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Colorado School of Public Health

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EPOCH

Exploring Perinatal Outcomes among Children


Dana Dabelea, MD, PhD, Principal Investigator.

EPOCH is a longitudinal study of adolescents and their long-term health outcomes related to whether they were exposed to mother’s diabetes during pregnancy. While it is known that a mother with diabetes during pregnancy increases the risk of childhood obesity and diabetes, many other things are not known, including whether infant or childhood feeding changes these outcomes.

Researchers Involved: Dana Dabelea, Katherine Sauder, Allison Shapiro​, Christy Hockett, Anna Bellatorre, Wei Perng 

Offspring diet quality modifies the effect of gestational diabetes exposure on adiposity outcomes: The EPOCH study

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

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.

Table: Measures of adiposity (mean, SE) among youth with high and low diet quality, stratified by GDM exposure.


Unexposed HEI < 60
Exposed
p-value Unexposed HEI > 60
Exposed
p-value HEI x GDM
p-value
BMI (kg/m2) 20.2 (1.0) 21.7 (1.0) 0.004 20.2 (1.0) 20.9 (1.0) 0.23 0.22
Waist to height ratio 1.46 (1.00) 1.49 (1.01) 0.0003 1.46 (1.00) 1.47 (1.01) 0.69 0.03
VAT (cm2) 22.1 (1.0) 26.4 (1.0) 0.01 21.8 (1.0) 23.5 (1.1) 0.43 0.28
SAT (cm2) 108.3 (1.0) 147.0 (1.1) 0.0007 106.9 (1.0) 130.9 (1.1) 0.06 0.29
VAT:SAT 1.23 (1.00) 1.19 (1.01) 0.003 1.22 (1.01) 1.19 (1.01) 0.10 0.79
Skinfold ratio 1.87 (1.01) 2.01 (1.02) 0.0001 1.90 (1.01) 1.93 (1.03) 0.56 0.08
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Sauder KA, Hockett CW, Ringham BM, Glueck DH, Dabelea D. Fetalovernutrition and offspring insulin resistance and beta-cell function: theExploring Perinatal Outcomes among Children (EPOCH) study. Diabet Med. 2017;34(10):1392-1399.

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.



Epigenetic Markers of In Utero Exposure to Diabetes

An EPOCH Ancillary Study

Dana Dabelea, MD, PhD, is the Principal Investigator. 

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.

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

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