Inflammation, insulin resistance, and adiposity - A study of first-degree relatives of type 2 diabetic subjects

OBJECTIVE - Inflammatory markers such as C-reactive Protein (CRP) are associated With insulin resistance, adiposity, and type 2 diabetes. Whether inflammation causes insulin resistance or is an epiphenomenon of obesity remains Unresolved. We aimed to determine whether first-degree relatives of type 2 diabetic subjects differ in insulin sensitivity from control subjects without a family history of diabetes, whether first-degree relatives of type 2 diabetic subjects and control subjects differ in CRP, adiponectin, and complement levels, and whether CRP is related to insulin sensitivity independently of adiposity. RESEARCH DESIGN AND METHODS - We studied 19 young normoglycemic non-obese first-degree relatives of type 2 diabetic subjects and 22 control subjects who were similar for age, sex, and BMI. Insulin sensitivity (glucose infusion rate [GIR]) was measured by the euglycemic-hyperinsulinemic clamp. Dual-energy X-ray absorptiometry determined total and abdominal adiposity. Magnetic resonance imaging Measured abdominal adipose tissue volumes. RESULTS - First-degree relatives of type 2 diabetic subjects had a 20% lower GIR than the control group (51.8 +/- 3.9 Vs. 64.9 +/- 4.6 mumol (.) min(-1) (.) kg fat-free mass(-1), P = 0.04). However, first-degree relatives of subjects With type 2 diabetes and those Without a family history Of diabetes had normal and comparable levels of CRP, adiponectin, and complement proteins. When the cohort was examined as a whole, CRP was inversely related to GIR (r = -0.33, P 0.04) and adiponectin (r = -0.34, P = 0.03) and positively related to adiposity (P < 0. 04). However, CRP was not related to GIR independently of fat mass. In contrast to C3 (r = 0.41, P 0.009) and factor B (r = 0.43, P = 0.005), CRP was unrelated to factor D. CONCLUSIONS - The insulin-resistant state is not associated with changes in inflammatory markers or complement proteins in subjects at high risk of type 2 diabetes. Our study confirms a strong relationship between CRP and fat mass. Increasing adiposity and insulin resistance may interact to raise CRP levels.