OBJECTIVE -The role of intrauterine hyperglycemia and future risk of type 2 diabetes in human offspring is debated. We studied glucose tolerance in adult offspring of women with either gestational diabetes mellitus (GDM) or type 1 diabetes, taking the impact of both intrauterine hyperglycemia and genetic predisposition to type 2 diabetes into account.RESEARCH DESIGN AND METHODS -The glucose tolerance status following a 2-h 75-g oral glucose tolerance test (OGTT) was evaluated in 597 subjects, primarily Caucasians, aged 18 -27 years. They were subdivided into four groups according to maternal glucose metabolism during pregnancy and genetic predisposition to type 2 diabetes: 1) offspring of women with diet-treated GDM (O-GDM), 2) offspring of genetically predisposed women with a normal OGTT (O-NoGDM), 3) offspring of women with type 1 diabetes (O-type 1), and 4) offspring of women from the background population (O-BP).RESULTS -The prevalence of type 2 diabetes and pre-diabetes (impaired glucose tolerance or impaired fasting glucose) in the four groups was 21, 12, 11, and 4%, respectively. In multiple logistic regression analysis, the adjusted odds ratios (ORs) for type 2 diabetes/pre-diabetes were 7.76 (95% CI 2.58 -23.39) in O-GDM and 4.02 (1.31-12.33) in O-type 1 compared with O-BP. In O-type 1, the risk of type 2 diabetes/pre-diabetes was significantly associated with elevated maternal blood glucose in late pregnancy: OR 1.41 (1.04 -1.91) per mmol/l. CONCLUSIONS -A hyperglycemic intrauterine environment appears to be involved in the pathogenesis of type 2 diabetes/pre-diabetes in adult offspring of primarily Caucasian women with either diet-treated GDM or type 1 diabetes during pregnancy. Diabetes Care 31:340-346, 2008T he rapid global rise in the prevalence of type 2 diabetes constitutes a health threat to the individual and is a major burden for health economy. Therefore, it is crucial to identify specific risk groups, targeting preventive strategies. Studies of developmental origins of health and disease have focused on the possible role of intrauterine hyperglycemia in the pathogenesis of type 2 diabetes (1). Maternal glucose crosses placenta easily, and maternal hyperglycemia leads to intrauterine hyperglycemia, fetal hyperinsulinemia, and possible modification of growth and development of the fetus (2).Pronounced hyperglycemia in relation to pregnancies of women with type 1 diabetes as well as mild hyperglycemia, as seen among women with gestational diabetes mellitus (GDM), are both associated with increased fetal growth and perinatal morbidity (3,4). Also, less severe forms of glucose intolerance are associated with increased feto-maternal morbidity (5).In animal studies, intrauterine hyperglycemia increases the risk of abnormal glucose tolerance, diabetes, overweight, and insulin resistance in offspring (6 -10). Despite very convincing animal studies, questions still exist concerning the long-term impact of intrauterine hyperglycemia in humans, especially regarding the impact in adult Caucasians. Observ...

Gestational diabetes mellitus (GDM) is defined as glucose intolerance of varying severity and is present in about 2-6% of all pregnancies in Europe, making it one of the most common pregnancy disorders. Aside from the short-term maternal, fetal and neonatal consequences associated with GDM, there are long-term consequences for both mother and child. Although maternal glucose tolerance often normalises shortly after pregnancy, women with GDM have a substantially increased risk of developing type 2 diabetes later in life. Studies have reported that women are more than seven times as likely to develop diabetes after GDM, and that approximately 50% of mothers with GDM will develop diabetes within 10 years, making GDM one of the strongest predictors of type 2 diabetes. In women with previous GDM, development of type 2 diabetes can be prevented or delayed by lifestyle intervention and/or medical treatment. Systematic follow-up programmes would be ideal to prevent progression of GDM to diabetes, but such programmes are unfortunately lacking in the routine clinical set-up in most countries. Studies have found that the risks of obesity, the metabolic syndrome, type 2 diabetes and impaired insulin sensitivity and secretion in offspring of mothers with GDM are two- to eightfold those in offspring of mothers without GDM. The underlying pathogenic mechanisms behind the abnormal metabolic risk profile in offspring are unknown, but epigenetic changes induced by exposure to maternal hyperglycaemia during fetal life are implicated. Animal studies indicate that treatment can prevent long-term metabolic complications in offspring, but this remains to be confirmed in humans. Thus, diabetes begets diabetes and it is likely that GDM plays a significant role in the global diabetes epidemic. This review summarises a presentation given at the 'Gestational diabetes: what's up?' symposium at the 2015 annual meeting of the EASD. It is accompanied by two other reviews on topics from this symposium (by Marja Vääräsmäki, DOI: 10.1007/s00125-016-3976-6 , and by Cuilin Zhang and colleagues, DOI: 10.1007/s00125-016-3979-3 ) and an overview by the Session Chair, Kerstin Berntorp (DOI: 10.1007/s00125-016-3975-7 ).

Adult offspring of women with diet-treated GDM or type 1 diabetes are risk groups for overweight and the metabolic syndrome. Intrauterine hyperglycemia may in addition to genetics and other factors contribute to the pathogenesis of overweight and the metabolic syndrome.