Abstract 3197: A New Method to Assess Myocardial Insulin Resistance In Vivo Using Nuclear Imaging of Glucose Transport.
Introduction: Insulin resistance (IR), implying depressed cellular sensitivity to insulin, is a central feature of the metabolic syndrome and a risk factor for cardiovascular disease. Currently, no simple method is available in clinical practice to evaluate organ IR. We hypothesized that nuclear imaging with the new tracer of glucose transport, [123I]-6-Deoxy-6-Iodo-D-glucose (6DIG) would provide a new method of myocardial IR measurement.
Methods: Two rat models of IR (n=7– 8) and their respective controls (n=5) were used in this study. Each group of anesthetized rat was injected with 6DIG before and after receiving a bolus injection of insulin (2.5 IU/kg). Scintigraphic images were acquired for 20 minutes following each tracer injection. 6DIG myocardial activity was determined from the images and 6DIG blood kinetic was obtained using blood sampling. We used a novel tri-compartmental mathematical model to analyse 6DIG kinetics. The ratio of the myocardial influx coefficient obtained under insulin to the one obtained under basal conditions gave an index (R) of myocardial IR for each animal. R was measured twice in a group of control rats (7 days apart, n=6) to test the reproducibility of this method. Finally, to evaluate its sensitivity, a seven days oral treatment with an insulin sensitizer (rosiglitazone, 3 mg/kg/day, n=6) or a placebo (water, n=6) was performed in insulin resistant rats.
Results: The R index was significantly lower in insulin resistant animals compared to their controls: 1.19 ± 0.39 versus 2.55 ± 0.52 (p < 0.02) in obese Zucker rats and 1.07 ± 0.23 vs. 1.98 ± 0.41 (p < 0.001) in diabetic ZDF rats. In addition, no significant variation of R was observed when measured twice in control rats. Finally, the 7-days treatment with rosiglitazone induced a two-fold increase in R index of insulin resistant rats: 2.27 ± 0.61 vs. 1.05 ± 0.10 (p < 0.05), whereas placebo treatment did not modify this index: 1.01 ± 0.05 vs. 1.05 ± 0.08 (NS).
Conclusion: These results show the efficiency of this new method of myocardial insulin resistance measurement with nuclear imaging.