Abstract. Landstedt-Hallin L, Englund A, Adamson U, Lins P-E (Karolinska Institute, Danderyd Hospital, Danderyd; and Uppsala University Hospital, Uppsala, Sweden). Increased QT dispersion during hypoglycaemia in patients with type 2 diabetes mellitus. J Intern Med 1999; 246: 299±307.Objectives. To study effects of insulin-induced hypoglycaemia on the cardiac repolarization, using QT interval measurements, in patients with type 2 diabetes. Design. Hypoglycaemia was induced by an i.v. insulin-infusion and blood glucose was clamped at 2.7 mmol L 21 for 60 min (T = 90±150 min) in two experiments, with (+GLIB) and without (±GLIB) glibenclamide. In a third experiment, with similar hyperinsulinaemia, glucose was clamped at a euglycaemic level (5 mmol L 21 ). ECG was continuously recorded for arrhythmia-monitoring, and 12-lead ECGs were recorded at T = 0 and 150 min. QT intervals were measured, and we determined QT dispersion (difference between the maximum and the minimum QT interval) reflecting interlead variability of repolarization.Subjects. Thirteen patients with type 2 diabetes, on combined insulin and glibenclamide treatment, were studied during hypoglycaemia, and eight of them participated in the euglycaemic experiment. Results. No significant arrhythmias were seen during hypoglycaemia but the mean QT intervals and QT dispersion increased significantly (P , 0.001), with no differences between ±GLIB and +GLIB. During the euglycaemic clamp all QT measurements remained unchanged. Serum potassium decreased significantly (P , 0.001) during all three clamps, but the decrease was more pronounced during hypoglycaemia. The change in potassium was not correlated to the degree of QT prolongation or QT dispersion. Conclusions. Significant changes in the repolarization of the heart can be seen during hypoglycaemia in patients with type 2 diabetes, indicating an increased risk of arrhythmia at low blood glucose levels.

PREDICTIVE (Predictable Results and Experience in Diabetes through Intensification and Control to Target: An International Variability Evaluation) is a large, multi-national, open-label, prospective, observational study assessing the safety and efficacy of insulin detemir in clinical practice. A total of 20,531 patients with type 1 or 2 diabetes from 11 countries were prescribed insulin detemir and followed up after a mean of 14.4 weeks. The primary endpoint was incidence of serious adverse drug reactions (SADRs), including major hypoglycaemia. Secondary endpoints were: haemoglobin A(1c) (HbA(1c)), mean self-monitored fasting glucose, within-patient fasting glucose variability and body weight change. Two hundred and fourteen patients (1%) reported SADRs, including major hypoglycaemia. The incidence of major hypoglycaemic episodes was reduced from 3.0/patient-year at baseline to 0.7/patient-year at follow-up in type 1 patients (p < 0.0001), and from 0.8 to 0.1/patient-year in type 2 patients (p < 0.0001). Insulin detemir improved glycaemic control in type 1 and type 2 patients, with reductions in mean HbA(1c) (0.5% and 0.9%, respectively, p < 0.0001 for both), fasting glucose (1.7 and 2.6 mmol/l, p < 0.0001 for both) and within-patient fasting glucose variability (0.7 and 0.5 mmol/l, p < 0.0001 for both). There was a small decrease in mean body weight in both type 1 and 2 patients (-0.1 kg, p < 0.01 and -0.4 kg, p < 0.0001 respectively). Insulin detemir was used once- or twice-daily in 49% and 50% of type 1 patients, and 77% and 23% of type 2 diabetes patients, respectively. The 14-week observations from PREDICTIVE support clinical trial data showing that insulin detemir improves glycaemic control, with a lowered risk of hypoglycaemia and no weight gain.

AimsMyocardial diastolic dysfunction (MDD) and impaired coronary flow reserve (CFR) are early signs of myocardial involvement in patients with diabetes. The important question of whether this may be reversed by glucose normalization has not been tested in a controlled clinical trial. We hypothesized that strict glycaemic control, particularly if insulin based, will improve MDD and CFR. Methods and resultsThirty-nine type 2 diabetes patients (mean age 61.0 + 7 years) with signs of diastolic dysfunction were randomly assigned to strict metabolic control by insulin (I-group; n ¼ 21) or oral glucose lowering agents (O-group; n ¼ 18). MDD and CFR were studied with Doppler-echocardiography including Tissue Doppler Imaging and myocardial contrast enhanced echocardiography. Fasting glucose (I-group ¼ 22.2 + 2.1; O-group 21.5 + 0.8 mmol/L) and HbA 1c were normalized (20.6 + 0.4 and 20.7 + 0.4%, respectively) in both groups, but this did not significantly improve MDD in either of the groups (P ¼ 0.65). There was no difference in CFR before and after improved glycaemic control. ConclusionThe hypothesis that strict glycaemic control would reverse early signs of MDD and improve CFR in patients with type 2 diabetes could not be confirmed, despite achieved normalization. Whether it is possible to influence a more pronounced diastolic dysfunction, particularly in less well-controlled diabetic patients, remains to be established.--

The limitations of current basal insulin preparations include concerns related to their pharmacokinetic and pharmacodynamic properties, hypoglycaemia, weight gain, and perception of management complexity, including rigid dosing schedules. Insulin degludec (IDeg) is a novel basal insulin with improved pharmacokinetic and pharmacodynamic properties compared to insulin glargine (IGlar) including a long half-life of ∼25 h and a duration of action >42 h at steady state, providing a flat and stable blood glucose-lowering effect when injected once daily. Evidence from phase 3a clinical trials with a treat-to-target design in patients with type 1 and type 2 diabetes has shown that IDeg has similar efficacy to IGlar, with a 9% and 26% reduction in risk of overall and nocturnal hypoglycaemia, respectively (in the pooled population) during the entire treatment period, and a 16% and 32% reduction during the maintenance period, respectively. Given its pharmacodynamic properties, IDeg offers a broad dosing window, allowing for flexible dose administration, if required. Two different formulations of IDeg are available (100 units/mL [U100] and 200 units/mL), the latter providing the same IDeg dose as the U100 formulation in half the injection volume. The unique pharmacokinetic profile of IDeg facilitates glycaemic control while minimising the risk of nocturnal hypoglycaemia.