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Background: High glycemic index (GI) and glycemic load (GL) as indicators of carbohydrate quality and quantity have been found to increase risk of metabolic outcomes in adults. Whether carbohydrate quality may influence metabolic programming already in early life is unknown. We examined the association of maternal GI and GL with offspring body mass index (BMI) in the first 7 years of life among 68,471 mother-offspring dyads from the Danish National Birth Cohort (DNBC). In a sub-cohort of offspring with clinical data (n = 1234) that included 608 dyads exposed to gestational diabetes mellitus (GDM), we also examined the relation to metabolic health at 9-16 years., Methods: Maternal GI and GL were quantified using a mid-pregnancy food frequency questionnaire. We used birth weight and length to calculate offspring's ponderal index. Age- and sex-specific BMI z scores at 5 mo, 12 mo, and 7 y were standardized against WHO reference data. In the clinical cohort, we quantified body composition, HOMA-IR, and HOMA-B. We used multivariable mixed linear and Poisson regression to model the associations., Results: Median (IQR) of GI and GL were 83 (63-111) and 241 (180-333) g/day, respectively. We found that GI (Q4 vs. Q1:1.09, 95%CI: 1.03, 1.15) and GL (Q4 vs. Q1:1.10, 95%CI: 1.05, 1.16) modestly increased the relative risk of large-for gestational age (LGA). In the clinical sub-cohort, we observed a potential increase in offspring HOMA-IR, adiposity, and metabolic syndrome z score with higher maternal GI and GI. These associations were stronger among the GDM-exposed offspring, but the CI included the null value., Conclusion: We found associations of GI and GL in pregnancy with offspring LGA. Potential long-term benefits to offspring exposed to GDM need to be confirmed in larger, well-powered studies.

Oily fish, an important source of marine n-3 long-chain polyunsaturated fatty acids (LCPUFA), has shown to reduce cardiometabolic risk in adults. Whether maternal fish intake affects offspring metabolic health is less established, especially among high-risk pregnancies. We aimed to examine the association of fish intake in pregnancy with offspring metabolic health who were either exposed or unexposed to gestational diabetes mellitus (GDM). Our study included 1234 mother-offspring dyads (608 with a GDM index pregnancy and 626 control dyads) nested within the Danish National Birth Cohort, which is a prebirth cohort. Maternal seafood and marine n-3 LCPUFA consumption was quantified by a food frequency questionnaire (gestational week 25) and a sub-sample with interview data (weeks 12 and 30). The offspring were clinically examined at 9⁻16 years, including a Dual energy X-ray Absorptiometry (DXA) scan and a fasting blood sample. We calculated multivariable effect estimates and 95% confidence intervals (CI) for anthropometric, adiposity, and metabolic parameters. The median (IQR) intake of total seafood was 23(24) g/day. We found largely no association for total seafood and marine n-3 LCPUFA with offspring metabolic parameters in either group. Using interview data, GDM-exposed women reporting no fish in week 12 and 30 (versus intake >2 times/week) had offspring with a higher Body Mass Index (BMI) (ratio of geometric means (RGM): 1.28, 95% CI: 1.06, 1.55), waist circumference (RGM: 1.22, 95% CI: 1.05, 1.40), triglycerides (RGM: 1.77, 95% CI: 1.03, 3.03), and homeostatic model assessment of insulin resistance HOMA-IR (RGM: 2.16, 95% CI: 1.17, 3.97). We found no associations of n-3 LCPUFA and seafood intake with offspring metabolic outcomes. However, GDM-exposed women who consistently reported eating no fish had offspring with a poorer metabolic profile. Fish intake in pregnancy may mitigate some adverse effects of intrauterine hyperglycemia, however, these findings need replication in better powered studies.

Objective: Offspring of pregnancies affected by gestational diabetes mellitus (GDM) are at increased risk of the development of type 2 diabetes. However, the extent to which these dysmetabolic traits may be due to offspring and/or maternal adiposity is unknown. We examined body composition and associated cardiometabolic traits in 561 9- to 16-year-old offspring of mothers with GDM and 597 control offspring., Research Design and Methods: We measured anthropometric characteristics; puberty status; blood pressure; and fasting glucose, insulin, C-peptide, and lipid levels; and conducted a DEXA scan in a subset of the cohort. Differences in the outcomes between offspring of mothers with GDM and control subjects were examined using linear and logistic regression models., Results: After adjustment for age and sex, offspring of mothers with GDM displayed higher weight, BMI, waist-to-hip ratio (WHR), systolic blood pressure, and resting heart rate and lower height. Offspring of mothers with GDM had higher total and abdominal fat percentages and lower muscle mass percentages, but these differences disappeared after correction for offspring BMI. The offspring of mothers with GDM displayed higher fasting plasma glucose, insulin, C-peptide, HOMA-insulin resistance (IR), and plasma triglyceride levels, whereas fasting plasma HDL cholesterol levels were decreased. Female offspring of mothers with GDM had an earlier onset of puberty than control offspring. Offspring of mothers with GDM had significantly higher BMI, WHR, fasting glucose, and HOMA-IR levels after adjustment for maternal prepregnancy BMI, and glucose and HOMA-IR remained elevated in the offspring of mothers with GDM after correction for both maternal and offspring BMIs., Conclusions: In summary, adolescent offspring of women with GDM show increased adiposity, an adverse cardiometabolic profile, and earlier onset of puberty among girls. Increased fasting glucose and HOMA-IR levels among the offspring of mothers with GDM may be explained by the programming effects of hyperglycemia in pregnancy., (© 2017 by the American Diabetes Association.)

Background: Recent years have seen strong tendencies toward high-protein diets. However, the implications of higher protein intake, especially during developmentally sensitive periods, are poorly understood. Conversely, evidence on the long-term developmental consequences of low protein intake in free-living populations remains limited. Objective: We examined the association of protein intake in pregnancy with offspring metabolic health at age 9-16 y in a longitudinal cohort that oversampled pregnancies with gestational diabetes mellitus (GDM). Design: Six hundred eight women with an index pregnancy affected by gestational diabetes mellitus and 626 controls enrolled in the Danish National Birth Cohort were used for the analysis. Protein (total, animal, vegetable) intake was assessed by using a food-frequency questionnaire in gestational week 25. The offspring underwent a clinical examination including fasting blood samples and a dual-energy X-ray absorptiometry scan (subset of 650) from which metabolic outcomes were derived. Multivariable analyses were conducted applying a 1:1 substitution of carbohydrates for protein. Results: The mean ± SD protein intake in pregnancy was 93 ± 15 g/d (16% ± 3% of energy) in GDM-exposed women and 90 ± 14 g/d (16% ± 2% of energy) in control women. There were overall no associations between maternal protein intake and offspring fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR). We found that maternal total protein intake was associated with a tendency for a higher abdominal fat mass percentage (quartile 4 compared with quartile 1: 0.40 SD; 95% CI: -0.03, 0.83 SD; P = 0.07) in GDM-exposed offspring and a tendency for a higher total fat mass percentage among male offspring (quartile 4 compared with quartile 1: 0.33 SD; 95% CI: -0.01, 0.66 SD; P = 0.06), but a small sample size may have compromised the precision of the effect estimates. GDM-exposed offspring of mothers with a protein intake in the lowest decile (≤12.5% of energy compared with >12.5% of energy) had lower fasting insulin (ratio of geometric means: 0.82; 95% CI: 0.68, 0.99; P = 0.04) and a tendency toward lower HOMA-IR (ratio of geometric means: 0.82; 95% CI: 0.66, 1.02; P = 0.07), but there was no evidence of associations with body composition. Male offspring seemed to derive a similar benefit from a maternal low protein intake as did GDM-exposed offspring. Conclusions: Overall, our results provide little support for an association of maternal protein intake in pregnancy with measures of offspring metabolic health. Further studies in larger cohorts are needed to determine whether low maternal protein intake in pregnancy may improve glucose homeostasis in GDM-exposed and male offspring., (© 2017 American Society for Nutrition.)

Background: Evidence from experimental studies has demonstrated that higher than normal iron concentrations can lead to pancreatic β cell dysfunction and impaired glucose metabolism. Studies on body iron stores in early pregnancy and subsequent gestational diabetes mellitus (GDM) risk are sparse., Objective: Our objective was to determine whether biomarkers of body iron stores measured in early pregnancy are associated with GDM risk., Methods: A case-control study of 350 GDM cases and 349 non-GDM controls was conducted in participants from the Danish National Birth Cohort. Blood was collected at a mean ± SD gestational age of 9.4 ± 3.2 wk. Plasma biomarkers of iron stores, including ferritin and soluble transferrin receptor (sTfR), were measured. Logistic regression was used to estimate the OR of GDM associated with quintiles of plasma biomarkers of body iron stores, controlling for maternal age, family history of diabetes, exercise in pregnancy, parity, and prepregnancy body mass index (BMI)., Results: Cases were older (mean ± SD age: 32.2 ± 4.3 compared with 29.9 ± 4.2 y) and had a higher BMI (in kg/m(2); mean ± SD: 28.7 ± 6.0 compared with 24.1 ± 4.6) than controls. Plasma concentrations of both ferritin and sTfR in early pregnancy were significantly higher in GDM cases than in controls [means ± SDs: 80.6 ± 56.0 compared with 71.8 ± 50.1 μg/L (P = 0.03) and 1.5 ± 0.7 compared with 1.4 ± 0.6 mg/L (P = 0.002) for ferritin and sTfR, respectively]. Ferritin was positively and significantly associated with GDM risk even after adjustment for major risk factors of GDM, including prepregnancy BMI. ORs across increasing quintiles of ferritin were 1.00 (reference), 1.25 (95% CI: 0.70, 2.22), 1.89 (95% CI: 1.06, 3.37), 0.82 (95% CI: 0.46, 1.48), and 2.34 (95% CI: 1.30, 4.21) (P-linear trend = 0.02)., Conclusion: These findings suggest that plasma ferritin measured in early pregnancy is significantly and positively associated with GDM risk., Competing Interests: 2Author disclosures: KA Bowers, SF Olsen, W Bao, TI Halldorsson, M Strøm, and C Zhang, no conflicts of interest., (© 2016 American Society for Nutrition.)

Women who developed gestational diabetes mellitus represent a high-risk population for hypertension later in life. The role of diet in the progression of hypertension among this susceptible population is unknown. We conducted a prospective cohort study of 3818 women with a history of gestational diabetes mellitus in the Nurses' Health Study II as part of the ongoing Diabetes & Women's Health Study. These women were followed-up from 1989 to 2011. Incident hypertension was identified through self-administered questionnaires that were validated previously by medical record review. Adherence scores for the alternative Healthy Eating Index 2010, the alternative Mediterranean diet, and the Dietary Approaches to Stop Hypertension were computed for each participant. Cox proportional hazard models were used to evaluate the associations between dietary scores and hypertension while adjusting for major risk factors for hypertension. We documented 1069 incident hypertension cases during a median of 18.5 years of follow-up. After adjustment for major risk factors for hypertension, including body mass index, alternative Healthy Eating Index 2010, alternative Mediterranean diet, and Dietary Approaches to Stop Hypertension scores were significantly inversely associated with the risk of hypertension; hazard ratio and 95% confidence interval comparing the extreme quartiles (highest versus lowest) were 0.76 (0.61-0.94; P for linear trend =0.03) for AHEI score, 0.72 (0.58-0.90; P for trend =0.01) for Dietary Approach to Stop Hypertension score, and 0.70 (0.56-0.88; P for trend =0.002) for alternative Mediterranean diet score. Adherence to a healthful dietary pattern was related to a lower subsequent risk of developing hypertension among women with a history of gestational diabetes mellitus., (© 2016 American Heart Association, Inc.)

Women who develop gestational diabetes mellitus or impaired glucose tolerance during pregnancy are at substantially increased risk for type 2 diabetes and comorbidities after pregnancy. Little is known about the role of genetic factors and their interactions with environmental factors in determining the transition from gestational diabetes mellitus to overt type 2 diabetes mellitus. These critical data gaps served as the impetus for this Diabetes & Women's Health study with the overall goal of investigating genetic factors and their interactions with risk factors amenable to clinical or public health interventions in relation to the transition of gestational diabetes mellitus to type 2 diabetes mellitus. To achieve the goal efficiently, we are applying a hybrid design enrolling and collecting data longitudinally from approximately 4000 women with a medical history of gestational diabetes mellitus in two existing prospective cohorts, the Nurses' Health Study II and the Danish National Birth Cohort. Women who had a medical history of gestational diabetes mellitus in one or more of their pregnancies are eligible for the present study. After enrollment, we follow study participants for an additional 2 years to collect updated information on major clinical and environmental factors that may predict type 2 diabetes mellitus risk as well as with biospecimens to measure genetic and biochemical markers implicated in glucose metabolism. Newly collected data will be appended to the relevant existing data for the creation of a new database inclusive of genetic, epigenetic and environmental data. Findings from the study are critical for the development of targeted and more effective strategies to prevent type 2 diabetes mellitus and its complications in this high-risk population., (© 2014 Nordic Federation of Societies of Obstetrics and Gynecology.)

Importance: Women with a history of gestational diabetes mellitus (GDM) are at substantially increased risk of type 2 diabetes mellitus (T2DM). The identification of important modifiable factors could help prevent T2DM in this high-risk population., Objective: To examine the role of physical activity and television watching and other sedentary behaviors, and changes in these behaviors in the progression from GDM to T2DM., Design, Setting, and Participants: Prospective cohort study of 4554 women from the Nurses' Health Study II who had a history of GDM, as part of the ongoing Diabetes & Women's Health Study. These women were followed up from 1991 to 2007., Exposures: Physical activity and television watching and other sedentary behaviors were assessed in 1991, 1997, 2001, and 2005., Main Outcomes and Measure: Incident T2DM identified through self-report and confirmed by supplemental questionnaires., Results: We documented 635 incident T2DM cases during 59,287 person-years of follow-up. Each 5-metabolic equivalent hours per week (MET-h/wk) increment of total physical activity, which is equivalent to 100 minutes per week of moderate-intensity physical activity, was related to a 9% lower risk of T2DM (adjusted relative risk [RR], 0.91; 95% CI, 0.88-0.94); this inverse association remained significant after additional adjustment for body mass index (BMI). Moreover, an increase in physical activity was associated with a lower risk of developing T2DM. Compared with women who maintained their total physical activity levels, women who increased their total physical activity levels by 7.5 MET-h/wk or more (equivalent to 150 minutes per week of moderate-intensity physical activity) had a 47% lower risk of T2DM (RR, 0.53; 95% CI, 0.38-0.75); the association remained significant after additional adjustment for BMI. The multivariable adjusted RRs (95% CIs) for T2DM associated with television watching of 0 to 5, 6 to 10, 11 to 20, and 20 or more hours per week were 1 (reference), 1.28 (1.04-1.59), 1.41 (1.11-1.79), and 1.77 (1.28-2.45), respectively (P value for trend <.001); additional adjustment for BMI attenuated the association., Conclusions and Relevance: Increasing physical activity may lower the risk of progression from GDM to T2DM. These findings suggest a hopeful message to women with a history of GDM, although they are at exceptionally high risk for T2DM, promoting an active lifestyle may lower the risk.