Impaired skeletal muscle glucose uptake by [18F]fluorodeoxyglucose-positron emission tomography in patients with peripheral artery disease and intermittent claudication.
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 [(18)F]fluorodeoxyglucose positron emission tomography, is reduced in patients with claudication.


RESULTS
Thirty-seven subjects with PAD and claudication and 11 healthy controls underwent [(18)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.


CONCLUSIONS
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.
Brigham and Women's Hospital, Boston, MA 02115, USA. rpande@partners.org
Reena L
RL
Pande
Mi-Ae
MA
Park
Todd S
TS
Perlstein
Akshay S
AS
Desai
Jeanne
J
Doyle
Nicole
N
Navarrete
Robert S
RS
Copeland-Halperin
Whitney
W
Redline
Marcelo F
MF
Di Carli
Mark A
MA
Creager
D000368:Aged; D001692:Biological Transport; D001786:Blood Glucose / Q000378:metabolism*; D001900:Boston; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003920:Diabetes Mellitus / Q000000981:diagnostic imaging / Q000378:metabolism; D005260:Female; D019788:Fluorodeoxyglucose F18; D015309:Glucose Clamp Technique; D006801:Humans; D007333:Insulin Resistance; D007383:Intermittent Claudication / Q000000981:diagnostic imaging / Q000378:metabolism*; D007700:Kinetics; D035002:Lower Extremity; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism*; D058729:Peripheral Arterial Disease / Q000000981:diagnostic imaging / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D019275:Radiopharmaceuticals
D001786:Blood Glucose; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18