TY - JOUR
T1 - Effect of Hyperglycemia on Mitochondrial Respiration in Type 2 Diabetes
AU - Rabøl, Rasmus
AU - Højberg, Patricia M V
AU - Almdal, Thomas
AU - Boushel, Robert
AU - Haugaard, Steen B
AU - Madsbad, Sten
AU - Dela, Flemming
AU - Rabøl, Rasmus
AU - Højberg, Patricia M V
AU - Almdal, Thomas
AU - Boushel, Robert
AU - Haugaard, Steen B
AU - Madsbad, Sten
AU - Dela, Flemming
N1 - 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
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
U2 - 10.1210/jc.2008-1475
DO - 10.1210/jc.2008-1475
M3 - Journal article
C2 - 19141588
SN - 0021-972X
VL - 94
SP - 1372
EP - 1378
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 4
ER -
