Aims: To test whether liraglutide suppresses postprandial elevations in lipids and thus protects against high saturated fatty acid (SFA) diet-induced insulin resistance.
Methods:In a randomized placebo-controlled crossover study, 32 participants with normal or mildly impaired glucose tolerance received liraglutide and placebo for 3 weeks each. Insulin suppression tests (IST) were conducted at baseline and after a 24-hour SFA-enriched diet after each treatment. Plasma glucose, insulin, triglycerides and non-esterified fatty acids (NEFA) were measured over the initial 8 hours (breakfast and lunch) on the SFA diet. A subset of participants underwent ex vivo measurements of insulin-mediated vasodilation of adipose tissue arterioles and glucose metabolism regulatory proteins in skeletal muscle.Results: Liraglutide reduced plasma glucose, triglycerides and NEFA concentrations during the SFA diet (by 50%, 25% and 9%, respectively), and the SFA diet increased plasma glucose during the IST (by 36%; all P < .01 vs placebo). The SFA diet-induced impairment of vasodilation on placebo (−9.4% vs baseline; P < .01) was ameliorated by liraglutide (−4.8%; P = .1 vs baseline).In skeletal muscle, liraglutide abolished the SFA-induced increase in thioredoxin-interacting protein (TxNIP) expression (75% decrease; P < .01 vs placebo) and increased 5 0 AMP-activated protein kinase (AMPK) phosphorylation (50% vs −3%; P = .04 vs placebo).Conclusions: Liraglutide blunted the SFA-enriched diet-induced peripheral insulin resistance.This effect may be related to improved microvascular function and modulation of TxNIP and AMPK pathways in skeletal muscle.
K E Y W O R D Sinsulin resistance, liraglutide, randomised trial
This study examined whether clinical benefits gained while participating in interdisciplinary diabetes shared medical appointments (SMAs) of finite duration (three to four monthly visits) are sustained after patients return to usual care. There are currently no publications confirming sustained clinical benefits beyond 9 months after SMA discharge without continued booster sessions to maintain benefits. At the end of the study, it was confirmed that both diabetes and cardiovascular benefits gained during multidisciplinary diabetes SMAs were sustained after patients were discharged to usual care without booster sessions for up to 3 years. The only exceptions were a statistically significant decrease in diastolic blood pressure at each yearly time point and a decrease in the percentage of patients meeting an A1C goal of <9% at year 2.
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