Diffuse Myocardial Injury With Diabetes-Related Advanced Glycation End Product Accumulation in Dilated Cardiomyopathy: Pathological Insights From an Autopsy Case.

Diabetes mellitus is a systemic metabolic disorder associated with diverse long-term complications, among which cardiovascular involvement is a major cause of morbidity and mortality. A central pathogenic mechanism linking diabetes to tissue injury is the formation and accumulation of advanced glycation end products (AGEs), which exert deleterious effects through receptor-mediated signaling via the receptor for AGEs (RAGE) and receptor-independent collagen cross-linking. However, pathological evidence directly demonstrating the contribution of AGE accumulation to advanced cardiac dysfunction in human autopsy cases remains limited. We report an autopsy case of a Japanese man in his late 60s with long-standing idiopathic dilated cardiomyopathy who subsequently developed diabetes mellitus and progressive heart failure. His clinical course was complicated by secondary pulmonary hypertension, followed by hepatic and renal dysfunction, and ultimately resulted in death due to multiple organ failure. Gross examination revealed marked cardiac enlargement with severe biventricular dilatation without ventricular wall hypertrophy. Histologically, the myocardium showed diffuse interstitial and perimyocytic fibrosis with transmural myocardial atrophy. The pulmonary arteries demonstrated fibrous intimal thickening consistent with secondary pulmonary hypertension. Renal pathology showed arteriolosclerotic nephropathy with superimposed diabetic nephropathy, and the liver exhibited features of congestive hepatopathy. Immunohistochemical analyses demonstrated prominent myocardial deposition of pentosidine, a representative AGE, along with increased expression of the oxidative stress marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) and immunoreactivity for RAGE. These findings suggest that diabetes-associated AGE accumulation and oxidative stress contributed to qualitative alterations of myocardial collagen within pre-existing diffuse fibrosis, potentially accelerating myocardial stiffening and progression of dilated cardiomyopathy.