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- Title
Influence of Hyperglycemia on Mitochondrial Function in Type 2 Diabetes.
- Authors
RabøL, Rasmus; Højberg, Patricia; Haugaard, Steen B.; Almdal, Thomas; Madsbad, Sten; Dela, Flemming
- Abstract
Introduction: Reduced mitochondrial function has been implicated as a cause of insulin resistance, possibly due to accumulation of intramyocellular lipid which inhibits insulin signaling. The cause of the reduced mitochondrial function is unknown, but genes encoding mitochondrial proteins have been shown to be downregulated in type 2 diabetes (T2DM). The present study was undertaken to examine the effect of poor and optimal glycemic control on skeletal muscle mitochondrial function in patients with T2DM. Material and methods: Eleven patients with T2DM (nine male, two female), with age 52.8 (2.5) years (SE) and BMI 30.2 (1.1) kg/m² Were included. All were treated with oral antidiabetic agents at inclusion. To optimize glycemic control, patients were after a wash out period treated with multiple insulin injections (Insulin aspart and isophan insulin) for a median period of 46 [31-59] days. Before and after insulin treatment muscle biopsies were taken from M. vastus lateralis for measurements of mitochondrial respiration. Eleven healthy subjects matched forage (53.3 (2.7) years), sex and BMI (30.6 (1.1) kg/m²) were included as controls. Results: Before insulin treatment HbA1c was 9.1 (0.5)% and mean blood glucose was 14.3 (0.5) mmol/L evaluated from seven point blood glucose profiles. After insulin treatment HbA1c had declined significantly to 7.5(0.3)% (p<0.001) and the mean blood glucose was 7.0 (0.2) mmol/L (p<0.0001). Mitochondrial respiration with substrates for complex 1 (malate, pyruvate and glutamate) was significantly lower in patients with T2DM compared to controls (-24% (p=0.01)), and respiration did not improve after near-normalization of blood glucose. Discussion: Mitochondrial function is not improved after near-normalization of blood glucose following intensive insulin treatment for approximately 5 to 8 weeks. Factors other than short term glycemic control must be responsible for the decreased mitochondrial function found in type 2 diabetes.
- Publication
Diabetes, 2007, Vol 56, pA63
- ISSN
0012-1797
- Publication type
Academic Journal