Prolonged QTc interval predicts mortality in patients with Type 1 diabetes mellitus.

AIMS: To evaluate prolonged QTc interval and QT dispersion as predictors of all-cause and cardiovascular mortality after adjustment for well-established risk factors in Type 1 diabetic patients. METHODS: From a cohort of all adult Type 1 diabetic patients, duration of diabetes >or= 5 years, attending the clinic in 1984 and followed in an observational study for 10 years (n = 939), all subjects with resting baseline electrocardiograms were identified (n = 697, 360 males). The QT length was measured and corrected for heart rate (QTc). Maximal QTc length (QTc max) and QT dispersion were determined. RESULTS: At baseline, 431 had normoalbuminuria (< 30 mg/24 h), 138 had microalbuminuria (30-299 mg/24 h) and 128 had macroalbuminuria (>or= 300 mg/24 h) of whom 66 (15%), 35 (25%) and 61 (48%) died during follow-up, respectively (26 (6%), 14 (10%), 21 (16%) from cardiovascular disease). QTc max. was 442 (1.2) ms (mean (SEM)) for survivors and 457 (3.7) in patients who died (P < 0.001). In a Cox proportional hazards model including baseline values of putative risk factors, independent predictors of death were QTc max (P = 0.03), age (P < 0.001), presence of hypertension (P = 0.001), male sex (P < 0.001), log urinary albumin excretion (P < 0.001), smoking (P = 0.04), log serum-creatinine (P < 0.001), height (P < 0.001), low social class (P = 0.04), whereas QT dispersion, heart rate, and HbA1c were not included. In the subgroup with macroalbuminuria, but not for all patients, QTc max was an independent risk factor for cardiovascular mortality. CONCLUSION: QTc prolongation, but not increased QT dispersion, is an independent marker of increased mortality in patients with Type 1 diabetes mellitus.

Second messengers and ion channels in acetylcholine-induced chloride secretion in hen trachea.

1. Hen tracheal epithelium can be stimulated by serosal application of acetylcholine (ACh) to secrete Cl- equal to approximately 60-90 microA/cm2. 2. Radio-ligand-displacement for IP3, cAMP and cGMP and ion channel selective drugs in voltage clamp set-ups were employed to characterize second messengers and Cl-, K+ and Ca2+ channels involved in the ACh response. 3. ACh induced a significant rise in IP3 in isolated tracheocytes, while ACh did not influence the production of cAMP in whole tissue, isolated tracheocytes or basolateral cell membrane vesicles. Further ACh desensitization did not effect cAMP level in tracheocytes. In addition neither ACh stimulation nor desensitization interfered with cAMP production in presence of 4.5 microM forskolin in tracheocytes, a level of forskolin rising base level cAMP by around five fold. 4. Around 35% of ACh Cl- secretion depends on Ca2+ mobilization from internal stores and about 65% on Ca2+ influx over basolateral membrane. The activated Ca2+ channel is insensitive to class I, II, III and IV Ca2+ antagonists. 5. A 23187 can mimic the ACh effect although 30% is indomethacin-sensitive demonstrating a prostaglandin activated adenylyl cyclase. 6. Two K+ channels are involved in ACh secretion, one sensitive to Ba2+ and quinine and both insensitive to 4-aminopyridine, apamin, charybdotoxin and TEA. 7. Flufenamate and triaminopyrimidine block a non-selective ion channel likely involved in the ACh response. An ACh activated apical Cl- channel is NPPB-sensitive.