The present study intended to evaluate the association between FFA and muscle indicators via a well-characterized Chinese T2D population, and found that SMI, grip strength and walking speed all showed significant negative correlation with the levels of FFA, and the above correlations were even significant after adjustment for age, sex, BMI and HbA1c. Importantly, FFA may serve as a new biomarker of muscle disorders.
T2D is a worldwide serious public health problem, mainly due to lifestyle changes, especially those involving dietary lipids [13]. Several studies show that the increased levels of FFA play an important role in the development of insulin resistance by inhibiting the oxidation of carbohydrates, which accentuates T2D to a certain degree [14]. FFA is one of the substances decomposed into neutral fat. When the activity-glycogen is depleted, adipose tissue will break down into FFA then can be used as energy. Therefore, FFA is considered as a substance required for sustained activities, and is composed of oleic acid, palmitic acid, linoleic acid, etc. Most of FFA is combined with albumin and exists in the blood circulation. elevated FFAs play a role in many deleterious downstream effects such as loss of pancreatic β-cells, atherosclerosis, and heart disease [15]. High concentrations of FFA can stimulate the highly reactive molecular oxygen clusters (ROS) and reactive nitrogen clusters (RNS) [10], these factors can initiate the oxidative stress and which can directly oxidize and damage DNA, proteins, and lipids, and thus act as functional molecular signals to activate a variety of stress-sensitive signaling pathways in cells [16]. These signaling are closely related to insulin resistance and impaired β-cell function, eventually lead to an increased glucose [10]. Thus, high levels of FFA manifested as continuous progress and deterioration of diabetes. A number of previous studies have found that elevated FFA levels are an early predictor of diabetes and a sign of poor prognosis [17]. Therefore, people with diabetes should pay attention to reducing FFA levels. However, the cut-off point of FFA is not clear. Previous studies have found that muscle dysfunction is served as the poor prognostic indicator of T2D patients [4, 5]. And our study found that FFA levels are closely related to the muscle indicators in adult T2D patients. Therefore, this study analyzes the relationships of FFA with muscle indicators to reveal the most suitable cut-off point for FFA in adult diabetic population. Considering the influence of glucose on the FFA level, this study further corrected a number of indicators including HbA1c, and found that FFA is still significant negatively correlated with muscle indicators. The results indicate that FFA is harmful to the maintenance of muscle function in patients with T2D independent of glucose. The best control levels of FFA is under 0.5mmol/L.
The mechanism research on the relationship between FFA and muscle indicators is still scarce. Micro research found that muscle satellite cells (SCs), the heterogeneous stem cells contributing to muscular regeneration and growth, can obtain property of adipocytes and human SCs even own a clear adipogenic potential, surprisingly, high plasma FFA serve as the initiating factors for above process [18]. The accumulation of intermuscular fat is an important reason for the decline of muscle function in the elderly [19], this may partly explain the high levels of FFA in diabetic patients with sarcopenia. Additionally, researches have reported that high concentration of FFA can lead to oxidative stress, insulin resistance and inflammation and these factors can also contribute to the process of muscle dysfunction [6], which may be the reason for the close correlation between FFA and muscle indicators found in our study.
The current study aims to search for the connections of FFA with muscle indicators and provides new ideas and perspectives for preventing the deterioration of muscle dysfunction in patients with T2D. However, there are still several limitations should be mentioned in this study. First, the treatment of diabetes and dietary habit are not included in this study, which may affect the levels of FFA, and thus can cause a bias. Second, the results are conducted in China, thus may not be widely applicable to other regions. Lastly, this observational study cannot gain causal relationship between FFA and muscle indicators. Further longitudinal studies should be practiced to determine causative correlation between FFA and muscle dysfunction. Nonetheless, these observations are powerful and can contribute to a better understanding of the associations between FFA and muscle dysfunction in adults with T2D.
In summary, the current study illustrated a significant negative correlation between FFA and muscle indicators, indicating that the high concentrations of FFA may contribute to reduced muscle mass and impaired muscle quality in patients with T2D. Therefore, FFA may play an important role in the pathological process of muscle dysfunction in adults with T2D, that is, a comprehensive treatment including a healthy and less oily eating habit is needed to improve the prognosis of diabetic patients with muscle disorders.