title: Myocardial insulin resistance associated with chronic hypertriglyceridemia and increased FFA levels in Type 2 diabetic patients.
abstract: We evaluated the influence of chronic hypertriglyceridemia and endothelial dysfunction on myocardial glucose uptake (MGU) in Type 2 diabetic patients without coronary heart disease. Patients were divided into two groups according to fasting triglyceride (TG) levels: 5.4 +/- 1.1 and 1.5 +/- 0.3 mmol/l for high- and normal-TG groups, respectively. Five subjects were assigned to the high-TG group and 11 to the normal-TG group. Age, gender, body mass index, systolic and diastolic blood pressure, glucose, insulin, HbA1c, cholesterol, and HDL cholesterol were similar in the two groups, whereas free fatty acid (FFA) levels were higher in the high-TG group basally and at the end of the clamp. Furthermore, five healthy subjects were subjected to the same protocol and used as the control group. MGU was assessed by using 18F-labeled 2-fluoro-2-deoxy-D-glucose under hyperglycemic-hyperinsulinemic conditions. Basal endothelin-1 and nitric oxide levels were significantly higher in the high-TG group than in the normal-TG and control groups, and cGMP and maximal postischemic vasodilation were significantly decreased in the high-TG group compared with the normal-TG and control groups. However, significant alterations were found in the same parameters in the normal-TG group compared with the control group. By the end of the hyperglycemic clamp, in the high-TG group, MGU was approximately 40 and 65% of that in the normal-TG and control groups. MGU negatively correlated with TG, FFA, and endothelin-1, whereas a positive correlation was found with cGMP and maximal postischemic vasodilation. In conclusion, increased TG and FFA levels are risks, in addition to Type 2 diabetes mellitus, for myocardial insulin resistance, endothelial dysfunction, and alteration of nitric oxide/cGMP levels.
authors.affiliation: Core Lab, Diabetology, Endocrinology, and Metabolic Disease Unit, Medicine Division, Istituto di Recovero e Cura a Carattere Scientifico Hospital San Raffaele, 20132 Milan, Italy. lucilla.monti@hsr.it
authors.forename: Lucilla D
authors.initials: LD
authors.lastname: Monti
authors.forename: Claudio
authors.initials: C
authors.lastname: Landoni
authors.forename: Emanuela
authors.initials: E
authors.lastname: Setola
authors.forename: Elena
authors.initials: E
authors.lastname: Galluccio
authors.forename: Pietro
authors.initials: P
authors.lastname: Lucotti
authors.forename: Emilia P
authors.initials: EP
authors.lastname: Sandoli
authors.forename: Anna
authors.initials: A
authors.lastname: Origgi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Lucignani
authors.forename: PierMarco
authors.initials: P
authors.lastname: Piatti
authors.forename: Ferruccio
authors.initials: F
authors.lastname: Fazio
mesh_terms: D016022:Case-Control Studies; D002908:Chronic Disease; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D015309:Glucose Clamp Technique; D006728:Hormones / Q000097:blood; D006801:Humans; D006943:Hyperglycemia / Q000000981:diagnostic imaging / Q000378:metabolism; D015228:Hypertriglyceridemia / Q000209:etiology*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D014055:Tomography, Emission-Computed; D014280:Triglycerides / Q000097:blood
chemical_list: D005230:Fatty Acids, Nonesterified; D006728:Hormones; D007328:Insulin; D014280:Triglycerides