using a good postmeal exercise workout helps the glucose profile for the rest of the day (57). ...
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Several evidence-based lifestyle habits focusing on the composition, timing, and sequence of meals and on pre- and postmeal exercise can improve diabetes management. Consuming low-carbohydrate, balanced meals and eating most carbohydrates early in the day are helpful habits. Eating the protein and vegetable components of a meal first and consuming the carbohydrates 30 minutes later can moderate glucose levels. Postmeal glucose surges can be blunted without precipitating hypoglycemia with moderate exercise 30-60 minutes before the anticipated peak. Short-duration, high-intensity exercise could also be effective. Premeal exercise can improve insulin sensitivity but can also cause post-exertion glucose elevations. Moreover, high-intensity premeal exercise may precipitate delayed hypoglycemia in some people. Glycemia benefits can be enhanced by eating a light, balanced breakfast after premeal exercise.
... One study, for example, showed improved glycemic control with brown versus white rice and even more benefit with the consumption of glutinous brown rice (32). A more recent study demonstrated that a low-carbohydrate breakfast improved glycemic variability over 24 hours (33). Eighty-seven percent of our patients noticed glucose changes from their food choices. ...
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OBJECTIVE | To explore the use of premixed insulin, a glucagon-like peptide 1 (GLP-1) receptor agonist, and metformin as combination therapy for type 2 diabetes. DESIGN AND METHODS | All adult patients with type 2 diabetes who had been prescribed premixed insulin and a GLP-1 receptor agonist simultaneously at our outpatient clinic were selected for retrospective review. We reviewed A1C, weight, cumulative daily insulin dose, and adverse events over 12 months. RESULTS | A total of 72 patients received premixed insulin and a GLP-1 receptor agonist, of which 32 met inclusion criteria. The average duration of type 2 diabetes for these patients was 14.2 ± 7.1 years. Mean A1C at baseline was 10.5 ± 2.1%. At 12 months, mean A1C was 8.3 ± 1.9%. The change in mean A1C after 12 months was −2.2% (95% CI −3.433 to −1.014, P <0.0001). At 12 months, the mean cumulative insulin dose was 33.3 units less than before the therapy change (95% CI −57.13 to −9.46, P = 0.0030). Average weight change at 12 months was −2.2 kg (95% CI −27.6 to 37.6, P = NS). After 12 months, 61% of included patients (19 of 31) had an A1C ≤8%. Six additional patients were not included in analysis because they stopped the regimen after <3 months because of adverse events. CONCLUSION | Despite a decreased cumulative daily dose of insulin, patients with historically uncontrolled type 2 diabetes using metformin, premixed insulin, and a GLP-1 receptor agonist in combination experienced improved glycemic control over 12 months. Prospective randomized trials are needed to better assess the potential benefit of this combination therapy.
... While in a randomized controlled trial eating high-glycemic index CH late in the day induced a higher postprandial glycemic control compared to when it was consumed in the morning [9]. A more recent study indicated that lowering CH intake at breakfast while increasing fat intake improves glycemic variability over the day [10]. Further studies have indicated that consuming CH at night at 23:00 worsens postprandial glucose profile the following morning compared to when the same amount is consumed earlier in the evening at 18:00 [11]. ...
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This study aims at combining time and quantity of carbohydrate (CH) intake in the definition of eating patterns in UK adults and investigating the association of the derived patterns with type 2 diabetes (T2D). The National Diet and Nutrition Survey (NDNS) Rolling Program included 6155 adults in the UK. Time of the day was categorized into 7 pre-defined time slots: 6-9 am, 9-12 noon, 12-2 pm, 2-5 pm, 5-8 pm, 8-10 pm, and 10 pm-6 am. Responses for CH intake were categorized into: no energy intake, CH <50% or ≥50% of total energy. Non-parametric multilevel latent class analysis (MLCA) was applied to identify eating patterns of CH consumption across daytime , as a novel method accounting for the repeated measurements of intake over 3-4 days nested within individuals. Survey-designed multivariable regression was used to assess the associations of CH eating patterns with T2D. Three CH eating day patterns (low, high CH percentage and frequent CH intake day) emerged from 24,483 observation days; based on which three classes of CH eaters were identified and characterized as: low (28.1%), moderate (28.8%) and high (43.1%) CH eaters. On average, low-CH eaters consumed the highest amount of total energy intake (7985.8 kJ) and had higher percentages of energy contributed by fat and alcohol, especially after 8 pm. Moderate-CH eaters consumed the lowest amount of total energy (7341.8 kJ) while they tended to have their meals later in the day. High-CH eaters consumed most of their carbohydrates and energy earlier in the day and within the time slots of 6-9 am, 12-2 pm and 5-8 pm, which correspond to traditional mealtimes. The high-CH eaters profile had the highest daily intake of CH and fiber and the lowest intake of protein and fat. Low-CH eaters had greater odds than high-CH eaters of having T2D in self-reported but not in previously undiagnosed diabetics. Further research using prospective longitudinal studies is warranted to ascertain the direction of causality in the association of CH patterns with type 2 diabetes.
... High postprandial plasma glucose levels are major arteriosclerosis promoting-factors and can trigger vascular endothelial damage and inflammation in cases of mild diabetes or those at risk (Tominaga et al. 1999). Spiking of plasma glucose levels have been observed to occur shortly after a meal, in which plasma glucose levels surge and return to normal levels (Chang et al. 2019). In people with this spiking, health examination measurements do not show high fasting plasma glucose levels and HbAlc values reflective of average plasma glucose levels over 1-2 months are normal; therefore, this condition is problematic, as it cannot be accurately detected in health examinations. ...
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... One study, for example, showed improved glycemic control with brown versus white rice and even more benefit with the consumption of glutinous brown rice (32). A more recent study demonstrated that a low-carbohydrate breakfast improved glycemic variability over 24 hours (33). Eighty-seven percent of our patients noticed glucose changes from their food choices. ...
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Fully automated closed-loop insulin delivery may offer a novel way to manage diabetes in hospital. However, postprandial glycaemic control remains challenging. We aimed to assess the effect of nutritional intake on postprandial glucose control in hospitalized patients with type 2 diabetes receiving fully closed-loop insulin therapy. The effects of different meal types and macronutrient composition on sensor glucose time in target (TIT, 3.9-10.0 mmol/L) and mean sensor glucose (MGL) were assessed with hierarchical linear models using a Bayesian estimation approach. TIT was lower, and MGL slightly higher, after breakfast compared to lunch and dinner whilst insulin dose was higher. Across meals, when carbohydrates were replaced by fat, or to a lesser extent by protein, postprandial glucose control improved. For breakfast, a 3.9% improvement in TIT was observed when 10% of the energy from carbohydrates was replaced by fat. Improvements were slightly lower during lunch and dinner (3.2 and 3.4%) or when carbohydrates were replaced by protein (2.2-2.7%). We suggest that reducing carbohydrate at the expense of fat or protein, could further improve glucose control during fully closed-loop insulin therapy in hospital. This article is protected by copyright. All rights reserved.
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Introduction While circadian control of glucose metabolism is well known, how glycemic index (GI) of carbohydrate-rich meals interacts with time of consumption (breakfast or dinner) to influence postprandial (PP) glucose homeostasis is less well established. The objective of the study was to assess markers of PP glucose homeostasis following high or low GI test meals (TM) consumed either at breakfast or at dinner and following consumption of the subsequent standardized meals (SSM). Research design and methods Randomized crossover trial in 34 healthy, Chinese, elderly volunteers (mean±SEM age, 56.8±0.83 years), who completed 4 separate study sessions per-protocol, consisting of a high-GI breakfast, low-GI breakfast, high-GI dinner and low-GI dinner TM, followed by a SSM at the subsequent eating occasion. Blood samples were taken for 3 hours after each TM and SSM for glucose, insulin, glucagon, free fatty acids (FFA) and triglycerides (TG) measurements. Results Consuming TM at dinner produced greater PP glycemia than breakfast both after TM and SSM (both p<0.0001), irrespective of GI. High-GI TM also produced greater PP glycemia than low-GI TM, both after TM and SSM (both p<0.01), irrespective of time of consumption. No interaction between GI and time were found on PP glycemia, indicating parallel, but independent effects. Combined total areas under the curve of TM+SSM for PP glucose (p<0.0001), PP TG (p<0.0001) and PP FFA (p<0.0001) were all greater when TM taken during dinner compared with breakfast. Conclusions Carbohydrate-rich meals consumed at dinner leads to significantly worse PP glucose homeostasis than when consumed at breakfast, on top of the independent GI effect of the meal. This may have implications to future type 2 diabetes risk. Moreover, future studies investigating GI/glycemic load (GL) and disease risk associations should factor in timing of GL consumption as an additional variable. Trial registration number NCT02927600 .
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The A1C (HbA1c test) is increasingly used as a diagnostic and screening test for type 2 diabetes (T2DM). With an estimated 8.8% of adults globally having diabetes, effective screening, diagnosis, and monitoring is of major global importance (1). The biomarker of A1C refers to glycated hemoglobin A molecules and has gained prominence in the diagnosis of type 2 diabetes because it offers certain advantages over plasma glucose testing regimens (2). It is well established that some of the hundreds of hemoglobin (Hb) variants, including the clinically relevant HbS, HbE, HbC, and HbD (3,4) may interfere with the validity of A1C results. Thus, testing strategies and tools employing A1C should ideally identify variants when they are present. Incidental findings of Hb variants present several ethical challenges for laboratories, health care providers, patients, and their families. These challenges have, to date, received little attention. This article reviews some of the advantages of detecting sickle cell trait, identified by the routine A1C test, but also several related ethical dilemmas. This article explores issues such as whether informed consent is necessary, how the results should be communicated, how the patient may be affected by knowing their carrier status, the timing of communications, complications caused by partial results, and being a 'healthy carrier' at the same time as potentially experiencing symptoms.
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Background: High-intensity interval training (HIIT) can improve several aspects of cardiometabolic health. Previous studies have suggested that adaptations to exercise training can be augmented with post-exercise milk or protein consumption, but whether this nutritional strategy can impact the cardiometabolic adaptations to HIIT in type 2 diabetes is unknown. Objective: To determine if the addition of a post-exercise milk or protein beverage to a high-intensity interval training (HIIT) intervention improves cardiometabolic health in individuals with type 2 diabetes. Design: In a proof-of-concept, double-blind clinical trial 53 adults with uncomplicated type 2 diabetes were randomized to one of three nutritional beverages (500 mL skim-milk, macronutrient control, or flavored water placebo) consumed after exercise (3 days/week) during a 12 week low-volume HIIT intervention. HIIT involved 10 X 1-min high-intensity intervals separated by 1-min low-intensity recovery periods. Two sessions per week were cardio-based (at ~90% of heart rate max) and one session involved resistance-based exercises (at RPE of 5–6; CR-10 scale) in the same interval pattern. Continuous glucose monitoring (CGM), glycosylated hemoglobin (HbA1c), body composition (dual-energy X-ray absorptiometry), cardiorespiratory fitness (V˙O2peak), blood pressure, and endothelial function (%FMD) were measured before and after the intervention. Results: There were significant main effects of time (all p < 0.05) but no difference between groups (Interaction: all p > 0.71) for CGM 24-h mean glucose (−0.5 ± 1.1 mmol/L), HbA1c (−0.2 ± 0.4%), percent body fat (−0.8 ± 1.6%), and lean mass (+1.1 ± 2.8 kg). Similarly, V˙O2peak (+2.5 ± 1.6 mL/kg/min) and %FMD (+1.4 ± 1.9%) were increased, and mean arterial blood pressure reduced (−6 ± 7 mmHg), after 12 weeks of HIIT (all p < 0.01) with no difference between beverage groups (Interaction: all p > 0.11). Conclusion: High-intensity interval training is a potent stimulus for improving several important metabolic and cardiovascular risk factors in type 2 diabetes. The benefits of HIIT are not augmented by the addition of post-exercise protein.
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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.
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To examine reproducibility and validity of visual analogue scales (VAS) for measurement of appetite sensations, with and without a diet standardization prior to the test days. On two different test days the subjects recorded their appetite sensations before breakfast and every 30 min during the 4.5 h postprandial period under exactly the same conditions. 55 healthy men (age 25.6+/-0.6 y, BMI 22.6+/-0.3 kg¿m2). VAS were used to record hunger, satiety, fullness, prospective food consumption, desire to eat something fatty, salty, sweet or savoury, and palatability of the meals. Subsequently an ad libitum lunch was served and energy intake was recorded. Reproducibility was assessed by the coefficient of repeatability (CR) of fasting, mean 4.5 h and peak/nadir values. CRs (range 20-61 mm) were larger for fasting and peak/nadir values compared with mean 4.5 h values. No parameter seemed to be improved by diet standardization. Using a paired design and a study power of 0.8, a difference of 10 mm on fasting and 5 mm on mean 4.5 h ratings can be detected with 18 subjects. When using desires to eat specific types of food or an unpaired design, more subjects are needed due to considerable variation. The best correlations of validity were found between 4.5 h mean VAS of the appetite parameters and subsequent energy intake (r=+/-0.50-0.53, P<0.001). VAS scores are reliable for appetite research and do not seem to be influenced by prior diet standardization. However, consideration should be given to the specific parameters being measured, their sensitivity and study power. International Journal of Obesity (2000)24, 38-48
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Increasing evidence suggests that the postprandial state is a contributing factor to the development of atherosclerosis. In diabetes, the postprandial phase is characterized by a rapid and large increase in blood glucose levels, and the possibility that the postprandial "hyperglycemic spikes" may be relevant to the onset of cardiovascular complications has recently received much attention. Epidemiological studies and preliminary intervention studies have shown that postprandial hyperglycemia is a direct and independent risk factor for cardiovascular disease (CVD). Most of the cardiovascular risk factors are modified in the postprandial phase in diabetic subjects and directly affected by an acute increase of glycemia. The mechanisms through which acute hyperglycemia exerts its effects may be identified in the production of free radicals. This alarmingly suggestive body of evidence for a harmful effect of postprandial hyperglycemia on diabetes complications has been sufficient to influence guidelines from key professional scientific societies. Correcting the postprandial hyperglycemia may form part of the strategy for the prevention and management of CVDs in diabetes.
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We tested the relative importance of a low-glycemic response versus a high glycemic response breakfast meal on postprandial serum glucose, insulin and free fatty acid (FFA) responses after consumption of a standardized mid-day meal in adult individuals with Type 2 diabetes mellitus (DM). Following an overnight fast of 8-10 h, a randomized crossover intervention using control and test meals was conducted over a 3-week-period. A fasting baseline measurement and postprandial measurements at various time intervals after the breakfast and mid-day meal were taken. Forty-five Type 2 DM subjects completed the requirements and were included in the study results. Two different breakfast meals were administered during the intervention: (A) a high glycemic load breakfast meal consisting of farina (kJ 1833; carbohydrate (CHO) 78 g and psylium soluble fiber 0 g), (B) a low-glycemic load breakfast meal consisting of a fiber-loop cereal (kJ 1515; CHO 62 g and psyllium soluble fiber 6.6 g). A standardized lunch was provided approximately 4 h after breakfast. Blood plasma concentrations and area under the curve (AUC) values for glucose, insulin and FFA were measured in response to the breakfast and mid-day lunch. Statistical analyses were performed using SAS software (8.02). Comparisons between diets were based on adjusted Bonferroni t-tests. In post-breakfast analyses, Breakfast B had significantly lower area under the curve (AUC) values for plasma glucose and insulin compared to Breakfast A (P<0.05) (95% confidence level). The AUC values for FFA were higher for Breakfast B than for Breakfast A (P<0.05) (95% confidence level). Post-lunch analyses indicated similar glucose responses for the two breakfast types. Insulin AUC values for Breakfasts B were significantly lower than Breakfast A (P<0.05) (95% confidence level). The AUC values for FFA were unaffected by breakfast type. These data indicate that ingesting a low-glycemic load meal containing psyllium soluble fiber at breakfast significantly improves the breakfast postprandial glycemic, insulinemic and FFA responses in adults with Type 2 DM. These data revealed no residual postprandial effect of the psyllium soluble fiber breakfast meal beyond the second meal consumed. Thus, there was no evidence of an improvement postprandially in the glycemic, insulinemic and FFA responses after the consumption of the lunch meal.
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To explore the possibility that oscillating glucose may outweigh A1C levels in determining the risk for cardiovascular diabetes complications. A euinsulinemic hyperglycemic clamp at 5, 10, and 15 mmol/l glucose was given in increasing steps as a single "spike" or oscillating between basal and high levels over 24 h in normal subjects and type 2 diabetic patients. Flow-mediated dilatation, a marker of endothelial function, and plasma 3-nitrotyrosine and 24-h urinary excretion rates of free 8-iso PGF2 alpha, two markers of oxidative stress, were measured over 48 h postclamp. Glucose at two different levels (10 and 15 mmol/l) resulted in a concentration-dependent fasting blood glucose-independent induction of both endothelial dysfunction and oxidative stress in both normal and type 2 diabetic patients. Oscillating glucose between 5 and 15 mmol/l every 6 h for 24 h resulted in further significant increases in endothelial dysfunction and oxidative stress compared with either continuous 10 or 15 mmol/l glucose. These data suggest that oscillating glucose can have more deleterious effects than constant high glucose on endothelial function and oxidative stress, two key players in favoring cardiovascular complications in diabetes. Concomitant vitamin C infusion can reverse this impairment.
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Large postprandial glucose peaks are associated with increased risk of diabetic complications and cardiovascular disease. We investigated the effect of carbohydrate distribution on postprandial glucose peaks with continuous blood glucose monitoring (CGMS), when consuming a moderate carbohydrate diet in energy balance in subjects with type 2 diabetes. Twenty-three subjects with type 2 diabetes were randomly assigned to each of four 3-d interventions in a crossover design with a 4-d washout period. Identical foods were provided for each treatment with a ratio of total carbohydrate to protein to fat of 40%:34%:26% but differing in carbohydrate content at each meal: even distribution (CARB-E; approximately 70 g carbohydrate), breakfast (CARB-B), lunch (CARB-L), and dinner(CARB-D), each providing approximately 125 g carbohydrate in the loaded meal in a 9-MJ diet. Glucose concentrations were continuously measured with CGMS. Outcomes were assessed by postprandial peak glucose (G(max)), time spent > 12 mmol/L (T > 12), and total area under the glucose curve (AUC(20)). Daily G(max) differed between treatments (P = 0.003) with CARB-L (14.2 +/- 1.0 mmol/L), CARB-E (14.5 +/- 0.9 mmol/L), and CARB-D (14.6 +/- 0.8 mmol/L) being similar but lower than CARB-B (16.5 +/- 0.8 mmol/L). Meal G(max) was weakly related to carbohydrate amount and glycemic load (r = 0.40-0.44). T > 12 differed between treatments (P = 0.014), and a treatment x fasting blood glucose (FBG) interaction (P = 0.003) was observed with CARB-L (184 +/- 74 min) < CARB-B (190 +/- 49 min) < CARB-D (234 +/- 87 min) < CARB-E (262 +/- 91 min). Total AUC(20) was not significantly different between treatments. After adjustment for FBG, treatment became significant (P = 0.006); CARB-L (10 049 +/- 718 mmol/L x 20 h) < CARB-E (10 493 +/- 706 mmol/L x 20 h) < CARB-B (10 603 +/- 642 mmol/L x 20 h) < CARB-D (10 717 +/- 638 mmol/L x 20 h). CARB-E did not optimize blood glucose control as assessed by postprandial peaks, whereas CARB-L provided the most favorable postprandial profile.
Article
Background: People with type 2 diabetes are advised to consume an even meal distribution of carbohydrate. Whether this distribution is optimal is unknown. Objective: Our objective was to show that omitting carbohydrate in the first meal after a fast would lead to an augmented lunch response. Design: Two diets of 1-d duration that differed only in the breakfast-meal composition (carbohydrate or no carbohydrate) were consumed on sequential days in a randomized crossover study. The procedure was repeated in the alternate order 1 wk later. Blood glucose concentrations were tested with the use of continuous glucose monitoring. The primary endpoints were the percentage of time spent with a blood glucose concentration >10 mmol/L (%T >10) and peak blood glucose (Gmax). The following 45 adults with type 2 diabetes were recruited: subjects with glycated hemoglobin (HbA1c) ≤7% and subjects with HbA1c ≥8%. Twenty-eight adults completed the study. Results: The daily Gmax was significantly lower after the no-carbohydrate breakfast than after the carbohydrate breakfast (11.0 ± 0.4 and 12.1 ± 0.4 mmol/L, respectively; P = 0.003) whereas the %T >10 throughout the day was a nonsignificant 22% less after the no-carbohydrate breakfast than after the carbohydrate breakfast (13% ± 10% compared with 10% ± 8%; P = 0.09). Gmax over 5 h after breakfast was significantly lower after the no-carbohydrate meal (by 1.9 ± 0.4 mmol/L; P < 0.001), and the %T >10 was lower after the no-carbohydrate meal than after the carbohydrate meal (11% ± 3% compared with 26% ± 4%, respectively; P < 0.001). Conclusions: The withholding of carbohydrate in the first meal results in significantly decreased Gmax after the meal, but the lunch response is not affected. Overall daily control is not significantly improved. This trial was registered at the Australian New Zealand Clinical Trials Registry as ACTRN12609000331235.
Article
The circadian system serves one of the most fundamental properties present in nearly all organisms: it generates 24-h rhythms in behavioral and physiological processes and enables anticipating and adapting to daily environmental changes. Recent studies indicate that the circadian system is important in regulating the daily rhythm in glucose metabolism. Disturbance of this circadian control or of its coordination relative to the environmental/behavioral cycle, such as in shift work, eating late, or due to genetic changes, results in disturbed glucose control and increased type 2 diabetes risk. Therefore, an in-depth understanding of the mechanisms underlying glucose regulation by the circadian system and its disturbance may help in the development of therapeutic interventions against the deleterious health consequences of circadian disruption.
Article
Both postprandial and fasting (basal) hyperglycaemia contribute to overall hyperglycaemia (ambient hyperglycaemia) in type 2 diabetes (T2D). Postprandial glucose is the main contributor in fairly well controlled individuals, whereas basal hyperglycaemia becomes the preponderant contributor in poorly controlled patients. A more generally acceptable description of the contribution of postprandial glucose is to simply say that the absolute impact of postprandial glucose to HbA1c remains constant at approximately 1% across the entire HbA1c spectrum of non-insulin-treated patients with T2D. While epidemiological and pathophysiological studies seem to indicate that excessive postprandial glucose excursions play a role in or are predictors of cardiovascular diseases, there is still currently a lack of clinical evidence that correcting post-meal hyperglycaemia can improve clinical outcomes. However, even in the absence of consensus, there are many reasons for thinking that excessive postprandial glucose might be an independent risk factor for diabetic complications as it contributes to both overall glucose exposure and glycaemic variability, especially in those who have HbA1c levels < 7.5-8%. Given that excessive glucose fluctuations from peaks to nadirs activate oxidative stress, it seems reasonable to consider that a key player in the pathogenesis of diabetic complications, according to the latest IDF guidelines, is post-meal glucose, thereby warranting its assessment and treatment when found at abnormally elevated levels. Nevertheless, healthcare professionals should bear in mind that targeting both post-meal and basal plasma glucose, giving equal consideration to both of them, is probably the best strategy for achieving optimal glycaemic control and thus preventing or reducing the risk of diabetic complications.
Article
Study objective: To evaluate the effect of acarbose on glycemic control and glycemic variability, using a continuous glucose-monitoring system, in patients with type 2 diabetes mellitus who were not well controlled on metformin and vildagliptin therapy. Design: Multicenter, randomized, double-blind, placebo-controlled study. Setting: Clinical research units at three hospitals in Italy. Patients: Fifty-three patients with type 2 diabetes who were taking stable dosages of metformin 850 mg 3 times/day and vildagliptin 50 mg twice/day for at least 3 months and who were not adequately controlled with these therapies. Intervention: Patients were randomized to either placebo or acarbose 100 mg 3 times/day to be added to their metformin-vildagliptin regimen. Measurements and main results: Glycemic excursions were assessed by using a continuous glucose-monitoring system for 1 week. Glycemic control was estimated as the mean blood glucose (MBG) level, the area under the glucose concentration-time curve for a glucose level above 70 mg/dl (AUC above 70) or 180 mg/dl (AUC above 180), and the percentage of time that the glucose level was above 70 mg/dl (T above 70) or 180 mg/dl (T above 180). Intraday glycemic variability was assessed by the standard deviation of the blood glucose level, the mean amplitude of glycemic excursions (MAGE), the M value, and continuous overlapping net glycemic action. Day-to-day glycemic variability was assessed as the mean of daily difference (MODD). The MBG level was ~20 mg/dl lower in the acarbose group than in the placebo group (p<0.05), particularly during the postprandial period. The AUC above 70 did not significantly differ between the two groups, whereas the AUC above 180 was ~40% lower in the acarbose group than in the placebo group during the daytime (p<0.01). The T above 180 was significantly higher in the placebo group than in the acarbose group (31% vs 8%, p<0.01. Moreover, the standard deviation and MAGE values were significantly lower in the acarbose group. The MODD value was not significantly changed in either group, and no significant differences were recorded between groups. All adverse events were mild in both groups, with only a significantly greater frequency of flatulence noted in the acarbose group (5% with acarbose vs 0.5% with placebo, p<0.05). Conclusion: The addition of acarbose to metformin and vildagliptin background therapy in patients with inadequately controlled type 2 diabetes decreased intraday glycemic variability, especially postprandial variability, but it was not associated with a significant change in interday glycemic variability.
Article
Background: The variability of postprandial plasma glucose is an independent risk factor for diabetes. The type and amount of carbohydrate may be important determinants of glycemic control. The aim of the study was to compare the effects of different proportions of carbohydrate in breakfast on postprandial blood glucose fluctuations in impaired glucose regulation (IGR) and normal glucose tolerance (NGT) subjects. Subjects and methods: This is a cross-sectional study of two groups including 55 subjects with IGR and 78 individuals with NGT. Their recorded breakfast was sorted into low-carbohydrate (LC) (carbohydrate <45%), medium-carbohydrate (MC) (carbohydrate 45-65%), and high-carbohydrate (HC) (carbohydrate >65%) meals according to the proportion of carbohydrate. Glucose concentrations were continuously measured with a continuous glucose monitoring system, and parameters such as the incremental area under the curve (iAUC) of glucose and postprandial glucose excursion (PPGE) were calculated to evaluate postprandial glucose fluctuations. Results: The postprandial fluctuations of glucose increased gradually with increased proportions of carbohydrate in breakfast in both IGR and NGT subjects. For the MC and HC meals, iAUC, PPGE, postprandial glucose spike (PGS), and mean blood glucose were significantly greater than those in the NGT group (P<0.05), respectively. The median time to PGS and the time period in which glucose concentrations decreased to baseline after the MC and HC meals in the IGR group were significantly longer than those in the NGT group (P<0.01), respectively. Compared with the NGT subjects for the HC meal, the IGR subjects consuming the MC meal had greater PGS, range of glucose concentrations, SD, and PPGE (P<0.05). Conclusions: The proportion of carbohydrate in breakfast contributes to glucose excursions in the NGT and IGR subjects. In the IGR subjects, a HC meal should be avoided and a LC meal should be recommended to prevent development of diabetes.
Article
Objective:  To describe the development and characteristics of a food categorisation system and its application to guide advice for diabetes treatment.Design and methods:  Foods commonly consumed by 16 adults with diabetes were grouped by macronutrient content and type of fat to form a set of reference food groups for dietary advice. Means for energy and macronutrients from individual food groups were then used to construct an overall intake pattern targeting 8000 kJ and relative amounts of carbohydrate, protein and fat (saturated fatty acids (SFA) < 10%E and (polyunsaturated fatty acids) PUFA ∼ 10%E). Variation in energy and macronutrients contributed by all foods partitioned into each food group was assessed by the coefficient of variation of data on the whole diet.Results:  To differentiate between sources of fat, 13 food groups emerged and 10 were deemed acceptable to nutritional guidelines for diabetes treatment. The food group pattern was judged adequate for the achievement of dietary recommendations with low-potential variation in total energy (5%) and macronutrient proportions (protein 6%, fat 6%, carbohydrate 3%), but higher for fat types (SFA 22%, (monounsaturated fatty acids) MUFA 11%, PUFA 12%). Targeted proportions for fat types were achieved only when daily servings of PUFA-rich, oils, nuts and oily fish or soy were included in an ideal intake pattern.Conclusions:  In theory, a dietary pattern constructed from food group sources of macronutrients and individual fat types results in low-potential variation from recommended nutrient targets and, therefore, is appropriate to guide advice for the treatment of diabetes.
Article
High-volume endurance exercise (END) improves glycaemic control in type 2 diabetes (T2D) but many individuals cite 'lack of time' as a barrier to regular participation. High-intensity interval training (HIT) is a time-efficient method to induce physiological adaptations similar to END, but little is known regarding the effect of HIT in T2D. Using continuous glucose monitoring (CGM), we examined the 24-h blood glucose response to one session of HIT consisting of 10 × 60 s cycling efforts at ~90% maximal heart rate, interspersed with 60 s rest. Seven adults with T2D underwent CGM for 24-h on two occasions under standard dietary conditions: following acute HIT and on a non-exercise control day (CTL). HIT reduced hyperglycaemia measured as proportion of time spent above 10 mmol/l (HIT: 4.5 ± 4.4 vs. CTL: 15.2 ± 12.3%, p = 0.04). Postprandial hyperglycaemia, measured as the sum of post-meal areas under the glucose curve, was also lower after HIT vs. CTL (728 ± 331 vs. 1142 ± 556 mmol/l·9 h, p = 0.01). These findings highlight the potential for HIT to improve glycaemic control in T2D.
Article
We hypothesized that consuming eggs for breakfast would significantly lower postprandial satiety and energy intake throughout the day. Using a crossover design, 21 men, 20 to 70 years old, consumed 2 isoenergetic test breakfasts, in a random order separated by 1 week. The macronutrient composition of the test breakfasts were as follows: (EGG, % CHO/fat/protein = 22:55:23) and (BAGEL, % CHO/fat/protein = 72:12:16). Fasting blood samples were drawn at baseline before the test breakfast and at 30, 60, 120, and 180 minutes after breakfast. After 180 minutes, subjects were given a buffet lunch and asked to eat until satisfied. Subjects filled out Visual Analog Scales (VAS) during each blood draw and recorded food intake the days before and after the test breakfasts. Plasma glucose, insulin, and appetite hormones were analyzed at each time point. Subjects consumed fewer kilocalories after the EGG breakfast compared with the BAGEL breakfast (P< .01). In addition, subjects consumed more kilocalories in the 24-hour period after the BAGEL compared with the EGG breakfast (P < .05). Based on VAS, subjects were hungrier and less satisfied 3 hours after the BAGEL breakfast compared with the EGG breakfast (P < .01). Participants had higher plasma glucose area under the curve (P < .05) as well as an increased ghrelin and insulin area under the curve with BAGEL (P < .05). These findings suggest that consumption of eggs for breakfast results in less variation of plasma glucose and insulin, a suppressed ghrelin response, and reduced energy intake.
Article
The changes in blood glucose and plasma free fatty acid (FFA), insulin, and human growth hormone (HGH) concentrations in response to oral and intravenous glucose and intravenous insulin were measured at 7 a.m. and 7 p.m., on both occasions after a ten hour fast, in thirteen normal males and two juvenile diabetics. Basal concentration of plasma FFA was lower and that of plasma insulin higher in the morning than in the evening. Blood glucose and plasma HGH levels did not differ at these times. In the normal subjects, glucose tolerance was diminished and plasma insulin response was delayed in the evening. The delay was significantly less with intravenous glucose than with oral glucose. When compared with the usually accepted criteria for diagnosis of diabetes mellitus, the normal subjects responded in the evening as mild diabetics. Two juvenile-onset diabetics, who had virtually no increase in plasma insulin concentrations after ingestion or injection of glucose, showed no diurnal variation in glucose tolerance. No diurnal variation was seen in the blood glucose response to intravenously injected insulin or in the plasma clearance rate of insulin; these findings suggest that impairment in glucose tolerance in the evening is due to diminished early insulin response to glucose, rather than to abnormal handling of glucose or insulin. The effect of tolbutamide, phentolamine, and theophylline on the diurnal variation of glucose tolerance was studied. In four subjects, intravenous injection of tolbutamide induced a greater insulin response and a greater fall in the blood glucose concentration in the morning than in the evening. The disappearance rate of intravenously injected glucose and both early and delayed insulin responses to the glucose were enhanced to a much greater degree in the morning than in the evening by the simultaneous intravenous injection of tolbutamide. Intravenous infusion of phentolamine, an alpha-adrenergic blocking agent, in five subjects failed to influence responses to intravenous injection of glucose. Intravenous infusion of theophylline, which inhibits cyclic 3′5′-adenosine monophosphate phosphodiesterase activity, in five subjects potentiated the plasma insulin response to intravenous glucose in the evening but not in the morning; the substance did not influence the disappearance rate of glucose.
Article
To investigate the effects of fat and carbohydrate on appetite, food intake and gastric emptying with and without the influence of orosensory factors, a group of nine healthy, fasted male subjects took part in two separate paired experiments involving high-fat and high-carbohydrate radiolabelled soup preloads. In the first experiment subjects received direct intragastric isocaloric infusions of either a high-fat tomato soup or a high-carbohydrate tomato soup (400 kcal in 425 mL) over 15 min, on two occasions. In the second paired experiment subjects ingested the same high-fat and high-carbohydrate soup over 15 min. In both experiments ratings of hunger and fullness were recorded over a period of 135 min and gastric emptying was measured by scintigraphy. Food intake was evaluated from a test meal (yoghurt drink) given 2 h after the end of the soup infusion/ingestion. When soup was administered intragastrically (Experiment 1) both the high-fat and high-carbohydrate soup preloads suppressed appetite ratings from baseline, but there were no differences in ratings of hunger and fullness, food intake from the test meal, or rate of gastric emptying between the two soup preloads. When the same soups were ingested (Experiment 2), the high-fat soup suppressed hunger, induced fullness, and slowed gastric emptying more than the high-carbohydrate soup and also tended to be more effective at reducing energy intake from the test meal. The results of these studies demonstrate that orosensory stimulation plays an important role in appetite regulation, and also indicate that subtle differences in orosensory stimulation produced by particular nutrients may profoundly influence appetite and gastrointestinal responses.
Article
Oxidative stress and its contribution to low-density lipoprotein (LDL) oxidation have been implicated in the pathogenesis of vascular diabetic complications. However, the relationship between hyperglycemia, hyperinsulinemia, hyperlipidemia, and oxidative stress is still debated. If plasma glucose and/or insulin and/or lipid are some of the most important determinants of oxidative stress in diabetes, then their typical postprandial elevations in diabetes would be expected to favor oxidative stress and LDL oxidation. To test this hypothesis, in type 2 diabetic patients, we evaluated the effects of two different standard meals designed to produce different levels of postprandial hyperglycemia on the plasma oxidative status and LDL oxidation. The meals were administered in randomized order to each of 10 type 2 diabetic patients. Blood samples were collected at baseline and 60 and 120 minutes after the meals. In every sample, plasma levels of glucose, insulin, cholesterol, triglycerides, nonesterified fatty acids (NEFAs), malondialdehyde (MDA), and the total radical-trapping antioxidant parameter (TRAP) were measured. LDL susceptibility to oxidation was evaluated at baseline and after 120 minutes. Plasma glucose, insulin, triglycerides, and MDA increased and NEFAs and TRAP significantly decreased after either meal. The variations in plasma glucose, MDA, and TRAP were significantly greater and LDL was more susceptible to oxidation after the meal that produced a significantly higher degree of hyperglycemia. These results suggest that postprandial hyperglycemia may contribute to oxidative stress in diabetic patients, providing a mechanistic link between hyperglycemia and diabetic vascular disease.
Article
Postprandial hypertriglyceridemia and hyperglycemia are considered risk factors for cardiovascular disease. Evidence suggests that postprandial hypertriglyceridemia and hyperglycemia induce endothelial dysfunction through oxidative stress; however, the distinct role of these two factors is a matter of debate. Thirty type 2 diabetic patients and 20 normal subjects ate 3 different meals: a high-fat meal; 75 g glucose alone; and high-fat meal plus glucose. Glycemia, triglyceridemia, nitrotyrosine, and endothelial function were assayed during the tests. Subsequently, diabetics took 40 mg/d simvastatin or placebo for 12 weeks. The 3 tests were performed again at baseline, between 3 to 6 days after the start, and at the end of each study. High-fat load and glucose alone produced a decrease of endothelial function and an increase of nitrotyrosine in normal and diabetic subjects. These effects were more pronounced when high fat and glucose were combined. Short-term simvastatin treatment had no effect on lipid parameters but reduced the effect on endothelial function and nitrotyrosine observed during each different test. Long-term simvastatin treatment was accompanied by a lower increase in postprandial triglycerides, which was followed by smaller variations of endothelial function and nitrotyrosine during the tests. This study shows an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on endothelial function, suggesting oxidative stress as common mediator of such effect. Simvastatin shows a beneficial effect on oxidative stress and endothelial dysfunction, which may be ascribed to a direct effect as well as the lipid-lowering action of the drug.
Article
The effects of a carbohydrate-restricted diet on weight loss and risk factors for atherosclerosis have been incompletely assessed. We randomly assigned 132 severely obese subjects (including 77 blacks and 23 women) with a mean body-mass index of 43 and a high prevalence of diabetes (39 percent) or the metabolic syndrome (43 percent) to a carbohydrate-restricted (low-carbohydrate) diet or a calorie- and fat-restricted (low-fat) diet. Seventy-nine subjects completed the six-month study. An analysis including all subjects, with the last observation carried forward for those who dropped out, showed that subjects on the low-carbohydrate diet lost more weight than those on the low-fat diet (mean [+/-SD], -5.8+/-8.6 kg vs. -1.9+/-4.2 kg; P=0.002) and had greater decreases in triglyceride levels (mean, -20+/-43 percent vs. -4+/-31 percent; P=0.001), irrespective of the use or nonuse of hypoglycemic or lipid-lowering medications. Insulin sensitivity, measured only in subjects without diabetes, also improved more among subjects on the low-carbohydrate diet (6+/-9 percent vs. -3+/-8 percent, P=0.01). The amount of weight lost (P<0.001) and assignment to the low-carbohydrate diet (P=0.01) were independent predictors of improvement in triglyceride levels and insulin sensitivity. Severely obese subjects with a high prevalence of diabetes or the metabolic syndrome lost more weight during six months on a carbohydrate-restricted diet than on a calorie- and fat-restricted diet, with a relative improvement in insulin sensitivity and triglyceride levels, even after adjustment for the amount of weight lost. This finding should be interpreted with caution, given the small magnitude of overall and between-group differences in weight loss in these markedly obese subjects and the short duration of the study. Future studies evaluating long-term cardiovascular outcomes are needed before a carbohydrate-restricted diet can be endorsed.
Article
It is not known how a low-carbohydrate, high-protein, high-fat diet causes weight loss or how it affects blood glucose levels in patients with type 2 diabetes. To determine effects of a strict low-carbohydrate diet on body weight, body water, energy intake and expenditure, glycemic control, insulin sensitivity, and lipid levels in obese patients with type 2 diabetes. Inpatient comparison of 2 diets. General clinical research center of a university hospital. 10 obese patients with type 2 diabetes. Usual diets for 7 days followed by a low-carbohydrate diet for 14 days. Body weight, water, and composition; energy intake and expenditure; diet satisfaction; hemoglobin A1c; insulin sensitivity; 24-hour urinary ketone excretion; and plasma profiles of glucose, insulin, leptin, and ghrelin. On the low-carbohydrate diet, mean energy intake decreased from 3111 kcal/d to 2164 kcal/d. The mean energy deficit of 1027 kcal/d (median, 737 kcal/d) completely accounted for the weight loss of 1.65 kg in 14 days (median, 1.34 kg in 14 days). Mean 24-hour plasma profiles of glucose levels normalized, mean hemoglobin A1c decreased from 7.3% to 6.8%, and insulin sensitivity improved by approximately 75%. Mean plasma triglyceride and cholesterol levels decreased (change, -35% and -10%, respectively). The study was limited by the short duration, small number of participants, and lack of a strict control group. In a small group of obese patients with type 2 diabetes, a low-carbohydrate diet followed for 2 weeks resulted in spontaneous reduction in energy intake to a level appropriate to their height; weight loss that was completely accounted for by reduced caloric intake; much improved 24-hour blood glucose profiles, insulin sensitivity, and hemoglobin A1c; and decreased plasma triglyceride and cholesterol levels. The long-term effects of this diet, however, remain uncertain.
Article
It’s a great honor to join the exceptional club of Banting Award winners, many of whom were my role models and mentors. In addition, giving the Banting Lecture also has a very personal meaning to me, because without Frederick Banting, I would have died from type 1 diabetes when I was 8 years old. However, it was already apparent at the time I was diagnosed that for too many people like me, Banting’s discovery of insulin only allowed them to live just long enough to develop blindness, renal failure, and coronary disease. For example, when I started college, the American Diabetes Association’s Diabetes Textbook had this to say to my parents: “The person with type 1 diabetes can be reassured that it is highly likely that he will live at least into his 30s.” Not surprisingly, my parents did not find this particularly reassuring. At the same time we were reading this in 1967, however, the first basic research discovery about the pathobiology of diabetic complications had just been published in Science the previous year. In my Banting Lecture today, I am thus going to tell you a scientific story that is also profoundly personal. I’ve divided my talk into three parts. The first part is called “pieces of the puzzle,” and in it I describe what was learned about the pathobiology of diabetic complications starting with that 1966 Science paper and continuing through the end of the 1990s. In the second part, I present a unified mechanism that links together all of the seemingly unconnected pieces of the puzzle. Finally, in the third part, I focus on three examples of novel therapeutic approaches for the prevention and treatment of diabetic complications, which are all based on the new paradigm of a unifying mechanism for the pathogenesis of diabetic complications. …
Article
To assess the efficacy and safety of initial combination therapy with sitagliptin and metformin in patients with type 2 diabetes and inadequate glycemic control on diet and exercise. In a 24-week, randomized, double-blind, placebo-controlled, parallel-group study, 1,091 patients with type 2 diabetes and A1C 7.5-11% were randomized to one of six daily treatments: sitagliptin 100 mg/metformin 1,000 mg (S100/M1000 group), sitagliptin 100 mg/metformin 2,000 mg (S100/M2000 group), metformin 1,000 mg (M1000 group), metformin 2,000 mg (M2000 group) (all as divided doses administered twice daily [b.i.d.]), sitagliptin 100 mg q.d. (S100 group), or placebo. Patients who had an A1C >11% or a fasting glucose value >280 mg/dl after the run-in period were not eligible to be randomized; these patients could participate in an open-label substudy and were treated with S100/M2000 for 24 weeks. The mean baseline A1C was 8.8% in the randomized patients. The placebo-subtracted A1C change from baseline was -2.07% (S100/M2000), -1.57% (S100/M1000), -1.30% (M2000), -0.99% (M1000), and -0.83% (S100) (P < 0.001 for comparisons versus placebo and for coadministration versus respective monotherapies). The proportion of patients achieving an A1C <7% and <6.5% was 66 and 44%, respectively, in the S100/M2000 group (P < 0.001 vs. S100 or M2000). For the open-label cohort (n = 117; baseline A1C 11.2%) treated with S100/M2000, the within-group mean A1C change from baseline was -2.9%. The incidence of hypoglycemia was low (0.5-2.2%) across active treatment groups and not significantly different from that in the placebo group (0.6%). The incidence of gastrointestinal adverse experiences was similar for coadministration therapies compared with their respective metformin monotherapy. The initial combination of sitagliptin and metformin provided substantial and additive glycemic improvement and was generally well tolerated in patients with type 2 diabetes.
Article
In experiment 1, normal weight male subjects were provided with three types of breakfast consumed in the Human Appetite Research Unit on separate experimental days 1 week apart. The intensity of hunger, fullness and other subjective feelings were tracked by means of visual analogue rating scales at intervals during the day. Energy and nutrient intakes were measured directly from ad libitum test meals consumed at lunch and dinner. During the rest of the day and until after breakfast the following day, food intake was measured indirectly through weighted food records. The test breakfasts comprised a basic meal 184 1 kJ (440 kcal) and the same meal supplemented with similar amounts of either fat (1515 kJ, 362 kcal) or carbohydrate (1527 kJ, 365 kcal). No differences were detected between the effects of the basic breakfast compared with the fat-supplemented breakfast. The carbohydrate supplement suppressed hunger ratings during a limited period after consumption (the post-ingestive window coinciding with the expected metabolism of carbohydrate. In experiment 2, a direct test of consumption during this post-ingestive window confirmed that the carbohydrate supplemented breakfast suppressed intake but the fat supplement did not. These results demonstrate that carbohydrate and fat can produce quiet different effects on satiety. Under these experimental conditions the supplement of fat produced no detectable effect on the expression of appetite and illustrates how dietary fat could lead to passive over-consumption of energy. However this effect may be modified by the particular pattern of food consumption during the course of a day.
Article
Diabetes is characterized by glycemic disorders that include both sustained chronic hyperglycemia and acute glucose fluctuations. There is now cogent evidence for the deleterious effects of sustained chronic hyperglycemia that results in excessive protein glycation and generation of oxidative stress. The role of glucose variability from peaks to nadirs is less documented, but there are many reasons to think that both upward (postprandial) and downward (interprandial) acute fluctuations of glucose around a mean value activate the oxidative stress. As a consequence, it is strongly suggested that a global antidiabetic strategy should be aimed at reducing to a minimum the different components of dysglycemia (i.e., A1C, fasting and postprandial glucose, as well as glucose variability). All the therapeutic agents that act on postprandial glucose excursions seem of particular interest for reducing the latter parameter (i.e., the glucose instability). Particular attention should be paid to such emerging therapeutic agents as the glucagon-like peptide 1 agonists and the dipeptidyl peptidase (DPP)-IV inhibitors that act through the incretin pathway.
Glycemic variability
  • Monnier
Association AD. Nutrition principles and recommendations in diabetes
Association AD. Nutrition principles and recommendations in diabetes. Diabetes care 2004;27(suppl 1):s36-s.
Dietary fat and appetite: similarities and differences in the satiating effect of meals supplemented with either fat or carbohydrate
  • J R Cotton
  • V J Burley
  • J A Weststrate
  • J E Bhmdell
Cotton JR, Burley VJ, Weststrate JA, Bhmdell JE. Dietary fat and appetite: similarities and differences in the satiating effect of meals supplemented with either fat or carbohydrate. J Hum Nutr Diet 1994;7(1):11-24.
Dietary fat and appetite: similarities and differences in the satiating effect of meals supplemented with either fat or carbohydrate
  • Cotton