Biomedical subjects

Dana Dabelea

Publications and source records attributed to Dana Dabelea.

3 recordsLinked to original sources

PubMed2026

Lung function after randomization to metformin, lifestyle intervention or placebo in the Diabetes Prevention Program Outcomes Study (DPPOS).

INTRODUCTION: Metformin and physical activity have been suggested as beneficial for chronic lung disease; however, there are no prior randomized trials. METHODS: The Diabetes Prevention Program (DPP) was a 3-year trial that randomized 3234 individuals at risk for diabetes to metformin, lifestyle intervention or placebo. After the DPP, 88% of participants enrolled in the DPP Outcomes Study that offered lifestyle intervention to all and open-label continuation of metformin. Spirometry was performed at approximately 19 and 22 years post-randomization. Lung function measures were compared in an intention-to-treat (ITT) analysis by original randomization group. Models were unadjusted and adjusted for demographics, body size, smoking and sitting/standing at spirometry. Additional analyses tested prevalence of obstruction (FEV1/FVC <70%), restrictive pattern (FVC < LLN and FEV1/FVC ≥70%), preserved ratio impaired spirometry (PRISm: FEV1 <80% predicted, FEV1/FVC ≥70%) and symptoms (COPD Assessment Test [CAT] score ≥10). RESULTS: The 1888 participants with spirometry were a mean (±SD) age of 68.2 ± 9.3 years, 70% female and 6% currently smoked and 33% had previously smoked cigarettes. Mean follow-up time was 19.0 ± 0.8 years. The mean FEV1 was 2.14 ± 0.60 L, FVC 2.74 ± 0.74 L, FEV1/FVC 78.4 ± 6.4%, mean BMI was 32.4 ± 6.7 kg/m2 and 58% had diabetes. In both unadjusted and adjusted ITT analyses, randomization group was not associated with FEV1, FVC or FEV1/FVC. Likewise, rates of obstruction, restrictive pattern, PRISm or symptoms did not differ by randomization group. CONCLUSIONS: In this long-term follow-up after a randomized trial, we found no significant associations between randomization to metformin or lifestyle intervention and lung function or respiratory symptoms.

Humans↗

PubMed2026

Maternal adverse childhood experiences and prenatal stress: Intergenerational transmission and offspring mental health in the ECHO Cohort.

BACKGROUND: The rising global prevalence of pediatric mental health problems requires the identification of preventable factors underlying their development. This study assessed whether maternal adverse childhood experiences (ACEs) and pregnancy stress were intergenerationally associated with offspring mental health. METHODS: This study used data from 34 sites in the nationwide Environmental Influences on Child Health Outcomes Cohort. Eligible parent-child dyads (child age: 1.5-18 years) provided data on at least one measure of maternal stress and at least one measure of child mental health. Study aims were evaluated using regression analyses, including interaction tests to determine potential effect modifiers. RESULTS: Participants were organized into three subsamples with data on (1) maternal ACEs (N = 2,906), (2) perceived prenatal stress (N = 4,441), and (3) both stress exposures (N = 834). After adjusting for confounders, maternal ACEs and prenatal stress were significantly associated with child mental health problems (B = 2.53 [95% confidence interval [CI]: 2.09, 2.96], p < 0.0001 and B = 2.36 [95% CI: 2.03, 2.68], p < 0.0001, respectively). Among participants with data on both stress exposures, maternal ACEs (B = 1.72, 95% CI: [0.96, 2.48], p < 0.0001) and prenatal stress (B = 2.05, 95% CI: [1.29, 2.80], p < 0.0001) were independently associated with child mental health problems. Neither maternal ACEs nor child sex modified the association between prenatal stress and child mental health problems. CONCLUSIONS: Maternal exposure to ACEs and pregnancy stress were associated with the development of child mental health problems. These findings highlight the need for policies and interventions that mitigate exposure to adversity and protect pregnant individuals and their children from the intergenerational transmission of mental health problems.

Humans↗

PubMed2024

Prenatal black carbon exposure and DNA methylation in umbilical cord blood.

BACKGROUND/OBJECTIVES: Prenatal exposure to ambient air pollution is associated with adverse cardiometabolic outcomes in childhood. We previously observed that prenatal black carbon (BC) was inversely associated with adiponectin, a hormone secreted by adipocytes, in early childhood. Changes to DNA methylation have been proposed as a potential mediator linking in utero exposures to lasting health impacts. METHODS: Among 532 mother-child pairs enrolled in the Colorado-based Healthy Start study, we performed an epigenome-wide association study of the relationship between prenatal exposure to a component of air pollution, BC, and DNA methylation in cord blood. Average pregnancy ambient BC was estimated at the mother's residence using a spatiotemporal prediction model. DNA methylation was measured using the Illumina 450K array. We used multiple linear regression to estimate associations between prenatal ambient BC and 429,246 cysteine-phosphate-guanine sites (CpGs), adjusting for potential confounders. We identified differentially methylated regions (DMRs) using DMRff and ENmix-combp. In a subset of participants (n = 243), we investigated DNA methylation as a potential mediator of the association between prenatal ambient BC and lower adiponectin in childhood. RESULTS: We identified 44 CpGs associated with average prenatal ambient BC after correcting for multiple testing. Several genes annotated to the top CpGs had reported functions in the immune system. There were 24 DMRs identified by both DMRff and ENmix-combp. One CpG (cg01123250), located on chromosome 2 and annotated to the UNC80 gene, was found to mediate approximately 20% of the effect of prenatal BC on childhood adiponectin, though the confidence interval was wide (95% CI: 3, 84). CONCLUSIONS: Prenatal BC was associated with DNA methylation in cord blood at several sites and regions in the genome. DNA methylation may partially mediate associations between prenatal BC and childhood cardiometabolic outcomes.

Humans↗