Diabetes with no ischemia linked with impaired LV function, myocardial substrate metabolism abnormalities

Patients with type 2 diabetes and no cardiac ischemia were more likely to have impaired left ventricular diastolic function and altered myocardial substrate metabolism than those without diabetes or ischemia.

Researchers enrolled 102 men in the study, 78 of whom were insulin-naive with diabetes who did not have cardiac ischemia; 24 were normoglycemic. They assessed myocardial LV function with MRI, and myocardial perfusion and substrate metabolism using PET. They evaluated cardiac high-energy phosphate metabolism using phosphorous P 31 magnetic resonance spectroscopy. LV diastolic function was characterized using a ratio of peak filling rates of the early filling phase to peak filling rates during atrial contraction (E/A ratio).

Myocardial blood flow was similar between the patients and those in the control group (P=.804). LV diastolic function (P=.003) and myocardial glucose uptake (P=.015) decreased in patients with diabetes vs. control patients. Myocardial nonesterified fatty acid uptake (P=.021) and myocardial fatty acid oxidation (P=.007) were higher in the patient group vs. the control group, whereas myocardial fatty acid esterification was lower in patients vs. those in the control group (P=.028). An inverse relationship between whole-body insulin sensitivity and nonesterified fatty acid (P=.001), myocardial fatty acid uptake (P=.042) and myocardial fatty acid oxidation (P=.021) was reported. Forward regression analysis suggested that heart rate, HbA1c and diastolic BP were independent determinants of E/A ratio (P<.001) and peak deceleration of the filling pressures of the early filling phase (P<.001).

“In the absence of myocardial ischemia, patients with uncomplicated type 2 diabetes showed impaired LV diastolic function and decreased compliance in addition to whole-body and myocardial insulin resistance, collectively leading to altered myocardial substrate metabolism, favoring nonesterified fatty acid over glucose as a substrate,” the researchers wrote. “Large-scale longitudinal studies using similar combined measurements should establish the influence of early metabolic and functional changes on the development of clinically relevant cardiac disease in type 2 diabetes over time, including congestive HF and cardiac ischemia, and further define the efficacy of targeted interventions to halt the progression of compensated diabetic cardiomyopathy into overt cardiac disease.”

Rijzewijk LJ. J Am Coll Cardiol. 2009;54:1524-1532.

These findings do not surprise me. It is only when ketone levels climb, as they do in low carb/high protein diets, that this may be a problem. This is also different than systolic dysfunction, where I believe there is a problem with the metabolic pathway.

- George Bakris, MD

Cardiology Today Editorial Board member