Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 77
Filtrar
1.
J Hypertens ; 35(12): 2501-2509, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29035939

RESUMO

AIM: It is important to know which factors predict the development of microalbuminuria in patients with diabetes mellitus type II. MATERIAL: Data from the Randomized Olmesartan and Diabetes Microalbuminuria Prevention Study were used to identify predictors for the new onset of microalbuminuria. Furthermore, the interaction of baseline albuminuria and baseline estimated glomerular filtration rate (eGFR) and the effects of treatment with olmesartan were investigated. RESULTS: A total of 4447 patients were randomized to receive 40-mg olmesartan or placebo for a median of 3.2 years. Baseline urinary albumin-creatinine ratio (UACR) was the most important predictor of microalbuminuria, followed by age, weight, glycosylated hemoglobin type A1C, blood glucose, total cholesterol, SBP number of antihypertensive drugs and heart rate. The development of microalbuminuria was not affected by hemodynamic factors. The incidence of microalbuminuria increased from the lower to the higher UACR tertile at all baseline eGFR tertiles. The effects of olmesartan on prevention of new onset microalbuminuria were more obvious in those with the highest baseline UACR at all baseline eGFR tertiles. The eGFR declined more significantly in the olmesartan group (from 85.0 to 80.1 ml/min per 1.73 m), whereas the decrease in the placebo group was smaller (from 84.7 to 83.7 ml/min per 1.73 m). The highest rate of eGFR decline in the olmesartan group was in patients with the highest baseline eGFR (>95 ml/min per 1.73 m) at all baseline UACR tertiles. The transition from normoalbuminuria to microalbuminuria in the olmesartan treated patients was not accompanied by preservation of renal function. CONCLUSION: Predictors of new onset microalbuminuria are the classical cardiovascular risk factors. Microalbuminuria development was associated with baseline UACR but not baseline eGFR, whereas eGFR decrease after introduction of olmesartan was dependent on baseline eGFR but not on baseline UACR. The effects of olmesartan on microalbuminuria development and on eGFR decrease are probably mediated by different mechanisms.Clinical Trials.gov number, NCT00185159.


Assuntos
Albuminúria/epidemiologia , Albuminúria/etiologia , Diabetes Mellitus Tipo 2/complicações , Rim/fisiopatologia , Adolescente , Adulto , Idoso , Albuminúria/fisiopatologia , Anti-Hipertensivos/uso terapêutico , Glicemia , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Taxa de Filtração Glomerular/fisiologia , Frequência Cardíaca/fisiologia , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Imidazóis/uso terapêutico , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Tetrazóis/uso terapêutico , Adulto Jovem
2.
BMC Med ; 15(1): 146, 2017 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-28851373

RESUMO

BACKGROUND: There is an increasing incidence of type 2 diabetes mellitus (T2DM) in young urban South-Asians. We tested the effect of a pragmatic trimonthly lifestyle modification (LSM) programme (P-LSM) versus a less-intensive 12-monthly control LSM (C-LSM) intervention on a primary composite endpoint of predictors of cardio-metabolic disease (new onset T2DM, hypertension, impaired glucose tolerance (IGT), impaired fasting glycaemia (IFG) and markers of cardio-renal disease) in participants aged 5-40 years with risk factors for T2DM. METHODS: This was a randomised controlled trial performed at the National Diabetes Centre, Sri-Lanka. We individually randomised 4672 participants at risk of T2DM, of whom 3539 (mean age 22.5 (range 6-40 years, 48% males) received either trimonthly (P-LSM n = 1726) or 12-monthly (C-LSM n = 1813) peer educator advice aimed at reducing weight, improving diet, reducing psychological stress and increasing physical activity. RESULTS: During a median follow-up of 3 years, the cumulative incidence of the primary endpoint was n = 479 in P-LSM (74 per 1000 person years) vs. 561 in C-LSM (96 per 1000 person years), with an incident rate ratio (IRR) of 0.89 (95% CI 0.83-0.96, P = 0.02). In post hoc analyses, new onset dysglycaemia (T2DM, IFG and IGT), was the major contributor to the composite and was significantly reduced by P-LSM (IRR 0.9, 95% CI 0.83-0.97, P = 0.01). A significant impact of P-LSM on the incidence of the composite endpoint was noted in 1725 participants (P-LSM n = 850, C-LSM n = 875) aged below 18; P-LSM n = 140 (48 per 1000 person years) versus C-LSM n = 174 (55.4 per 1000 person years), with an IRR of 0.83 (95% CI 0.73-0.94, P = 0.004). CONCLUSIONS: In a young at-risk South-Asian population, a pragmatic LSM programme significantly reduces the incidence of predictors of cardio-metabolic disease. Our results highlight the importance of early intervention in young at-risk subjects. TRIAL REGISTRATION: World Health Organization international clinical trial registry platform ( SLCTR/2008/003 ). Registration Date: March 28, 2008. Retrospectively registered.


Assuntos
Diabetes Mellitus Tipo 2/prevenção & controle , Estilo de Vida , Adolescente , Adulto , Povo Asiático , Criança , Pré-Escolar , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Intolerância à Glucose/epidemiologia , Humanos , Incidência , Masculino , Fatores de Risco , Sri Lanka/epidemiologia , Resultado do Tratamento , População Urbana , Adulto Jovem
3.
J Am Heart Assoc ; 6(4)2017 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-28360227

RESUMO

BACKGROUND: The objective of this study was to evaluate whether aortic pulse wave velocity (Ao-PWV) predicts estimated glomerular filtration rate (eGFR) decline in patients with type 2 diabetes mellitus. METHODS AND RESULTS: This prospective single-center cohort study investigated 211 type 2 diabetes mellitus patients with eGFR ≥45 mL/min with a baseline mean age of 60.1 years (range, 30-82 years). The mean±SD baseline eGFR was 85±26.1 mL/min. We divided the cohort into 2 groups above (n=117, "older") and below (n=94, "younger") the mean age to evaluate whether Ao-PWV predicted progression of kidney disease differentially in older and younger patients. The primary end point was reaching a final eGFR below the median for the age group and an eGFR fall ≥1 mL/min per year. Median follow-up was 9 years (range, 3-11 years) and ≈50% of patients in both groups reached the primary end point. In older patients, Ao-PWV was similar in those who did and did not reach the primary end point. By contrast, younger patients who reached the primary end point had a higher Ao-PWV at baseline compared with those who did not (10.8 m/s versus 9.5 m/s, respectively; mean difference of 1.36 m/s [95% CI, 0.38-2.33], P=0.007). Ao-PWV was an independent predictor of the primary end point (incident risk ratio, 1.09; 95% CI, 1.02-1.18) after adjustment for traditional risk factors only in younger patients (P=0.02). A 1m/s increase in Ao-PWV was associated with a mean fall in eGFR of 2.1 mL/min per year (95% CI, 0.09-4.1) independent of other risk factors in younger patients (P=0.04). CONCLUSIONS: Ao-PWV predicts eGFR decline, before the onset of advanced renal dysfunction, and is a potential target for renoprotection in younger patients with type 2 diabetes mellitus.


Assuntos
Aorta/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Taxa de Filtração Glomerular , Insuficiência Renal Crônica/fisiopatologia , Rigidez Vascular , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 2/complicações , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Análise de Onda de Pulso , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/metabolismo , Fatores de Risco
4.
Br J Nutr ; 116(4): 719-27, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27358019

RESUMO

South Asian populations are predisposed to early onset of the metabolic syndrome. Lifestyle intervention programmes have demonstrated a reduction in the metabolic syndrome and CVD risk; however, the most effective components of the multi-faceted lifestyle interventions are unknown. We studied 2637 Sri Lankan males (n 1237) and females (n 1380), with a mean BMI of 23·9 (sd 4·2) kg/m2, aged 22·5 (sd 10·0) years, who had participated in a 5-year lifestyle-modification programme to examine the effect of dietary changes on distinct components of the metabolic syndrome. The dietary intervention comprised advice to replace polished starches with unpolished starches, high-fat meat and dairy products with low-fat products and high-sugar beverages and snacks with low-sugar varieties. For the purposes of this analysis, data from the control and intensive lifestyle groups were combined. Anthropometric and biochemical data were recorded, and a FFQ was completed annually. Multiple regression was used to determine the effect of the dietary changes on distinct components of the metabolic syndrome. The ratio unpolished:polished rice was inversely related to change in fasting glucose (ß=-0·084, P=0·007) and TAG (ß=-0·084, P=0·005) and positively associated with change in HDL-cholesterol (ß=0·066, P=0·031) at the 5-year follow-up after controlling for relevant confounders. Red meat intake was positively associated with fasting glucose concentrations (ß=0·05, P=0·017), whereas low-fat (ß=-0·046, P=0·018) but not high-fat dairy products (ß=0·003, P=0·853) was inversely related to glucose tolerance at the follow-up visit. Replacement of polished with unpolished rice may be a particularly effective dietary advice in this and similar populations.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Dieta com Restrição de Gorduras/métodos , Estilo de Vida , Síndrome Metabólica/dietoterapia , Comportamento de Redução do Risco , Antropometria , Índice de Massa Corporal , Doenças Cardiovasculares/etiologia , Laticínios , Feminino , Humanos , Masculino , Síndrome Metabólica/complicações , Análise de Regressão , Fatores de Risco , Sri Lanka , Adulto Jovem
5.
Nat Rev Nephrol ; 11(3): 132-4, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25599623

RESUMO

The authors of a new study report that independent of renal disease, any level of glycaemia is associated with increased mortality risk in patients with type 1 diabetes mellitus. However, this view may be overly simplistic­a multifactorial approach is required to reduce excess mortality in this population.


Assuntos
Diabetes Mellitus Tipo 1/mortalidade , Hemoglobinas Glicadas/metabolismo , Feminino , Humanos , Masculino
6.
BMC Nephrol ; 15: 180, 2014 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-25407798

RESUMO

BACKGROUND: Type 2 diabetes is a major risk factor for chronic kidney disease, which substantially increases the risk of cardiovascular disease mortality. This Phase IIb safety study (AleNephro) in patients with stage 3 chronic kidney disease and type 2 diabetes, evaluated the renal effects of aleglitazar, a balanced peroxisome proliferator-activated receptor-α/γ agonist. METHODS: Patients were randomized to 52 weeks' double-blind treatment with aleglitazar 150 µg/day (n=150) or pioglitazone 45 mg/day (n=152), followed by an 8-week off-treatment period. The primary endpoint was non-inferiority for the difference between aleglitazar and pioglitazone in percentage change in estimated glomerular filtration rate from baseline to end of follow-up. Secondary endpoints included change from baseline in estimated glomerular filtration rate and lipid profiles at end of treatment. RESULTS: Mean estimated glomerular filtration rate change from baseline to end of follow-up was -2.7% (95% confidence interval: -7.7, 2.4) with aleglitazar versus -3.4% (95% confidence interval: -8.5, 1.7) with pioglitazone, establishing non-inferiority (0.77%; 95% confidence interval: -4.5, 6.0). Aleglitazar was associated with a 15% decrease in estimated glomerular filtration rate versus 5.4% with pioglitazone at end of treatment, which plateaued to 8 weeks and was not progressive. Superior improvements in high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglycerides, with similar effects on glycosylated hemoglobin were observed with aleglitazar versus pioglitazone. No major safety concerns were identified. CONCLUSIONS: The primary endpoint in AleNephro was met, indicating that in stage 3 chronic kidney disease patients with type 2 diabetes, the decrease in estimated glomerular filtration rate after 52 weeks' treatment with aleglitazar followed by 8 weeks off-treatment was reversible and comparable (non-inferior) to pioglitazone. TRIAL REGISTRATION: NCT01043029 January 5, 2010.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Hipolipemiantes/uso terapêutico , Rim/efeitos dos fármacos , Oxazóis/uso terapêutico , PPAR alfa/agonistas , PPAR gama/agonistas , Insuficiência Renal Crônica/tratamento farmacológico , Tiofenos/uso terapêutico , Idoso , Diabetes Mellitus Tipo 2/sangue , Nefropatias Diabéticas/fisiopatologia , Método Duplo-Cego , Dislipidemias/sangue , Dislipidemias/complicações , Dislipidemias/tratamento farmacológico , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemiantes/farmacologia , Hipolipemiantes/farmacologia , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Oxazóis/farmacologia , Pioglitazona , Insuficiência Renal Crônica/fisiopatologia , Equivalência Terapêutica , Tiazolidinedionas/farmacologia , Tiazolidinedionas/uso terapêutico , Tiofenos/farmacologia
7.
J Am Heart Assoc ; 3(2): e000810, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24772521

RESUMO

BACKGROUND: The Randomized Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) study showed that 40 mg Olmesartan medoxomil (OM) versus placebo delayed microalbuminuria onset in patients with type 2 diabetes and normoalbuminuria. METHODS AND RESULTS: One thousand seven hundred and fifty-eight ROADMAP patients (placebo arm: 877; OM arm: 881) participated in the observational follow up (OFU) with an average of 3.3 years. They received standard medical care and micro- and macrovascular events were documented. During observational follow-up 62.9% and 60.1% in the former OM and placebo group, respectively, received treatment with a RAS blocking agent. During the OFU period the systolic blood pressure (SBP) increased to mean values of 135 mm Hg in both groups. Patients who had developed microalbuminuria during ROADMAP had a higher incidence of cardio- and cerebrovascular events (OR 1.77, CI 1.03 to 3.03, P=0.039) during the OFU period compared with patients in whom this was not the case. Diabetic retinopathy was significantly reduced in the former OM group (8 [0.9%] versus 23 [2.6%], OR: 0.34, CI 0.15 to 0.78, P=0.011) and the rate of microalbuminuria was numerically reduced. Congestive heart failure requiring hospitalization (3 [0.3%] versus 12 [1.4%], OR: 0.23, CI 0.06 to 0.85, P=0.027) was reduced and there was a trend of reduced cardio-/cerebrovascular events (OM versus Pb: 73 [8.3%] versus 86 [9.8%] patients). Seven (0.8%) deaths (including 2 CV events) were reported in former placebo patients versus 3 (0.3%) (non-CV events) in former OM patients. CONCLUSIONS: Development of microalbuminuria is a valid marker for future CV events. RAS blockade with Olmesartan might cause sustained reduction (legacy effect) of micro- and macrovascular events.


Assuntos
Albuminúria/prevenção & controle , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Angiopatias Diabéticas/prevenção & controle , Nefropatias Diabéticas/prevenção & controle , Imidazóis/uso terapêutico , Sistema Renina-Angiotensina/efeitos dos fármacos , Tetrazóis/uso terapêutico , Idoso , Albuminúria/diagnóstico , Albuminúria/etiologia , Albuminúria/fisiopatologia , Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/diagnóstico , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/fisiopatologia , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/fisiopatologia , Feminino , Seguimentos , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/fisiopatologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Olmesartana Medoxomila , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
8.
J Am Soc Nephrol ; 25(5): 1083-93, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24722445

RESUMO

Despite optimal treatment, including renin-angiotensin system (RAS) inhibitors, patients with type 2 diabetic nephropathy have high cardiorenal morbidity and mortality related to residual albuminuria. We evaluated whether or not atrasentan, a selective endothelin A receptor antagonist, further reduces albuminuria when administered concomitantly with maximum tolerated labeled doses of RAS inhibitors. We enrolled 211 patients with type 2 diabetes, urine albumin/creatinine ratios of 300-3500 mg/g, and eGFRs of 30-75 ml/min per 1.73 m(2) in two identically designed, parallel, multinational, double-blind studies. Participants were randomized to placebo (n=50) or to 0.75 mg/d (n=78) or 1.25 mg/d (n=83) atrasentan for 12 weeks. Compared with placebo, 0.75 mg and 1.25 mg atrasentan reduced urine albumin/creatinine ratios by an average of 35% and 38% (95% confidence intervals of 24 to 45 and 28 to 47, respectively) and reduced albuminuria≥30% in 51% and 55% of participants, respectively. eGFR and office BP measurements did not change, whereas 24-hour systolic and diastolic BP, LDL cholesterol, and triglyceride levels decreased significantly in both treatment groups. Use of atrasentan was associated with a significant increase in weight and a reduction in hemoglobin, but rates of peripheral edema, heart failure, or other side effects did not differ between groups. However, more patients treated with 1.25 mg/d atrasentan discontinued due to adverse events. After stopping atrasentan for 30 days, measured parameters returned to pretreatment levels. In conclusion, atrasentan reduced albuminuria and improved BP and lipid spectrum with manageable fluid overload-related adverse events in patients with type 2 diabetic nephropathy receiving RAS inhibitors.


Assuntos
Albuminúria/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/tratamento farmacológico , Endotelina-1/antagonistas & inibidores , Pirrolidinas/uso terapêutico , Idoso , Albuminúria/etiologia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Atrasentana , Pressão Sanguínea/efeitos dos fármacos , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Testes de Função Renal , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Pirrolidinas/farmacologia
9.
Clin J Am Soc Nephrol ; 9(3): 490-8, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24408122

RESUMO

BACKGROUND AND OBJECTIVES: The Avosentan on Time to Doubling of Serum Creatinine, End Stage Renal Disease or Death (ASCEND) trial tested the renoprotective effect of the endothelin receptor antagonist avosentan in patients with diabetes and nephropathy, but the study was terminated due to an excess of congestive heart failure (CHF) events in the avosentan arms, likely due to fluid retention. The aim of this study was to identify risk markers of CHF after treatment with avosentan. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a post hoc analysis of the ASCEND trial (N=1392 participants), we assessed which baseline characteristics predicted CHF risk during avosentan treatment. Furthermore, postrandomization changes between baseline and the first available measurement of body weight and hemoglobin were examined as potential clinical indicators of fluid retention for their relationship with CHF development. RESULTS: Relative to placebo, avosentan increased CHF risk (hazard ratio, 2.76; 95% confidence interval, 1.68 to 4.54). The avosentan-related CHF risk was higher with lower baseline cholesterol levels (P interaction=0.003) and concomitant statin use (P interaction=0.06), whereas it was lower with a lower estimated GFR (P interaction=0.04). Patients allocated to avosentan had a median body weight increase of 0.6 kg (interquartile range, 0.0 to 2.0 kg) and a median hemoglobin decrease of 1.4 g/dl (interquartile range, -2.1 to -0.7 g/dl) at the first postrandomization measurement. The body weight increase induced by avosentan was associated with CHF development (P interaction=0.04), whereas hemoglobin decrease was not (P interaction=0.64). The increase in body weight was particularly pronounced in patients with a cardiovascular disease history and in patients using statins. CONCLUSIONS: In avosentan-treated patients, body weight increase, but not hemoglobin decrease, was associated with CHF development, indicating that close body weight monitoring could provide an early signal of CHF development in future trials with endothelin receptor antagonists.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Antagonistas dos Receptores de Endotelina , Insuficiência Cardíaca/induzido quimicamente , Falência Renal Crônica/prevenção & controle , Rim/efeitos dos fármacos , Piridinas/efeitos adversos , Pirimidinas/efeitos adversos , Idoso , Biomarcadores/sangue , Creatinina/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidade , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/mortalidade , Nefropatias Diabéticas/fisiopatologia , Método Duplo-Cego , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Insuficiência Cardíaca/diagnóstico , Hemoglobinas/metabolismo , Humanos , Rim/metabolismo , Rim/fisiopatologia , Falência Renal Crônica/sangue , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/etiologia , Falência Renal Crônica/mortalidade , Falência Renal Crônica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Receptores de Endotelina/metabolismo , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Aumento de Peso/efeitos dos fármacos
11.
Clin J Am Soc Nephrol ; 8(11): 1899-905, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23929932

RESUMO

BACKGROUND AND OBJECTIVES: Soluble Klotho is an anti-aging phosphaturic protein associated with vascular-renal protection. In vitro and in vivo studies have demonstrated that renin-angiotensin system (RAS) blockade increases soluble Klotho levels. The effect of RAS blockers on soluble Klotho in patients with diabetic kidney disease (DKD) is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Plasma-soluble Klotho was measured in a secondary analysis of a randomized controlled clinical trial performed at a single university hospital center (ClinicalTrials.gov number NCT001715, from March 2003 to September 2006). Seventy-six patients with type 2 diabetes and DKD (all with albuminuria and serum creatinine <1.7 mg/dl) were studied at baseline and at 24 weeks (study end) after randomization to valsartan/hydrochlorothiazide (n=37) or amlodipine (n=39) treatment. Aortic-pulse wave velocity by applanation tonometry and albuminuria (from three timed urine collections) were also measured at baseline and 24 weeks. RESULTS: Valsartan/hydrochlorothiazide treatment significantly increased mean (± SD) soluble Klotho (from 432.7 ± 179 to 506.4 ± 226.8 pg/ml; P=0.01) and reduced serum phosphate (from 3.25 ± 1.18 to 2.60 ± 0.96 mg/dl; P=0.04) compared with amlodipine (from 430.1 ± 145.8 to 411.9 ± 157.6 pg/ml and from 2.94 ± 0.56 to 2.69 ± 1.52 mg/dl, respectively). There was a significant difference between treatment groups in soluble Klotho (mean 91.9 pg/ml; 95% confidence interval, 19.9 to 162) and serum phosphate levels (mean -0.68 mg/dl; 95% confidence interval, -0.15 to -1.33) with valsartan/hydrochlorothiazide treatment (P=0.03 and P=0.04, respectively). Attained BP was similar in the two groups and levels of soluble Klotho were not associated with aortic-pulse wave velocity and albuminuria, variables that fell significantly only with valsartan/hydrochlorothiazide. CONCLUSIONS: Treatment with a RAS blocker, valsartan, is associated with an increase in soluble Klotho, which may contribute to the BP-independent cardiorenal benefits of these drugs in DKD.


Assuntos
Albuminúria/tratamento farmacológico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Glucuronidase/sangue , Hipertensão/tratamento farmacológico , Sistema Renina-Angiotensina/efeitos dos fármacos , Tetrazóis/uso terapêutico , Valina/análogos & derivados , Idoso , Albuminúria/sangue , Albuminúria/diagnóstico , Albuminúria/etiologia , Albuminúria/fisiopatologia , Anlodipino/uso terapêutico , Biomarcadores/sangue , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/fisiopatologia , Diuréticos/uso terapêutico , Feminino , Hospitais Universitários , Humanos , Hidroclorotiazida/uso terapêutico , Hipertensão/sangue , Hipertensão/diagnóstico , Hipertensão/etiologia , Hipertensão/fisiopatologia , Proteínas Klotho , Londres , Masculino , Pessoa de Meia-Idade , Fosfatos/sangue , Análise de Onda de Pulso , Sístole , Fatores de Tempo , Resultado do Tratamento , Valina/uso terapêutico , Valsartana
12.
Clin J Am Soc Nephrol ; 8(2): 225-32, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23184569

RESUMO

BACKGROUND AND OBJECTIVES: Thiazolidinediones (pioglitazone and rosiglitazone) induce renal epithelial sodium channel (ENaC)-mediated sodium reabsorption, resulting in plasma volume (PV) expansion. Incidence and long-term management of fluid retention induced by thiazolidinediones remain unclear. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a 4-week run-in period, rosiglitazone, 4 mg twice daily, was added to a background anti-diabetic therapy in 260 South Indian patients with type 2 diabetes mellitus. Patients with PV expansion (absolute reduction in hematocrit in run-in, ≥1.5 percentage points) entered a randomized, placebo-controlled study to evaluate effects of amiloride and spironolactone on attenuating rosiglitazone-induced fluid retention. Primary endpoint was change in hematocrit in each diuretic group versus placebo (control group). RESULTS: Of the 260 patients, 70% (n=180) had PV expansion. These 180 patients (70% male; mean age, 47.8 years [range, 30-80 years]) were randomly assigned to rosiglitazone, 4 mg twice daily, plus spironolactone, 50 mg once daily; rosiglitazone, 4 mg twice daily, plus amiloride, 10 mg once daily; or rosiglitazone, 4 mg twice daily, plus placebo for 24 weeks. Hematocrit continued to decrease significantly in control and spironolactone groups (mean absolute change, -1.2 [P=0.01] and -0.7 [P=0.02] percentage points, respectively), suggesting continued PV expansion. No change occurred with amiloride (mean change, 0.0 percentage points). Amiloride, but not spironolactone, was superior to control (mean hematocrit difference [95% confidence interval] relative to control, 1.27 [0.21-2.55] and 0.49 [-0.79-1.77] percentage points [P=0.04 and P=0.61], respectively). CONCLUSIONS: Prevalence of rosiglitazone-induced fluid retention in South Indian patients with type 2 diabetes is high. Amiloride, a direct ENaC blocker, but not spironolactone, prevented protracted fluid retention in these patients.


Assuntos
Amilorida/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diuréticos/uso terapêutico , Edema/induzido quimicamente , Edema/tratamento farmacológico , Espironolactona/uso terapêutico , Tiazolidinedionas/efeitos adversos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rosiglitazona
13.
J Hypertens ; 30(4): 811-8; discussion 818, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22418908

RESUMO

BACKGROUND: We have previously demonstrated in the Randomized Olmesartan and Diabetes Microalbuminuria Prevention study that the angiotensin receptor blocker (ARB) olmesartan delays the onset of microalbuminuria in patients with type 2 diabetes. Now, we investigated the effect in the subpopulation with hypertension. METHODS: Overall, 4020 patients with type 2 diabetes and hypertension at baseline (defined by a SBP/DBP ≥130/80 mmHg or use of antihypertensive medication) received either 40 mg olmesartan once daily or placebo for a median of 3.2 years in a randomized, double-blind, multicenter, controlled trial. Additional antihypertensive drugs (except angiotensin-converting enzyme inhibitors or ARBs) were used as needed to lower blood pressure (BP) to less than 130/80 mmHg. RESULTS: The average BP was 126.3/74.7 and 129.5/76.6 mmHg, respectively (P < 0.001). Olmesartan delayed the time to onset of microalbuminuria by 25% (hazard ratio = 0.75; 95% confidence interval = 0.61-0.92, P = 0.007). Patients with a baseline SBP above the median of 136.7 mmHg and a SBP reduction above the median of 17.45 mmHg had a lower incidence of microalbuminuria than patients with a SBP reduction of less than 17.45 (8.1 vs. 11.2%, P < 0.0001). Independent from the baseline BP and the degree of BP reduction a 15-39% increase in the time to onset of microalbuminuria was detectable by olmesartan treatment. Cardiovascular events were comparable and occurred in 93 (4.6%) patients taking olmesartan and 86 (4.4%) taking placebo. CONCLUSION: Patients with a better BP reduction are less likely to develop microalbuminuria. Treatment with olmesartan delayed the onset of microalbuminuria independent of the baseline BP and the degree of BP reduction.


Assuntos
Albuminúria/prevenção & controle , Anti-Hipertensivos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipertensão/tratamento farmacológico , Imidazóis/uso terapêutico , Tetrazóis/uso terapêutico , Albuminúria/etiologia , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/urina , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Hipertensão/complicações , Hipertensão/urina , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
14.
PLoS One ; 7(2): e31309, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22348068

RESUMO

BACKGROUND: South-Asian's are predisposed to early onset type 2 diabetes (T2DM). The prevalence of cardio-metabolic risk-factors in young Sri-Lankans is unknown. METHODOLOGY/PRINCIPAL FINDINGS: To determine by questionnaire and anthropometry the prevalence of first degree family history (FH) of T2DM, physical inactivity, raised waist circumference (WC) and raised body mass index (BMI) in a representative healthy urban population selected by cluster sampling. Those with ≥ 2 risk-factors were evaluated for metabolic syndrome (MS) and recruited for an intervention trial. Of 23,296 participants screened, 22,507 (53% Female) were eligible [8,497 aged 10-14 yrs, 4,763 aged 15-19 yrs and 9,247 aged 20-40 yrs]. 51% had none of the 4 risk-factors, 26% 1 risk-factor and 23% (5,163) ≥ 2 risk-factors of whom 4,532 were assessed for MS. Raised BMI was noted in 19.7% aged 10-14 yrs, 15.3% between 15-19 yrs, and between 20-40 yrs, 27.4% of males vs. 21.8% of females p<0.001. Prevalence of raised WC was greater in females for each age group: 42.7% vs. 32.1%; 28.1% vs. 16.1%; 34.5% vs. 25.7% (p<0.05 for all) as was physical inactivity: 39.9% vs. 14.5%; 51.7% vs. 20.0%; 62.7% vs. 41.3% which rose in both sexes with age (p<0.05 for all). FH of T2DM was present in 26.2%. In 4532 (50%<16 yrs) with ≥ 2 risk-factors, impaired fasting glycaemia/impaired glucose tolerance (pre-diabetes) prevalence was 16%. MS was more prevalent in males [10-16 yrs (13.0% vs. 8.8%), 16-40 yrs (29.5% vs. 20.0%) p<0.001 for both]. CONCLUSIONS/SIGNIFICANCE: There is a high prevalence of modifiable cardio-metabolic risk-factors in young urban Sri-Lankans with significant gender differences. A primary prevention intervention trial is ongoing in this cohort. Clinical Trial Registration Number SLCTR/2008/World Health Organization (WHO) international clinical trial registry platform.


Assuntos
Doenças Cardiovasculares/epidemiologia , Síndrome Metabólica/epidemiologia , Adulto , Distribuição por Idade , Antropometria , Feminino , Humanos , Masculino , Prevalência , Fatores de Risco , Fatores Sexuais , Sri Lanka/epidemiologia , Inquéritos e Questionários , População Urbana/estatística & dados numéricos , Adulto Jovem
15.
Trials ; 12: 209, 2011 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-21943067

RESUMO

BACKGROUND: Urban South-Asian's are predisposed to early onset of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). There is an urgent need for country specific primary prevention strategies to address the growing burden of cardio-metabolic disease in this population. The aim of this clinical trial is to evaluate whether intensive (3-monthly) lifestyle modification advice is superior to a less-intensive (12 monthly; control group) lifestyle modification advice on a primary composite cardio-metabolic end point in 'at risk' urban subjects aged between 5-40 years. METHODS/DESIGN: This is an open randomised controlled parallel group clinical trial performed at a single centre in Colombo, Sri-Lanka. A cluster sampling strategy was used to select a large representative sample of subjects aged between 5-40 years at high risk of T2DM and CVD for the intervention study. We have screened 23,298 (males 47% females 53%) healthy subjects for four risk factors: obesity, elevated waist circumference, family history of diabetes and physical inactivity, using a questionnaire and anthropometry. Those with two or more risk-factors were recruited to the intervention trial. We aim to recruit 4600 subjects for the intervention trial. The primary composite cardio-metabolic end point is; new onset T2DM, impaired glucose tolerance, impaired fasting glycaemia, new onset hypertension and albuminuria, following 5 years of intervention. The effect of the intervention on pre-specified secondary endpoints will also be evaluated. The study will be conducted according to good clinical and ethical practice, data analysis and reporting guidelines. DISCUSSION: DIABRISK-SL is a large population based trial to evaluate the prevalence of diabetes, pre-diabetes and cardio-metabolic risk factors among young urban Sri-Lankans and the effect of a primary prevention strategy on cardio-metabolic disease end points. This work will enable country specific and regional cardio-metabolic risk scores to be derived. Further if the proposed intervention is successful the results of this study can be translated and implemented as a low-cost primary prevention tool in Sri-Lanka and other low/middle income developing countries. TRIAL REGISTRATION: The trial is registered with the World Health Organisation and Sri-Lanka clinical trial registry number SLCTR/2008/003.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Protocolos Clínicos , Diabetes Mellitus Tipo 2/prevenção & controle , Estilo de Vida , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Projetos de Pesquisa , Sri Lanka
16.
Clin J Am Soc Nephrol ; 6(5): 1032-40, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21454723

RESUMO

BACKGROUND AND OBJECTIVES: In ADOPT (A Diabetes Outcomes Prevention Trial), initial monotherapy with rosiglitazone provided more durable glycemic control than metformin or glyburide in patients with recently diagnosed type 2 diabetes. Herein, we examine differences in albumin excretion, renal function (estimated GFR), and BP over 5 years between treatment groups. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A total of 4351 recently diagnosed, drug-naïve patients with type 2 diabetes were treated and followed for up to 5 years with rosiglitazone, metformin, or glyburide and were examined with periodic assessments of albumin/creatinine ratio (ACR), modification of diet in renal disease (MDRD)-estimated GFR, and BP. RESULTS: The ACR rose slowly with metformin. It fell with rosiglitazone and less so with glyburide over the first 2 years, and then rose slowly over time. Estimated GFR (eGFR) with all therapies rose into the high normal range over the first 3 to 4 years, more so with rosiglitazone, and then declined, more so with glyburide. Systolic BP was stable over time, values with rosiglitazone being lower, and diastolic BP declined over time, more so with rosiglitazone than with metformin or glyburide. There was no difference among groups in the incidence of emergent albuminuria (ACR ≥30 mg/g), hypertension, or impaired eGFR (<60 ml/min per 1.73 m(2)). CONCLUSIONS: Over a 5-year period, initial monotherapy with rosiglitazone retards the rise of ACR compared with metformin, preserves eGFR compared with glyburide, and lowers BP relative to both comparators.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Glibureto/administração & dosagem , Rim/efeitos dos fármacos , Metformina/administração & dosagem , Tiazolidinedionas/administração & dosagem , Adulto , Idoso , Albuminúria/tratamento farmacológico , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Creatinina/urina , Nefropatias Diabéticas/fisiopatologia , Feminino , Seguimentos , Taxa de Filtração Glomerular/efeitos dos fármacos , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/administração & dosagem , Rim/fisiologia , Masculino , Pessoa de Meia-Idade , Rosiglitazona , Resultado do Tratamento
17.
N Engl J Med ; 364(10): 907-17, 2011 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-21388309

RESUMO

BACKGROUND: Microalbuminuria is an early predictor of diabetic nephropathy and premature cardiovascular disease. We investigated whether treatment with an angiotensin-receptor blocker (ARB) would delay or prevent the occurrence of microalbuminuria in patients with type 2 diabetes and normoalbuminuria. METHODS: In a randomized, double-blind, multicenter, controlled trial, we assigned 4447 patients with type 2 diabetes to receive olmesartan (at a dose of 40 mg once daily) or placebo for a median of 3.2 years. Additional antihypertensive drugs (except angiotensin-converting-enzyme inhibitors or ARBs) were used as needed to lower blood pressure to less than 130/80 mm Hg. The primary outcome was the time to the first onset of microalbuminuria. The times to the onset of renal and cardiovascular events were analyzed as secondary end points. RESULTS: The target blood pressure (<130/80 mm Hg) was achieved in nearly 80% of the patients taking olmesartan and 71% taking placebo; blood pressure measured in the clinic was lower by 3.1/1.9 mm Hg in the olmesartan group than in the placebo group. Microalbuminuria developed in 8.2% of the patients in the olmesartan group (178 of 2160 patients who could be evaluated) and 9.8% in the placebo group (210 of 2139); the time to the onset of microalbuminuria was increased by 23% with olmesartan (hazard ratio for onset of microalbuminuria, 0.77; 95% confidence interval, 0.63 to 0.94; P=0.01). The serum creatinine level doubled in 1% of the patients in each group. Slightly fewer patients in the olmesartan group than in the placebo group had nonfatal cardiovascular events--81 of 2232 patients (3.6%) as compared with 91 of 2215 patients (4.1%) (P=0.37)--but a greater number had fatal cardiovascular events--15 patients (0.7%) as compared with 3 patients (0.1%) (P=0.01), a difference that was attributable in part to a higher rate of death from cardiovascular causes in the olmesartan group than in the placebo group among patients with preexisting coronary heart disease (11 of 564 patients [2.0%] vs. 1 of 540 [0.2%], P=0.02). CONCLUSIONS: Olmesartan was associated with a delayed onset of microalbuminuria, even though blood-pressure control in both groups was excellent according to current standards. The higher rate of fatal cardiovascular events with olmesartan among patients with preexisting coronary heart disease is of concern. (Funded by Daiichi Sankyo; ClinicalTrials.gov number, NCT00185159.).


Assuntos
Albuminúria/prevenção & controle , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Imidazóis/uso terapêutico , Tetrazóis/uso terapêutico , Adolescente , Adulto , Idoso , Albuminúria/epidemiologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Doença das Coronárias/complicações , Diabetes Mellitus Tipo 2/complicações , Método Duplo-Cego , Feminino , Seguimentos , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Imidazóis/efeitos adversos , Masculino , Pessoa de Meia-Idade , Tetrazóis/efeitos adversos , Adulto Jovem
18.
Diabetes ; 60(5): 1552-60, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21415383

RESUMO

OBJECTIVE: ADOPT (A Diabetes Outcome Progression Trial) demonstrated that initial monotherapy with rosiglitazone provided superior durability of glycemic control compared with metformin and glyburide in patients with recently diagnosed type 2 diabetes. Herein, we examine measures of ß-cell function and insulin sensitivity from an oral glucose tolerance test (OGTT) over a 4-year period among the three treatments. RESEARCH DESIGN AND METHODS: Recently diagnosed, drug-naïve patients with type 2 diabetes (4,360 total) were treated for a median of 4.0 years with rosiglitazone, metformin, or glyburide and were examined with periodic metabolic testing using an OGTT. RESULTS: Measures of ß-cell function and insulin sensitivity from an OGTT showed more favorable changes over time with rosiglitazone versus metformin or glyburide. Persistent improvements were seen in those who completed 4 years of monotherapy and marked deterioration of ß-cell function in those who failed to maintain adequate glucose control with initial monotherapy. CONCLUSIONS: The favorable combined changes in ß-cell function and insulin sensitivity over time with rosiglitazone appear to be responsible for its superior glycemic durability over metformin and glyburide as initial monotherapy in type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Glibureto/uso terapêutico , Hipoglicemiantes/uso terapêutico , Células Secretoras de Insulina/efeitos dos fármacos , Metformina/uso terapêutico , Tiazolidinedionas/uso terapêutico , Idoso , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Humanos , Resistência à Insulina/fisiologia , Masculino , Pessoa de Meia-Idade , Rosiglitazona
19.
Int J Cardiol ; 151(2): 136-42, 2011 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-20837369

RESUMO

BACKGROUND: Aleglitazar is a new, balanced dual peroxisome proliferator-activated receptor (PPAR)α/γ agonist designed to optimize lipid and glycemic benefits and minimize PPAR-related adverse effects. METHODS: SESTA R was a 26-week, randomized, double-blind, multicenter study comparing the effects of a supratherapeutic dosage of aleglitazar (600 µg/day) with pioglitazone (45 mg/day) on change in measured GFR (mGFR) in 174 patients with type 2 diabetes and normal to mildly impaired renal function (estimated GFR [eGFR] 60 to 120 ml/min/1.73 m(2)). RESULTS: In 118 patients with evaluable GFR measurements, baseline mean (± SD) mGFR was 97.6 ± 17.5 ml/min/1.73 m(2) in the aleglitazar group and 101.9±21.6ml/min/1.73m(2) in the pioglitazone group. Mean percent change from baseline mGFR was -16.9% (90% confidence interval -22.0 to -11.5) with aleglitazar and -4.6% (-10.15 to 1.35) with pioglitazone, a mean treatment difference of -13.0% (-19.0 to -6.5). The 17% decrease from baseline in mGFR was consistent with the 19% decrease in eGFR Modification of Diet in Renal Disease (MDRD) observed with aleglitazar, which reached a plateau after 4weeks, with no further progression until treatment discontinuation. Following aleglitazar withdrawal, eGFR values returned to pretreatment levels within the 4-8-week follow-up, which suggests reversible hemodynamic changes in renal function. CONCLUSIONS: Despite the increased incidence of expected, dose-dependent PPAR class side effects (e.g., peripheral edema, weight gain, and congestive heart failure) limiting further development of this supratherapeutic dosage of aleglitazar (600 µg/day), these data, together with the data from the dose-ranging SYNCHRONY study, suggest aleglitazar may be a potential new treatment for cardiovascular risk reduction in post-acute coronary syndrome patients at the therapeutic 150 µg daily dose.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Taxa de Filtração Glomerular/efeitos dos fármacos , Oxazóis/efeitos adversos , Insuficiência Renal/induzido quimicamente , Tiofenos/efeitos adversos , Adolescente , Adulto , Idoso , Diabetes Mellitus Tipo 2/fisiopatologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Oxazóis/administração & dosagem , Prognóstico , Insuficiência Renal/fisiopatologia , Estudos Retrospectivos , Tiofenos/administração & dosagem , Adulto Jovem
20.
J Am Soc Nephrol ; 21(12): 2020-7, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21051738

RESUMO

The development of albuminuria in diabetics is closely associated with an enhanced risk of renal and cardiovascular disease. However, the role of albuminuria in the pathogenesis of these clinical conditions remains controversial. Whether albuminuria is simply a biomarker or qualifies as a surrogate endpoint for cardiorenal disease has wide-ranging implications from the monitoring and treatment of patients to the design of clinical trials and drug development. We critically review available data to determine whether the association between albuminuria and cardiorenal disease is causative. Current evidence suggests the significance of albuminuria depends on its severity (degree or level) and on the specific clinical outcome under consideration. For diabetic kidney disease, there is convincing epidemiologic and experimental evidence to assign clinical albuminuria status as a surrogate endpoint, but for lower levels of albuminuria (microalbuminuria and normoalbuminuria), the evidence is inconclusive or not available. Albuminuria of any degree is unlikely to be causally related to diabetic cardiovascular disease, but its onset might be useful to identify those subjects at cardiovascular risk and to detect and treat other modifiable risk factors.


Assuntos
Albuminúria/epidemiologia , Diabetes Mellitus/epidemiologia , Cardiomiopatias Diabéticas/epidemiologia , Nefropatias Diabéticas/epidemiologia , Proteinúria/epidemiologia , Albuminúria/diagnóstico , Causalidade , Comorbidade , Diabetes Mellitus/diagnóstico , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Cardiomiopatias Diabéticas/fisiopatologia , Nefropatias Diabéticas/diagnóstico , Progressão da Doença , Feminino , Humanos , Testes de Função Renal , Masculino , Prevalência , Prognóstico , Proteinúria/diagnóstico , Medição de Risco , Índice de Gravidade de Doença
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...