Adults with fetal alcohol spectrum disorders (FASD) may have an increased risk of type 2 diabetes, and other metabolic abnormalities such as low HDL cholesterol and elevated levels of triglycerides compared to people without FASD, according to a new study supported by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health. The research team confirmed their findings in a zebrafish model of FASD and gained insight into the mechanisms that may play a role in these metabolic issues.
FASD is a term that refers to the broad range of lifelong birth defects and neurodevelopmental abnormities that occur as a result of prenatal alcohol exposure. People with FASD may have facial abnormalities, cognitive and behavioral deficits, and growth impairments. However, little is known about the occurrence of metabolic issues in adults with FASD.
In the study, a team of Harvard Medical School researchers led by senior author Wolfram Goessling, M.D., Ph.D., and first author Olivia Weeks, sought to gain a better understanding of the metabolic issues associated with prenatal alcohol exposure. Using a patient database registry at a large academic health system, the researchers identified 208 patients age 18 or older with FASD and a set of patients without FASD who were similar in age, sex, race, and ethnicity. They found that patients with FASD had an increased incidence of type 2 diabetes, lower HDL (“good”) cholesterol, and elevated triglyceride levels compared to those without FASD. Low HDL cholesterol and elevated triglyceride levels are associated with increased risk of stroke and heart attack. The team also found that female patients with FASD were more likely to be overweight and obese than their male counterparts. Additionally, patients with FASD were more likely to have two or more metabolic abnormalities than patients without FASD.
The scientists then used a zebrafish model to investigate the mechanisms underlying the connection between metabolic abnormalities and prenatal alcohol exposure. During the embryo stage, zebrafish were exposed to no alcohol or levels of alcohol equivalent to prolonged heavy drinking in humans. The researchers found that in adult zebrafish challenged with a high-fat, high-cholesterol diet, embryonic alcohol exposure increased the tendency for obesity and fasting hyperglycemia. Fasting hyperglycemia, or high levels of glucose in the blood, is an indicator of diabetes in humans. Embryonic alcohol exposure was also associated with reduced physical activity, increased abdominal fat, abnormal liver development, and unique molecular changes related to diet in adult zebrafish. The researchers hypothesize that these changes may indicate differences in how prenatal alcohol exposure affects nutrient intake in adults.
Taken together, these findings demonstrate that prenatal alcohol exposure may be a risk factor for metabolic disease in adults and shed light on potential mechanisms that may contribute to metabolic problems associated with prenatal alcohol exposure.
Weeks, O.; Bossé, G.D.; Oderberg, I.M.; Akle, S.; Houvras,Y.; Wrighton, P.; LaBella, K.; Iversen, I.; Tavakoli, S.; Adatto, I.; Schwartz, A.; Kloosterman, D.; Tsomides, A; Charness, M.E.; Peterson, R.T.; Steinhauser, M.L.; Fazeli, P.K.; and Goessling, W. Fetal alcohol spectrum disorder predisposes to metabolic abnormalities in adulthood. J Clin Invest. 2020 Mar 23. pii: 132139. doi: 10.1172/JCI132139. [Epub ahead of print]