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.

OBJECTIVEImpaired glucose effectiveness (GE) plays a role in the deterioration of glucose metabolism. Our aim was to validate a surrogate of GE derived from an oral glucose tolerance test (OGTT) and to assess the impact of degrees of obesity and of glucose tolerance on it.RESEARCH DESIGN AND METHODSThe OGTT-derived surrogate of GE (oGE) was validated in obese adolescents who underwent an OGTT and an intravenous glucose tolerance test (IVGTT). We then evaluated anthropometric determinants of the oGE and its impact on the dynamics of glucose tolerance in a cohort of children with varying degrees of obesity.RESULTSThe correlation of oGE and IVGTT-derived GE in 98 obese adolescents was r = 0.35 (P < 0.001) as a whole and r = 0.51 (P < 0.001) in subjects with normal glucose tolerance. In a cohort of 1,418 children, the adjusted GE was associated with increasing obesity (P < 0.001 for each category of obesity). Quartiles of oGE and the oral disposition index were associated with 2-h glucose levels (P < 0.001 for both). Among 421 nondiabetic obese subjects (276 subjects with normal glucose tolerance/145 subjects with impaired glucose tolerance who repeated their OGTT after a mean time of 28 ± 16 months), oGE changes were tightly associated with weight (r = 0.83, P < 0.001) and waist circumference changes (r = 0.67, P < 0.001). Baseline oGE and changes in oGE over time emerged as significant predictors of the change in 2-h glucose levels (standardized B = −0.76 and B = −0.98 respectively, P < 0.001 for both).CONCLUSIONSThe oGE is associated with the degree of and changes in weight and waist circumference and is an independent predictor of glucose tolerance dynamics.

No abstract

No abstract

No abstract