Impact of an Additional Pregnancy on the Natural History of Insulin Sensitivity, Beta-cell Function and Glycemia in Parous Women

OBJECTIVE: It has been postulated that pregnancies may contribute to the lifetime risk of type 2 diabetes (T2DM) in women, though direct evidence is lacking. In this context, we hypothesized that pregnancy may impact the long-term natural history of the pathophysiologic determinants of T2DM: insulin sensitivity and beta-cell function. We sought to evaluate 10-year trajectories of these features in parous women with and without an additional pregnancy. RESEARCH DESIGN AND METHODS: Three-hundred-and-three women underwent metabolic characterization at 1-year postpartum and on ≥3 more occasions over the decade thereafter. Each assessment included oral glucose tolerance test, enabling serial evaluation of insulin sensitivity/resistance (Matsuda index; HOMA-IR), beta-cell function (Insulin Secretion-Sensitivity Index-2; insulinogenic index/HOMA-IR) and glycemia. Linear mixed-effect models adjusted for diabetes risk factors were constructed to evaluate the natural time trend of these measures over 10-years in those with (n=78) and without (n=225) an additional pregnancy. RESULTS: At baseline, women who subsequently had an additional pregnancy were younger (p