Shristi Rawal

Risk factors for gestational diabetes: is prevention possible?

Gestational diabetes mellitus (GDM), a common pregnancy complication, continues to be a significant public health and clinical problem. It carries significant short-term and long-term adverse health outcomes for both mother and offspring, which reinforces the significance of understanding risk factors, in particular modifiable factors, for GDM and of preventing the condition. Research in the past decade from observational studies has identified a few diet and lifestyle factors that are associated with GDM risk and demonstrated that time frames both before and during pregnancy may be relevant to the development of GDM. Findings from intervention studies on the effect of diet and lifestyle on the prevention of GDM have been largely controversial and inconsistent. Variations in study population, types of intervention, timing and duration of intervention and diagnostic criteria for GDM may all at least partly account for the large heterogeneity in the findings from these intervention studies. This review provides an overview of emerging diet, lifestyle, and other factors that may help to prevent GDM, and the challenges associated with prevention. It also discusses major methodological concerns about the available epidemiological studies on GDM risk factors. Findings from both observational and intervention studies are discussed. 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 Peter Damm and Colleagues, DOI: 10.1007/s00125-016-3985-5, and by Marja Vääräsmäki, DOI: 10.1007/s00125-016-3976-6) and an overview by the Session Chair, Kerstin Berntorp (DOI: 10.1007/s00125-016-3975-7).

Maternal consumption of artificially sweetened beverages during pregnancy, and offspring growth through 7 years of age: a prospective cohort study

Background Artificial sweeteners are widely replacing caloric sweeteners. Data on long-term impact of artificially sweetened beverage (ASB) consumption during pregnancy on offspring obesity risk are lacking. We prospectively investigated intake of ASBs and sugar-sweetened beverages (SSBs) during pregnancy in relation to offspring growth through age 7 years among high-risk children born to women with gestational diabetes. Methods In a prospective study of 918 mother-singleton child dyads from the Danish National Birth Cohort, maternal dietary intake was assessed by a food frequency questionnaire during pregnancy. Offspring body mass index z-scores (BMIZ) and overweight/obesity status were derived using weight and length/height at birth, 5 and 12 months and 7 years. Linear regression and Poisson regression with robust standard errors were used, adjusting for major risk factors. Results Approximately half of women reported consuming ASBs during pregnancy and 9% consumed daily. Compared to never consumption, daily ASB intake during pregnancy was positively associated with offspring large-for-gestational age [adjusted relative risk (aRR) 1.57; 95% CI: 1.05, 2.35 at birth], BMIZ (adjusted β 0.59; 95% CI: 0.23, 0.96) and overweight/obesity (aRR 1.93; 95% CI; 1.24, 3.01) at 7 years. Per-serving-per-day substitution of ASBs with water during pregnancy was related to a lower overweight/obesity risk at 7 years (aRR 0.83; 95% CI: 0.76, 0.91), whereas SSB substitution with ASBs was not related to a lower risk (aRR 1.14; 95% CI: 1.00, 1.31). Conclusions Our findings illustrated positive associations between intrauterine exposure to ASBs and birth size and risk of overweight/obesity at 7 years. Data with longer follow-up are warranted.

A longitudinal study of sleep duration in pregnancy and subsequent risk of gestational diabetes: findings from a prospective, multiracial cohort.

BACKGROUND: Both short and prolonged sleep duration have been linked to impaired glucose metabolism. Sleep patterns change during pregnancy, but prospective data are limited on their relation to gestational diabetes. OBJECTIVE: We sought to prospectively examine the trimester‐specific (first and second trimester) association between typical sleep duration in pregnancy and subsequent risk of gestational diabetes, as well as the influence of compensatory daytime napping on this association. STUDY DESIGN: In the prospective, multiracial Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies‐Singleton Cohort, 2581 pregnant women reported their typical sleep duration and napping frequency in the first and second trimesters. Diagnosis of gestational diabetes (n = 107; 4.1%) was based on medical records review. Adjusted relative risks with 95% confidence intervals for gestational diabetes were estimated with Poisson regression, adjusting for demographics, prepregnancy body mass index, and other risk factors. RESULTS: From the first and second trimester, sleep duration and napping frequency declined. Sleeping duration in the second but not first trimester was significantly related to risk of gestational diabetes. The association between second‐trimester sleep and gestational diabetes differed by prepregnancy obesity status (P for interaction = .04). Among nonobese but not obese women, both sleeping >8‐9 hours or <8‐9 hours were significantly related to risk of gestational diabetes: 5‐6 hours (adjusted relative risk, 2.52; 95% confidence interval, 1.27–4.99); 7 hours (adjusted relative risk, 2.01; 95% confidence interval, 1.09–3.68); or ≥10 hours (adjusted relative risk, 2.17; 95% confidence interval, 1.01–4.67). Significant effect modification by napping frequency was also observed in the second trimester (P for interaction = .03). Significant and positive association between reduced sleep (5‐7 hours) and gestational diabetes was observed among women napping rarely/never (adjusted relative risk, 2.48; 95% confidence interval, 1.20–5.13), whereas no comparable associations were observed among women napping most/sometimes. CONCLUSION: Our data suggest a U‐shaped association between sleep duration and gestational diabetes, and that napping and prepregnancy obesity status may modify this association.

Dietary iron intake, iron status, and gestational diabetes

Pregnant women are particularly vulnerable to iron deficiency and related adverse pregnancy outcomes and, as such, are routinely recommended for iron supplementation. Emerging evidence from both animal and population-based studies, however, has raised potential concerns because significant associations have been observed between greater iron stores and disturbances in glucose metabolism, including increased risk of type 2 diabetes among nonpregnant individuals. Yet, the evidence is uncertain regarding the role of iron in the development of gestational diabetes mellitus (GDM), a common pregnancy complication which has short-term and long-term adverse health ramifications for both women and their children. In this review, we critically and systematically evaluate available data examining the risk of GDM associated with dietary iron, iron supplementation, and iron status as measured by blood concentrations of several indicators. We also discuss major methodologic concerns regarding the available epidemiologic studies on iron and GDM.

Plasma concentrations of lipids during pregnancy and the risk of gestational diabetes mellitus: A longitudinal study

Abnormal lipid profiles have been associated with gestational diabetes mellitus (GDM), but studies with longitudinal measures of lipids throughout pregnancy are sparse. The aim of the present study was to characterize longitudinal changes in lipid profiles throughout pregnancy and prospectively examine the associations of plasma lipid concentrations with risk of GDM.

Maternal dietary intakes of refined grains during pregnancy and growth through the first 7 y of life among children born to women with gestational diabetes

Background: Refined grains, a major source of dietary carbohydrates, have been related to impaired glucose homeostasis and obesity. Emerging animal data suggest that in utero exposure to dietary refined carbohydrates may predispose offspring to an obese phenotype, indicating a potential role for nutritional programming in the early origins of obesity, but intergenerational human data are lacking.Objective: We prospectively investigated refined-grain intake during pregnancy in association with offspring growth through age 7 y among high-risk children born to women with gestational diabetes mellitus (GDM).Design: The analysis included 918 mother-singleton child dyads from the Danish National Birth Cohort. Offspring body mass index z scores (BMIZs) were calculated by using weight and length or height measured at birth, 5 and 12 mo, and 7 y. Overweight or obesity was defined by WHO cutoffs. Linear and Poisson regressions were used, with adjustment for maternal demographic, lifestyle, and dietary factors.Results: Refined-grain intake during pregnancy was positively associated with offspring BMIZ (adjusted β per serving increase per day: 0.09; 95% CI: 0.02, 0.15) and risk of overweight or obesity at age 7 y [adjusted RR (aRR) comparing the highest with the lowest quartile: 1.80; 95% CI: 1.09, 2.98; P-trend = 0.032]. The association appeared to be more pronounced among children who were breastfed <6 mo. The substitution of 1 serving refined grains/d with an equal serving of whole grains during pregnancy was related to a 10% reduced risk of offspring overweight or obesity at 7 y of age (aRR: 0.90; 95% CI: 0.82, 0.98). No associations were observed between refined-grain intake and infant growth.Conclusions: Higher maternal refined-grain intake during pregnancy was significantly related to a greater BMIZ and a higher risk of overweight or obesity at age 7 y among children born after pregnancies complicated by GDM. The findings highlight pregnancy as a potential window of susceptibility associated with offspring growth and obesity risk among this high-risk population. Data with longer follow-up are warranted.

Genetic variants of gestational diabetes mellitus: a study of 112 SNPs among 8722 women in two independent populations

Aims/hypothesisGestational diabetes mellitus (GDM) is a common complication of pregnancy that has substantial short- and long-term adverse health implications for women and their children. However, large-scale studies on genetic risk loci for GDM remain sparse.MethodsWe conducted a case–control study among 2636 women with GDM and 6086 non-GDM control women from the Nurses’ Health Study II and the Danish National Birth Cohort. A total of 112 susceptibility genetic variants confirmed by genome-wide association studies for type 2 diabetes were selected and measured. A weighted genetic risk score (GRS) was created based on variants that were significantly associated with risk of GDM after correcting for the false discovery rate.ResultsFor the first time, we identified eight variants associated with GDM, namely rs7957197 (HNF1A), rs10814916 (GLIS3), rs3802177 (SLC30A8), rs9379084 (RREB1), rs34872471 (TCF7L2), rs7903146 (TCF7L2), rs11787792 (GPSM1) and rs7041847 (GLIS3). In addition, we confirmed three variants, rs10830963 (MTNR1B), rs1387153 (MTNR1B) and rs4506565 (TCF7L2), that had previously been significantly associated with GDM risk. Furthermore, compared with participants in the first (lowest) quartile of weighted GRS based on these 11 SNPs, the ORs for GDM were 1.07 (95% CI 0.93, 1.22), 1.23 (95% CI 1.07, 1.41) and 1.53 (95% CI 1.34, 1.74) for participants in the second, third and fourth (highest) quartiles, respectively. The significant positive associations between the weighted GRS and risk of GDM persisted across most of the strata of major risk factors for GDM, including family history of type 2 diabetes, smoking status, BMI and age.Conclusions/interpretationIn this large-scale case–control study with women from two independent populations, eight novel GDM SNPs were identified. These findings offer the potential to improve our understanding of the aetiology of GDM, and particularly of biological mechanisms related to beta cell function.

Validation of Self-Reported Diagnosis of Gestational Diabetes at Six Weeks Postpartum.

Background: Self-report is often used in identifying gestational diabetes events in epidemiologic studies; however, validity data are limited, with little to no data on self-reported severity or treatment. Methods: We aimed to assess the validity of self-reported gestational diabetes diagnosis and evaluate the accuracy of glucose diagnosis results and gestational diabetes treatment self-reported at 6-week postpartum. Data were from 82 and 83 women with and without gestational diabetes, respectively, within the prospective National Institute Child Health and Human Development Fetal Growth Studies-Singletons (2009–2013). Medical record data were considered the gold standard. Results: Sensitivity was 95% (95% confidence interval [CI] = 88, 98), and specificity was 100% (95% CI = 96, 100); four women with gestational diabetes incorrectly reported not having the disease, and none of the women without gestational diabetes reported having gestational diabetes. Sensitivity did not vary substantially across maternal characteristics including race/ethnicity. For women who attempted to recall their values (84/159 women), self-reported glucose challenge test results did not differ from the medical records (median difference: 0; interquartile range: 0–0 mg/dl). Medical records indicated that 42 (54%) of 78 women with confirmed gestational diabetes were treated by diet only and 33 (42%) were treated by medication. All 42 women with diet-treated gestational diabetes correctly reported having had diet and lifestyle modification, and 28 (85%) of 33 women with medication-treated gestational diabetes indicated postpartum that they had medication treatment. Conclusions: At 6-week postpartum, regardless of race/ethnicity or socioeconomic status, women accurately recalled whether they had gestational diabetes and, as applicable, their treatment method.

A Longitudinal Study of Thyroid Markers across Pregnancy and the Risk of Gestational Diabetes.

Context T3 is the biologically active thyroid hormone involved in glucose metabolism. The free T3 (fT3)/free T4 (fT4) ratio, a marker indicating conversion of fT4 to fT3, is also implicated in glucose homeostasis. Objective To examine associations of fT3 and the fT3/fT4 ratio with gestational diabetes mellitus (GDM). Design In a case-control study, thyroid markers (fT3, fT4, TSH) were measured and the fT3/fT4 ratio was derived across four visits in pregnancy, including first (gestational weeks 10 to 14) and second (weeks 15 to 26) trimester. Conditional logistic regression adjusting for thyroid autoimmunity status and major GDM risk factors estimated trimester-specific associations of thyroid markers with subsequent GDM risk. Setting Twelve US clinical centers. Participants One hundred seven GDM cases and 214 non-GDM controls from a multiracial pregnancy cohort of 2802 women. Main Outcome Measures GDM diagnosis ascertained from medical records. Results Both fT3 and the fT3/fT4 ratio were positively associated with GDM: adjusted OR (95% CI) comparing the highest vs lowest fT3 quartile was 4.25 (1.67, 10.80) at the first trimester and 3.89 (1.50, 10.10) at the second trimester. Similarly, the corresponding risk estimates for the fT3/fT4 ratio were 8.63 (2.87, 26.00) and 13.60 (3.97, 46.30) at the first and second trimester, respectively. Neither TSH nor fT4 was significantly associated with GDM. Conclusions Higher fT3 levels, potentially resulting from de novo synthesis or increased fT4 to fT3 conversion, may be an indicator of GDM risk starting early in pregnancy.

HbA1c Measured in the First Trimester of Pregnancy and the Association with Gestational Diabetes.

We aimed to examine the prospective association between first trimester HbA1c and gestational diabetes (GDM) and explore the utility of HbA1c for prediction of GDM. We used data from a case-control study within the prospective NICHD Fetal Growth Studies-Singleton Cohort (2009–2013), which enrolled 2,802 women at 12 U.S. clinical centers. HbA1c was measured in GDM cases (n = 107) and matched controls (n = 214) targeted at 8–13, 16–22, 24–29, and 34–37 gestational weeks. We excluded women with HbA1c ≥ 6.5% (48 mmol/mol) at enrollment (n = 3) or who had a hemoglobin variant (n = 6). At 8–13 gestational weeks, women who later developed GDM had significantly higher HbA1c (5.3[standard deviation 0.3]%; 34[4]mmol/mol) than women without GDM (5.1[0.3]%; 32[3] mmol/mol) (P ≤ 0.001); this difference remained significant throughout pregnancy. Each 0.1% (1 mmol/mol) HbA1c increase at 8–13 weeks was associated with an adjusted 22% increased GDM risk (95% confidence interval 1.09–1.36). First trimester HbA1c significantly improved GDM prediction over conventional risk factors (AUC 0.59 vs 0.65; P = 0.04). In conclusion, women who develop GDM may have impaired glucose homeostasis early in or prior to pregnancy, as indicated by their elevated first trimester HbA1c. First trimester HbA1c may aid in early identification of at risk women.