Differential dietary intake and contribution of ultra-processed foods during pregnancy according to nutritional status.

Introduction: Frequent consumption of ultra-processed foods (UPFs) during pregnancy is linked to excess intake of added sugar, fat, and sodium and inadequacy of several micronutrients. Diet quality during pregnancy should be maximized as inadequate levels of key nutrients and excessive intake of energy and added sugar might influence mother-child health. We aimed to estimate the contribution (% of total calories) of ultra-processed products to the total energy intake by pre-gestational body mass index (BMI) categories and Hb status during pregnancy in participants from the MAS-Lactancia Cohort. Methods: Pre-gestational weight, hemoglobin levels, 24-h dietary intake recall interviews, and sociodemographic data were collected during the second and third trimesters of pregnancy. Reported consumed foods were categorized using the NOVA classification, and the contribution of calories from each NOVA category was estimated using the Mexican Food Database. We estimated medians and interquartile ranges (p25 and p75) for dietary intake and energy contributions. The comparison of intake between the second and third trimesters was done using the Wilcoxon test. In addition, a quantile regression model with an interaction between pre-gestational BMI and Hb levels status in tertiles over the percentage of energy from UPFs was adjusted by age and socioeconomic status. Results: The contribution to total energy intake from UPFs was 27.4% in the second trimester and 27% in the third trimester (with no statistical difference). The percentage of energy intake from UPFs was higher in women who started pregnancy with obesity and presented the lowest levels of Hb (1st tertile), 23.1, 35.8, and 44.7% for the 25th, 50th, and 75th percentiles, respectively, compared to those with normal BMI and the highest tertile of Hb levels: 18, 29.0, and 38.6% for the 25th, 50th, and 75th percentiles, respectively. Conclusion: In conclusion, UPF intake in pregnant women is similar to the general population and was higher for those with pre-gestational obesity and the lowest tertile of Hb levels. UPF contributes also to sugar, saturated fat, and sodium, which may adversely affect the health of mothers and their offspring.

Skeletal muscle fibre type and enzymatic activity in adult offspring following placental and peripheral malaria exposure in foetal life.

Background: Maternal malaria may restrict foetal growth. Impaired utero-placental blood flow due to malaria infection may cause hypoxia-induced altered skeletal muscle fibre type distribution in the offspring, which may contribute to insulin resistance and impaired glucose metabolism. This study assessed muscle fibre distribution 20 years after placental and/or peripheral in-utero malaria exposure compared to no exposure, i.e., PPM+, PM+, and M-, respectively. Methods: We traced 101 men and women offspring of mothers who participated in a malaria chemosuppression study in Muheza, Tanzania. Of 76 eligible participants, 50 individuals (29 men and 21 women) had skeletal muscle biopsy taken from m. vastus lateralis in the right leg. As previously reported, fasting and 30 min post-oral glucose challenge plasma glucose values were higher, and insulin secretion disposition index was lower, in the PPM+ group. Aerobic capacity (fitness) was estimated by an indirect VO2max test on a stationary bicycle. Muscle fibre sub-type (myosin heavy chain, MHC) distribution was analysed, as were muscle enzyme activities (citrate synthase (CS), 3-hydroxyacyl-CoA dehydrogenase, myophosphorylase, phosphofructokinase, lactate dehydrogenase, and creatine kinase activities. Between-group analyses were adjusted for MHC-I %. Results: No differences in aerobic capacity were found between groups. Despite subtle elevations of plasma glucose levels in the PPM+ group, there was no difference in MHC sub-types or muscle enzymatic activities between the malaria-exposed and non-exposed groups. Conclusion: The current study did not show differences in MHC towards glycolytic sub-types or enzymatic activity across the sub-groups. The results support the notion of the mild elevations of plasma glucose levels in people exposed to placental malaria in pregnancy being due to compromised pancreatic insulin secretion rather than insulin resistance.

Independent phenotypic plasticity axes define distinct obesity sub-types.

Studies in genetically 'identical' individuals indicate that as much as 50% of complex trait variation cannot be traced to genetics or to the environment. The mechanisms that generate this 'unexplained' phenotypic variation (UPV) remain largely unknown. Here, we identify neuronatin (NNAT) as a conserved factor that buffers against UPV. We find that Nnat deficiency in isogenic mice triggers the emergence of a bi-stable polyphenism, where littermates emerge into adulthood either 'normal' or 'overgrown'. Mechanistically, this is mediated by an insulin-dependent overgrowth that arises from histone deacetylase (HDAC)-dependent ß-cell hyperproliferation. A multi-dimensional analysis of monozygotic twin discordance reveals the existence of two patterns of human UPV, one of which (Type B) phenocopies the NNAT-buffered polyphenism identified in mice. Specifically, Type-B monozygotic co-twins exhibit coordinated increases in fat and lean mass across the body; decreased NNAT expression; increased HDAC-responsive gene signatures; and clinical outcomes linked to insulinemia. Critically, the Type-B UPV signature stratifies both childhood and adult cohorts into four metabolic states, including two phenotypically and molecularly distinct types of obesity.

Influence of placental and peripheral malaria exposure in fetal life on cardiometabolic traits in adult offspring.

INTRODUCTION: Fetal malaria exposure may lead to intrauterine growth restriction and increase the risk of developing diabetes and cardiovascular diseases in adulthood. We investigated the extent to which fetal peripheral and placental malaria exposure impacts insulin sensitivity and secretion, body composition and cardiometabolic health 20 years after in utero malaria exposure. RESEARCH DESIGN AND METHODS: We traced 101 men and women in Muheza district, Tanga region whose mothers participated in a malaria chemosuppression during a pregnancy study in 1989-1992. All potential participants were screened for malaria, hepatitis B and HIV to ascertain study eligibility. Seventy-six individuals (44 men, 32 women) were included in this cohort study. The participants underwent a thorough clinical examination including anthropometric measurements, ultrasound scanning for abdominal fat distribution, blood pressure, 75 g oral glucose tolerance test, an intravenous glucose tolerance test followed by a hyperinsulinemic euglycemic clamp and a submaximal exercise test. RESULTS: Offspring exposed to placental malaria during pregnancy had significantly higher 30-minute plasma post-glucose load levels, but no significant difference in peripheral insulin resistance, insulin secretion or other cardiometabolic traits compared with non-exposed individuals. CONCLUSIONS: Using the state-of-the-art euglycemic clamp technique, we were unable to prove our a priori primary hypothesis of peripheral insulin resistance in young adult offspring of pregnancies affected by malaria. However, the subtle elevations of plasma glucose might represent an early risk marker for later development of type 2 diabetes if combined with aging and a more obesogenic living environment.

Cumulative Lactation and Clinical Metabolic Outcomes at Mid-Life among Women with a History of Gestational Diabetes.

Lactation is associated with a lower risk of subsequent cardiometabolic disease among parous women; however, the underlying mechanisms are unknown. Further, the potential protective effects of lactation on cardiometabolic risk markers at mid-life among high-risk women with past gestational diabetes (GDM) are not established. Using data from the Diabetes & Women's Health Study (2012−2014; n = 577), a longitudinal cohort of women with past GDM from the Danish National Birth Cohort (1996−2002), we assessed associations of cumulative lactation duration (none, <6 months, 6−12 months, ≥12−24 months, and ≥24 months) with clinical metabolic outcomes (including type 2 diabetes [T2D], prediabetes, and obesity) and cardiometabolic biomarkers (including biomarkers of glucose/insulin metabolism, fasting lipids, inflammation, and anthropometrics) 9−16 years after enrollment when women were at mid-life. At follow-up, women were 43.9 years old (SD 4.6) with a BMI of 28.7 kg/m2 (IQR 24.6, 33.0); 28.6% of participants had T2D, 39.7% had prediabetes, and 41.2% had obesity. Relative risks (95% CI) of T2D for 0−6, 6−12, 12−24, and ≥24 months of cumulative lactation duration compared to none were 0.94 (0.62,1.44), 0.88 (0.59,1.32), 0.73 (0.46,1.17), and 0.71 (0.40,1.27), respectively. Cumulative lactation duration was not significantly associated with any other clinical outcome or continuous biomarker. In this high-risk cohort of middle-aged women with past GDM, T2D, prediabetes, and obesity were common at follow-up, but not associated with history of cumulative lactation duration 9−16 years after the index pregnancy. Further studies in diverse populations among women at mid-age are needed to understand associations of breastfeeding with T2D.

Lactation Duration and Long-term Risk for Incident Type 2 Diabetes in Women With a History of Gestational Diabetes Mellitus.

OBJECTIVE: We examined the association of lactation duration with incident type 2 diabetes among women with a history of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: We monitored 4,372 women with a history of GDM participating in the Nurses' Health Study II for incident type 2 diabetes over 25 years up to 2017. Lactation history was obtained through follow-up questionnaires to calculate lactation duration. Follow-up blood samples were collected from a subset of these women at median age of 58 years through the Diabetes & Women's Health Study. RESULTS: We documented 873 incident cases of type 2 diabetes during 87,411 person-years of follow-up. Longer duration of lactation was associated with lower risk of type 2 diabetes for both total lactation (hazard ratio 1.05 [95% CI 0.83-1.34] for up to 6 months, 0.91 [0.72-1.16] for 6-12 months, 0.85 [0.67-1.06] for 12-24 months, and 0.73 [0.57-0.93] for >24 months, compared with 0 months; P-trend = 0.003) and exclusive breastfeeding (P-trend = 0.002) after adjustment for age, ethnicity, family history of diabetes, parity, age at first birth, smoking, diet quality, physical activity, and prepregnancy BMI. Longer duration of lactation was also associated with lower HbA1c, fasting plasma insulin, and C-peptide concentrations among women without type 2 diabetes at follow-up (all adjusted P-trend ≤0.04). CONCLUSIONS: Longer duration of lactation is associated with a lower risk of type 2 diabetes and a favorable glucose metabolic biomarker profile among women with a history of GDM. The underlying mechanisms and impact on diabetes complications, morbidity, and mortality remain to be determined.

Nut Consumption and Renal Function Among Women With a History of Gestational Diabetes.

OBJECTIVE: Nut intake has been associated with reduced cardiometabolic risk, but few studies have examined its association with renal function. We examined associations between nut intake and renal function among women with previous gestational diabetes mellitus (GDM), a population with an increased risk for renal dysfunction. DESIGN AND METHODS: This study included 607 women with a history of GDM who participated in the Diabetes & Women's Health Study (2012-2014) follow-up clinical examination in Denmark. At the clinic, biospecimens were collected, and habitual intake of nuts (9 types) in the past year was assessed using a food frequency questionnaire. A total of 330 women free of major chronic diseases were included in the analysis. Total nut intake was classified as none (≤1 serving/month), monthly (2-3 servings/month), weekly (1-6 servings/week), and daily (≥1 serving/day). One serving was defined as 28 g. Renal function markers included estimated glomerular rate (eGFR) and urinary albumin-to-creatinine ratio (UACR), calculated based on plasma creatinine (mg/dL), and urinary albumin (mg/L), and creatinine (mg/dL) measurements, respectively. We estimated percent differences with 95% confidence intervals for each outcome by nut intake, adjusted for current body mass index, age, physical activity, energy intake, alcohol consumption, and vegetables intake. RESULTS: We observed a nonlinear association between total nut intake and UACR with lowest UACR values among women with weekly intake. Compared to women with weekly intake (n = 222), the adjusted UACR values were higher by 86% [95% confidence interval: 15%, 202%], 24% [-1%, 54%], and 117% [22%, 288%] among women with no (n = 13), monthly (n = 86), and daily (n = 9) intake, respectively. Compared to weekly consumers, daily nut consumers also had 9% [0%, 19%] significantly higher eGFR values, but eGFR values were similar among women with no and monthly intake. CONCLUSION: Moderate nut consumption may be beneficial to kidney health among women with prior GDM.

Genetic factors and risk of type 2 diabetes among women with a history of gestational diabetes: findings from two independent populations.

OBJECTIVE: Women with a history of gestational diabetes mellitus (GDM) have an exceptionally high risk for type 2 diabetes (T2D). Yet, little is known about genetic determinants for T2D in this population. We examined the association of a genetic risk score (GRS) with risk of T2D in two independent populations of women with a history of GDM and how this association might be modified by non-genetic determinants for T2D. RESEARCH DESIGN AND METHODS: This cohort study included 2434 white women with a history of GDM from the Nurses' Health Study II (NHSII, n=1884) and the Danish National Birth Cohort (DNBC, n=550). A GRS for T2D was calculated using 59 candidate single nucleotide polymorphisms for T2D identified from genome-wide association studies in European populations. An alternate healthy eating index (AHEI) score was derived to reflect dietary quality after the pregnancy affected by GDM. RESULTS: Women on average were followed for 21 years in NHSII and 13 years in DNBC, during which 446 (23.7%) and 155 (28.2%) developed T2D, respectively. The GRS was generally positively associated with T2D risk in both cohorts. In the pooled analysis, the relative risks (RRs) for increasing quartiles of GRS were 1.00, 0.97, 1.25 and 1.19 (p trend=0.02). In both cohorts, the association appeared to be stronger among women with poorer (AHEI

Abdominal fat distribution measured by ultrasound and aerobic fitness in young Danish men born with low and normal birth weight.

Abdominal subcutaneous and visceral adipose tissue thickness was examined by ultrasound in 17 men with low birth weight (LBW) and 26 with normal BW control individuals to determine if abdominal obesity in LBW individuals is due to increased visceral or subcutaneous fat mass/thickness, or both. Men born with LBW had an increased waist-to-hip ratio (P = 0.04), greater abdominal fat thickness (P = 0.05) and increased visceral (VAT) and subcutaneous adipose tissue (SAT) thickness compared with controls, however the latter not statistically significant (P = 0.08, P = 0.10). A significant difference between birth weight groups in both SAT (P = 0.04) and VAT (P = 0.03) was found after adjustment for weight, whereas no significant difference in either SAT (P = 0.93) or VAT (P = 0.30) was found after adjustment for BMI. Increased waist-to-hip ratio in LBW individuals is due to increased total abdominal fat including both subcutaneous and visceral fat.

Increased leptin, decreased adiponectin and FGF21 concentrations in adolescent offspring of women with gestational diabetes.

OBJECTIVE: Fetal exposure to gestational diabetes mellitus (GDM) increases the risk of metabolic diseases in the offspring. Leptin, adiponectin, and fibroblast growth factor 21 (FGF21) may play potential roles in the underlying disease mechanisms. We investigated the impact of fetal exposure to GDM on leptin, adiponectin, and FGF21 concentrations and their associations with measures of adiposity and metabolic traits during childhood/adolescence. DESIGN AND METHODS: The follow-up study included 504 GDM and 540 control offspring aged 9-16 from the Danish National Birth Cohort. Anthropometric measurements, fasting blood samples, puberty status and fat percentages by dual-energy X-ray absorptiometry were examined. Serum concentrations of leptin, adiponectin, and FGF21 were measured by validated immune assays. RESULTS: GDM offspring had 38% (95% CI: 22-55%) higher leptin, 0.6 mg/L (95% CI: -1.2, -0.04 mg/L) lower adiponectin, and 32% (95% CI: -47%, -12%) lower FGF21 concentrations than control offspring (P < 0.05). After adjustment for confounders including maternal pre-pregnancy BMI, GDM offspring had borderline higher leptin (P = 0.06) and significantly lower FGF21 concentrations (P = 0.006). When accounting for offspring BMI z-score, GDM exposure had no significant independent effect on leptin or adiponectin concentrations, whereas FGF21 was still significant. In univariate analyses, leptin and adiponectin were associated with fasting insulin, HOMA-IR, and adiposity, and FGF21 with total fat percentage. CONCLUSIONS: GDM offspring had higher leptin, lower adiponectin and FGF21 concentrations than control offspring. Elevated leptin and decreased adiponectin concentrations associated with adverse metabolic traits and were most likely driven by higher obesity prevalence among GDM offspring. The functional implications of decreased FGF21 concentrations among GDM offspring need to be further explored.

Diabetes in pregnancy and epigenetic mechanisms-how the first 9 months from conception might affect the child's epigenome and later risk of disease.

Diabetes in pregnancy is not only associated with increased risk of pregnancy complications and subsequent maternal metabolic disease, but also increases the risk of long-term metabolic disease in the offspring. At the interface between genetic and environmental factors, epigenetic variation established in utero represents a plausible link between the in utero environment and later disease susceptibility. The identification of an epigenetic fingerprint of diabetes in pregnancy linked to the metabolic health of the offspring might provide novel biomarkers for the identification of offspring most at risk, before the onset of metabolic dysfunction, for targeted monitoring and intervention. In this Personal View, we (1) highlight the scale of the problem of diabetes in pregnancy, (2) summarise evidence for the variation in offspring epigenetic profiles following exposure to diabetes in utero, and (3) outline potential future approaches to further understand the mechanisms by which exposure to maternal metabolic dysfunction in pregnancy is transmitted through generations.

Prospective study of gestational diabetes and fatty liver scores 9 to 16 years after pregnancy.

BACKGROUND: Women with gestational diabetes mellitus (GDM) may be at an increased risk of liver complications because chronic hyperglycemia is a risk factor for liver fat accumulation and potential liver dysfunction. Large prospective studies examining liver fat accumulation following a GDM pregnancy are lacking. METHODS: The Diabetes & Women's Health Study (2012-2014) examined the association between GDM and subsequent fatty liver scores among 607 women with and 619 women without GDM in the Danish National Birth Cohort. Nine to 16 years postpartum, a clinical examination was performed, with measurement of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transferase, from which fatty liver scoring indices were calculated to assess liver fat score, fatty liver index, hepatic steatosis index, and liver fat percentage. Relative risks (RR) with 95% confidence intervals (CI) for elevated liver scoring indices by GDM status were assessed adjusting for major risk factors, including prepregnancy body mass index. RESULTS: Women with prior GDM had higher adjusted ALT and AST levels than women without GDM (by 6.7% [95% CI 1.7-12.0] and 4.8% [95% CI 0.6-9.1], respectively). Women with GDM also had adjusted increased risks for elevated liver fat score (RR 2.34; 95% CI 1.68-3.27), fatty liver index (RR 1.59; 95% CI 1.27-1.99), and hepatic steatosis index (RR 1.44; 95% CI 1.21-1.71). CONCLUSIONS: Women with GDM during pregnancy were at an increased risk for fatty liver 9 to 16 years postpartum. Gestational diabetes mellitus may serve as another risk indicator for the early identification and prevention of liver fat accumulation.

TCF7L2 Expression Is Regulated by Cell Differentiation and Overfeeding in Human Adipose Tissue.

Aim: The TCF7L2 gene variant rs7903146 has the largest effect on type 2 diabetes risk reported in genome-wide association studies, however its role in adipose tissue development and function is unknown. We investigate the association between gene variant rs7903146 and metabolic parameters and examine in vitro and ex vivo gene expression of TCF7L2 in human adipose tissue and progenitor cells from two independent populations of young healthy men with increased risk of type 2 diabetes due to low birth weight (LBW). Design: Adipose tissue biopsies were excised from 40 healthy young men with low and normal birth weights (NBW) after a control and 5-day high-fat overfeeding diet. In another cohort including 13 LBW and 13 NBW men, adipocyte progenitor cells were isolated and cultivated. Transcriptome-wide expression was performed on RNA extracted from biopsies or cell cultures. Results: Diet-induced peripheral insulin resistance is more pronounced in carriers of the T-risk allele rs7903146, whereas no association with hepatic insulin resistance was shown. TCF7L2 expression increased during adipogenesis in isolated preadipocytes from both LBW and NBW men (p < 0.001) and correlated positively with markers of progenitor cell proliferation and maturation capacity. In the mature adipose tissue, LBW men had lower expression of TCF7L2 compared to NBW men at baseline (p = 0.03) and TCF7L2 expression was suppressed by short-term overfeeding in NBW men (p = 0.005). Conclusions: The results suggest a regulation of TCF7L2 expression during adipogenesis and in mature adipose tissue upon overfeeding, and further that young men exposed to an adverse intrauterine environment have reduced mature adipose tissue TCF7L2 expression.

Associations between ambient air pollution and noise from road traffic with blood pressure and insulin resistance in children from Denmark.

BACKGROUND: Road traffic is a major source of air pollution and noise. Both exposures may contribute to increased blood pressure and metabolic disease; however, few studies have examined these relationships in children. OBJECTIVES: We aimed to investigate whether long-term exposures to air pollution and noise from road traffic were associated with increased blood pressure and insulin resistance in children. METHODS: Cardiometabolic outcomes were derived from a follow-up examination of 629 children (10-15 years old) enrolled in the Danish National Birth Cohort. We evaluated associations with prenatal and postnatal residential exposure to nitrogen dioxide (NO2) and noise from road traffic (Lden) using historical addresses and linear regression models. RESULTS: A 10-unit increase in postnatal exposure to NO2 and Lden was associated with a 0.31 (-0.87, 1.48) and 0.18 (-0.61, 0.96) mmHg changes in diastolic blood pressure, respectively. In contrast, both exposures were associated with decreased systolic blood pressure. After adjustment and mutual adjustment for NO2, exposure to Lden was associated with a statistical significant decrease in systolic blood pressure both during prenatal and postnatal life, but the majority of the associations evaluated did not reach statistical significance. Inverse associations were observed for plasma fasting glucose, insulin, and HOMA of insulin resistance for both exposures, exposure windows, before and after adjustment. CONCLUSIONS: The findings do not support evidence of associations between long-term exposures to air pollution and road traffic noise, increased blood pressure, and a metabolic profile characteristic of increased risk for glucose intolerance or type 2 diabetes later in life.

Fish Intake in Pregnancy and Offspring Metabolic Parameters at Age 9⁻16-Does Gestational Diabetes Modify the Risk?

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.

Risk factors of pre-hypertension and hypertension among non-pregnant women of reproductive age in northeastern Tanzania: a community based cross-sectional study.

OBJECTIVES: To determine risk factors of pre-hypertension and hypertension in a cohort of 1247 rural Tanzanian women before conception. METHODS: Demographic and socioeconomic data, anthropometric measurements, past medical and obstetric history and other risk factors for pre-hypertension and hypertension were collected using a structured questionnaire. Multiple logistic regression analysis was used to evaluate the associations between anthropometric indices and other risk factors of pre-hypertension and hypertension. The predictive power of different anthropometric indicators for identification of pre-hypertension and hypertension patients was determined by Receiver Operating Characteristic curves (ROC). RESULTS: The median (range) age was 28.0 (18-40) years. The age-standardised prevalences of pre-hypertension and hypertension were 37.2 (95% CI 34.0-40.6) and 8.5% (95%CI 6.7-10.8), respectively. Of hypertensive patients (n = 98), only 20 (20.4%) were aware of their condition. In multivariate analysis, increasing age, obesity and haemoglobin levels were significantly associated with pre-hypertension and hypertension. CONCLUSION: Despite a low prevalence of hypertension, over one third of the women had pre-hypertension. This poses a great challenge ahead as pre-hypertensive women may progress into hypertension as they grow older without appropriate interventions. Obesity was the single most important modifiable risk factor for pre-hypertension and hypertension.

Lactation Duration and Long-Term Thyroid Function: A Study among Women with Gestational Diabetes.

Lactation is associated with reduced postpartum weight retention and a lower risk of several cardiometabolic disorders in population-based studies. We examined the association between lactation and long-term thyroid function among women with history of gestational diabetes mellitus (GDM), a high-risk population for subsequent metabolic complications. The study included 550 women who developed GDM in the Danish National Birth Cohort (1996⁻2002) and followed-up in the Diabetes & Women's Health Study (2012⁻2014). We assessed adjusted associations between cumulative lactation duration and concentrations of thyroid stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) measured at follow-up. Women with longer cumulative lactation duration tended to have higher fT3 levels (adjusted ß and 95% confidence interval (CI) for ≥12 months vs. none: 0.19 (0.03⁻0.36); p-trend = 0.05). When restricted to women with a single lifetime pregnancy to control for parity (n = 70), women who lactated for >6 months (vs. none) had higher fT3 levels (0.46 pmol/L (0.12⁻0.80); p-trend = 0.02) and a higher fT3:fT4 ratio (0.61 (0.17⁻1.05); p-trend = 0.007). Our findings suggested that a longer duration of lactation may be related to greater serum fT3 levels and fT3:fT4 ratio 9⁻16 years postpartum among Danish women with a history of GDM. The association was particularly pronounced among women who only had one lifetime pregnancy.

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

AIMS/HYPOTHESIS: Gestational 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. METHODS: We 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. RESULTS: For 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/INTERPRETATION: In 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.

Gestational Diabetes Mellitus and Renal Function: A Prospective Study With 9- to 16-Year Follow-up After Pregnancy.

OBJECTIVE: To examine whether gestational diabetes mellitus (GDM), independent of subsequent diabetes, is an early risk factor for renal impairment long term after the index pregnancy. RESEARCH DESIGN AND METHODS: In the Diabetes & Women's Health (DWH) study (2012-2016), we examined the independent and joint associations of GDM and subsequent diabetes with long-term renal function among 607 women with and 619 women without GDM in the Danish National Birth Cohort (DNBC) index pregnancy (1996-2002). At median follow-up of 13 years after the index pregnancy, serum creatinine (mg/dL) and urinary albumin (mg/L) and creatinine (mg/dL) were measured, from which estimated glomerular filtration rate (eGFR) (mL/min/1.73 m2) and urinary albumin-to-creatinine ratio (UACR) (mg/g) were derived. RESULTS: Compared with women without GDM or subsequent diabetes, women with a GDM history had significantly higher eGFR even if they had not subsequently developed diabetes (adjusted ß-coefficient [95% CI] = 3.3 [1.7, 5.0]). Women who had a GDM history and later developed diabetes (n = 183) also had significantly higher UACR [exponent ß = 1.3 [95% CI 1.1, 1.6]) and an increased risk of elevated UACR (≥20 mg/g) [adjusted relative risk [95% CI] = 2.3 [1.1, 5.9]) compared with women with neither. After adjusting for potential confounders including prepregnancy BMI and hypertension, GDM without subsequent diabetes was not related to UACR. CONCLUSIONS: Women who develop GDM in pregnancy were more likely to show increased eGFR levels 9-16 years postpartum, which could indicate early stages of glomerular hyperfiltration and renal damage. However, only those who subsequently developed diabetes showed overt renal damage as evidenced by elevated UACR.

Telomere length is reduced in 9- to 16-year-old girls exposed to gestational diabetes in utero.

AIMS/HYPOTHESIS: Shortened telomere length is a marker of cell damage and is associated with oxidative stress, chronic inflammation and metabolic disease. We hypothesised that the offspring of women with gestational diabetes mellitus (GDM) with increased risk of cardiovascular and metabolic diseases might exhibit shorter telomere length. METHODS: We investigated telomere length in 439 GDM and 469 control group offspring, aged between 9 and 16 years, recruited from the Danish National Birth Cohort. Relative telomere length was measured in peripheral blood DNA (n = 908) using a quantitative PCR approach. Multivariate regression analysis was used to investigate the association between mothers' GDM status and telomere length in the offspring. RESULTS: Female offspring had longer telomeres than males. Offspring of mothers with GDM had significantly shorter telomere length than control offspring, but this difference was observed only in girls. There was a negative association between telomere length and GDM exposure among the female offspring (14% shorter telomeres, p = 0.003) following adjustment for the age of the offspring. Telomere length in female offspring was negatively associated with fasting insulin levels and HOMA-IR (p = 0.03). Maternal age, smoking, gestational age, birthweight and the offspring's anthropometric characteristics were not associated with telomere length (p ≥ 0.1). CONCLUSIONS/INTERPRETATION: The 9- to 16-year-old girls of mothers with GDM had shorter telomeres than those from the control population. Further studies are needed to understand the extent to which shortened telomere length predicts and/or contributes to the increased risk of disease later in life among the offspring of women with GDM.