Effect of Hyperglycemia on Mitochondrial Respiration in Type 2 Diabetes

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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.
Original languageEnglish
JournalJournal of Clinical Endocrinology and Metabolism
Issue number4
Pages (from-to)1372-78
Publication statusPublished - 2009

Bibliographical note

Keywords: Adult; Aged; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Female; Fructosamine; Hemoglobin A, Glycosylated; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin, NPH; Male; Middle Aged; Mitochondria, Muscle; Muscle, Skeletal; Oxygen Consumption

ID: 12771838