Long-term maternal cardiometabolic outcomes 22 years after gestational diabetes mellitus.

AIMS/INTRODUCTION: Women with gestational diabetes mellitus are at increased risk for type 2 diabetes. We characterized the association between maternal glycemia during pregnancy with long-term outcomes. METHODS AND METHODS: In this prospective nested case-cohort study, participants were recalled for follow up with detailed evaluation including oral glucose tolerance test at 8, 15 and 22 years. Logistic regression was used to estimate the risk of developing impaired glucose tolerance/type 2 diabetes and metabolic syndrome at follow up. The association between maternal glycemia at pregnancy and follow up was evaluated by linear regression. We also charted trajectory of ß-cell function during follow up. RESULTS: The analysis included 121 women with a mean follow-up period of 22.5 years, and a mean age of 50.3 years. Gestational diabetes was associated with an adjusted odds ratio of 2.48 (95% confidence interval 1.03-5.99) for combined diabetes/impaired glucose tolerance at follow up (P = 0.04). Women with a pre-pregnancy body mass index ≥23 had an odds ratio of 5.43 (95% confidence interval 1.87-15.72) for metabolic syndrome at follow up, compared with those with body mass index <23 (P = 0.002). Both fasting and 2-h glucose during pregnancy were strongly associated with glycemic indices at follow up (P-value <0.001-0.016). Gestational diabetes was associated with impaired ß-cell function that remained relatively stable after the index pregnancy. CONCLUSIONS: Chinese women with a history of gestational diabetes have a high prevalence of impaired glucose tolerance/type 2 diabetes at 22-year follow up. Glucose levels during mid-pregnancy are strongly associated with those of middle age.

Maternal diabetes, gestational diabetes and the role of epigenetics in their long term effects on offspring.

There is a global epidemic of obesity and diabetes, and current efforts to curb the diabetes epidemic have had limited success. Epidemiological studies have highlighted increased risk of obesity, diabetes and cardiovascular complications in offspring exposed to maternal diabetes, and gestational diabetes increases the risk of diabetes in subsequent generations, thereby setting up a vicious cycle of "diabetes begetting diabetes". This relationship between maternal hyperglycaemia and long-term health in the offspring is likely to become even more important with an increasing proportion of young woman being affected by diabetes, and the number of pregnancies complicated by hyperglycaemia continuing to rise. Animal models of gestational diabetes or maternal hyperglycaemia have highlighted long-term changes in the offspring with some instances of sex bias, including increased adiposity, insulin resistance, ß-cell dysfunction, hypertension, as well as other structural and functional changes. Furthermore, several of these changes appear to be transmissible to later generations through the maternal line. Epigenetic changes play an important role in regulating gene expression, especially during early development. Recent studies have identified a number of epigenetic modifications in the offspring associated with maternal hyperglycaemia. In this review, we provide an overview of the epidemiological evidence linking maternal hyperglycaemia with adverse long-term outcome in the offspring, as well as of some of the studies that explore the underlying epigenetic mechanisms. A better understanding of the pathways involved may provide novel approaches for combating this global epidemic.