Fatty Liver Among Adolescent Offspring of Women With Type 1 Diabetes (the EPICOM Study)

Abstract

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

The long-term metabolic and neurocognitive risks in offspring of women with type 1 diabetes mellitus

“…There was no association between maternal HbA1c during pregnancy and offspring FLI group. In OT1D, a WHtR>0.496 was associated with a significantly higher maternal HbA1c in the third trimester of pregnancy (p=0.04), but not in the pregestational period, the first or second trimester [25].…”

“…In contrast, Weiss et al showed that metabolic differences were more distinct in male than in female offspring [24]. In Knorr et al, there was a higher female proportion in the groups with FLI 30-60 and FLI60, although the difference between FLI groups was not significant [25]. In addition, the group with WHtR>0.469 included significantly more females (p=0.01) [25].…”

“…Another study found a higher average BMI-SDS increase per year increase in age in OT1D compared to controls, as well as a 13% relative increase in overweight risk per year increase in age [5]. Knorr et al found that age was significantly higher in the group with WHtR>0.469 (a cut-off to rule in NAFLD), but did not find such statistical difference in FLI groups [25]. In studies evaluating neurocognitive outcomes, eight adjusted for age or birth year (Table 3).…”

“…In Knorr et al, there was a higher female proportion in the groups with FLI 30-60 and FLI60, although the difference between FLI groups was not significant [25]. In addition, the group with WHtR>0.469 included significantly more females (p=0.01) [25]. Among studies with neurocognitive outcomes, nine made adjustments for sex (Table 3).…”

“…Only one study reported on fatty liver disease in OT1D [25]. OT1D showed a significantly higher fatty liver index (FLI) than ONDM, with median values of 5.3 versus 3.6 respectively (p=0.001) (Table 2).…”