Premixed insulin aspart 30 (BIAsp 30) versus premixed human insulin 30 (BHI 30) in gestational diabetes mellitus: a randomized open-label controlled study

A randomized, open-label, parallel study was conducted to assess the efficacy and safety of premixed insulin aspart 30 (biphasic insulin aspart [BIAsp] 30) in managing gestational diabetes mellitus (GDM). A total of 323 women with GDM registered at a single center in India were randomly assigned to receive 6 U of either BIAsp 30 (Group A) or premixed human insulin (biphasic human insulin [BHI] 30; Group B) in a 1:1 ratio. Subjects performed home glucose monitoring and visited their care provider twice a month. The primary outcome was the degree of neonatal macrosomia (neonatal birth weight >90th percentile). Groups A and B were demographically comparable at study entry. Before labor onset, Groups A and B achieved similar degrees of fasting plasma glucose and postprandial plasma glucose control (92.97 ± 14.44 vs. 95.43 ± 18.96 and 127.59 ± 28.99 vs. 126.98 ± 29.89, respectively; both p = NS). Neonatal macrosomia frequency was 6.3% in Group A and 6.9% in Group B; however, this difference was not statistically significant. By last visit, the required insulin dose was significantly lower for Group A than Group B (19.83 ± 15.75 IU vs. 26.34 ± 23.15 IU, respectively; p = 0.006). BIAsp 30 was noninferior to BHI 30, producing comparable fetal outcomes when administered during pregnancy. Based on final doses, BIAsp 30 may offer greater treat-to-target potential for pregnant women.     

双时相门冬胰岛素30联合艾塞那肽对血糖控制不佳2型糖尿病的疗效及安全性分析

目的:探讨双时相门冬胰岛素30联合艾塞那肽在口服降糖药物和基础胰岛素血糖控制不佳的2型糖尿病的疗效及安全性。方法:将在我院接受治疗的72例既往使用的口服降糖药联合基础胰岛素治疗血糖控制不佳的2型糖尿病患者随机、平行、开放平分成治疗组(BIAsp30+艾塞那肽治疗,早餐和晚餐前注射BIAsp30和艾塞那肽注射液)和对照组(睡前1次皮下注射甘精胰岛素),两组均与二甲双胍联合用药。比较两组治疗前后8点血糖谱;比较两组日胰岛素用量、BMI、HbA1c以及低血糖发生次数;比较两组不良事件。结果:治疗8周、16周后,两组8个点血糖与治疗前相比均有明显下降,差异有显著性(P0.05);治疗8周后、16周后,治疗组早餐前和早餐后2小时血糖、午餐前和午餐后2小时血糖值分别与对照组的血糖相比,有统计学差异(P0.05);两组之间的晚餐前和晚餐后2小时血糖、睡觉前血糖(晚上10点)和凌晨3点血糖相互比较无显著性差异(P0.05);治疗16周后,每天胰岛素类似物用量、BMI组间比较无统计学意义(P0.05);两组治疗后HbA1c分别与治疗前相比有统计学意义(P0.05),治疗组治疗后HbA1c与对照组治疗后HbA1c相比,差异有显著性(P0.05);两组低血糖发生次数有明显差异(P0.05);两组不良事件次数相互比较无统计学意义(P0.05)。结论:BIAsp30联合艾塞那肽可显著改善基础胰岛素联合OAD血糖控制不佳的2型糖尿病患者的血糖控制,有效控制血糖,并具有良好的安全性。     

A comparison of the effectiveness, tolerability and safety of high and low carbohydrate diets in women with gestational diabetes

INTRODUCTION: Nutrition therapy is an integral part of the management of gestational diabetes mellitus (GDM). Most women with GDM are treated by nutritional management alone. The goal of our study was to compare low and high carbohydrate diets in their effectiveness, safety and tolerability in women with GDM. MATERIAL AND METHODS: The study group consisted of 30 Caucasian women newly diagnosed with GDM, with a mean age of 28.7 +/- 3.7 years and pregnancy duration of 29.2 +/- 5.4 weeks. The patients were randomised into two groups: those on a low and those on a high carbohydrate diet (45% vs. 65% respectively of energy supply coming from carbohydrates). The presence of urine ketones was controlled every day. After two weeks daily glucose profiles and compliance with the recommended diets were analysed. RESULTS: Glucose concentration before implementation of the diet regimen did not differ between groups. No changes in fasting blood glucose were noticed in the group that had followed a low carbohydrate diet, although a significant decrease in glucose concentration was observed after breakfast (102 +/- 16 vs. 94 +/- 11 mg/dl), lunch (105 +/- 12 vs. 99 +/- 9 mg/dl) and dinner (112 +/- 16 vs. 103 +/- 13 mg/dl) (p < 0.05). In the high carbohydrate diet group fasting and after-breakfast glucose concentration did not change. A significant decrease in glycaemia was noticed after lunch (106 +/- 15 vs. 96 +/- 7 mg/dl) and dinner (107 +/- 12 vs. 97 +/- 7 mg/dl) (p < 0.05). Ketonuria was not observed in either group. Obstetrical outcomes did not differ between groups. CONCLUSIONS: Both high and low carbohydrate diets are effective and safe. A diet with carbohydrate limitation should be recommended to women who experience the highest glycaemia levels after breakfast.     

Effect of twice daily subcutaneous administration of a long-acting somatostatin analog on 24-hour plasma glucose profiles in patients with insulin-dependent diabetes mellitus

To determine the effect of twice daily subcutaneous administration of a long-acting somatostatin analog on diabetic glycemic control, seven insulin-dependent diabetic subjects were treated with mixtures of insulin (regular and lente) given 30 minutes before breakfast and supper alone or along with WY-41, 747, a long-acting somatostatin analog. Postprandial hyperglycemia was markedly reduced after breakfast and supper (peak values 123 +/- 15 vs. 207 +/- 1 mg/dl, P less than 0.01 and 150 +/- 13 vs. 235 +/- 29 mg/dl, P less than 0.02, WY-41,747 + insulin vs. insulin alone, respectively). Although values after lunch and the evening snack were not significantly different, overall mean 24 hr plasma glucose concentrations were significantly less with WY-41,747 plus insulin than with insulin alone (136 +/- 9 vs. 176 +/- 13, P less than 0.05). No serious adverse effects were noted. We conclude that administration of a long-acting somatostatin analog such as WY-41,747 twice daily along with insulin may permit some diabetic patients to achieve satisfactory glycemic control without having to inject insulin 3-4 times daily prior to each meal.     

Insulin glargine maintains equivalent glycemic control and better lipometabolic control than NPH insulin in type 1 diabetes patients who missed a meal.

Our goal was to investigate blood glucose and lipometabolism control in type 1 diabetes patients who missed breakfast and the accompanying insulin injection of NPH insulin (NPH) or insulin glargine (glargine) as part of a basal-bolus regimen. This was a multi-center, open-label, controlled study in adults (> or =18 years) with HbA (1c)< or =11.5% on insulin therapy with NPH as basal insulin. Patients were randomized to receive prandial insulin plus either bedtime glargine (n=28) or NPH (n=32). Insulin was titrated to target fasting blood glucose levels 80-130 mg/dl at 06:00-07:00. Patients had no intake of insulin or food between 22:00 and 12:00 the next day. The change in blood glucose levels (07:00-11:00) was similar (27.5 mg/dl vs. 35.4 mg/dl), but the mean blood glucose level was higher with glargine vs. NPH at 22:00 (158.2 mg/dl vs. 130.2 mg/dl). During the period without insulin or food intake, blood glucose decreased with glargine (-25.8 mg/dl) and increased with NPH (+9.1 mg/dl; p=0.0284). Nonesterified fatty acid (07:00 and 09:00-12:00) and beta-hydroxybutyrate (07:00 and 10:00-12:00) levels were lower with glargine vs. NPH (both p<0.05). For patients who miss a morning meal, glargine is associated with maintained glycemic and lipometabolic control compared with NPH insulin.     

Meal energy content is related to features of meal-related ghrelin profiles across a typical day of eating in non-obese premenopausal women.

Some features of the meal-related profile of ghrelin correspond to acute energy intake, suggesting a role in short-term energy homeostasis. Yet, no studies have examined this relationship across a typical day of eating when effects of time of day and or cumulative energy intake may also exist. AIM OF STUDY: To examine the relation between ghrelin and acute energy intake by quantifying changes in ghrelin over 24 hours in response to three typical meals and a snack occurring throughout the day. METHODS: Fourteen non-obese women consumed three meals and a snack at specific times; total ghrelin was measured repeatedly over 24 hours. RESULTS: Significant correlations existed between: 1) meal calories and the post-meal trough (r = - 0.36; p < 0.05), and 2) the sum of breakfast and lunch calories and subsequent dinner rise (r = - 0.45; p < 0.02) and 3) the sum of breakfast and lunch calories and dinner peak (r = - 0.54; p < 0.003). Thus, as energy intake increased across the day, pre-meal rises of subsequent meals were reduced. CONCLUSION: Meal-related profiles of ghrelin are not only associated with the energy content of specific meals, but also with the accumulated calories prior to a subsequent meal, suggesting a role in the modulation of acute energy homeostasis.     

每日2次和3次皮下注射诺和锐30疗效临床分析

目的:比较诺和锐30每日2次和3次皮下注射的疗效和安全性。方法:为期3个月的随机、开放式试验,100例2型糖尿病(T2DM)患者随机分为诺和锐30皮下注射2次(每日早、晚餐前)、3次(早、中、晚餐前)组,观测两组患者空腹血糖(FPG),中餐前血糖,晚餐前血糖,睡前的血糖值以及糖化血红蛋白(HbA1c),低血糖事件及其他不良事件差异。结果:诺和锐30皮下注射3次组总体血糖水平低于2次组,低血糖事件和其他不良反应发生次数无显著性差异。结论:两组治疗方法均能有效地降低血糖,3次治疗组控制餐后血糖更具优势,HbA1c降低更好,未增加低血糖风险。     

A Comparison of Twice-Daily Biphasic Insulin Aspart 70/30 and Once-Daily Insulin Glargine in Persons With Type 2 Diabetes Mellitus Inadequately Controlled on Basal Insulin and Oral Therapy: A Randomized,Open-Label Study

ObjectiveTo compare efficacy and safety of biphasic insulin aspart 70/30 (BIAsp 30) with insulin (glargine) in type 2 diabetic patients who were not maintaining glycemic control on basal insulin and oral antidiabetic drugs.MethodsIn a 24-week, open-label, parallel-group trial, type 2 diabetic patients who were not maintaining glycemic control on basal insulin (glargine or neutral protamine Hagedorn) + oral antidiabetic drugs were randomly assigned to twice-daily BIAsp 30 + metformin or oncedaily glargine + metformin + secretagogues (secretagogues were discontinued in the BIAsp 30 arm).ResultsOne hundred thirty-seven patients were randomly assigned to the BIAsp 30 group and 143 patients were randomly assigned to the glargine group. Of 280 patients randomized, 229 (81.8%) completed the study. End-of-trial hemoglobin A_1c reductions were − 1.3% (BIAsp 30) vs − 1.2% (glargine) (treatment difference: 95% confidence interval, − 0.06 [− 0.32 to 0.20]; P = .657). Of patients taking BIAsp 30, 27.3% reached a hemoglobin A_1c level < 7.0% compared with 22.0% of patients taking glargine (treatment difference: P = .388). Glucose increment averaged over 3 meals was lower in the BIAsp 30 arm (treatment difference: − 17.8 mg/dL, P = .001). Fasting plasma glucose reductions from baseline were − 13.8 mg/ dL (BIAsp 30) vs − 42.5 mg/dL (glargine) (P = .0002). Final minor hypoglycemia rate, insulin dose, and weight change were higher in the BIAsp 30 arm (6.5 vs 3.4 events/patient per year, P <.05; 1.19 vs 0.63 U/kg; and 3.1 vs 1.4 kg, P = .0004, respectively).ConclusionsDespite not receiving secretagogues, patients taking BIAsp 30 + metformin achieved similar hemoglobin A_1c levels and lower postprandial plasma glucose compared with those receiving glargine + metformin + secretagogues. The large improvement in the glargine group suggests the patients were not true basal failures at randomization. While switching to BIAsp 30 improves glycemic control in this patient population, remaining on basal insulin and optimizing the dose may be equally effective in the short term. (Endocr Pract. 2011;17:41-50)     

Relationship between diurnal glucose levels and HbA1c in type 2 diabetes.

AIMS AND METHODS: Study results still conflict on the contribution of diurnal blood glucose (BG) values to Hb (A1c) in type 2 diabetes. We investigated the relationship between Hb (A1c) and diurnal BG obtained under standardized conditions - before breakfast, two hours after breakfast, before lunch, two hours after lunch, before dinner, two hours after dinner, and at 10 PM, 12 midnight and 3 AM in 68 type 2 diabetic patients before and after optimizing glycemic control. The areas under the curve above fasting BG (AUC1) and above 5.6 mmol/l (AUC2) were calculated for further evaluation. Hb (A1c) was measured at baseline and after a mean of 89 (74 to 108) days. RESULTS: Each BG value at baseline and after treatment optimization significantly correlated with baseline and follow-up Hb (A1c), respectively. The pre-breakfast BG showed the closest correlation with Hb (A1c). The relative contribution of postprandial BG concentrations (AUC1) to overall hyperglycemia (AUC2) decreased with poorer glycemic control. However, treatment optimization mainly resulted in improved blood glucose values in patients with the poorest glycemic control at baseline. Multiple regression analysis demonstrated that fasting (AUC2-AUC1) and postprandial (AUC1) hyperglycemia independently determined Hb (A1c) or the change in Hb (A1c) after treatment optimization. CONCLUSIONS: Our findings indicate that intensive blood glucose monitoring during fasting and postprandial states is important for glycemic control, and is therefore an essential part of good clinical practice.     

Metabolic efficacy and safety of once-daily pioglitazone monotherapy in patients with type 2 diabetes: a double-blind, placebo-controlled study.

Pioglitazone is a novel oral anti-diabetic agent belonging to the thiazolidinedione class. Pioglitazone has been shown to be effective and well tolerated in the treatment of patients with type 2 diabetes, as it reduces insulin resistance and improves glycaemic control and abnormal lipid profiles. This double-blind, randomised, placebo-controlled study was conducted for further evaluation of the efficacy and tolerability of once-daily administration of pioglitazone monotherapy alongside dietary measures in patients with type 2 diabetes. Following a 10-week washout period, 251 patients received one of three treatment regimens for 26 weeks: placebo + diet (n = 84), pioglitazone 15 mg once-daily + diet (n = 89), or pioglitazone 30 mg once-daily + diet (n = 78). Pioglitazone, both 15 and 30 mg/day, in addition to dietary control, was associated with significant reductions (vs. placebo) in mean levels of both glycosylated haemoglobin (HbA 1C ) and fasting blood glucose (FBG). HbA 1C was reduced by 0.92 % and 1.05 %, respectively, and FBG was reduced by 34.3 and 36.0 mg/dl, respectively, compared with the control group. Pioglitazone at 15 and 30 mg/day significantly reduced postprandial blood glucose levels at all visits (- 163 and - 165 mg/dl/hour, respectively) compared with an increase of 47.7 mg/dl/hour on placebo. The profile and frequency of adverse events were similar in all treatment groups. These results indicate that pioglitazone monotherapy together with dietary control is both effective and safe in patients with type 2 diabetes.     

Improved meal-related insulin processing contributes to the enhancement of B-cell function by the DPP-4 inhibitor vildagliptin in patients with type 2 diabetes.

The aim of this study was to evaluate the contribution of insulin processing to the improved meal-related B-cell function previously shown with the DPP-4 inhibitor vildagliptin. Fifty-five patients with type 2 diabetes (56.5+/-1.5 years; BMI=29.6+/-0.5 kg/m(2); FPG=9.9+/-0.2 mmol/l; HbA1c=7.7+/-0.1 %) were studied: 29 patients were treated with vildagliptin and 26 patients with placebo, both added to an ongoing metformin regimen (1.5-3.0 g/day). A standardized breakfast was given at baseline and after 52 weeks of treatment, and proinsulin related to insulin secretion was measured with C-peptide in the fasting and postprandial (over 4 h post-meal) states to evaluate B-cell function. The between-treatment difference (vildagliptin-placebo) in mean change from baseline in fasting proinsulin to C-peptide ratio (fastP/C) was -0.007+/-0.009 (p=0.052). Following the standard breakfast, 52 weeks of treatment with vildagliptin significantly decreased the dynamic proinsulin to C-peptide ratio (dynP/C) relative to placebo by 0.010+/-0.008 (p=0.037). Importantly, when the P/C was expressed in relation to the glucose stimulus (i.e., the fasting glucose and glucose AUC(0-240 min), respectively), the P/C relative to glucose was significantly reduced with vildagliptin vs. placebo, both in the fasting state (p=0.023) and postprandially (p=0.004). In conclusion, a more efficient B-cell insulin processing provides further evidence that vildagliptin treatment ameliorates abnormal B-cell function in patients with type 2 diabetes.     

Effect of nutrient ingestion on glucagon-like peptide 1 (7-36 amide) secretion in human type 1 and type 2 diabetes.

Exogenous glucagon-like peptide 1(GLP-1) bioactivity is preserved in type 2 diabetic patients, resulting the peptide administration in a near-normalization of plasma glucose mainly through its insulinotropic effect. GLP-1 also reduces meal-related insulin requirement in type 1 diabetic patients, suggesting an impairment of the entero-insular axis in both diabetic conditions. To investigate this metabolic dysfunction, we evaluated endogenous GLP-1 concentrations, both at fasting and in response to nutrient ingestion, in 16 type 1 diabetic patients (age = 40.5 +/- 14yr, HbA1C = 7.8 +/- 1.5%), 14 type 2 diabetics (age = 56.5 +/- 13yr, HbA1C = 8.1 +/- 1.8%), and 10 matched controls. In postabsorptive state, a mixed breakfast (230 KCal) was administered to all subjects and blood samples were collected for plasma glucose, insulin, C-peptide and GLP-1 determination during the following 3 hours. In normal subjects, the test meal induced a significant increase of GLP-1 (30', 60': p < 0.01), returning the peptide values towards basal concentrations. In type 2 diabetic patients, fasting plasma GLP-1 was similar to controls (102.1 +/- 1.9 vs. 97.3 +/- 4.01 pg/ml), but nutrient ingestion failed to increase plasma peptide levels, which even decreased during the test (p < 0.01). Similarly, no increase in postprandial GLP-1 occurred in type 1 diabetics, in spite of maintained basal peptide secretion (106.5 +/- 1.5 pg/ml). With respect to controls, the test meal induced in both diabetic groups a significant increase in plasma glucagon levels at 60' (p < 0.01). In conclusion, either in condition of insulin resistance or insulin deficiency chronic hyperglycemia, which is a common feature of both metabolic disorders, could induce a progressive desensitization of intestinal L-cells with consequent peptide failure response to specific stimulation.     

Evaluation of the new software program DegifXL4 in the determination of the glycaemic indices of foodstuffs

Aims: There is no standardized protocol for measuring glycemic index (GI) that takes time-of-day effects into account. The software DegifXL2 and Medtronic-Minimed's CGMS and Solutions, makes the GI calculation at breakfast and dinner time possible. The aim of this study was to assess the enhanced data processing software (DegifXL4) enabling the GI calculation at breakfast, lunch, afternoon snack and dinner times. Methods: The glucose levels of 20 healthy volunteers were monitored after they consumed either 50 g of glucose or one of ten alternative foodstuffs either for breakfast and dinner or for lunch or snack. Within the 9-day test period, 10 such meals were monitored in 3 replicates for each volunteer. Specifically, CGMS was used to monitor plasma glucose levels at 5-minute intervals for a period of 120 min following the foodstuff ingestion. Results: Using the enhanced spreadsheed DegifXL 4, a total of 640 profiles were obtained and 491 (77 %) accomplished the criteria for further processing. The percentage of successful tests in each foodstuff varied from 57 to 87 %. Conclusions: The use of the new software DegifXL4 offers accurate GI estimates for foodstuffs eaten for breakfast, lunch, snacks and dinners in three replicates. In combination with the CGMS Solutions Software is DegifXL4 an enhanced efficient and comfortable way to routinely measure GI values.     

Comparison of vildagliptin twice daily vs. sitagliptin once daily using continuous glucose monitoring (CGM): Crossover pilot study (J-VICTORIA study)

ABSTRACT: BACKGROUND: No previous studies have compared the DPP-4 inhibitors vildagliptin and sitagliptin in terms of blood glucose levels using continuous glucose monitoring (CGM) and cardiovascular parameters. METHODS: Twenty patients with type 2 diabetes mellitus were randomly allocated to groups who received vildagliptin then sitagliptin, or vice versa. Patients were hospitalized at 1 month after starting each drug, and CGM was used to determine: 1) mean (+/- standard deviation) 24-hour blood glucose level, 2) mean amplitude of glycemic excursions (MAGE), 3) fasting blood glucose level, 4) highest postprandial blood glucose level and time, 5) increase in blood glucose level after each meal, 6) area under the curve (AUC) for blood glucose level [greater than or equal to]180 mg/dL within 3 hours after each meal, and 7) area over the curve (AOC) for daily blood glucose level <70 mg/dL. Plasma glycosylated hemoglobin (HbA1c), glycoalbumin (GA), 1,5-anhydroglucitol (1,5AG), immunoreactive insulin (IRI), C-peptide immunoreactivity (CPR), brain natriuretic peptide (BNP), and plasminogen activator inhibitor-1 (PAI-1) levels, and urinary CPR levels, were measured. RESULTS: The mean 24-hour blood glucose level was significantly lower in patients taking vildagliptin than sitagliptin (142.1 +/- 35.5 vs. 153.2 +/- 37.0 mg/dL; p = 0.012). In patients taking vildagliptin, MAGE was significantly lower (110.5 +/- 33.5 vs. 129.4 +/- 45.1 mg/dL; p = 0.040), the highest blood glucose level after supper was significantly lower (206.1 +/- 40.2 vs. 223.2 +/- 43.5 mg/dL; p = 0.015), the AUC ([greater than or equal to]180 mg/dL) within 3 hours was significantly lower after breakfast (484.3 vs. 897.9 mg/min/dL; p = 0.025), and urinary CPR level was significantly higher (97.0 +/- 41.6 vs. 85.2 +/- 39.9 mug/day; p = 0.008) than in patients taking sitagliptin. There were no significant differences in plasma HbA1c, GA, 1,5AG, IRI, CPR, BNP, or PAI-1 levels between patients taking vildagliptin and sitagliptin. CONCLUSIONS: CGM showed that mean 24-hour blood glucose, MAGE, highest blood glucose level after supper, and hyperglycemia after breakfast were significantly lower in patients with type 2 diabetes mellitus taking vildagliptin than those taking sitagliptin. There were no significant differences in BNP and PAI-1 levels between patients taking vildagliptin and sitagliptin. Trial registration UMIN000007687 KEYWORDS: Vildagliptin; Sitagliptin; Continuous glucose monitoring (CGM); Brain natriuretic peptide (BNP); plasminogen activator inhibitor-1 (PAI-1).     

Superiority of insulin analogues versus human insulin in the treatment of diabetes mellitus

The modern goals of insulin replacement in Type 1 and Type 2 diabetes mellitus (T1, T2DM) are A1C <6.5% long-term, and prevention of hypoglycaemia (blood glucose, BG <70 mg/dl). In addition to appropriate education and motivation of diabetic subjects, the use of rapid- and long-acting insulin analogues, is critical to achieve these goals. The benefits of rapid-acting analogues (lispro, aspart and glulisine have similar pharmacodynamic effects) compared with non-modified human regular insulin, are: (a) lower 1- and 2-h post-prandial blood glucose; (b) lower risk of late post-prandial hypoglycaemia (and therefore lower BG variability); (c) better quality of life (greater flexibility in timing and dosing of insulin). In T1DM, rapid-acting analogues improve A1C only by the extent to which replacement of basal insulin is optimized at the same time, either by multiple daily NPH administrations, or continuous subcutaneous insulin infusion (CSII), or use of the long-acting insulin analogues glargine or detemir. In T2DM, rapid-acting analogues reduce post-prandial hyperglycaemia more than human regular insulin, but systematic studies are needed to examine the effects on A1C. The benefits of long-acting insulin analogues glargine and detemir vs. NPH, are: (1) lower fasting BG combined with lower risk of hypoglycaemia in the interprandial state (night); (2) lower variability of BG. Glargine and detemir differ in terms of potency and duration of action. Detemir should be given twice daily in the large majority of people with T1DM, and in a large percentage of subjects with T2DM as well, usually at doses greater vs those of the once daily glargine. However, when used appropriately for individual pharmacokinetics and pharmacodynamics, glargine and detemir result into similar effects on BG, risk of hypoglycaemia and A1C. Rapid- and long-acting insulin analogues should always be combined in the treatment of T1 and T2DM.     

Comparison of the Effect of Insulin Glulisine to Insulin Aspart on Breakfast Postprandial Blood Glucose Levels in Children with Type 1 Diabetes Mellitus on Multiple Daily Injections

ObjectiveRapid-acting insulins, including insulin aspart (NovoLog) and lispro (Humalog), do not seem to effectively control postprandial glycemic excursions in children with type 1 diabetes mellitus (T1DM). The objective of this study was to determine if insulin glulisine (Apidra), another rapid-acting insulin analog, would be superior in controlling postprandial hyperglycemia in children with T1DM.MethodsThirteen prepubertal children ages 4 to 11 years completed this study. Inclusion criteria included T1DM ≥6 months, glycosylated hemoglobin (HbAlC) 6.9 to 10%, blood glucose (BG) levels in adequate control for 1 week prior to study start, multiple daily injections (MDI) with insulin glargine or determir once daily and aspart or lispro premeal. If fasting BG was 70 to 180 mg/dL, subjects received insulin glulisine alternating with aspart prior to a prescribed breakfast with a fixed amount of carbohydrate (45, 60, or 75 g) for 20 days. Postprandial BG values were obtained at 2 and 4 hours.ResultsMean baseline BG values for insulin glulisine (136.4 ± 15.7 mg/dL; mean ± SD) and aspart (133.4 ± 14.7 mg/dL) were similar (P = .34). Mean increase in 2-hour postprandial BG was higher in glulisine (+113.5 ± 65.2 mg/dL) than aspart (+98.6 ± 66.9 mg/dL), (P = .01). BG remained higher at 4 hours (glulisine: 141.9 ± 36.5 mg/ dL, aspart: 129.0 ± 37.0 mg/dL) (P = .04). Although statistically insignificant, more hypoglycemic events occurred at 2-and 4-hours postprandial with insulin aspart.ConclusionInsulin aspart appears to be more effective than insulin glulisine in controlling 2-and 4-hour postprandial BG excursions in prepubertal children with T1DM. (Endocr Pract. 2013;19:614-619)     

Cardioprotection by glucose-insulin-potassium: dependence on KATP channel opening and blood glucose concentration before ischemia

We tested the hypothesis that glucose-insulin-potassium (GIK)-induced protection against myocardial infarction depends on ATP-dependent K(+) (K(ATP)) channel activation and is abolished by hyperglycemia before the ischemia. Dogs were subjected to a 60-min coronary artery occlusion and 3-h reperfusion in the absence or presence of GIK (25% dextrose; 50 IU insulin/l; 80 mM/l KCl infused at 1.5 ml x kg(-1) x h(-1)) beginning 75 min before coronary artery occlusion or 5 min before reperfusion. The role of K(ATP) channels was evaluated by pretreatment with glyburide (0.1 mg/kg). The efficacy of GIK was investigated with increases in blood glucose (BG) concentrations to 300 or 600 mg/dl or experimental diabetes (alloxan/streptozotocin). Infarct size (IS) was 29 +/- 2% of the area at risk in control experiments. GIK decreased (P < 0.05) IS when administered beginning 5 min before reperfusion. This protective action was independent of BG (13 +/- 2 and 12 +/- 2% of area at risk; BG = 80 or 600 mg/dl, respectively) but was abolished in dogs receiving glyburide (30 +/- 4%), hyperglycemia before ischemia (27 +/- 4%), or diabetes (25 +/- 3%). IS was unchanged by GIK when administered before ischemia independent of BG (31 +/- 3, 27 +/- 2, and 35 +/- 3%; BG = 80, 300, and 600 mg/dl, respectively). The insulin component of GIK promotes cardioprotection by K(ATP) channel activation. However, glucose decreases K(ATP) channel activity, and this effect predominates when hyperglycemia is present before ischemia.     

Mathematical modeling shows exenatide improved beta-cell function in patients with type 2 diabetes treated with metformin or metformin and a sulfonylurea.

The incretin mimetic exenatide improved glycemic control and reduced body weight in patients with type 2 diabetes inadequately controlled with metformin+/-a sulfonylurea. We assessed postprandial beta-cell function by mathematical modeling, independent of confounding effects from differing ambient glucose levels among treatments. Subjects were 63% males, 55+/-10 years, BMI 33+/-6 kg/m2, HbA1C 8.1+/-1.1% (+/- SD) randomized to 5 microg exenatide or placebo twice daily for 4 weeks. Subsequently, one arm remained at 5 microg twice daily, one arm escalated to 10 microg twice daily, and one treatment arm remained on placebo for 26 weeks. Subjects continued metformin+/-a sulfonylurea. A subset with meal tests at baseline and week 30 were analyzed (n=73). Outcome measures were the model-based beta-cell function parameters dose-response relating insulin secretion to glucose concentration, rate sensitivity, and potentiation. Exenatide reduced postprandial glucose excursions. Modeling predicted an upward shift of the beta-cell dose-response. Model-predicted insulin secretion rate at a reference glucose concentration increased 72% (10 microg), increased 40% (5 microg), or decreased 21% (placebo) at week 30 [ p=0.015 (10 microg); p=0.045 (5 microg); vs. placebo]. At week 30, the 2-hour post-meal to basal potentiation factor ratio was increased to 1.53+/-0.10 (10 microg; p=0.0142 vs. placebo) or 1.40+/-0.08 (5 microg; p=0.0402 vs. placebo) compared with 1.15+/-0.06 (placebo). Exenatide caused an upward shift of the beta-cell dose-response and enhanced potentiation of insulin secretion. This model suggests exenatide improved beta-cell function in patients with type 2 diabetes treated with metformin+/-a sulfonylurea.     

Postprandial endothelial function does not differ in women by race: an insulin resistance paradox?

Insulin resistance is associated with endothelial dysfunction. Because African-American women are more insulin-resistant than white women, it is assumed that African-American women have impaired endothelial function. However, racial differences in postprandial endothelial function have not been examined. In this study, we test the hypothesis that African-American women have impaired postprandial endothelial function compared with white women. Postprandial endothelial function following a breakfast (20% protein, 40% fat, and 40% carbohydrate) was evaluated in 36 (18 African-American women, 18 white women) age- and body mass index (BMI)-matched (age: 37 ± 11 yr; BMI: 30 ± 6 kg/m(2)) women. Endothelial function, defined by percent change in brachial artery flow-mediated dilation (FMD), was measured at 0, 2, 4, and 6 h following a meal. There were no significant differences between the groups in baseline FMD, total body fat, abdominal visceral fat, and fasting levels of glucose, insulin, total cholesterol, low-density lipoprotein cholesterol, or serum estradiol. Although African-American women were less insulin-sensitive [insulin sensitivity index (mean ± SD): 3.6 ± 1.5 vs. 5.2 ± 2.6, P = 0.02], both fasting triglyceride (TG: 56 ± 37 vs. 97 ± 49 mg/dl, P = 0.007) and incremental TG area under the curve (AUC(0-6hr): 279 ± 190 vs. 492 ± 255 mg·dl(-1)·min(-1)·10(-2), P = 0.008) were lower in African-American than white women. Breakfast was associated with a significant increase in FMD in whites and African-Americans, and there was no significant difference in postprandial FMD between the groups (P > 0.1 for group × time interactions). Despite being insulin-resistant, postprandial endothelial function in African-American women was comparable to white women. These results imply that insulin sensitivity may not be an important determinant of racial differences in endothelial function.