Abstract 5089: Impaired Calf Skeletal Muscle Glucose Uptake in Subjects With Peripheral Artery Disease and Intermittent Claudication
Objectives: Severity of claudication symptoms does not correlate well with ankle brachial index (ABI) in patients with peripheral artery disease (PAD), suggesting that non-hemodynamic mechanisms may play an important role. Given the association of PAD with insulin resistance, we hypothesized that local calf muscle glucose uptake is impaired in PAD, and therefore that local insulin resistance may contribute to the pathophysiology of claudication.
Methods: We studied 37 subjects with PAD (ABI ≤ 0.9) and stable claudication and 11 healthy controls who underwent dynamic positron emission tomography (PET) imaging of the legs with 18-FDG during a hyperinsulinemic-euglycemic clamp (insulin @ 2 mU/kg/min). Using fused PET/CT images, regions of interest were drawn in the primary muscle groups of the lower leg. Average glucose uptake was quantified using the graphical Patlak analysis. Whole body insulin sensitivity was assessed as the glucose disposal rate (M) from the insulin clamp. Data are presented as median [interquartile range, IQR] or mean± standard error (SE).
Results: Compared to healthy, age-matched controls, PAD subjects were insulin resistant (M = 3.4 mg/kg/min [IQR 2.7– 4.8] vs. 5.0 [3.7– 6.6], p=0.019) even after excluding those with diabetes (24% of PAD subjects), p=0.04. Average calf muscle glucose uptake was significantly lower in PAD subjects (48.6±2.6 mmol/kg/min) compared with healthy controls (62.9±6.5 mmol/kg/min), p=0.009. Similar impairments were observed in the subgroup of PAD subjects without diabetes (49.5±3.1, p=0.04 vs. healthy controls). Whole body insulin sensitivity explained 10% of the variability in local calf muscle glucose uptake (r2=0.10, p=0.04).
Conclusions: We demonstrate that subjects with claudication are insulin resistant and have reduced calf muscle glucose uptake, independent of coexistent diabetes. The poor correlation between whole body insulin sensitivity and lower extremity glucose uptake suggests unique determinants of leg glucose uptake in PAD. These findings support our underlying hypothesis that impaired calf muscle substrate utilization due to local insulin resistance may be a novel mechanism underlying the pathophysiology of intermittent claudication.