The objective of this study was to determine the role of maximum mitochondrial capacity on the variation in insulin sensitivity within a population of patients with type 2 diabetes mellitus (T2DM).

Fifty-eight participants enrolled in a cross-sectional design: eight active controls [maximum aerobic capacity (VO_2max) > 40 ml/kg · min], 17 healthy sedentary controls without a family history (FH−) and seven with a family history (FH+) of diabetes, four obese participants, and 21 patients with T2DM. Mitochondrial capacity was measured noninvasively using ³¹P magnetic resonance spectroscopy of the vastus lateralis. Maximal ATP synthetic rate (ATP_max) was determined from the rate of phosphocreatine (PCr) recovery after short-term isometric exercise.

ATP_max was lower (P < 0.001) in T2DM and higher (P < 0.001) in active as compared with healthy sedentary FH− (active, 1.01 ± 0.2; FH−, 0.7 ± 0.2; FH+, 0.6 ± 0.1; obese, 0.6 ± 0.1; T2DM, 0.5 ± 0.2 mm ATP/sec; ANOVA P < 0.0001). Insulin sensitivity, measured by euglycemic-hyperinsulinemic (80 mIU/m² · min) clamp was also reduced in T2DM (P < 0.001) (active, 12.0 ± 3.2; FH−, 7.8 ± 2.2; FH+, 6.8 ± 3.5; obese, 3.1 ± 1.0; T2DM, 3.4 ± 1.6; mg/kg estimated metabolic body size · min; ANOVA P < 0.0001). Unexpectedly, there was a broad range of ATP_max within the T2DM population where 52% of subjects with T2DM had ATP_max values that were within the range observed in healthy sedentary controls. In addition, 24% of the T2DM subjects overlapped with the active control group (range, 0.65–1.27 mm ATP/sec). In contrast to the positive correlation between ATP_max and M-value in the whole population (r² = 0.35; P < 0.0001), there was no correlation between ATP_max and M-value in the patients with T2DM (r² = 0.004; P = 0.79).

Mitochondrial capacity is not associated with insulin action in T2DM.