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1 Lab L20,Core Lab, Diabetology, Endocrinology and Metabolic Disease Unit, Medicine Division, IRCCS H. San Raffaele, Milan, Italy
2 Division of Nuclear Medicine, IRCCS H. San Raffaele, Milan, Italy
3 Cardiovascular and Metabolic Rehabilitation Unit, IRCCS H. San Raffaele, Milan, Italy
4 Imaging and Radiotherapy Unit, University of Milan, Milan, Italy
* To whom correspondence should be addressed. E-mail: lucilla.monti{at}hsr.it.
The aim of this study was to evaluate the influence of chronic hypertriglyceridemia and endothelial dysfunction on myocardial glucose uptake (MGU) in type 2 diabetic patients in the absence of CHD. A cross-sectional study was conducted in sixteen patients with type 2 diabetes, with a negative history of cardiovascular disease, normal heart rate and normal resting ECG and M-mode and two-dimensional echocardiogram, were recruited from the outpatient diabetic clinic. Myocardial glucose uptake was assessed by using [18F]-2-fluoro-2-deoxy-D-glucose ([18F]FDG) under hyperglycemic hyperinsulinemic conditions. The patients were divided into two groups according with fasting triglyceride levels (High TG 5.4±1.1 mmol/l vs Normal TG 1.5±0.3 mmol/l). Five subjects pertained to the High TG group while 11 subjects were allocated into the Normal TG group. Age, gender, BMI, systolic and diastolic blood pressure, glucose, insulin, HbA1c, cholesterol and HDL cholesterol were similar in the two groups, while FFA levels were higher in the high TG group basally and at the end of the clamp. Furthermore, five healthy sujects were submitted to the same protocol as Controls group. Basal ET-1 and NOx levels were significantly higher while cGMP and maximal post-ischemic vasodilation were significantly decreased in High TG group than in the other two groups. However, significant alterations were found in the same parameters in the Normal TG group compared with Controls group. By the end of the hyperglycemic clamp, in High TG group, MGU was about 40% and 65% those obtained in Normal TG and Controls groups, respectively and M/I ratio, index of whole body insulin sensitivity, was decreased by 50% and 65%, respectively. MGU negatively correlated with triglyceride, FFA and ET-1 while a positive correlation was found with cGMP and maximal post-ischemic vasodilation. A positive correlation was also found between M/I and cGMP and between M/I and MGU. The present study demonstrated that increased TG and FFA levels are additional risks, in addition to type 2 diabetes mellitus, for myocardial insulin resistance associated with endothelial dysfunction and alteration of nitric oxide/cGMP levels.
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