Research Projects

About the Study: ​Lifecourse epidemiology is the study of chronic disease risk associated with the long‐term effects of physical, metabolic, behavioral, social and psychosocial exposures occurring throughout the life. Current statistical methods for risk factor trajectories fail with multiple outcomes, inconsistent timing or multiple risk factor trajectories, or can fail to replicate. A multidisciplinary team of biostatisticians and lifecourse epidemiologists proposes to address the gaps. We build on the strength of our previous R01, during which we published 22 peer‐reviewed journal articles, gave 20 invited talks and 1 webinar, and built free, point‐and‐ click, power and sample size software, used more than 500 times each month, by more than 350 unique scientists. The examples in the proposal come from a funded study of the primordial causes of diabetes and obesity, which will use maternal gestational blood pressure trajectory as a predictor of future childhood obesity. Better design and analysis tools will allow lifecourse epidemiologists to better answer crucial questions about the importance of risk factor trajectories in the etiology of diseases.

We have four aims. 1) Develop novel data analysis methods for lifecourse epidemiology studies that assess the association between one or more outcomes and trajectories of risk factors, examine the direct and mediated effects of risk factor trajectories, and determine critical periods within risk factor trajectories. 2) Derive new sample size methods for lifecourse studies involving risk factor trajectories. 3) Extend our widely used free, open‐source, point‐and‐click sample size software for studies of risk factor trajectories to allow scientists to use the new sample size methods. 4) Widely disseminate the new techniques and free software through articles and seminars. Leverage our NIH funding to extend our short courses and massive open online course (R​25GM111901), add chapters to a book‐in‐progress (NLM G13LM011879), and produce more tutorials for our power and sample size website, currently visited by over 350 scientists each month (NIDCR R01 DE020832). While the research was inspired by a study of fetal programming, the results apply broadly to any study in which hypotheses about relating risk factor trajectories to outcomes are of interest. Risk factor trajectories are increasingly being examined for diseases as diverse as obesity, cardiovascular disease, stroke, diabetes, and cancer. Finally, extending our widely used power and sample size software to most classes of mixed models will bring accurate, easy‐to‐use, point‐and‐click study design to hundreds more NIH supported scientists.

Free power and sample size software.

Principal Investigator: Jill Kaar, PhD, Principal Investigator

Researchers Involved: Jill Kaar, Dana Dabelea

About the Study: The goal of this study is to examine how health behaviors associated with early childhood obesity pattern together to produce negative outcomes, and how this association is influenced by a child’s sleep duration.

Principal Investigator: Katherine Sauder, PhD

Researchers Involved: Katherine Sauder, Dana Dabelea

About the Study: Cardiovascular (CV) disease is the leading cause of death in the United States. Intrauterine exposures, including micronutrient deficiencies, may lead to an increased risk for CV disease in offspring. Evidence suggests that vitamin D influences CV health by regulating both vascular smooth muscle cell proliferation and the renin-angiotensin system. During pregnancy, women obtain vitamin D from foods, dietary supplements, and sunlight exposure. Animal studies have shown that low vitamin D exposure during the prenatal and postnatal periods is associated with increased blood pressure in adolescence, but human studies are limited in number and scope. Prior studies have not examined how maternal prenatal and offspring postnatal vitamin D intake are related to childhood vascular health, nor have they evaluated if neonatal bioavailable 25OHD (versus total 25OHD) predicts childhood subclinical CV risk.

This research gap is being explored by examining the association of (1) vitamin D intake in pregnancy and infancy and (2) bioavailable 25OHD at birth with offspring blood pressure, pulse wave velocity (PWV), and adiposity (percent fat mass) at 4-6 years of age.

Publication: Sauder KA, Koeppen HJ, Shapiro ALB, Kalata, K. E., Stamatoiu, A. V., Ringham, B. M., Glueck, D. H., Norris, J. M., Dabelea, D. Prenatal Vitamin D Intake, Cord Blood 25-Hydroxyvitamin D, and Offspring Body Composition: The Healthy Start Study. Nutrients. 2017;9(7). ​ ​

Principal Investigator: Dana Dabelea, MD, PhD

Researchers Involved: Dana Dabelea, Steve Abman, John Adgate, Richard Boles, Kristen Boyle, Jed Friedman, Thomas Jansson, Susan Johnson, Katerina Kechris, Sheryl Magzamen, Brianna Moore, Brandy Ringham, Katherine Sauder, Allison Shapiro, Anne Starling, Lisa Testaverde, Ivana Yang, Weiming Zhang

About the Study: This is a national collaborative project to harmonize 84 separate cohort studies of mothers and children in the United States (including Healthy Start) to increase greatly the ability to detect environmental influences on childhood health outcomes. The environmental factors that will be studied include chemical and metals exposures, air pollution, pregnancy habits (diet, activity, medications), feeding habits after birth (breast, bottle, sold food introduction), the built environment (parks, traffic, safety), mental health issues and other social factors, among many others.

Principal Investigators: Dana Dabelea, MD, PhD, John Adgate, PhD, and Richard Hamman, MD, DrPH

Researchers Involved: Dana Dabelea, John Adgate, Antonio Calafat (CDC), Richard Hamman, Kristin Polinski, Anne Starling, Ivana Yang, Weiming Zhang ​​

About the Study: Fetal exposure to endocrine-disrupting chemicals during pregnancy (such as phthalates, perfluorinated compounds, and phenols such as BPA and BPS) are suspected of being associated with the development of obesity-related outcomes in offspring

Principal Investigator: Anne Starling, PhD

Researchers Involved: Anne Starling, Dana Dabelea​​​​​

About the Study: An in-depth evaluation of the role that prenatal exposure to traffic-related air pollution may play in offspring adiposity and early childhood overweight and obesity, considering as mediators both inflammatory markers in maternal and umbilical cord blood, and epigenetic markers of DNA methylation in umbilical cord blood.

Authors: Sauder KA, Bekelman TA, Harrall K, Glueck DH, Dabelea D. Poster presentation at American Diabetes Association 79th Scientific Sessions, San Francisco, CA, June 2019.

Abstract: Intrauterine exposure to gestational diabetes (GDM) is associated with increased adiposity; however, not all exposed offspring exhibit excess adiposity, indicating that additional factors are involved. We examined whether higher diet quality in childhood and adolescence modifies the association between GDM exposure and adiposity outcomes. In 499 offspring (n=88 GDM-exposed), we assessed dietary intake (via food frequency questionnaire) and adiposity (BMI, waist-to-height ratio, visceral and subcutaneous adipose tissue [VAT, SAT], and subscapular-to-triceps skinfold ratio) at 6-12 and 12-19 years of age. Diet quality was estimated with the Healthy Eating Index (HEI). Linear mixed models were used to examine the association between GDM exposure and adiposity among those with higher (HEI>60) versus lower (HEI<60) diet quality, adjusting for sex, race/ethnicity, age, and pubertal status. Among those with lower diet quality, exposure to GDM was associated with increased adiposity for all outcomes (all p<0.05; Table). Among those with higher diet quality, there was no association between GDM exposure and adiposity outcomes (all p>0.05). Our results suggest that higher diet quality in childhood and adolescence may be a potential postnatal strategy for reducing adiposity among offspring exposed to GDM.

Authors: Sauder KA, Hockett CW, Ringham BM, Glueck DH, Dabelea D.

Abstract:

To exa​​​​​mine the associations of intrauterine exposure to maternal diabetes and obesity with offspring insulin resistance, beta-cell function and oral disposition index in a longitudinal observational study of ethnically diverse offspring. METHODS: A total of 445 offspring who were exposed (n=81) or not exposed (n=364) to maternal diabetes in utero completed two fasting blood measurements at mean (sd) ages of 10.5 (1.5) and 16.5 (1.2) years, respectively, and an oral glucose tolerance test at the second visit. We used linear mixed models and general linear univariate models to evaluate the associations of maternal diabetes and pre-pregnancy BMI with offspring outcomes. RESULTS: Maternal diabetes in utero predicted increased insulin resistance [18% higher updated homeostatic model assessment of insulin resistance (HOMA2-IR), P=0.01; 19% lower Matsuda index, P=0.01 and 9% greater updated homeostatic model assessment of beta-cell function (HOMA2-beta), P=0.04]. Each 5-kg/m(2) increase in pre-pregnancy BMI predicted increased insulin resistance (11% greater HOMA2-IR, P<0.001; 10% lower Matsuda index, P<0.001; 6% greater HOMA2-beta, P<0.001). Similar results were obtained in a combined model with both exposures. After adjustment for offspring BMI, only maternal diabetes was associated with higher HOMA2-IR (beta=1.12, P=0.03) and lower Matsuda index (beta=0.83, P=0.01). Neither exposure was associated with early insulin response or oral disposition index. CONCLUSIONS: Intrauterine exposure to diabetes or obesity is associated with greater offspring insulin resistance than non-exposure, supporting the hypothesis that fetal overnutrition results in metabolic abnormalities during childhood and adolescence.

Principal Investigator: Dana Dabelea, MD, PhD

Researchers Involved: Dana Dabelea, Katerina Kechris, Ivana Yang, Weiming Zhang​

About the Study:
Epigenetics is a method for turning on and off genes without changing the genes themselves (like a program on a computer that does not change the computer itself). One of the possible ways that a mother’s diabetes during pregnancy might affect their offspring is through this mechanism.