DIABETIC CARDIOMYOPATHY

Diabetic cardiomyopathy as a distinct entity was first recognized by R ubler et al. in diabetics with congestive heart failure (CHF), who had no evidence of coronary atherosclerosis. The Framingham study showed a 2.4-fold increased incidence of CHF in diabetic men and a 5.1-fold i ncrease in diabetic women over 18 years. Pathological studies show lef t ventricular hypertrophy and fibrosis with varying degrees of small v essel disease, the functional significance of which is uncertain. Hype rtension was recognized as an important cofactor in the development of fatal congestive heart failure in diabetics. On cardiac catheterizati on, in patients symptomatic of heart failure, either congestive or res trictive patterns have been observed. In contrast, asymptomatic diabet ics had decreased left ventricular compliance but normal systolic func tion on hemodynamic study. Noninvasive studies show alterations in sys tolic and especially diastolic function, particularly in diabetics wit h microvascular complications and/or coexistent hypertension. Using lo ad-independent measures of contractility, however, systolic function w as generally found to be normal in asymptomatic normotensive diabetics . Experimental studies have focused on the mildly diabetic dog and the severely diabetic rat. Decreased left ventricular compliance and incr eased interstitial connective tissue were observed in chronically diab etic dogs. In contrast, ventricular myocardium from diabetic rats exhi bits a reversible decrease in the speed of contraction, prolongation o f contraction, and a delay in relaxation. These mechanical changes are associated with a decreased myosin ATPase, a shift in myosin isoenzym e distribution, alterations in a variety of Ca2+ fluxes, and changes i n responses to alpha- and beta-adrenergic and cholinergic stimulation. These biochemical changes may be secondary to alterations in carbohyd rate, lipid, and adenine nucleotide metabolism in the diabetic heart. When drug induced diabetes was combined with hypertension, a lethal ca rdiomyopathy with increased left ventricular hypertrophy and fibrosis, increased microvascular pathology and pulmonary congestion were obser ved. Compared to animals with isolated diabetes or hypertension, great er changes in papillary muscle function, isolated perfused heart perfo rmance, cellular electrophysiology, and contractile protein biochemist ry were observed. Several studies suggest a protective effect of calci um channel blockers (verapamil and diltiazem) in experimental diabetic cardiomyopathy. Currently the clinical approach to this disorder emph asizes control of hyperglycemia and coexistent hypertension.