Abstract

Abstract Aim The aim was to assess the relationship between adipokines including interleukin 6 (IL-6), leptin and adiponectin with development of type 2 diabetes and assess the role of obesity and insulin resistance in these relationships.

Abstract Methods A prospective study of 3599 non-diabetic men aged 60-79 followed up for a mean period of 5 years during which there were 108 incident cases of type 2 diabetes.

Abstract Results Elevated IL-6 and leptin and low adiponectin were associated with increased risk of type 2 diabetes even after adjustment for BMI, lifestyle factors, pre-existing cardiovascular disease and systolic blood pressure. The relative risks (95% CI) (3rd versus 1^st third) were 2.02 (1.14,3.58) for IL6, 1.91 (0.97,3.76) for leptin, and 0.40 (0.23,0.70) for adiponectin. Further adjustment for insulin resistance made minor differences to the IL-6 diabetes relationship [adjusted RR 2.1 (1.18,3.81), weakened the associations with adiponectin (adjusted RR 0.59 (0.33,1.04) and abolished the association between leptin and diabetes [adjusted RR 1.12 (0.55,2.26)]. The inverse relation between low adiponectin and diabetes was significantly stronger in men who were obese (waist circumference >102 or BMI > 30kg/m) [adjusted RR 0.30 (0.11,0.7)] relative to leaner men [adjusted RR 0.93 (0.44,1.55)] (test for interaction p=0.04).

Abstract Conclusion The association between leptin and incident diabetes is mediated by insulin resistance. By contrast the positive association between IL-6 and diabetes appeared to be independent of obesity and insulin resistance. Finally, the association between low adiponectin and increased risk of diabetes appears to be significantly stronger in obese men than leaner counterparts.