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Maternal diabetes exposure associated with insulin resistance, decreased insulin sensitivity in offspring
Children exposed to maternal diabetes in utero are more likely to experience insulin resistance during childhood and adolescence vs. children not exposed to maternal diabetes, independent of maternal prepregnancy obesity and offspring BMI, according to findings from a longitudinal study.
“The intrauterine environment appears to be particularly important for the development of early-onset type 2 diabetes; however, among people aged at least 20 years, less is known about how intrauterine exposures are related to metabolic abnormalities that are precursors to overt type 2 diabetes, including insulin resistance and altered insulin secretion,” Katherine A. Sauder, PhD, assistant professor of pediatrics at the University of Colorado School of Medicine, and colleagues wrote. “Given that half of women are overweight or obese prior to pregnancy and at least 9% of pregnancies are complicated by maternal diabetes in the USA, a better understanding of how these exposures are associated with offspring diabetes risk is needed to guide early intervention efforts.”
Sauder and colleagues analyzed data from 445 offspring who were exposed (n = 81) or not exposed (n = 364) to maternal diabetes in utero from the Exploring Perinatal Outcomes among Children (EPOCH), a longitudinal cohort recruited from the Kaiser Permanente of Colorado perinatal database between 2005 and 2010. Researchers determined maternal diabetes and obesity status, including prepregnancy BMI, from medical records. Over two visits, researchers measured fasting blood glucose and insulin; visit two included a 2-hour, 75-g oral glucose tolerance test with blood samples at baseline and 30 and 120 minutes. Researchers calculated updated homeostatic model assessment of insulin resistance (HOMA2-IR) and updated homeostatic model assessment of beta-cell function (HOMA2-beta); whole-body insulin sensitivity was assessed via the Matsuda index. Early insulin response and oral disposition index were also calculated. Researchers used linear mixed models and general linear univariate models to evaluate associations between maternal diabetes and prepregnancy BMI with offspring outcomes.
At visit one, mean age of offspring was 11 years; mean BMI was 19 kg/m²; 43% were white; 18% were exposed to maternal diabetes. At visit two, mean age of offspring was 17 years; mean BMI was 23.6 kg/m²; 46% were white; 21% were exposed to maternal diabetes.
Researchers found that exposure to diabetes in utero was associated with an 18% increase in HOMA2-IR (P = .01) and a 19% decrease in Matsuda insulin sensitivity (P = .01), as well as a 9% decrease in HOMA2-beta (P = .04). In addition, researchers found that each 5 kg/m² increase in maternal pregnancy BMI was associated with an 11% increase in HOMA2-IR (P < .001), a 10% decrease in Matsuda insulin sensitivity (P < .001) and a 6% increase in HOMA2-beta (P < .001). There were no associations between maternal diabetes or obesity exposure and early insulin response or oral disposition index, according to researchers.
In a combined model that included offspring BMI, exposure to maternal diabetes was associated with a 12% increase in HOMA2-IR (P = .04) and a 17% decrease in Matsuda insulin sensitivity (P = .01); however, any association between maternal BMI and HOMA2-IR, HOMA2-beta and Matsuda insulin sensitivity were attenuated.
“Given the high prevalence of obesity and diabetes among women of childbearing age, a substantial proportion of contemporary children are being exposed to an adverse intrauterine environment with potentially lifelong consequences,” the researchers wrote. “Efforts to reduce maternal obesity and prevent maternal diabetes are needed urgently to halt the transgenerational transmission of diabetes and obesity.” – by Regina Schaffer
Disclosures: The authors report no relevant financial disclosures.