Introduction: Skeletal muscle accounts for approximately 80% of insulin-stimulated glucose uptake and a key defect in the aetiology of type 2 diabetes (T2D) is the development of skeletal muscle insulin resistance [1]. There is strong evidence linking oxidative stress and skeletal muscle insulin resistance in rodents [2, 3]. However, despite the promising evidence of antioxidants reducing skeletal muscle insulin resistance in rodents [2, 3], evidence to support antioxidant therapies for the treatment of skeletal muscle insulin resistance in humans is lacking. We therefore investigated the potential ameliorative effects of antioxidant ascorbic acid (AA) supplementation on skeletal muscle insulin sensitivity and oxidative stress in people with T2D.
Methods: Participants with stable glucose control (HbA1C 7.6 ± 0.2%, mean ± SEM) commenced a randomized cross-over study involving four months of AA (2 x 500 mg/day) or placebo supplementation with a 1 month washout between treatments. Skeletal muscle insulin sensitivity was assessed using a 40 mU/m2 hyperinsulinaemic, euglycaemic clamp coupled with infusion of 6,6-D2 glucose. Muscle biopsies were measured for AA concentration and oxidative stress markers.
Results: Compared with placebo supplementation, AA supplementation significantly increased skeletal muscle insulin sensitivity (~60%), AA concentration (~31%), but significantly decreased levels of insulin-stimulated oxidative stress (~67%).
Conclusions/interpretation: In summary, AA supplementation improves insulin-stimulated oxidative stress and insulin sensitivity in skeletal muscle of people with type 2 diabetes. Findings implicate AA supplementation as a potentially cheap, convenient, and effective adjunct therapy in the treatment of insulin resistance in people with type 2 diabetes.