Diabetes Mellitus “Comorbidity” or an Important Risk Factor?

Diabetes is a complex metabolic syndrome and its involvement in cardiovascular disease is manifold with varying manifestations and different clinical symptoms and prognosis. Although being probably the most important risk factor, diabetes is often considered an “accompanying comorbidity” for cardiac or peripheral artery disease, hypertension, or stroke. We should focus more on diabetes being an independent disease with a “2-faced appearance” of diabetes-related cardiomyopathy. One form being the restrictive type with preserved LVEF, the other form appearing as dilative cardiomyopathy with reduced LVEF. The restrictive form with diastolic dysfunction seems to be a coronary microvascular endothelial dysfunction problem induced by hyperglycemia, lipotoxicity, and hyperinsulinemia and is more often encountered in obese patients with type 2 diabetes; the dilative form is linked to cardiomyocyte cell death induced by an autoimmune-prone pathophysiologic mechanism and occurs more often in patients with type 1 diabetes. Both types of diabetic cardiomyopathy are caused by impaired glucose metabolism, seem not to be successive stages, and develop independently. They should be separated from macrocoronary artery disease and other forms of nonischemic cardiomyopathy. How much diabetic cardiomyopathy affects outcome of other cardiac diseases is still a matter of research. Situations with hypogylcemia or hyperglycemia increase the risk of cardiovascular events, arrhythmias, sudden death, and all-cause mortality. An interesting study demonstrated that the risk of sudden cardiac death is at least 2-fold higher in patients who are diabetic compared with those who are nondiabetic, regardless of the extent of cardiac dysfunction or symptoms of heart failure. In contrast, the risk of nonsudden cardiac death was not significantly different between the 2 groups. The question arises which pathophysiologic mechanism is responsible for the higher risk of arrhythmic death in patients who are diabetic? One actual focus of interest is the diabetic autonomic neuropathy with autonomic dysfunction, which is present in at least one-third of patients who are diabetic. Noninvasive electrocardiography-based risk stratification should become the most important field of risk stratification for ICD therapy, particularly in patients who are diabetic with normal or only mildly reduced LVEF. However, further research is needed in this field prior to launching randomized studies. In summary, the presented data from this registry demonstrate that less impaired LV function in patients who are diabetic carries a higher mortality risk than low LVEF in patients who are nondiabetic. These findings stimulate us to reconsider the accepted LVEF-guided ICD therapy, particularly for patients with diabetes. However, the discussed ICD protection for patients who are diabetic with less reduced LV function seems to be premature when based only on global overall outcome data. The data calls for future prospective, randomized trials focusing specifically on diabetes patients. It clearly signals to the cardiology community that patients with diabetes are at high risk of arrhythmic risk, even without severely reduced LVEF. Future studies should not fail because of poor patient enrollment. Perhaps, sodium-glucose cotransporter inhibitors will become the new “medical defibrillators”. However, even this important new study did not reveal the effect of sodium-glucose cotransporter inhibitors specifically on sudden cardiac death outcome.