RESUMO
OBJECTIVE: The GUARDIAN (Genetics UndeRlying DIAbetes in HispaNics) consortium is described, along with heritability estimates and genetic and environmental correlations of insulin sensitivity and metabolic clearance rate of insulin (MCRI). METHODS: GUARDIAN is comprised of seven cohorts, consisting of 4,336 Mexican-American individuals in 1,346 pedigrees. Insulin sensitivity (SI ), MCRI, and acute insulin response (AIRg) were measured by frequently sampled intravenous glucose tolerance test in four cohorts. Insulin sensitivity (M, M/I) and MCRI were measured by hyperinsulinemic-euglycemic clamp in three cohorts. Heritability and genetic and environmental correlations were estimated within the family cohorts (totaling 3,925 individuals) using variance components. RESULTS: Across studies, age, and gender-adjusted heritability of insulin sensitivity (SI , M, M/I) ranged from 0.23 to 0.48 and of MCRI from 0.35 to 0.73. The ranges for the genetic correlations were 0.91 to 0.93 between SI and MCRI; and -0.57 to -0.59 for AIRg and MCRI (all P < 0.0001). The ranges for the environmental correlations were 0.54 to 0.74 for SI and MCRI (all P < 0.0001); and -0.16 to -0.36 for AIRg and MCRI (P < 0.0001-0.06). CONCLUSIONS: These data support a strong familial basis for insulin sensitivity and MCRI in Mexican Americans. The strong genetic correlations between MCRI and SI suggest common genetic determinants.
Assuntos
Diabetes Mellitus Tipo 2/genética , Resistência à Insulina/genética , Insulina/metabolismo , Taxa de Depuração Metabólica/genética , Americanos Mexicanos/genética , Adulto , Idoso , Estudos de Coortes , Colorado , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Estudo de Associação Genômica Ampla , Técnica Clamp de Glucose , Teste de Tolerância a Glucose , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Estudos Retrospectivos , TexasRESUMO
OBJECTIVE: To study the relationships between nontraditional cardiovascular (CV) risk factors and components of the metabolic syndrome in Native Canadian children, a population at risk of future CV disease. STUDY DESIGN: CV risk factors were evaluated in a population-based study of a Canadian Oji-Cree community, involving 236 children aged 10 to 19 years. RESULTS: Using an age- and sex-specific case definition, 18.6% of the children met criteria for pediatric metabolic syndrome. As the number of metabolic syndrome component criteria increased, C-reactive protein, leptin, and ratio of apolipoprotein B to apolipoprotein A1 levels rose (all P < .0001) and adiponectin concentration decreased (P = .0006). Principal factor analysis using both traditional and nontraditional CV risk factors revealed 5 underlying core traits, defined as follows: adiposity, lipids/adiponectin, inflammation, blood pressure, and glucose. CONCLUSIONS: Nontraditional CV risk factors accompany the accrual of traditional risk factors early in the progression to pediatric metabolic syndrome. Furthermore, inclusion of these factors in factor analysis suggests that 5 core traits underlie the early development of an enhanced CV risk factor profile in Native children.
Assuntos
Doenças Cardiovasculares/sangue , Síndrome Metabólica/sangue , Adiponectina/sangue , Adolescente , Adulto , Apolipoproteína A-I/sangue , Glicemia/análise , Pressão Sanguínea , Constituição Corporal , Proteína C-Reativa/análise , Canadá/epidemiologia , Doenças Cardiovasculares/etiologia , Criança , HDL-Colesterol/sangue , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Análise Fatorial , Jejum , Feminino , Humanos , Interleucina-6/sangue , Leptina/sangue , Masculino , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Fatores de Risco , Proteína Amiloide A Sérica/análise , Fatores Sexuais , Triglicerídeos/sangueRESUMO
To determine and formally compare the ability of simple indexes of insulin resistance (IR) to predict type 2 diabetes, we used combined prospective data from the San Antonio Heart Study, the Mexico City Diabetes Study, and the Insulin Resistance Atherosclerosis Study, which include well-characterized cohorts of non-Hispanic white, African-American, Hispanic American, and Mexican subjects with 5-8 years of follow-up. Poisson regression was used to assess the ability of each candidate index to predict incident diabetes at the follow-up examination (343 of 3,574 subjects developed diabetes). The areas under the receiver operator characteristic (AROC) curves for each index were calculated and statistically compared. In pooled analysis, Gutt et al.'s insulin sensitivity index at 0 and 120 min (ISI(0,120)) displayed the largest AROC (78.5%). This index was significantly more predictive (P < 0.0001) than a large group of indexes (including those by Belfiore, Avignon, Katz, and Stumvoll) that had AROC curves between 66 and 74%. These findings were essentially similar both after adjustment for covariates and when analyses were conducted separately by glucose tolerance status and ethnicity/study subgroups. In conclusion, we found substantial differences between published IR indexes in the prediction of diabetes, with ISI(0,120) consistently showing the strongest prediction. This index may reflect other aspects of diabetes pathogenesis in addition to IR, which might explain its strong predictive abilities despite its moderate correlation with direct measures of IR.