Genetic Risk Score for Type 2 Diabetes and Traits Related to Glucose-Insulin Homeostasis in Youth: The Exploring Perinatal Outcomes Among Children (EPOCH) Study.

Abstract

OBJECTIVE:

The metabolic phenotype of youth-onset type 2 diabetes (T2D) differs from that of adult-onset T2D, but little is known about genetic contributions. We aimed to evaluate the association between a T2D genetic risk score (GRS) and traits related to glucose-insulin homeostasis among healthy youth.

RESEARCH DESIGN AND METHODS:

We used data from 356 youth (mean age 16.7 years; 50% female) in the Exploring Perinatal Outcomes Among Children (EPOCH) cohort to calculate a standardized weighted GRS based on 271 single nucleotide polymorphisms associated with T2D in adults. We used linear regression to assess associations of the GRS with log-transformed fasting glucose, 2-h glucose, HOMA of insulin resistance (HOMA-IR), oral disposition index, and insulinogenic index adjusted for age, sex, BMI z score, in utero exposure to maternal diabetes, and genetic principal components. We also evaluated effect modification by BMI z score, in utero exposure to maternal diabetes, and ethnicity.

RESULTS:

Higher weighted GRS was associated with lower oral disposition index (β = -0.11; 95% CI -0.19, -0.02) and insulinogenic index (β = -0.08; 95% CI -0.17, -0.001), but not with fasting glucose (β = 0.01; 95% CI -0.01, 0.02), 2-h glucose (β = 0.03; 95% CI -0.0004, 0.06), or HOMA-IR (β = 0.02; 95% CI -0.04, 0.07). BMI z score and in utero exposure to maternal diabetes increased the effect of the GRS on glucose levels.

CONCLUSIONS:

Our results suggest that T2D genetic risk factors established in adults are relevant to glucose-insulin homeostasis in youth and that maintaining a healthy weight may be particularly important for youth with high genetic risk of T2D.

• Authors: Maggie A Stanislawski, Elizabeth Litkowski, Sridharan Raghavan, Kylie K Harrall, Jessica Shaw, Deborah H Glueck, Ethan M Lange, Dana Dabelea, Leslie A Lange
• Journal: Diabetes care (Diabetes Care) Vol. 44 Issue 9 Pg. 2018-2024 (09 2021) ISSN: 1935-5548 [Electronic] United States
• PMID: 34257098 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 by the American Diabetes Association.

Chemical References

• Blood Glucose
• Insulin
• Glucose

Topics

• Adolescent
• Blood Glucose
• Child
• Diabetes Mellitus, Type 2 (epidemiology, genetics)
• Female
• Glucose
• Homeostasis
• Humans
• Insulin
• Insulin Resistance (genetics)
• Male
• Phenotype
• Pregnancy
• Risk Factors