Refining the diagnosis of gestational diabetes mellitus: a systematic review and meta-analysis.

BACKGROUND: Perinatal outcomes vary for women with gestational diabetes mellitus (GDM). The precise factors beyond glycemic status that may refine GDM diagnosis remain unclear. We conducted a systematic review and meta-analysis of potential precision markers for GDM. METHODS: Systematic literature searches were performed in PubMed and EMBASE from inception to March 2022 for studies comparing perinatal outcomes among women with GDM. We searched for precision markers in the following categories: maternal anthropometrics, clinical/sociocultural factors, non-glycemic biochemical markers, genetics/genomics or other -omics, and fetal biometry. We conducted post-hoc meta-analyses of a subset of studies with data on the association of maternal body mass index (BMI, kg/m2) with offspring macrosomia or large-for-gestational age (LGA). RESULTS: A total of 5905 titles/abstracts were screened, 775 full-texts reviewed, and 137 studies synthesized. Maternal anthropometrics were the most frequent risk marker. Meta-analysis demonstrated that women with GDM and overweight/obesity vs. GDM with normal range BMI are at higher risk of offspring macrosomia (13 studies [n = 28,763]; odds ratio [OR] 2.65; 95% Confidence Interval [CI] 1.91, 3.68), and LGA (10 studies [n = 20,070]; OR 2.23; 95% CI 2.00, 2.49). Lipids and insulin resistance/secretion indices were the most studied non-glycemic biochemical markers, with increased triglycerides and insulin resistance generally associated with greater risk of offspring macrosomia or LGA. Studies evaluating other markers had inconsistent findings as to whether they could be used as precision markers. CONCLUSIONS: Maternal overweight/obesity is associated with greater risk of offspring macrosomia or LGA in women with GDM. Pregnancy insulin resistance or hypertriglyceridemia may be useful in GDM risk stratification. Future studies examining non-glycemic biochemical, genetic, other -omic, or sociocultural precision markers among women with GDM are warranted.

Gestational Diabetes (GDM) is high blood sugar that develops during pregnancy and may cause complications. GDM diagnosis is centered on blood sugar levels. Despite everyone receiving standard treatment, the clinical outcomes may vary from one individual to another. This indicates a need to identify factors that may help GDM diagnosis and result in improved classification of those at greatest risk for complications. Here, we systematically analyzed all published evidence for potential markers that could identify those with GDM who have greater risk of complications. We find that high maternal weight is a risk factor for offspring born larger for their gestational age. Other promising markers were identified, but further analysis is needed before they can be applied in the clinic.

Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine.

Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.

Novel Metabolic Subtypes in Pregnant Women and Risk of Early Childhood Obesity in Offspring.

Importance: The in utero metabolic milieu is associated with offspring adiposity. Standard definitions of maternal obesity (according to prepregnancy body mass index [BMI]) and gestational diabetes (GDM) may not be adequate to capture subtle yet important differences in the intrauterine environment that could be involved in programming. Objectives: To identify maternal metabolic subgroups during pregnancy and to examine associations of subgroup classification with adiposity traits in their children. Design, Setting, and Participants: This cohort study included mother-offspring pairs in the Healthy Start prebirth cohort (enrollment: 2010-2014) recruited from University of Colorado Hospital obstetrics clinics in Aurora, Colorado. Follow-up of women and children is ongoing. Data were analyzed from March to December 2022. Exposures: Metabolic subtypes of pregnant women ascertained by applying k-means clustering on 7 biomarkers and 2 biomarker indices measured at approximately 17 gestational weeks: glucose, insulin, Homeostatic Model Assessment for Insulin Resistance, total cholesterol, high-density lipoprotein cholesterol (HDL-C), triglycerides, free fatty acids (FFA), HDL-C:triglycerides ratio, and tumor necrosis factor α. Main Outcomes and Measures: Offspring birthweight z score and neonatal fat mass percentage (FM%). In childhood at approximately 5 years of age, offspring BMI percentile, FM%, BMI in the 95th percentile or higher, and FM% in the 95th percentile or higher. Results: A total of 1325 pregnant women (mean [SD] age, 27.8 [6.2 years]; 322 [24.3%] Hispanic, 207 non-Hispanic Black [15.6%], and 713 [53.8%] non-Hispanic White), and 727 offspring with anthropometric data measured in childhood (mean [SD] age 4.81 [0.72] years, 48% female) were included. We identified the following 5 maternal metabolic subgroups: reference (438 participants), high HDL-C (355 participants), dyslipidemic-high triglycerides (182 participants), dyslipidemic-high FFA (234 participants), and insulin resistant (IR)-hyperglycemic (116 participants). Compared with the reference subgroup, women in the IR-hyperglycemic and dyslipidemic-high FFA subgroups had offspring with 4.27% (95% CI, 1.94-6.59) and 1.96% (95% CI, 0.45-3.47) greater FM% during childhood, respectively. There was a higher risk of high FM% among offspring of the IR-hyperglycemic (relative risk, 8.7; 95% CI, 2.7-27.8) and dyslipidemic-high FFA (relative risk, 3.4; 95% CI, 1.0-11.3) subgroups; this risk was of greater magnitude compared with prepregnancy obesity alone, GDM alone, or both conditions. Conclusions and Relevance: In this cohort study, an unsupervised clustering approach revealed distinct metabolic subgroups of pregnant women. These subgroups exhibited differences in risk of offspring adiposity in early childhood. Such approaches have the potential to refine understanding of the in utero metabolic milieu, with utility for capturing variation in sociocultural, anthropometric, and biochemical risk factors for offspring adiposity.

Antimüllerian hormone and adiposity across midlife among women in Project Viva.

OBJECTIVE: This study aimed to examine the association of antimüllerian hormone (AMH) with concurrent and prospective measures of adiposity during approximately 9 years of follow-up. METHODS: Participants were 697 parous women from the Project Viva prebirth cohort without polycystic ovarian syndrome. We measured AMH at approximately 3 years postpartum (baseline). Outcomes were weight, body mass index (BMI), and waist circumference assessed at baseline, 4, and 9 years later; % body fat was assessed by bioimpedance at the 4- and 9-year visit. We used linear mixed-effect models including all outcome time points and accounting for age across follow-up and hormonal contraception prescription. In an additional model, we further adjusted for height. RESULTS: Median AMH was 1.97 ng/mL (interquartile range, 0.83-4.36 ng/mL), 29.1% had AMH <1.0 ng/mL, and mean age at AMH measurement was 36.7 years (SD, 4.9 y; range, 20-48 y). AMH was inversely associated with average weight, BMI, and waist circumference over follow-up. In age-adjusted models, women with AMH <1.0 versus ≥1.0 ng/mL were 4.92 kg (95% CI, 2.01-7.82 kg) heavier, had a 2.51 cm (95% CI, 0.12-4.89 cm) greater waist circumference, and a 1.46 kg/m 2 (95% CI, 0.44-2.48 kg/m 2 ) greater BMI across the 9 years of follow-up. Findings were similar after covariate adjustment and when AMH was modeled continuously. AMH was also inversely associated with higher fat mass %; however, the CI crossed the null. CONCLUSION: Low AMH at baseline was associated with greater adiposity concurrently and across approximately 9 years of follow-up. Whether low AMH is a useful marker of metabolic risk across midlife requires further research.

Metabolomic Profiles in Childhood and Adolescence Are Associated with Fetal Overnutrition.

Fetal overnutrition predisposes offspring to increased metabolic risk. The current study used metabolomics to assess sustained differences in serum metabolites across childhood and adolescence among youth exposed to three typologies of fetal overnutrition: maternal obesity only, gestational diabetes mellitus (GDM) only, and obesity + GDM. We included youth exposed in utero to obesity only (BMI ≥ 30; n = 66), GDM only (n = 56), obesity + GDM (n = 25), or unexposed (n = 297), with untargeted metabolomics measured at ages 10 and 16 years. We used linear mixed models to identify metabolites across both time-points associated with exposure to any overnutrition, using a false-discovery-rate correction (FDR) <0.20. These metabolites were included in a principal component analysis (PCA) to generate profiles and assess metabolite profile differences with respect to overnutrition typology (adjusted for prenatal smoking, offspring age, sex, and race/ethnicity). Fetal overnutrition was associated with 52 metabolites. PCA yielded four factors accounting for 17−27% of the variance, depending on age of measurement. We observed differences in three factor patterns with respect to overnutrition typology: sphingomyelin-mannose (8−13% variance), skeletal muscle metabolism (6−10% variance), and 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF; 3−4% variance). The sphingomyelin-mannose factor score was higher among offspring exposed to obesity vs. GDM. Exposure to obesity + GDM (vs. GDM or obesity only) was associated with higher skeletal muscle metabolism and CMPF scores. Fetal overnutrition is associated with metabolic changes in the offspring, but differences between typologies of overnutrition account for a small amount of variation in the metabolome, suggesting there is likely greater pathophysiological overlap than difference.

Exposure to maternal fuels during pregnancy and offspring hepatic fat in early childhood: The healthy start study.

BACKGROUND: Intrauterine overnutrition has been associated with paediatric nonalcoholic fatty liver disease (NAFLD), but the exact mechanisms involved remain unclear. OBJECTIVE: To examine whether maternal fuels and metabolic markers during pregnancy are associated with offspring hepatic fat in childhood. METHODS: This analysis included 286 mother-child pairs from the Healthy Start Study, a longitudinal pre-birth cohort in Colorado. Fasting blood draws were collected in early pregnancy (~17 weeks) and mid-pregnancy (~27 weeks). Offspring hepatic fat was assessed by magnetic resonance imaging (MRI) at ~5 years. RESULTS: In early pregnancy, maternal triglycerides (TGs) and free fatty acids (FFAs) were positively associated with offspring hepatic fat [Back-transformed ß (95% CI): 1.15 (1.05, 1.27) per 1 standard deviation (SD) TGs; 1.14 (1.05, 1.23) per 1 SD FFAs]. Maternal total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were also associated with offspring hepatic fat, but only among boys [1.22 (1.08, 1.37) per 1 SD TC; 1.21 (1.07, 1.37) per 1 SD LDL-C]. In mid-pregnancy, only maternal TGs remained associated with offspring hepatic fat. Adjusting for potential confounders or mediators did not affect associations. CONCLUSIONS: Maternal lipid concentrations, especially in early pregnancy, are associated with higher offspring hepatic fat, and may, therefore, be targeted in future interventions among pregnant women.

Maternal Diet Quality Is Associated with Placental Proteins in the Placental Insulin/Growth Factor, Environmental Stress, Inflammation, and mTOR Signaling Pathways: The Healthy Start ECHO Cohort.

BACKGROUND: Maternal nutritional status affects placental function, which may underlie the intrauterine origins of obesity and diabetes. The extent to which diet quality is associated with placental signaling and which specific pathways are impacted is unknown. OBJECTIVES: To examine sex-specific associations of maternal diet quality according to the Healthy Eating Index (HEI)-developed to align with recommendations from the Dietary Guidelines for Americans-with placental proteins involved in metabolism and mediators of environmental stress, inflammation, and growth factors. METHODS: Among 108 women from the Healthy Start cohort with a mean ± SD age of 29.0 ± 6.1 y and a prepregnancy BMI (in kg/m2) of 24.8 ± 5.3, we conducted multivariable linear regression analysis stratified by offspring sex. We adjusted for maternal race or ethnicity, age, education, prenatal smoking habits, and physical activity and tested for an association of maternal HEI >57 compared with ≤57 and the abundance and phosphorylation of key proteins involved in insulin/growth factor signaling; mediators of environmental stress, inflammation, and growth factors; mechanistic target of rapamycin signaling proteins; and energy sensing in placental villus samples. HEI >57 was chosen given its prior relevance among Healthy Start mother-child dyads. RESULTS: In adjusted models, HEI >57 was associated with greater abundance of insulin receptor ß (0.80; 95% CI: 0.11, 1.49) in placentas of females. In males, maternal HEI >57 was associated with greater activation and abundance of select placental nutrient-sensing proteins and environmental stress, inflammation, and growth factor proteins (S6K1Thr389/S6K1: 0.81; 95% CI: 0.21, 1.41; JNK1Thr183/Tyr185/JNK1: 0.82; 95% CI: 0.27, 1.37; JNK2Thr183/Tyr185/JNK2: 0.57; 95% CI: 0.02, 1.11). CONCLUSIONS: Higher-quality diet had sex-specific associations with placental protein abundance/phosphorylation. Given that these proteins have been correlated with neonatal anthropometry, our findings provide insight into modifiable factors and placental pathways that should be examined in future studies as potential links between maternal diet and offspring metabolic health. This trial was registered at clinicaltrials.gov as NCT02273297.

Maternal Proinflammatory Adipokines Throughout Pregnancy and Neonatal Size and Body Composition: A Prospective Study.

BACKGROUND: Increased maternal adiposity and inflammation have impacts on fetal growth. OBJECTIVES: The purpose of this prospective study was to investigate the associations of 3 proinflammatory adipokines in pregnancy with neonatal anthropometry. METHODS: In a sample of 321 US pregnant women from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singleton Cohort (NCT00912132), plasma IL-6, fatty acid binding protein-4 (FABP4), and chemerin were measured in plasma samples collected at 10-14, 15-26, 23-31, and 33-39 weeks of gestation. Generalized linear models were used to estimate associations of adipokines with neonatal weight, thigh, and crown-heel length, and skinfolds at birth. Models adjusted for age, race/ethnicity, education, nulliparity, prepregnancy BMI, and weeks of gestation at blood collection. RESULTS: At each time point, higher IL-6 was associated with lower neonatal birthweight and thigh length. At 15-26 weeks of gestation, a 1 SD pg/mL increase in IL-6 was associated with -84.46 g lower neonatal birthweight (95% CI: -150.70, -18.22), -0.17 cm shorter thigh length (95% CI: -0.27, -0.07), -0.43 cm shorter crown-heel length (95% CI: -0.75, -0.10), and -0.75 mm smaller sum of skinfolds (95% CI: -1.19, -0.31), with similar associations at 23-31 and 33-39 weeks of gestation. There were no associations of FABP4 and chemerin with neonatal anthropometry. CONCLUSIONS: Starting as early as 15 weeks of gestation, higher maternal IL-6 concentrations in pregnancy were associated with lower neonatal birthweight, thigh and crown-heel length, and skinfolds. These data provide insight into the relevance of maternal inflammatory markers with neonatal anthropometry.

Maternal diet quality during pregnancy is associated with biomarkers of metabolic risk among male offspring.

AIMS/HYPOTHESIS: Limited data exist on the association between maternal diet quality during pregnancy and metabolic traits in offspring during early childhood, which is a sensitive period for risk of obesity-related disorders later in life. We aimed to examine the association of maternal diet quality, as indicated by the Healthy Eating Index-2010 (HEI), in pregnancy with offspring metabolic biomarkers and body composition at age 4-7 years. METHODS: We used data from 761 mother-offspring pairs from the Healthy Start study to examine sex-specific associations of HEI >57 vs ≤57 with offspring fasting glucose, leptin, cholesterol, HDL, LDL, percentage fat mass, BMI z score and log-transformed insulin, 1/insulin, HOMA-IR, adiponectin, triacylglycerols, triacylglycerols:HDL, fat mass, and sum of skinfolds. Multivariable linear regression models accounted for maternal race/ethnicity, age, education, smoking habits during pregnancy and physical activity, and child's age. RESULTS: During pregnancy, mean (SD) HEI score was 55.0 (13.3), and 43.0% had an HEI score >57. Among boys, there was an inverse association of maternal HEI with offspring glucose, insulin, HOMA-IR and adiponectin. For instance, maternal HEI >57 was associated with lower fasting glucose (-0.11; 95% CI -0.20, -0.02 mmol/l), and lower concentrations of: insulin by 15.3% (95% CI -24.6, -5.0), HOMA-IR by 16.3% (95% CI -25.7, -5.6) and adiponectin by 9.3% (95% CI -16.1, -2.0). Among girls, there was an inverse association of maternal HEI with insulin and a positive association with LDL. However, following covariate adjustment, all estimates among girls were attenuated to the null. CONCLUSIONS/INTERPRETATION: Greater compliance with the USA Dietary Guidelines via the HEI may improve the maternal-fetal milieu and decrease susceptibility for poor metabolic health among offspring, particularly boys. Future studies are warranted to confirm these associations and determine the underlying mechanisms.

Pre- and Perinatal Correlates of Ideal Cardiovascular Health during Early Childhood: A Prospective Analysis in the Healthy Start Study.

OBJECTIVES: To characterize prevalence of ideal cardiovascular health (ICVH) during early childhood (4-7 years of age), and to identify pre- and perinatal biological, sociodemographic, metabolic, and behavioral correlates of ICVH. STUDY DESIGN: Among 350 mother-child pairs in the Healthy Start Study, we defined ICVH as no exposure to second hand smoke; ≥1 hour/day of moderate-to-vigorous physical activity; body mass index ≤85th percentile; systolic and diastolic blood pressure <90th percentile; cholesterol <170 mg/dL, fasting glucose <100 mg/dL; and healthy diet, per the American Heart Association. Pre- and perinatal characteristics were obtained from questionnaires, medical records, and in-person visits. Because of low prevalence of ICVH, we focused on prevalence of meeting ≥6 metrics in the analysis. We examined bivariate associations of each characteristic with % meeting ≥6 metrics and included those that were significant (P < .05) in a multivariable logistic regression model. RESULTS: ICVH prevalence at mean ± SD age 4.7±0.6 years was 6.9%; boys had twice the prevalence as girls (9% vs 4.4%). Most (>85%) children met criteria for second hand smoke, body mass index, blood pressure, cholesterol, and glucose, and only one-third met criteria for physical activity (31.4%) and diet (35.1%). In multivariable analyses, key correlates of ICVH were maternal weight status (ORoverweight/obese vs nonoverweight/obese = 0.41 [0.23, 0.73]) and offspring sex (ORmale vs female = 2.14 [1.22, 3.65]). CONCLUSIONS: At age 4-7 years, ICVH prevalence is already low, with diet and adequate physical activity being the limiting factors. Healthy maternal weight prior to pregnancy and male sex are potential determinants of childhood ICVH. Additional work is required to explore associations of early-life ICVH with future health outcomes.

Health behaviors of American pregnant women: a cross-sectional analysis of NHANES 2007-2014.

BACKGROUND: This study examined engagement in five health behaviors among pregnant women in the USA. METHODS: Pregnant women who participated in the National Health and Nutrition Examination Survey 2007-2014 were included in this study. Five health behaviors were examined: adequate fruit and vegetable consumption, prenatal multivitamin use, physical activity, sleep and smoking. Multivariable regressions were used to estimate the odds ratio and 95% confidence interval of characteristics associated with health behaviors. RESULTS: Among 248 pregnant women, only 10.2% engaged in all five health behaviors and 35.4% consumed adequate fruits and vegetables. For adequate fruit and vegetable consumption, Hispanic and women of 'other' race were more likely to meet the recommendation compared to non-Hispanic white (P = 0.01 and P = 0.03, respectively); high school graduates were less likely to meet the recommendation compared to those with at least some college education or more (P = 0.04). CONCLUSIONS: Adequate fruit and vegetable consumption among pregnant women was poor and differed by race/ethnicity and education status. Because of the cross-sectional design, we cannot examine engagement in health behaviors continuously throughout pregnancy. Future research with longitudinal data over the course of pregnancy is needed to confirm these results.

Third trimester maternal vitamin D and early childhood socioemotional development.

BACKGROUND: Whether maternal vitamin D affects offspring socioemotional development in early childhood has been underexplored. OBJECTIVES: This study examined associations between maternal vitamin D during in the 3rd trimester and offspring socioemotional development between 30 and 59 months. METHODS: Data from 87 maternal-offspring pairs enrolled in the National Children's Study were used. Total plasma maternal vitamin D (25-hydroxyergocalciferol + 25-hydroxycholecalciferol) was measured between 28 and 35 gestational weeks and categorised as quartiles (Q). Multivariable regression models, adjusting for maternal race/ethnicity, education, and prepregnancy body mass index (BMI [kg/m2 ]), were used to estimate the association between vitamin D and offspring scores on the Brief Infant-Toddler Social and Emotional Assessment (BITSEA). RESULTS: The mean (standard deviation) vitamin D concentration was 86.5 (27.8) nmol/L. The median (range) BITSEA problem score was 6.0 (0.0-30.0), and competence score was 19.0 (7.0-22.0). Maternal vitamin D was inversely related to offspring problem scores. Compared to offspring of women with 25(OH)D in Q1, offspring problem scores were -4.80 (95% confidence interval [CI] -8.29, -1.33) units lower for Q2 vs Q1, -5.64 (95% CI -9.60, -1.68) units lower for Q3 vs Q1, and -4.70 (95% CI -8.59, -0.82) units lower for Q4 vs Q1. Vitamin D was not associated with offspring competence score. CONCLUSIONS: Higher maternal vitamin D was associated with lower offspring behaviour problems and not associated with socioemotional competence. These data indicate the association of maternal vitamin D and offspring development may be dependent on the specific developmental component being investigated.

Maternal blood glucose level and offspring glucose-insulin homeostasis: what is the role of offspring adiposity?

AIMS/HYPOTHESIS: The aim of this work was to investigate the association of maternal HbA1c during mid-pregnancy with biomarkers of glucose-insulin homeostasis during early childhood (4-7 years of age) and to assess whether and how offspring adiposity at birth and at age 4-7 years mediates this relationship among 345 mother-child pairs in the Healthy Start Study. METHODS: The exposure was maternal HbA1c (mmol/mol) measured at 20-34 gestational weeks and categorised into tertiles. The outcomes were offspring fasting glucose, 1/insulin, HOMA2-IR, and HOMA2-B at age 4-7 years. The mediators were per cent fat mass (%FM) at birth, %FM at age 4-7 years, and the sum of the two as a metric of cumulative adiposity. Mediation analyses were conducted via a counterfactual-based approach. All models accounted for maternal race/ethnicity, offspring age and sex. RESULTS: There was a significant total effect of maternal HbA1c on offspring glucose and 1/insulin. Specifically, we observed a positive trend across tertiles of HbA1c and offspring glucose (p trend <0.001), and an inverse trend across tertiles of HbA1c and offspring 1/insulin (p trend = 0.04). For instance, compared with offspring of women in the lowest tertile of HbA1c, those whose mothers were in the second and third tertiles had 0.04 mmol/l (95% CI -0.05, 0.13) and 0.17 mmol/l (95% CI 0.08, 0.26) higher fasting glucose concentrations at age 4-7 years, respectively. Adjustment for pre-pregnancy BMI did not appreciably change the results. We found no evidence of mediation by offspring adiposity at any life stage. CONCLUSIONS/INTERPRETATION: Offspring of women with higher HbA1c during pregnancy had higher fasting glucose and lower insulin sensitivity by early childhood. These relationships were largely unaffected by the child's own adiposity. Graphical abstract.

Adipokines in early and mid-pregnancy and subsequent risk of gestational diabetes: a longitudinal study in a multiracial cohort.

INTRODUCTION: Several adipokines are implicated in the pathophysiology of gestational diabetes mellitus (GDM), however, longitudinal data in early pregnancy on many adipokines are lacking. We prospectively investigated the association of a panel of adipokines in early and mid-pregnancy with GDM risk. RESEARCH DESIGN AND METHODS: Within the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singletons cohort (n=2802), a panel of 10 adipokines (plasma fatty acid binding protein-4 (FABP4), chemerin, interleukin-6 (IL-6), leptin, soluble leptin receptor (sOB-R), adiponectin, omentin-1, vaspin, and retinol binding protein-4) were measured at gestational weeks (GWs) 10-14, 15-26, 23-31, and 33-39 among 107 GDM cases (ascertained on average at GW 27) and 214 non-GDM controls. Conditional logistic regression was used to estimate ORs of each adipokine and GDM, controlling for known GDM risk factors including pre-pregnancy body mass index. RESULTS: Throughout pregnancy changes in chemerin, sOB-R, adiponectin, and high-molecular-weight adiponectin (HMW-adiponectin) concentrations from 10-14 to 15-26 GWs were significantly different among GDM cases compared with non-GDM controls. In early and mid-pregnancy, FABP4, chemerin, IL-6 and leptin were positively associated with increased GDM risk. For instance, at 10-14 GWs, the OR comparing the highest versus lowest quartile (ORQ4-Q1) of FABP4 was 3.79 (95% CI 1.63 to 8.85). In contrast, in both early and mid-pregnancy adiponectin (eg, ORQ4-Q1 0.14 (0.05, 0.34) during 10-14 GWs) and sOB-R (ORQ4-Q1 0.23 (0.11, 0.50) during 10-14 GWs) were inversely related to GDM risk. At 10-14 GWs a model that included conventional GDM risk factors and FABP4, chemerin, sOB-R, and HMW-adiponectin improved the estimated prediction (area under the curve) from 0.71 (95% CI 0.66 to 0.77) to 0.77 (95% CI 0.72 to 0.82). CONCLUSIONS: A panel of understudied adipokines including FABP4, chemerin, and sOB-R may be implicated in the pathogenesis of GDM with significant associations detected approximately 10-18 weeks before typical GDM screening.

Sex-Specific Metabolite Biomarkers of NAFLD in Youth: A Prospective Study in the EPOCH Cohort.

CONTEXT: Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in developed nations. There are currently no accurate biomarkers of NAFLD risk in youth. OBJECTIVE: Identify sex-specific metabolomics biomarkers of NAFLD in a healthy cohort of youth. DESIGN/SETTING: This prospective study included 395 participants of the EPOCH cohort in Colorado, who were recruited 2006-2009 ("T1 visit") and followed for 5 years ("T2 visit"). We entered 767 metabolites measured at T1 into a reduced rank regression model to identify the strongest determinants of hepatic fat fraction (HFF) at T2, separately for boys and girls. We compared the capacity of metabolites versus conventional risk factors (overweight/obesity, insulin, alanine transaminase, aspartate transaminase) to predict NAFLD (HFF ≥5%) and high HFF (fourth vs first quartile) using area under the receiver operating characteristic curve (AUC). RESULTS: Prevalence of NAFLD was 7.9% (8.5% of boys, 7.1% of girls). Mean ± SD HFF was 2.5 ± 3.1%. We identified 13 metabolites in girls and 10 metabolites in boys. Metabolites were in lipid, amino acid, and carbohydrate metabolism pathways. At T1, the metabolites outperformed conventional risk factors in prediction of high HFF but not NAFLD. At T2, the metabolites were superior to conventional risk factors as predictors of high HFF (AUC for metabolites vs conventional risk factors for boys: 0.9565 vs 0.8851, P = 0.02; for girls: 0.9450 vs 0.8469, P = 0.02) with similar trends for NAFLD, although the differences were not significant. CONCLUSIONS: The metabolite profiles identified herein are superior predictors of high HFF when assessed 5 years prior and concurrently in a general-risk setting.

Adherence to DASH dietary pattern is inversely associated with osteoarthritis in Americans.

Osteoarthritis (OA) is one of the most common diseases that cause disability among older adults. The objective of this study was to assess the association between adherence to the Dietary Approaches to Stop Hypertension (DASH) and OA in American adults. This study included adults (≥ aged 20 years) who participated in the National Health and Examination Survey (NHANES) 2007-2016 in the United States. Adherence to the DASH score was calculated from 8 food groups. Higher scores indicate better adherence to the DASH dietary pattern. Among the 21,901 participants included in this study, 10.26% reported having OA. Results of our multivariable logistic regression indicated a statistically significant inverse association between DASH score tertiles and OA. The adjusted ORs (95% CI) were 1.00 (ref), 0.89 (0.72; 1.10), and 0.78 (0.60; 1.00) across increasing DASH score tertiles (P for trend = 0.045). In this representative sample of American adults, greater adherence to the DASH dietary pattern was associated with lower likelihood of having OA.

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.

Association Between Prior Insurance and Health Service Utilization Among the Long-Term Uninsured in South Carolina.

Purpose: Strong evidence supports the relationship between health coverage and improved health status. Little is known about the lasting impact of prior health insurance on the prior insured's use of health services. We aimed to examine the association between prior insurance status and health service utilization (HSU) among the long-term uninsured (LTU) in South Carolina. Methods: The current study used data from in-person interviews of the LTU collected in a 2014 cross-sectional South Carolina survey. Men and women between 18-64 years of age who reported not having health insurance for at least 24 months at the time of data collection were included. Propensity score analysis was used to examine the associations between prior insurance status and three outcome variables: (1) having a usual source of care, (2) HSU, and (3) delaying health care needs. Results: Prior health insurance significantly predicted a greater likelihood of having a usual source of care (effect size: 9.2%, p=0.004) and having had at least one preventive visit during the past 2 years (effect size: 6.4%, p=0.035). Prior insurance coverage was positively associated with delayed health care utilization, but the result was not statistically significant (p=0.703). Conclusions: Among the LTU, ever having insurance coverage was positively associated with having a usual source of care and HSU. The lasting impact of insurance coverage on HSU behavior extends beyond the period of insurance coverage, which provides a more comprehensive and deeper understanding of the long-term implications of national and local efforts in expanding insurance coverage.