The effects of FFA on hepatic insulin clearance were studied in the in situ perfused rat liver. Clearance decreased with increasing body weight (age) of the rats. When FFA were added to the perfusate a 40% reduction of hepatic removal of insulin was found over the normal, physiological range (< 1,000 ,umol/ liter), less pronounced in heavier rats. When perfusion was started with high concentrations of FFA, inhibition was rapidly reversible, a phenomen again blunted in heavier rats. In contrast to FFA, different glucose concentrations in the perfusate did not affect the hepatic insulin uptake in the presence of FFA within physiological concentrations.Thus, hepatic clearance of insulin is proportional to rat weight (age) and portal FFA concentrations. Other studies have recently shown that fatty acids inhibit insulin binding, degradation, and function in isolated rat hepatocytes, and that hepatic clearance is inversely dependent on hepatic triglyceride concentrations, both inhibitions reversible by prevention of fatty acid oxidation. It is suggested that the diminished hepatic clearance of insulin in heavier (older) rats is at least partly due to their relative obesity and increased hepatic triglyceride contents. This effect as well as that of portal FFA is probably mediated via fatty acid oxidation in the liver. This mechanism may have implications for the regulation of hepatic metabolism, and peripheral insulin concentrations. (J. Clin. Invest.

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Six men and three women with insulin-dependent diabetes (without complications) participated in physical training three times a week for 20 weeks. Physical training did not change the concentration of fasting blood-glucose, glucose excretion in urine or glucosylated haemoglobin (HbA1). However, the glucose disposal rate during euglycaemic clamp increased after training. In two patients a minor reduction of insulin dosage was necessary to alleviate slight hypoglycaemic episodes. The training resulted in significant increases in quadriceps isometric and dynamic strength and endurance. Maximal oxygen uptake increased by 8%, the activity of glycolytic enzymes in vastus lateralis muscle by 47% for hexokinase, and 30% for tri-osephosphate dehydrogenase and 25% for lactic dehydrogenase, the activity of oxidative enzymes by 42% for citrate synthase and 46% for 3-hydroxy-acyl-CoA-dehydrogenase. The glycogen concentration in the vastus lateralis muscle did not change significantly. Lipoprotein lipase activity did not change in muscle, nor in adipose tissue. The mean muscle fibre area increased by 25% and the area of FTa fibres by 30%. The new formation of capillaries around different muscle fibres was significant for FTb fibres (26%). The proliferation of capillaries, however, appeared to be insufficient to cope with the increased area of muscle fibres. As a result, the mean area of muscle fibre supplied by one capillary (a measure of diffusion distance) significantly increased after training for FTa fibres. It is concluded that with the exception of deficient proliferation of capillaries, patients with insulin-dependent diabetes mellitus show a normal central and peripheral adaptation to physical training. Physical training does not apparently improve blood glucose control in most cases, despite an increased insulin sensitivity.

The BM-Test-Glycemie 1-44 test strip facilitates self-monitoring without the use of a photometer. In a population of 33 diabetic patients (age 24.8f2.9 years) 94 % took part in home monitoring for 6-10 months. Of 29 who answered a quect' i ionnaire 25 preferred blood glucose testing +O wine testing. In a "beta-cell school" it was taugh' that it is rational if home monitoring of blood glucow s> ':nn'. bined with a tailored insulin treatment con isting of long-acting insulin (Ultralente) as a basal in d i n and regular insulin (Actrapid) as a meal insu' n. In a group of 24 labile diabetic patients 17 preft rred this regime compared to earlier use of intermel iate acting insulin and regular insulin. Six of these preferred the regular insulin to be taken in three doses. Hypoglycemia, when it occurred, was less distr.:ssing in symptoms than previously. Among patients with recent onset of diabetes active participation with dose reduction was seen during the honey-moon stage. The regime is logical and generative, offers a basis for an individualized therapy and a high remission frequency may be expected.

Metabolic effects of physical exercise in type I diabetes are reviewed. Physical training leads to an increased insulin sensitivity but does not seem to influence the metabolic control. However, the metabolic control is of importance for the exercise results. Patients in a good control do not differ from normal individuals concerning working capacity, recovery after hypoglycemia and hormonal balance. Furthermore, abnormalities in the blood glucose homeostasis during exercise in type I diabetes are discussed as well as potential beneficial effects of physical training in the prevention of cardiovascular disease.