Unravelling the conundrums of the diabetic heart diagnosed in 1876: prelude to genetics.

During the past two decades epidemiological, clinical and laboratory studies have confirmed the existence of the diabetic heart in some patients with diabetes mellitus. The diagnosis was made in patients in whom other known etiological factors, such as coronary artery disease, alcoholism or hypertensive cardiovascular disease, were ruled out. The newer concept of the diabetic hypertensive heart is clinically based on a higher incidence of congestive heart failure caused by extensive myocardial involvement. In patients with hypertension and hypertension associated with diabetes, the intramyocardial arterioles present medial hypertrophy and a diminished lumen, increased periarteriolar fibrosis, accumulation of fibrillar collagen and patent extramural coronary arteries. Such confirmatory findings have been previously seen in experimental animals and in patients with diabetes and no hypertension. In the genetically diabetic rat, diabetes may be prevented by neonatal thymectomy, suggesting the existence of an autoimmune deficiency syndrome. Furthermore, conversion of Ala 776 into Thr 776 on the polyprotein by a point mutation results in loss of diabetogenicity. Abnormalities in systole and diastole related to lowering of CK-M and CK-B mRNA levels are normalized following insulin therapy. Identification of the genetic factors in the diabetic heart may lead to the identification of its pathogenic mechanisms.