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Objective: To evaluate the predictive role of increased corrected QT (QTc) and QT interval dispersion (QTd) on all-cause and cardiovascular mortality in a large, unselected type 2 diabetic population., Research Design and Methods: The prospective study included 1,357 type 2 diabetic patients from the Casale Monferrato Study. At baseline, QTc intervals >0.44 s and QTd intervals >0.08 s were considered abnormally prolonged. Both all-cause and cardiovascular mortality were assessed 15 years after the baseline examination., Results: During the follow-up period, 862 subjects per 12,450 person-years died. Multivariate analysis showed that the hazard ratio (HR) of cardiovascular mortality was significantly increased in subjects with prolonged QTd (1.26 [95% CI 1.02-1.55]) and was only slightly reduced after multiple adjustments. Conversely, prolonged QTc did not increase the HRs for all-cause or cardiovascular mortality., Conclusions: Increased QTd predicts cardiovascular mortality after a long-term follow-up period in a large, unselected population of type 2 diabetic subjects.

Unlabelled: AIMS Although left ventricular hypertrophy (LVH) defined by either standard 12-lead ECG or echocardiography strongly predicts cardiovascular mortality, its prevalence in Type 2 diabetes is largely unknown. We have assessed prevalence of ECG-LVH and its relationship with clinical and metabolic variables in an Italian population-based cohort of subjects with Type 2 diabetes. METHODS The study-base was 965 (61.3%) subjects with Type 2 diabetes of the population-based cohort living in Casale Monferrato (Italy). LVH was defined by ECG Cornell voltage-duration product. All measurements were centralized. RESULTS ECG-LVH was diagnosed in 165/965 subjects, giving a prevalence of 17.1% (95% CI 14.7-19.5). Large sex differences were found, with higher prevalence in women (23.5%, 19.9-27.0) than in men (8.4%, 5.6-11.0), even after adjustment for age, BMI and hypertension (OR 3.83, 95% CI 2.5-5.9). At the examination, subjects with ECG-LVH were older than those without it. Similar age- and sex-adjusted values of HbA(1c), plasma lipids, fibrinogen, uric acid and creatinine were found in the two subgroups. No differences in prevalence of hypertension, CHD, increased QT duration or dispersion, micro- and macro-albuminuria were found between subjects with ECG-LVH and those without it. In logistic regression analysis, variables independently associated with ECG-LVH, after age-adjustment, were sex and diastolic blood pressure., Conclusions: This population-based study shows: (i) a high prevalence of ECG-LVH in Type 2 diabetic subjects; (ii) 3-fold higher risk in women than in men, independently of age, BMI, and blood pressure; (iii) an independent association between ECG-LVH and diastolic blood-pressure. Screening for ECG-LVH in diabetic subjects is therefore recommended, particularly in diabetic women., (Copyright 2004 Diabetes UK)

Insulin secretion is one of the functions mediated by CD38, a nonlineage pleiotropic cell surface receptor. The molecule is the target of an autoimmune response, because serum autoantibodies (aAbs) to CD38 have been detected in diabetic patients. In the healthy Caucasian population, the CD38 gene is bi-allelic (86% CD38*B and 14% CD38*A), whereas an Arg140Trp mutation has been identified in Japanese diabetic patients. We investigated the relationship between CD38 and diabetes in Caucasian patients by characterizing anti-CD38 aAbs in terms of prevalence and function (agonistic/nonagonistic activity) and by exploring the potential influence of the CD38 genetic background. A novel enzymatic immunoassay, using recombinant soluble CD38 as the target antigen, was developed for the analysis of anti-CD38 aAb titers. Sera from 19.15% of type 1 and 16.67% of type 2 diabetic patients were positive. The majority of anti-CD38 aAbs (57.14%) displayed agonistic properties, i.e., they demonstrated the capability to trigger Ca2+ release in lymphocytic cell lines. In agreement with these functional features, the presence of anti-CD38 aAbs in type 2 diabetic patients was associated with significantly higher levels of fasting plasma C-peptide and insulin, as compared with anti-CD38-counterparts. No diabetic subject carrying the Arg140Trp mutation and no preferential association between diabetes or aAb status and the CD38*A allele was found in the study population. These results show the significance of anti-CD38 aAbs as a new diagnostic marker of beta-cell autoimmunity in diabetes. Moreover, the prevalent agonistic activity of these aAbs suggests that they could mediate relevant effects on target cells by means of Ca2+ mobilization.

Background and Aim: Serum apolipoprotein H (Apo H) levels are increased in hyperlipidemic subjects and type 2 diabetics, but unknown in microalbuminuria, another disorder with an increased cardiovascular risk. We looked to see whether increased Apo H levels are associated with microalbuminuria in type 2 diabetes., Methods and Results: Serum Apo H was calculated in 20 normoalbuminuric and 17 microalbuminuric type 2 diabetics matched for age, sex, body mass index (BMI), glycosylated haemoglobin, plasma lipids and duration of diabetes, and also compared with 20 non-diabetic controls matched for age, sex, BMI and plasma lipids. Mean serum Apo H was significantly higher in the microalbuminuric patients (31.12 +/- 1.58 SEM vs 25.25 +/- 1.52 and 24.72 +/- 0.99 mg/dL, p = 0.003)., Conclusion: Serum apo H levels are increased in type 2 diabetics with microalbuminuria.