Postprandial Glucose Excursions In Patients Research Articles

Impact of glucagon response on early postprandial glucose excursions irrespective of residual β-cell function in type 1 diabetes: A cross-sectional study using a mixed meal tolerance test.

Aims/IntroductionControlling postprandial glucose levels in patients with type 1 diabetes is challenging even under the adequate treatment of insulin injection. Recent studies showed that dysregulated glucagon secretion exacerbates hyperglycemia in type 2 diabetes patients, but little is known in type 1 diabetes patients. We investigated whether the glucagon response to a meal ingestion could influence the postprandial glucose excursion in patients with type 1 diabetes.Materials and MethodsWe enrolled 34 patients with type 1 diabetes and 23 patients with type 2 diabetes as controls. All patients underwent a liquid mixed meal tolerance test. We measured levels of plasma glucose, C‐peptide and glucagon at fasting (0 min), and 30, 60 and 120 min after meal ingestion. All type 1 diabetes patients received their usual basal insulin and two‐thirds of the necessary dose of the premeal bolus insulin.ResultsThe levels of plasma glucagon were elevated and peaked 30 min after the mixed meal ingestion in both type 1 diabetes and type 2 diabetes patients. The glucagon increments from fasting to each time point (30, 60 and 120 min) in type 1 diabetes patients were comparable to those in type 2 diabetes patients. Among the type 1 diabetes patients, the glucagon response showed no differences between the subgroups based on diabetes duration (<5 vs ≥5 years) and fasting C‐peptide levels (<0.10 vs ≥0.10 nmol/L). The changes in plasma glucose from fasting to 30 min were positively correlated with those in glucagon, but not C‐peptide, irrespective of diabetes duration and fasting C‐peptide levels in patients with type 1 diabetes.ConclusionsThe dysregulated glucagon likely contributes to postprandial hyperglycemia independent of the residual β‐cell functions during the progression of type 1 diabetes.

Effects of Insulin Lispro Mix 25 and Insulin Lispro Mix 50 on Postprandial Glucose Excursion in Patients with Type 2 Diabetes: A Prospective, Open-Label, Randomized Clinical Trial.

IntroductionWe compared the effects of insulin lispro mix 25 (LM25) and insulin lispro mix 50 (LM50) on postprandial glucose excursion in patients with type 2 diabetes mellitus (T2DM).MethodsIn this randomized, open-label, investigator-initiated trial, 81 T2DM patients treated with premixed human insulin 70/30 (PHI70/30) for more than 90 days were randomly divided into two groups and received a crossover protocol of either LM25 or LM50 twice daily for 16 weeks. Continuous glucose monitoring (CGM) was performed for 72 h at baseline and at the end of each treatment phase to evaluate glycemic excursions in the subjects.ResultsThe LM50 regimen resulted in significantly smaller postprandial glycemic excursions than the LM25 regimen after breakfast (1.3 ± 2.5 vs. 2.4 ± 2.6 mmol/L, P = 0.046) and dinner (1.5 ± 2.8 vs. 2.8 ± 2.4 mmol/L, P = 0.036). Glycosylated hemoglobin levels were similar for the patients on the three regimens. The percentage of patients who achieved their glycosylated hemoglobin target was significantly higher for the LM25 and LM50 regimens than for the PHI70/30 regimen, regardless of whether the target was set at 7.0% or 6.5%. The proportion of the patients who were hypoglycemic for a high percentage (> 10%) of the time was lower for the LM50 regimen than for the LM25 and PHI70/30 regimens.ConclusionsLM50 may provide better glycemic excursion control after breakfast and dinner than LM25 in T2DM patients.Trial Registrationhttp://www.chictr.org.cn # ChiCTR-TTRCC-12002516.FundingLilly Suzhou Pharmaceutical Co., Ltd. (Shanghai Branch, China) and National Key Program of Clinical Science of China (WBYZ 2011-873).

Mechanisms by which vildagliptin reduces postprandial glucose excursions in patients with type 2 diabetes

Objective: The dipeptidyl peptidase IV (DPP-4) inhibitor vildagliptine (VILDA) increases postprandial (pp) GLP-1 levels 2–4 fold. Major effects of GLP-1 involve increases in pp insulin secretion, suppression of pp glucagon secretion and delay of gastric emptying (GE). The potential effects of acute 100mg Vilda p.o. adminstration on pp glucose (GLU) fluxes are unknown.

Abstract #278: Exenatide and Insulin Glargine Differentially Affect Postprandial Glucose Excursions in Patients With Type 2 Diabetes

Abstract #278: Exenatide and Insulin Glargine Differentially Affect Postprandial Glucose Excursions in Patients With Type 2 Diabetes

Insulin Glulisine

Insulin glulisine is a rapid-acting human insulin analogue that has a faster onset of action and shorter duration of action than regular human insulin (RHI) in patients with type 1 or 2 diabetes mellitus and is efficacious in controlling prandial blood glucose levels in these patients. In large, well designed trials in patients with type 1 diabetes, insulin glulisine demonstrated a similar degree of glycaemic control, as measured by glycosylated haemoglobin (HbA(1c)) levels, to RHI after 12 weeks and insulin lispro after 26 weeks. Pre-meal insulin glulisine was also more effective than RHI at controlling 2-hour post-prandial glucose excursions in patients with type 1 or 2 diabetes over a period of 12 weeks. In patients with type 2 diabetes, insulin glulisine induced significantly greater reductions in HbA(1c) levels and 2-hour post-breakfast and post-dinner blood glucose levels than RHI over a period of 26 weeks. Insulin glulisine was generally well tolerated by patients with type 1 or 2 diabetes and had a similar safety profile to insulin lispro or RHI. Severe hypoglycaemia was experienced by similar proportions of insulin glulisine or comparator insulin (insulin lispro or RHI) recipients with type 1 or type 2 diabetes.

Effects of Pramlintide on Postprandial Glucose Excursions and Measures of Oxidative Stress in Patients With Type 1 Diabetes

Oxidative stress has been shown to be increased in the postprandial period in patients with diabetes and has been implicated in the pathogenesis of micro- and macrovascular complications. The aim of this post hoc analysis was to assess the effects of pramlintide, an amylin analog shown to reduce postprandial glucose excursions in patients with diabetes, on markers of oxidative stress in the postprandial period. In a randomized, single-blind, placebo-controlled, crossover study, 18 evaluable subjects with type 1 diabetes underwent two standardized breakfast meal tests and received pramlintide or placebo in addition to their preprandial insulin. The plasma concentrations of glucose and markers of oxidative stress (nitrotyrosine, oxidized LDL [ox-LDL], and total radical-trapping antioxidant parameter [TRAP]) were measured at baseline and during the 4-h postprandial period. Compared with placebo, pramlintide treatment significantly reduced postprandial excursions of glucose, nitrotyrosine, and ox-LDL and prevented a decline in TRAP (P < 0.03 for all comparisons). Correlation analyses adjusted for treatment revealed a significant association between postprandial mean incremental area under the curve from 0 to 4 h (AUC(0-4 h)) for glucose and postprandial mean incremental AUC(0-4 h) for each measure of oxidative stress (r = 0.75, 0.54, and -0.63 for nitrotyrosine, ox-LDL, and TRAP, respectively; P < 0.001 for all correlations). These findings indicate that the postprandial glucose-lowering effect of pramlintide in type 1 diabetes is associated with a significant reduction in postprandial oxidative stress.

Repaglinide is more efficient than glimepiride on insulin secretion and post-prandial glucose excursions in patients with type 2 diabetes. A short term study

To compare the effect of Repaglinide vs Glimepiride on glucose- and meal-induced insulin secretion and on meal-test induced postprandial glucose excursions. After 2 weeks washout period, a 3-Month randomised, cross-over parallel group trial of R (1 mg x 2/die) vs G (2 mg/die) in 14 patients with type 2 diabetes "naive" in diet treatment was made. Both R and G significantly but similarly lowered fasting glucose levels and improved fasting plasma insulin levels vs baseline. Hyperglycemic clamp showed that both 1st (129.15 +/- 23.6 vs 106.90 +/- 18.6 pmol/L; p=0.01) and 2nd phase (189.42 +/- 34.4 vs 144.21 +/- 37.3 pmol/L; p=0.003) B-cell response to glucose as well as area under the curve (52.07 +/- 10.86 vs 39.54 +/- 10.27 micromol/L x 120'; p=0.005) were greater in R than G groups. Insulin action (4.0 +/- 1.1 vs 3.2 +/- 0.9 mg x Kg x 60'/microU/mL; p=0.046) was also improved by R than G administration. In the meal test, R therapy produced a more rapId induction of insulin secretion during the first part. In fact, the mean rise in insulin secretion peaked at 45 min in R (p=0.001 vs G) and at 60 min in G (p=0.001 vs R). Consequently, glucose spike at 60 min was higher in G group compared to glucose spike at 45 min in R group (p=0.002). Our study demonstrates that R is more efficient that G on improving glucose- and meal- induced insulin secretion as well as on controlling for postprandial glucose excursion.

Repaglinide: a review of its therapeutic use in type 2 diabetes mellitus.

Repaglinide, a carbamoylmethyl benzoic acid derivative, is the first of a new class of oral antidiabetic agents designed to normalise postprandial glucose excursions in patients with type 2 diabetes mellitus. Like the sulphonylureas, repaglinide reduces blood glucose by stimulating insulin release from pancreatic beta-cells, but differs from these and other antidiabetic agents in its structure, binding profile, duration of action and mode of excretion. In clinical trials of up to 1-year's duration, repaglinide maintained or improved glycaemic control in patients with type 2 diabetes mellitus. In comparative, 1-year, double-blind, randomised trials (n = 256 to 544), patients receiving repaglinide (0.5 to 4mg before 3 daily meals) achieved similar glycaemic control to that in patients receiving glibenclamide (glyburide) < or = 15 mg/day and greater control than patients receiving glipizide < or = 15 mg/day. Changes from baseline in glycosylated haemoglobin and fasting blood glucose levels were similar between patients receiving repaglinide and glibenclamide in all studies; however, repaglinide was slightly better than glibenclamide in reducing postprandial blood glucose in I short term study (n = 192). Patients can vary their meal timetable with repaglinide: the glucose-lowering efficacy of repaglinide was similar for patients consuming 2, 3 or 4 meals a day. Repaglinide showed additive effects when used in combination with other oral antidiabetic agents including metformin, troglitazone, rosiglitazone and pioglitazone, and intermediate-acting insulin (NPH) given at bedtime. In 1-year trials, the most common adverse events reported in repaglinide recipients (n = 1,228) were hypoglycaemia (16%), upper respiratory tract infection (10%), rhinitis (7%), bronchitis (6%) and headache (9%). The overall incidence of hypoglycaemia was similar to that recorded in patients receiving glibenclamide, glipizide or gliclazide (n = 597) [18%]; however, the incidence of serious hypoglycaemia appears to be slightly higher in sulphonylurea recipients. Unlike glibenclamide, the risk of hypoglycaemia in patients receiving repaglinide was not increased when a meal was missed in 1 trial. In conclusion, repaglinide is a useful addition to the other currently available treatments for type 2 diabetes mellitus. Preprandial repaglinide has displayed antihyperglycaemic efficacy at least equal to that of various sulphonylureas and is associated with a reduced risk of serious hypoglycaemia. It is well tolerated in a wide range of patients, including the elderly, even if a meal is missed. Furthermore, glycaemic control is improved when repaglinide is used in combination with metformin. Thus, repaglinide should be considered for use in any patient with type 2 diabetes mellitus whose blood glucose cannot be controlled by diet or exercise alone, or as an adjunct in patients whose glucose levels are inadequately controlled on metformin alone.

The acute effect of preprandial exogenous and endogenous sulphonylurea-stimulated insulin secretion on postprandial glucose excursions in patients with type 2 diabetes.

Sulphonylureas improve glucose tolerance by stimulating insulin secretion. Whether improved glucose tolerance results from enhanced early insulin release or greater total insulin secretion is not clear. Insulin response to a test meal in Type 2 diabetic subjects with and without a single dose (2.5 mg) of oral and intravenous glipizide were, therefore, measured. Intravenous glipizide enhanced early insulin release more than oral glipizide (134% and 80% vs control; p < 0.01), whereas total insulin release was equally improved (78% and 54% vs control; p < 0.01). Despite slight differences in insulin release, there was no difference in glucose tolerance (median area under concentration curve (AUC); 66.6 vs 61.9 mmol x min l-1; NS). The test meal was repeated after a bolus of intravenous insulin at the beginning of the meal. This allowed comparison of the effect of exogenous and endogenous insulin supply on postprandial glucose excursions. In spite of an early and fivefold larger rise in serum insulin after intravenous administration of the hormone than after intravenous glipizide (725% vs 134%; p < 0.01), postprandial glucose was no better than after glipizide (median AUC; 87.8 vs 66.6 mmol x min l-1; NS). In contrast, glucose tolerance was better after oral glipizide compared to intravenous insulin (median AUC; 61.9 vs 87.8 mmol x min l-1; p < 0.05). In conclusion, the total amount of insulin secreted seems more important than the timing of the insulin release for the postprandial glucose tolerance in Type 2 diabetic subjects. Neither endogenous nor peripheral premeal supply of insulin could normalize postprandial glucose excursions in patients with Type 2 diabetes.