Glucose-Dependent Insulinotropic Polypeptide Is Associated With Lower Low-Density Lipoprotein But Unhealthy Fat Distribution, Independent of Insulin: The ADDITION-PRO Study

Context: Glucose-dependent insulinotropic polypeptide (GIP) may increase lipid clearance by stimulating lipid uptake. However, given that GIP promotes release of insulin by the pancreas and insulin is anti-lipolytic, the effect may be indirect. Objective: In this study we examined the association between GIP and lipid metabolism in individuals with low to high risk of type 2 diabetes and assessed whether the associations were modified by or mediated through insulin. Design, Setting, and Participants: Analyses were based on the Danish cross-sectional ADDITIONPRO study (n 1405). Lipid metabolism was measured by fasting plasma lipids and obesity incluDing abdominal fat distribution assessed by ultrasonography. GIP and insulin were measured during an oral glucose tolerance test (0, 30 and 120 min). Linear regression analysis was used to study the associations between GIP, plasma lipids, and obesity measures. Results: A doubling in fasting GIP levels was associated with lower low-density lipoprotein in both men (mean [95% CI]0.10 mmol/l [0.18-0.03]) and women (0.14 mmol/l [0.23-0.04]) and with higher high-density lipoprotein in women (0.06 mmol/l [0.02-0.10]). In men, a doubling in stimulated GIP was associated with 0.13 cm less 0.01-0.25 sc fat but with more visceral abdominal fat (0.45 cm [0.12-0.78]) and higher waist-hip ratio (0.011 [0.004-0.019]). Conclusions: Contrary to what was previously thought, GIP may be associated with improved low-density lipoprotein clearance but with an unhealthy fat distribution independent of insulin. The effect of GIP on obesity measures was substantially different between men and women. The potential effect of GIP on visceral and sc adipose tissue physiology warrants further examination.