The major finding of this study is that at resting state, the soleus T2* value was significantly correlated with age and associated with the presence of diabetes (or elevated HbA1c) (see ). The diabetic soleus T2* was abnormally short compared to the age-matched controls and the surrounding anterior tibialis and gastrocnemius ( and ). Underlying physiologic factors contribute to the T2 and T2* values of anterior tibialis, gastrocnemius, and soleus muscles of the subjects in this study. The T2 values were prolonged in anterior tibialis, soleus, and gastrocnemius of the T2DM and the age matched healthy controls reflecting increased fluid levels, and increased lipid levels mostly seen in T2DM, because of the disease and age-related propensity to accumulate fluid and lipid in the lower legs compared to the young, healthy individuals (). This explanation is consistent with the results measured independently by the isotope dilution method in a separate study 
and is supported by the relatively long T2 values of subcutaneous fat. The longer T2* values in the anterior tibialis and gastrocnemius of T2DM subjects, as well as in the soleus muscles of older healthy subjects, were consistent with the prolonged T2 values due to accumulation of fluid and lipid.
The shorter T2* values in the soleus muscles of T2DM subjects ( and ), however, may result from underlying pathophysiology despite the longer regional T2 value. It is known that gastrocnemius and anterior tibialis muscles are composed of predominantly fast-twitch fibers, while soleus consists largely of slow-twitch fibers 
. Soleus is rich in mitochondria and capillary vessels and consumes more oxygen due to the characteristic energetic metabolism of slow-twitch fibers. Previous studies of animal muscles indicate that the diabetic state is associated with a reduction in capillaries capable of supporting red blood cell (RBC) perfusion 
. These muscle capillary defects have been confirmed in diabetic patients by thallium-201 scanning 
. Interestingly, Cosson et al found the calf muscle perfusion defects were also significantly correlated with elevated HbA1c levels, similar to our findings (). Therefore, the reduced perfusion in the microvascular bed of the soleus muscle could lead to an increase in regional deoxyhemoglobin levels and unusually low regional T2* compared to gastrocnemius and anterior tibialis. This is consistent with the present findings.
Abnormally low soleus T2* values in diabetic calf muscle have been observed in a previous study. Ledermann et al applied a cuff compression paradigm for reactive hyperemia and BOLD MRI with four-echo EPI to patients with peripheral arterial occlusive disease (PAOD) and found soleus had the larger T2* changes (ΔT2*) and longer time-to-peak compared to anterior tibialis and gastrocnemius after cuff deflation 
. Although they did not report resting state T2* values for the soleus, the large ΔT2* implied a lower soleus T2* among the calf muscles at baseline, consistent with the findings of the current study.
In addition to the lower soleus T2*, lipid significantly accumulated, and was noticeably visible in the MR images as a thickening subcutaneous fat layer, with infiltration into the gastrocnemius and soleus of the T2DM subjects ( and ). This characteristic of T2DM skeletal muscle likely resulted from insulin resistance, impaired glycogen synthesis, and impairments in mitochondria. Nonetheless, the non-significant correlation between soleus T2* and regional lipid levels, as illustrated in , suggests that the T2DM state (or elevated HbA1c) is the dominant contributor to the abnormally low soleus T2* value.
Compared to muscle exercise and kinetic paradigms, resting state studies use a lower temporal resolution and a higher spatial resolution to measure the T2* values in calf muscles. This imaging scheme is simple, short in duration (less than 7 minutes for acquisitions of both T2 and T2* images), and more acceptable to patients with clinical disabilities and may thus have broader utility in applications that require high spatial resolution. The resting state approach may provide complementary information regarding regional tissue oxygen consumption, to perfusion studies in nuclear medicine 
or to exercise and kinetic paradigms 
. Moreover, these MRI techniques may provide information that allows clinicians to avoid a potentially harmful biopsy and serve as a valuable diagnostic alternative for diabetic patients with vascular complications, since many of these patients may have coexisting diabetic nephropathy, to reduce the risk associated with the administration of gadolinium-based contrast agents. Clinical use of these techniques may provide valuable information for investigating and clinically evaluating the systemic microvascular and macrovascular changes that lead to the more well-recognized diabetic complications such as retinopathy, neuropathy, or cardiovascular disease.
In summary, we have measured T2 and T2* values of calf muscles at rest and found that soleus T2* is significantly correlated with age, the presence of T2DM or elevated HbA1c. The T2* of T2DM soleus muscle was significantly lower than that of age matched healthy controls and that of young and healthy controls as well as the T2* values of T2DM anterior tibialis and gastrocnemius. Our data indicate that the soleus T2* measures provide valuable information reflecting underlying physiology and are consistent with previous findings of other studies. Among factors that may contribute to T2* values, the lowered T2* in the T2DM soleus muscle is most consistent with a combination of high oxygen consumption and poor regional microvascular circulation which suggests that the T2DM soleus is likely under tissue oxygenation stress.