Bacha et al. (1) studied the relationship of serum adiponectin concentrations with hepatic and peripheral insulin sensitivity, body fat distribution, and components of the metabolic syndrome in adolescents. In addition, they reported a negative association between fasting serum proinsulin and the fasting serum proinsulin-to-insulin ratio with adiponectin levels, which was independent of adiposity. They conclude that hypoadiponectinemia may be a marker of β-cell dysfunction.

These data are novel and appear to be suggestive of a primary role of adiponectin in β-cell function. We consider this hypothesis to be valid, especially since expression of adiponectin receptor 1 and 2 was recently detected in β-cells (2). In addition, administration of adiponectin to β-cells seems to inhibit palmitic acid–induced apoptosis (3). However, it is not readily obvious that the correlations of serum adiponectin with fasting serum proinsulin and serum proinsulin-to-insulin ratio indicate a direct effect of adiponectin on insulin secretory function in vivo. First, the proinsulin-to-insulin ratio was negatively associated with acute insulin response only in subjects with type 2 diabetes (4) but not in individuals without diabetes (5), indicating that this ratio can be used as a parameter for β-cell function only when a more severe insulin secretory defect is present. Second, as discussed by Roder et al. (5), this ratio is associated with insulin sensitivity in a group of subjects covering a broad range of insulin resistance. Thus, because in the article by Bacha et al. the proinsulin-to-insulin ratio was adjusted for BMI but not for insulin sensitivity, it remains unclear whether the relationship with adiponectin simply reflects insulin sensitivity.

Based on the findings in the study by Bacha et al., we investigated whether plasma adiponectin is associated with parameters of insulin secretory function in our database from the Tübingen Family Study. A total of 685 normal glucose tolerant subjects (aged 36 ± 0.4 years [mean ± SE]) were included and underwent a 75-g oral glucose tolerance test (OGTT). We measured insulin and proinsulin and determined the fasting proinsulin-to-insulin ratio. The 30-min C-peptide plasma concentrations during the OGTT and the first-phase insulin secretory index (ISI) proposed by Stumvoll et al. (6) were used as an estimate of β-cell function. Insulin sensitivity was calculated as proposed by Matsuda et al. (7). In multiple linear regression models, neither proinsulin-to-insulin ratio (r = 0.03, P = 0.46) nor 30-min C-peptide plasma concentrations (r = 0.01, P = 0.79) or ISI (r = 0.01, P = 0.80) during the OGTT were associated with fasting plasma adiponectin concentrations after adjustment for age, sex, percentage body fat, and insulin sensitivity. These findings argue against an association of plasma adiponectin concentrations with β-cell function.

Bacha F, Saad R, Gungor N, Arslanian SA: Adiponectin in youth: relationship to visceral adiposity, insulin sensitivity and β-cell function.
Diabetes Care
Kharroubi I, Rasschaert J, Eizirik DL, Cnop M: Expression of adiponectin receptors in pancreatic beta cells.
Biochem Biophys Res Commun
Rakatzi I, Mueller H, Ritzeler O, Tennagels N, Eckel J: Adiponectin counteracts cytokine- and fatty acid-induced apoptosis in the pancreatic beta-cell line INS-1.
Roder ME, Porte D Jr, Schwartz RS, Kahn SE: Disproportionately elevated proinsulin levels reflect the degree of impaired B cell secretory capacity in patients with noninsulin-dependent diabetes mellitus.
J Clin Endocrinol Metab
Roder ME, Schwartz RS, Prigeon RL, Kahn SE: Reduced pancreatic B cell compensation to the insulin resistance of aging: impact on proinsulin and insulin levels.
J Clin Endocrinol Metab
Stumvoll M, Mitrakou A, Pimenta W, Jenssen T, Yki-Järvinen H, Van Haeften T, Renn W, Gerich J: Use of the oral glucose tolerance test to assess insulin release and insulin sensitivity.
Diabetes Care
Matsuda M, DeFronzo RA: Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp.
Diabetes Care