Glycemic variability correlates strongly with postprandial beta-cell dysfunction in a segment of type 2 diabetic patients using oral hypoglycemic agents

Diabetes Care. 2009 Jun;32(6):1058-62. doi: 10.2337/dc08-1956. Epub 2009 Feb 24.

Abstract

Objective: Glucose fluctuations trigger activation of oxidative stress, a main mechanism leading to secondary diabetes complications. We evaluated the relationship between glycemic variability and beta-cell dysfunction.

Research design and methods: We conducted a cross-sectional study in 59 patients with type 2 diabetes (aged 64.2 +/- 8.6 years, A1C 6.5 +/- 1.0%, and BMI 29.8 +/- 3.8 kg/m(2)[mean +/- SD]) using either oral hypoglycemic agents (OHAs) (n = 34) or diet alone (nonusers). As a measure of glycemic variability, the mean amplitude of glycemic excursions (MAGE) was computed from continuous glucose monitoring data recorded over 3 consecutive days. The relationships between MAGE, beta-cell function, and clinical parameters were assessed by including postprandial beta-cell function (PBCF) and basal beta-cell function (BBCF) obtained by a model-based method from plasma C-peptide and plasma glucose during a mixed-meal test as well as homeostasis model assessment of insulin sensitivity, clinical factors, carbohydrate intake, and type of OHA.

Results: MAGE was nonlinearly correlated with PBCF (r = 0.54, P < 0.001) and with BBCF (r = 0.31, P = 0.025) in OHA users but failed to correlate with these parameters in nonusers (PBCF P = 0.21 and BBCF P = 0.07). The stepwise multiple regression analysis demonstrated that PBCF and OHA combination treatment were independent contributors to MAGE (R(2) = 0.50, P < 0.010), whereas insulin sensitivity, carbohydrate intake, and nonglycemic parameters failed to contribute.

Conclusions: PBCF appears to be an important target to reduce glucose fluctuations in OHA-treated type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Area Under Curve
  • Blood Glucose / metabolism*
  • Body Mass Index
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / blood
  • Insulin-Secreting Cells / physiology*
  • Metformin / therapeutic use
  • Middle Aged
  • Models, Biological
  • Oxidative Stress
  • Postprandial Period / physiology*
  • Sulfonylurea Compounds / therapeutic use

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Sulfonylurea Compounds
  • Metformin