The QT interval reflects the total duration of ventricular myocardial depolarization and repolarization: a prolonged QT interval is associated with sudden death and poor survival in apparently healthy subjects [1]. The relation of QT interval prolongation with diabetes complications, poor survival prognosis and sudden death has recently received considerable interest. It has been postulated that QT prolongation accounts for higher mortality in people with diabetes and its complications as the prevalence of QT interval prolongation is higher among patients with Type I (insulin-dependent) diabetes mellitus [2], ischaemic heart disease (IHD) [3±7], end stage renal disease [8] and autonomic neuropathy [2, 9±12].Data on QT interval in diabetic patients are, however, mainly derived from small, selected samples [9±15]. In particular, the prevalence of QT interval prolongation and its relation with cardiac autonomic neuropathy has been evaluated in only one cross-sec- Diabetologia (1999) Summary The prevalence of QT interval prolongation is higher in people with diabetes and its complications. Sudden death has been reported as a common cause of death in insulin-dependent diabetic patients affected by autonomic neuropathy. It has been postulated that QT prolongation predisposes to cardiac arrhythmias and sudden death. In this analysis the prevalence of QT interval prolongation and its relation with diabetic complications were evaluated in the EURODIAB IDDM Complications Study (3250 insulin-dependent diabetic patients attending 31 centres in 16 European countries). Five consecutive RR and QT intervals were measured with a ruler on the V5 lead of the resting ECG tracing and the QT interval corrected for the previous cardiac cycle length was calculated according to the Bazett's formula. The prevalence of an abnormally prolonged corrected QT was 16 % in the whole population, 11 % in males and 21 % in females (p < 0.001). The mean corrected QT was 0.412 s in males and 0.422 s in females (p < 0.001). Corrected QT duration was independently associated with age, HbA 1 c and blood pressure. Corrected QT was also correlated with ischaemic heart disease and nephropathy but this relation appeared to be stronger in males than in females. Male patients with neuropathy or impaired heart rate variability or both showed a higher mean adjusted corrected QT compared with male patients without this complication. The relation between corrected QT prolongation and autonomic neuropathy was not observed among females. In conclusion we have shown that corrected QT in insulin-dependent diabetic female patients is longer than in male patients, even in the absence of diabetic complications known to increase the risk of corrected QT prolongation. [Diabetologia (1999) 42: 68±75]

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.

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.

This population-based study showed high prevalence of micro- and macroalbuminuria in NIDDM subjects, who were characterized by a more adverse pattern of cardiovascular risk factors.

The question as to whether the QTc interval correlates with five cardiovascular tests (deep breathing test, 30/15 ratio test, lying to standing test, cough test, and postural blood pressure test) for the diagnosis of diabetic autonomic neuropathy (DAN) was investigated in 168 (38 Type 1, 130 Type 2) consecutive outpatients (mean age 54.9 +/- 11.2 years). QT interval was measured on an ECG recorded at rest and QTc calculated according to Bazett's formula. The percentage of patients with a QTc greater than 0.440 s was: absent DAN = 11% (n = 7), probable DAN = 7% (n = 4), definite DAN = 23% (n = 12) (p < 0.05), and the mean (+/- SD) QTc values were 0.403 +/- 0.028 s, 0.405 +/- 0.023 s, and 0.421 +/- 0.026 s, respectively. A significant correlation between QTc duration and DAN score of autonomic cardiovascular test results (r = 0.34, p < 0.0001) was observed. The calculated specificity, sensitivity, positive and negative predictive values were 89%, 15%, 70% and 37%, respectively. In conclusion, QTc can be considered as an additional specific test in the assessment of diabetic autonomic neuropathy, but cannot replace the standard battery of cardiovascular tests.