Hormonal and glycaemic responses to serial meals in newly diagnosed non insulin dependent diabetic patients.

The hormonal and glycaemic responses to serial test meals have been well documented in normal subjects and in patients with insulin dependent diabetes. There is less information in patients with non-insulin dependent diabetes. We studied 39 newly diagnosed previously untreated non-insulin dependent diabetics. Each patient received four identical test meals over a 24 hour period and their plasma glucose and insulin levels were determined at frequent intervals throughout the study period. The results show that all the non-insulin dependent patients at diagnosis had large post-prandial glucose excursions, and that the post-prandial rise in insulin was delayed. The study also demonstrates that glucose and insulin profiles are dependent on the degree of obesity of the patient. Patients with non-insulin dependent diabetes have a greater degree of glucose intolerance in the morning in contrast to normal subjects whose glucose tolerance is best in the morning.

The influence of aprotinin on regional absorption of soluble human insulin.

1. The absorption of 6U of soluble human insulin following subcutaneous injection into the anterior abdominal wall, thigh and into the thigh following admixture with aprotinin was assessed in normal subjects. The plasma immunoreactive insulin profiles were determined during a 6 h post injection period in subjects receiving concomitantly somatostatin to suppress endogenous insulin secretion. 2. Subcutaneous injection of human insulin into the anterior abdominal wall compared with the thigh led to significantly higher incremental insulin levels between 30 and 50 min (P less than 0.05) followed by lower values at 240-300 min (P less than 0.05). The absorption of soluble human insulin from a subcutaneous depot is faster from the anterior abdominal wall compared with the thigh associated with a faster clearance from plasma. 3. Injection into the thigh of insulin admixed with aprotinin resulted in higher plasma insulin levels at 10 min (P less than 0.001) and 20 min (P less than 0.05) compared with insulin given alone. Similarly, the insulin level was significantly higher with the admixture between 10 and 20 min (P less than 0.05) compared with insulin into the anterior abdominal wall. 4. Admixture of insulin with aprotinin therefore leads to an acceleration of the early phase of absorption from subcutaneous tissue due to a local hyperaemic effect.

Soluble and Lente human insulin mixtures in normal man.

The interaction between soluble (Actrapid HM) and Lente (Monotard HM) human insulin preparations was examined in normal subjects. Incremental plasma insulin levels were determined following the subcutaneous administration of 6 U of soluble insulin admixed with 0.14 ml soluble insulin diluting medium, or 0.14 ml Lente diluting medium and injected either immediately or 5 min after preparation. For comparison separate but simultaneous injections of soluble (6 U) and Lente insulin (14 U) were administered subcutaneously. All injection volumes were identical. The incremental insulin levels were significantly greater between 60 and 90 min (p less than 0.05-0.01) following the administration of soluble insulin admixed with its own medium compared to the soluble insulin/Lente medium admixtures injected immediately and 5 min after preparation. There was no difference, however, in the plasma insulin profiles between the two soluble insulin/Lente medium schedules. The separate simultaneous administration of soluble and Lente insulin resulted in significantly higher plasma insulin levels at 30 and 90 min (p less than 0.05) when compared to the admixture injected immediately after preparation and from 30-120 min (p less than 0.05-0.01) compared to the admixture injected after 5 min. The two soluble/Lente insulin admixtures achieved similar plasma insulin profiles. Therefore when soluble human insulin is admixed with Lente human insulin and administered by subcutaneous injection immediately after admixing there is a significant reduction in the plasma insulin levels during the first 90 min in contrast to when the two preparations are given simultaneously by separate injection. Delaying the injection of the admixture for 5 min results in significantly lower insulin levels up to 120 min. These differences are reflected in the hypoglycaemic responses observed.

Cholesterol-lowering effect of mevinolin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme a reductase, in healthy volunteers.

Mevinolin reduces cholesterol synthesis by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase. The safety and effectiveness of this agent was evaluated in a double-blind, placebo-controlled study in 59 healthy men (serum cholesterol 3.88--7.76 mmol/liter) in five centers. Subjects maintained their usual diet and activities. Doses of 6.25, 12.5, 25, or 50 mg twice daily for 4 wk produced mean reductions of total serum cholesterol fo 23--27% [vs. placebo (4%), P less than 0.01]. Mean low density lipoprotein cholesterol fell 35--45%, while high density lipoprotein and very low density lipoprotein cholesterol, and triglycerides were not significantly affected. Mean apolipoprotein B fell 27--34%. 50 mg was not significantly more effective than 6.25 mg. Mevinolin was generally well tolerated, and no serious clinical or laboratory abnormalities occurred. One subject (12.5 mg) was withdrawn because of abdominal pain and diarrhea. These results suggest that if long-term safety can be demonstrated, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase are likely to prove useful in the treatment of hypercholesterolemia.

The effect of propranolol on thyroid hormones in T3 toxicosis.

Serum thyroid hormone concentrations were measured before and during 6 months treatment with propranolol (160 mg/day) in eight patients with T3 (triiodothyronine) toxicosis. Serum total T3 concentrations showed a significant (p less than 0.01) and sustained fall to approximately 80% of pre-treatment values. Six of the patients, however, remained clinically and biochemically hyperthyroid and our data do not support the use of propranolol as sole therapy in T3 toxicosis.

Beta-adrenoreceptor blocking drugs and thyroid hormones in hyperthyroid subjects.

Serum thyroid hormone concentrations were measured before and during 10 days' treatment with atenolol (200 mg/day), acebutolol (400 mg/day), oxprenolol (160 mg/day) and propranolol (160 mg/day) in 24 hyperthyroid patients. During propranolol treatment serum triiodothyronine (T3) concentrations fell significantly (P less than 0.05) but there was no change in thyroid hormone concentrations in the other groups although all patients reported a symptomatic improvement.