Dorte Møller Jensen

High Prevalence of Type 2 Diabetes and Pre-Diabetes in Adult Offspring of Women with Gestational Diabetes Mellitus or Type 1 Diabetes – The Role of Intrauterine Hyperglycemia

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.

Overweight and the metabolic syndrome in adult offspring of women with diet-treated gestational diabetes mellitus or type 1 diabetes.

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/m(2) 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.

The LiP (Lifestyle in Pregnancy) study: a randomized controlled trial of lifestyle intervention in 360 obese pregnant women

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.

Peri-Conceptional A1C and Risk of Serious Adverse Pregnancy Outcome in 933 Women With Type 1 Diabetes

OBJECTIVE To study the association between peri-conceptional A1C and serious adverse pregnancy outcome (congenital malformations and perinatal mortality). RESEARCH DESIGN AND METHODS Prospective data were collected in 933 singleton pregnancies complicated by type 1 diabetes. RESULTS The risk of serious adverse outcome at different A1C levels was compared with the background population. The risk was significantly higher when peri-conceptional A1C exceeded 6.9%, and the risk tended to increase gradually with increasing A1C. Women with A1C exceeding 10.4% had a very high risk of 16%. Congenital malformation rate increased significantly at A1C above 10.4%, whereas perinatal mortality was increased even at A1C below 6.9%. CONCLUSIONS These results support recent guidelines of preconceptional A1C levels <7% in women with type 1 diabetes.

Adverse pregnancy outcome in women with mild glucose intolerance: is there a clinically meaningful threshold value for glucose?

Background. The diagnostic criteria of gestational diabetes mellitus (GDM) have been based on the risk of future maternal diabetes rather than the short‐term risk of mother and infant. Our aim was to illustrate the relation between various adverse pregnancy outcomes and maternal glucose levels in women with mild glucose intolerance using a graphical approach. Methods. Observational study of 2,885 pregnant women examined with a 2‐h, 75‐g oral glucose tolerance test (OGTT) based on risk indicators. Only women with 2‐h capillary blood glucose <9.0 mmol/l were included, as women with 2‐h values ≥9.0 mmol/l were treated for GDM. Empirical frequencies of adverse outcomes were related to 2‐h values by linear and quadratic logistic models. Adjustments for well‐known confounders were performed by a multiple logistic model. Results. Linear trends were demonstrated for the outcomes: shoulder dystocia, caesarean section rate (univariate analysis only), spontaneous preterm delivery, and macrosomia (large‐for‐gestational age infants). None of the outcomes deviated significantly from linearity. No significant trend was found for hypertension or neonatal hypoglycaemia and jaundice. Conclusions. A gradually increasing risk for a number of adverse pregnancy outcomes was found with increasing glucose levels. No obvious threshold value for GDM was demonstrated for 2‐h values up to 9.0 mmol/l.

Maternal and neonatal outcomes in pregnancies complicated by gestational diabetes. a nation-wide study

Abstract Objective: To estimate the association between gestational diabetes mellitus (GDM) and adverse pregnancy and neonatal outcomes in Denmark. Methods: A population-based cohort study including all singleton pregnancies in Denmark from 2004 to 2010 (n = 403 092). Maternal complications during pregnancy and delivery and fetal complications were classified according to the International Classification of Diseases 10th Revision. Results: The final study population consisted of 398 623 women. Of these, 9014 (2.3%) had GDM. Data were adjusted for maternal age, parity, smoking, gestational age, birth weight, BMI, gender of the fetus and calendar year. The risk of preeclampsia, caesarean section (both planned and emergency) and shoulder dystocia was increased in women with GDM. In the unadjusted analysis, the risk of thrombosis was increased by a factor 2 in the GDM patients, but in the adjusted analysis this association disappeared. Post-partum hemorrhage was similar in the two groups. The GDM women had an increased risk of giving birth to a macrosomic neonate although the unadjusted analysis did not show any difference between the two groups. Low Apgar score was increased in the GDM, but this association disappeared in the adjusted analysis. Stillbirth was comparable in the two groups. Conclusions: Women with GDM still have increased incidence of obstetric and neonatal complications, which could imply that treatment of women with GDM should be tightened.

DALI: Vitamin D and lifestyle intervention for gestational diabetes mellitus (GDM) prevention: an European multicentre, randomised trial - study protocol

BackgroundGestational diabetes mellitus (GDM) is an increasing problem world-wide. Lifestyle interventions and/or vitamin D supplementation might help prevent GDM in some women.Methods/designPregnant women at risk of GDM (BMI≥29 (kg/m2)) from 9 European countries will be invited to participate and consent obtained before 19+6 weeks of gestation. After giving informed consent, women without GDM will be included (based on IADPSG criteria: fasting glucose<5.1mmol; 1 hour glucose <10.0 mmol; 2 hour glucose <8.5 mmol) and randomized to one of the 8 intervention arms using a 2×(2×2) factorial design: (1) healthy eating (HE), 2) physical activity (PA), 3) HE+PA, 4) control, 5) HE+PA+vitamin D, 6) HE+PA+placebo, 7) vitamin D alone, 8) placebo alone), pre-stratified for each site. In total, 880 women will be included with 110 women allocated to each arm. Between entry and 35 weeks of gestation, women allocated to a lifestyle intervention will receive 5 face-to-face, and 4 telephone coaching sessions, based on the principles of motivational interviewing. The lifestyle intervention includes a discussion about the risks of GDM, a weight gain target <5kg and either 7 healthy eating ‘messages’ and/or 5 physical activity ‘messages’ depending on randomization. Fidelity is monitored by the use of a personal digital assistance (PDA) system. Participants randomized to the vitamin D intervention receive either 1600 IU vitamin D or placebo for daily intake until delivery. Data is collected at baseline measurement, at 24–28 weeks, 35–37 weeks of gestation and after delivery. Primary outcome measures are gestational weight gain, fasting glucose and insulin sensitivity, with a range of obstetric secondary outcome measures including birth weight.DiscussionDALI is a unique Europe-wide randomised controlled trial, which will gain insight into preventive measures against the development of GDM in overweight and obese women.Trial registrationISRCTN70595832

Proposed diagnostic thresholds for gestational diabetes mellitus according to a 75-g oral glucose tolerance test. Maternal and perinatal outcomes in 3260 Danish women

Aims To study if established diagnostic threshold values for gestational diabetes based on a 75‐g, 2‐h oral glucose tolerance test can be supported by maternal and perinatal outcomes.

Pregnancy in women with type 1 diabetes: Have the goals of St. Vincent declaration been met concerning foetal and neonatal complications?

Abstract Objective: In 1989 the St. Vincent declaration set a five-year target for approximating outcomes of pregnancies in women with diabetes to those of the background population. We investigated and quantified the risk of adverse pregnancy outcomes in pregnant women with type 1 diabetes (T1DM) to evaluate if the goals of the 1989 St. Vincent Declaration have been obtained concerning foetal and neonatal complications. Methods: Twelve population-based studies published within the last 10 years with in total 14 099 women with T1DM and 4 035 373 women from the background population were identified. The prevalence of four foetal and neonatal complications was compared. Results: In women with T1DM versus the background population, congenital malformations occurred in 5.0% (2.2–9.0) (weighted mean and range) versus 2.1% (1.5–2.9), relative risk (RR) = 2.4, perinatal mortality in 2.7% (2.0–6.6) versus 0.72% (0.48–0.9), RR = 3.7, preterm delivery in 25.2% (13.0–41.7) versus 6.0% (4.7–7.1), RR = 4.2 and delivery of large for gestational infants in 54.2% (45.1–62.5) versus 10.0%, RR = 4.5. Early pregnancy HbA1c was positively associated with adverse pregnancy outcomes. Conclusion: The risk of adverse pregnancy outcomes was two to five times increased in women with T1DM compared with the general population. The goals of the St. Vincent declaration have not been achieved.

Microalbuminuria, Preeclampsia, and Preterm Delivery in Pregnant Women With Type 1 Diabetes Results from a nationwide Danish study

OBJECTIVE To study the association between microalbuminuria and development of preeclampsia and preterm delivery in pregnant women with type 1 diabetes. RESEARCH DESIGN AND METHODS This was a population-based prospective study in 846 normoalbuminuric or microalbuminuric women with type 1 diabetes without antihypertensive treatment in early pregnancy. Data were collected prospectively by one to three caregivers in each center and reported to a central registry. RESULTS The prevalence of microalbuminuria in the first trimester was 10%, median diabetes duration was 11 years, and third-trimester A1C was 6.6%. The frequencies of preeclampsia and preterm delivery before 34 weeks in the microalbuminuric group were 40 and 13%, both significantly higher than those in the normoalbuminuric group (12 and 6%, respectively, P < 0.001). After adjustments for possible confounders, significant predictors for development of preeclampsia were microalbuminuria (odds ratio 4.0 [95% CI]), nulliparity (3.1 [1.9–5.1]), and third-trimester A1C (1.3 [1.1–1.5] per 1% increase). Delivery before 34 weeks was associated with early microalbuminuria in univariate analyses, but in multivariate analyses A1C was the only significant predictor of this outcome. Preeclampsia was associated with a threefold higher risk of delivery before 34 weeks. CONCLUSIONS The presence of microalbuminuria in early pregnancy is associated with a fourfold increased risk of developing preeclampsia. A1C values during pregnancy are highly predictive of both preeclampsia and preterm delivery. Future research with antihypertensive treatment in normotensive, microalbuminuric pregnant women to prevent preeclampsia is proposed.