Differential effects of age and sex on insulin sensitivity and body composition in adolescent offspring of women with type 1 diabetes: results from the EPICOM study

Lohse, Zuzana; Knorr, Sine; Bytoft, Birgitte; Clausen, Tine D.; Jensen, Rikke Beck; Oturai, Peter; Beck‐Nielsen, Henning; Gravholt, Claus Højbjerg; Damm, Peter; Højlund, Kurt; Jensen, Dorte Møller

doi:10.1007/s00125-017-4458-1

Cited by 14 publications

(15 citation statements)

References 40 publications

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“…The opposite applied to the EPICOM cohort, where female offspring had the highest FLI and WHtR. In the EPICOM study, we have previously described reduced insulin sensitivity among the oldest offspring of women with type 1 diabetes (17+ years), and especially among the female participants (31). We also described adiponectin to be significantly lower among the type 1 diabetes-exposed female offspring from the EPICOM cohort, indicating sex differences among the type 1 diabetes-exposed offspring (32).…”

Section: Discussionmentioning

confidence: 75%

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

et al. 2019

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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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Section: Discussionmentioning

confidence: 75%

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

et al. 2019

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“…At the other end of the spectrum, intrauterine exposure to hyperglycemia and/or maternal obesity also increases the risk of later life obesity and impaired glucose tolerance [22, 65, 66]. A recent study describes how intrauterine exposure to hyperglycemia affects the offspring in a sex-specific way, with females being more prone to the effects [67]. The same study describes how intrauterine exposure to hyperglycemia to a greater extent impairs OGTT-derived indexes of insulin resistance compared to indexes of insulin secretion.…”

Section: The Influence Of Early Life Environment On Later Life Inmentioning

confidence: 99%

Determinants of Maternal Insulin Resistance during Pregnancy: An Updated Overview

Kampmann

Knorr

Fuglsang

et al. 2019

Journal of Diabetes Research

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Insulin resistance changes over time during pregnancy, and in the last half of the pregnancy, insulin resistance increases considerably and can become severe, especially in women with gestational diabetes and type 2 diabetes. Numerous factors such as placental hormones, obesity, inactivity, an unhealthy diet, and genetic and epigenetic contributions influence insulin resistance in pregnancy, but the causal mechanisms are complex and still not completely elucidated. In this review, we strive to give an overview of the many components that have been ascribed to contribute to the insulin resistance in pregnancy. Knowledge about the causes and consequences of insulin resistance is of extreme importance in order to establish the best possible treatment during pregnancy as severe insulin resistance can result in metabolic dysfunction in both mother and offspring on a short as well as long-term basis.

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“…Gestational diabetes mellitus (GDM) is a prevalent disease associated with health risks for both the mother and the child . In addition to the short‐term fetal and neonatal adverse outcomes, programming of metabolic diseases in the offspring has been shown in women with pregestational diabetes and GDM as well as in experimental models of diabetes and pregnancy . Previously, we have reported that female offspring from rats with mild diabetes develop GDM, as these animals have normal glucose and insulin circulating levels before mating, and increased fasting glucose and insulin circulating levels at late pregnancy .…”

Section: Introductionmentioning

confidence: 99%

Diet Enriched with Olive Oil Attenuates Placental Dysfunction in Rats with Gestational Diabetes Induced by Intrauterine Programming

Capobianco

Ribot

Fornes

et al. 2018

Molecular Nutrition Food Res

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Differential effects of age and sex on insulin sensitivity and body composition in adolescent offspring of women with type 1 diabetes: results from the EPICOM study

Cited by 14 publications

References 40 publications

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

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

Determinants of Maternal Insulin Resistance during Pregnancy: An Updated Overview

Diet Enriched with Olive Oil Attenuates Placental Dysfunction in Rats with Gestational Diabetes Induced by Intrauterine Programming

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