A low disposition index in adolescent offspring of mothers with gestational diabetes: a risk marker for the development of impaired glucose tolerance in youth

AIMS/HYPOTHESIS: With the increase in gestational diabetes mellitus (GDM), there is a growing need to understand the effects of intrauterine glucose exposure on the newborn at birth and later in life. The risk of developing impaired glucose tolerance (IGT) in individuals exposed to diabetes in utero has not been adequately investigated. METHODS: We studied 255 obese adolescents with normal glucose tolerance. All of them were investigated for in utero exposure to GDM and underwent an OGTT, which was repeated after approximately 2.8 years. RESULTS: 210 (82.3%) participants were not exposed to GDM (NGDM group), and 45 (17.7%) were exposed to GDM (EGDM group). In the NGDM group, only 8.6% (n = 18) developed either IGT or type 2 diabetes compared with 31.1% (n = 14) of the EGDM group who developed either IGT or type 2 diabetes (p < 0.001). Exposure to GDM was the most significant predictor of developing IGT or type 2 diabetes (OR 5.75, 95% CI 2.19, 15.07, p < 0.001). At baseline and at follow-up, the EGDM group showed a reduction in beta cell function determined by the oral disposition index (p = 0.03 and p = 0.01, respectively), and, at follow-up, they also displayed a reduction in insulin sensitivity compared with the NGDM group (p = 0.05). CONCLUSIONS/INTERPRETATION: Obese youth exposed in utero to GDM show early inability of the beta cell to compensate adequately in response to decreasing levels of insulin sensitivity.