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Fetal overnutrition and offspring insulin resistance and β‐cell function: the Exploring Perinatal Outcomes among Children ( EPOCH ) study
Author(s) -
Sauder K. A.,
Hockett C. W.,
Ringham B. M.,
Glueck D.H.,
Dabelea D.
Publication year - 2017
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1111/dme.13417
Subject(s) - offspring , medicine , insulin resistance , overnutrition , homeostatic model assessment , endocrinology , diabetes mellitus , pregnancy , body mass index , insulin , gestational diabetes , obesity , gestation , biology , genetics
Aims To examine the associations of intrauterine exposure to maternal diabetes and obesity with offspring insulin resistance, β‐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 ( HOMA 2‐ IR ), P =0.01; 19% lower Matsuda index, P =0.01 and 9% greater updated homeostatic model assessment of β‐cell function ( HOMA 2‐β), P =0.04]. Each 5‐kg/m 2 increase in pre‐pregnancy BMI predicted increased insulin resistance (11% greater HOMA 2‐ IR , P <0.001; 10% lower Matsuda index, P <0.001; 6% greater HOMA 2‐β, 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 HOMA 2‐ IR (β=1.12, P =0.03) and lower Matsuda index (β=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.