Serum advanced glycation end products (AGEs) are associated with insulin resistance

Background: In addition to the important role of advanced glycation end products (AGEs) in the pathogenesis of diabetic vascular complications, recent data suggest that advanced glycation end products can also impair insulin action in vitro. We have investigated whether circulating advanced glycation end products are associated with insulin resistance in human subjects independent of metabolic parameters.

Methods: Two hundred and seven healthy non-obese non-diabetic subjects (97 male, 110 female) were recruited from the community. Serum levels of advanced glycation end products, adiponectin, malondialdehyde and high sensitivity C-reactive protein were assayed. Insulin resistance was determined by the homeostasis model assessment index (HOMA-IR).

Results: Male subjects had significantly higher body mass index, waist circumference and lower adiponectin level than female subjects and were more insulin resistant. Serum advanced glycation end products (3.67 ± 1.15 unit/mL versus 3.23 ± 1.15, p < 0.05) and malondialdehyde levels (p < 0.05) were also higher in male than in female subjects. Serum advanced glycation end products correlated with HOMA-IR in both male (r = 0.32, p = 0.004) and female subjects (r = 0.28, p = 0.003). Serum adiponectin inversely correlated with HOMA-IR in female (r = - 0.38, p < 0.001) but not in male subjects. On multiple regression analysis, serum AGEs remained an independent determinant of HOMA-IR even after adjusting for age, gender, body mass index, waist, smoking, adiponectin and markers of oxidative stress and inflammation.

Conclusions: Formation and accumulation of advanced glycation end products progress during normal ageing. We have demonstrated that the circulating level of advanced glycation end products is associated with insulin resistance even in non-obese, non-diabetic subjects independent of adiponectin.