Increased metabolic risk in adolescent offspring of mothers with type 1 diabetes: the EPICOM study

Abstract

Aims/hypothesis We aimed to investigate metabolic risk factors, insulin sensitivity and insulin secretion in adolescent offspring of mothers with type 1 diabetes compared with offspring of non-diabetic mothers. Methods During 1993-1999, pregnancies of women with type 1 diabetes in Denmark were prospectively reported to a central registry in the Danish Diabetes Association. Data included information on maternal demography, diabetes status and pregnancy outcome. We invited 746 eligible children from this cohort (index offspring) to a follow-up examination. Control offspring were identified through The Danish Central Office of Civil Registration and matched with respect to date of birth, sex and postal code. Anthropometric measurements and blood sampling for metabolic characterisation, including an oral glucose tolerance test, were performed.Results We examined 278 index offspring (mean age 16.7 years; range 13.0-19.8 years) and 303 control offspring (mean age 16.8 years; range 13.5-20.4 years). Index offspring had higher BMI SD score (0.44: 95% CI 0.21, 0.66) compared with controls, after adjustments for pubertal development and maternal pre-pregnancy BMI. Furthermore, index offspring had a higher prevalence of components included in metabolic syndrome and prediabetes (impaired fasting glucose and/or impaired glucose tolerance), with reduced insulin sensitivity and relative insulin secretion deficiency, compared with controls. Maternal HbA 1c levels in pregnancy were not directly associated with offspring metabolic outcomes. Conclusions/interpretation Adolescent offspring of mothers with type 1 diabetes had a less favourable metabolic profile and higher frequency of prediabetes than the background population. Significant associations between these outcomes and Electronic supplementary material The online version of this article (doi:10.1007/s00125-015-3589-5) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Long-term Cognitive Implications of Intrauterine Hyperglycemia in Adolescent Offspring of Women With Type 1 Diabetes (the EPICOM Study)

“…EPICOM (EPIgenetic, genetic and environmental effects on COgnitive and Metabolic functions in offspring of mothers with type 1 diabetes) is a Danish prospective nationwide follow-up study focusing on the long-term effects of intrauterine hyperglycemia (9). During 1993-1999 all pregnant women with type 1 diabetes in Denmark were prospectively reported to a central register in the Danish Diabetes Association (n = 1,215) (1).…”

“…The cognitive tests were completed by 277 (37.1%) exposed and 301 (15.7%) unexposed offspring. Details about the inclusion process and follow-up have recently been published (9).…”

“…Offspring of women with ketoacidosis or hypoglycemia tended to perform worse than offspring of women without these complications, and their participation rate was lower than that for the entire diabetes-exposed group (28% vs. 37%), implying no selection of children with lower performance in the exposed group. The cognitive tests were a minor part of a comprehensive examination plan (9). None of the offspring chose to confine their participation to the cognitive tests, so we do not consider these tests as the primary motivation for participation in either of the groups.…”

“…Intrauterine hyperglycemia has both short-term and long-term implications on offspring morbidity and mortality, which are associated with the degree of maternal glycemic control before and during pregnancy (1)(2)(3)(4)(5)(6)(7)(8)(9).…”

Social, Familial and Psychological Risk Factors for Endocrine, Nutritional and Metabolic Disorders in Childhood and Early Adulthood: a Birth Cohort Study Using the Danish Registry System

“…Parental history of type 2 diabetes and obesity consistently increase the risk of both disorders among offspring (Lyssenko et al 2008;Reilly et al 2005). Vlachová et al (2015) investigated metabolic risk-factors, prevalence of metabolic syndrome (MetS), and prediabetes in a Danish sample of adolescents with diabetic (type 1) mothers compared to a control group of adolescents of non-diabetic mothers. They reported that adolescents of diabetic mothers had a higher frequency of metabolic riskfactors, decreased insulin sensitivity, insufficient insulin secretion and a higher prevalence prediabetes compared to controls.…”