Improved skeletal muscle energy metabolism relates to the recovery of β cell function by intensive insulin therapy in drug naïve type 2 diabetes.

Abstract

Diminished energy turnover of skeletal muscle is involved in the development of type 2 diabetes. Intensive insulin therapy has been reported to maintain glycaemic control in newly diagnosed type 2 diabetes, while the underlying mechanism remains unclear. Herein, we aimed to characterize the contribution of muscular mitochondrial oxidative phosphorylation (OxPhos) activity to insulin-induced glycaemic control. There were 21 drug naïve patients with type 2 diabetes receiving continuous subcutaneous insulin infusion for 7days. Nine nondiabetics matched for age, body mass index, and physical activity were recruited as controls. We applied 31 P magnetic resonance spectroscopy to record in vivo muscular phosphocreatine (PCr) flux in controls and diabetics before and after insulin therapy. The mitochondrial OxPhos rate was calculated as ΔPCr/Δtime during the first 50seconds after cessation of exercise. In drug naïve type 2 diabetes, muscular mitochondrial OxPhos rate was restored after insulin therapy. Notably, this alteration was positively associated with the improvements of 1,5-anhydroglucitol, a serum marker for glucose control over the last 1week, as well as homeostasis model assessment of β cell function and C-peptide/glucose ratio t0 , two indices for basal insulin secretion. Furthermore, patients with diabetes family history and more severe glucotoxicity tend to achieve greater improvement in mitochondrial function by insulin. This study provides evidence that intensive insulin therapy facilitates muscular energy metabolism in drug naïve type 2 diabetes. It correlates to the recovery of β cell function, contributing to insulin-induced glucose control.