Quantitative analysis of myocardial structure in insulin-dependent diabetes mellitus: effects of immediate and delayed insulin replacement.

The effects of severe, chronic diabetes mellitus and of immediate or delayed insulin replacement on the different components of the myocardium and cardiocytes were quantified and correlated. A significant decrease in cardiocyte cross-sectional area occurred during the first 12 weeks of diabetes and then stabilized. This was accompanied by decreases in the relative volume densities (RVDs) of myofibrils and mitochondria, resulting in absolute loss of more than 40% of each of these cellular components after 26 weeks of diabetes. Interstitial and perivascular deposition of extracellular matrix produced a tripling of its RVD in the myocardium over 26 weeks of diabetes at the expense of both cardiocytes and capillaries. Capillary density and diameter also exhibited progressive decreases of more than 20% over 26 weeks of diabetes. Insulin treatment which maintained euglycemia and restored normal growth prevented this structural pathology when begun three days after induction of diabetes. When delayed for 12 weeks, insulin reversed the changes in cardiocyte and capillary RVD, and in capillary diameter within 6 weeks, ultrastructural changes within 12 weeks, and cardiocyte cross-sectional area after 26 weeks. However, even after 26 weeks of treatment, the extracellular matrix remained more than twice that observed in nondiabetic animals, with a consequent decrease in the number of capillaries per unit volume of tissue. This study demonstrates that diabetes produces a progressive, marked disorganization of the myocardium which can be prevented, but only selectively reversed, by insulin treatment. These structural changes are relevant to the functional changes which occur in diabetic cardiomyopathy.