RESUMO
AIMS: To verify whether elevated fasting levels of circulating carboxymethyl lysine (CML), an advanced glycation end product, predict the development of diabetes in middle-age adults. METHODS: Using a stratified case-cohort design, we followed 543 middle-aged individuals who developed diabetes and 514 who did not over a median 9 years in the Atherosclerosis Risk in Communities Study. Weighted Cox proportional hazards analyses were used to account for the design. RESULTS: In weighted analyses, correlation between CML levels and anthropometric, inflammatory or metabolic variables was minimal (Pearson correlations usually < 0.10). CML, when modelled as a continuous variable and after adjustment for age, sex, race, centre, parental history of diabetes, BMI, waist-to-hip ratio, non-esterified fatty acids, oxidized LDL-cholesterol, GFR, smoking, an inflammation score, adiponectin, leptin, insulin and glucose levels, was associated with an increased risk of diabetes [Hazard ratio (HR) = 1.35; 95% confidence interval (CI) 1.09-1.67, for each 100 ng/ml CML increment]. Baseline glucose level and race each modified the association (P < 0.05 for interaction), which was present only among those with impaired fasting glucose (≥ 5.6 mmol/l, HR = 1.61, 95% CI 1.26-2.05) and among white participants (HR = 1.50, 95% CI 1.13-1.99). CONCLUSIONS: Elevated fasting CML, after adjustment for multiple risk factors for diabetes, predicts the development of incident diabetes, the association being present among those with impaired fasting glucose and in white participants. These prospective findings suggest that advanced glycation end products might play a role in the development of diabetes.
Assuntos
Diabetes Mellitus/sangue , Diabetes Mellitus/epidemiologia , Lisina/análogos & derivados , Aterosclerose/sangue , Estudos de Casos e Controles , Estudos de Coortes , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/epidemiologia , Feminino , Produtos Finais de Glicação Avançada/sangue , Humanos , Incidência , Lisina/sangue , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
To efficiently examine the association of glutamic acid decarboxylase antibody (GADA) positivity with the onset and progression of diabetes in middle-aged adults, we performed a case-cohort study representing the ~9-year experience of 10,275 Atherosclerosis Risk in Communities Study participants, initially aged 45-64 years. Antibodies to glutamic acid decarboxylase (GAD65) were measured by radioimmunoassay in 580 incident diabetes cases and 544 non-cases. The overall weighted prevalence of GADA positivity (>or=1 U/mL) was 7.3%. Baseline risk factors, with the exception of smoking and interleukin-6 (P
Assuntos
Autoanticorpos/sangue , Diabetes Mellitus/imunologia , Glutamato Descarboxilase/imunologia , Idade de Início , Autoanticorpos/imunologia , Biomarcadores/sangue , Estudos de Coortes , Diabetes Mellitus/enzimologia , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Radioimunoensaio , Fatores de RiscoRESUMO
To efficiently examine the association of glutamic acid decarboxylase antibody (GADA) positivity with the onset and progression of diabetes in middle-aged adults, we performed a case-cohort study representing the ~9-year experience of 10,275 Atherosclerosis Risk in Communities Study participants, initially aged 45-64 years. Antibodies to glutamic acid decarboxylase (GAD65) were measured by radioimmunoassay in 580 incident diabetes cases and 544 non-cases. The overall weighted prevalence of GADA positivity (³1 U/mL) was 7.3 percent. Baseline risk factors, with the exception of smoking and interleukin-6 (P ú 0.02), were generally similar between GADA-positive and -negative individuals. GADA positivity did not predict incident diabetes in multiply adjusted (HR = 1.04; 95 percentCI = 0.55, 1.96) proportional hazard analyses. However, a small non-significant adjusted risk (HR = 1.29; 95 percentCI = 0.58, 2.88) was seen for those in the highest tertile (³2.38 U/mL) of positivity. GADA-positive and GADA-negative non-diabetic individuals had similar risk profiles for diabetes, with central obesity and elevated inflammation markers, aside from glucose, being the main predictors. Among diabetes cases at study's end, progression to insulin treatment increased monotonically as a function of baseline GADA level. Overall, being GADA positive increased risk of progression to insulin use almost 10 times (HR = 9.9; 95 percentCI = 3.4, 28.5). In conclusion, in initially non-diabetic middle-aged adults, GADA positivity did not increase diabetes risk, and the overall baseline profile of risk factors was similar for positive and negative individuals. Among middle-aged adults, with the possible exception of those with the highest GADA levels, autoimmune pathophysiology reflected by GADA may become clinically relevant only after diabetes onset.
Assuntos
Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Autoanticorpos/sangue , Diabetes Mellitus/imunologia , Glutamato Descarboxilase/imunologia , Idade de Início , Autoanticorpos/imunologia , Biomarcadores/sangue , Estudos de Coortes , Progressão da Doença , Diabetes Mellitus/enzimologia , Seguimentos , Radioimunoensaio , Fatores de RiscoRESUMO
AIMS/HYPOTHESIS: The aim of this study was to investigate the association of leptin levels with incident diabetes in middle-aged adults, taking into account factors purportedly related to leptin resistance. SUBJECTS AND METHODS: We conducted a case-cohort study (570 incident diabetes cases and 530 non-cases) representing the 9-year experience of 10,275 participants of the Atherosclerosis Risk in Communities Study. Plasma leptin was measured by direct sandwich ELISA. RESULTS: In proportional hazards models adjusting for age, study centre, ethnicity and sex, high leptin levels (defined by sex-specific cut-off points) predicted an increased risk of diabetes, with a hazard ratio (HR) comparing the upper with the lower quartile of 3.9 (95% CI 2.6-5.6). However, after further adjusting additionally for obesity indices, fasting insulin, inflammation score, hypertension, triglycerides and adiponectin, high leptin predicted a lower diabetes risk (HR=0.40, 95% CI 0.23-0.67). Additional inclusion of fasting glucose attenuated this protective association (HR=0.59, 95% CI 0.32-1.08, p<0.03 for linear trend across quartiles). In similar models, protective associations were generally seen across subgroups of sex, race, nutritional status and smoking, though not among those with lower inflammation scores or impaired fasting glucose (interaction p=0.03 for both). CONCLUSIONS/INTERPRETATION: High leptin levels, probably reflecting leptin resistance, predict an increased risk of diabetes. Adjusting for factors purportedly related to leptin resistance unveils a protective association, independent of adiponectin and consistent with some of leptin's described protective effects against diabetes.
Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Leptina/sangue , Adiponectina/sangue , Negro ou Afro-Americano/estatística & dados numéricos , Glicemia/análise , Índice de Massa Corporal , Estudos de Casos e Controles , Estudos de Coortes , Diabetes Mellitus Tipo 2/sangue , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Incidência , Inflamação/sangue , Insulina/sangue , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Fatores de Risco , Fumar , Triglicerídeos/sangue , Estados Unidos/epidemiologia , População Branca/estatística & dados numéricosRESUMO
A close relationship between alcohol consumption and hypertension has been established, but it is unclear whether there is a threshold level for this association. In addition, it has infrequently been studied in longitudinal studies and in black people. In a cohort study, 8334 of the Atherosclerosis Risk in Communities (ARIC) Study participants, aged 45 to 64 years at baseline, who were free of hypertension and coronary heart disease had their blood pressures ascertained after 6 years of follow-up. Alcohol consumption was assessed by dietary interview. The type of alcoholic beverage predominantly consumed was defined by the source of the largest amount of ethanol consumed. Incident hypertension was defined as a systolic blood pressure >/=140 mm Hg or diastolic blood pressure >/=90 mm Hg or use of antihypertensive medication. There was an increased risk of hypertension in those who consumed large amounts of ethanol (>/=210 g per week) compared with those who did not consume alcohol over the 6 years of follow-up. The adjusted odds ratios (95% confidence interval) were 1.2 (0.85 to 1.67) for white men, 2.02 (1.08 to 3.79) for white women, and 2.31 (1.11 to 4.86) for black men. Only 4 black women reported drinking >210 g ethanol per week. At low to moderate levels of alcohol consumption (1 to 209 g per week), the adjusted odds ratios (95% confidence interval) were 0.88 (0.71 to 1.08) in white men, 0.89 (0.73 to 1.09) in white women, 1.71 (1.11 to 2.64) in black men, and 0.88 (0.59 to 1.33) in black women. Systolic and diastolic blood pressures were higher in black men who consumed low to moderate amounts of alcohol compared with the nonconsumers but not in the 3 other race-gender strata. Models with polynomial terms of alcohol exposure suggested a nonlinear association in white and black men. Higher levels of consumption of all types of alcoholic beverages were associated with a higher risk of hypertension for all race-gender strata. The consumption of alcohol in amounts >/=210 g per week is an independent risk factor for hypertension in free-living North American populations. The consumption of low to moderate amounts of alcohol also appears to be associated with a higher risk of hypertension in black men.
Assuntos
Consumo de Bebidas Alcoólicas , Hipertensão/epidemiologia , Arteriosclerose/etiologia , Estudos de Coortes , Feminino , Humanos , Hipertensão/complicações , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estatística como AssuntoRESUMO
PURPOSE: Weight gain is an important risk factor for the development of the metabolic syndrome, and inflammatory mediators are strongly associated with this syndrome. Our aim was to investigate whether inflammation predicts the development of weight gain in populations. RESEARCH METHODS AND PROCEDURES: We investigated selected markers of inflammation in the prediction of weight gain over an approximately 3-year period in a biethnic cohort of 13,017 men and women, 45 to 64 years of age, using multiple linear and logistic regression modeling. RESULTS: In adjusted models, those in the highest quartile of fibrinogen gained, during the first 3 years of follow-up, an estimated 0.23 kg/year more than those in the lowest quartile (p < 0.001). Adjusted odds of a large (greater than the 90th percentile) weight gain for those in the highest quartile of fibrinogen were 1.65 (95% confidence interval [CI], 1.38 to 1.97) times those in the lowest quartile. Similarly adjusted odds ratios for a large weight gain for those with high levels of white blood cell count, factor VIII, and von Willebrand factor were 1.38 (1.14 to 1.67), 1.28 (1.08 to 1.53), and 1.28 (1.08 to 1.51), respectively. DISCUSSION: Fibrinogen and other putative markers of inflammation predict weight gain in middle-aged adults. Given the known links between the inflammatory response and intermediary metabolism and the methodological strengths of the Atherosclerosis Risk in Communities (ARIC) cohort, these findings, though without immediate clinical applicability, suggest that inflammatory processes play a role in the development of the metabolic syndrome and cardiovascular disease in part through stimulation of weight gain.
Assuntos
Biomarcadores/sangue , Fibrinogênio/análise , Inflamação/sangue , Aumento de Peso , Arteriosclerose/sangue , Estudos de Coortes , Fator VIII/análise , Feminino , Humanos , Contagem de Leucócitos , Modelos Lineares , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fator de von Willebrand/análiseRESUMO
OBJECTIVE: Our objective was to evaluate whether selected hemostasis variables, some of which may reflect inflammation or endothelial dysfunction, are independently associated with the development of diabetes. RESEARCH DESIGN AND METHODS: We studied a biethnic cohort of 12,330 men and women, 45-64 years of age, of the Atherosclerosis Risk in Communities Study. New cases of diabetes were diagnosed by a reported physician diagnosis, hypoglycemic medication use, or a casual or fasting serum glucose level of > or = 11.1 or > or = 7 mmol/l, respectively. RESULTS: Over an average follow-up of 7 years, 1,335 new cases of diabetes were detected. The odds ratios (4th versus 1st quartile) of developing diabetes, adjusted by logistic regression for age, sex, race, study center, family history of diabetes, fasting glucose, physical activity, and smoking, were 1.2 (95% CI 1.0-1.5) for fibrinogen and 1.4 (1.1-1.6) for factor VII. Associations for factor VIII, von Willebrand factor, and activated partial thromboplastin time were found to be 1.8 (1.3-2.3), 1.4 (1.1-1.8), and 0.63 (0.49-0.82), respectively, in women. Although further adjustment for BMI and waist-to-hip ratio diminished the relationships, a highly statistically significant association (P = 0.001) remained for factor VIII (1.6 [1.2-2.1]) in women. CONCLUSIONS: Factor VIII and other hemostasis variables are associated with the development of diabetes in middle-aged adults. These findings support a role for inflammation and, particularly in women, endothelial dysfunction in the pathogenesis of type 2 diabetes.
Assuntos
Arteriosclerose/epidemiologia , Fatores de Coagulação Sanguínea/análise , Diabetes Mellitus/epidemiologia , Fator VIII/análise , Hemostasia , Arteriosclerose/prevenção & controle , Constituição Corporal , Índice de Massa Corporal , Estudos de Coortes , Diabetes Mellitus/sangue , Etnicidade , Feminino , Fibrinogênio/análise , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial , Fatores de Risco , Fatores Sexuais , Estados Unidos , Fator de von Willebrand/análiseRESUMO
BACKGROUND: Type 2 diabetes mellitus and atherosclerotic cardiovascular disease have common antecedents. Since markers of inflammation predict coronary heart disease and are raised in patients with type 2 diabetes, we investigated whether they predict whether people will develop type 2 diabetes. METHODS: 12,330 men and women, aged 45-64 years, were followed up for a mean of 7 years. We analysed the association between different markers of acute inflammation and subsequent diagnosis of diabetes. In a subgroup of 610 individuals selected originally for an unrelated atherosclerosis case-control study, we also investigated diabetes associations with total sialic acid and orosomucoid, haptoglobin, and alpha1-antitrypsin. FINDINGS: 1335 individuals had a new diagnosis of diabetes. Adjusted odds ratios for developing diabetes for quartile extremes were 1.9 (95% CI 1.6-2.3) for raised white-cell count, 1.3 (1.0-1.5) for low serum albumin, and 1.2 (1.0-1.5) for raised fibrinogen. In the subgroup analysis, individuals with concentrations of orosomucoid and sialic acid of more than the median had odds ratios of 7.9 (2.6-23.7) and 3.7 (1.4-9.8), respectively. Adjustment for body-mass index and waist-to-hip ratio lessened the associations; those for white-cell count (1.5 [1.3-1.8]), orosomucoid (7.1 [2.1-23.7]), and sialic acid (2.8 [1.0-8.1]) remained significant. INTERPRETATION: Markers of inflammation are associated with the development of diabetes in middle-aged adults. Although autoimmunity may partly explain these associations, they probably reflect the pathogenesis of type 2 diabetes.
Assuntos
Diabetes Mellitus Tipo 2/sangue , Autoimunidade , Biomarcadores , Estudos de Coortes , Diabetes Mellitus Tipo 2/imunologia , Feminino , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Orosomucoide/análise , Prognóstico , Fatores de Risco , Ácidos Siálicos/sangueRESUMO
Clustering of elevated triglycerides, decreased high-density lipoprotein cholesterol (HDL-C), hyperuricemia, diabetes, and hypertension has been related to insulin resistance/high insulin levels and central and/or overall obesity. The extent to which these abnormalities cluster and whether hyperinsulinemia, central adiposity, and overall obesity each independently associate with this clustering were evaluated in 14,481 US whites and African-Americans 45 to 64 years of age. With the exception of hypertension, abnormalities rarely existed in isolated form. Clustering greatly exceeded chance association (P < .001). Although this clustering was greater in relative terms (ratio of observed to expected cluster frequency) in the lean and less centrally obese, it was greater in absolute terms (observed minus expected cluster frequency as a percent of total population) in the more centrally and more generally obese. The greatest excesses were found for clusters that included both hypertriglyceridemia and low HDL-C. Multiple logistic regression models showed strong and independent graded relationships of clusters with quintiles of fasting insulin (fifth quintile odds ratio, 10 to 54, P < .001) and to a lesser degree with quintiles of the waist to hip ratio (2.2 to 5.4, P < .001 for most) and of body mass index (1.6 to 4.5, P < .05 for most). In conclusion, all abnormalities cluster in excess of that predicted by chance, with clusters showing remarkable and graded independent associations with fasting hyperinsulinemia and to a lesser extent with central and overall obesity. Thus, a metabolic syndrome occurs in both lean and obese middle-aged US adults.
Assuntos
Diabetes Mellitus/epidemiologia , Hiperlipidemias/epidemiologia , Hipertensão/epidemiologia , Obesidade/epidemiologia , Ácido Úrico/sangue , Análise por Conglomerados , Complicações do Diabetes , Humanos , Hiperlipidemias/complicações , Hipertensão/complicações , Insulina/sangue , Pessoa de Meia-Idade , Obesidade/complicações , Razão de ChancesRESUMO
OBJECTIVE: To describe clustering of hypertriglyceridemia, low HDL cholesterol, hypertension, diabetes, and hyperuricemia and its association with fasting insulin, waist-to-hip ratio (WHR), and BMI for African-American and white men and women. RESEARCH DESIGN AND METHODS: Observed frequencies of clusters were compared with those expected in 14,481 participants, 45-64 years of age, of the Atherosclerosis Risk in Communities (ARIC) baseline survey, 1987-1989. Associations of clusters with insulin, central adiposity, and overall obesity, as well as with abnormalities, were analyzed through multiple logistic regression. RESULTS: Clustering beyond chance was observed in all four sex/ethnic groups (P < 0.001), with 7% of the sample presenting 30% of the abnormalities in large clusters (> or = 3 abnormalities per individual). The odds ratio (OR) for the association of each abnormality with clustering of the remaining four ranged from 1.6 to 8.8 (P < 0.01). These odds of clustering were notably large in white women. Of the abnormalities, hypertriglyceridemia demonstrated the highest OR (5.0-8.8) and diabetes had the lower OR in African-American subjects than in white subjects (P < 0.001). Insulin, WHR, and BMI were statistically associated with clustering in all groups (P < 0.001, except for BMI in African-Americans.