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.

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.

OBJECTIVE—The aim of this study was to compare pregnancy outcomes in type 1 diabetic pregnancies with the background population. RESEARCH DESIGN AND METHODS—This nationwide prospective multicenter study took place in eight Danish centers treating pregnant women with type 1 diabetes during 1993–1999. A total of 990 women with 1,218 pregnancies and delivery after 24 weeks (n = 1,215) or early termination due to severe congenital malformations (n = 3) were included. Data were collected prospectively by one to three caregivers in each center and reported to a central registry. RESULTS—The perinatal mortality rate was 3.1% in type 1 diabetic pregnancies compared with 0.75% in the background population (RR 4.1 [95% CI 2.9–5.6]), and the stillbirth rate was 2.1% compared with 0.45 (4.7 [3.2–7.0]). The congenital malformation rate was 5.0% in the study population and 2.8% (1.7 [1.3–2.2]) in the background population. Six of the perinatal deaths (16%) were related to congenital malformations. Only 34% of women performed daily home monitoring of blood glucose at conception, and 58% received preconceptional guidance. Pregnancies with serious adverse outcomes (perinatal death and/or congenital malformations) were characterized by higher HbA_1c values before and during pregnancy and a lesser degree of maternal self-care and preconceptional guidance. Women who performed daily self-monitoring of blood glucose at any time during pregnancy had lower HbA_1c values than women who did not measure their daily profile. Likewise, daily self-monitoring was associated with a reduction in serious adverse outcomes. The caesarean section rate was 55.9 and 12.6%, respectively, and the risk of preterm delivery was 41.7 and 6.0%, respectively. CONCLUSIONS—Type 1 diabetic pregnancies are still complicated by considerably higher rates of severe perinatal complications compared with the background population, and women with poor self-care are at the highest risk. Adequate glycemic control using daily glucose monitoring before and during pregnancy is a crucial step toward reaching the goals of the St. Vincent declaration.

OBJECTIVE: To study the effects of lifestyle intervention on gestational weight gain (GWG) and obstetric outcomes. RESEARCH DESIGN AND METHODS: The LiP (Lifestyle in Pregnancy) study was a randomized controlled trial in 360 obese women allocated in early pregnancy to lifestyle intervention or control. The intervention program included dietary guidance, free membership in fitness centers, physical training, and personal coaching. RESULTS: A total of 360 obese pregnant women were included, and 304 (84%) were followed up until delivery. The intervention group had a significantly lower median (range) GWG compared with the control group of 7.0 (4.7–10.6) vs. 8.6 kg (5.7–11.5; P = 0.01). The Institute of Medicine (IOM) recommendations on GWG were exceeded in 35.4% of women in the intervention group compared with 46.6% in the control group (P = 0.058). Overall, the obstetric outcomes between the two groups were not significantly different. CONCLUSIONS: Lifestyle intervention in pregnancy resulted in limited GWG in obese pregnant women. Overall obstetric outcomes were similar in the two groups. Lifestyle intervention resulted in a higher adherence to the IOM weight gain recommendations; however, a significant number of women still exceeded the upper threshold.

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 …