Plasma IL-1Ra: linking hyperapoB to risk factors for type 2 diabetes independent of obesity in humans.

ABSTRACT:

Background/objective

Plasma apoB predicts the incidence of type 2 diabetes (T2D); however, the link between apoB-linpoproteins and risks for T2D remain unclear. Insulin resistance (IR) and compensatory hyperinsulinemia characterize prediabetes, and the involvement of an activated interleukin-1 (IL-1) family, mainly IL-1? and its receptor antagonist (IL-Ra), is well documented. ApoB-lipoproteins were reported to promote IL-1? secretion in immune cells; however, in vivo evidence is lacking. We hypothesized that obese subjects with hyperapoB have an activated IL-1 system that explains hyperinsulinemia and IR in these subjects.

Subjects/methods

We examined 81 well-characterized normoglycemic men and postmenopausal women (?27?kg?m(-2), 45-74 years, non-smokers, sedentary, free of chronic disease). Insulin secretion and sensitivity were measured by the gold-standard Botnia clamp, which is a combination of a 1-h intravenous glucose tolerance test (IVGTT) followed by 3-h hyperinsulinemic euglycemic clamp.

Results

Plasma IL-1? was near detection limit (0.071-0.216?pg?ml(-1)), while IL-1Ra accumulated at 1000-folds higher (77-1068?pg?ml(-1)). Plasma apoB (0.34-1.80?g?l(-1)) associated significantly with hypersinsulinemia (totalIVGTT: C-peptide r=0.27, insulin r=0.22), IR (M/I=-0.29) and plasma IL-1Ra (r=0.26) but not with IL-1?. Plasma IL-1Ra associated with plasma IL-1? (r=0.40), and more strongly with hyperinsulinemia and IR than apoB, while the association of plasma IL-1? was limited to second phase and total insulin secretion (r=0.23). Adjusting the association of plasma apoB to hyperinsulinemia and IR for IL-1Ra eliminated these associations. Furthermore, despite equivalent body composition, subjects with hyperapoB (?80th percentile, 1.14?g?l(-1)) had higher C-peptide secretion and lower insulin sensitivity than those with low plasma apoB (?20th percentile, 0.78?g?l(-1)). Adjustment for plasma IL-1?Ra eliminated all group differences.

Conclusion

Plasma apoB is associated with hyperinsulinemia and IR in normoglycemic obese subjects, which is eliminated upon adjustment for plasma IL-1Ra. This may implicate the IL-1 family in elevated risks for T2D in obese subjects with hyperapoB.

SUBMITTER: Bissonnette S 

PROVIDER: S-EPMC4657760 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature