Effects of continuous subcutaneous insulin infusion on renal morphology in experimental diabetes. I. Blood glucose levels, body size, kidney weight and glomerulotubular morphometry.

Observations have been made over a period of 16 weeks on three groups of rats: controls, untreated streptozotocin-diabetics and diabetics treated with continuous subcutaneous insulin infusion. Good control of circadian and diurnal blood glucose levels was achieved in the insulin-treated diabetics. Body weights and tibial lengths were reduced in untreated diabetics and improved, but not normalized, by insulin therapy. Kidney weights were similar in all groups. Glomerular size and number, tubule volume, glomerular basement membrane volume and surface area were essentially the same in all groups. However, the untreated diabetics possessed tubules of larger diameter and shorter length than those in controls. Both variables were preserved at normal values by insulin infusion therapy. These results illustrate the value of early blood glucose control for preventing at least some of the structural alterations associated with experimental diabetic nephropathy.

Effects of continuous subcutaneous insulin infusion on renal morphology in experimental diabetes. II. Glomerular basement membrane thickness.

Stereological studies were performed on renal glomeruli from control rats, untreated streptozotocin-diabetic rats and diabetics treated by subcutaneous infusion of insulin for 16 weeks. Estimates of glomerular basement membrane thickness were obtained by dividing membrane volume by membrane surface area. In addition, arithmetic and harmonic mean thicknesses were calculated from orthogonal intercept lengths, and used to provide information on the variability of basement membrane thickness. In untreated diabetics, both arithmetic and harmonic mean thicknesses were significantly greater than values found in control animals. The thickening of the basement membrane appeared to be generalized rather than markedly focal. All thickness variables were normalized by insulin infusion therapy. These findings underline the importance of good glycaemic control and early intervention in experimental diabetes and one of its main complications.

The effect of continuous subcutaneous insulin infusion therapy on morphological and biochemical abnormalities of peripheral nerves in experimental diabetes.

Diabetes mellitus was induced in rats by the administration of streptozotocin and observations have been made over a period of 2 months in 3 groups of animals: controls, untreated diabetics and diabetics treated with continuous subcutaneous insulin infusion (CSII) therapy, using a 14-day Alzet osmotic minipump. Optimal control of day-to-day and 24-h blood glucose levels was achieved in diabetic animals treated with CSII. Body weight and skeletal growth, assessed by measurements of tibial length, were decreased in untreated diabetic rats and were normalized by insulin treatment. The concentrations of glucose, sorbitol and fructose in the nerves of diabetic animals were significantly increased and that of myoinositol significantly decreased; CSII therapy normalized these levels to those of age-matched controls. External myelinated fibre diameter in the tibial nerve was significantly less in untreated diabetic rats as compared with age-matched controls. In the insulin-treated group, fibre diameter significantly increased as compared with untreated diabetics and there was no significant difference between insulin-treated and control animals. Teased fibre preparations from the tibial nerve revealed very few abnormal fibres in all the three groups and no significant difference was detected between any of the groups. Continuous subcutaneous insulin infusion therapy, therefore, corrected biochemical abnormalities and also normalized myelinated fibre diameter in the peripheral nerves of experimental diabetic animals. The paradoxical excess of axonal degeneration that has been reported with conventional insulin treatment was not observed.