Down Syndrome Youth Have a High Prevalence of Dyslipidemia and Prediabetes

Two-thirds of youth with Down syndrome have a BMI percentile at or above 85, but is this a marker for prediabetes and dyslipidemia in this population?  

A recent Pediatrics study investigated whether body mass index is an accurate reflection of cardiometabolic risk in youth with Down syndrome. Thanks to modern medicine, the life expectancy of patients with Down syndrome has increased significantly to an average of 60 years. Still, minimal data is available for chronic health conditions in this population. Recent data revealed that people with Down syndrome are at an increased risk of cardiovascular disease and diabetes.   

In youth, body mass index has limited value in determining adiposity, and researchers believe this may be magnified in a child with Down syndrome. This study investigated body mass index in youth with Down syndrome and its role in adiposity and cardiometabolic risk. Youth aged 10-20 years with Down syndrome were compared to children without Down syndrome. There were no significant differences in age, sex, race, ethnicity, pubertal stage, BMI, BMI z score, and BMI percentile. The study design included 150 youth with Down syndrome and 103 children without. Exclusion criteria included: major organ illnesses like polycystic kidney disease, liver disease, sickle cell disease, and brain tumor. Other exclusions include current or previous cancer, heart disease, pulmonary hypertension, type 1 diabetes, pregnancy, familial hypercholesterolemia, and treatment with drugs that affect insulin sensitivity or lipids.     

Body mass index was calculated by the Centers for Disease Control and Prevention growth charts for both groups. Weight was categorized as BMI within a percentile as normal (5th-85th percentile), overweight (85th-95th percentile), and obese (≥95th percentile) for youth aged 10-19 years. For youth 20 years old, weight was explicitly categorized by BMI as normal (18.5-25 BMI), overweight (BMI ≥25), and obese (BMI ≥30). Body scans using X-ray absorptiometry were used to determine the percentage of body fat, whole-body lean mass, whole-body fat mass, and visceral fat area. Glucose tolerance tests were given to any patient determined to be overweight or obese. Patients with impaired fasting glucose also underwent a plasma glucose test for confirmation. This study’s primary outcome was high-density lipoprotein cholesterol levels since this is highly predictive of cardiovascular disease. This study was adequately powered and is considered clinically relevant.    

As hypothesized, youth with Down syndrome had higher LDL-C concentrations, triglycerides, non-HDL-C, and triglycerides/HDL and lower HDL-C levels. When comparing the youth with overweight or obesity from each group, Down syndrome youth had a higher number of children with dyslipidemia. When comparing youth with a normal BMI, Down syndrome children still have a higher number of children with dyslipidemia. However, only non-HDL-C reached borderline statistical significance. It was also found that the Down syndrome group had higher fasting glucose levels but surprisingly had lower HbA1c levels. Conversely, the prevalence of prediabetes was more significant in the Down syndrome group.    

BMI, BMI z score, tri-ponderal mass index, waist circumference, waist-to-height ratio, and waist-to-hip ratio were significantly associated with non-HDL-C, triglycerides/HDL in youth with Down syndrome. Youth with Down syndrome have a greater prevalence of prediabetes, but there is no significant difference in HOMA-IR between the groups. The results indicate that BMI is superior to other adiposity measures when predicting non-HDL-C or triglycerides/HDL levels in Down syndrome youth. Down syndrome patients are at an increased risk of atherosclerosis, and the Down syndrome specific phenomena may predispose these patients to dyslipidemia. These findings indicate the need to evaluate screening recommendations in youth with Down syndrome, but additional research must confirm results.    

Practice Pearls:   

• Youth with Down syndrome have a greater prevalence of prediabetes but have lower HbA1c levels, and the reason is not clearly understood.    
• BMI is superior to other adiposity measures when predicting non-HDL-C or triglycerides/HDL levels in youth with Down syndrome.    
• Youth with Down syndrome have worse lipid profiles when compared to a child without Down syndrome.    

Reference:    

Magge, S. N., Zemel, B. S., Pipan, M. E., Gidding, S. S., & Kelly, A. (2019). Cardiometabolic Risk and Body Composition in Youth With Down Syndrome. Pediatrics. doi:10.1542/peds.2019-0137   

Kassey James, Pharm.D. Candidate, LECOM School of Pharmacy   

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