ESPE Yearbook of Paediatric Endocrinology

Brief summary: This meta-analysis examined the association of autism spectrum disorders (ASD) with cardiometabolic diseases. The study included 276 173 individuals with autism and found a 69.4% higher relative risk of dyslipidemia, indicating higher risks of heart disease and stroke. The risk of type 2 diabetes mellitus (T2D) was 247% higher in individuals with autism, and the risk of type 1 diabetes mellitus (T1D) was 64% higher. Genetic factors, obesity, and autoimmune diseases contribute to these increased risks.

Comment: People with autism are far more likely to experience cardiovascular and metabolic conditions than their peers without autism. In particular, among children with autism compared to age-matched children without, risks of diabetes and hypertension were 2.8 and 2.5 times greater, respectively.

About 1:36 children has been identified with ASD, according to estimates from the CDC’s Autism and Developmental Disabilities Monitoring Network.¹ ASD is nearly four times more common among boys than girls. Autism is associated with multiple medical, neurologic and psychiatric comorbidities. Obesity has emerged as an important comorbidity of autism. However, evidence regarding the risk of these obesity-associated comorbidities remains ambiguous due to inconsistencies in recent observational studies.

The aim of this meta-analysis was to examine associations of ASD with cardiometabolic disease (i.e., diabetes mellitus, hypertension and dyslipidemia) and with atherosclerotic macrovascular disease (i.e., cardiovascular, cerebrovascular and peripheral vascular diseases). Data were retrieved from 34 studies, comprising 276 173 individuals with autism, and 7 733 306 individuals without autism (mean [range] age, 31.2 [3.8–72.8] years). The relative risk of dyslipidemia was 69.4% higher among individuals with than without autism. Specifically, triglyceride levels were significantly higher (by 26 mg/dL) and HDL levels were significantly lower (by 9.35 mg/dL). These patterns are consistent with increased risks of both heart disease and stroke. LDL levels did not differ between the groups.

A few risk factors have been identified as contributing to dyslipidemia in autism. These include variations in the genes NPC1 and DHCR24, which are associated with cholesterol metabolism; altered proteins involved in lipid transport (e.g., apolipoprotein B100) and metabolism pathways; and increased lipoprotein lipase activity.

The relative risk of developing T2D was 247% higher among individuals with autism than controls, and was higher among the children with autism than the children without autism. The reasons for higher T2DM and dyslipidemia risks could be multifactorial. Firstly, it could be secondary to the increased prevalence of obesity in autism. Secondly, it could be due to ASD-associated genetic variants (e.g., 16p11.2 deletion, microdeletion 11p14.1). Finally, it could be the result of medications, toxins, prematurity or intrauterine growth retardation. The risk of T1D was 64% higher among individuals with autism than among controls, possibly attributed to an increased risk of autoimmune disease in autism.

An accompanying editorial¹ states that overall, people with autism die much younger than expected, on average by 12 to 30 years earlier. Clinicians should be aware of the specific risk factors among persons with autism, and should implement appropriate preventive measures. To provide appropriate standard of care, clinicians should consider the challenges that these vulnerabilities pose, as well as the structural barriers that people with autism face in accessing high-quality health care.

Reference: 1. Weir EM. Autism, physical health conditions, and a need for reform. JAMA Pediatr. 2023;177(3):229–230. doi: 10.1001/jamapediatrics.2022.5639.