Metformin may improve insulin resistance (IR) and vascular health in adolescents with type 1 diabetes (T1D), according to a study recently published in Circulation.
Glycemic control is particularly difficult to achieve in adolescents with T1D. Investigators hypothesized that adolescents with T1D exhibit impaired vascular function and that metformin would improve IR and have cardioprotective properties in these patients.
Inclusion criteria included adolescents aged 12 to 21 years, Tanner Stage>1, diabetes duration of greater than or equal to 1 year, and T1D. The study enrolled 48 adolescents with T1D (40% body mass index [BMI] ≥ 90th percentile; 56% female) and 24 adolescents without diabetes of similar age, BMI, and sex distribution to serve as controls.
The participants underwent baseline MRI of the ascending aorta (AA) and descending aorta (DA) to assess pulse wave velocity (PWV), relative area change (RAC), maximal wall shear stress (WSSMAX) and time-averaged wall shear stress (WSSTA).
Additionally, patients underwent baseline ultrasound to assess carotid intima-media thickness (cIMT), DynaPulse to assess brachial distensibility (BrachD), fasting labs following overnight glycemic control, and hyperinsulinemic-euglycemic clamp to assess insulin sensitivity.
Adolescents with T1D were randomized 1:1 to receive either 2000 mg metformin or placebo daily for 3 months. Post-treatment, baseline tests were repeated.
Compared with nondiabetic controls, adolescents with T1D exhibited impaired aortic health with elevated AA and DA PWV; low AA and DA RAC; and high AA, DA WSSMAX, and WSSTA. Metformin vs placebo analysis showed improved glucose infusion rate/insulin, reduced weight, BMI, and fat mass.
Insulin sensitivity also improved in normal-weight adolescents. AA WSSMAX, AA PWV, and far-wall diastolic cIMT all decreased in the metformin group compared with placebo.
Investigators discovered that adolescents with T1D exhibited IR and impaired vascular health. Regardless of BMI weight, fat mass, insulin dose, or aortic and carotid health, metformin improves IR and shows promise as a cardioprotective measure in adolescents with T1D.
Bjornstad P, Schäfer M, Truong U, et al. Metformin improves insulin sensitivity and vascular health in youth with type 1 diabetes: A randomized control trial [published online September 27, 2018]. Circulation. doi: 10.1161/CIRCULATIONAHA.118.035525