Replacement treatment with insulin in diabetes mellitus: problems and promise

The results of epidemiological and clinical studies of diabetes in man and of studies of experimental diabetes in animals provide strong evidence: (1) that insulin-dependent diabetes mellitus is due to absolute or severe deficiency of insulin; (2) that replacement treatment with insulin is potentially capable of normalizing the metabolic abnormalities; and (3) that normalization of the metabolic abnormalities can be expected to prevent or ameliorate the complications of the disease. However, consideration of the problems involved in replacement treatment with insulin raises practical and physiological questions regarding the appropriate patterns and routes of delivery of the hormone. Studies with glucose-controlled automatic infusion systems delivering into systemic or portal vessels point to the question whether the homeostatic mechanism can be viewed as one dominated by the responses of the endocrine pancreas to glucose. Nevertheless, empirical studies with non-glucose-controlled portable programmed infusion systems delivering insulin by intravenous, subcutaneous, or intraperitoneal routes have suggested that these techniques can produce near-normoglycemia under everyday conditions in a high proportion of insulin-dependent diabetic subjects. The blood levels of biologically active insulin resulting from these treatments are not higher, and may be lower, than those with conventional depot injection therapy. It appears also that the results of intensive depot injection therapy making use of 3 or 4 injections day-1 of crystalline and intermediate-acting insulins can approximate the effects of insulin infusion treatment. It is argued that the intensive insulin treatment regimens with continuous or intermittent use of the subcutaneous route of delivery can be viewed as options in the management of insulin-dependent diabetes mellitus when adequate supervision and monitoring is available, and that clinical systems fulfilling these conditions must be provided.