Mary Helen Black

Background: Hypertensive disorders in pregnancy, including preeclampsia/eclampsia (PE/E) are associated with long-term cardiovascular disease risk. However, little is known about the effect of these conditions on risk for prehypertension (preHTN) or hypertension (HTN) in the early years after delivery. Methods: The cohort consisted of women who had prenatal care and delivered a live singleton neonate at Kaiser Permanente Bellflower Medical Center in 2005–2010. Women with prepregnancy HTN or preHTN were excluded from analysis. Multivariable robust Poisson regression models were used to assess associations between any hypertensive disorder or PE/E and development of preHTN/HTN in the year after delivery, adjusted for maternal age, race/ethnicity, parity, smoking, prepregnancy weight status, gestational weight gain, gestational diabetes, and gestational age. Results: Among 5960 women who were normotensive prior to pregnancy, 358 (6.0%) developed a hypertensive disorder in pregnancy, of whom 215 (60.1%) had PE/E. Overall, 63 (1.1%) developed HTN and 902 (15.1%) preHTN in the year after delivery. After accounting for all potential confounders, women with a hypertensive disorder in pregnancy and those with PE/E were 2.36 (95% confidence interval: 1.97–2.83) and 2.48 (95% confidence interval: 1.99–3.11) times as likely, respectively, to develop preHTN/HTN in the year after delivery as those without pregnancy-related HTN. Results were similar with and without adjustment for gestational diabetes. Conclusion: Our findings highlight the need for prospective studies aimed at determining whether early postpartum screening and improved follow-up of women with hypertensive disorders first identified in pregnancy may prevent future cardiovascular disease.

Context: Peroxisome proliferator-activated receptor gamma (PPARG) is a susceptibility locus for type 2 diabetes mellitus (T2DM). Although cross-sectional associations have been reported, primarily for Pro12Ala, few longitudinal studies in nondiabetic populations have been conducted. Objective: This study aimed to examine whether and to what extent variation in PPARG is associated with longitudinal changes in anthropometric and metabolic traits in Mexican Americans at risk for T2DM. Setting and Design: Subjects were participants of BetaGene, a family-based study of obesity, insulin resistance, and β-cell function, who completed a baseline and follow-up study visit (n = 378; mean followup, 4.6 ± 1.5 y). Phenotypes included body fat assessed by dual-energy x-ray absorptiometry; insulin sensitivity (S_I), acute insulin response, and β-cell function (disposition index; DI) were estimated from iv glucose tolerance tests with Minimal Model analysis. Eighteen tag single nucleotide polymorphisms (SNPs) capturing variation in a 156-kb region surrounding PPARG were tested for association with changes in longitudinal traits. P-values were Bonferroni-corrected for multiple testing. Results: Six SNPs (rs2972164, rs11128598, rs17793951, rs1151996, rs1175541, rs3856806) were significantly associated with rate of change in S_I after adjustment for age, sex, and body fat percentage, but not with changes in adiposity. rs17793951 also had a significant effect on change in DI over time. Association between rs1175541 and change in S_I varied by changes in adiposity such that only carriers of the minor allele who reduced body fat over followup improved S_I. rs1306470 (captured Pro12Ala, r² = 0.9) was not associated with rates of change in any traits and its effects were not modified by changes in adiposity. Conclusions: Variation in PPARG, but not Pro12Ala, contributes to declining S_I and concomitant deterioration in β-cell function in Mexican Americans at risk for T2DM.

Asthma is the most common chronic condition of childhood, yet the relationship between obesity and asthma risk and the impact of obesity on clinical asthma outcomes are not well understood. For this population-based, longitudinal study, demographic and clinical data were extracted from administrative and electronic health records of 623,358 patients aged 6–19 years who were enrolled in the Kaiser Permanente Southern California health plan in 2007–2011. Crude asthma incidence ranged from 16.9 per 1,000 person-years among normal-weight youth to 22.3 per 1,000 person-years among extremely obese youth. The adjusted risks of asthma for overweight, moderately obese, and extremely obese youth relative to those of normal weight youth were 1.16 (95% confidence interval: 1.13, 1.20), 1.23 (95% confidence interval: 1.19, 1.28), and 1.37 (95% confidence interval: 1.32, 1.42), respectively (P_trend < 0.0001). The relationship between obesity and asthma risk was strongest in Asian/Pacific Islanders and in the youngest girls (aged 6–10 years), compared with other groups. Among youth who developed asthma, those who were moderately or extremely obese had more frequent asthma exacerbations requiring emergency department services and/or treatment with oral corticosteroids. In conclusion, obese youth are not only more likely to develop asthma, but they may be more likely to have severe asthma, resulting in a greater need for health care utilization and aggressive asthma treatment.

Consumption of energy-dense, nutrient-poor foods has contributed to the rising incidence of obesity and may underlie insulin resistance and β-cell dys

OBJECTIVE The International Association of Diabetes in Pregnancy Study Groups (IADPSG) criteria for diagnosis of gestational diabetes mellitus (GDM) identifies women and infants at risk for adverse outcomes, which are also strongly associated with maternal overweight, obesity, and excess gestational weight gain. RESEARCH DESIGN AND METHODS We conducted a retrospective study of 9,835 women who delivered at ≥20 weeks’ gestation; had a prenatal, 2-h, 75-g oral glucose tolerance test; and were not treated with diet, exercise, or antidiabetic medications during pregnancy. Women were classified as having GDM based on IADPSG criteria and were categorized into six mutually exclusive prepregnancy BMI/GDM groups: normal weight ± GDM, overweight ± GDM, and obese ± GDM. RESULTS Overall, 5,851 (59.5%) women were overweight or obese and 1,892 (19.2%) had GDM. Of those with GDM, 1,443 (76.3%) were overweight or obese. The prevalence of large-for-gestational-age (LGA) infants was significantly higher for overweight and obese women without GDM compared with their normal-weight counterparts. Among women without GDM, 21.6% of LGA infants were attributable to maternal overweight and obesity, and the combination of being overweight or obese and having GDM accounted for 23.3% of LGA infants. Increasing gestational weight gain was associated with a higher prevalence of LGA in all groups. CONCLUSIONS Prepregnancy overweight and obesity account for a high proportion of LGA, even in the absence of GDM. Interventions that focus on maternal overweight/obesity and gestational weight gain, regardless of GDM status, have the potential to reach far more women at risk for having an LGA infant.

Objectives To examine human leukocyte antigen HLA DRB1–DQB1 haplotypes within a multi‐ethnic cohort and assess their association with characteristics of diabetes onset. Methods The sample included 1662 participants from the SEARCH for Diabetes in Youth Study who tested positive for GADA and/or IA‐2A autoantibodies. Blood drawn at the study visit was used to measure fasting C‐peptide (FCP) and genotype HLA DRB1 and DQB1 loci. Diabetic ketoacidosis (DKA) at diagnosis was determined from medical records. Multivariable linear and logistic regression models stratified by race/ethnicity were used to assess associations with DRB1–DQB1 haplotypes. Results The frequency of DRB1*03 susceptibility haplotypes ranged 27.5–28.9% in all racial/ethnic groups. The frequency of susceptibility DRB1*04–DQB1*0302 was higher in non‐Hispanic White (NHW; 34.1%) and Hispanic (38.9%) compared to non‐Hispanic Black (NHB; 20.8%) youth. Neutral and protective haplotypes were low frequency in all groups. DBR1*03 haplotypes were associated with younger age at diagnosis in NHW and positivity for multiple autoantibodies in Hispanics. DRB1*04–DQB1*0302 haplotypes were associated with multiple autoantibody positivity in NHW and Hispanics, and lower FCP and higher odds of DKA in Hispanics only. Although protective DRB1*04–DQB1*0301 haplotypes were associated with older age at diagnosis in NHW, they were also associated with multiple autoantibody positivity in these youth. Protective DRB1*13 haplotypes were associated with decreased odds of multiple autoantibody positivity in NHB youth. Conclusions The distribution of DRB1–DQB1 haplotypes and their association with onset‐related characteristics of autoimmune diabetes varies across major racial/ethnic groups in the USA. This may contribute to variation in clinical presentation of autoimmune diabetes by race/ethnicity.