Abstract

Purpose: To identify factors associated with declining β-cell compensation for insulin resistance.

Methods: In a cohort of Hispanic women with recent gestational diabetes mellitus, oral (OGTT) and intravenous (IVGTT) glucose tolerance tests and bioelectrical impedance measurements were performed at 15-month intervals for up to five years or until fasting plasma glucose exceeded 140 mg/dl (7.8 mmol/l). Data were analyzed to identify predictors of declining β-cell compensation for insulin resistance (the disposition index; “DI”) and to examine the mechanism of weight gain and changes in circulating levels of selected adipokines and inflammatory markers on β-cell compensation decline.

Results: 60 non-diabetic women had a median of four sets of OGTT+IVGTT during a median follow-up of 52 months. Fourteen of the women developed diabetes. None of the baseline characteristics were significantly predictive of a decline in DI. There were significant univariate associations between declining DI and weight gain (specifically fat gain), declining adiponectin and rising C-reactive protein (CRP). Multivariate analysis showed that the weight gain was the most significant factor associated with declining DI, The amount of association between weight gain and declining DI was explained 31% by changes in adiponectin and CRP, and 40% by changes in insulin resistance.

Conclusions: These results identify weight gain as the strongest factor associated with declining β-cell compensation for insulin resistance in Hispanic women at high risk for type 2 diabetes. Such effect may be mediated through at least two effects: alterations in adipokine levels and increasing insulin resistance.