No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
The Loss of Postprandial Glycemic Control Precedes Stepwise Deterioration of Fasting With Worsening Diabetes
Abstract
The aim of the study was to determine whether the loss of fasting and postprandial glycemic control occurs in parallel or sequentially in the evolution of type 2 diabetes.
In 130 type 2 diabetic patients, 24-h glucose profiles were obtained using a continuous glucose monitoring system. The individuals with type 2 diabetes were divided into five groups according to A1C levels: 1 (<6.5%, n = 30), 2 (6.5-6.9%, n = 17), 3 (7-7.9%, n = 32), 4 (8-8.9%, n = 25), and 5 (> or =9%, n = 26). The glucose profiles between the groups were compared. The overall glucose concentrations for the diurnal, nocturnal, and morning periods, which represent the postprandial, fasting, and the dawn phenomenon states, respectively, were also compared.
Glucose concentrations increased steadily from group 1 to 5 in a stepwise manner. The initial differences in mean glucose concentrations reaching statistical significance occurred 1) between groups 1 and 2 (6.4 vs. 7.7 mmol/l, P = 0.0004) for daytime postprandial periods, followed by differences; 2) between groups 2 and 3 (7.5 vs. 9.3 mmol/l, P = 0.0003) for the morning periods (dawn phenomenon); and finally 3) between groups 3 and 4 (6.3 vs. 8.4 mmol/l, P < 0.0001) for nocturnal fasting periods.
The deterioration of glucose homeostasis in individuals with type 2 diabetes progressed from postprandial to fasting hyperglycemia following a three-step process. The first step related to the three diurnal postmeal periods considered as a whole, the second step occurred during the morning period, and the third and final step corresponded to sustained hyperglycemia over the nocturnal fasting periods. Such a description of the key stages in the evolution of type 2 diabetes may be of interest for implementing antidiabetes treatment.
... The modulation function governing endogenous glucose production during overnight fasting was considered to be specific to T2DM and excluded from the T1DM model. 24 In turn, an additional feedback compartment was introduced to account for the increased gluconeogenesis after exogenous insulin administration in T1DM. This feedback follows the dynamics of the plasma insulin with a delay and allows to describe the short-term plasma glucose recovery after the administration of various mixtures of insulin aspart and lispro. ...
... The model could describe the long-term benefits of dapagliflozin treatment when compared to the observed data from phase III clinical trials; however, the trend in the observed HbA1c data apparently follows a nonlinear pattern of an initial 0.6% decline (weeks 4-12) with a subsequent increase by ~0.2% (weeks [18][19][20][21][22][23][24], also noted in another publication. 48 Assuming that the insulin and dapagliflozin doses are stable throughout the 24-week period, the model is unable to capture this behavior. ...
Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by abnormally high blood glucose concentrations due to dysfunction of the insulin-producing beta-cells in the pancreas. Dapagliflozin, an inhibitor of renal glucose reabsorption, has the potential to improve often suboptimal glycemic control in patients with T1DM through insulin-independent mechanisms and to partially mitigate the adverse effects associated with long-term insulin administration. In this work, we have adapted a systems pharmacology model of type 2 diabetes mellitus to describe the T1DM condition and characterize the effect of dapagliflozin on short- and long-term glycemic markers under various treatment scenarios. The developed platform serves as a quantitative tool for the in silico evaluation of the insulin-glucose-dapagliflozin crosstalk, optimization of the treatment regimens, and it can be further expanded to include additional therapies or other aspects of the disease.
... Hind Furaij Al Otaibi et al.,2020 Pharmacophore, 11(4) 2020, Pages 113-127 controlling blood glucose levels is through expanding physical activity [10][11][12]. It has shown that enhancements in fasting blood glucose levels, normal 24-hour blood glucose level, in addition to the post-prandial glycemic reaction after moderateforce exercise training [12,13]. ...
... Physical inactivity is a significant risk factor for type-2diabetes [16]. Moreover, physical exercise has been shown to improve diabetes control [9][10][11]. Hence, this research was designed to explore an essential factor both in the prevention and control of type-2 diabetes, i.e., physical activity. ...
Background: It is properly established that physical activity is a powerful non-pharmacological interference to enhance diabetes manipulation and should be an integral component of the care strategy of diabetic patients. Aim Of The Study: To explore a potential strategy for diabetes control and avoidance of diabetes-related complications through the encouragement of physical activity about style two diabetes mellitus. Objectives: To evaluate knowledge, attitude, and practice of style two (DM) patients attending primary healthcare centers (PHCCs) in Jeddah city, regarding physical activity. Methods: A cross-sectional descriptive study was carried out among a multistage random sample of type-2 diabetic patients registered at “Al-Rehab” and “Al-Safa-2”PHCCs in Jeddah city, Saudi Arabia. The data collection tool included four parts; socio-demographic and medical data, nineteen True/False questions on knowledge regarding physical activity, five statements related to attitude toward physical activity, and the General Practice Physical Activity Questionnaire (GPPAQ) to assess the practice of physical exercise among the participants. Results: The study included 223 types, 2 diabetic patients. Their age ranged between 18 and 87 years (47.6±14.1 years). Their total knowledge score about physical activity ranged between 11 and 17 with a median (IQR) of 12 (10- 14). Professional workers (p=0.022) and patients with higher income p=0.034) were more knowledgeable than their counterparts. Saudi patients expressed more positive attitude than non- Saudis, p-0.001. The commonest reported barriers for practicing physical exercise were not having energy which helps to do exercises (43.9%). Conclusion: Awareness about the physical activity of style two diabetics is overall acceptable. Their attitude toward physical activity is encouraging. However, their physical activity practice is deficient.
... It was appreciated that measurement of glycated haemoglobin (Hb1Ac) was predictive of both the development and progression of the microvascular complications of diabetes, so that management should, ideally, be targeted to achieve a Hb1Ac ≤ 7.0% or even less. Moreover, as a result of the seminal work by Monnier et al [5], it was recognised that the contribution of postprandial blood glucose excursions to Hb1Ac is substantial, and when Hb1Ac is ≤ 7.5% it is the dominant determinant. Approaches to management were also essentially 'glucocentric' with the aim of delaying, if not preventing, microvascular complications. ...
This editorial is stimulated by the article by Alqifari et al published in the World Journal of Diabetes (2024). Alqifari et al focus on practical advice for the clinical use of glucagon-like-peptide-1 (GLP-1) receptor agonists (GLP-1RAs) in the management of type 2 diabetes and this editorial provides complementary information. We initially give a brief historical perspective of the development of GLP-1RAs stimulated by recognition of the ‘incretin effect’, the substantially greater insulin increase to enteral when compared to euglycaemic intravenous glucose, and the identification of the incretin hormones, GIP and GLP-1. In addition to stimulating insulin, GLP-1 reduces postprandial glucose levels by slowing gastric emptying. GLP-1RAs were developed because native GLP-1 has a very short plasma half-life. The majority of current GLP-1RAs are administered by subcutaneous injection once a week. They are potent in glucose lowering without leading to hypoglycaemia, stimulate weight loss in obese individuals and lead to cardiovascular and renal protection. The landscape in relation to GLP-1RAs is broadening rapidly, with different formulations and their combination with other peptides to facilitate both glucose lowering and weight loss. There is a need for more information relating to the effects of GLP-1RAs to induce gastrointestinal symptoms and slow gastric emptying which is likely to allow their use to become more effective and personalised.
... However, it is still controversial whether it is more beneficial to target postprandial or fasting blood glucose concentrations, with basal insulin. Monnier et al. (21,22) provided data to explain the relative contribution of fasting and postprandial blood glucose to HbA1C in patients with mild-to-moderate hyperglycemia (A1C <7.5%) than in those with more severe hyperglycemia Insulin therapy in type 2 diabetes can range from a single daily injection to basal-bolus replacement regimens with multiple daily injections. Insulin glargine is a long-acting insulin analog that is widely used in clinical practice for basal insulin replacement. ...
Unfortunately, a Significant number of type 2 diabetic patients on oral hypoglycemic agents are not achieving the desired and recommended target of glycemic control in terms of reduction of HbA1c and fasting plasma glucose, this is largely because most of them are reluctant to use insulin injections for many reasons, mainly the painful injection, fear of hypoglycemia or inability to adapt to a complex regimen of multiple insulin injections. it has been recommended by many diabetes associations ( the American diabetes association(ADA) and the European association for the study of diabetes(EASD) ), in their algorithm of management of hyperglycemia in patients with uncontrolled diabetes (HbA1c < 7 %) to add a basal ( long acting) insulin to their oral drug regimen as a more simple initial step of adding insulin that is acceptable by most patients and capable of achieving target glycemic levels. insulin glargine is the preferred long acting insulin analogue for its pharmacodynamic properties (peakless action profile with low incidence of hypoglycemia and longer duration of action) , furthermore, its pen formulary makes it less painful than conventional human insulin syringe injections.
... Prediabetes is characterized by decreased metabolic flexibility, which impairs the ability to respond to blood glucose changes (13). Since decreased metabolic flexibility and altered postprandial metabolite profiles may be present years before prediabetes develops (14), metabolite levels after a glucose challenge may be more informative for prediabetes risk in young people than fasting metabolites. ...
OBJECTIVE
Prediabetes in young people is an emerging epidemic that disproportionately impacts Hispanic populations. We aimed to develop a metabolite-based prediction model for prediabetes in young people with overweight/obesity at risk for type 2 diabetes.
RESEARCH DESIGN AND METHODS
In independent, prospective cohorts of Hispanic youth (discovery; n = 143 without baseline prediabetes) and predominately Hispanic young adults (validation; n = 56 without baseline prediabetes), we assessed prediabetes via 2-h oral glucose tolerance tests. Baseline metabolite levels were measured in plasma from a 2-h postglucose challenge. In the discovery cohort, least absolute shrinkage and selection operator regression with a stability selection procedure was used to identify robust predictive metabolites for prediabetes. Predictive performance was evaluated in the discovery and validation cohorts using logistic regression.
RESULTS
Two metabolites (allylphenol sulfate and caprylic acid) were found to predict prediabetes beyond known risk factors, including sex, BMI, age, ethnicity, fasting/2-h glucose, total cholesterol, and triglycerides. In the discovery cohort, the area under the receiver operator characteristic curve (AUC) of the model with metabolites and known risk factors was 0.80 (95% CI 0.72–0.87), which was higher than the risk factor-only model (AUC 0.63 [0.53–0.73]; P = 0.001). When the predictive models developed in the discovery cohort were applied to the replication cohort, the model with metabolites and risk factors predicted prediabetes more accurately (AUC 0.70 [95% CI 40.55–0.86]) than the same model without metabolites (AUC 0.62 [0.46–0.79]).
CONCLUSIONS
Metabolite profiles may help improve prediabetes prediction compared with traditional risk factors. Findings suggest that medium-chain fatty acids and phytochemicals are early indicators of prediabetes in high-risk youth.
... Dapagliflozin significantly reduced both fasting and postprandial hyperglycemia, which are important to achieve optimal glucose control and to prevent microvascular and macrovascular complications, as it has been confirmed the role of postprandial hyperglycemia with the development of long-term complications, cardiovascular morbidity and mortality in T2DM (Heine et al., 2004) (Monnier et al., 2007). In addition, postprandial hyperglycemia was found to influence HbA1c more and faster than fasting hyperglycemia when HbA1c levels approach target values (Faruqui, 2017). ...
Evaluate the efficacy of dapagliflozin on glycaemic and non-glycaemic indices and assess quality of life in type 2 diabetes patients (T2DM) with inadequate glycaemic control on three oral antidiabetic agents (OADs). Patients with uncontrolled type 2 diabetes [Haemoglobin A1c 7.0%-12.0%] on sulfonylurea, metformin and gliptin were selected to receive dapagliflozin 5mg/day for 16 weeks (n=40). Fasting and postprandial plasma glucose, glycated haemoglobin A1c, body weight, and waist circumference were measured. Assessment of patients’ quality of life was performed using Quality of Life Scale for Iraqi Diabetic patients (QOLSID) at baseline and after administration of dapagliflozin. Dapagliflozin showed high significant reduction in fasting and postprandial plasma glucose, glycated haemoglobin A1c (HbA1c), body mass index (BMI) and index of central obesity (ICO) (p<0.001). High significant changes in the QOLSID score after treatment (p<0.001). High BMI is negative predictor for patients’ quality of life. Dapagliflozin improved both glycaemic and non-glycaemic parameters in T2DM patients who already on three OADs. This is promising results in short period makes the treatment a suitable alternative to insulin specially in patients not prefer to use injected medication. Dapagliflozin showed an improvement in the patients’ physical and psychological condition and consequently overall QOL.
... In T2D, to a certain degree, the measurement of non-fasting blood glucose is more valuable than that of fasting glucose. Monnier et al. [15]. reported that the deterioration of glucose homeostasis progressed from postprandial to fasting hyperglycemia. ...
... Treatment with basal insulin enables proper glycemic control in about 50-60% of people with T2D uncontrolled by OADs only [23]. In the remaining cases, we consider adding prandial insulin injections or exploring the full potential of combining ''new'' glucose-lowering agents, like GLP-1 RAs among them, with basal insulin [24,25]. On the basis of these facts, Rosenstock et al. performed an open-label, multinational, multicenter, randomized, parallel-group clinical trial (LixiLan-O study) in a group of 1170 people with T2D receiving a suboptimal treatment (mean baseline HbA 1c = 8.1%) with metformin and/or other oral antidiabetic agents [21]. ...
iGlarLixi is a fixed-ratio combination of insulin glargine 100 U/mL and lixisenatide used in the treatment of type 2 diabetes. iGlarLixi has proven clinical benefits in terms of glycemia, weight control, and safety, defined by the risk of hypoglycemia. It simultaneously targets many pathophysiologic abnormalities which are at the root of type 2 diabetes and thus presents a complementary mode of action. Finally, it may also address diabetes treatment burden, and, by decreasing the complexity of treatment, it may improve patient adherence and persistence and fight against clinical inertia. This article reviews the results of major randomized controlled trials in people with type 2 diabetes that compared iGlarLixi to other therapeutic regimens, representing different intensification strategies, such as basal supported oral therapy, oral antidiabetic drugs, and a combination of the latter with glucagon-like peptide 1 receptor agonists. Moreover, as a supplement to randomized trials, data from real-world evidence have also been included.
... Instead, organizations began to focus on the numerous prospective and retrospective studies that clearly showed the relationship between postprandial glucose and the chronic complications of diabetes. [28][29][30][31][32][33][34] These studies and others were foundational for the International Diabetes Foundation (IDF) Postmeal Glucose guidelines, published in 2007. 35 Ongoing digitization of health care data has led to the development of massive databases that can be easily queried to assess demographic information, medical records, pharmacy prescriptions, outpatient care, hospitalizations, and emergency department utilization for large groups of patients. ...
Diabetes technologies such as continuous glucose monitoring (CGM) continue to evolve at an increasingly rapid pace. Seventeen new CGM devices have been introduced to the market during the past decade. The introduction of each new system is supported by well-designed randomized controlled trials and real-world retrospective and prospective studies. However, translation of the evidence into clinical guidelines and coverage policies often lags. This article reviews the major limitations of the current approach to clinical evidence assessment and presents a more appropriate method for evaluating rapidly evolving technologies such as CGM.
... In the present study, a significant increase in ∆Cor was observed in the BS group, but not in the XR group. Appropriate postbreakfast glucose management is thought to contribute substantially to improving diurnal glucose fluctuations, and thus HbA1c levels [11,22]. Based on the results of this study, XR is considered a better choice for longacting insulin because it stabilizes nocturnal glucose levels and improves post-breakfast glucose levels. ...
We investigated the pathophysiology of the dawn phenomenon by examining the effects of changes in blood glucose levels from late night to early morning on various hormones in a group taking glargine BS and a group taking Lantus XR, with the goal of achieving better glycemic control. Patients with types 1 and 2 diabetes scheduled for inpatient education were divided into BS and XR groups. Blood glucose levels were tracked from 0:00 to 7:00, while blood samples were extracted at 3:00 and 7:00 to measure glucose levels and hormones related to the dawn phenomenon. Overall, we analyzed blood sample and intermittently scanned Continuous Glucose Monitoring data of 43 and 40 patients, respectively. From 0:00 to 7:00, the mean blood glucose was significantly lower in the BS group, although the fluctuation was similar (p < 0.0001). The BS group also exhibited significantly higher ∆ACTH (p = 0.0215) and ∆ cortisol (p = 0.0430) than the XR group. In the BS group, ∆Glu exhibited a significant negative correlation with ∆ACTH and ∆cortisol (p = 0.0491). Similar findings were not observed in the XR group. These results suggest that XR may be a better choice for long-acting insulin since it is less likely to induce cortisol secretion. Further, analysis of the dawn phenomenon and non-dawn phenomenon groups showed the mean CPR levels at 3:00 and 7:00 were significantly higher in the latter (p = 0.0135). This supports the conventional belief that appropriate basal insulin replacement therapy is a beneficial treatment for the dawn phenomenon.
... 5 Since 2003, debates on contribution of postprandial glucose excursions and basal glucose increments to overall hyperglycemia have been pivotally initiated. [6][7][8][9] However, most of these studies have focused on type 2 diabetes (T2D) particiapnts treated with or without insulin, 10 or mixed cohorts but composed of only a small percentage of T1D populations, 8 or analyzed glucose exposure from limited 24-hour or single glucose value collected via fingerstick blood glucose monitoring (see Supplementary Table S1). Evidence for the exact contribution of daily postprandial glucose exposure in HbA1c in individuals with T1D is few, [11][12][13] with even less for Asian populations. ...
Aim:
Evidence for contribution of basal and postprandial glucose increment, and glycemic variability to glycated hemoglobin (HbA1c) among adults with type 1 diabetes (T1D) is limited. This study aimed to capture glycemic fluctuation patterns and quantify contributions of these factors to HbA1c levels among adults with T1D.
Methods:
HbA1c, continuous glucose monitoring (CGM), and diet diaries were collected and pooled from two clinical trials. Available data sets were divided into HbA1c quartiles: group 1 (≤6.7%), group 2 (6.7%-7.3%), group 3 (7.3%-7.8%), and group 4 (≥7.8%). Area under curve above 110 mg/dL (AUC>110mg/dL ) in 24-h profile was defined as overall hyperglycemia and stratified with postprandial hyperglycemia (PHG, AUC>110mg/dL in 3-h period after meals) and basal hyperglycemia (BHG, AUC>110mg/dL in remaining period). Linear regression analysis was used to estimate the proportion of variance in HbA1c explained by BHG, preprandial glucose, PHG, glycemic variability, and non-glycemic factors (age, body mass index, hemoglobin, and duration).
Results:
A total of 169 550 glucose data in 2409 meals recorded from 102 patients (male/female, 34/68) were included. Age and duration were 35.2 ± 12.6 and 8.9 (2.9, 13.0) years, with 51.0% using pumps. Overall, BHG was four times higher than PHG (p all <.05) and between-group comparisons showed BHG exhibited a progressive increase (group 1 vs. 2, 3, 4, p = .053, .086, .006) with fasting contribution of 76.1%, 82.6%, 81.5%, and 84.3% from group 1 to 4. The increment was not significant among groups 2, 3, and 4 (p > .05). Factors included in analysis explained a total of 74% of the variance in HbA1c, in which BHG accounted for 32.1% of variance whereas PHG accounted for 24.4%. In group with HbA1c >7.3%, BHG accounted for a higher percentage with 33.8% of the variance in HbA1c.
Conclusions:
In our study, basal hyperglycemia better predicts overall glycemic control than postprandial hyperglycemia among adults with T1D. The relative contribution of basal hyperglycemia increased gradually with HbA1c increasing and predominant strategy for insulin titration among T1D is different among different levels of glycemic control.
... With the development of the continuous glucose monitoring (CGM) technique, several studies found that the glucose fluctuation and post-prandial glucose excursions were significantly higher in women diagnosed with GDM during pregnancy and with normal glucose tolerance by OGTT at post-partum follow-up, as compared to women with normal glucose metabolism during pregnancy (6,7). Glucose fluctuations during post-prandial periods exhibited a more specific triggering effect on oxidative stress than chronic sustained hyperglycemia, promoting the development and progression of T2DM (8,9). Thus, it is suggested that interventional trials in such a population should be initiated early after delivery, targeting not only HbA1c and mean glucose concentrations but also acute post-prandial glucose excursions (10). ...
Background
Increased post-prandial glycemic excursions contribute to the development of diabetes and have been observed in women with recent gestational diabetes mellitus (GDM) and with normal glucose tolerance at post-partum. As a convenient meal replacement, low-GI biscuits are helpful for improving glycemic excursions in patients with type 2 diabetes. However, it is unknown whether low-GI biscuits as pre-loads or mid-meal snacks have a better effect in diminishing post-prandial glycemic excursions from the individual level in women with recent GDM. Therefore, the aim of this trial is to tailor a better dietary strategy utilizing low-GI biscuits (Fitmeal) to improve post-prandial glycemic excursions through within-subject comparison in such a population and observe the long-term effect of a tailored dietary approach in glycemic control.
Methods
We have designed a two-phase trial including a randomized, crossover, non-blinded trial in the first phase, followed by a 4-week tailored intervention in the second phase. A total of 52 post-partum women with recent GDM will be allocated into four meal plans: (1) Fitmeal pre-load 30 min before standard lunch meal (P+L), (2) Fitmeal as a mid-meal snack 2 h before standard lunch meal (S+L), (3) isocaloric standard control with co-ingestion of Fitmeal and standard lunch meal (CL) at the same time, and (4) placebo control with 200 ml of water taken 30 min before standard lunch meal (W + L), on four consecutive days. Acute post-prandial glycemic response (PGR) measured by continuous glucose monitoring (CGM) will be compared among the four meals. In the second phase, all participants will receive a 4-week tailored intervention using Fitmeal as pre-loads or mid-meal snacks based on within-subject PGR results from the first phase. Glycemic metrics, dietary behaviors, and psychosocial factors (e.g., quality of life, self-efficacy, perceived stress, and depression) will be examined at baseline and end-point.
Discussion
This trial is expected to optimize the use of low-GI biscuits as pre-loads or mid-meal snacks in improving individual post-prandial glycemic excursions among women with recent GDM. Furthermore, the findings of this study will provide novel information on how to deliver an effective dietary intervention at the individual level and guide future clinical practice of medical nutrition therapy for diabetes prevention.
Trial registration number
Chinese clinical trial registry, ChiCTR2200060923.
... PPHG is defined as a sharp rise in plasma glucose concentrations following food intake and is influenced by many factors including the timing, quantity and composition of a consumed meal. [3] The state of post-prandial hyperglycemia begins when plasma glucose rises above the level of 140 mg/dL (7.8 mmol/L), One to two hours after ingestion of food in individuals without DM and >180 mg/dL (10.0 mmol/L) in individuals with DM. [4][5] A degree of fluctuation in blood glucose is common after food intake, especially with meals containing carbohydrate, but broadly speaking, in individuals without DM, glucose levels peak approximately 1 hour after the start of a meal and return to baseline within two to three hours. [6] Most meals peak below 140 mg/dl. ...
Continuous glucose monitoring has become a common adjunct in the management of Diabetes Mellitus. However, there has been a recent trend among individuals without diabetes using these devices as a means of monitoring their health. The increased visibility of glucose data has allowed users to study the effect lifestyle has upon post-prandial glucose levels. Although post-prandial hyperglycemia is well understood in the setting of diabetes, its impact in individuals without diabetes is less well defined. This article reviews those factors which contribute to post-prandial hyperglycemia in individuals without diabetes and how the data obtained from continuous glucose monitoring can be used to improve an individual's metabolic health.
... Eine Diabetestherapie ohne Insulin lässt nur bedingt eine Therapieanpassung zu, weshalb kein dauerhafter, sondern nur ein intermittierender Einsatz von CGM bei entsprechender Indikation adäquat erscheint. Aus den gewonnenen Glukoseprofilen kann auf den Krankheitsstatus des Typ-2-Diabetes bei dem jeweiligen MmD geschlossen werden, was vorteilhaft für den zielgerichteten Einsatz von Antidiabetika ist [34]. ...
... Specifically, in T1D, where the endogenous insulin secretion is absent or very low, the good glycemic control depends on rapid insulin bolus. In this way, today, several tactics have been proposed to optimize these insulin boluses [7][8][9][10]. ...
Background
A main factor contributing to insufficient glycemic control, during basal/bolus insulin therapy, is poor self-management bolus. Insulin bolus administration frequency is strongly associated with glycated hemoglobin (A1c) in Type 1 Diabetes (T1D). In the present study, we analyzed the performance of two-bolus calculator’s software that could be accessible to T1D patients from a Public Health Service to improve glycemic time in range (TIR) and A1c.
Methods
This prospective, controlled, randomized, parallel intervention clinical trial was carried out with 111 T1D participants on basal/bolus therapy [multiple daily insulin injections (MDI) or subcutaneous infusion pump (CSII)] with basal A1c ≥ 8.5% for 24 weeks. Patients were divided into 3 groups: 2 interventions: COMBO ® (bolus calculator) and GLIC (mobile application) and 1 control (CSII group). Anthropometrics and metabolic variables were assessed on basal, 3 and 6 months of follow-up.
Results
TIR was increased in 9.42% in COMBO group (29 ± 12% to 38.9 ± 12.7%; p < 0.001) in 8.39% in the GLIC® group (28 ± 15% to 36.6 ± 15.1%; p < 0.001) while remained stable in CSII group (40 ± 11% to 39.3 ± 10.3%). A1c decrease in 1.08% (p < 0.001), 0.64% (p < 0.001) and 0.38% (p = 0.01) at 6 months in relation to basal in the COMBO, GLIC and CSII respectively. Daily basal insulin dose was reduced by 8.8% (p = 0.01) in the COMBO group.
Conclusion
The COMBO and a mobile applicative (GLIC) bolus calculator had a similar and a good performance to optimize the intensive insulin treatment of T1D in the public health system with increase in the TIR and reduction in A1C without increase hypoglycemia prevalence.
... The findings suggested that the relative contribution of postprandial hyperglycemia decreased gradually while the relative contribution of fasting hyperglycemia increased progressively with increasing levels of HbA1c. These results also reflected a basic biological characteristic of T2DM: the postprandial hyperglycemia seemed to appear early in the natural history of T2DM, whereas the fasting hyperglycemia appeared later after further β-cell dysfunction [25]. Other studies also supported the relative contribution of postprandial hyperglycemia at lower HbA1c levels and fasting hyperglycemia at higher levels [26,27]. ...
Background:
To explore the correlations between glycosylated hemoglobin (HbA1c) and glucose levels in older adults with newly diagnosed type 2 diabetes mellitus (T2DM).
Methods:
A total of 783 participants aged ≥60 years were enrolled. The 75-g oral glucose tolerance test (OGTT) was conducted and HbA1c was measured. The participants were divided into normal glucose tolerance (NGT)HbA1c, Pre-DMHbA1c, and T2DMHbA1c groups based on the HbA1c diagnostic criteria. The correlations between HbA1c and glucose levels of the OGTT were analyzed.
Results:
When HbA1c ≥ 6.5% in older people, HbA1c was positively correlated with Glucose 0 min and 120 min of the OGTT (r = 0.335, 0.247; all p < 0.05, respectively). When HbA1c was between 5.7% and 6.4%, HbA1c was positively correlated with Glucose 0 min and 120 min (r = 0.298, 0.474; all p < 0.01, respectively). When HbA1c ≤ 5.6%, HbA1c was positively correlated with Glucose 0 min and 120 min (r = 0.301, 0.357; all p < 0.01, respectively). HbA1c was positively correlated with HOMA-IR (r = 0.368, p < 0.01), while it was negatively correlated with HOMA-β, ΔI30/ΔG30, IG120, and GDI(r = -0.267, -0.397,-0.364,-0.397; all p < 0.01, respectively). After adjustment for confounders, the correlations of HbA1c with Glucose 0 min and 120 min, insulin sensitivity and β-cell function indexes still existed. When HbA1c ≥ 6.5%, there were 93.3% T2DMOGTT and 6.7% Pre-DMOGTT subjects. When HbA1c < 6.5%, there were 17.7% T2DMOGTT, 39.5% Pre-DMOGTT (including 2.5% IFGOGTT, 36.1% IGTOGTT and 0.9% IGROGTT), and 42.8% NGTOGTT subjects.
Discussion:
When HbA1c ≥ 6.5% in older people, HbA1c shows the highest correlation with Glucose 0 min of the OGTT. When HbA1c < 6.5%, postprandial hyperglycemia is a main characteristic of older people, and HbA1c shows the highest correlation with Glucose 120 min of the OGTT.
... Saat ini, penyedia layanan kesehatan gagal mempertimbangkan fenomena fajar sebagai salah satu target dalam pengelolaan gangguan tersebut. Ada kemungkinan untuk memprediksi ada atau tidaknya fenomena fajar dengan menghitung penurunan atau kenaikan antara kadar glukosa sebelum sarapan dan yang diamati pada titik waktu sebelum makan lainnya (Louis Monnier, Colette, Dunseath, & Owens, 2007). ...
Early morning hyperglycaemia in diabetics can be caused by the dawn phenomenon, the Somogyi effect, or poor glycaemic control. The dawn phenomenon occurs when endogenous insulin secretion decreases or when the effect of exogenous insulin given to the patient the day before disappears, along with a physiological increase in insulin antagonist hormone. When people with diabetes eat too late at night, consume alcohol, or use insulin too late, it will cause a spike in blood sugar levels in the morning. This condition is known as the Somogyi effect and is caused by the human activity itself. The Somogyi effect is present in the case of excessive amounts of exogenous insulin. The dawn phenomenon is more common than the Somogyi effect. This research method uses a case study to explore the problem of nursing care in patients with diabetes mellitus at St Paul University Hospital, Philippines. Data were collected using interviews, observation, physical examination, and documentation. The data obtained were analysed by descriptive method, compiled from diagnosis to evaluation using three diabetic patients as sampling. To diagnose this dawn phenomenon, it is important for nurses to measure plasma glucose levels over several nights between 3 am and 5 am or use a continuous glucose monitoring system. Although the treatments are different, the best way to prevent the dawn phenomenon and the Somogyi effect is to control diabetes optimally with insulin therapy. It is hoped that nurses, clients, and families can monitor the patient's glucose levels periodically to prevent complications in diabetes. Keywords : Diabetic, Somogyi, Down Phenomenon Effect, case study
... Around 382 million individuals are viewed as living with diabetes from one side of the planet to the other, and scientific predictions reveal that the number will increase to around 471 million individuals by 2035 [19]. Postprandial hyperglycemia has been embroiled in the advancement of insulin opposition [20], being quite possibly the earliest marker of glucose homeostasis liberation [21]. Furthermore, hypertension, cardiovascular illness, and diabetic neuropathy are linked to this issue [22,23]. ...
Veronica (Plantaginaceae) and Schoenoplectus have a unique chemotaxonomic and phytochemical importance and are widely utilized in Turkish and Traditional Chinese Herbal Medicine (TCM) for treating tonics, influenza, diuretics, expectorants, restoratives, and respiratory diseases, and both are very useful in treating infectious and metabolic disorders as well. This study evaluates two medicinal plant species, Veronica biloba and Schoenoplectus triqueter (L.) Palla; extraction was performed through Soxhlet and maceration methods as well as determination of free and bound phenolics. Evaluated biological screening of (extracts and phenolics) angiotensin-I converting enzyme (ACE), Type-II diabetes (α-glucosidase and α-amylase), and antioxidants potential was performed using modified assays. The angiotensin-I converting enzyme (ACE) 50% inhibition potential in Veronica biloba was found at IC50 = 210.68 μg/mL and in Schoenoplectus triqueter (L.) Palla at IC50 = 229.40 µg/mL, respectively. Meanwhile Type-II diabetes with α-amylase 50% inhibition shown by bound phenolics of Veronica biloba at IC50 = 219.66 µg/mL and its water extract at IC50 = 110.09 µg/mL possesses higher potential, and α-glucosidase potential by free phenolics was found to be active at IC50 = 469.56 µg/mL, while water and ethyl acetate extracts showed higher potential, IC50 = 78.65 µg/mL and IC50 = 97.03 µg/mL, than the standard acarbose, recorded lower. In case of amylase, α-glucosidase showed IC50 = 88.73 μg/mL. Our results showed that both plants possess a direct relationship with the increase in the concentration of extracts and inhibited very strongly angiotensin-I converting enzyme (ACE) and Type-II diabetes (α-glucosidase and α-amylase). The properties of enzyme hindrance may be associated with phenolic compounds and rich phenolic plant antioxidant potential provides a route to the elucidation of natural antihypertension and antidiabetes.
... This way, the sample size could be attained at a minimal cost. The twohour OGTT clinical reference was chosen because it is is a more sensitive than either the FPG or HBA 1C tests and better at mimicing postprandial hyperglycemia, the earliest form of dysglycemia [19,20]. ...
Background and objectives
To understand the utility of glycated haemoglobin (HBA 1C ) in screening for diabetes and Abnormal Glucose Regulation (AGR) in primary care, we compared its performance to that of the fasting plasma glucose (FPG) test.
Methods
This was a prospective diagnostic accuracy study conducted in eastern Uganda. Patients eligible for inclusion were consecutive adults, 30–75 years, receiving care at the outpatient department of a general hospital in eastern Uganda. We determined the sensitivity, specificity and optimum cut-off points for HBA 1C and FPG tests using the oral glucose tolerance test (OGTT) as a clinical reference standard.
Results
A total of 1659 participants underwent FPG testing of whom 310 were also HBA 1C and OGTT tested. A total of 113 tested positive for diabetes and 168 for AGR on the OGTT. At recommended cut-off points for diabetes, the HBA 1C and FPG tests had comparable sensitivity [69.8% (95% CI 46.3–86.1) versus 62.6% (95% CI 41.5–79.8), respectively] and specificity [98.6% (95% CI 95.4–99.6) versus 99.4% (95% CI 98.9–99.7), respectively]. Similarly, the sensitivity of HBA 1C and the FPG tests for Abnormal Glucose Regulation (AGR) at ADA cut-offs were comparable [58.9% (95% CI 46.7–70.2) vs 47.7% (95% CI 37.3–58.4), respectively]; however, the HBA 1C test had lower specificity [70.7% (95% CI 65.1–75.8)] than the FPG test [93.5% (95% CI 88.6–96.4)]. At the optimum cut-offs points for diabetes [45.0 mmol/mol (6.3%) for HBA 1C and 6.4 mmol/L (115.2 mg/dl) for FPG], HBA 1C and FPG sensitivity [71.2% (95% CI 46.9–87.8) versus 72.7% (95% CI 49.5–87.8), respectively] and specificity [95.1% (95% CI91.8 97.2) versus 98.7% (95% CI 98.0 99.2), respectively] were comparable. Similarly, at the optimum cut-off points for AGR [42.0 mmol/mol (6.0%) for the HBA 1C and 5.5 mmol/l (99.0 mg/dl) for the FPG test], HBA 1C and FPG sensitivity [42.3% (95% CI 31.8–53.6) and 53.2 (95% CI 43.1–63.1), respectively] and specificity [89.1% (95% CI 84.1 92.7) and 92.7% (95% CI 91.0 94.1), respectively] were comparable.
Discussion
HBA 1C is a viable alternative diabetes screening and confirmatory test to the FPG test; however, the utility of both tests in screening for prediabetes in this outpatient population is limited.
... Insulin resistance and cardiovascular risk factors, including obesity, hyperlipidemia, and hypertension, are the hallmarks of T2DM pathogenesis (7-9). Given the epidemic of diabetes-related cardiovascular events and economic burden of T2DM, exploring cost-effective and promising therapeutic approaches should be of substantial importance (6)(7)(8)(9)(10). ...
Objective
Nigella sativa (N. sativa) from the family Ranunculaceae has medicinal properties. Previous studies have reported promising findings showing that N. sativa may benefit cardiometabolic health; however, current evidence on its cardiometabolic effects on those with prediabetes and type 2 diabetes mellitus (T2DM) is still unclear. Hence, we conducted a systematic review and meta-analysis to assess the efficacy of N. sativa on cardiometabolic parameters in population with prediabetes and T2DM.
Methods
PubMed/Medline, ISI Web of Science, Scopus, and Cochrane library were systematically searched up to June 20, 2022. Meta-analyses using random-effects models were used.
Results
Eleven randomized controlled trials (RCTs) were included in the meta-analysis. N. sativa intervention resulted in significant changes in fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), c-reactive protein (CRP), and malondialdehyde (MDA), without overall changes in glucose levels after oral glucose tolerance test (OGTT), fasting insulin, homeostatic model assessment of insulin resistance (HOMA-IR), triglyceride, high-density lipoprotein cholesterol (HDL-C), and body mass index (BMI) when compared with the control group. In subgroup analyses, N. sativa supplementation enhanced serum levels of HDL-C in subjects with baseline HDL-C lower than 40 mg/dL. Furthermore, HOMA-IR and BMI values decreased in the N. sativa-supplemented group compared with the control group, when the length of follow-up was more than 8 weeks and the dose was more than 1 g/day for N. sativa supplementation, respectively.
Conclusion
Our findings indicate that N. sativa supplementation may effectively improve cardiometabolic profiles in individuals with prediabetes and T2DM.
... In some cases, hypoglycaemia occurs in the period following food intake as a kind of rebond effect. This lack of a "quiet" blood glucose profile is due to the lack of endogenous insulin secretion (Monnier et al. 2007). The subject is totally dependent on the resorption of injected or infused insulins and life events such as emotions, annoyances, meals and physical activity are no longer compensated by the adaptation of insulin secretion. ...
In diabetes mellitus (DM), continuous glucose monitoring (CGM) linked to insulindelivery presents a major advance but is still limited by current algorithms and thenature of glucose sensors. DIABLO is a multidisciplinary project from diabetology, isletbiology, and microelectronics to automation control, with the objective to establish anew model of CGM (i) by high-resolution techniques to decipher and model islet'sendogenous algorithms, (ii) by design of novel control algorithms inspired byaeronautics and (iii) by the proof of concept of maintaining glucose homeostasis bythis hybrid biosensor. DIABLO will impact research by multi-physics system modellingand healthcare technology as well as life quality in DM by novel algorithms and aninnovative module for the artificial pancreas. The project will also advance for DM andother chronic diseases monitoring of stem-cell derived therapeutic means and thedevelopment of Organs-on-Chip.
... Postprandial glycemia may contribute as much or more than fasting blood glucose to the pathogenesis of impaired insulin sensitivity and insulin secretion seen in the progression towards type 2 diabetes [6,7]. Indeed, the loss of postprandial glucose control often manifests before derangements in fasting indices, along the path towards type 2 diabetes in at-risk individuals [8]. Therefore, strategies to attenuate postprandial glucose excursions may be of particular importance in the effort to reduce the global burden of disease. ...
A Mediterranean-style healthy eating pattern (MED-HEP) supports metabolic health, but the utility of including low-glycemic index (GI) foods to minimize postprandial glucose excursions remain unclear. Therefore, we investigated the relative contribution of GI towards improvements in postprandial glycemia and glycemic variability after adopting a MED-HEP. We conducted a randomized, controlled dietary intervention, comparing high- versus low-GI diets in a multi-national (Italy, Sweden, and the United States) sample of adults at risk for type 2 diabetes. For 12 weeks, participants consumed either a low-GI or high-GI MED-HEP. We assessed postprandial plasma glucose and insulin responses to high- or low-GI meals, and daily glycemic variability via continuous glucose monitoring at baseline and post-intervention. One hundred sixty adults (86 females, 74 males; aged 55 ± 11 y, BMI 31 ± 3 kg/m2, mean ± SD) with ≥two metabolic syndrome traits completed the intervention. Postprandial insulin concentrations were greater after the high-GI versus the low-GI test meals at baseline (p = 0.004), but not post-intervention (p = 0.17). Postprandial glucose after the high-GI test meal increased post-intervention, being significantly higher than that after the low-GI test meal (35%, p < 0.001). Average daily glucose concentrations decreased in both groups post-intervention. Indices of 24-h glycemic variability were reduced in the low-GI group as compared to baseline and the high-GI intervention group. These findings suggest that low-GI foods may be an important feature within a MED-HEP.
... The regulation of HGP and the mechanism(s) driving its increase in T2D are complex. No animal model can be said to faithfully recapitulate the human disease process, partly because the latter is likely heterogeneous and dynamic, i.e., it changes over the course of the disease depending on patient features, degree of glycemic control, and therapies employed (Monnier et al., 2007). Rodent models are a compromise choice: the benefits of being able to discover genes and manipulate their functions being offset by the more ''hepatocentric'' nature of murine glucose metabolism (Lauro et al., 1998) and by the glaring differences in lipid profiles . ...
Increased hepatic glucose production (HGP) contributes to hyperglycemia in type 2 diabetes. Hormonal regulation of this process is primarily, but not exclusively, mediated by the AKT-FoxO1 pathway. Here, we show that cAMP and dexamethasone regulate the high-mobility group superfamily member TOX4 to mediate HGP, independent of the insulin receptor/FoxO1 pathway. TOX4 inhibition decreases glucose production in primary hepatocytes and liver and increases glucose tolerance. Combined genetic ablation of TOX4 and FoxO1 in liver has additive effects on glucose tolerance and gluconeogenesis. Moreover, TOX4 ablation fails to reverse the metabolic derangement brought by insulin receptor knockout. TOX4 expression is increased in livers of patients with steatosis and diabetes and in diet-induced obese and db/db mice. In the latter two murine models, knockdown Tox4 decreases glycemia and improves glucose tolerance. We conclude that TOX4 is an insulin receptor-independent regulator of HGP and a candidate contributor to the pathophysiology of diabetes.
... Indeed, the peak value following breakfast is observed approximately at 70 min after the start of the meal in individuals with type 2 diabetes whereas the 2 h glucose value following breakfast is already within the decreasing glycaemic slope-an observation independent of the various HbA 1c concentrations. 27 37 and Look AHEAD (the Action for Health in Diabetes study) 38 suggest that, in type 2 diabetes, glucose variability is correlated with an increased risk of microvascular and macrovascular compli cations and all-cause mortality. In addition, a large population-based study showed a correlation between HbA 1c variability and a large range of microvascular and macrovascular complications. ...
HbA1c is the most used parameter to assess glycaemic control. However, evidence suggests that the concept of hyperglycaemia has profoundly changed and that different facets of hyperglycaemia must be considered. A modern approach to glycaemic control should focus not only on reaching and maintaining optimal HbA1c concentrations as early as possible, but to also do so by reducing postprandial hyperglycaemia, glycaemic variability, and to extend as much as possible the time in range in near-normoglycaemia. These goals should be achieved while avoiding hypoglycaemia, which, should it occur, should be reverted to normoglycaemia. Modern technology, such as intermittently scanned glucose monitoring and continuous glucose monitoring, together with new drug therapies (eg, ultra-fast insulins, SGLT2 inhibitors, and GLP-1 receptor agonists), could help to change the landscape of glycaemia management based on HbA1c in favour of a more holistic approach that considers all the different aspects of this commonly oversimplified pathophysiological feature of diabetes.
... Nowhere is this challenge more apparent than in the liver, a central organ in the pathogenesis of two key abnormalities in diabetes: increased production of atherogenic lipoproteins that increase the diabetic's susceptibility to heart disease (1) and increased glucose production predisposing to microvascular complications (4). In addition, the progressive nature of the latter defect (5), together with declining β-cell function (6), likely underlies the therapeutic failure of antidiabetic drugs (7). Among drugs directly targeting hepatic glucose production, the diabetic pharmacopeia remains woefully limited to metformin (8). ...
Significance
The liver is a source of excess lipid, atherogenic lipoproteins, and glucose in patients with type 2 diabetes. These factors predispose to micro- and macrovascular complications. The underlying pathophysiology is not well understood, and mechanistic insight into it may provide better tools to prevent, treat, and reverse the disease. Here, we propose an alternative explanation for this pathophysiologic conundrum by illustrating a transcriptional “logic” underlying the regulation of different classes of genes. These findings can be interpreted to provide an integrated stepwise model for the coexistence of lipid and glucose abnormalities in hepatic insulin resistance.
An early-morning elevation of blood glucose levels known as the dawn phenomenon and consequent postbreakfast hyperglycemia occur in some individuals with type 1 diabetes (T1D). Whereas insulin pump therapy can mitigate this phenomenon, some individuals prefer or are limited to alternative treatments. We have now assessed the effectiveness of early-morning administration of rapid-acting insulin for amelioration of the dawn phenomenon in individuals with T1D.
Thirteen individuals with T1D who experienced the dawn phenomenon as determined by continuous glucose monitoring (CGM) and who received a small dose of rapid-acting insulin on waking were included in this retrospective study. We evaluated the change in sensor glucose levels during a 2-h period from before to after breakfast consumed at 0700 h. The change in blood glucose levels during additional time intervals, average daily sensor glucose values, CGM indices, and insulin dose were also evaluated.
The early-morning administration of 0.5–1 unit of rapid-acting insulin was associated with a significant reduction in 2-h glucose variability between before (0700 h) and after breakfast from a median of 90.7–51.0 mg/dL. The glucose variability from 0300 to 0700 or 0900 h was also significantly decreased, from 67.7 to 29.0 mg/dL and from 172.5 to 78.3 mg/dL, respectively. Average sensor glucose levels throughout the day were significantly reduced (from 192.7 to 156.7 mg/dL), as was the daily total insulin dose.
Early-morning administration of rapid-acting insulin effectively managed the dawn phenomenon and subsequent postbreakfast hyperglycemia in individuals with T1D.
Diabetes mellitus (DM) is a serious chronic metabolic disease that can lead to many serious complications, such as cardiovascular disease, retinopathy, neuropathy, and kidney disease. Once diagnosed with diabetes, patients need to take oral hypoglycemic drugs or use insulin to control blood sugar and slow down the progression of the disease. This has a significant impact on the daily life of patients, requiring constant monitoring of the side effects of medication. It also imposes a heavy financial burden on individuals, their families, and even society as a whole. Adipose-derived stem cells (ADSCs) have recently become an emerging therapeutic modality for DM and its complications. ADSCs can improve insulin sensitivity and enhance insulin secretion through various pathways, thereby alleviating diabetes and its complications. Additionally, ADSCs can promote tissue regeneration, inhibit inflammatory reactions, and reduce tissue damage and cell apoptosis. The potential mechanisms of ADSC therapy for DM and its complications are numerous, and its extensive regenerative and differentiation ability, as well as its role in regulating the immune system and metabolic function, make it a powerful tool in the treatment of DM. Although this technology is still in the early stages, many studies have already proven its safety and effectiveness, providing new treatment options for patients with DM or its complications. Although based on current research, ADSCs have achieved some results in animal experiments and clinical trials for the treatment of DM, further clinical trials are still needed before they can be applied in a clinical setting.
Insulin therapy is indispensable for achieving glycemic control in all patients with type 1 diabetes mellitus and many patients with type 2 diabetes mellitus. Insulin injections are associated with negative connotations in patients owing to administration discomfort and adverse effects such as hypoglycemia and weight gain. Insulin administered orally can overcome these limitations by providing a convenient and effective mode of delivery with a potentially lower risk of hypoglycemia. Oral insulin mimics the physiologic process of insulin secretion, absorption into the portal circulation, and subsequent peripheral delivery, unlike the subcutaneous route that results in peripheral hyperinsulinemia. Insulin tregopil (IN-105), a new generation human recombinant insulin, methoxy (polyethylene glycol) hexanoyl human recombinant insulin, is developed by Biocon as an ultra-fast onset short-acting oral insulin analog. This recombinant oral insulin is a single short-chain amphiphilic oligomer modified with the covalent attachment of methoxy-triethylene-glycol-propionyl moiety at Lys-β29-amino group of the B-chain via an amide linkage. Sodium caprate, an excipient in the insulin tregopil formulation, is a permeation enhancer that increases its absorption through the gastrointestinal tract. Also, meal composition has been shown to non-significantly affect its absorption. Several global randomized, controlled clinical trials have been conducted in type 1 and type 2 diabetes patients towards the clinical development of insulin tregopil. The formulation shows post-prandial glucose control that is more effective than placebo throughout the meal period; however, compared with an active comparator insulin aspart, the post-prandial control is more effective mainly in the early post-meal period. It shows a good safety profile with a lower incidence of clinically significant hypoglycemia. This review covers the overall clinical development of insulin tregopil establishing it as an ultra-fast onset, short-acting oral insulin analog for optimizing post-prandial glucose.
Continuous glucose monitoring has become a common adjunct in the management of Diabetes Mellitus. However, there has been a recent trend among individuals without diabetes using these devices as a means of monitoring their health. The increased visibility of glucose data has allowed users to study the effect lifestyle has upon post-prandial glucose levels. Although post-prandial hyperglycemia is well understood in the setting of diabetes, its impact in individuals without diabetes is less well defined. This article reviews the factors which contribute to post-prandial hyperglycemia in individuals without diabetes and how the data obtained from continuous glucose monitoring can be used to improve an individual's metabolic health.
The term "prediabetes" has traditionally been used to describe the state of abnormal glucose homeostasis (dysglycemia) that could eventually lead to developing clinical type 2 diabetes. The HbA1c, oral glucose tolerance testing, and fasting glucose measurements represent the standard approaches for assessing risk. However, they do not predict with complete accuracy, nor do they provide individualized risk assessment to determine who will develop diabetes. Use of continuous glucose monitoring (CGM) provides a more complete picture of inter- and intraday glucose excursions that may help clinicians and patients quickly identify dysglycemia and make informed personalized intervention decisions. This article discusses the utility of CGM as a tool for both risk assessment and risk management.
Aim:
To investigate the relationship of 1,5 anhydroglucitol (1,5 AG) with HbA1c in patients with type 2 diabetes (T2D) with different ranges of glycemic control.
Methods:
One hundred outpatients with T2D ≥ 18 years old were studied. In addition, HbA1c, glycemia, 1,5 AG, lipids, albuminuria, estimated glomerular filtration rate, and clinical data were registered.
Results:
The patient's median age was 62.5 years, with a median of 10 years with T2D. Those with HbA1c <7 % had higher 1,5 AG than those with HbA1c ≥ 7 %, 16.8 ug/ml vs. 4.90 (p=0.00001).1,5 AG correlated inversely with HbA1c (r= -0.7910, p=0.00001), glycemia (r= -0.6307, p=0.00001), cholesterol (r= -0.2257, p= 0.0239), LDL-cholesterol (r= -0.2240 , p=0.0266), albuminuria (r= -0.3644, p=0.0002) and heart rate (r= -0.267 ,p=0.0072). Those on insulin therapy also had lower 1,5 AG (p=0.000). The scatter plot of 1,5 AG and HbA1c fitted a second-degree fractional polynomic regression model, with dispersion of 1 5 AG when HbA1c < 7.5%. An HbA1c ≥ 7.5 % predicted a 1,5 AG <10 ug/ml CONCLUSION: Dispersion of 1,5 AG values at HbA1c < 7.5 % indicates postprandial glucose excursions that may impair glucose control and increase the cardiovascular risk in these patients.
Aim:
To evaluate the efficacy of iGlarLixi in Asian Pacific (AP) population with type 2 diabetes (T2D) using derived time-in-ranges calculated from seven-point self-measured blood glucose.
Methods:
Two phase III trials were analyzed. LixiLan-O-AP was performed in insulin-naive T2D patients (n=878) randomized to iGlarLixi, glargine 100 units/mL (iGlar), or lixisenatide (Lixi). LixiLan-L-CN was performed in insulin-treated T2D patients (n=426) randomized to iGlarLixi or iGlar. Changes in derived time-in-ranges from baseline to end-of-treatment (EOT) and estimated treatment differences (ETDs) were analyzed. The proportions of patients achieving ≥70% derived time-in-range (dTIR), ≥5% dTIR improvement, and the composite triple target (≥70% dTIR, <4% derived time-below-the-range [dTBR], and <25% derived time-above-the-range [dTAR]) were calculated.
Results:
The changes from baseline to EOT in dTIR with iGlarLixi were greater versus iGlar (ETD1 : 11.45% [95% CI, 7.66 to 15.24]) or Lixi (ETD2 : 20.54% [95% CI, 15.74 to 25.33]) in LixiLan-O-AP, and versus iGlar (ETD: 16.59% [95% CI, 12.09 to 21.08]) in LixiLan-L-CN. In LixiLan-O-AP, the proportions of patients achieving ≥70% dTIR or ≥5% dTIR improvement at EOT with iGlarLixi were 77.5% and 77.8%, respectively, higher than with iGlar (61.1% and 75.3%) or Lixi (47.0% and 53.0%). In LixiLan-L-CN, the proportions of patients achieving ≥70% dTIR or ≥5% dTIR improvement at EOT were 71.4% and 59.8% with iGlarLixi, greater than with iGlar (45.4% and 39.5%). More patients achieved the triple target with iGlarLixi compared with iGlar or Lixi.
Conclusion:
iGlarLixi achieved greater improvements in dTIR parameters vs. iGlar or Lixi in insulin-naïve and insulin-experienced AP people with T2D. This article is protected by copyright. All rights reserved.
The maintenance of appropriate glycemic control is important for the prevention of diabetic complications in people with type 2 diabetes (T2D). Numerous oral antidiabetic drugs are now clinically available, but in particular, the introduction of injection regimens using insulin and/or glucagon-like peptide-1 receptor agonist (GLP-1RA)s represents promising step-up options for oral antidiabetic drug treatment. The recently licensed fixed-ratio combination (FRC) products, which comprise basal insulin and a GLP-1RA, have potent anti-hyperglycemic effects and reduce the undesirable side-effects of each component, such as body weight gain, hypoglycemia, and gastrointestinal symptoms. Two FRCs-insulin degludec/Liraglutide and insulin glargine/Lixisenatide-are now clinically available and, to date, several phase II/III trials have been conducted in particular groups of subjects with T2D. However, their utility in real-world clinical settings is of interest for most clinicians. Recently reported real-world clinical trials of these two FRCs in various situations have demonstrated their efficacy regarding glycemic control and the quality of life of people with T2D. Their long-term safety and efficacy require confirmation, but a treatment strategy that includes an FRC may be compatible with the concept of "well-balanced" therapy in certain groups of patients with T2D who have inadequate glycemic control.
Résumé
C’est une véritable évidence de dire que précision et efficience sont, respectivement, une qualité dans la démarche clinique et un objectif, destinés à individualiser la prise en charge des personnes ayant une maladie chronique comme le diabète. L’efficience thérapeutique est la somme non-arithmétique de l’efficacité, de la sécurité, de la qualité de vie, de la satisfaction du patient, et du coût du traitement. Au sein de cette chaîne caténaire, qui va de l’efficacité au coût, la hiérarchie doit être respectée et, de ce fait, toute faille dans l’une des composantes les plus distales de cette chaîne invalide la pertinence des composantes situées en amont. Par exemple, Il est difficile de promouvoir une stratégie thérapeutique trop coûteuse sur une large échelle, même si cette thérapeutique est considérée comme efficace et sûre. La même remarque peut s’appliquer aux traitements qui entraînent trop de contraintes et qui altèrent la qualité de vie. La médecine de précision qui vise la qualité a émergé en tant que nouvelle démarche thérapeutique dans le diabète. De ce fait, une attention accrue devrait être portée sur la technologie de l’enregistrement glycémique continu qui a permis de définir de nouveaux marqueurs de l’équilibre glycémique et de nouvelles cibles thérapeutiques dans la prise en charge clinique du diabète. De plus, le futur est probablement de développer une médecine de précision pour sélectionner de la manière la plus appropriée, au niveau individuel, les nouveaux agents anti-hyperglycémiants déjà opérationnels, comme les inhibiteurs du co-transporteur sodium-glucose de type 2 (SGLT2) et les préparations hebdomadaires d’agonistes du récepteur du glucagon-like peptide-1 (GLP-1), ou prometteurs, comme le tirzépatide. La description de nouvelles typologies peut être utile pour démembrer l’hétérogénéité clinique, biologique et génétique des états diabétiques. Toutefois, cette nouvelle approche a des failles principalement liées au fait que les outils proposés pour sa réalisation ne sont pas suffisamment précis ou validés. La conclusion est, qu’à l’avenir, efficience et précision devraient être associées, mais, pour l’instant, la symphonie reste inachevée.
Background:
Adding basal insulin to existing oral antidiabetic drugs (OADs) can enhance glycaemic control and achieve HbA1c targets (HbA1c < 7.0%). Our study explored the effect of active insulin titration versus usual titration on glycaemic control in patients with type 2 diabetes mellitus uncontrolled with OADs.
Methods:
In a 24-week, prospective and randomized study, 172 patients with uncontrolled type 2 diabetes were randomly assigned to either active titration or usual titration. Efficacy and safety outcomes included changes in HbA1c and fasting plasma glucose, percentage of individuals achieving HbA1c <7.0% and hypoglycaemic events.
Results:
At week 24, change in HbA1c was -1.08±1.60% in the active titration group and -0.95±1.34% in the usual titration group (P=0.569). The percentages of individuals achieving HbA1c <7% were 29.4% and 16.1% in the active and usual titration groups, respectively (P=0.037). There was no significant difference in the incidence of hypoglycaemia between the two groups. Multivariate logistic regression indicated that with active titration, baseline HbA1c levels and postprandial glucose excursion were significantly associated with achieving HbA1c <7%.
Conclusion:
Addition of basal insulin using active titration for 24 weeks provided a higher rate of HbA1c target achievement without significant hypoglycaemia compared to usual titration in individuals with uncontrolled T2DM. (ClinicalTrials.gov number: NCT01281605) This article is protected by copyright. All rights reserved.
Prediabetes is a very prevalent condition associated with an increased risk of developing diabetes and/or other chronic complications, in particular cardiovascular disorders. Early detection is therefore mandatory since therapeutic interventions may limit the development of these complications. Diagnosis of prediabetes is currently based on glycemic criteria (fasting plasma glucose (PG), and/or glycemia at 120 minutes during a 75 g oral glucose tolerance test (OGTT) and/or glycated hemoglobin (HbA1c). Accumulating longitudinal evidence suggests that a 1-hour PG ≥155 mg/dl (8.6 mmol/l) during the OGTT is an earlier marker of prediabetes than fasting PG, 2-h post-load PG, or HbA1c. There is substantial evidence demonstrating that the 1-h post-load PG is a more sensitive predictor of type 2 diabetes, cardiovascular disease, microangiopathy and mortality compared with conventional glucose criteria.
The aim of this review is to highlight the paramount importance of detecting prediabetes early in its pathophysiological course. Accordingly, as recommended by an international panel in a recent petition, 1-h post-load PG could replace current criteria for diagnosing early stages of “prediabetes” before prediabetes evolves as conventionally defined.
Background:
Whether time in range (TIR), a parameter derived from continuous glucose monitoring (CGM), is a marker of postprandial hyperglycemia remains to be determined. Here we examined the association between TIR and postprandial glucose in non-insulin-treated type 2 diabetic patients.
Methods:
Our cross-sectional study included 729 non-insulin-treated patients with type 2 diabetes who underwent CGM without any changes in drug therapy on admission. The 24-hr CGM record was analyzed for average glucose, standard deviation, percentage coefficient of variation, time above range, TIR, time below range, area under the curve (AUC) of basal glucose, AUC of postprandial glucose, and postprandial glucose contribution rate (%). The primary endpoint was the association between TIR and the postprandial glucose contribution rate.
Results:
We made TIR groups divided into 10% increments for a 7-group and compared with <40% to > 90%. The basal and postprandial glucose AUCs correlated negatively with TIR. The postprandial glucose contribution rate correlated with TIR. The cutoff value for TIR, where postprandial glucose contribution rate was lower than the basal glucose contribution rate, was 66.3%.
Conclusions:
In non-insulin-treated type 2 diabetic patients, postprandial glucose AUC was higher in the high TIR group, while the basal glucose AUC was higher in the low TIR group. Good glycemic control can be achieved with therapeutic interventions that target postprandial glucose and basal glucose in patients with TIR ≥66.3% and <66.3%, respectively.
Zusammenfassung
CGM mit Darstellung der aktuellen Glukosewerte (rtCGM) ist aktuell einer der wichtigsten diagnostischen Optionen in der Diabetologie. Es ermöglicht eine umfangreiche und unmittelbare Unterstützung und Erleichterung des Diabetesmanagements, besonders wenn eine Insulintherapie angewendet wird. Weiterhin stellt rtCGM den notwendigen Systempartner für die Steuerung der automatisierten Insulinabgabe in AID-Systemen dar. In Verbindung mit Smart-Pens unterstützt ein rtCGM die korrekte Durchführung des Insulinmanagements und erinnert an Bolusinjektionen.
RtCGM-Daten sind heute das Fundament des personalisierten Datenmanagements und Alltagscoachings und stellen die Basis der Digitalisierung und telemedizinischen Intervention dar. Die Möglichkeit der interoperablen Nutzung ist aus therapeutischer Sicht eine zentrale Eigenschaft eines rtCGMs und kann zur Erweiterung der Indikationen, unabhängig von Diabetestyp oder Therapieform führen. Dies könnte auch den vorübergehenden oder intermittierenden Einsatz bei Menschen mit Typ-2-Diabetes ohne Insulinbehandlung betreffen. Kürzlich veröffentlichte internationale Leitlinien, z.B. der Amerikanischen Gesellschaft für klinische Endokrinologie (AACE) fordern auf der Basis umfangreicher Evidenz, dass die Glukosemessung mit einem rtCGM für alle Menschen mit Diabetes nutzbar und verfügbar sein sollte. Bereits in der Phase gestörter Glukosetoleranz kann ein rtCGM-System als Alltagscoaching oder Biofeedback bei Einbettung in ein Gesamtbehandlungskonzept unterstützen, mit dem Ziel aktiver und fundierter Handlungen des Anwenders im Diabetesalltag.
Die Vielfalt der Nutzungsoptionen und die immer schnelleren technischen Innovationszyklen von rtCGM-Systemen wurden mit Blick auf aktuelle Anforderungen und die notwendigen Strukturanpassungen des Gesundheitssystems von einer rtCGM-erfahrenen Expertengruppe diskutiert. Ziel war es, konkrete Lücken in der Versorgungsstruktur sowie potenzielle Handlungsfelder in der Diabetologie zu identifizierten und mögliche Indikationserweiterungen für den Einsatz von rtCGM darzustellen. Dieses, sowie die Erkenntnisse und Schlussfolgerungen der Diskussionen werden in diesem Artikel dargestellt.
Advances in the development of innovative medical devices and telehealth technologies create the potential to improve the quality and efficiency of diabetes care through collecting, aggregating, and interpreting relevant health data in ways that facilitate more informed decisions among all stakeholder groups. Although many medical societies publish guidelines for utilizing these technologies in clinical practice, we believe that the methodologies used for the selection and grading of the evidence should be revised. In this article, we discuss the strengths and limitations of the various types of research commonly used for evidence selection and grading and present recommendations for modifying the process to more effectively address the rapid pace of device and technology innovation and new product development.
Objective:
To determine differences in glucose control and cardiovascular disease risk factors following three weeks of added soda, 100% fruit juice, or water in apparently healthy, college-aged adults.
Participants:
Thirty-six adults (18 males; 18 females) between the ages of 18 and 30 years of age.
Methods:
A 3-arm randomized controlled parallel-arm trial; at baseline and after three weeks consuming the assigned beverage, participants completed glucose control and cardiovascular disease risk factor assessments.
Results:
There were no significant differences between beverage conditions for glucose control or cardiovascular disease risk factors (ps > 0.05). There were no significant changes in caloric intake or differences in caloric intake between conditions, p = 0.17.
Conclusions:
In healthy, young adults, under free-living conditions, short-term consumption of two commercially packaged servings of SBs did not lead to significant glucose control or cardiovascular disease risk factor changes, indicating potential compensation and/or resilience to negative short-term effects.
The liver is a key metabolic organ that undertakes a multitude of physiological processes over the course of a day, including intrahepatic lipid and glucose metabolism which plays a key role in the regulation of systemic lipid and glucose concentrations. It serves as an intermediary organ between exogenous (dietary) and endogenous energy supply to extrahepatic organs. Thus, perturbations in hepatic metabolism can impact widely on metabolic disease risk. For example, the accumulation of intra-hepatocellular TAG (IHTG), for which adiposity is almost invariably a causative factor may result in dysregulation of metabolic pathways. Accumulation of IHTG is likely due to an imbalance between fatty acid delivery, synthesis and removal (via oxidation or export as TAG) from the liver; insulin plays a key role in all of these processes.
Background Improved blood-glucose control decreases the progression of diabetic microvascular disease, but the effect on macrovascular complications is unknown. There is concern that sulphonylureas may increase cardiovascular mortality in patients with type 2 diabetes and that high insulin concentrations may enhance atheroma formation. We compared the effects of intensive blood-glucose control with either sulphonylurea or insulin and conventional treatment on the risk of microvascular and macrovascular complications in patients with type 2 diabetes in a randomised controlled trial. Methods 3867 newly diagnosed patients with type 2 diabetes, median age 54 years (IQR 48-60 years), who after 3 months' diet treatment had a mean of two fasting plasma glucose (FPG) concentrations of 6.1-15.0 mmol/L were randomly assigned intensive policy with a sulphonylurea (chlorpropamide, glibenclamide, or. glipizide) or with insulin, or conventional policy with diet. The aim in the intensive group was FPG less than 6 mmol/L. in the conventional group, the aim was the best achievable FPG with diet atone; drugs were added only if there were hyperglycaemic symptoms or FPG greater than 15 mmol/L. Three aggregate endpoints were used to assess differences between conventional and intensive treatment: any diabetes-related endpoint (sudden death, death from hyperglycaemia or hypoglycaemia, fatal or non-fatal myocardial infarction, angina, heart failure, stroke, renal failure, amputation [of at least one digit], vitreous haemorrhage, retinopathy requiring photocoagulation, blindness in one eye,or cataract extraction); diabetes-related death (death from myocardial infarction, stroke, peripheral vascular disease, renal disease, hyperglycaemia or hypoglycaemia, and sudden death); all-cause mortality. Single clinical endpoints and surrogate subclinical endpoints were also assessed. All analyses were by intention to treat and frequency of hypoglycaemia was also analysed by actual therapy. Findings Over 10 years, haemoglobin A(1c) (HbA(1c)) was 7.0% (6.2-8.2) in the intensive group compared with 7.9% (6.9-8.8) in the conventional group-an 11% reduction. There was no difference in HbA(1c) among agents in the intensive group. Compared with the conventional group, the risk in the intensive group was 12% lower (95% CI 1-21, p=0.029) for any diabetes-related endpoint; 10% lower (-11 to 27, p=0.34) for any diabetes-related death; and 6% lower (-10 to 20, p=0.44) for all-cause mortality. Most of the risk reduction in the any diabetes-related aggregate endpoint was due to a 25% risk reduction (7-40, p=0.0099) in microvascular endpoints, including the need for retinal photocoagulation. There was no difference for any of the three aggregate endpoints the three intensive agents (chlorpropamide, glibenclamide, or insulin). Patients in the intensive group had more hypoglycaemic episodes than those in the conventional group on both types of analysis (both p<0.0001). The rates of major hypoglycaemic episodes per year were 0.7% with conventional treatment, 1.0% with chlorpropamide, 1.4% with glibenclamide, and 1.8% with insulin. Weight gain was significantly higher in the intensive group (mean 2.9 kg) than in the conventional group (p<0.001), and patients assigned insulin had a greater gain in weight (4.0 kg) than those assigned chlorpropamide (2.6 kg) or glibenclamide (1.7 kg). Interpretation Intensive blood-glucose control by either sulphonylureas or insulin substantially decreases the risk of microvascular complications, but not macrovascular disease, in patients with type 2 diabetes. None of the individual drugs had an adverse effect on cardiovascular outcomes. All intensive treatment increased the risk of hypoglycaemia.
To compare the abilities and associated hypoglycemia risks of insulin glargine and human NPH insulin added to oral therapy of type 2 diabetes to achieve 7% HbA(1c).
In a randomized, open-label, parallel, 24-week multicenter trial, 756 overweight men and women with inadequate glycemic control (HbA(1c) >7.5%) on one or two oral agents continued prestudy oral agents and received bedtime glargine or NPH once daily, titrated using a simple algorithm seeking a target fasting plasma glucose (FPG) <or=100 mg/dl (5.5 mmol/l). Outcome measures were FPG, HbA(1c), hypoglycemia, and percentage of patients reaching HbA(1c) <or=7% without documented nocturnal hypoglycemia.
Mean FPG at end point was similar with glargine and NPH (117 vs. 120 mg/dl [6.5 vs. 6.7 mmol/l]), as was HbA(1c) (6.96 vs. 6.97%). A majority of patients ( approximately 60%) attained HbA(1c) <or=7% with each insulin type. However, nearly 25% more patients attained this without documented nocturnal hypoglycemia (<or=72 mg/dl [4.0 mmol/l]) with glargine (33.2 vs. 26.7%, P < 0.05). Moreover, rates of other categories of symptomatic hypoglycemia were 21-48% lower with glargine.
Systematically titrating bedtime basal insulin added to oral therapy can safely achieve 7% HbA(1c) in a majority of overweight patients with type 2 diabetes with HbA(1c) between 7.5 and 10.0% on oral agents alone. In doing this, glargine causes significantly less nocturnal hypoglycemia than NPH, thus reducing a leading barrier to initiating insulin. This simple regimen may facilitate earlier and effective insulin use in routine medical practice, improving achievement of recommended standards of diabetes care.
We describe a multinational evaluation of the Menarini-Arkray HA 8140 hemoglobin (Hb) A1c analyzer, which utilizes a high degree of automation, including bar code reading, cap piercing, and whole-blood sampling. With-in- and between-batch CVs were < 2%. Linearity was confirmed throughout the working range of the analyzer. Common Hb variants, including Hb S, Hb C, and Hb F, did not interfere with the Hb A1c separation, and the potentially interfering labile Schiff base was effectively removed during the chromatographic procedure. The HA 8140 analyzer displayed good correlation to the Bio-Rad Variant analyzer, Tinaquant immunoassay, affinity chromatography, and an optimized "in-house" HPLC Hb A1c method. The methods when compared by Altman and Bland plots showed bias (upper, lower 95% confidence limits) of: Variant minus HA 8140 = 0.99 (0.23, 1.74), Tinaquant minus HA 8140 = 0.14 (-0.71, 0.98); affinity minus HA 8140 (after log transformation) = 1.13 (0.90, 1.41), and "in house" HPLC minus HA 8140 (after log transformation) = 0.91 (0.82, 1.01).
The pathogenesis of type 2 diabetes involves abnormalities in insulin action, insulin secretion, and endogenous glucose output (EGO). However, the sequence with which these abnormalities develop and their relative contributions to the deterioration in glucose tolerance remain unclear in the absence of a detailed longitudinal study. We measured insulin action, insulin secretion, and EGO longitudinally in 17 Pima Indians, in whom glucose tolerance deteriorated from normal (NGT) to impaired (IGT) to diabetic over 5.1 +/- 1.4 years. Transition from NGT to IGT was associated with an increase in body weight, a decline in insulin-stimulated glucose disposal, and a decline in the acute insulin secretory response (AIR) to intravenous glucose, but no change in EGO. Progression from IGT to diabetes was accompanied by a further increase in body weight, further decreases in insulin-stimulated glucose disposal and AIR, and an increase in basal EGO. Thirty-one subjects who retained NGT over a similar period also gained weight, but their AIR increased with decreasing insulin-stimulated glucose disposal. Thus, defects in insulin secretion and insulin action occur early in the pathogenesis of diabetes. Intervention to prevent diabetes should target both abnormalities.
Type 2 diabetes mellitus is increasingly common, primarily because of increases in the prevalence of a sedentary lifestyle and obesity. Whether type 2 diabetes can be prevented by interventions that affect the lifestyles of subjects at high risk for the disease is not known.
We randomly assigned 522 middle-aged, overweight subjects (172 men and 350 women; mean age, 55 years; mean body-mass index [weight in kilograms divided by the square of the height in meters], 31) with impaired glucose tolerance to either the intervention group or the control group. Each subject in the intervention group received individualized counseling aimed at reducing weight, total intake of fat, and intake of saturated fat and increasing intake of fiber and physical activity. An oral glucose-tolerance test was performed annually; the diagnosis of diabetes was confirmed by a second test. The mean duration of follow-up was 3.2 years.
The mean (+/-SD) amount of weight lost between base line and the end of year 1 was 4.2+/-5.1 kg in the intervention group and 0.8+/-3.7 kg in the control group; the net loss by the end of year 2 was 3.5+/-5.5 kg in the intervention group and 0.8+/-4.4 kg in the control group (P<0.001 for both comparisons between the groups). The cumulative incidence of diabetes after four years was 11 percent (95 percent confidence interval, 6 to 15 percent) in the intervention group and 23 percent (95 percent confidence interval, 17 to 29 percent) in the control group. During the trial, the risk of diabetes was reduced by 58 percent (P<0.001) in the intervention group. The reduction in the incidence of diabetes was directly associated with changes in lifestyle.
Type 2 diabetes can be prevented by changes in the lifestyles of high-risk subjects.
Multiple laboratory tests are used in the diagnosis and management of patients with diabetes mellitus. The quality of the scientific evidence supporting the use of these assays varies substantially.
An expert committee drafted evidence-based recommendations for the use of laboratory analysis in patients with diabetes. An external panel of experts reviewed a draft of the guidelines, which were modified in response to the reviewers' suggestions. A revised draft was posted on the Internet and was presented at the AACC Annual Meeting in July, 2000. The recommendations were modified again in response to oral and written comments. The guidelines were reviewed by the Professional Practice Committee of the American Diabetes Association.
Measurement of plasma glucose remains the sole diagnostic criterion for diabetes. Monitoring of glycemic control is performed by the patients, who measure their own plasma or blood glucose with meters, and by laboratory analysis of glycated hemoglobin. The potential roles of noninvasive glucose monitoring, genetic testing, autoantibodies, microalbumin, proinsulin, C-peptide, and other analytes are addressed.
The guidelines provide specific recommendations based on published data or derived from expert consensus. Several analytes are of minimal clinical value at the present time, and measurement of them is not recommended.
When glucose is taken orally, insulin secretion is stimulated much more than it is when glucose is infused intravenously so as to result in similar glucose concentrations. This effect, which is called the incretin effect and is estimated to be responsible for 50 to 70% of the insulin response to glucose, is caused mainly by the two intestinal insulin-stimulating hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Their contributions have been confirmed in mimicry experiments, in experiments with antagonists of their actions, and in experiments where the genes encoding their receptors have been deleted. In patients with Type 2 diabetes, the incretin effect is either greatly impaired or absent, and it is assumed that this could contribute to the inability of these patients to adjust their insulin secretion to their needs. In studies of the mechanism of the impaired incretin effect in Type 2 diabetic patients, it has been found that the secretion of GIP is generally normal, whereas the secretion of GLP-1 is reduced, presumably as a consequence of the diabetic state. It might be of even greater importance that the effect of GLP-1 is preserved whereas the effect of GIP is severely impaired. The impaired GIP effect seems to have a genetic background, but could be aggravated by the diabetic state. The preserved effect of GLP-1 has inspired attempts to treat Type 2 diabetes with GLP-1 or analogues thereof, and intravenous GLP-1 administration has been shown to be able to near-normalize both fasting and postprandial glycaemic concentrations in the patients, perhaps because the treatment compensates for both the impaired secretion of GLP-1 and the impaired action of GIP. Several GLP-1 analogues are currently in clinical development and the reported results are, so far, encouraging.
Safety and efficacy of biphasic insulin aspart 70/30 (BIAsp 70/30, prebreakfast and presupper) were compared with once-daily insulin glargine in type 2 diabetic subjects inadequately controlled on oral antidiabetic drugs (OADs).
This 28-week parallel-group study randomized 233 insulin-naive patients with HbA(1c) values >/=8.0% on >1,000 mg/day metformin alone or in combination with other OADs. Metformin was adjusted up to 2,550 mg/day before insulin therapy was initiated with 5-6 units BIAsp 70/30 twice daily or 10-12 units glargine at bedtime and titrated to target blood glucose (80-110 mg/dl) by algorithm-directed titration.
A total of 209 subjects completed the study. At study end, the mean HbA(1c) value was lower in the BIAsp 70/30 group than in the glargine group (6.91 +/- 1.17 vs. 7.41 +/- 1.24%, P < 0.01). The HbA(1c) reduction was greater in the BIAsp 70/30 group than in the glargine group (-2.79 +/- 0.11 vs. -2.36 +/- 0.11%, respectively; P < 0.01), especially for subjects with baseline HbA(1c) >8.5% (-3.13 +/- 1.63 vs. -2.60 +/- 1.50%, respectively; P < 0.05). More BIAsp 70/30-treated subjects reached target HbA(1c) values than glargine-treated subjects (HbA(1c) </=6.5%: 42 vs. 28%, P < 0.05; HbA(1c) <7.0%: 66 vs. 40%, P < 0.001). Minor hypoglycemia (episodes/year) was greater in the BIAsp 70/30 group than in the glargine group (3.4 +/- 6.6 and 0.7 +/- 2.0, respectively; P < 0.05). Weight gain and daily insulin dose at study end were greater for BIAsp 70/30-treated subjects than for glargine-treated subjects (weight gain: 5.4 +/- 4.8 vs. 3.5 +/- 4.5 kg, P < 0.01; insulin dose: 78.5 +/- 39.5 and 51.3 +/- 26.7 units/day, respectively).
In subjects with type 2 diabetes poorly controlled on OADs, initiating insulin therapy with twice-daily BIAsp 70/30 was more effective in achieving HbA(1c) targets than once-daily glargine, especially in subjects with HbA(1c) >8.5%.
To compare the efficacy and safety of adding once-daily basal insulin versus switching to twice-daily premixed insulin in type 2 diabetic patients insufficiently controlled by oral antidiabetic agents (OADs).
In a 24-week, multinational, multicenter, open, parallel group clinical trial, 371 insulin-naive patients with poor glycemic control (fasting blood glucose [FBG] >/=120 mg/dl, HbA(1c) 7.5-10.5%) on OADs (sulfonylurea plus metformin) were randomized to once-daily morning insulin glargine plus glimepiride and metformin (glargine plus OAD) or to 30% regular/70% human NPH insulin (70/30) twice daily without OADs. Insulin dosage was titrated to target FBG </=100 mg/dl (both insulins) and predinner blood glucose </=100 mg/dl (70/30 only) using a weekly forced-titration algorithm.
Mean HbA(1c) decrease from baseline was significantly more pronounced (-1.64 vs. -1.31%, P = 0.0003), and more patients reached HbA(1c) </=7.0% without confirmed nocturnal hypoglycemia (45.5 vs. 28.6%, P = 0.0013) with glargine plus OAD than with 70/30. Similarly, FBG decrease was greater with glargine plus OAD (adjusted mean difference -17 mg/dl [-0.9 mmol/l], P < 0.0001), and more patients reached target FBG </=100 mg/dl with glargine plus OAD than with 70/30 (31.6 vs. 15.0%, P = 0.0001). Glargine plus OAD patients had fewer confirmed hypoglycemic episodes than 70/30 patients (mean 4.07 vs. 9.87/patient-year, P < 0.0001).
Initiating insulin treatment by adding basal insulin glargine once daily to glimepiride plus metformin treatment was safer and more effective than beginning twice-daily injections of 70/30 and discontinuing OADs in type 2 diabetic patients inadequately controlled with OADs.
In type 2 diabetic patients we compared 9 months of combination therapy with insulin glargine and metformin with 9 months of NPH insulin combined with metformin. The primary focus was changes in HbA(1c); secondary focus was diurnal glucose profiles and symptomatic hypoglycaemia.
In this investigator-initiated open, parallel-group clinical trial involving seven centres, 110 insulin-naive type 2 diabetic patients with poor glycaemic control (HbA(1c) >or=8.0%) on oral hypoglycaemic agents (90% using sulfonylurea plus metformin) were randomised to receive bedtime insulin glargine with metformin (G+MET) or bedtime NPH with metformin (NPH+MET) for 36 weeks. The patients were taught how to self-adjust their insulin dose and use a modem to send the results of home glucose monitoring to treatment centres. The goal was to achieve a fasting plasma glucose (FPG) of 4.0 to 5.5 mmol/l in both groups.
During the last 12 weeks, FPGs averaged 5.75+/-0.02 and 5.96+/-0.03 mmol/l (p<0.001) and insulin doses were 68+/-5 and 70+/-6 IU/day (0.69+/-0.05 and 0.66+/-0.04 IU kg(-1) day(-1), NS) in the G+MET and NPH+MET groups, respectively. At 36 weeks, mean HbA(1c) was 7.14+/-0.12 and 7.16+/-0.14%, respectively (NS). Symptomatic, but not confirmed symptomatic, hypoglycaemia was significantly lower during the first 12 weeks in the G+MET group (4.1+/-0.8 episodes/patient-year) than in the NPH+MET group (9.0+/-2.3 episodes/patient-year, p<0.05), but not significantly different thereafter. Glucose levels before dinner were higher in the NPH+MET group (10.1+/-0.3 mmol/l) than in the G+MET group (8.6+/-0.3 mmol/l, p=0.002) throughout the 36-week study. With regard to baseline characteristics such as initial glycaemia or C-peptide, there was no difference between patients who achieved good glycaemic control (HbA(1c) <7.0%) and those who did not. Differences were seen in the following: between study centres, weight gain during the run-in period and insulin therapy, and FPG during the last 12 weeks (5.7+/-0.2 vs 6.7+/-0.3 mmol/l for patients reaching vs those not reaching target, p<0.01).
Good glycaemic control can be achieved with both G+MET and NPH+MET. Use of G+MET reduces symptomatic hypoglycaemia during the first 12 weeks and dinner time hyperglycaemia compared with NPH+MET.
Postprandial hyperglycemia characterizes early type 2 diabetes. We investigated whether ameliorating postprandial hyperglycemia with acarbose would prevent or delay progression of diabetes, defined as progression to frank fasting hyperglycemia, in subjects with early diabetes (fasting plasma glucose [FPG] <140 mg/dl and 2-h plasma glucose > or =200 mg/dl).
Two hundred nineteen subjects with early diabetes were randomly assigned to 100 mg acarbose t.i.d. or identical placebo and followed for 5 years or until they reached the primary outcome (two consecutive quarterly FPG measurements of > or =140 mg/dl). Secondary outcomes included measures of glycemia (meal tolerance tests, HbA(1c), annual oral glucose tolerance tests [OGTTs]), measures of insulin resistance (homeostasis model assessment [HOMA] of insulin resistance and insulin sensitivity index from hyperglycemic clamps), and secondary measures of beta-cell function (HOMA-beta, early- and late-phase insulin secretion, and proinsulin-to-insulin ratio).
Acarbose significantly reduced postprandial hyperglycemia. However, there was no difference in the cumulative rate of frank fasting hyperglycemia (29% with acarbose and 34% with placebo; P = 0.65 for survival analysis). There were no significant differences between groups in OGTT values, measures of insulin resistance, or secondary measures of beta-cell function. In a post hoc analysis of subjects with initial FPG <126 mg/dl, acarbose reduced the rate of development of FPG > or =126 mg/dl (27 vs. 50%; P = 0.04).
Ameliorating postprandial hyperglycemia did not appear to delay progression of early type 2 diabetes. Factors other than postprandial hyperglycemia may be greater determinants of progression of diabetes. Alternatively, once FPG exceeds 126 mg/dl, beta-cell failure may no longer be remediable.
Purpose of review: The purpose of this review is to summarize the current literature on continuous glucose monitors, focusing on devices that have been approved or are pending approval in the United States.
Recent findings: Two continuous glucose sensors are currently available; one for retrospective analysis of glucose values while the other provides readings in real time. Both of these sensors have been thoroughly evaluated for accuracy using the traditional methods used to assess accuracy of home glucose meters. New measures are being developed to assess the accuracy of continuous glucose sensors in identifying glucose trends and predicting hypo and hyperglycemic events. Studies to assess the impact of these sensors on diabetes management have not shown a major benefit; however, most of these studies have only used the sensors for 4 to 20% of study days. Several new sensors may soon be available that provide glucose values in real time with alarms for hypo and hyperglycemia. These devices may potentially replace most discrete home blood glucose tests.
Summary: Continuous glucose monitoring systems are currently less accurate than home glucose meters, but provide information every 5 to 10 minutes throughout the day and night with alarms for pending hyper and hypoglycemia. When sensors are worn almost continuously at home over extended periods of time, there will be a real possibility of making significant improvements in glycemic control.
Purpose of review: Current treatments for type 2 diabetes are effective, but a substantial number of patients continue to have difficulty in achieving and maintaining satisfactory control of blood glucose. The available data suggest that enhancing the action of glucagon-like peptide 1 through the use of glucagon-like peptide 1 receptor agonists, or by preventing the degradation of glueagbh-like peptide 1 by inhibition of dipeptidyl peptidase IV, may be useful therapeutic approaches for the treatment of type 2 diabetes. Herein we focus on the status of current approaches, based on enhancement of incretin action, for the treatment of type 2 diabetes. Recent findings: Degradation-resistant glucagon-like peptide 1 receptor agonists acutely lower blood glucose in human beings by improvement in β cell function, inhibition of gastric emptying, and reduction of glucagon secretion. Treatment with these agents added to existing diabetes therapies, as exemplified by studies of the injectable glucagon-like peptide 1 receptor agonist exenatide, demonstrates significant reduction in HbA1c, together with prevention of weight gain and, in many individuals, significant weight loss over a 30-week study period. Dipeptidyl peptidase IV inhibitors are orally available effective antidiabetic agents that seem to be well tolerated but may not produce weight loss. Less information is currently available about the consequences of long-term treatment with Dipeptidyl peptidase IV inhibitors. Summary: Both glucagon-like peptide 1 receptor agonists and dipeptidyl peptidase IV inhibitors represent promising new approaches for the treatment of type 2 diabetes. The long-term safety and efficacy of these agents remain to be determined, but the available evidence suggests that these new drag classes will provide novel therapeutic alternatives for the management of diabetes.
DIABETES mellitus is characterized by both fasting hyperglycemia and exaggerated postprandial increases in the plasma glucose level. Understanding the causes of these abnormalities is important for the rational use of current treatments and for developing more effective therapy. In this seminar, we review the physiology of normal carbohydrate metabolism and the pathophysiology of abnormalities in diabetes mellitus. Normal Physiology: Postabsorptive State The term "postabsorptive state" refers to the period 6 to 12 hours after a meal during which the transition from the postprandial to the fasting state occurs. At this time plasma glucose levels are at a nearly steady state; . . .
The dawn phenomenon is a condition recently described in patients with insulin-dependent diabetes mellitus (IDDM) that is characterized by abrupt increases in fasting levels of plasma glucose or insulin requirements or both between 5 and 9 a.m., in the absence of antecedent hypoglycemia. To determine its potential clinical relevance, we assessed its frequency and reproducibility in 20 patients with IDDM and in 13 patients with non-insulin-dependent diabetes mellitus (NIDDM) during overnight closed-loop (feedback-controlled) intravenous insulin infusion. After 6 a.m., plasma glucose levels increased similarly in NIDDM (89 +/- 2 mg per deciliter, midnight to 6 a.m., vs. 98 +/- 2 mg per deciliter, 6 to 9 a.m.; P less than 0.01). Insulin requirements increased at least 50 per cent for 1 1/2 hours in 77 per cent of patients with NIDDM and in 75 per cent of patients with IDDM. In five patients with IDDM who were studied on four occasions, the phenomenon occurred during 17 of the 20 observation periods, with insulin requirements after 6 a.m. increasing 225 +/- 34 per cent; coefficients of variation in individual patients ranged from 4 to 25 per cent. Thus, the dawn phenomenon occurs commonly in both NIDDM and IDDM, but its potential variability must be taken into consideration when one is attempting to adjust insulin doses.
Diurnal variation in insulin sensitivity in patients with NIDDM has long been suspected but has been difficult to document mainly because of the interdependence of changes in glucose and insulin. Stable serum insulin levels during hyperglycemic clamping in patients with NIDDM in the present study provided the opportunity to examine changes in insulin sensitivity unaffected by changes in blood glucose and insulin concentrations. Six patients with NIDDM (four men and two women, BMI 33.9 +/- 2.5) underwent hyperglycemic (11.1 mmol/l, approximately 200 mg/dl) clamping for 72 h. Measured were serum insulin, free fatty acid (FFA), cortisol, and growth hormone concentrations and rates of insulin secretion, insulin clearance, and glucose infusion rate (GIR) needed to maintain hyperglycemia. In addition, five patients (three men and two women, BMI 32.6 +/- 0.6) underwent hyperglycemic clamping for 24 h with hourly determinations of hepatic glucose production (HGP) and glucose disappearance rates (GRd). GIR, reflecting insulin sensitivity, changed rhythmically with a cycle duration of 22.9 +/- 1.4 h and an amplitude of 47.8 +/- 11.2%. GIR was lowest at 8:31 a.m. (+/- 52 min) and highest at 7:04 p.m. (+/- 58 min). Circadian changes in GIR were completely accounted for by changes in HGP, while GRd remained unchanged. Plasma levels of FFAs and cortisol also exhibited circadian fluctuations, and their blood levels correlated negatively with GIR (r = -0.72 and -0.64, respectively). We concluded that insulin sensitivity in patients with NIDDM changed with circadian (approximately 24 h) rhythmicity (decreasing during the night and increasing during the day). These changes were unrelated to blood levels of glucose and insulin, insulin clearance, exercise, food intake, and sleep. They were caused by circadian changes in HGP, which in turn were closely correlated with circadian changes in blood FFA and cortisol levels. We believe that recognition of these circadian changes has implications for the diagnosis and the treatment of patients with NIDDM.
Patients with Type II (non-insulin-dependent) diabetes mellitus manifest abnormalities in insulin action and insulin secretion. It is widely accepted that insulin resistance is an early finding, evident before the onset of hyperglycaemia and predictive of the subsequent development of diabetes. Whether abnormalities in insulin secretion also precede and predict diabetes has been debated. However, recent studies clearly indicate that early insulin secretion plays a critical role in maintaining normal glucose homeostasis. Cross-sectional analyses show that acute insulin secretory responses (AIR) to intravenous glucose are lower in subjects with impaired glucose tolerance and those at high risk for developing diabetes. Prospectively, a low AIR predicts the development of diabetes in several populations. In longitudinal studies, AIR declines dramatically as patients progress from normal to impaired glucose tolerance and ultimately to diabetes. Early insulin secretion is important for the rapid and efficient suppression of endogenous glucose production after a meal. Thus, loss of early insulin secretion initially leads to post-prandial hyperglycaemia which, as the disease progresses, worsens to clinical hyperglycaemia. Strategies that enhance early insulin secretion improve glucose tolerance and represent a novel and more physiologic approach to improving glycaemic control in patients with Type II diabetes mellitus.
The analytical performance of a new automated HPLC system, for the determination of HbA1C in blood (Tosoh HLC-723 G7), was studied.
The study design included the evaluation of imprecision, linearity, interference and carryover. Comparison study was performed by comparing HbA1C results with those obtained from an established method (Bio-Rad Variant II).
Total imprecision was less than 1.34% and the results were linear up to 17.2% HbA1C. The method showed a wide analytical range, and no carryover between specimens. Comparison study yielded, r=0.989, Sy.x=0.255, regression equation (y=0.9895x-0.35); Bland-Altman plot showed a mean bias=- 0.43% HbA1C with confidence limits ranging from -0.48% to -0.38% HbA1C. The presence of abnormal hemoglobin was clearly revealed, and no interference from labile HbA1C was apparent.
The HLC-723 G7 instrument seems to be a reliable system for routine assay of HbA1C.
Increased fasting plasma glucose (FPG) and 2-hour postchallenge plasma glucose (PCPG) levels with normal hemoglobin A1c (HbA1c) levels are recognized as risk factors for cardiovascular disease. We undertook this study to determine the relationships between FPG and 2-hour PCPG levels over the normal HbA1c range and to assess the need to control FPG and 2-hour PCPG levels to achieve HbA1c targets recommended by the American Diabetes Association (ADA), International Diabetes Federation (IDF), and American College of Endocrinology (ACE).
The data of all healthy individuals with HbA1c values less than 7.0% (N = 457) who underwent oral glucose tolerance tests between 1986 and 2002 for either screening as potential research volunteers (93%) or diagnostic purposes (7%) were analyzed.
Of 404 individuals with normal HbA1c levels (<6.0%), 60% had normal glucose tolerance, 33% had impaired glucose tolerance, 1% had isolated impaired FPG, and 6% had type 2 diabetes mellitus. Of 161 individuals without normal glucose tolerance, 80% had normal FPG levels. Both FPG and 2-hour PCPG levels increased as HbA1c increased and were significantly correlated (r = 0.63, P<.001), but the 2-hour PCPG level increased at a rate 4 times greater than FPG and accounted for a greater proportion of HbA1c. People who met the IDF and ACE HbA1c targets (<6.5%) had significantly lower 2-hour PCPG levels than those who met the ADA target (<7.0%) (P =.03), whereas FPG levels were similar.
Most individuals with HbA1c values between 6.0% and 7.0% have normal FPG levels but abnormal 2-hour PCPG levels, suggesting that an upper limit of normal for FPG at 110 mg/dL (6.11 mmol/L) is too high and that attempts to lower HbA1c in these individuals will require treatment preferentially directed at lowering postprandial glucose levels.
The exact contributions of postprandial and fasting glucose increments to overall hyperglycemia remain controversial. The discrepancies between the data published previously might be caused by the interference of several factors. To test the effect of overall glycemic control itself, we analyzed the diurnal glycemic profiles of type 2 diabetic patients investigated at different levels of HbA(1c).
In 290 non-insulin- and non-acarbose-using patients with type 2 diabetes, plasma glucose (PG) concentrations were determined at fasting (8:00 A.M.) and during postprandial and postabsorptive periods (at 11:00 A.M., 2:00 P.M., and 5:00 P.M.). The areas under the curve above fasting PG concentrations (AUC(1)) and >6.1 mmol/l (AUC(2)) were calculated for further evaluation of the relative contributions of postprandial (AUC(1)/AUC(2), %) and fasting [(AUC(2) - AUC(1))/AUC(2), %] PG increments to the overall diurnal hyperglycemia. The data were compared over quintiles of HbA(1c).
The relative contribution of postprandial glucose decreased progressively from the lowest (69.7%) to the highest quintile of HbA(1c) (30.5%, P < 0.001), whereas the relative contribution of fasting glucose increased gradually with increasing levels of HbA(1c): 30.3% in the lowest vs. 69.5% in the highest quintile (P < 0.001).
The relative contribution of postprandial glucose excursions is predominant in fairly controlled patients, whereas the contribution of fasting hyperglycemia increases gradually with diabetes worsening. These results could therefore provide a unifying explanation for the discrepancies as observed in previous studies.
The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of Type 2 diabetes have been debated extensively. The concept that a feedback loop governs the interaction of the insulin-sensitive tissues and the beta cell as well as the elucidation of the hyperbolic relationship between insulin sensitivity and insulin secretion explains why insulin-resistant subjects exhibit markedly increased insulin responses while those who are insulin-sensitive have low responses. Consideration of this hyperbolic relationship has helped identify the critical role of beta-cell dysfunction in the development of Type 2 diabetes and the demonstration of reduced beta-cell function in high risk subjects. Furthermore, assessments in a number of ethnic groups emphasise that beta-cell function is a major determinant of oral glucose tolerance in subjects with normal and reduced glucose tolerance and that in all populations the progression from normal to impaired glucose tolerance and subsequently to Type 2 diabetes is associated with declining insulin sensitivity and beta-cell function. The genetic and molecular basis for these reductions in insulin sensitivity and beta-cell function are not fully understood but it does seem that body-fat distribution and especially intra-abdominal fat are major determinants of insulin resistance while reductions in beta-cell mass contribute to beta-cell dysfunction. Based on our greater understanding of the relative roles of insulin resistance and beta-cell dysfunction in Type 2 diabetes, we can anticipate advances in the identification of genes contributing to the development of the disease as well as approaches to the treatment and prevention of Type 2 diabetes.
Inhibitors of the regulatory protease dipeptidyl peptidase-IV (DPP-IV) are currently under development in preclinical and clinical studies (several pharmaceutical companies, now in Phase III) as potential drugs for the treatment of type 2 diabetes. Their development is based on the observation that DPP-IV rapidly inactivates the incretin hormone glucagon-like peptide-1 (GLP-1), which is released postprandially from the gut and increases insulin secretion. DPP-IV inhibitors stabilise endogenous GLP-1 at physiological concentrations, and induce insulin secretion in a glucose-dependent manner; therefore, they do not demonstrate any hypoglycaemic effects. Furthermore, they are orally bioavailable. In addition to their ability to protect GLP-1 against degradation, DPP-IV inhibitors also stabilise other incretins, including gastric inhibitory peptide and pituitary adenylate cyclase-activating peptide. They also reduce the antagonistic and desensitising effects of the fragments formed by truncation of the incretins. In clinical studies, when used for the treatment of diabetes over a 1-year period, DPP-IV inhibitors show improved efficacy over time. This finding can be explained by a GLP-1-induced increase in the number of beta cells. Potential risks associated with DPP-IV inhibitors include the prolongation of the action of other peptide hormones, neuropeptides and chemokines cleaved by the protease, and their interaction with DPP-IV-related proteases. Based on their mode of action, DPP-IV inhibitors seem to be of particular value in early forms of type 2 diabetes, either alone or in combination with other types of oral agents.
American Diabetes Association: Standards of medical care for patients with diabetes mellitus (Position Statement)
American Diabetes Association: Standards of medical care for patients with diabetes mellitus (Position Statement).
Diabetes Care 25 (Suppl. 1):S33–S49,
2002
Diabetes Prevention Program Research Group: Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin
Diabetes Prevention Program Research
Group: Reduction in the incidence of type
2 diabetes with lifestyle intervention or
metformin. N Engl J Med 346:393-403,
2002
The glycemic index: aspects of some vitamins, minerals and enzymes in health and disease
- Tms Wolever
Wolever TMS: The glycemic index: aspects of some vitamins, minerals and enzymes in health and disease. World Rev
Nutr Diet 62:120 -185, 1990
American Diabetes Association: Standards of medical care in diabetes-2006 (Position Statement)
American Diabetes Association: Standards of medical care in diabetes-2006
(Position Statement). Diabetes Care 29
(Suppl. 1):S4 -S42, 2006
Continuous glucose monitoring
- B Buckingham
- J Blȧck
- D M Wilson