Intrauterine exposure to maternal type 1 diabetes is associated with a less favorable metabolic profile later in life. Nonalcoholic fatty liver disease is the hepatic manifestation of a cluster of metabolic abnormalities linked to insulin resistance. This study aimed to evaluate the effect of maternal pregestational type 1 diabetes on the presence of fatty liver in offspring and the association between maternal BMI, glycemic control during pregnancy, offspring metabolic risk factors, and offspring level of soluble CD163 (sCD163) (a marker of macrophage activation) and risk of fatty liver. RESEARCH DESIGN AND METHODS This study was a prospective nationwide follow-up study of offspring (n = 278) of mothers with pregestational type 1 diabetes between 1993 and 1999 and matched control subjects (n = 303). Mean age at the time of follow-up was 16.7 years (range 13.0-20.4 years). We used the fatty liver index (FLI) and waist-to-height ratio (WHtR) to evaluate the presence of fatty liver among the offspring. An FLI ‡60 or WHtR >0.469 were used as cutoff points for fatty liver. RESULTS More type 1 diabetes-exposed offspring had high FLI and WHtR indices compared with unexposed control subjects. We found significant associations between increasing maternal prepregnancy BMI, being born large for gestational age, offspring level of sCD163, as well as offspring metabolic risk factors (decreasing adiponectin and HDL cholesterol and increasing leptin, HOMA of insulin resistance, and HOMA of insulin secretion) and degree of fatty liver. CONCLUSIONS Intrauterine exposure to maternal type 1 diabetes and higher maternal prepregnancy BMI may predispose to fatty liver in the offspring. Offspring metabolic risk factors, including sCD163 levels, are associated with indices of fatty liver. Along with the worldwide increase in obesity, the prevalence of nonalcoholic fatty liver disease (NAFLD) is rising, and in the pediatric population, NAFLD is now considered one of the leading causes of hepatic disease (1). Offspring of women with diabetes have an increased risk of developing type 2 diabetes, prediabetes, and obesity (2). This applies to both offspring of mothers with pregestational diabetes as well as gestational diabetes mellitus, and our research group has previously published data from the EPICOM (Epigenetic, Genetic, and Environmental Effects on Growth, Cognitive Functions, and Metabolism in Offspring of Women

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