Interleukin-6 gene polymorphism and insulin sensitivity

Type 2 diabetes and the insulin resistance syndrome have been hypothesized to constitute manifestations of an ongoing acute-phase response. We aimed t o study an interleukin-6 (IL-6) gene polymorphism in relation to insulin se nsitivity (IL-6 is the main cytokine involved in an acute-phase response). Subjects homozygous for the C allele at position -174 of the IL-8 gene (Sfa NI genotype), associated to lower plasma IL-6 levels, showed significantly lower integrated area under the curve of serum glucose concentrations (AUC( glucose)) after an oral glucose tolerance test, lower blood glycosylated he moglobin, lower fasting insulin levels, lower total and differential white blood cell count (a putative marker of peripheral IL-6 action), and an incr eased insulin sensitivity index than carriers of the G allele, despite simi lar age and body composition. A gene dosage effect was especially remarkabl e for AUC(glucose) (6.4 vs. 9.3 vs. 9.7 mmol/l in C/C, C/G, and G/G individ uals, respectively). The serum concentration of fully glycosylated cortisol binding globulin (another marker of IL-6 action), suggested by concanavali n A adsorption, was lower in C/C subjects than in G/G individuals (32.6 +/- 2.9 vs. 37.6 +/- 4.6 mg/l, P = 0.03). In summary, a polymorphism of the IL -6 gene influences the relationship among insulin sensitivity, postload glu cose levels, and peripheral white blood cell count.