Relationship of fetuin-A levels to weight-dependent insulin resistance and type 2 diabetes mellitus

Objective: Weight gain and obesity are of substantial importance for the development of insulin-resistance and type-2 diabetes mellitus. Fetuin-A, a liver-derived glycoprotein, may also play a role in these alterations. Several studies have demonstrated an association between fetuin-A and body weight which, however, was within a fairly small range at the border of overweight to obesity. The present study examines the relationship between fetuin-A and a wide range of BMI, together with basal insulin, and HOMA-IR. In addition, matched groups of non-diabetic patients and those with type-2 diabetes mellitus were compared. Methods: We examined the relationship between fetuin-A and BMI, insulin, HOMA-IR, glucose and HbA1c in a cohort of 445 non-diabetic obese subjects and 150 obese patients with type-2-diabetes mellitus (DM2). Results: In relation to quintiles of fetuin-A a significant increase of BMI, basal insulin and HOMA-IR was observed between the 1st and 2nd quintile with no further change thereafter. Correspondingly, fetuin-A levels increased significantly only between the 1st and 2nd quintile of BMI, insulin or HOMA-IR, respectively. When patients with type 2 diabetes were compared with non-diabetic subjects matched for BMI, insulin, and age median fetuin-A levels were not significantly different. Conclusion: At the early stage of weight gain fetuin-A could be of relevance for the development of insulin resistance. For the further progressive resistance with increasing weight in the obesity range the present data do not support a role of fetuin-A. Similarly its contribution to the resistance of type-2diabetes seems to be of minor importance.