Effect of hyperglycemia on mitochondrial respiration in type 2 diabetes

J Clin Endocrinol Metab. 2009 Apr;94(4):1372-8. doi: 10.1210/jc.2008-1475. Epub 2009 Jan 13.

Abstract

Aim: Skeletal muscle mitochondrial content is reduced in type 2 diabetes mellitus (T2DM). Whether hyperglycemia inhibits mitochondrial biogenesis and/or function is unknown. This study examined the effect of different levels of glycemia on skeletal muscle mitochondrial function in patients with T2DM.

Patients and methods: Eleven patients with T2DM [9 males, 2 females; age, 52.8 +/- 2.5 yr (mean +/- se); body mass index, 30.2 +/- 1.1 kg/m(2)] in poor glycemic control were treated with insulin aspart and NPH insulin for a median period of 46 d (range, 31-59). Mitochondrial respiration and citrate synthase activity (a marker of mitochondrial content) were measured before and after treatment. Eleven healthy subjects (age, 53.3 +/- 2.7 yr; body mass index, 30.6 +/- 1.1 kg/m(2)) were included as controls.

Results: Hemoglobin A1c (9.1 +/- 0.5 to 7.5 +/- 0.3%; P < 0.001) and fasting plasma glucose (12.7 +/- 1.1 to 6.5 +/- 0.3 mmol/liter; P < 0.001) were reduced after treatment. Mitochondrial respiration per milligram muscle was lower in T2DM compared to controls [substrates for complex I, 24% lower (P < 0.05); substrates for complex I+II, 17% lower (P < 0.05)]. Mitochondrial respiration and citrate synthase activity did not differ before and after improvements in glycemic control, but mitochondrial respiration correlated with fasting plasma glucose before (r(2) = 0.53; P < 0.05) but not after treatment [r(2) = 0.0024; not significant (NS)]. Mitochondrial respiration normalized to mitochondrial content did not differ between control subjects and patients with T2DM.

Discussion: Mitochondrial respiration and content was not improved after significant improvements in glycemic control. However, severe hyperglycemia inhibited respiration reversibly, but moderate hyperglycemia and mitochondrial function were not correlated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Body Mass Index
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / metabolism*
  • Female
  • Fructosamine / blood
  • Glycated Hemoglobin A / drug effects
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hyperglycemia / drug therapy
  • Hyperglycemia / metabolism*
  • Hypoglycemic Agents / therapeutic use
  • Insulin / analogs & derivatives
  • Insulin / therapeutic use
  • Insulin Aspart
  • Insulin, Isophane / therapeutic use
  • Male
  • Middle Aged
  • Mitochondria, Muscle / metabolism*
  • Muscle, Skeletal / metabolism
  • Oxygen Consumption / drug effects
  • Oxygen Consumption / physiology*

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Fructosamine
  • Insulin, Isophane
  • Insulin Aspart