Impaired Skeletal Muscle Glucose Uptake by [18F]Fluorodeoxyglucose–Positron Emission Tomography in Patients With Peripheral Artery Disease and Intermittent Claudication

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 31; no. 1; pp. 190 - 196
• Main Authors: Pande, Reena L., Park, Mi-Ae, Perlstein, Todd S., Desai, Akshay S., Doyle, Jeanne, Navarrete, Nicole, Copeland-Halperin, Robert S., Redline, Whitney, Di Carli, Marcelo F., Creager, Mark A.
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.01.2011; Lippincott Williams & Wilkins
• Subjects: Aged; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Biological Transport; Blood and lymphatic vessels; Blood Glucose - metabolism; Boston; Cardiology. Vascular system; Cardiovascular system; Case-Control Studies; Chi-Square Distribution; Diabetes Mellitus - diagnostic imaging; Diabetes Mellitus - metabolism; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Female; Fluorodeoxyglucose F18; Glucose Clamp Technique; Humans; Insulin Resistance; Intermittent Claudication - diagnostic imaging; Intermittent Claudication - metabolism; Kinetics; Lower Extremity; Male; Medical sciences; Middle Aged; Muscle, Skeletal - blood supply; Muscle, Skeletal - diagnostic imaging; Muscle, Skeletal - metabolism; Peripheral Arterial Disease - diagnostic imaging; Peripheral Arterial Disease - metabolism; Pharmacology. Drug treatments; Positron-Emission Tomography; Predictive Value of Tests; Radiopharmaceuticals; Vasodilator agents. Cerebral vasodilators; Endocrinopathy; Human; Claudication; 2-deoxy-2-fluoroglucose; Metabolic diseases; Cardiovascular disease; peripheral arterial disease; Glucose; Striated muscle; Uptake; intermittent claudication; Arterial disease; Vascular disease; Target tissue resistance; Intermittent; Atherosclerosis; Occlusive arterial disease; Insulin resistance; Positron emission tomography; Emission tomography
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/ATVBAHA.110.217687

OBJECTIVE—Reduced limb perfusion from arterial stenosis does not adequately account for intermittent claudication symptoms in peripheral artery disease (PAD). Insulin resistance is associated with PAD and may contribute to claudication by impairing skeletal muscle metabolism. We aimed to determine whether skeletal muscle glucose uptake, assessed by [F]fluorodeoxyglucose positron emission tomography, is reduced in patients with claudication. METHODS AND RESULTS—Thirty-seven subjects with PAD and claudication and 11 healthy controls underwent [F]fluorodeoxyglucose–positron emission tomography imaging of the legs during hyperinsulinemic-euglycemic clamp. Calf glucose uptake was quantified by graphical Patlak analysis, and whole-body insulin sensitivity was assessed as the glucose disposal rate (M) from the insulin clamp. Compared with healthy controls, PAD subjects were insulin resistant (M=3.4 mg/kg per minute [interquartile range, 2.7 to 4.8] versus 5.0 [3.7 to 6.6], P=0.019). Calf muscle glucose uptake was significantly lower in PAD compared with healthy subjects (48.6±2.6 μmol/kg per minute versus 62.9±6.5 μmol/kg per minute, P=0.009) and correlated with systemic insulin sensitivity (r=0.37, P=0.03) in PAD subjects. These abnormalities persisted even after exclusion of PAD subjects with diabetes. CONCLUSION—Patients with claudication have impaired calf muscle glucose uptake. Future studies are required to assess whether calf muscle insulin resistance contributes to exercise limitation in patients with intermittent claudication.