Type 2 Diabetes in Youth: the Role of Early Life Exposures
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PATHOGENESIS OF TYPE 2 DIABETES AND INSULIN RESISTANCE (ME PATTI, SECTION EDITOR)
Type 2 Diabetes in Youth: the Role of Early Life Exposures Ankur Rughani 1 & Jacob E. Friedman 1 & Jeanie B. Tryggestad 1
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose of Review This review examines the impact of early life exposures on glucose metabolism in the offspring and explores potential metabolic mechanisms leading to type 2 diabetes in childhood. Recent Findings One in five adolescents is diagnosed with prediabetes. Recent studies have elucidated the impact of early exposures such as maternal diabetes, but also hyperglycemia below the threshold of gestational diabetes, obesity, hyperlipidemia, and paternal obesity on the future metabolic health of the offspring. Mechanisms affecting the developmental programing of offspring toward type 2 diabetes include epigenetic modifications, alterations in stem cell differentiation, metabolome and microbiome variation, immune dysregulation, and neonatal nutrition. Summary The risk of type 2 diabetes in offspring is increased not only by diabetes exposure in utero but also by exposure to a heterogeneous milieu of factors that accompany maternal obesity that provoke a vicious cycle of metabolic disease. The key period for intervention to prevent type 2 diabetes is within the first 1000 days of life. Keywords Obesity . Type 2 diabetes . Fetal programming . Gestational diabetes
Introduction Type 2 diabetes (T2DM) among youth has risen dramatically over the past decade. According to the data from the National SEARCH for Diabetes in Youth (SEARCH) study, the incidence of type 2 diabetes between the ages of 10 and 19 years was 12.5 cases per 100,000 between 2011 and 2012 as compared with 9.0 cases per 100,000 between 2002 and 2003, an annual increase of 7.1% with a higher increase in ethnic minorities [1]. According to the most recent National Health and Nutrition Examination Survey (NHANES) data, an estimated 18% of adolescents have prediabetes [2]. Lastly, according to the Centers for Disease Control and Prevention, 1 in 3 children born in 2000 in the USA is predicted to develop diabetes in their lifetime [3].
This article is part of the Topical Collection on Pathogenesis of Type 2 Diabetes and Insulin Resistance
T2DM in youth has also proven to be more aggressive than T2DM that presents in adulthood. In the treatment options for Type 2 Diabetes in Adolescents and Youth (TODAY) study, almost half of the participants demonstrated treatment failure, as evidenced by an A1C greater than 8% for 6 months or inability to taper insulin after a metabolic decompensation, less than 1 year into the study [4]. In contrast to the Diabetes Prevention Program, intensive lifestyle intervention with metformin did not prove to be any more effective in preserving glucose control than metformin alone, but early intensification with rosiglitazone did prove beneficial [4]. Given the aggressiveness of T2DM in youth and earlier onset, much focus has been placed on early l
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