RESUMO
OBJECTIVE: Chronic kidney disease (CKD) predicts cardiovascular disease (CVD) in the general population. We investigated the effects of stages of renal function using the estimated glomerular filtration rate (eGFR) on all-cause mortality and cardiovascular end points in a prospective cohort of Chinese type 2 diabetic patients. RESEARCH DESIGN AND METHODS: Between 1995 and 2000, 4,421 patients without macrovascular disease or end-stage renal disease were recruited. Renal function was assessed by eGFR, as calculated by the abbreviated Modification of Diet in Renal Disease Study Group formula. Clinical end points included all-cause mortality, cardiovascular end point (cardiovascular death, new admissions due to angina, myocardial infarction, stroke, revascularization, or heart failure), and renal end point (reduction in eGFR by >50%, progression of eGFR to stage 5, or dialysis or renal death). RESULTS: After a median follow-up period of 39.4 months (interquartile range 20.3-55), all-cause mortality rate increased from 1.2% (95% CI 0.8-1.7) to 18.3% (9.1-27.5) (P for trend <0.001) as renal function deteriorated from stage 1 (eGFR > or =90 ml/min per 1.73 m(2)) to stage 4 (15-29 ml/min per 1.73 m(2)). The respective rate of new cardiovascular end points also increased from 2.6% (2.0-3.3) to 25.3% (15.0-35.7) (P for trend <0.001). After adjustment for covariates (age, sex, albuminuria, use of renin-angiotensin-aldosterone system [RAAS] inhibitors, lipids, blood pressure, and glycemic control), hazard ratios across different stages of eGFR (> or =90, 60-89, 30-59, and 15-29 ml/min per 1.73 m(2)) for all-cause mortality were 1.00, 1.27, 2.34, and 9.82 (P for trend <0.001), for cardiovascular end points were 1.00, 1.04, 1.05, and 3.23 (P for trend <0.001), and for renal end points were 1.00, 1.36, 3.34, and 27.3 (P for trend <0.001), respectively. CONCLUSIONS: Chinese type 2 diabetic patients with reduced eGFR were at high risk of developing cardiovascular end points and all-cause mortality, independent of albuminuria and metabolic control.
Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Taxa de Filtração Glomerular , Insuficiência Renal/fisiopatologia , Adulto , Idoso , Análise de Variância , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Insuficiência Renal/complicações , Insuficiência Renal/mortalidade , Fatores de Risco , Taxa de SobrevidaRESUMO
BACKGROUND: Herpesvirus infection is a possible risk factor for atherogenesis, and diabetics may be at particular risk. Endothelial dysfunction is an early marker for atherosclerosis, and the present study tests the hypotheses that (1) prior infection with cytomegalovirus (CMV) and herpes simplex virus (HSV) is associated with endothelial dysfunction and (2) this may be more marked in diabetics. METHODS AND RESULTS: Serum samples were tested for anti-IgG antibodies to CMV and HSV from 400 subjects (mean age for diabetics and nondiabetics, 37.8+/-4.3 and 37.9+/-3.7 [SD]). We also assessed Helicobacter pylori and Chlamydia pneumoniae serology. Coronary atheroma was quantified by means of electron beam computed tomography. Subjects (n=157) underwent venous occlusion plethysmography with acetylcholine, bradykinin, glyceryl trinitrate, norepinephrine, and l-NG-monomethyl-l-arginine. Individuals who were seropositive for CMV had reduced responses to bradykinin (P=0.005) and glyceryl trinitrate (P=0.006). The reduced response to bradykinin remained significant (P=0.045) after adjusting for the response to glyceryl trinitrate and was independent of conventional risk factors. Positive serology for the other organisms did not have an independent effect on reactivity. There was a weaker association between CMV and coronary artery calcification (P=0.09). Positive serology for each of the other pathogens did not affect reactivity, but there was a relation between total pathogen burden and impaired vascular reactivity. No significant differences were found between diabetics and nondiabetics. CONCLUSIONS: This study shows that CMV-seropositive individuals have endothelial dysfunction and impaired responses to NO. This association was independent of conventional risk factors and may be associated with increased atherosclerosis burden.
Assuntos
Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/fisiopatologia , Sistema Vasomotor/fisiopatologia , Adulto , Anticorpos Antivirais/sangue , Área Sob a Curva , Pressão Sanguínea , Proteína C-Reativa/análise , Infecções por Chlamydophila/diagnóstico , Infecções por Chlamydophila/epidemiologia , Infecções por Chlamydophila/fisiopatologia , Estudos de Coortes , Comorbidade , Doença da Artéria Coronariana/epidemiologia , Infecções por Citomegalovirus/epidemiologia , Diabetes Mellitus/epidemiologia , Feminino , Antebraço/irrigação sanguínea , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/fisiopatologia , Herpes Simples/diagnóstico , Herpes Simples/epidemiologia , Herpes Simples/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fluxo Sanguíneo Regional , Estudos Soroepidemiológicos , Distribuição por Sexo , Classe Social , Reino Unido/epidemiologia , VasodilatadoresRESUMO
CONTEXT: Age-related declines in testosterone and IGF-I are associated with deposition of visceral fat, a component of the metabolic syndrome (MES). OBJECTIVE: Testosterone and IGF-I may interact with familial disposition to diabetes mellitus to increase the association with MES. DESIGN: We conducted a cross-sectional cohort study. SETTING: The study was conducted in a university teaching hospital. SUBJECTS: Study subjects included 179 middle-aged men with a family history of diabetes (FH) (aged 39.1 +/- 8.1 yr) and 128 men without FH (aged 43.8 +/- 8.5 yr). MAIN OUTCOME MEASURES: Clinical characteristics, frequency of MES using the World Health Organization criteria with Asian definitions of obesity (body mass index > or = 25 kg/m2), and serum levels of total testosterone, IGF-I, and high-sensitive C-reactive protein (hs-CRP) were measured. RESULTS: Men with FH had higher frequency of MES than those without FH [39.1 vs. 23.4% (P = 0.004)]. On multivariate analysis, smoking (former and current smokers), low total testosterone, and IGF-I but elevated hs-CRP levels explained 35% of the MES variance in men with FH. The frequency of MES increased with declining tertiles of total testosterone and IGF-I but increasing tertiles of hs-CRP. After adjustment for age and smoking history, subjects with all three risk factors had a 13-fold increase in risk association with MES compared with those without hormonal and inflammatory risk factors. These risk associations were not found in men without FH in whom only smoking (ex and current) and low total testosterone level were independent predictors for MES, which explained 14% of the variance. CONCLUSIONS: Clustering of FH, hormonal abnormalities, and high hs-CRP is associated with MES in Chinese middle-aged men.
Assuntos
Povo Asiático/genética , Proteína C-Reativa/metabolismo , Diabetes Mellitus Tipo 2/genética , Fator de Crescimento Insulin-Like I/metabolismo , Síndrome Metabólica/sangue , Testosterona/sangue , Adulto , Estudos de Coortes , Estudos Transversais , Humanos , Masculino , Prontuários Médicos , Síndrome Metabólica/etiologia , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
OBJECTIVES: There are close associations among raised white blood cell (WBC) count, coronary heart disease, and metabolic syndrome in the general population. The association between WBC count and vascular complications of diabetes has not been explored. We carried out a cross-sectional cohort study to determine the association between WBC count and the presence of macro- and microvascular complications in type 2 diabetes. RESEARCH DESIGN AND METHODS: In this study, 3,776 patients with type 2 diabetes and normal WBC count (3.5-12.5 x 10(9)/l) underwent a comprehensive assessment of complications and cardiovascular risk factors based on the European DiabCare protocol. Demographic and anthropometric parameters were recorded. Metabolic profiles, including complete blood picture and urinary albumin excretion, were measured. RESULTS: Patients with higher WBC counts (categorized into quintiles) had adverse metabolic profiles as evidenced by higher blood pressure, BMI, HbA(1c), fasting plasma glucose, LDL cholesterol, triglycerides, and urinary albumin excretion, but lower HDL cholesterol (all P <0.001 for trend). The prevalence of macro- and microvascular complications increased in a dosage-related manner with WBC count. After adjustments for smoking and other known cardiovascular risk factors, a 1-unit (1 x 10(9)/l) increment of WBC count was associated with a 15.8% (95% CI 9.3-22.6; P < 0.001) and 12.3% increase (5.8-19.1; P < 0.001) in the prevalence of macro- and microvascular complications, respectively. CONCLUSIONS: Elevated WBC count, even within the normal range, is associated with both macro- and microvascular complications in type 2 diabetes. Chronic inflammation, as indicated by a higher WBC count, may play a linkage role in the development of macro- and microvascular complications in diabetes.
Assuntos
Povo Asiático , Diabetes Mellitus Tipo 2/epidemiologia , Angiopatias Diabéticas/epidemiologia , Contagem de Leucócitos , Albuminúria/epidemiologia , Glicemia/análise , Pressão Sanguínea , Índice de Massa Corporal , Colesterol/sangue , Creatinina/sangue , Nefropatias Diabéticas/epidemiologia , Retinopatia Diabética/epidemiologia , Feminino , Hong Kong/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Fumar , Triglicerídeos/sangueRESUMO
The effect of biphosphonate therapy on bone mineral density (BMD) in patients with primary hyperparathyroidism (PHP) is unknown. Forty postmenopausal women (mean age, 70 yr) with PHP were randomized to receive alendronate 10 mg/d or placebo for 48 wk, followed by treatment withdrawal for 24 wk. The mean (+/-SD) changes in BMD at femoral neck (+4.17 +/- 6.01% vs. -0.25 +/- 3.3%; P = 0.011) and lumbar spine (+3.79 +/- 4.04% vs. 0.19 +/- 2.80%; P = 0.016) were significantly higher with alendronate at 48 wk. Serum calcium was reduced with alendronate but not placebo (-0.09 vs. +0.01 mmol/liter; P = 0.018). Serum bone-specific alkaline phosphatase activity was lower with alendronate from 12 wk onward and increased 24 wk after treatment withdrawal (21.1 +/- 12.8 to 7.3 +/- 4.9 IU/liter at 48 wk, and 15.0 +/- 14.8 IU/liter 24 wk after withdrawal; P = 0.002 for trend). Osteocalcin concentration decreased at 48 wk and increased 24 wk after alendronate withdrawal (P = 0.019 for trend of change over time) but not with placebo. Urinary N-telopeptide/creatinine ratio decreased with alendronate at 48 wk and increased 24 wk after treatment withdrawal (P = 0.008 for trend). N-telopeptide/creatinine ratio did not change with placebo. Alendronate improves BMD and reduces bone turnover markers in postmenopausal women with PHP.
Assuntos
Alendronato/administração & dosagem , Densidade Óssea/efeitos dos fármacos , Hiperparatireoidismo/tratamento farmacológico , Administração Oral , Idoso , Alendronato/efeitos adversos , Biomarcadores , Cálcio/sangue , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Pós-MenopausaAssuntos
Anti-Hipertensivos/efeitos adversos , Diabetes Mellitus Tipo 2/induzido quimicamente , Hipertensão/tratamento farmacológico , Idoso , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Estudos de Coortes , Diabetes Mellitus Tipo 2/epidemiologia , HumanosRESUMO
Metabolic syndrome, also known as the insulin resistance syndrome (IRS), dysmetabolic syndrome or syndrome X, is a burgeoning global epidemic. This constellation of risk factors, namely glucose intolerance, hypertension, dyslipidemia (high triglyceride and low HDL cholesterol), central obesity, pro-inflammatory and prothrombotic state, culminating to the development of premature cardiovascular and renal disease, has significant impact on life expectancy, societal productivity and quality of life. The underlying mechanism of this complex syndrome remains to be elucidated. In recent years, light has been shed on the roles of neuroendocrine system and adipocytokines on the pathogenesis of IRS. In this review, we summarize the possible links between insulin and various hormones (growth hormones (GH), catecholamines, glucocorticoids and sex hormones), partly mediated through visceral adiposity and adipocytokines (notably adiponectin, leptin, resistin, visfatin, tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6)) in the pathogenesis of this syndrome.
Assuntos
Adipocinas/fisiologia , Adiponectina/fisiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Síndrome Metabólica/fisiopatologia , Envelhecimento , Animais , Intolerância à Glucose/fisiopatologia , Hormônio do Crescimento/fisiologia , Hormônio do Crescimento Humano/fisiologia , Humanos , Resistência à Insulina , Interleucina-6/fisiologia , Modelos Biológicos , Fator de Necrose Tumoral alfa/fisiologiaRESUMO
The Metabolic syndrome (MetS), obesity and type 2 diabetes are growing global epidemics especially in Asian populations. In light of the differences in body build between people from the West and the East, definitions of obesity in Asians have been modified accordingly. Data from Hong Kong, an epitome of future China, may provide important insight into the potential interactions between nature and nurture in this global epidemic. Now supported by large scale studies, it is clear that Chinese type 2 diabetic patients exhibit marked phenotypic heterogeneity in terms of risk profiles and complications. Apart from genetic differences, age- and stress-related neurohormonal dysregulation may also contribute to the increasing prevalence of obesity, type 2 diabetes and MetS in Chinese living in modern societies. In this mini-review, we aim to summarise findings from our group collected during the last decade in our attempt to understand this epidemic and to develop evidence-based care models to reduce the impact of this health hazard.
RESUMO
PURPOSE: We developed a disease management program for patients with Type 2 diabetic nephropathy and evaluated its effects on the time to onset of end-stage renal disease or all-cause death compared with usual care. METHODS: In a 2-year, prospective cohort study, we compared the clinical outcomes of patients managed by a structured care protocol (n = 80) to a group receiving usual care (n=80) in the same hospital. Patients aged < or =80 years with type 2 diabetes, serum creatinine 150-400 micromol/L, and micro- or macroalbuminuria were recruited. The structured care protocol was implemented by a pharmacist-diabetes specialist team with particular emphasis on periodic laboratory assessments, patient adherence, risk factors control, and use of renin-angiotensin system inhibitor. The primary endpoint was the composite of end-stage renal disease or all-cause death. Other endpoints were the rate of renal decline, processes-of-care measures, and control of risk factors. RESULTS: During 22.8+/-7.9 months of follow-up, the primary endpoint developed in 24 and 40 patients in the structured care and usual care groups, respectively (adjusted risk reduction, 60%, P< .001). Structured care (hazard ratio [95% confidence interval (CI)], 0.40 [0.23-0.68]), age (0.95 [0.93-0.98]), baseline systolic blood pressure (BP) (1.014 [1.003-1.026]), logarithm (base 10) of baseline serum creatinine (34 441 [2290-517915]), and macroalbuminuria (8.95 [1.22-65.38]) were independent predictors for the primary endpoint. Structured care slowed the rate of renal decline (P=.032). More intensive laboratory measurements, increased use of renin-angiotensin system inhibitor, and greater reductions in BP and low-density lipoprotein (LDL) cholesterol were reported by patients receiving structured care. CONCLUSIONS: Structured care delivered by a pharmacist-diabetes specialist team reduced the incidence of end-stage renal disease or death compared with usual care in patients with type 2 diabetic nephropathy.
Assuntos
Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/terapia , Gerenciamento Clínico , Falência Renal Crônica/mortalidade , Falência Renal Crônica/prevenção & controle , Equipe de Assistência ao Paciente , Adulto , Idoso , Causas de Morte , Determinação de Ponto Final , Feminino , Humanos , Falência Renal Crônica/etiologia , Masculino , Medicina , Pessoa de Meia-Idade , Farmacêuticos , Estudos Prospectivos , Fatores de Risco , EspecializaçãoRESUMO
BACKGROUND: Von Willebrand factor (vWF) has generally been regarded as a good predictor of vascular risk. However, no previous studies have examined its relationship with coronary calcification. The aim of this study was to determine whether vWF activity is higher in type 1 diabetic patients than controls; its relationship with cardiovascular risk factors; and to endothelial nitric oxide production and coronary artery calcification. MATERIAL/METHODS: Von Willebrand factor activity was measured in 181 type 1 diabetic patients and 188 controls. Coronary artery calcification was measured by Electron Beam Computed Tomography. Forearm blood flow was measured by venous plethysmography in response to intra-brachial infusion of bradykinin, glyceryl trinitrate, noradrenaline and NG-monomethyl-L-arginine (L-NMMA) in 149 subjects. RESULTS: Von Willebrand factor was significantly increased in diabetic patients compared to controls (median 100% vs 87%, p=0.001). Von Willebrand factor activity was significantly higher in diabetic patients with micro/macroalbuminuria than those with normoalbuminuria (109% vs 93%, p<0.001). Among diabetic subjects, being in the top quartile for vWF was associated with a lower response to L-NMMA (p=0.009). There was no association between vWF activity and coronary artery calcification in either the diabetic (p=0.9) or control group (p=0.8). CONCLUSIONS: Cardiovascular risk factors including albuminuria do not explain the high vWF activity in type 1 diabetic patients. There is some evidence that vWF correlates with endothelial nitric oxide production. The lack of correlation with coronary artery calcification indicates that vWF is not a useful marker of atheroma burden.
Assuntos
Calcinose/metabolismo , Doença da Artéria Coronariana/metabolismo , Diabetes Mellitus Tipo 1/sangue , Endotélio Vascular/metabolismo , Óxido Nítrico/metabolismo , Fator de von Willebrand/metabolismo , Adulto , Albuminúria/metabolismo , Área Sob a Curva , Bradicinina/metabolismo , Bradicinina/uso terapêutico , Calcinose/patologia , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/patologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/metabolismo , Inibidores Enzimáticos/uso terapêutico , Feminino , Humanos , Masculino , Nitroglicerina/metabolismo , Nitroglicerina/uso terapêutico , Fatores de Risco , Estatística como Assunto , Vasodilatadores/metabolismo , Vasodilatadores/uso terapêutico , ômega-N-Metilarginina/metabolismo , ômega-N-Metilarginina/uso terapêuticoRESUMO
We assessed the effects of angiotensin-converting enzyme (ACE) inhibition on survival and cardiorenal outcomes in a consecutive cohort of Chinese type 2 diabetic patients with varying degree of albuminuria, ranging from normoalbuminuria to macroalbuminuria. A total of 3773 consecutive Chinese type 2 diabetic patients were followed prospectively for a mean period of 35.8 months. Clinical end points included all-cause mortality, with cardiovascular end point defined as first hospitalization because of ischemic heart disease, congestive heart failure, revascularization procedures, or cerebrovascular accident as well as renal end point defined as dialysis, doubling of baseline plasma creatinine, or plasma creatinine > or =500 micromol/L. The use of ACE inhibitor was 26.3% in normoalbuminuric (NA), 70.1% in microalbuminuric (MI), and 82.6% in macroalbuminuric (MA) groups. Albuminuria was a major predictor for all-cause mortality with 4-fold difference between NA and MA patients. The 7-year cumulative mortality rate was 7.1%, 10.8%, and 21.7% in the NA, MI, and MA groups, respectively. The use of ACE inhibition was associated with significant reduction of mortality (hazard ratio 0.41 and 95% confidence interval, 0.29, 0.58) in the entire group and was most evident in high-risk patients who had cardiorenal complications or retinopathy at baseline for all albuminuric groups (NA 0.76 [0.31,1.87]; MI 0.32 [0.16, 0.65]; and MA 0.20 [0.13, 0.33]). The prognostic value of albuminuria for death in type 2 diabetes and the beneficial effects of ACE inhibitors in Chinese type 2 diabetic patients with micro- or macroalbuminuria has been confirmed. The effects of ACE inhibitors in type 2 diabetic patients with normoalbuminuria require further evaluation.