RESUMEN
BACKGROUND: Retinol binding protein 4 (RBP4) has been described as a link between impaired glucose uptake in adipocytes and systemic insulin sensitivity. OBJECTIVE: To determine whether RBP4 fasting levels predict the development of type 2 diabetes. METHODS: Using a case-cohort design, we followed 543 middle-aged individuals who developed diabetes and 537 who did not over ~9 years within the population-based Atherosclerosis Risk in Communities Study. Weighted Cox proportional hazards analyses permitted statistical inference of the RBP4 - incident diabetes associations to the entire cohort. RESULTS: Women in the highest tertile of RBP4 presented greater risk of developing diabetes (HR = 1.74; 95%CI 1.03 - 2.94) in analyses adjusted for age, ethnicity, study center, parental history of diabetes, hypertension, glomerular filtration rate, body mass index, waist-hip ratio, nonesterified fatty acids, adiponectin, leptin, triglycerides and HDL-C. When additionally adjusted for fasting insulin, this association's significance became borderline (HR = 1.68; 95%CI 1.00 - 2.82). No association between RBP4 levels and incident diabetes was found in men. CONCLUSION: These findings suggest that RBP4 levels may be directly involved in the pathogenesis of type 2 diabetes in women.
Asunto(s)
Diabetes Mellitus Tipo 2/epidemiología , Proteínas Plasmáticas de Unión al Retinol/análisis , Negro o Afroamericano , Aterosclerosis/sangre , Aterosclerosis/diagnóstico , Estudios de Cohortes , Ayuno , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Medición de Riesgo , Factores de Tiempo , Población BlancaRESUMEN
BACKGROUND: Chronic inflammation is related to both obesity and diabetes. Our aim was to investigate to what extent this inflammation contributes to the association between obesity and diabetes. METHODS: Using a case-cohort design, we followed 567 middle-aged individuals who developed diabetes and 554 who did not over 9 years within the ARIC Study. Weighted Cox proportional hazards analyses permitted statistical inference to the entire cohort. RESULTS: Obese individuals (BMI≥30 kg/m2), compared to those with BMI<25 kg/m2, presented a large increased risk of developing diabetes (HR[obesity]=6.4, 95%CI 4.5-9.2), as did those in the highest (compared to the lowest) quartile of waist circumference (HR[waist]=8.3, 95%CI 5.6-12.3), in analyses adjusted for age, gender, ethnicity, study center, and parental history of diabetes. Notably, further adjustment for adiponectin and inflammation markers halved the magnitude of these associations (HR[obesity]=3.2, 95%CI 2.1-4.7; and HR[waist]=4.2, 95%CI 2.8-6.5). In similar modeling, attenuation obtained by adding fasting insulin, instead of these markers, was only slightly more pronounced HR[obesity]=2.7, 95%CI 1.7-4.1; and HR[waist]=3.6, 95%CI 2.3-5.8). CONCLUSIONS: The marked decrease in the obesity-diabetes association after taking into account inflammation markers and adipokines indicates their major role in the pathways leading to adult onset of diabetes in obese individuals.
RESUMEN
Background: Retinol binding protein 4 (RBP4) has been described as a link between impaired glucose uptake in adipocytes and systemic insulin sensitivity. Objective: To determine whether RBP4 fasting levels predict the development of type 2 diabetes. Methods: Using a case-cohort design, we followed 543 middle-aged individuals who developed diabetes and 537 who did not over ~9 years within the population-based Atherosclerosis Risk in Communities Study. Weighted Cox proportional hazards analyses permitted statistical inference of the RBP4 – incident diabetes associations to the entire cohort. Results: Women in the highest tertile of RBP4 presented greater risk of developing diabetes (HR = 1.74; 95%CI 1.03 – 2.94) in analyses adjusted for age, ethnicity, study center, parental history of diabetes, hypertension, glomerular filtration rate, body mass index, waist-hip ratio, nonesterified fatty acids, adiponectin, leptin, triglycerides and HDL-C. When additionally adjusted for fasting insulin, this association's significance became borderline (HR = 1.68; 95%CI 1.00 – 2.82). No association between RBP4 levels and incident diabetes was found in men. Conclusion: These findings suggest that RBP4 levels may be directly involved in the pathogenesis of type 2 diabetes in women. .
Introdução: A proteína carreadora de retinol 4 (RBP4) tem sido descrita como elo entre uma menor captura de glicose pelos adipócitos e sensibilidade sistêmica à insulina. Objetivo: Determinar se os níveis de RBP4 em jejum predizem diabetes tipo 2. Método: Em um delineamento de caso-coorte, foram acompanhados 543 indivíduos de meia-idade que desenvolveram diabetes e 537 que não desenvolveram diabetes ao longo de 9 anos no estudo Atherosclerosis Risk in Communities Study (ARIC). Foi realizada análise ponderada de riscos proporcionais de Cox para inferência estatística da associação entre os níveis de RBP4 e diabetes incidente na coorte. Resultados: Mulheres com níveis de RBP4 no terceiro tercil apresentaram maior risco de desenvolver diabetes (HR = 1,74; 95% CI 1,03 – 2,94) em análises ajustadas para idade, etnia, centro, história familiar de diabetes, hipertensão, taxa de filtração glomerular, índice de massa corporal, razão cintura-quadril, níveis de ácidos graxos não esterificados, adiponectina, leptina, triglicerídeos e HDL-C. Quando adicionalmente ajustado para os níveis de insulina de jejum, a significância dessa associação se tornou limítrofe (HR = 1,68; 95% CI 1,00 – 2,82). Nenhuma associação foi observada entre RBP4 e diabetes incidente em homens. Conclusão: Esses achados sugerem que os níveis de RBP4 possam estar diretamente envolvidos na patogênese do diabetes tipo 2 em mulheres. .
Asunto(s)
Femenino , Humanos , Masculino , Persona de Mediana Edad , /epidemiología , Proteínas Plasmáticas de Unión al Retinol/análisis , Negro o Afroamericano , Aterosclerosis/sangre , Aterosclerosis/diagnóstico , Estudios de Cohortes , Población Blanca , Ayuno , Valor Predictivo de las Pruebas , Medición de Riesgo , Factores de TiempoRESUMEN
OBJECTIVE: Dipeptidyl peptidase IV (DPP-IV) is not only important in beta-cell function but also has proinflammatory actions. We aimed to investigate whether it could act as a link between low-grade chronic inflammation and diabetes. RESEARCH DESIGN AND METHODS: Using a case-cohort design, we followed 546 middle-aged individuals who developed diabetes and 538 who did not over approximately 9 years within the Atherosclerosis Risk in Communities study. RESULTS: In weighted analyses, the correlation between DPP-IV levels and anthropometric, inflammatory, or metabolic variables was minimal (Spearman correlations <0.11). Those who developed diabetes had mean DPP-IV values similar to those who did not (P = 0.18). Individuals in the highest quartile of DPP-IV were not at greater risk of diabetes (hazard ratio 0.88 [95% CI 0.62-1.24]) in Cox proportional hazards models adjusting for age, sex, race, study center, and multiple additional diabetes risk factors. CONCLUSIONS: Fasting DPP-IV levels do not appear to predict incident diabetes.
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Aterosclerosis/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Dipeptidil Peptidasa 4/sangre , Inflamación/epidemiología , Aterosclerosis/sangre , Aterosclerosis/inmunología , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/inmunología , Dipeptidil Peptidasa 4/inmunología , Ayuno , Femenino , Humanos , Incidencia , Inflamación/sangre , Inflamación/inmunología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Factores de Riesgo , Fumar/epidemiologíaRESUMEN
OBJECTIVE: To develop and evaluate clinical rules to predict risk for diabetes in middle-aged adults. RESEARCH DESIGN AND METHODS: The Atherosclerosis Risk in Communities is a cohort study conducted from 1987-1989 to 1996-1998. We studied 7,915 participants 45-64 years of age, free of diabetes at baseline, and ascertained 1,292 incident cases of diabetes by clinical diagnosis or oral glucose tolerance testing. RESULTS: We derived risk functions to predict diabetes using logistic regression in a random half of the sample. Rules based on these risk functions were evaluated in the other half. A risk function based on waist, height, hypertension, blood pressure, family history of diabetes, ethnicity, and age was performed similarly to one based on fasting glucose (area under the receiver-operating characteristic curve [AUC] 0.71 and 0.74, respectively; P = 0.2). Risk functions composed of the clinical variables plus fasting glucose (AUC 0.78) and additionally including triglycerides and HDL cholesterol (AUC 0.80) performed better (P < 0.001). Evaluation of scores based on the metabolic syndrome as defined by the National Cholesterol Education Program or with slight variations showed AUCs of 0.75 and 0.78, respectively. Rules based on all these approaches, while identifying 20-56% of the sample as screen positive, achieved sensitivities of 40-87% and specificities of 50-86%. CONCLUSIONS: Rules derived from clinical information, alone or combined with simple laboratory measures, can characterize degrees of diabetes risk in middle-aged adults, permitting preventive actions of appropriate intensity. Rules based on the metabolic syndrome are reasonable alternatives to rules derived from risk functions.
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Arteriosclerosis/epidemiología , Diabetes Mellitus/epidemiología , Glucemia/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Lípidos/sangre , Masculino , Persona de Mediana Edad , Estado Prediabético/epidemiología , Factores de Riesgo , Factores de Tiempo , Estados Unidos/epidemiologíaRESUMEN
To examine the association of low-grade systemic inflammation with diabetes, as well as its heterogeneity across subgroups, we designed a case-cohort study representing the approximately 9-year experience of 10,275 Atherosclerosis Risk in Communities Study participants. Analytes were measured on stored plasma of 581 incident cases of diabetes and 572 noncases. Statistically significant hazard ratios of developing diabetes for those in the fourth (versus first) quartile of inflammation markers, adjusted for age, sex, ethnicity, study center, parental history of diabetes, and hypertension, ranged from 1.9 to 2.8 for sialic acid, orosomucoid, interleukin-6, and C-reactive protein. After additional adjustment for BMI, waist-to-hip ratio, and fasting glucose and insulin, only the interleukin-6 association remained statistically significant (HR = 1.6, 1.01-2.7). Exclusion of GAD antibody-positive individuals changed associations minimally. An overall inflammation score based on these four markers plus white cell count and fibrinogen predicted diabetes in whites but not African Americans (interaction P = 0.005) and in nonsmokers but not smokers (interaction P = 0.13). The fully adjusted hazard ratio comparing white nonsmokers with score extremes was 3.7 (P for linear trend = 0.008). In conclusion, a low-grade inflammation predicts incident type 2 diabetes. The association is absent in smokers and African-Americans.