Diabetes care · 2021
Genetic Risk Score for Type 2 Diabetes and Traits Related to Glucose-Insulin Homeostasis in Youth: The Exploring Perinatal Outcomes Among Children (EPOCH) Study.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Stanislawski Maggie A, Litkowski Elizabeth, Raghavan Sridharan, Harrall Kylie K, Shaw Jessica, Glueck Deborah H, Lange Ethan M, Dabelea Dana, Lange Leslie A
Аннотация
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.
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.