Showing papers by "Anny H. Xiang published in 2017"

Maternal obesity, gestational diabetes, breastfeeding and childhood overweight at age 2 years

Abstract: SummaryBackground Maternal obesity, excessive gestational weight gain (EGWG), gestational diabetes mellitus (GDM) and breastfeeding are four important factors associated with childhood obesity. Objectives The objective of the study was to assess the interplay among these four factors and their independent contributions to childhood overweight in a cohort with standard clinical care. Methods The cohort included 15 710 mother–offspring pairs delivered in 2011. Logistic regression was used to assess associations between maternal exposures and childhood overweight (body mass index >85th percentile) at age 2 years. Results Mothers with pre-pregnancy obesity or overweight were more likely to have EGWG, GDM and less likely to breastfeed ≥6 months. Mothers with GDM had 40–49% lower EGWG rates and similar breastfeeding rates compared with mothers without GDM. Analysis adjusted for exposures and covariates revealed an adjusted odds ratio (95% confidence interval) associated with childhood overweight at age 2 years of 2.34 (2.09–2.62), 1.50 (1.34–1.68), 1.23 (1.12–1.35), 0.95 (0.83–1.10) and 0.76 (0.69–0.83) for maternal obesity, overweight, EGWG, GDM and breastfeeding ≥6 months vs. <6 months, respectively. Conclusions In this large clinical cohort, GDM was not associated with, but maternal pre-pregnancy obesity or overweight and EGWG were independently associated with an increased risk, and breastfeeding ≥6 months was associated with a decreased risk of childhood overweight at age 2 years.

A genome-wide association study of IVGTT-based measures of first-phase insulin secretion refines the underlying physiology of type 2 diabetes variants

Abstract: Understanding the physiological mechanisms by which common variants predispose to type 2 diabetes requires large studies with detailed measures of insulin secretion and sensitivity. Here we performed the largest genome-wide association study of first-phase insulin secretion, as measured by intravenous glucose tolerance tests, using up to 5,567 individuals without diabetes from 10 studies. We aimed to refine the mechanisms of 178 known associations between common variants and glycemic traits and identify new loci. Thirty type 2 diabetes or fasting glucose–raising alleles were associated with a measure of first-phase insulin secretion at P HNF1A , IGF2BP2 , KCNQ1 , HNF1B , VPS13C/C2CD4A , FAF1 , PTPRD , AP3S2 , KCNK16 , MAEA , LPP, WFS1 , and TMPRSS6 loci. The fasting glucose–raising allele near PDX1 , a known key insulin transcription factor, was strongly associated with lower first-phase insulin secretion but has no evidence for an effect on type 2 diabetes risk. The diabetes risk allele at TCF7L2 was associated with a stronger effect on peak insulin response than on C-peptide–based insulin secretion rate, suggesting a possible additional role in hepatic insulin clearance or insulin processing. In summary, our study provides further insight into the mechanisms by which common genetic variation influences type 2 diabetes risk and glycemic traits.

Epstein-Barr virus, cytomegalovirus, and multiple sclerosis susceptibility: A multiethnic study

Abstract: Objective: To determine whether Epstein-Barr virus (EBV) or cytomegalovirus (CMV) seropositivity is associated with multiple sclerosis (MS) in blacks and Hispanics and to what extent measures of the hygiene hypothesis or breastfeeding could explain these findings. EBV and CMV have been associated with MS risk in whites, and the timing and frequency of both viruses vary by factors implicated in the hygiene hypothesis. Methods: Incident cases of MS or its precursor, clinically isolated syndrome (CIS), and matched controls (blacks, 111 cases/128 controls; Hispanics, 173/187; whites, 235/256) were recruited from the membership of Kaiser Permanente Southern California. Logistic regression models accounted for HLA-DRB1*1501 status, smoking, socioeconomic status, age, sex, genetic ancestry, and country of birth. Results: Epstein-Barr nuclear antigen-1 (EBNA-1) seropositivity was independently associated with an increased odds of MS/CIS in all 3 racial/ethnic groups ( p p = 0.02 for Hispanics). In contrast, CMV seropositivity was associated with a lower risk of MS/CIS in Hispanics ( p = 0.004) but not in blacks ( p = 0.95) or whites ( p = 0.96). Being born in a low/middle-income country was associated with a lower risk of MS in Hispanics ( p = 0.02) but not after accounting for EBNA-1 seropositivity. Accounting for breastfeeding did not diminish the association between CMV and MS in Hispanics. Conclusions: The consistency of EBNA-1 seropositivity with MS across racial/ethnic groups and between studies points to a strong biological link between EBV infection and MS risk. The association between past CMV infection and MS risk supports the broader hygiene hypothesis, but the inconsistency of this association across racial/ethnic groups implies noncausal associations.

A Genome-Wide Association Study of IVGTT-Based Measures of First-Phase Insulin Secretion Refines the Underlying Physiology of Type 2 Diabetes Variants

Abstract: Understanding the physiological mechanisms by which common variants predispose to type 2 diabetes requires large studies with detailed measures of insulin secretion and sensitivity. Here we performed the largest genome-wide association study of first-phase insulin secretion, as measured by intravenous glucose tolerance tests, using up to 5,567 individuals without diabetes from 10 studies. We aimed to refine the mechanisms of 178 known associations between common variants and glycemic traits and identify new loci. Thirty type 2 diabetes or fasting glucose–raising alleles were associated with a measure of first-phase insulin secretion at P HNF1A , IGF2BP2 , KCNQ1 , HNF1B , VPS13C/C2CD4A , FAF1 , PTPRD , AP3S2 , KCNK16 , MAEA , LPP, WFS1 , and TMPRSS6 loci. The fasting glucose–raising allele near PDX1 , a known key insulin transcription factor, was strongly associated with lower first-phase insulin secretion but has no evidence for an effect on type 2 diabetes risk. The diabetes risk allele at TCF7L2 was associated with a stronger effect on peak insulin response than on C-peptide–based insulin secretion rate, suggesting a possible additional role in hepatic insulin clearance or insulin processing. In summary, our study provides further insight into the mechanisms by which common genetic variation influences type 2 diabetes risk and glycemic traits.

Understanding the Capacity for Exercise in Post-Bariatric Patients.

Abstract: Purpose The aim of this study is to conduct a pilot randomized trial testing an exercise program specifically adapted for post-bariatric patients.

Association of Perinatal Risk Factors with Autism Spectrum Disorder

Abstract: Objective To examine the association between exposures to perinatal factors and autism spectrum disorders (ASD). Study Design A retrospective cohort study of ASD among children born in Kaiser Permanente Southern California hospitals between 1991 and 2009 (n = 594,638). Medical records were used to determine exposure to perinatal (antepartum and intrapartum) complications. ASD was diagnosed using DSM-IV criteria. Multivariable Cox regression was used to estimate hazard ratios (HRs). Result Children with ASD were more likely to be exposed to perinatal complications (HR = 1.15, 95% confidence interval [CI]: 1.09–1.21) than neurotypical children. Children exposed to antepartum (HR = 1.22, 95% CI: 1.10–1.36) and intrapartum (HR = 1.10, 95% CI: 1.04–1.17) complications were at increased risk of ASD. The risk was even greater when both antepartum and intrapartum conditions were present (HR = 1.44, 95% CI: 1.26–1.63). Conclusion Exposure to antepartum or intrapartum complications increases the risk of ASD in the offspring. Therefore, pregnancy complications may help identify children who could benefit from early screening and intervention for this common neurodevelopmental condition.

Influence of Statins and Cholesterol on Mortality Among Patients With Pancreatic Cancer

Abstract: Background Recent studies have suggested associations between statins and enhanced survival among patients with pancreatic ductal adenocarcinoma (PDAC). However, the relationship between statins, cholesterol, and survival remains unclear. Methods We conducted a retrospective cohort study on 2142 PDAC patients in a regional integrated healthcare system from 2006 to 2014. Electronic pharmacy records were used to abstract information on the type, length, and dosage of statin exposures starting in the year prior to diagnosis. The cumulative and individual effects of simvastatin, lovastatin, atorvastatin, pravastatin, and rosuvastatin on mortality were assessed using Cox proportional hazards regression. Statins were evaluated as any use (pre- and postdiagnosis as a time-dependent variable) and baseline use (prediagnosis only). We also evaluated whether low-density lipoprotein (LDL) cholesterol, measured at various time windows prior to diagnosis, had an independent influence on survival. Additional analyses were performed to examine whether cholesterol mediated the relationship between statins and mortality. All models included age, race, stage, surgery, gemcitabine-based chemotherapy, and the Charlson comorbidity index as covariates. Results Any (hazard ratio [HR] = 0.87, 95% confidence interval [CI] = 0.79 to 0.97) and baseline (HR = 0.88, 95% CI = 0.79 to 0.98) statin use were both associated with a decreased risk in mortality. When assessing individual statins, we found reduced mortality among simvastatin (HR = 0.87, 95% CI = 0.77 to 0.98) and atorvastatin (HR = 0.58, 95% CI = 0.46 to 0.72) users. Cholesterol was not associated with mortality and did not mediate any relationships between statins and survival. Conclusions Statin use rather than cholesterol level was associated with lower mortality risk in patients with pancreatic cancer. Statins appear to improve survival through a lipid-independent mechanism.

Breastfeeding, ovulatory years, and risk of multiple sclerosis.

Abstract: Objective: To determine whether women who breastfeed their infants longer or have fewer ovulatory years are at lower risk of developing multiple sclerosis (MS). Methods: We recruited women with newly diagnosed MS or its precursor, clinically isolated syndrome (CIS) (n = 397), and matched controls (n = 433) into the MS Sunshine Study from the membership of Kaiser Permanente Southern California. A structured in-person questionnaire was administered to collect the behavioral (pregnancies, breastfeeding, hormonal contraceptive use) and biological (age at menarche and menopause, amenorrhea) factors to make up ovulatory years. Results: Among women who had live births, a cumulative duration of breastfeeding for ≥15 months was associated with a reduced risk of MS/CIS (adjusted odds ratio [OR] 0.47, 95% confidence interval [CI] 0.28–0.77; p = 0.003 compared to 0–4 months of breastfeeding). Being ≥15 years of age at menarche was also associated with a lower risk of MS/CIS (adjusted OR 0.56, 95% CI 0.33–0.96; p = 0.035). Total ovulatory years and the remaining factors that determine it, including gravidity, parity, episodes of amenorrhea, and hormonal contraceptive use, as well as age at first birth, showed no significant association with the risk of MS/CIS. Conclusions: Mothers who breastfeed longer may be at lower subsequent risk of developing multiple sclerosis. This is consistent with the other known maternal health benefits of breastfeeding and with our previous observation that women with MS who breastfeed exclusively are at lower risk of postpartum relapses.

The Association of Estrogen Receptor-β Gene Variation With Salt-Sensitive Blood Pressure.

Abstract: Author(s): Manosroi, Worapaka; Tan, Jia Wei; Rariy, Chevon M; Sun, Bei; Goodarzi, Mark O; Saxena, Aditi R; Williams, Jonathan S; Pojoga, Luminita H; Lasky-Su, Jessica; Cui, Jinrui; Guo, Xiuqing; Taylor, Kent D; Chen, Yii-Der I; Xiang, Anny H; Hsueh, Willa A; Raffel, Leslie J; Buchanan, Thomas A; Rotter, Jerome I; Williams, Gordon H; Seely, Ellen W | Abstract: ContextHypertension in young women is uncommon compared with young men and older women. Estrogen appears to protect most women against hypertension, with incidence increasing after menopause. Because some premenopausal women develop hypertension, estrogen may play a different role in these women. Genetic variations in the estrogen receptor (ER) are associated with cardiovascular disease. ER-β, encoded by ESR2, is the ER predominantly expressed in vascular smooth muscle.ObjectiveTo determine an association of single nucleotide polymorphisms in ESR2 with salt sensitivity of blood pressure (SSBP) and estrogen status in women.MethodsCandidate gene association study with ESR2 and SSBP conducted in normotensive and hypertensive women and men in two cohorts: International Hypertensive Pathotype (HyperPATH) (n = 584) (discovery) and Mexican American Hypertension-Insulin Resistance Study (n = 662) (validation). Single nucleotide polymorphisms in ESR1 (ER-α) were also analyzed. Analysis conducted in younger (l51 years, premenopausal, "estrogen-replete") and older women (≥51 years, postmenopausal, "estrogen-deplete"). Men were analyzed to control for aging.ResultsMultivariate analyses of HyperPATH data between variants of ESR2 and SSBP documented that ESR2 rs10144225 minor (risk) allele carriers had a significantly positive association with SSBP driven by estrogen-replete women (β = +4.4 mm Hg per risk allele, P = 0.004). Findings were confirmed in Hypertension Insulin-Resistance Study premenopausal women. HyperPATH cohort analyses revealed risk allele carriers vs noncarriers had increased aldosterone/renin ratios. No associations were detected with ESR1.ConclusionsThe variation at rs10144225 in ESR2 was associated with SSBP in premenopausal women (estrogen-replete) and not in men or postmenopausal women (estrogen-deplete). Inappropriate aldosterone levels on a liberal salt diet may mediate the SSBP.