Research Recap: February 28 - March 25
An overview of recent studies published by Institute investigators and their collaborators spans a wide variety of topics, including:
Genetic links between gestational diabetes mellitus and type 2 diabetes; childhood health equity in the Medicaid program; maternal Mediterranean diet and newborn DNA methylation; neighborhood contextual factors and inflammatory biomarkers; predicting insulin sensitivity during pregnancy; optimism, stressors, and well-being; ACA Medicaid Expansion and physician location; effects of HSA-HDHPs on medication cost and use for bipolar disorder; gestational PFAS and DNA methylation; sexual orientation- and gender identity-related U.S. state laws; association of inhaled corticosteroid therapy with adrenal suppression; affordable access versus industry interest in high-cost therapies; and SNAP participation and health care expenditures in children.
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Multi-ancestry GWAS reveals genetic links between gestational diabetes mellitus and type 2 diabetes
Gestational diabetes mellitus (GDM) is associated with increased risk of pregnancy complications, adverse perinatal outcomes, and with increased risk of subsequent diagnosis of type 2 diabetes (T2D). To understand the extent to which aetiological factors and molecular processes driving the occurrence of GDM overlap with T2D pathophysiology, the GENetics of Diabetes In Pregnancy (GenDIP) Consortium assembled genome-wide association studies (GWAS) of diverse ancestry in women with and without GDM. A team of researchers including Marie-France Hivert and Emily Oken conducted a multi-ancestry meta-analysis to identify five loci with genome-wide significant association. Results, published in Human Molecular Genetics, supported the hypothesis that GDM and T2D are part of the same underlying pathology but that there are genetic determinants of GDM that are specific to glucose regulation in pregnancy.
Promoting Child Health Equity Through Medicaid Innovation
Black, Latino/a/e, American Indian, and Alaska Native children often receive lower quality health care than White children. As the predominant health insurer for medically underserved populations, Medicaid plays a critical role in advancing socioeconomic and racial health equity. In a recent article published in Pediatric Annals, a group of investigators led by Alon Peltz describe structural barriers to health equity in the Medicaid program and potential steps for improving long-standing socioeconomic and racial health inequities through programmatic innovation. The article identifies opportunities for expanding care models for holistically addressing the social determinants of health, aligning clinical care delivery around health equity principles, diversifying the clinical workforce, and promoting meaningful and consistent provider participation in Medicaid. Authors encourage practitioners and policy makers to undertake these steps to set the stage for more sweeping reforms that can help achieve national health equity goals for children.
Institute Investigator(s): Alon Peltz
An investigation of potential associations between a maternal Mediterranean diet in pregnancy and newborn DNA methylation
Higher adherence to the Mediterranean diet during pregnancy is related to a lower risk of preterm birth and to better offspring cardiometabolic health. To determine whether DNA methylation may be an underlying biological mechanism, a team of investigators including Marie-France Hivert and Emily Oken evaluated whether maternal adherence to the Mediterranean diet was associated with offspring cord blood DNA methylation. Findings, published in Epigenetics, did not identify associations with childhood gene expression or enriched biological pathways, and the association did not persist into childhood. Results did find that maternal adherence to the Mediterranean diet during pregnancy was associated with cord blood DNA methylation level at one CpG located in the WNT5B gene. Researchers suggest further study in the potential mediation of DNA methylation in associations with offspring health.
How your neighborhood could affect your health – examining associations between neighborhood contextual factors and inflammatory biomarkers Neighborhood deprivation is linked with inflammation, which may explain poorer health across populations. Behavioral risk factors are assumed to largely mediate these relationships, but few studies have examined this. A team of researchers including Peter James examined three neighborhood contextual factors that could exert direct effects on inflammation: (1) neighborhood socioeconomic status, (2) an index of concentration at extremes (that measures segregation), and (3) surrounding vegetation (greenness). Investigators used blood samples and addresses collected from prospective cohorts of male and female health professionals with at least one inflammatory marker to examine associations between these neighborhood contextual factors and inflammatory biomarkers. Results, published in Environment International, found that for both women and men, higher neighborhood socioeconomic status and participants in neighborhoods with higher concentrations of high-income households were both associated with lower inflammation score. However, surrounding greenness of each participant's address was associated with lower inflammation score in women, but not men. These findings findings support the hypothesis that adverse neighborhood environments may contribute to inflammation through pathways independent of behavioral risk factors, including psychosocial stress and toxic environments.
Institute Investigator(s): Peter James
First trimester plasma microRNAs levels predict insulin sensitivity between 24th and 29th week of pregnancy
Gestational diabetes mellitus is a consequence of an imbalance between insulin sensitivity (IS) and secretion during pregnancy. MicroRNAs (miRNAs) are small and secreted RNA molecules stable in blood and known to regulate physiological processes including glucose homeostasis. A group of investigators including Marie-France Hivert conducted a study to identify plasmatic miRNAs detectable in early pregnancy predicting IS at 24th-29th week of pregnancy. Results, published in BMJ Open Diabetes Research & Care, identified first trimester plasmatic miRNAs predictive of Matsuda Index-estimated IS in late second trimester of pregnancy. These miRNAs could also contribute to initiate and support IS adaptation to pregnancy potentially through lipid metabolism regulation.
Institute Investigator(s): Marie-France Hivert
Optimism, Daily Stressors, and Emotional Well-Being
Growing evidence supports optimism as a health asset, yet how optimism influences well-being and health remains uncertain. A team of investigators including Peter James evaluated one potential pathway - the association of optimism with daily stress processes - and tested two hypotheses: 1) the stressor exposure hypothesis posits that optimism would preserve emotional well-being by limiting exposure to daily stressors, and 2) the buffering hypothesis posits that higher optimism would be associated with lower emotional reactivity to daily stressors and more effective emotional recovery from them. Results, published in The Journals of Gerontology: Series B, demonstrate that optimism was unrelated to emotional reactivity to or recovery from daily stressors, but lower stressor exposure mediated the association of higher optimism with lower daily Negative Affect, supporting the stressor exposure hypothesis. These findings suggest that optimism may be associated with more favorable emotional well-being in later life through differences in stressor exposure rather than emotional stress response. Optimism may preserve emotional well-being among older adults by engaging emotion regulation strategies that occur relatively early in the emotion-generative process.
Institute Investigator(s): Peter James
How the ACA Medicaid Expansion changed the geographical distribution of physicians across the United States
A recent study found that states that expanded Medicaid under the Affordable Care Act (ACA) gained new general internists who were establishing their first practices, whereas nonexpansion states lost them. A group of investigators including Yanlei Ma and senior author Hao Yu conducted a study to examine and compare the level of social disadvantage of these areas using American Community Survey data, AMA Physician Masterfile data, and information on states' Medicaid expansion status, to compare where new physicians located during the 6 years following the expansion to where they located during the 5 years preceding the expansion. Results, published in Medical Care, demonstrate that new general internists were more likely to locate in expansion states after the expansion, a finding that held for high, medium, and low disadvantage areas, compared with preexpansion patterns. Furthermore, a highly disproportionate share of the physicians lost by nonexpansion states were lost from high disadvantage areas, potentially compromising access for all residents irrespective of insurance coverage.
High-Deductible Health Plans paired with Health Savings Accounts substantially increased out-of-pocket burdens for essential medications for individuals with Bipolar Disorder
High-deductible health plans paired with health savings accounts (HSA-HDHPs) require substantial out-of-pocket spending for most services, including medications. A team of researchers led by Chris Lu and including Dennis Ross-Degnan, Stephen Soumerai, and Fang Zhang, examined effects of HSA-HDHPs on medication out-of-pocket spending and use among people with bipolar disorder. Results, published in The Journal of Clinical Psychiatry, found that HSA-HDHP members with bipolar disorder experienced substantial increases in out-of-pocket burdens for medications essential for their functioning and well-being. Although HSA-HDHPs were not associated with detectable reductions in medication use, high out-of-pocket costs could cause financial strain for lower-income enrollees
Associations of gestational perfluoroalkyl substances exposure with longitudinal DNA methylation measures
DNA methylation alterations may underlie associations between gestational perfluoroalkyl substances (PFAS) exposure and later-life health outcomes, but no longitudinal studies have examined the associations between gestational PFAS and DNA methylation. A team of researchers including Marie-France Hivert and Emily Oken examined associations of gestational PFAS exposure with longitudinal DNA methylation measures at birth and in adolescence using data from Project Viva and the Health Outcomes and Measures of the Environment (HOME) Study. Results, published in Environmental Health Perspectives, found that in these longitudinal data, PFAS biomarkers were associated with differences in several cytosine-guanine dinucleotide (CpG) sites at birth and at 12 years of age in or near genes linked to some PFAS-associated health outcomes. Investigators recommend that future studies should examine whether DNA methylation mediates associations between gestational PFAS exposure and health.
Advancing sexual and gender minority health research and practice through an examination of sexual orientation- and gender identity-related laws across the U.S.
In an effort to advance sexual and gender minority (SGM) health research and practice, a team of researchers including Brittany Charlton developed a multiyear database of sexual orientation- and gender identity-related U.S. state laws. Investigators used this database to assess variability in U.S. state laws from 1996 through 2016 across all U.S. states and D.C. Through a systematic examination of a state-level legal database of 30 sexual orientation- and gender identity-related U.S. state laws in 9 legal domains, investigators calculated descriptive statistics and created maps to observe the distribution of these laws. Findings, published in LGBT Health, describe progress in some domains including same-sex marriage, adoption, and employment discrimination, but significant challenges to SGM rights persist, especially with regard to HIV criminalization, transgender rights, and discrimination in health care settings. Additionally, notable variation exists in the presence of protective LGBTQ state laws across states and D.C. Efforts to repeal harmful U.S. state laws are needed, as are new laws, policies, regulations, practices, and norms that advance social justice and health equity for all SGM people.
Institute Investigator(s): Brittany Charlton
Could adrenal suppression in asthma patients treated with ICS represent a larger public health problem than previously thought?
The application of large-scale metabolomic profiling provides new opportunities for realizing the potential of omics-based precision medicine for asthma. A team of researchers including Ann Wu leveraged data from over 14,000 individuals in four distinct cohorts to identify and independently replicate 17 steroid metabolites whose levels were significantly reduced in individuals with prevalent asthma, with the largest reductions associated with inhaled corticosteroid (ICS) treatment. Results, published in Nature Medicine, found that that cortisol levels were substantially reduced throughout the entire 24-hour daily period in patients with asthma who were treated with ICS compared to those who were untreated and to patients without asthma. Additionally, patients with asthma who were treated with ICS showed significant increases in fatigue and anemia as compared to those without ICS treatment. Investigators suggest that adrenal suppression in patients with asthma treated with ICS might represent a larger public health problem than previously recognized, recommending regular cortisol monitoring of patients with asthma treated with ICS to provide the optimal balance between minimizing adverse effects of adrenal suppression while capitalizing on the established benefits of ICS treatment.
Institute Investigator(s): Ann Chen Wu
Ultraexpensive gene therapies, industry interests, and the right to health: a case study
A case study of onasemnogene abeparvovec, the world’s most expensive treatment to date, published in BMJ Global Health, highlights the ever-growing chasm between the promise of medical innovation and affordable access for those who need it in resource-constrained health systems. Onasemnogene abeparvovec received Brazilian marketing authorization for the treatment of spinal muscular atrophy in 2020, but the Brazilian drug pricing authority later approved a price that was 77% lower than the manufacturer’s intended price, resulting in the drug manufacturer’s decision not to commercialize onasemnogene abeparvovec in Brazil. In response, courts in Brazil have urged the Ministry of Health to fund the treatment at prices that are more than three times higher than the maximum price approved, citing the right to health legislation. Authors of the study, including Anita Wagner, point to this as an example of a country’s regulatory and pricing system being rendered ineffective and the entire health system threatened by a multinational pharmaceutical company and call for efforts to strictly enforce existing regulatory, pricing, and coverage regulations.
Institute Investigator(s): Anita Wagner
SNAP participation benefits child health outcomes, but what about health care costs?
The Supplemental Nutrition Assistance Program (SNAP) has well-established positive impacts on child health outcomes, including increased birth weight and decreased likelihood of underweight status. Studies in adult populations suggest that SNAP is associated with lower health care costs, although less is known in children. A team of investigators with senior author Alon Peltz conducted a retrospective analysis of U.S. children living in low-income households to model the effect of continuous SNAP enrollment on health expenditures as compared to non-enrollees. Results, published in BMC Pediatrics, did not identify differences in short term health care costs based on SNAP enrollment when accounting for differences in sociodemographic and clinical factors, including emergency department, inpatient, outpatient, and prescription costs. Despite demonstrated child health benefits, investigators concluded that sustained enrollment in SNAP over a two-year period did not generate significant short-term health care cost reductions. Findings suggest that although SNAP is intended to act as a benefit towards the health and well-being of its recipients, unlike among adults, it may not reduce health care costs among children.
Institute Investigator(s): Alon Peltz