Assuntos
Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/mortalidade , Idoso , Doenças Cardiovasculares/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Doença Pulmonar Obstrutiva Crônica/complicações , Fatores de RiscoRESUMO
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: The census classification of Hispanic origin is used in epidemiological studies to group individuals, even though there is geographical, cultural, and genetic diversity within Hispanic Americans of purportedly similar backgrounds. We observed differences in our measures of adiposity between our two Mexican American populations, and examined whether these differences were attributed to social, behavioral, physiologic or genetic differences between the two populations. RESEARCH DESIGN AND METHODS: In the IRAS Family Study, we examined 478 Hispanics from San Antonio, Texas and 447 Hispanics from the San Luis Valley, Colorado. Associations with body mass index (BMI), visceral adipose tissue area (VAT), and subcutaneous adipose tissue area (SAT) using social, behavioral, physiologic and genetic variables were examined. RESULTS: Hispanics of Mexican origin in our clinic population in San Antonio had significantly higher mean BMI (31.09 vs. 28.35 kg/m2), VAT (126.3 vs. 105.5 cm2), and SAT (391.6 vs. 336.9 cm2), than Hispanics of Mexican origin in the San Luis Valley. The amount of variation in adiposity explained by clinic population was 4.5% for BMI, 2.8% for VAT, and 2.7% for SAT. After adjustment, clinic population was no longer associated with VAT and SAT, but remained associated with BMI, although the amount of variation explained by population was substantially less (1.0% for BMI). CONCLUSION: Adiposity differences within this population of Mexican origin can be largely explained by social, behavioral, physiologic and genetic differences.
Assuntos
Adiposidade/genética , Adiposidade/fisiologia , Americanos Mexicanos/genética , Adulto , Índice de Massa Corporal , Distribuição de Qui-Quadrado , Colorado/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Marcadores Genéticos , Genótipo , Comportamentos Relacionados com a Saúde , Humanos , Estilo de Vida , Masculino , Fenótipo , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Texas/epidemiologia , Vitamina D/sangueRESUMO
CONTEXT: Mexican-Americans have more diabetes than non-Hispanic whites, but the extent to which insulin resistance and insulin secretion explain the ethnic difference is unknown. OBJECTIVE: We analyzed selected indices of insulin resistance and secretion for both the ethnic difference and predictive discrimination. DESIGN AND SETTING: The San Antonio Heart Study is a longitudinal population-based study with a follow-up period of 7.5 yr. PARTICIPANTS: A total of 1540 nondiabetic individuals aged 25-64 yr were enrolled from January 1984 to December 1988. INTERVENTIONS: Homeostasis model assessment (HOMA) of insulin resistance and secretion were estimated by available formulas (HOMA-IR and HOMA ß-cell) and computer program (HOMA2S and HOMA2B). Matsuda index and insulinogenic index from 0 to 30 and 0 to 120 min (ΔI0-30/ΔG0-30 and ΔI0-120/ΔG0-120) were also calculated. MAIN OUTCOME MEASURE: Incident diabetes was defined by the 2003 American Diabetes Association criteria. RESULTS: Incident diabetes was in excess in Mexican-Americans [odds ratio 2.26 (95% confidence interval, 1.53-3.34)]. Matsuda index explained a larger proportion of the ethnic difference than did HOMA-IR (49.2 vs. 31.0%; P<0.001). The ethnic difference was not explained by measures of insulin secretion. Matsuda index and ΔI0-30/ΔG0-30 had a better predictive discrimination than their HOMA equivalents and ΔI0-120/ΔG0-120. HOMA estimates by the computer program offered no advantage over simple formulas for HOMA. CONCLUSIONS: Insulin resistance accounts for a large and significant proportion of the excess risk of diabetes in Mexican-Americans. Matsuda index is better than HOMA-IR for both explaining the ethnic difference and predicting diabetes.
Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etiologia , Resistência à Insulina/fisiologia , Americanos Mexicanos , Adulto , Glicemia , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Seguimentos , Teste de Tolerância a Glucose , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Risco , Fatores de RiscoRESUMO
The authors explored whether the waist circumference (WC) cutoffs currently proposed to define abdominal obesity (AO) are associated with diabetes and cardiovascular disease (CVD) in Latin America. Primary care physicians in 12 countries were randomly chosen to measure WC and body mass index and record the presence of diabetes and CVD in all consecutive adult patients, consulting them on 2 prespecified half-days. Overall, 70% of 9719 men, and 76% of 18,526 women had AO. Diabetes was reported in 10% of men and 9% of women and CVD in 9% of men and 7% of women. AO was significantly related with diabetes (age-adjusted odds ratio, 1.63 for men and 2.86 for women) and with CVD (odds ratio, 1.41 for men and 1.62 for women). Obesity was also significantly related with diabetes and CVD. Strikingly, abdominal adiposity was very frequent in women with normal body mass index, suggesting that an evidence-based definition of abdominal adiposity in Latin America is needed.
Assuntos
Gordura Abdominal , Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Obesidade/complicações , Adulto , Fatores Etários , Índice de Massa Corporal , Doenças Cardiovasculares/epidemiologia , Intervalos de Confiança , Feminino , Hispânico ou Latino , Humanos , América Latina/epidemiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Fatores SexuaisRESUMO
OBJECTIVE: We hypothesized that interaction between PPARG2 Pro12Ala and variants in the promoter region of HNF4A are associated with type 2 diabetes-related quantitative traits in Mexican-American families of a proband with previous gestational diabetes. RESEARCH DESIGN AND METHODS: The BetaGene project genotyped PPARG2 Pro12Ala and nine HNF4A single nucleotide polymorphisms (SNPs) in 473 individuals in 89 families. Members of the proband generation had fasting glucose <126 mg/dl and were phenotyped by oral and intravenous glucose tolerance tests. RESULTS: Neither PPARG2 Pro12Ala nor any of the nine HNF4A SNPs were independently associated with type 2 diabetes-related quantitative traits. However, the interaction between PPARG2 Pro12Ala and HNF4A rs2144908 was significantly associated with both insulin sensitivity (S(I)) (Bonferroni P = 0.0006) and 2-h insulin (Bonferroni P = 0.039). Subjects with at least one PPARG2 Ala allele and homozygous for the HNF4A rs2144908 A allele had 40% higher S(I) compared with individuals with at least one G allele. S(I) did not vary by rs2144908 genotype among PPARG2 Pro/Pro. The interaction result for S(I) was replicated by the Insulin Resistance Atherosclerosis Family Study (P = 0.018) in their San Antonio sample (n = 484) where subjects with at least one PPARG2 Ala allele and homozygous for the HNF4A rs2144908 A allele had a 29% higher S(I) compared with individuals with at least one G allele. However, the interaction was not replicated in their San Luis Valley sample (n = 496; P = 0.401). CONCLUSIONS: Together, these results suggest that variation in PPARG2 and HNF4A may interact to regulate insulin sensitivity in Mexican Americans at risk for type 2 diabetes.
Assuntos
Diabetes Mellitus Tipo 2/genética , Diabetes Gestacional/genética , Variação Genética , Fator 4 Nuclear de Hepatócito/metabolismo , Hispânico ou Latino/genética , Insulina/fisiologia , PPAR gama/metabolismo , Regiões Promotoras Genéticas , Substituição de Aminoácidos , Feminino , Humanos , Masculino , Fenótipo , Polimorfismo de Nucleotídeo Único , Gravidez , Fatores de Risco , São Francisco , Irmãos , TexasRESUMO
OBJECTIVE: The purpose of this study was to test whether carotid intima-media thickness (IMT) is already increased in normotensive subjects who progress to hypertension (confirmed prehypertensives) independently of known determinants of vessel wall thickness. METHODS AND RESULTS: Common carotid artery (CCA) far-wall IMT was measured (B-mode ultrasound) in 1536 subjects from the population-based Mexico City Diabetes Study at baseline and 3.5 years later. In the 136 confirmed prehypertensives, CCA-IMT (720 [253] microm, median[interquartile range]) was intermediate between normotensives (615 [140] microm) and hypertensives (725 [215] microm). After multiadjusting for gender, age, BMI, blood pressure, total cholesterol, antihypertensive therapy, and diabetes, converter status was independently associated with a higher CCA-IMT (+93+/-14 microm). At follow-up, CCA-IMT increased by 35 [180] microm. Gender, age, blood pressure, and presence of diabetes, but not the converter status, were significant independent predictors of CCA-IMT progression. In a model adjusting for gender, age, blood pressure (level, status and treatment), diabetes status, total and HDL-cholesterol, the G variant of the 45T/G polymorphism of the adiponectin gene was associated with a hazard ratio of 1.45 (95% CI: 1.04 to 2.01) of a baseline CCA-IMT in the top quintile. CONCLUSIONS: In confirmed prehypertensives, CCA-IMT is increased independently of blood pressure and known determinants of wall thickness, but short-term CCA-IMT progression is not accelerated.
Assuntos
Doenças das Artérias Carótidas/patologia , Artéria Carótida Primitiva/patologia , Hipertensão/complicações , Túnica Íntima/patologia , Túnica Média/patologia , Adiponectina/genética , Adulto , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/etiologia , Doenças das Artérias Carótidas/genética , Artéria Carótida Primitiva/diagnóstico por imagem , Bases de Dados como Assunto , Progressão da Doença , Feminino , Seguimentos , Predisposição Genética para Doença , Humanos , Hipertensão/diagnóstico por imagem , Hipertensão/genética , Hipertensão/patologia , Modelos Logísticos , Estudos Longitudinais , Masculino , México , Pessoa de Meia-Idade , Polimorfismo Genético , Medição de Risco , Fatores de Risco , Fatores de Tempo , Túnica Íntima/diagnóstico por imagem , Túnica Média/diagnóstico por imagem , UltrassonografiaAssuntos
Síndrome Metabólica/epidemiologia , Relação Cintura-Quadril , Biomarcadores/sangue , Glicemia/análise , Proteína C-Reativa/análise , Humanos , Inflamação/fisiopatologia , Resistência à Insulina , Síndrome Metabólica/sangue , Síndrome Metabólica/fisiopatologia , México/epidemiologia , Obesidade/complicações , Valores de Referência , Fatores de Risco , Espanha/epidemiologiaRESUMO
OBJECTIVE: We have carried out international comparisons of the metabolic syndrome using the International Diabetes Federation (IDF) and National Cholesterol Education Program-Adult Treatment Panel III (ATP III) definitions. This analysis could help to discern the applicability of these definitions across populations. RESEARCH DESIGN AND METHODS: Nondiabetic subjects aged 35-64 years were eligible for analysis in population-based studies from San Antonio (Mexican Americans and non-Hispanic whites, n = 2,473), Mexico City (n = 1,990), Spain (n = 2,540), and Peru (n = 346). Kappa statistics examined the agreement between metabolic syndrome definitions. RESULTS: Because of the lower cutoff points for elevated waist circumference, the IDF definition of the metabolic syndrome generated greater prevalence estimates than the ATP III definition. Prevalence difference between definitions was more significant in Mexican-origin and Peruvian men than in Europid men from San Antonio and Spain because the IDF definition required ethnic group-specific cutoff points for elevated waist circumference. ATP III and IDF definitions disagreed in the classification of 13-29% of men and 3-7% of women. In men, agreement between these definitions was 0.54 in Peru, 0.43 in Mexico City, 0.62 in San Antonio Mexican Americans, 0.69 in San Antonio non-Hispanic whites, and 0.64 in Spain. In women, agreement between definitions was 0.87, 0.89, 0.86, 0.87, and 0.93, respectively. CONCLUSIONS: The IDF definition of the metabolic syndrome generates greater prevalence estimates than the ATP III definition. Agreement between ATP III and IDF definitions was lower for men than for women in all populations and was relatively poor in men from Mexico City.
Assuntos
Síndrome Metabólica/classificação , Adulto , Feminino , Inquéritos Epidemiológicos , Humanos , Internacionalidade , Masculino , Síndrome Metabólica/epidemiologia , México/epidemiologia , Pessoa de Meia-Idade , Peru/epidemiologia , Prevalência , Espanha/epidemiologia , Texas/epidemiologia , Instituições Filantrópicas de SaúdeRESUMO
OBJECTIVE: Trends in the metabolic syndrome might follow trends in obesity. We examined this hypothesis in the Mexico City Diabetes Study (MCDS), a study that showed rising trends in obesity, and the effect of the metabolic syndrome on the risk of coronary heart disease (CHD). RESEARCH DESIGN AND METHODS: Designed as a population-based study, the MCDS enrolled subjects in 1990-1992 (n = 2,282). Follow-up visits were held in 1993-1995 (n = 1,764) and 1997-1999 (n = 1,754). We used the revised metabolic syndrome definition of the National Cholesterol Education Program and the Framingham equations to estimate the 10-year CHD risk. RESULTS: In men, the age-adjusted prevalence of the metabolic syndrome was 38.9% in 1990-1992, 43.4% in 1993-1995, and 39.9% in 1997-1999; in women, the prevalences were 65.4, 65.7, and 59.9%, respectively. The prevalence did not change in men (P = 0.349) between 1990-1992 and 1997-1999, but decreased in women (P < 0.001). A prevalence increase was demonstrated for elevated waist circumference (men, P < 0.001; women, P < 0.050), elevated fasting glucose value (men and women, P < 0.001), and low HDL cholesterol level (men, P < 0.050; women, P < 0.010); a prevalence decrease was seen for high blood pressure (men and women, P < 0.001) and hypertriglyceridemia (men, P < 0.001; women, P < 0.010). CHD risk decreased marginally in men (P < 0.050) but did not change in women (P = 0.943). CONCLUSIONS: Neither the prevalence of the metabolic syndrome nor CHD risk has increased in Mexico City. Lower blood pressure and triglyceride values appear to have counteracted increases in central obesity and fasting glucose.