Heart and skeletal muscle insulin resistance but not myocardial blood flow reserve could be related to chronic use of thiazolidione in patients with type-2 diabetes

Heart and skeletal muscle insulin resistance and abnormal myocardial flow reserve (MFR) occurs in patients with type-II diabetes. Improvement of heart and skeletal muscle insulin resistance with rosiglitazone use over 16 weeks have been reported. However, it is not clear whether chronic use of troglitazone can improve heart and skeletal muscle insulin resistance and MFR. Materials and Methods: To test the hypothesis whether effects of troglitazone on heart and skeletal muscle insulin resistance and MFR in patients with type-II diabetes, rest and dipyridamole stress perfusion positron emission tomography (PET) with 13N-ammonia and heart and skeletal muscle 18FDG PET scans under insulin clamping were undertaken before and 12 month after the initiation of troglitazone therapy (400 mg/day) in 23 patients with type-II diabetes. Twenty patients with type-II diabetes without CAD and without medications were served as controls. In controls, any medications were not added from the first PET study and 12 months after the second PET study. Results: Baseline myocardial blood flow (MBF) was comparable before and after the troglitazone group as was the controls. MBF during dipyridamole administration (0.56 mg/min/kg) was not significantly improved in troglitazone group and controls. MFR was not improved in troglitazone group and controls. In troglitazone group, whole body glucose disposal rate (GDR;μmole/min/kg) significantly improved (pre;19.0 ± 9.55, post;28.7 ± 15.3, p as did the skeletal muscle glucose utilization rate (SMGU (μmole/min/kg);pre;20.3 ± 12.0, post;34.8 ± 10.6, p insulin resistance is implicated in patients with type-II diabetes and impaired MFR is uncoupled with insulin resistance in the whole body and heart and skeletal muscle in patients with type-II diabetes.

Functional imaging of skeletal muscle glucose metabolism by ¹⁸FDG PET to characterize insulin resistance in patients at high risk for coronary artery disease

Insulin resistance is associated with several coronary risk factors and is thought to play a critical role for the development of coronary artery disease. Insulin resistance has several causes, including an impaired skeletal muscle glucose utilization rate (SMGU), reduced peripheral blood flow, and altered fatty tissue metabolism, with SMGU being considered the most important. Nonetheless, insulin resistance has only been estimated by the glucose disposal rate (GDR) in previous studies. Methods: Skeletal muscle metabolic imaging with 18FDG and positron emission tomography (PET) was undertaken to measure SMGU during hyperinsulinemiceuglycemic clamping in 22 normotensive type-2 diabetics under no medications (T2- DM), 17 normotensive non-diabetic hypertriglyceridemics, 22 patients with hypertension, and 12 agematched controls. Whole body insulin resistance was assessed by the GDR during hyperinsulinemiceuglycemic insulin clamping. Results: The SMGU and GDR were significantly reduced in T2DM (32.1 ± 16.6 μmol/min/kg and 24.3 ± 13.0 μmol/min/kg, respectively), hypertriglyceridemics (36.5 ± 13.5 μmol/min/ kg and 22.7 ± 8.07 μmol/min/kg respectively) and patients with hypertension (35.4 ± 26.6 μmol/min/kg and 29.0 ± 9.90 μmol/min/kg, respectively) compared with controls (72.2 ± 44.1 μmol/min/kg and 43.0 ± 22.9 μmol/min/kg, p < 0.01, respectively). In all groups studied, SMGU was significantly correlated with GDR (r = 0.76, p < 0.01) and GDR (F = 13.9) was independently related to SMGU (r = 0.81, p < 0.01). Conclusion: Insulin resistance is significantly associated with SMGU to a similar degree among patients with T2DM, essential hypertension and hypertriglyceridemia. 18FDG PET functional imaging allows insulin resistance to be assessed.

Measurement of lumbar muscle glucose utilization rate can be as useful in estimating skeletal muscle insulin resistance as that of thigh muscle

Background: Skeletal muscle glucose utilization (SMGU) can be accessed by positron emission tomography (PET) and18F-FDG to characterize insulin resistance. The quantity of skeletal muscle in the lumbar is sufficient to indicate that SMGU in the lumbar (SMGU- lumbar) can be measured with18F-FDG PET of the chest instead of obtaining thigh muscle SMGU (SMGU-thigh). This would reduce PET scan time to avoid thigh muscle PET scan. This study was aimed to compare SMGU-lumbar and thigh muscle SMGU under insulin clamping to identify the validity of measurements of SMGU in the lumbar for studies of insulin resistance. Methods: Thirty-three patients underwent sequential dynamic18F-FDG PET of both the thoracic (37 min) and thigh region (22 min) during hyperinsulinemic euglycemic insulin clamping. Both SMGU-lumbar and SMGU-thigh were calculated by Patlak graphical analysis. Whole body insulin resistance was assessed by a whole body glucose disposal rate during hyperinsulinemic euglycemic insulin clamping. Input function was obtained from the time activity curve of the descending aorta and venous blood sampling as previously validated. Results: SMGU-thigh (0.0506 ± 0.0334 μmol/min/g) was comparable to SMGU-lumbar (0.0497 ± 0.0255 μmol/min/g). The Bland-Altman method of difference plot analysis showed a significant correlationship between SMGU- thigh and SMGU-lumbar (r = 0.506, p = 0.0028). There were seen very good significant correlationship between whole body glucose utilization rate in both thigh (r = 0.737, p = 0.0001) and lumbar (r = 0.772, p = 0.0001). Conclusion: These results support the validity of measuring SMGU-lumbar to estimate insulin resistance during PET imaging of the chest.

Skeletal muscle and whole body insulin resistance but not cardiac muscle insulin resistance could be improved by troglitazone therapy within 12 weeks in type-2 diabetes

Background: Existence of myocardial insulin resistance (IR) has been reported in type II diabetics (T2- DM) and coronary artery disease (CAD). Improvement in heart and skeletal muscle IR after thiazolidinedione’s therapy was reported in T2DM and CAD. However effects of troglitazone therapy (TRO) on myocardial IR remain uncertain. To clarify heart and skeletal muscle and whole body IR in T2DM without CAD by TRO to clarify whether TRO would provide different results. Methods: We analyzed data on 15 T2DM patients who underwent dynamic PET with 18F-FDG under insulin clamping before and during TRO (200 mg/day) and 17 controls. Results: Whole body glucose disposal rate (WBGR mg/min/kg) in T2DM before TRO (3.41 ± 1.72) was significantly lower than in controls (9.76 ± 2.97, p < 0.01) as was the skeletal muscle glucose utilization rate (SMGU mg/min/kg);T2DM (0.367 ± 0.217) vs. controls (1.34 ± 0.613, p < 0.01) and myocardial glucose utilization rate (MGU mg/min/kg;T2DM 5.86 ± 2.03 vs. controls 7.34 ± 1.80, p < 0.05). WBGR in T2DM during TRO (5.17 ± 2.75, p < 0.05) was significantly higher than that before TRO, as was the SMGU (0.782 ± 0.20, p < 0.05). The MGU in T2DM during TRO (6.59 ± 0.72) was comparable with that before TRO. Conclusion: Myocardial IR response to TRO differed from that in skeletal muscle and the whole body in T2DM without CAD.