[Combination therapy with insulin/sulfonylurea in the long-term therapy of type II diabetes following "secondary failure"]. / Die Kombinationstherapie Insulin/Sulfonylharnstoff in der Langzeittherapie des Typ-II-Diabetes nach "Sekundärversagen".

In type 2 diabetes with "secondary failure of sulfonylurea therapy" good metabolic control can seldom be achieved by insulin therapy even with high insulin doses. Hyperinsulinemia however is a possible risk factor of cardiovascular disease in type 2 diabetes. Maintaining the effects of sulfonylurea action insulin should be added in as small amounts as possible to avoid hyperinsulinemia and to ameliorate hyperglycemia. 16 type 2 diabetics with "secondary failure" were treated either with insulin alone (group A; n = 8) or with 3.5 mg b.i.d. glibenclamide plus small amounts of intermediate insulin (group B; n = 8) in a randomised order. After the inpatient period outpatient control was performed monthly up to six months, later on four times a year up to two years. Both groups were comparable with regard to age, duration of diabetes, body weight and metabolic control. The daily insulin dose was 14 +/- 2 IU (means +/- SEM) after one month and 19 +/- 2 IU after two years in group B. In contrast 30 +/- 3 IU and 43 +/- 5 IU respectively were needed in group A (p less than 0.001). All patients B were treated with one daily injection, all patients A needed two injections. Resulting in nearly identical metabolic control in group A basal insulin levels exceeded those in group B after two years significantly (28.6 +/- 3.7 vs. 18.6 +/- 1.6 mcU/ml; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Increased thromboplastic potential in diabetes: a multifactorial phenomenon.

Coagulation parameters, platelet aggregation, and thromboxane production as well as metabolic parameters were measured in 31 diabetic patients, 12 without and 19 with clinically manifest late complications, and in 14 healthy control subjects. Spontaneous in vitro aggregation as well as ADP, collagen, and arachidonic acid induced aggregation were higher in both groups of diabetic patients, without an increase in thromboxane B2 production. In diabetic patients with late complications an increase in fibrinogen, fibrinogen cyanogen bromide peptide, factor VIII related antigen, C1-esterase inhibitor, and antithrombin III was observed in comparison to healthy subjects. Fibrinogen, C1-esterase inhibitor, and factor VIII related antigen were already elevated in diabetic patients without clinically manifest late vascular complications. No strict correlations were found between serum glucose, glycosylated hemoglobin, and glycosylated albumin, on the one hand, and coagulation promoting or inhibiting factors, aggregation or thromboxane B2 production, on the other, in either control or diabetic subjects. Also no correlations existed between the coagulation parameters and the aggregation results. In vitro incubation of pooled normal plasma with different glucose concentrations had no influence on the methods by which the coagulation parameters were measured. These data indicate that rather early in the diabetic state many changes take place in different phases of the thrombostatic process, all resulting in an increased hemostatic diathesis.

Crossover study with human insulin (recombinant DNA) in type I diabetic subjects.

The activity of three combinations of regular and NPH human insulin (recombinant DNA) has been compared to that of an intermediate-acting pork insulin in a crossover study in type I diabetic subjects. After a prephase, the patients injected each insulin subcutaneously for 1 wk in different order. During the 5-wk period, daily glucose profiles were self-monitored, except at the end of each week, when blood was sampled for the determination of glucose, HbA1, glycosylated albumin, C-peptide, glucagon, and routine laboratory parameters. Fasting as well as mean daily glucose and mean amplitude of glucose excursions were similar during the treatment with pork and the various human insulin preparations. There was also no significant difference in C-peptide, glucagon, HbA1 or the routine laboratory parameters with each insulin tested. Glycosylated albumin, however, was significantly lower during the test period with intermediate-acting pork insulin and human insulin (25:75 regular:NPH), when compared with the prephase. We conclude that in type I diabetic subjects human insulin in special galenic preparations shows very similar metabolic activity to pork insulin.