Effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. VII. Mortality and selected nonfatal events with insulin treatment.

The University Group Diabetes Program is a long-term prospective clinical trial designed to evaluate the effects of various hypoglycemic agents on vascular complications in patients with asymptomatic adult-onset diabetes. Mortality and blood glucose levels were determined as well as certain nonfatal events for patients assigned to diet alone or to either of two insulin treatment regimens. Lower levels of blood glucose with mean values close to normoglycemia were achieved in the treatment group in which the insulin dosage was adjusted to achieve normoglycemia compared with the levels achieved in patients treated with diet alone or with a fixed dose of insulin. In spite of differences in blood glucose levels among the treatment groups, there were only minor differences in the occurrence of fatal or nonfatal events.

Emergence of overt diabetes in offspring of rats with induced latent diabetes.

A single subdiabetogenic dose of alloxan administered to the weanling rat induces a persistent state of latent diabetes which progresses to fasting hyperglycemia by the seventh generation. Initial descendants of alloxan-treated animals have hyperinsulinism which progresses to insulinopenia in later generations. Later generation animals develop ketoacidosis when challenged with a dose of alloxan that has no effect on control animals. The significant sex difference in glucose tolerance rates disappears as the animals become more diabetic and decreased fertility and parity become apparent. One explanation for this data remains the hypothesis of paramutation, induced by alloxan, affecting regulator gene activity. Light microscopy of diabetic animals shows no pathology.