Abstract 18394: Gastric Inhibitory Polypeptide is Associated with Metabolic Disorder and Cardiovascular Disease Independent of Glucose in Humans
Background- Emerging animal studies have reported the beneficial effect of interrupting gastric inhibitory polypeptide (GIP) receptor signaling in metabolic disorders including extreme fat deposition with insulin resistance and glucose intolerance. These results propose the hypothesis that hyper GIP secretion may contribute to the development of cardiovascular disease (CVD) in humans. However, most studies have focused on incretin responses to glucose loading, and the association between endogenous GIP levels and cardiometabolic disorders has not been well defined in humans.
Methods and Results- To examine the association between fasting GIP and cardiometabolic disorders or CVD independent of plasma glucose (PG) levels, we analysed 300 non-diabetic subjects. Furthermore we performed in vitro functional analysis using human macrophage cells. Simple regression analysis demonstrated that the fasting total GIP was correlated with cardiometabolic disorders such as waist to hip ratio, hyperinsulinemia, and HOMA-IR. ANCOVA and logistic analysis after adjustment for age, gender, BMI, smoking, HOMA-IR, hypertension, LDL cholesterol, HDL cholesterol, eGFR and PG, revealed that fasting GIP was increased in the subjects with CVD than non-CVD (53.7 ± 32.2 v.s. 28.2 ± 18.1, p<0.01), and each tertile increase in fasting GIP was associated with the prevalence of CVD (odds ratio 3.12 per tertile, 95% CI 1.73 to 5.62; p <0.01). Furthermore, molecular analysis revealed that GIP receptor was present in human monocyte/macrophage, T-lymphocyte, and human carotid atherosclerotic lesion. In vitro analysis revealed that GIP stimulation up-regulated gene expression of interleukin 6, CC chemokine receptor (CCR) 2, CCR5, and scavenger receptor type A in human THP-1 macrophages.
Conclusions- These results suggest that oversecretion of GIP may contribute to cardiometabolic disorder, resulting in the development of CVD independent of PG in humans.
- © 2012 by American Heart Association, Inc.