Relationship Between Coronary Microvascular Dysfunction and Cardiac Energetics Impairment in Type 1 Diabetes Mellitus

Abstract

Background-Asymptomatic subjects with diabetes mellitus have an impaired cardiac energetics status that may play a significant role in the development of heart failure. In the present study, we assessed the role of microvascular dysfunction in the development of impaired cardiac energetics in subjects with type 1 diabetes mellitus. Methods and Results-Twenty-five asymptomatic subjects with type 1 diabetes mellitus (mean age Ϯ1 SD 33Ϯ8 years) and 26 age-, sex-, and body mass index-matched healthy control subjects (32Ϯ8 years old) were recruited into the study. The type 1 diabetes mellitus subjects were divided into 2 age-matched groups (newly diagnosed [Ͻ5 years] and longer-duration [Ͼ10 years] diabetes) to assess the impact of microvascular disease. All subjects had an echocardiogram and an exercise ECG performed, followed by magnetic resonance spectroscopy and stress magnetic resonance imaging. Compared with healthy control subjects, the phosphocreatine/␥-ATP ratio was reduced significantly both in subjects with longer-term (2.1Ϯ0.5 versus 1.5Ϯ0.4, PϽ0.000) and newly diagnosed (2.1Ϯ0.5 versus 1.6Ϯ0.2, PϽ0.000) diabetes. The phosphocreatine/␥-ATP ratio was similar in newly diagnosed diabetes subjects and those with longer-term disease (1.6Ϯ0.2 versus 1.5Ϯ0.4, Pϭ0.32). The mean myocardial perfusion reserve index in the longer-term type 1 diabetes mellitus subjects was significantly lower than in healthy control subjects (1.7Ϯ0.6 versus 2.3Ϯ0.4, Pϭ0.005). On univariate analysis, there was no significant correlation of phosphocreatine/␥-ATP ratio with myocardial perfusion reserve index (rϭ0. 21, Pϭ0.26). Conclusions-We demonstrate that young subjects with uncomplicated type 1 diabetes mellitus have impaired myocardial energetics irrespective of the duration of diabetes and that the impaired cardiac energetics status is independent of coronary microvascular function. We postulate that impairment of cardiac energetics in these subjects primarily results from metabolic dysfunction rather than microvascular impairment. (Circulation. 2010;121:1209-1215.)

Association Between Diffuse Myocardial Fibrosis by Cardiac Magnetic Resonance Contrast-Enhanced T 1 Mapping and Subclinical Myocardial Dysfunction in Diabetic Patients

“…[1][2][3] Although the underlying pathogenesis is likely to be multifactorial, [1][2][3][4] there is eventually accelerated cellular apoptosis and necrosis, resulting in increased perivascular and diffuse interstitial fibrosis within the myocardium. 2 More important, previous studies have demonstrated histological evidence of increased diffuse microscopic fibrosis in the myocardium of diabetic patients.…”

A high-fat diet impairs cardiac high-energy phosphate metabolism and cognitive function in healthy human subjects

“…This not only suggests that improvement in heart function was associated with correction of the metabolic abnormalities caused by elevated FFAs, but also supports the concept that diabetic cardiomyopathy may be a reversible metabolic abnormality. Increased FFAs and microvascular dysfunction are related to impaired cardiac highenergy phosphate metabolism in diabetic patients-another potential mechanism of altered PCr/ATP seen in this study (15,46).…”

“…Accompanying their impaired cardiac energetics and function, heart failure patients also have chronically elevated plasma FFAs (43) and cognitive impairment, although a causal link between the metabolic and functional abnormalities has not been established (19). In support of the association between substrate alterations in impaired cardiac energy metabolism, patients with diabetes have low cardiac PCr/ATP ratios, unrelated to the duration of diabetes and independent of microvascular dysfunction (15,(44)(45)(46), but that correlate negatively with circulating FFA concentrations (15). There is also evidence that abnormal high-energy phosphate metabolism precedes the contractile impairment observed in heart disease (41,47).…”

Predictors and diagnosis of cardiac autonomic nervous dysfunction in patients with type 1 and type 2 diabetes mellitus

“…МР-изображения, полученные в покое и при стресс-нагрузке (инфузия аденозина), обработанные посредством программы ViewForum, были проанализи-рованы Shivu G. с соавт. [58], на их основе рассчитаны пиковые повышения свечения миокарда ЛЖ по отно-шению к крови в его полости. ИРМП рассчитывался как отношение пикового свечения при стресс-нагрузке к пиковому свечению в покое.…”