ADA 2021: Genetic Risk Score for Type 2 Diabetes and Traits Related to Glucose

Genetic risk scores can help provide insight into the problem of increasing youth-onset type 2 diabetes rates.  

Type 2 diabetes is a condition that accounts for 20-50% of new cases of diabetes among the youth in the United States. Disease prevalence projections estimate a four-fold increase in youth populations by the year 2050. Youth-onset of type 2 diabetes is very distinct as compared to adult-onset. Youth-onset is associated with obesity, higher incidence of complications, aggressive progression of the disease, and reduced response to treatment. The prevalence among youth in all ethnicities is increasing, but in non-Hispanic black youth is growing much faster. Genomic-wide association studies (GWAS) have recognized over 300 single nucleotide polymorphisms (SNPs) correlating to type 2 diabetes. Understanding risk factors and the rate progression of disease-associated to them would be essential in managing type 2 diabetes. 

This study’s objective was to evaluate the association between type 2 diabetes genetic risk scores (GRS) and glycemic traits during childhood. Researchers conducted a case-control study using data from the Exploring Perinatal Outcomes Among Children (EPOCH) study. Researchers measured the outcomes of fasting glucose, post-challenge glucose, homeostasis model of insulin resistance, oral disposition index, and insulinogenic index. A log regression was applied to the data and adjusted for age, sex, BMI z-score, genetic components, utero diabetes, and Tanner stage.  

Data from 356 subjects were stratified and assessed. Baseline characteristics showed an average age of 16.9 years, 50% of the cohort was female, and subjects were majority classified as overweight. Researchers observed significant findings in weighted risk scores of the insulinogenic index (95% CI -4.71 (-9.4,-0.03) (p<0.05) and oral disposition index (95% CI -6.19 (-10.78,-1.6) (p<0.05) scores, respectively, which were both associated to higher scores. The unweighted risk scores revealed that fasting glucose (95% CI 1.06 (0.21, 1.91) (p<0.05) was associated with higher scores, but only with a higher BMI z-score. Researchers obtained effect modifications using a BMI z-score, and researchers observed that fasting and 2-hour glucose levels were higher for children exposed to maternal diabetes.  

The study concluded that genetic risk scores based on SNPs associated with type 2 diabetes typically found in adults show associations to glycemic and insulin metabolic traits in a multi-ethnic youth population. In addition, higher genetic risk scores for fasting glucose were associated with higher BMI levels. Lastly, BMI z-score and exposure in utero to maternal diabetes modify genetic risk scores on glucose levels. These findings add to the ongoing study of the genetic etiology of type 2 diabetes in youth populations.  

Practice Pearls: 

• Higher genetic risk scores for fasting glucose were associated with higher BMI levels. 
• BMI z-score and exposure in utero to maternal diabetes modify genetic risk scores on glucose levels. 
• Genetic risk scores based on SNPs associated with type 2 diabetes typically found in adults show associations to glycemic and insulin metabolic traits in a multi-ethnic youth population.  

Stanislawski, M. A et al. (2021, June). Genetic Risk Score for Type 2 Diabetes (T2D) and Traits Related to Glucose- Insulin Homeostasis in Youth: Exploring Perinatal Outcomes Among Children (EPOCH) Study. American Diabetes Association. (Requires ADA Symposium login.) 

Torré Anderson, II, Fourth Year Doctor of Pharmacy Candidate, Florida A&M University College of Pharmacy and Pharmaceutical Sciences, Institute of Public Health