Value of diagnostic tools for myocardial ischemia used in routine clinical practice to predict cardiac events in patients with type 2 diabetes mellitus: a prospective study.

OBJECTIVE: To analyze tests used in routine clinical practice for the diagnosis of myocardial ischemia to predict the development of cardiac events in type 2 diabetic patients. METHODS: The occurrence of cardiac events (new myocardial infarct, myocardial re-vascularization procedures, congestive heart failure, acute pulmonary edema, sudden death, and death after myocardial infarction or pulmonary edema) were prospectively assessed in a cohort of 135 type 2 diabetic patients after up to seven years of follow-up. At baseline, coronary artery disease was assessed by the WHO cardiovascular questionnaire, resting electrocardiogram, and stress myocardial scintigraphy. RESULTS: Forty-eight cardiac events were observed in 41 patients (10.5 events/100 patients-year). In a Cox's proportional-hazard model only the presence of symptoms of coronary artery disease on the WHO cardiovascular questionnaire alone (RR = 2.13, 95% CI 1.11-4.07, P= 0.022) or in combination with abnormalities on resting ECG (RR= 2.03, 95% CI 1.05-3.92, P= 0.034) or on myocardial scintigraphy (RR= 1.89, 95% CI 1.001-3.57, P= 0.050) predicted cardiac events, adjusted for fasting plasma glucose, mean blood pressure, body mass index, peripheral vascular disease and diabetic nephropathy. CONCLUSION: The WHO cardiovascular questionnaire, a simple tool for the diagnosis of coronary artery disease, is a significant predictor of cardiac events in type 2 diabetic patients.

Value of diagnostic tools for myocardial ischemia used in routine clinical practice to predict cardiac events in patients with type 2 diabetes mellitus: a prospective study

OBJETIVO: Analisar os testes usados na prática clínica de rotina para diagnóstico de isquemia miocárdica na predição do desenvolvimento de eventos cardíacos em pacientes com diabetes mellitus tipo 2 (DM2). MÉTODOS: A ocorrência de eventos cardíacos (novo infarto do miocárdio [IM], procedimentos de re-vascularização miocárdica, insuficiência cardíaca congestiva, edema agudo de pulmão, morte súbita e morte após IM ou edema pulmonar) foi avaliada prospectivamente em uma coorte de 135 pacientes com DM2 após até 7 anos de acompanhamento. Na condição basal, a doença arterial coronariana (DAC) foi avaliada pelo questionário cardiovascular da OMS, eletrocardiograma de repouso e cintilografia do miocárdio sob stress. RESULTADOS: 48 eventos cardíacos foram observados em 41 pacientes (10,5 eventos/100 pacientes-ano). No modelo de risco proporcional de Cox apenas a presença de sintomas de DAC no questionário cardiovascular da OMS isoladamente (RR= 2,13, 95% CI 1,11­4,07, P= 0,022) ou em combinação com anormalidades no ECG de repouso (RR= 2,03, 95% CI 1,05­3,92, P= 0,034) ou cintilografia do miocárdio (RR= 1,89, 95% CI 1,001­3,57, P= 0,050) predisseram eventos cardíacos, ajustados para a glicemia de jejum, pressão arterial média, índice de massa corporal, doença vascular periférica e nefropatia diabética. CONCLUSÃO: O questionário cardiovascular da OMS, um procedimento simples para o diagnóstico da DAC, é um preditor significativo de eventos cardíacos em pacientes com DM2.

Cellular basis of diabetic nephropathy: II. The transforming growth factor-beta system and diabetic nephropathy lesions in type 1 diabetes.

Transforming growth factor-beta (TGF-beta) may be critical in the development of diabetic nephropathy (DN), and genetic predisposition is an important determinant of DN risk. We evaluated mRNA expression levels of TGF-beta system components in cultured skin fibroblasts (SFs) from type 1 diabetic patients with fast versus slow development of DN. A total of 125 long-standing type 1 diabetic patients were ranked by renal mesangial expansion score (MES) based on renal biopsy findings and diabetes duration. Patients in the highest quintile of MES who were also microalbuminuric or proteinuric (n = 16) were classified as "fast-track" for DN, while those in the lowest quintile who were also normoalbuminuric (n = 23) were classsified as "slow-track" for DN. Twenty-five normal subjects served as control subjects. SFs were cultured in medium with 25 mmol/l glucose for 36 h. SF mRNA expression levels for TGF-beta1, TGF-beta type II receptor (TGF-beta RII), thrombospondin-1, and latent TGF-beta binding protein-1 (LTBP-1) were measured by real-time RT-PCR. LTBP-1 mRNA expression was reduced in slow-track (0.99 +/- 0.38) versus fast-track patients (1.65 +/- 0.52, P = 0.001) and control subjects (1.41 +/- 0.7, P = 0.025). mRNA levels for TGF-beta1, TGF-beta RII, and thrombospondin-1 were similar in the three groups. Reduced LTBP-1 mRNA expression in SFs from slow-track patients may reflect genetically determined DN protection and suggests that LTBP-1 may be involved in the pathogenesis of DN through the regulation of TGF-beta activity.

ACE and PC-1 gene polymorphisms in normoalbuminuric Type 1 diabetic patients: a 10-year prospective study.

The aim of this study was to analyze the role of ACE gene insertion/deletion (I/D) and PC-1 gene K121Q polymorphisms in the changes of glomerular filtration rate (GFR), urinary albumin excretion rate (UAER), and blood pressure (BP) levels in a cohort of normoalbuminuric Type 1 diabetic patients. This is a 10.2+/-2.0-year prospective study of 30 normotensive normoalbuminuric Type 1 diabetic patients. UAER (immunoturbidimetry), GFR ((51)Cr-EDTA single injection technique), GHb (ion exchange chromatography), and BP levels were measured at baseline and at 1.7+/-0.6-year intervals. The presence of ACE gene I/D and PC-1 gene K121Q polymorphisms was determined by polymerase chain reaction (PCR) and restriction enzyme techniques. Three patients developed diabetic nephropathy (DN), all carriers of allele D. The presence of allele D was the only predictor (R(2)=.15, F=4.92, P=.035) of the observed GFR decline (-0.29+/-0.34 ml/min/month, P<.05). UAER increased during the study (log UAER=0.0275+/-0.042 microg/min/month, P=.002) and was associated with baseline UAER levels only (R(2)=.17, F=5.72, P=.024). A significant increase (P<.05) in cases of hypertension and retinopathy were observed in ID/DD (n=19) and not in II patients (n=11). Patients with the KQ/QQ genotype (n=8) presented a significant increase (P=.045) in new cases of retinopathy. In conclusion, the presence of the ACE gene D allele in this sample of normoalbuminuric normotensive Type 1 diabetic patients was associated with a higher proportion of microvascular complications and hypertension.

An increase in the cell component of the cortical interstitium antedates interstitial fibrosis in type 1 diabetic patients.

BACKGROUND: Interstitial expansion is important in the progression of a variety of kidney diseases, including diabetic nephropathy (DN). However, the interstitial elements that constitute interstitial expansion in DN are unknown and are the subject of this report. METHODS: Interstitial composition was analyzed in 15 long-standing type 1 diabetic patients, 8 with mild ( congruent with 1.5 x normal) and 7 with moderate ( congruent with 2 x normal) increases in cortical interstitial fractional volume [Vv(Int/cortex]. The mild group was 29 +/- 5 (mean +/- SD) years old with diabetes duration of 17 +/- 5 years. The moderate group was older (41 +/- 7 years; P < 0.03), had longer diabetes duration (28 +/- 7 years; P = 0.002), lower creatinine clearance (90 +/- 14 mL/min/1.73 m2 vs. 109 +/- 18 mL/min/1.73 m2; P = 0.05) and used antihypertensive medications more frequently (0/8 vs. 4/7; P < 0.03) compared to the mild group. Age- and gender-matched normal controls (N = 9) also were studied. Interstitial composition was evaluated by morphometric analysis of electron microscopic (EM) micrographs systematically obtained without bias at high (x 7500) and low (x 1500) magnification. RESULTS: Mild interstitial expansion was associated with an congruent with 50% increase in fractional volume of interstitial cells (P < 0.001) and congruent with 70% increase in fractional volume of interstitial nuclei (P < 0.01). Numerical density of interstitial nuclei was normal in these patients, suggesting that the interstitial cells might be larger rather than simply more numerous. An increase over normal in the interstitial fractional volume of fibrillary collagen of congruent with 50% was seen only with moderate expansion (P < 0.001), when creatinine clearance was already decreased. Interstitial expansion was associated with a decrease in volume and surface of peritubular capillaries as well as with a reduction in surface ratio of capillaries to tubules. CONCLUSIONS: In contrast to early mesangial expansion where matrix accumulation plays a dominant role, mild interstitial expansion in long-standing type 1 diabetic patients is largely due to an increase in the cell component of the interstitium. Increased fractional volume of interstitial fibrillary collagen is only seen at later stages of the disease, when the glomerular filtration rate is already reduced. Different pathogenetic processes may be operative in early diabetic glomerular and interstitial diseases.

Simulaçöes clínicas en medicina interna / Clinical simulations in internal medicine

Simulaçöes säo um instrumento didático valioso para o treinamento da tomada de decisöes clínicas, aspecto fundamental na formaçäo médica. O uso do computador pode tornar esse método mais ágil e eficiente. É nosso objetivo implementá-lo nas disciplinas do departamento de Medicina Interna da Faculdade de Medicina da Universidade Federal do Rio Grande do Sul. Com o auxílio de um microcomputador, dezessete simulaçöes clínicas estäo sendo experimentalmente aplicadas em uma turma do sexto semestre cursando a disciplina de Medicina Interna. A experiência inicial näo permite uma avaliaçäo da efetividade do método