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.

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 ).

Context: In animal studies, exposure to intrauterine hyperglycemia increases the risk of cardiovascular disease through only partly understood epigenetic mechanisms. Human long-term follow-up studies on the same topic are few. Objective: The aim was to study the risk of overweight and the metabolic syndrome in adult offspring of women with diet-treated gestational diabetes mellitus (GDM) or type 1 diabetes, and additionally to study associations between estimates of maternal hyperglycemia and outcome in the offspring. Design and Setting: We conducted a follow-up study of 1066 primarily Caucasian women aged 18–27 yr in the Center for Pregnant Women with Diabetes, Rigshospitalet, Copenhagen, Denmark. Participants: Offspring of women with diet-treated GDM (n = 168) and an unexposed reference group (n = 141) participated, as well as offspring of women with type 1 diabetes (n = 160) and offspring from the background population representing an unexposed reference group (n = 128). The follow-up rate was 56% (597 of 1066). Main Outcome Measures: Women with body mass index of at least 25 kg/m² were considered overweight. The metabolic syndrome was determined by the International Diabetes Federation 2006 criteria. Results: The risk of overweight was doubled in offspring of women with diet-treated GDM or type 1 diabetes compared with offspring from the background population, whereas the risk of the metabolic syndrome was 4- and 2.5-fold increased, respectively. Offspring risk of the metabolic syndrome increased significantly with increasing maternal fasting blood glucose as well as 2-h blood glucose (during oral glucose tolerance test). Conclusions: 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.

Advancement in medical and clinical science is based upon new concepts, most often in combination with the development of new techniques or new laboratory procedures. This also is the case with the study of renal involvement in diabetes which constitutes a major' health problem (1). Although urinary protein assessment is one of the most commonly used clinical tests, including diabetology, this area has been grossly underdeveloped due to the very crude, nonquanitative screening methods used. The lack of precision of the most commonly used tests contrasts sharply to the severe consequences of microalbuminuria, proteinuria, and nephropathy for the patient (1-6). It is the long-term microvascular complications, specifically diabetic nephropathy and associated retinopathy, neuropathy, and large vessel disease, that are the main determinants of disability and increased mortality in diabetics.

Strict glycemic control is essential to minimize the maternal and fetal morbidity and mortality of pregnancies complicated by diabetes (1–3). In addition to home blood glucose measurement, which may not always reflect the true average blood glucose level (4), HbA1c is a useful parameter in metabolic regulation (5–8). Thus, supplementation with HbA1c, as is common outside pregnancy, seems appropriate. Before pregnancy, the target for metabolic control in women with diabetes is HbA1c values near the normal range (9). However, the upper normal range of HbA1c during normal pregnancy is only sparsely investigated with different methods (10), mainly in late pregnancy (5,6,11,12), and reference ranges are generally established from the nonpregnant state (4). Increased third-trimester HbA1c levels are associated with an increased risk of preeclampsia (3,13), macrosomia (1), and stillbirth (2), leading to speculations that the target for HbA1c in pregnancy should be even lower than outside pregnancy to prevent adverse events. There is a need to establish the reference range of HbA1c during normal pregnancy with an internationally recognized Diabetes Control and Complications Trial (DCCT)-aligned method. In this study, we evaluated the normal upper range of HbA …