Department of Endocrinology, Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, China.
Department of Radiology, Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, China.
Diabetes Metab Res Rev. 2019 Oct;35(7):e3177. doi: 10.1002/dmrr.3177. Epub 2019 May 27.
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 7 days. Nine nondiabetics matched for age, body mass index, and physical activity were recruited as controls. We applied 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 50 seconds 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 1 week, as well as homeostasis model assessment of β cell function and C-peptide/glucose ratio t , 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.
骨骼肌能量代谢降低与 2 型糖尿病的发生有关。强化胰岛素治疗已被报道可维持新诊断的 2 型糖尿病患者的血糖控制，但潜在机制尚不清楚。在此，我们旨在描述肌肉线粒体氧化磷酸化（OxPhos）活性对胰岛素诱导血糖控制的贡献。
21 名新诊断的 2 型糖尿病患者接受连续皮下胰岛素输注 7 天。招募了 9 名年龄、体重指数和体力活动相匹配的非糖尿病患者作为对照。我们应用 P 磁共振波谱法记录对照组和糖尿病患者在胰岛素治疗前后的肌肉磷酸肌酸（PCr）通量。线粒体 OxPhos 率计算为运动停止后前 50 秒内 PCr 的变化量/时间。
在新诊断的 2 型糖尿病患者中，肌肉线粒体 OxPhos 率在胰岛素治疗后得到恢复。值得注意的是，这种改变与过去 1 周内 1,5-脱水葡萄糖醇（一种反映血糖控制的血清标志物）的改善以及β细胞功能和 C 肽/葡萄糖比 t 的稳态模型评估呈正相关，这两个指标均反映了基础胰岛素分泌。此外，有糖尿病家族史和更严重糖毒性的患者通过胰岛素治疗更能改善线粒体功能。
本研究提供了证据表明，强化胰岛素治疗可促进新诊断的 2 型糖尿病患者的肌肉能量代谢。它与β细胞功能的恢复相关，有助于胰岛素诱导的血糖控制。
