OBJECTIVE -The aim of this study was to assess in an 11-year survival follow-up of a population-based cohort of type 2 diabetes the predictive role of World Health Organizationdefined metabolic syndrome, independent of conventional cardiovascular risk factors. -up (1991-2001), 1,565 patients were regularly examined with centralized measurements of HbA 1c . The independent role of the metabolic syndrome as a predictor of all-cause and cardiovascular mortality was assessed with multivariate Cox proportional hazards modeling. RESEARCH DESIGN AND METHODS -During the followRESULTS -At baseline, the prevalence of the metabolic syndrome was 75.6% (95% CI 73.6 -77.9). Results are based on 685 deaths (520 with the metabolic syndrome and 165 without it) in 10,890.2 person-years of observations. With respect to subjects without the metabolic syndrome, those with the metabolic syndrome had a similar hazard ratio (HR) of cardiovascular mortality after adjustment for age, sex, smoking, total cholesterol level, and coronary heart disease. In contrast, relative to subjects with diabetes only, the HR of subjects with only one component of the syndrome was 2.92 (1.16 -7.33), independent of other risk factors.CONCLUSIONS -We found that 1) the prevalence of the metabolic syndrome in a population-based cohort of type 2 diabetes is high (75.6%); 2) the metabolic syndrome is not a predictor of 11-year all-cause and cardiovascular mortality; and 3) more than twofold higher cardiovascular risk, independent of conventional risk factors, is evident in diabetic subjects with only one component of the syndrome compared with those with diabetes only. Categorizing type 2 diabetic subjects as having or not having the metabolic syndrome does not provide further prediction compared with the knowledge of its single components.

Abstract. Veglio M, Bruno G, Borra M, Macchia G, Bargero G, D'Errico N, Pagano GF, Cavallo-Perin P (Evangelico Valdese Hospital, Torino; University of Torino, Torino; and S. Spirito Hospital, Casale Monferrato; Italy). Prevalence of increased QT interval duration and dispersion in type 2 diabetic patients and its relationship with coronary heart disease: a population-based cohort. J Intern Med 2002; 251: 317-324.Objective. To evaluate the prevalence of prolonged QT interval and dispersion in a population-based cohort of type 2 diabetic patients and their relationship with clinical and metabolic variables. Design. Cross-sectional population-based cohort. Setting. Diabetes clinics and general practitioners in Casale Monferrato (Northern Italy). Subjects. A total of 1357 patients with known type 2 diabetes (70% of the cohort). Main outcome measures. Albumin excretion rate and coronary heart disease (CHD); a standard supine 12-lead electrocardiogram (ECG) was recorded and coded according to the Minnesota code criteria. QT interval corrected for heart rate (QTc) > 0.44 s and QTc dispersion > 0.080 s were considered abnormally prolonged.Results. Prevalence of increased QTc duration and QTc dispersion were 25.8% (95% CI 23.5-28.3) and 33.1% (95% CI 30.6-35.7), with no sex differences. No metabolic differences were found, apart from fibrinogen and creatinine levels, which were higher in patients with increased QTc dispersion. Patients with CHD had higher mean adjusted values of QTc and QTc dispersion, whereas no association was found with albumin excretion rate (AER) and diabetes treatment. QTc duration and QTc dispersion were significantly correlated (0.17, P < 0.001). In multiple regression analysis, only CHD was independently associated with QTc, after adjustment for age and sex (b ¼ 0.010, P < 0.001, R 2 ¼ 2.5%); as regards QTc dispersion, a similar association with CHD was found (b ¼ 0.20, P < 0.001, R 2 ¼ 4.8%). Conclusions. This population-based study shows a considerably high prevalence of increased QTc and QTc dispersion in type 2 diabetic patients and their association with CHD. These findings have both epidemiological and clinical relevance, as they might be implicated in the excess mortality risk of type 2 diabetic patients.

Aims/hypothesis Estimated glomerular filtration rate (eGFR) predicts mortality in non-diabetic populations, but its role in people with type 2 diabetes is unknown. We assessed to what extent a reduction in eGFR in people with type 2 diabetes predicts 11-year all-cause and cardiovascular mortality, independently of AER and other cardiovascular risk factors. Materials and methods The study population was the population-based cohort (n=1,538; median age 68.9 years) of the Casale Monferrato Study. GFR was estimated by the abbreviated Modification of Diet in Renal Disease Study equation. Results At baseline, the prevalence of chronic kidney disease (eGFR <60 ml min −1 1.73 m −2 ) was 34.3%(95% CI 33.0-36.8). There were 670 deaths in 10,708 person-years of observation. Hazard ratios of 1.23 (95% CI 1.03-1.47) for all-cause mortality and 1.18 (95% CI 0.92-1.52) for cardiovascular mortality were observed after adjusting for cardiovascular risk factors and AER. When five levels of eGFR were analysed we found that most risk was conferred by eGFR 15-29 ml min −1 1.73 m −2 , whereas no increased risk was evident in people with eGFR values between 30 and 59 ml min −1 1.73 m −2 . In an analysis stratified by AER categories, a significant increasing trend in risk with decreasing eGFR was evident only in people with macroalbuminuria. Conclusions/interpretation Our study suggests that in type 2 diabetes macroalbuminuria is the main predictor of mortality, independently of both eGFR and cardiovascular risk factors, whereas eGFR provides no further information in normoalbuminuric people.

OBJECTIVE -The first sign of diabetic nephropathy is microalbuminuria, but its predictive role of progression to overt nephropathy in type 2 diabetes has not yet been clarified. The aims of this study were to assess during 7 years of follow-up the incidence rate of overt nephropathy and the predictive role of microalbuminuria and other baseline variables (blood pressure, lipids, fibrinogen, uric acid, smoking, and HbA 1c cumulative average during follow-up). RESEARCH DESIGN AND METHODS-A prospective population-based study was performed in Casale Monferrato, Italy, including 1,253 type 2 diabetic patients recruited at baseline (1991)(1992), 765 with normoalbuminuria (albumin excretion rate [AER] Ͻ20 g/ min) and 488 with microalbuminuria (AER 20 -200 g/min). All measurements were centralized. A nested case-control study within the cohort was performed, selecting four control subjects, frequency matched for age and attained individual time of follow-up with each case. Conditional regression analysis was performed to assess variables independently associated with risk of progression to overt nephropathy.RESULTS -Of 1,253 total patients, 1,103 (88.0%) were included in the follow-up examination (median 5.33 years); their age and duration of disease at baseline were 68.4 Ϯ 10.5 years and 10.4 Ϯ 6.6 years, respectively. Cases of overt nephropathy were 202, giving an incidence rate of 37.0/1,000 person-years (95% CI 32.3-42.6). In conditional logistic regression analyses, microalbuminuria provided a 42% increased risk with respect to normoalbuminuria (95% CI 0.98 -2.06), independently of duration of diabetes, hypertension, and systolic blood pressure. Other variables independently associated with progression to overt nephropathy were HbA 1c cumulative average (P ϭ 0.002), apolipoprotein B (P ϭ 0.013), fibrinogen (P ϭ 0.02), and HDL cholesterol (P ϭ 0.03).CONCLUSIONS -Of type 2 diabetic patients, 3.7% progress every year to overt nephropathy. Microalbuminuria is associated with a 42% increased risk of progression to overt nephropathy. Other independent predictors are HbA 1c , HDL cholesterol, apolipoprotein B, and fibrinogen. Diabetes Care 26:2150 -2155, 2003T emporal trends of end-stage renal disease (ESRD) caused by diabetic nephropathy are increasing worldwide, so that diabetes represents the second leading cause of dialysis in most centers (1,2). The first sign of renal involvement is microalbuminuria, which affects 20 -40% of patients with type 2 diabetes (3). When macroalbuminuria occurs, glomerular filtration rate declines, with an average reduction of 10 -12 ml ⅐ min Ϫ1 ⅐ yearThe predictive role of microalbuminuria in progression to overt nephropathy in type 2 diabetes has not yet been clarified, however (4 -6). With respect to previous studies, more recent ones have suggested a lesser predictive role (5,6). A benefit of lipid-lowering treatment on risk of progression to overt nephropathy has also been hypothesized (7). Abnormalities in lipoprotein metabolism, such as elevations in triglycerides and apolipoprotein...

Patients with non-insulin-dependent diabetes mellitus had a high prevalence of hyperfibrinogenemia. Fibrinogen level was independently associated with hemoglobin A1c value and albumin excretion rate, which suggests that fibrinogen may be involved in the increased cardiovascular risk of patients with diabetes mellitus.