Metformin Blunts Vascular Insulin Sensitivity After Exercise Training in Adults at Risk for Metabolic Syndrome
Abstract
Context: Metformin is the first-line pharmacotherapy for treating hyperglycemia, and it lowers cardiovascular disease risk. Prior work suggests that metformin can, however, interfere with metabolic adaptations to exercise. To date, no work has tested if metformin (Met) alters exercise training mediated vascular insulin sensitivity, and whether this is exercise intensity dependent.
Objective: This work aimed to test the hypothesis that Met blunts vascular insulin sensitivity in an intensity-based manner among adults at risk for metabolic syndrome.
Methods: In a double-blind, placebo-controlled trial, participants were randomly assigned to low-intensity exercise plus placebo (∼55% VO2max 5d/wk, LoEx + PL, n = 22) or metformin (2000 mg/d, LoEx + Met, n = 21) and high-intensity exercise plus placebo (∼85% VO2max 5d/wk, HiEx + PL, n = 24) or metformin (HiEx + Met, n = 24) for 16 weeks. A 120-minute euglycemic-hyperinsulinemic clamp (40 mU/m2/min, 90 mg/dL) was conducted pre and post treatment to assess macrovascular insulin sensitivity via brachial artery flow-mediated dilation (%FMD, conduit artery) as well as microvascular insulin sensitivity using contrast-enhanced ultrasound (eg, microvascular blood volume [MBV, perfusion] and microvascular blood flow [MBF]). Fasting and clamp-derived glucose, insulin, inflammatory measures (eg, endothelin-1 [ET-1], tumor necrosis factor α [TNF-α], soluble receptor for advanced glycation end products [sRAGE]), and nitric oxide…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 24 participants or records.
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