Early-Life Exposure to Substance Abuse and Risk of Type 2 Diabetes in Adulthood

Abstract

Type 2 diabetes (T2D) is a chronic non-communicable disease that is driven by insulin resistance as a result of increasing obesity and decreasing activity levels that occur with increasing age. This disease generally develops after the age of 40, but it is now increasingly diagnosed in children and young adults. Increasing evidence, however, suggests that T2D can originate during early development. It has been repeatedly found that malnutrition during the gestational period can result in intrauterine growth restriction and low birth weight, which in combination with postnatal catch-up growth may subsequently lead to the development of T2D. There is ample evidence that T2D may also be programmed by maternal substance abuse (the harmful use of psychoactive substances such as illicit drugs or alcohol) during pregnancy and/or lactation. The research activity in this field is currently mainly focused on the childhood health problems following prenatal exposures to substance abuse. The delayed programming effects on adult-onset disorders, including metabolic syndrome and T2D, however, have been reported only rarely. This review provides animal and human evidence that early-life exposure to substance abuse, including alcohol, nicotine, and cocaine, may program not only childhood health outcomes but also life-long metabolic health status, including risk of T2D and related conditions.

Early-Life Nutritional Programming of Type 2 Diabetes: Experimental and Quasi-Experimental Evidence

“…Seasonality of birth has been demonstrated for many aspects of metabolic syndrome, including high systolic blood pressure [82], obesity [83,84] and also dyslipidaemia, insulin resistance and CVD [85]. The seasonal pattern of birth for childhood autoimmune (type 1) diabetic patients was reported repeatedly (see, e.g., [96]), while the seasonality of birth for T2D adult persons was observed only in a few studies.…”

Epigenetics and obesity cardiomyopathy: From pathophysiology to prevention and management

“…Similar to the human Dutch Hunger Winter famine case during World War II, environmental exposure to factors including nutritional, psychological, and social stress, toxins and substance abuse in early life may serve as triggers for epigenetic programming for various comorbidities later (Vaiserman, 2015a;Vaiserman, 2015b). In mammals, the epigenome may be subject to major epigenetic modifications during gametogenesis and early embryogenesis (Messerschmidt et al, 2014;Vaiserman, 2015a;Vaiserman, 2015b). In the early embryo, methylation levels are minimal to allow removal of gamete-specific methylation inherited from parents for the purpose of pluripotency.…”

“…Demethylation process is considered near complete in primordial germ cells, whereas methylation of imprinted regions is protected in early embryos, thus allowing expression of specific parent-of-origin genes in early embryos (Messerschmidt et al, 2014). Therefore, epigenetic modifications elicited by environmental influences during these critical periods pertain across the life course, possibly resulting in unfavorable consequences in adulthood (Messerschmidt et al, 2014;Vaiserman, 2015a;Vaiserman, 2015b).…”

“…Deacetylation and dephosphorylation of histone H3 has also been reported in the hearts of diabetic Sprague-Dawley rats, responsible for changes in gene expression in the extracellular matrix (ECM) and cardiac hypertrophy (Gaikwad et al, 2010). Global histone methylation is relatively unclear in obesity, although substantially decreased levels of histone H3 lysine 4 dimethylation has been reported in adipocytes from overweight individuals while increased levels of lysine 4 trimethylation were noted in obese/diabetic patients (van Dijk et al, 2015).…”

Children Born by Women With Rheumatoid Arthritis and Increased Susceptibility for Chronic Diseases: A Nationwide Cohort Study

“…Such concerns are highly relevant, as there might be a genetic susceptibility to passing RA or other autoimmune diseases on to the offspring. Furthermore, it has been repeatedly found that fetal programming during the gestational period can result in intrauterine growth restriction and low birthweight, which can subsequently lead to the development of chronic diseases in adulthood . Early adverse fetal life exposures, such as maternal chronic disease, might thus program not only adverse birth outcomes but also have a lifelong impact on the health status of the exposed children .…”