Glycemic Control, Skeletal Muscle Insulin Sensitivity, and Skeletal Muscle Mitochondrial Complex I-V Content in Type 2 Diabetics

Abstract

PURPOSE: In type 2 diabetes (T2D), 46% of patients are poorly controlled (HbA1c ≥ 7.0%) and poor glycemic control is linked to low skeletal muscle insulin sensitivity (SI). Skeletal muscle mitochondrial dysfunction is a hallmark of T2D. We hypothesized that skeletal muscle mitochondrial content would be lower in poor (PCD; N = 4) controlled (HbA1c: 8.8 ± 0.3%) versus well (WCD; N = 6) controlled (HbA1c: 6.3 ± 0.1%) T2D and linked to HbA1c and SI. METHODS: Skeletal muscle mitochondrial content was assessed by Western blot for OXPHOS subunits complex I-V content. An insulin modified intravenous glucose tolerance test was performed and SI was calculated using minimal model analysis. RESULTS: There was no difference in OXPHOS subunits complex I (WCD: 0.9 ± 0.1 AU; PCD: 1.0 ± 0.1 AU), complex II (WCD: 1.3 ± 0.1 AU; PCD: 1.4 ± 0.1 AU), complex III (WCD: 1.2 ± 0.2 AU; PCD: 1.1 ± 0.1 AU), complex IV (WCD: 1.2 ± 0.1 AU; PCD: 1.0 ± 0.1 AU), or complex V (WCD: 1.0 ± 0.1 AU; WCD: 0.9 ± 0.1 AU). SI was lower in PCD vs. WCD (PCD: 0.2 ± 0.1; WCD: 2.4 ± 0.2). Linear regression revealed significant relationships between the OXPHOS subunits complex I, II, III, and IV, but not with complex V. There were no relationships between OXPHOS subunits complex I-V and HbA1c or SI, but high HbA1c was linked to low SI (r = -0.80; p < 0.01). CONCLUSIONS: These results suggest that differences in skeletal muscle mitochondrial content (OXPHOS subunits complex I-V) do not explain differences in glycemic control or skeletal muscle insulin sensitivity between poor and well controlled T2D.