Faculty Bibliography

OBJECTIVE:Exposure to per- and polyfluoroalkyl substances (PFAS) may increase the risk of gestational diabetes mellitus (GDM), with adverse consequences for pregnant women and their offspring. However, epidemiologic studies have shown inconsistent results. We addressed this question in a large, pooled sample of U.S. women. RESEARCH DESIGN AND METHODS/METHODS:Participants (n = 5,229) from 16 cohorts had singleton pregnancies. PFAS were quantified in a single plasma or serum sample during pregnancy (1999-2021); six PFAS detected in ≥60% of participants were analyzed. The primary outcome was GDM diagnosis based on self-report or medical record documentation. The secondary outcome, among 1,213 participants, was fasting glucose. We estimated associations between each PFAS and GDM using generalized estimating equations models with Poisson distribution and robust variance, and estimated associations between each PFAS and fasting glucose using generalized estimating equations models for linear regression. Effect modification by prepregnancy BMI or race and ethnicity was evaluated via interaction terms and stratification. We quantified the combined effect of the PFAS mixture using quantile-based g-computation. RESULTS:Associations between individual PFAS and GDM were null or weakly inverse; the association with the six-PFAS mixture was negative (prevalence ratio [95% CI] per quartile increase: 0.75 [0.58, 0.96]). Certain PFAS were more strongly negatively associated with GDM among participants with BMI <25 kg/m2. Associations between PFAS and fasting glucose were largely null, although both positive and negative associations were observed in specific race and ethnicity strata. CONCLUSIONS:In a large, pooled sample of U.S. pregnant women, greater concentrations of PFAS were not associated with higher prevalence of GDM.

OBJECTIVE:To examine associations between patient-reported health-related social needs (HRSNs) and clinical quality measure (CQM) performance in an urban federally qualified health center (FQHC) network. METHODS:This cross-sectional study included adult patients (≥18 years) screened for HRSNs at a general internal medicine clinic, Clinic-1, and a prenatal healthcare clinic, Clinic-2, within a FQHC network, between January 1, 2018, and July 31, 2022. HRSNs were assessed across 9 domains. Performance was assessed for 13 process and 2 outcome-based CQMs at Clinic-1 and 5 process-based CQMs at Clinic-2. Prevalence ratios (PR) were estimated using logistic regression to compare CQM performance by HRSN status, adjusted for relevant demographic, clinical, and clinician factors. RESULTS:At Clinic-1, reporting a HRSN was associated with lower hemoglobin A1c control (PR, 0.81; 95%CI, 0.69, 0.95). At Clinic-2, reporting a HRSN was associated with higher cervical cancer screening (PR, 1.07; 95%CI, 1.03, 1.11). No other CQMs differed significantly by HRSN status. CONCLUSIONS:HRSNs were not associated with differences in performance for most CQMs at this FQHC network. Exceptions were observed negative associations with diabetes A1c control and positive associations with cervical cancer screening. Further research is needed to elucidate mechanisms through which unmet HRSNs impact CQMs across care settings.

CONTEXT/UNASSIGNED:Plasticizers such as bisphenols and phthalates are endocrine-disrupting chemicals and lead to development of metabolic diseases. OBJECTIVE/UNASSIGNED:To examine associations of prenatal exposure to bisphenols and phthalates with metabolic dysfunction. DESIGN/UNASSIGNED:This study was nested in the New York University (NYU) Children's Health and Environment Study, a prospective birth cohort. SETTING/UNASSIGNED:Participants were recruited at three NYU-affiliated hospitals. PATIENTS OR OTHER PARTICIPANTS/UNASSIGNED:Eligible participants were ≥18 years old, <18 weeks pregnant, and had a medically stable pregnancy. EXPOSURES/UNASSIGNED:Twelve phthalate metabolites and two bisphenols were measured in early and mid-pregnancy (<18 and 18-25 weeks) urine samples. Bisphenols were summed, and phthalate metabolites were grouped based by molecular weights and relevant parent compounds. MAIN OUTCOME MEASURES/UNASSIGNED:Logistic and linear regression models assessed chemicals groups' associations with gestational diabetes mellitus (GDM), glucose disturbance (including impaired glucose tolerance (IGT)), and blood glucose response to glucose challenge test (GCT), adjusting for sociodemographic and pregnancy-related factors. RESULTS/UNASSIGNED:Seventy-nine (6.8%) had GDM, 303 (26.1%) had IGT, and blood glucose response to GCT ranged from 22-386 mg/dL. Bisphenol A (BPA) was negatively associated with blood glucose response to GCT (-1.47 [-2.84, -0.10]), while diethylhexyl phthalate (DEHP; 2.67 [0.98, 4.36]) and high molecular weight phthalates (1.94, [0.17, 3.71]) were positively associated with blood glucose response to GCT. DEHP was also linked to glucose disturbance (1.16 [1.02, 1.31]). CONCLUSION/UNASSIGNED:Our findings suggest that phthalate exposure is associated with GDM. Further mechanistic studies are warranted, particularly given the inverse associations with BPA exposure.

The prevalence and incidence of prediabetes in children and youth continue to increase in parallel with the obesity epidemic. While prediabetes is defined by elevated HbA1c and/or impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG), the risk of clinical disease is a continuum. Individuals with prediabetes are at a higher risk of developing youth-onset type 2 diabetes, which is considered a more aggressive form of the disease. This condition is associated with increased cardiovascular and metabolic risks and leads to an earlier onset of complications compared to adults with type 2 diabetes. Additionally, significant damage to beta cells may occur even before dysglycemia develops. Recent data indicate that mortality rates are higher in youths with type 2 diabetes compared to those with type 1 diabetes. Childhood prediabetes and cardiovascular complications associated with it are a significant health concern. This review provides the latest insights into this complex issue. We will present an overview of pathophysiology, screening methods, and therapeutic options to prevent the progression from prediabetes to type 2 diabetes in children. In summary, it is crucial to identify prediabetes in children, as this underscores the importance of appropriate screening and timely intervention.

OBJECTIVE:To evaluate inhaled technosphere insulin (TI) in children with diabetes. RESEARCH DESIGN AND METHODS/METHODS:230 youth 4-17 years old with type 1 (98%) or type 2 (2%) diabetes treated with multiple daily injections of insulin were randomly assigned 1:1 to TI or rapid-acting analog (RAA) insulin plus continuation of long-acting basal insulin and continuous glucose monitoring (CGM) for 26 weeks. The primary outcome was change in HbA1c, tested for noninferiority with margin of 0.4%. RESULTS:In intent-to-treat analysis, mean HbA1c (% ± SD) was 8.22 ± 0.87 at baseline and 8.41 ± 1.38 at 26 weeks with TI and 8.21 ± 0.96 and 8.21 ± 1.10, respectively, with RAA (adjusted difference = 0.18; 95% CI -0.07, 0.43; noninferiority P = 0.091). CGM-measured time in range 70-180 mg/dL was not significantly different between groups (adjusted difference -2.2%; 95% CI -7.0, 2.7; P = 0.38). Two severe hypoglycemic events occurred in the TI group and one in the RAA group. Change in forced expiration volume in 1 s from baseline to 26 weeks did not differ comparing TI and RAA (P = 0.53). The TI group reported greater treatment satisfaction (P = 0.004) and had less gain in weight and BMI percentile (P = 0.009) than did the RAA group. CONCLUSIONS:The primary analysis did not meet the prespecified criteria for HbA1c noninferiority. However, TI use was safe over 26 weeks without affecting pulmonary function and was associated with greater treatment satisfaction and less weight gain compared with RAA, supporting TI as a treatment option for some pediatric patients with type 1 diabetes.

OBJECTIVES/OBJECTIVE:Edentulism and diabetes mellitus (DM) are frequently seen among older adults. However, the joint effect of edentulism and DM on mortality was understudied. We aim to examine the joint effect of edentulism and DM on all-cause mortality and to what extent the joint effect varies by race/ethnicity. METHODS:Analysis of US Health and Retirement Study (HRS) data (2006-2018) included 11,813 non-Hispanic Whites, 2216 non-Hispanic Blacks, and 1337 Hispanics aged ≥ 50 years old. Mortality data came from the National Death Index or HRS surveys. Edentulism was self-reported and DM was determined by self-reported diagnosis, medication use, or glycosylated hemoglobin. Cox proportional-hazard models with inverse probability treatment weighting were applied. RESULTS:During mean follow-up of 9.6 years, 2874 Whites, 703 Blacks, and 441 Hispanics died. DM was associated with higher mortality across all groups (Whites: HR = 1.43, 95% CI = 1.25-1.64; Blacks: HR = 1.62, 95% CI = 1.28-2.04; Hispanics: HR = 1.46, 95% CI = 1.07-1.99). However, edentulism predicted higher mortality only in Whites (HR = 1.65, 95% CI = 1.51-1.80). Having both conditions showed highest mortality risk in all groups (Whites: HR = 2.31, 95% CI = 1.56-3.42; Blacks: HR = 1.94, 95% CI = 1.45-2.59; Hispanics: HR = 1.77, 95% CI = 1.16-2.70), with a significant additive interaction observed only in Whites (relative excess risk due to interaction = 0.22, p < 0.05). CONCLUSIONS:DM and edentulism pose an additive risk for mortality in Whites, and there are racial/ethnic differences in edentulism-related mortality.

BACKGROUND:The associations between different types of diabetes, characterized by distinct pathophysiology and genetic architecture, and pancreatic ductal adenocarcinoma (PDAC) risk are not understood. METHODS:We investigated associations of genetic susceptibility to type 2 diabetes (T2D), eight T2D mechanistic clusters, type 1 diabetes (T1D), and maturity-onset diabetes of the young (MODY) with PDAC risk. We used genome-wide association study (GWAS) summary-level statistics for T2D (242,283 cases, 1,569,734 controls), T1D (18,942 cases, 501,638 controls), and PDAC (10,244 cases and 360,535 controls) in individuals of European ancestry. RESULTS:Two-sample Mendelian randomization (MR) using the Robust Adjusted Profile Score (MR-RAPS) method indicated that genetically predicted T2D was associated with PDAC risk (OR = 1.10; 95% CI 1.05-1.15), particularly the T2D obesity (OR = 1.28; 95% CI 1.15-1.42) and lipodystrophy (OR = 1.25; 95% CI 1.03-1.51) clusters. No association was observed for T1D with PDAC risk (OR = 1.01; 95% CI 0.99-1.02). Pathway/gene-set analysis using the summary-based Adaptive Rank Truncated Product (sARTP) method revealed a significant association between the MODY gene-sets and PDAC risk (P = 1.5 × 10-8), which remained after excluding 20 known PDAC GWAS loci (P = 7.6 × 10-4). HNF1A, FOXA3, and HNF4A were the top contributing genes after excluding the previously identified GWAS loci regions. CONCLUSIONS:Our results from this genetic association study support that T2D, particularly the obesity and lipodystrophy mechanistic clusters, and MODY genomic susceptibility regions play a role in the etiology of PDAC.

INTRODUCTION/BACKGROUND:Communities disproportionately burdened by adverse neighborhood-level social and structural factors may experience greater vulnerability to environmental exposures, contributing to health inequities, including adverse COVID-19. We assessed the effects of chronic air pollution on COVID-19 morbidities in NYC and examined whether these effects varied by neighborhood-level vulnerability. METHODS:)) was assigned using residential ZIP Code (NYC Community Air Survey; 2009-2019). Modified Poisson regression estimated risk of acute respiratory distress syndrome (ARDS), pneumonia, ventilation, and dialysis, and Cox regression estimated risk of discharge, adjusting for age, sex, BMI, smoking, asthma, diabetes, and hypertension. We assessed effect modification by neighborhood-level environmental vulnerability index (NEVI) tertiles. RESULTS:and pneumonia's relationship was stronger in individuals within higher NEVI tertiles (T1: aRR: 1.13, 95%CI: 1.02-1.25; T2: aRR: 2.11, 95%CI: 1.73-2.56; T3: aRR: 6.36, 95%CI: 4.71-8.60). DISCUSSION/CONCLUSIONS:Differences in neighborhood-level social and structural factors contribute to unequal health burdens associated with air pollution. Public health resources targeted toward neighborhoods with greater environmental vulnerability can encourage population-level pandemic preparedness.