1436-P: Metformin Increases Skeletal Muscle Mitochondrial Function and Acute Phase Insulin Sensitivity in Obstructive Sleep Apnea

Abstract

Introduction: Obstructive sleep apnea (OSA) is a prevalent sleep disorder with high type 2 diabetes (T2D) risk. OSA therapy includes positive airway pressure (PAP) treatment, which resolves breathing events but modestly improves metabolic health. Metformin is recommended for T2D prevention but is not advocated in patients with OSA. Our pilot study evaluated the effects of metformin on glucose metabolism and mitochondrial function in OSA patients. Methods: Sixteen adults (50.5±1.6 years, BMI: 36.4±0.8 kg/m2) with OSA (apnea hypopnea index: 53.2±21.1 events/hour) were randomized to receive placebo (n=8) or metformin (n=8) treatment along with PAP for 3 months in a double-blind parallel-group design. Whole body and adipose tissue-specific insulin sensitivity (IS) was determined by oral glucose tolerance test (OGTT) . Skeletal muscle mitochondrial function was determined by high-resolution respirometry using biopsies obtained at baseline and after 3 months of treatment. Results: Change in whole body IS (Matsuda index) was not different in metformin or placebo treated groups (p=0.46) . However, improved acute phase responses during OGTT - glucose uptake (p=0.02) , insulin release (p=0.03) , and suppressed lipolysis (p=0.03) were observed with metformin treatment relative to control. Increased skeletal muscle mitochondrial function was evident with metformin relative to control. Specifically, metformin increased complex I phosphorylation and complex IV electron transfer capacity. Conclusion: Metformin treatment improves acute phase IS and insulin suppression of lipolysis in OSA patients. Strikingly, metformin improved skeletal muscle mitochondrial function independent of changes in second phase glucose disposal and BMI, indicating improved tissue metabolic function. These data suggest that in patients with OSA, improvement in tissue level metabolic function may precede changes in whole-body IS and metformin may improve metabolism. Disclosure E.R.M.Zunica: None. E.C.Heintz: None. R.C.Hebert: None. M.C.Tanksley: None. E.C.Mader: None. J.P.Kirwan: None. C.L.Axelrod: None. P.Singh: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (DK123456789) ;National Institute of General Medical Sciences (GM123456789)