Pulsatile insulin infusion and glucose-homeostasis in well-controlled type 1 (insulin-dependent) diabetic patients.

Pulsatile, intravenous insulin infusion designed to mimic the portal insulin concentrations that emerge physiologically after a meal, has been postulated to improve glucose tolerance in Type 1 (insulin-dependent) diabetic patients. We studied the effects of insulin pulsing (10 i.v. pulses of human insulin of 0.035 U kg-1 idealised body weight were given, each of 20 s duration, with intervals of 6 min, three times per day covered with adequate administration of glucose) on 2 successive days on glucose-tolerance in nine well-controlled Type 1 diabetic patients on continuous subcutaneous insulin infusion therapy (age 26 (7) years, mean (SD); duration of diabetes 10 (7) years; body mass index 23.4 (2.3) kg m-2; HbA1c 6.0 (0.6)%). On the days before and after the insulin pulsing, the patients were subjected to metabolic assessments by an oral glucose tolerance test (1 g glucose kg-1 body weight) 30 min after the subcutaneous injection of 0.15 U kg-1 body weight regular human insulin and a subsequent bicycle-ergometer test. During these metabolic assessments, plasma free insulin concentrations, plasma glucagon and the non-protein respiratory quotient remained unaffected by the insulin pulsing. However, glucose tolerance deteriorated significantly (maximal glucose concentration 120 min after glucose load was 10.0 mmol l-1 before and 13.9 mmol l-1 after insulin pulsing, P less than 0.01). In conclusion, the pattern of insulin pulsing used in this study did not ameliorate oral glucose homeostasis in well-controlled Type 1 (insulin dependent) diabetic patients.

Clinical outcome of using insulin at 40 IU/ml and 100 IU/ml in pump treatment. Results of a controlled multi-center trial.

In three different diabetes centers the use of insulin at a strength of 40 IU/ml (U40) and 100 IU/ml (U100) in continuous subcutaneous insulin infusion (CSII) treatment of insulin dependent (Type I) diabetic patients was compared in a randomized cross-over design. Forty-six Type I diabetic patients, all previously treated with CSII for at least one year, completed consecutively two 13-week periods of treatment with U40 and U100. Body weight and insulin requirements were identical at the end of the two periods. Slightly higher levels of glycemia were recorded during U40 when compared to U100 treatment: mean blood glucose was 142 +/- 34 (SD) vs. 133 +/- 34 mg/dl (2 p less than 0.01). The same tendency was observed in the mean glycosylated hemoglobin value (6.84 +/- 1.35 vs. 6.65 +/- 1.13%, 2 p greater than 0.1). There were no significant differences between U40 and U100 in the number of catheters used and the number of catheter blockages reported, while the development of subcutaneous nodules at the insertion sites was significantly more frequent during U40 treatment. It is concluded that the implementation of insulin in the strength of 100 IU/ml is as effective as the use of insulin in the strength of 40 IU/ml for CSII therapy, and might even be associated with slightly improved glycemic control and less subcutaneous side-effects.

Day to day variations in morphology and duration of fragmented ventricular potentials during the late post-myocardial infarction phase in conscious dogs.

The relationship between the inducibility of ventricular tachyarrhythmias and the presence of fractionated epicardial ventricular electrograms ('late potentials') was studied daily between days 3 and 8 after experimental myocardial infarction in 15 conscious dogs. Before each programmed stimulation, epicardial infarct zone electrograms were recorded from implanted 'composite' electrodes during sinus rhythm. There was considerable daily variation in the morphology and duration of delayed ventricular activation, but no significant difference in duration of infarct zone electrograms was seen between studies resulting in ventricular fibrillation (108 +/- 62 ms, mean +/- SD), sustained ventricular tachycardia (87 +/- 18 ms), nonsustained (94 +/- 41 ms) or no tachycardia (78 +/- 5 ms). Although fractionated ventricular electrograms were commonly recorded early after infarction, their presence and duration could not predict the inducibility of malignant ventricular tachyarrhythmias. Similar limitations may apply in clinical practice to the use of surface signal averaging of ventricular late potentials in the early post-myocardial infarction period.

Day-to-day variations in inducibility of ventricular tachyarrhythmias during the late postmyocardial infarction phase in conscious dogs.

The inducibility of ventricular tachyarrhythmias was studied daily on days 3 through 8 after experimental myocardial infarction in 15 conscious dogs. Although a sustained ventricular tachyarrhythmia was produced on one or more occasions in 11 of 15 dogs (73%), there was marked daily variation in the results of programmed stimulation. Ventricular fibrillation or sustained ventricular tachycardia was elicited in six dogs on day 3 after infarction. In two of these dogs, no sustained tachycardia could be induced by day 7. In nine dogs sustained ventricular arrhythmias were not inducible on day 3. By day 6 to 7, sustained ventricular tachycardia was inducible in five of these dogs. In clinical practice similar variation in the inducibility of sustained ventricular arrhythmias may conceivably complicate the use of results of programmed ventricular stimulation as determinants of risk of sudden death after myocardial infarction.

Actions of disopyramide on potential reentrant pathways and ventricular tachyarrhythmias in conscious dogs during the late post-myocardial infarction phase.

The effect of intravenous disopyramide (plasma level 3.7 +/- 1.6 micrograms/ml, mean +/- standard deviation) on reentrant ventricular tachyarrhythmias was studied by programmed ventricular stimulation in 11 conscious dogs 3 to 8 days after experimental myocardial infarction. Sustained ventricular tachycardia (VT) was induced in 4 dogs (mean cycle length 173 +/- 14 ms) and nonsustained VT in 7 (8 +/- 4 beats, mean cycle length 136 +/- 18 ms). Disopyramide prevented induction of VT in 1 of 4 dogs with sustained VT and 3 of 7 with nonsustained VT, and increased VT cycle length by more than 30% in 2 dogs with sustained VT and 2 of 7 with nonsustained VT. Disopyramide prolonged refractoriness in the infarct zone, measured by analysis of electrograms from an implanted "composite" electrode, by 38 to 53%, depending on the mode of pacing. These values were significantly greater than the increase produced by disopyramide in ventricular effective refractory period (13 +/- 12%), QRS duration and QT interval. Disopyramide has a selective effect on potential reentry circuits in ischemic myocardium, and prolongs refractoriness in abnormal myocardium to a greater extent than its effect on the normal ventricle.

Action of sotalol on potential reentrant pathways and ventricular tachyarrhythmias in conscious dogs in the late postmyocardial infarction phase.

Sotalol is a beta-adrenergic blocker that also prolongs action potential duration and myocardial refractoriness over the short term (class III effect). Its short-term antiarrhythmic effects were compared with those of metoprolol, which has neither short-term class III nor membrane-stabilizing action, on reentrant ventricular arrhythmias produced by programmed stimulation in 17 conscious dogs 3 to 8 days after myocardial infarction. Ventricular arrhythmias were prevented or significantly slowed by sotalol in 11 of 19 studies (58%) compared with in one of 14 (7%) studies with metoprolol. Sotalol prolonged refractoriness in the infarct zone, measured from an implanted "composite" electrode, by 41 +/- 45% (mean +/- SD, p less than .01), which was significantly greater than the increases it produced in effective refractory period of the normal ventricle (14.0 +/- 5.5%) or QT interval (12.5 +/- 7.8%). Metoprolol had no effect on infarct-zone refractoriness. Sotalol differentially increases refractoriness in potential reentry circuits in ischemic myocardium. Its antiarrhythmic effect in this model is not due to beta-blockade, and is presumably related to prolongation of action potential duration.