Effects of weight loss and insulin reduction on arterial stiffness in the SAVE trial

Timothy M Hughes, Andrew D Althouse, Nancy A Niemczyk, Marquis S Hawkins, Allison L Kuipers, Kim Sutton-Tyrrell, Timothy M Hughes, Andrew D Althouse, Nancy A Niemczyk, Marquis S Hawkins, Allison L Kuipers, Kim Sutton-Tyrrell

Abstract

Background: Chronic arterial stiffness contributes to the negative health effects of obesity and insulin resistance, which include hypertension, stroke, and increased cardiovascular and all-cause mortality. Weight loss and improved insulin sensitivity are individually associated with improved central arterial stiffness; however, their combined effects on arterial stiffness are poorly understood. The purpose of this study was to determine how insulin levels modify the improvements in arterial stiffness seen with weight loss in overweight and obese young adults.

Methods: To assess the effects of weight loss and decreased fasting insulin on vascular stiffness, we studied 339 participants in the Slow the Adverse Effects of Vascular Aging (SAVE) trial. At study entry, the participants were aged 20-45, normotensive, non-diabetic, and had a body-mass index of 25-39.9 kg/m2. Measures of pulse wave velocity (PWV) in the central (carotid-femoral (cfPWV)), peripheral (femoral-ankle (faPWV)), and mixed (brachial-ankle (baPWV)) vascular beds were collected at baseline and 6 months. The effects of 6-month change in weight and insulin on measures of PWV were estimated using multivariate regression.

Results: After adjustment for baseline risk factors and change in systolic blood pressure, 6-month weight loss and 6-month change in fasting insulin independently predicted improvement in baPWV but not faPWV or cfPWV. There was a significant interaction between 6-month weight change and change in fasting insulin when predicting changes in baPWV (p < 0.001). Individuals experiencing both weight loss and insulin reductions showed the greatest improvement in baPWV.

Conclusions: Young adults with excess weight who both lower their insulin levels and lose weight see the greatest improvement in vascular stiffness. This improvement in vascular stiffness with weight loss and insulin declines may occur throughout the vasculature and may not be limited to individual vascular beds.

Trial registration: ClinicalTrials.gov NCT00366990.

Figures

Figure 1
Figure 1
Adjusted* mean changes in baPWV by insulin- and weight-loss groups in the SAVE trial. Baseline and 6-month mean PWV measures are plotted by weight and insulin-loss groups where groups are split by median changes in weight and fasting insulin levels. *Adjusted for age, sex, race, smoking status and baseline BMI, mean arterial pressure, HDLc, triglycerides, CRP, fasting insulin, baPWV and change in mean arterial pressure. baPWV: brachial-ankle pulse-wave velocity.

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