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
PY - 2009
Y1 - 2009
N2 - Aim: Skeletal muscle mitochondrial content is reduced in type 2 diabetes (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. Material and methods: Eleven patients with T2DM (M/F:9/2, age: 52.8 +/- 2.5 years (mean +/- SE), BMI: 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 [range: 31-59] days. Mitochondrial respiration and citrate synthase (CS) activity (a marker of mitochondrial content) were measured before and after treatment. Eleven healthy subjects (age: 53.3 +/- 2.7 years, BMI: 30.6 +/- 1.1 kg/m(2)) were included as controls. Results: HbA1c (9.1 +/- 0.5% to 7.5 +/- 0.3%, p<0.001) and fasting plasma glucose (12.7 +/- 1.1 mmol/L to 6.5 +/- 0.3 mmol/L, p<0.001) were reduced after treatment. Mitochondrial respiration per mg muscle was lower in T2DM compared to controls (substrates for complex I: - 24% (p<0.05), substrates for complex I+II: - 17% (p<0.05). Mitochondrial respiration and CS 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, NS). Mitochondrial respiration normalized to mitochondrial content did not differ between control subjects and patients with type 2 diabetes. Discussion: Mitochondrial respiration and content was not improved following significant improvements in glycemic control. However, severe hyperglycemia inhibited respiration reversibly but moderate hyperglycemia and mitochondrial function was not correlated.
AB - Aim: Skeletal muscle mitochondrial content is reduced in type 2 diabetes (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. Material and methods: Eleven patients with T2DM (M/F:9/2, age: 52.8 +/- 2.5 years (mean +/- SE), BMI: 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 [range: 31-59] days. Mitochondrial respiration and citrate synthase (CS) activity (a marker of mitochondrial content) were measured before and after treatment. Eleven healthy subjects (age: 53.3 +/- 2.7 years, BMI: 30.6 +/- 1.1 kg/m(2)) were included as controls. Results: HbA1c (9.1 +/- 0.5% to 7.5 +/- 0.3%, p<0.001) and fasting plasma glucose (12.7 +/- 1.1 mmol/L to 6.5 +/- 0.3 mmol/L, p<0.001) were reduced after treatment. Mitochondrial respiration per mg muscle was lower in T2DM compared to controls (substrates for complex I: - 24% (p<0.05), substrates for complex I+II: - 17% (p<0.05). Mitochondrial respiration and CS 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, NS). Mitochondrial respiration normalized to mitochondrial content did not differ between control subjects and patients with type 2 diabetes. Discussion: Mitochondrial respiration and content was not improved following significant improvements in glycemic control. However, severe hyperglycemia inhibited respiration reversibly but moderate hyperglycemia and mitochondrial function was 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 - The Journal of clinical endocrinology and metabolism
JF - The Journal of clinical endocrinology and metabolism
IS - 4
ER -