RESUMO
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 (ß = -0.11; 95% CI -0.19, -0.02) and insulinogenic index (ß = -0.08; 95% CI -0.17, -0.001), but not with fasting glucose (ß = 0.01; 95% CI -0.01, 0.02), 2-h glucose (ß = 0.03; 95% CI -0.0004, 0.06), or HOMA-IR (ß = 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.
Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Adolescente , Glicemia , Criança , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Feminino , Glucose , Homeostase , Humanos , Insulina , Resistência à Insulina/genética , Masculino , Fenótipo , Gravidez , Fatores de RiscoRESUMO
OBJECTIVE: To examine associations of dietary changes from childhood to adolescence with adolescent hepatic fat and whether the PNPLA3 rs738409 risk allele, a strong genetic risk factor for hepatic fat, modifies associations. STUDY DESIGN: Data were from 358 participants in the Exploring Perinatal Outcomes among CHildren (EPOCH) study, a longitudinal cohort in Colorado. Diet was assessed by food frequency questionnaire in childhood (approximately 10 years of age) and adolescence (approximately 16 years of age) and converted to nutrient densities. Hepatic fat was assessed in adolescence by magnetic resonance imaging. Linear regression was used to test associations of dietary changes from childhood to adolescence with adolescent hepatic fat. RESULTS: Increases in fiber, vegetable protein, and polyunsaturated fat intake from childhood to adolescence were associated with lower adolescent hepatic fat, and increases in animal protein were associated with higher hepatic fat (ß per 5-unit increase on log-hepatic fat: -0.12 [95% CI, -0.21 to -0.02] for âµfiber; -0.26 [95% CI, -0.45 to -0.07] for âµvegetable protein; -0.18 [95% CI, -0.35 to -0.02] for âµpolyunsaturated fat; 0.13 [95% CI, 0.04-0.22] for âµanimal protein). There was evidence of effect modification by PNPLA3 variant, whereby inverse associations of âµfiber and âµvegetable protein and positive associations of âµsaturated fat with adolescent hepatic fat were stronger in risk allele carriers. Most conclusions were similar after adjusting for obesity in adolescence, but associations of âµsaturated fat with hepatic fat were attenuated toward the null. CONCLUSIONS: Our results suggest that nutrient intake changes between childhood and adolescence, particularly decreases in fiber and vegetable protein and increases in saturated fat intake, interact with the PNPLA3 variant to predict higher hepatic fat in adolescence, and may be targets for reducing hepatic fat in high-risk youth.
Assuntos
Dieta/efeitos adversos , Fígado Gorduroso/etiologia , Adolescente , Comportamento do Adolescente , Criança , Comportamento Infantil , Dieta/psicologia , Inquéritos sobre Dietas , Fígado Gorduroso/diagnóstico por imagem , Fígado Gorduroso/genética , Fígado Gorduroso/psicologia , Feminino , Interação Gene-Ambiente , Marcadores Genéticos , Predisposição Genética para Doença , Comportamentos Relacionados com a Saúde , Humanos , Modelos Lineares , Lipase/genética , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Proteínas de Membrana/genética , Estudos Prospectivos , Fatores de Risco , AutorrelatoRESUMO
OBJECTIVE: To assess the importance of genetic and nongenetic risk factors contributing to hepatic fat accumulation in a multiethnic population of youth. STUDY DESIGN: We investigated the relationship between genetic factors and hepatic fat fraction (HFF) in 347 children aged 12.5-19.5 years. We examined 5 single nucleotide polymorphisms previously associated with HFF and a weighted genetic risk score (GRS) and examined how these associations varied with ethnicity (Hispanic vs non-Hispanic white) and body mass index (BMI) category. We also compared how much variation in HFF was explained by genetic factors vs cardiometabolic factors (BMI z-score and the Homeostasis Model of Insulin Resistance) or diet. RESULTS: PNPLA3 rs738409 and the GRS were each associated with HFF among Hispanic (ß = 0.39; 95% CI, 0.16-0.62; P = .001; and ß = 0.20; 95% CI, 0.05-0.34; P = .007, respectively) but not non-Hispanic white (ß = 0.04; 95% CI, -0.18 to 0.26; P = .696; and ß = 0.03; 95% CI, -0.09 to 0.14; P = .651, respectively) youth. Cardiometabolic risk factors explained more of the variation in HFF than genetic risk factors among non-lean Hispanic individuals (27.2% for cardiometabolic markers vs 6.4% for rs738409 and 4.3% for the GRS), and genetic risk factors were more important among lean individuals (2.7% for cardiometabolic markers vs 12.6% for rs738409 and 4.4% for the GRS). CONCLUSIONS: Poor cardiometabolic health may be more important than genetic factors when predicting HFF in overweight and obese young populations. Genetic risk is an important contributor to pediatric HFF among lean Hispanics, but further studies are necessary to elucidate the strength of the association between genetic risk and HFF in non-Hispanic white youth.
Assuntos
Fígado Gorduroso/epidemiologia , Fígado Gorduroso/genética , Tecido Adiposo/anatomia & histologia , Adolescente , Índice de Massa Corporal , Criança , Estudos de Coortes , Feminino , Hispânico ou Latino , Humanos , Fígado/anatomia & histologia , Masculino , Polimorfismo de Nucleotídeo Único , Medição de Risco , População Branca , Adulto JovemRESUMO
BACKGROUND: Little is known about facility-level variation in the use of revascularization procedures for the management of stable obstructive coronary artery disease. Furthermore, it is unknown if variation in the use of coronary revascularization is associated with use of other cardiovascular procedures. METHODS AND RESULTS: We evaluated all elective coronary angiograms performed in the Veterans Affairs system between September 1, 2007, and December 31, 2011, using the Clinical Assessment and Reporting Tool and identified patients with obstructive coronary artery disease. Patients were considered managed with revascularization if they received percutaneous coronary intervention (PCI) or coronary artery bypass grafting within 30 days of diagnosis. We calculated risk-adjusted facility-level rates of overall revascularization, PCI, and coronary artery bypass grafting. In addition, we determined the association between facility-level rates of revascularization and post-PCI stress testing. Among 15 650 patients at 51 Veterans Affairs sites who met inclusion criteria, the median rate of revascularization was 59.6% (interquartile range, 55.7%-66.7%). Across all facilities, risk-adjusted rates of overall revascularization varied from 41.5% to 88.1%, rate of PCI varied from 23.2% to 80.6%, and rate of coronary artery bypass graftingvariedfrom 7.5% to 36.5%. Of 6179 patients who underwent elective PCI, the median rate of stress testing in the 2 years after PCI was 33.7% (interquartile range, 30.7%-47.1%). There was no evidence of correlation between facility-level rate of revascularization and follow-up stress testing. CONCLUSIONS: Within the Veterans Affairs system, we observed large facility-level variation in rates of revascularization for obstructive coronary artery disease, with variation driven primarily by PCI. There was no association between facility-level use of revascularization and follow-up stress testing, suggesting use rates are specific to a particular procedure and not a marker of overall facility-level use.