Reduced T2* Values in Soleus Muscle of Patients with Type 2 Diabetes Mellitus

Tissue water transverse relaxation times (T2) are highly sensitive to fluid and lipid accumulations in skeletal muscles whereas the related T2* is sensitive to changes in tissue oxygenation in addition to factors affecting T2. Diabetes mellitus (DM) affects muscles of lower extremities progressively by impairing blood flow at the macrovascular and microvascular levels. This study is to investigate whether T2 and T2* are sensitive enough to detect abnormalities in skeletal muscles of diabetic patients in the resting state. T2 and T2* values in calf muscle of 18 patients with type 2 DM (T2DM), 22 young healthy controls (YHC), and 7 age-matched older healthy controls (OHC) were measured at 3T using multi-TE spin echo and gradient echo sequences. Regional lipid levels of the soleus muscle were also measured using the Dixon method in a subset of the subjects. Correlations between T2, T2*, lipid levels, glycated hemoglobin (HbA1c) and presence of diabetes were evaluated. We found that T2 values were significantly higher in calf muscles of T2DM subjects, as were T2* values in anterior tibialis, and gastrocnemius muscles of T2DM participants. However, soleus T2* values of the T2DM subjects were significantly lower than those of the older, age-matched HC cohort $(22.9\pm 0.5 vs 26.7\pm 0.4 ms, p<0.01)$. The soleus T2* values in the T2DM cohort were inversely correlated with the presence of diabetes (t = −3.46, p<0.001) and with an increase in HbA1c, but not with body mass index or regional lipid levels. Although multiple factors may contribute to changes in T2* values, the lowered T2* value observed in the T2DM soleus muscle is most consistent with a combination of high oxygen consumption and poor regional perfusion. This finding is consistent with results of previous perfusion studies and suggests that the soleus in individuals with T2DM is likely under tissue oxygenation stress

Postexercise phosphocreatine recovery, an index of mitochondrial oxidative phosphorylation, is reduced in diabetic patients with lower extremity complications

To identify differences in postexercise phosphocreatine (PCr) recovery, an index of mitochondrial function, in diabetic patients with and without lower extremity complications. METHODS: We enrolled healthy control subjects and three groups of patients with type 2 diabetes mellitus: without complications, with peripheral neuropathy, and with both peripheral neuropathy and peripheral arterial disease. We used magnetic resonance spectroscopic measurements to perform continuous measurements of phosphorous metabolites (PCr and inorganic phosphate [Pi]) during a 3-minute graded exercise at the level of the posterior calf muscles (gastrocnemius and soleus muscles). Micro- and macrovascular reactivity measurements also were performed. RESULTS: The resting Pi/PCr ratio and PCr at baseline and the maximum reached during exercise were similar in all groups. The postexercise time required for recovery of Pi/PCr ratio and PCr levels to resting levels, an assessment of mitochondrial oxidative phosphorylation, was significantly higher in diabetic patients with neuropathy and those with both neuropathy and peripheral arterial disease (P < .01 for both measurements). These two groups also had higher levels of tumor necrosis factor-\u3b1 (P < .01) and granulocyte colony-stimulating factor (P < .05). Multiple regression analysis showed that only granulocyte colony-stimulating factor, osteoprotegerin, and tumor necrosis factor-\u3b1 were significant contributing factors in the variation of the Pi/PCr ratio recovery time. No associations were observed between micro- and macrovascular reactivity measurements and Pi/PCr ratio or PCr recovery time. CONCLUSIONS: Mitochondrial oxidative phosphorylation is impaired only in type 2 diabetes mellitus patients with neuropathy whether or not peripheral arterial disease is present and is associated with the increased proinflammatory state observed in these groups

Summary of the subject information including age, BMI, HbA1c, and circumference of the calf.

<p>Summary of the subject information including age, BMI, HbA1c, and circumference of the calf.</p

Figure 4

<p>a Plot of FSR versus age for young (squares) and old (triangles) healthy controls as well as T2DM subjects (circles); x's represent the group averages of the DM and the healthy controls (both young and old) and the bars represent standard deviations. b Plot of soleus T2* versus BMI for healthy and T2DM subjects. c Bar plot of soleus T2* change versus anterior tibilias, HbA1c, and lipid index (FRS) for the young and older healthy controls (YHC and OHC) and T2DM (DM) subjects scanned in this study.</p

Figure 1

<p>a–f T2* weighted images and T2* maps of calves of a young healthy control (a,b), a 64 year old T2DM subject (c,d), and a 68 year old T2DM subject (e,f) acquired at 3T. g–h representative T2 maps of healthy (g) and T2DM (h) calves. Due to relatively long T2s of the subcutaneous lipid and bone marrow (∼115 ms), the contrast among the muscles was less dramatic than that of T2*.</p

Figure 2

<p>a. T2* distribution among anterior tibialis, soleus, and gastrocnemius of young healthy controls (YHC), older age-matched healthy controls (OHC), and T2DM subjects (DM). The error bars represent the standard errors of the means. The difference between the control and the T2DM soleus is significant. The difference between the AT and S is not significant in healthy controls, but it is in T2DM subjects. b. T2 distribution among anterior tibialis, soleus, and gastrocnemius of young healthy controls (YHC), older age-matched healthy controls (OHC), and T2DM (DM). The error bars represent the standard errors of the means. The difference between the control and the T2DM soleus is significant. Compared to T2*, the most dramatic difference is the much longer T2 of the diabetic soleus than observed in either the young or older healthy controls.</p

Representative maps of fat (out-of-phase) (a,c) and water (in-phase) (b,d) of healthy controls (a,b) and T2DM subjects (c,d).

<p>A dramatic increase of lipid can be seen in the diabetic soleus and gastrocnemius.</p

Summary of linear regression analysis between T2* and variables age, BMI, FSR, and group (HC = 0, DM = 1), where constant is the regression constant.

<p>Summary of linear regression analysis between T2* and variables age, BMI, FSR, and group (HC = 0, DM = 1), where constant is the regression constant.</p