The risk for developing diabetic foot ulcers in patients with diabetes over their lifetimes ranges from 19 to 34% [1
]. Diabetic foot is associated with a very high mortality rate and is currently the main cause of nontraumatic lower limb amputation (LEA). [3
] The mortality rate after LEA for diabetic foot was estimated at 13–40% within 1 year, 35–65% within 3 years, and 39–80% within 5 years, which is worse than that observed in malignancies [4
]. Recently, Lavery et al. reported that mortality after diabetes-related amputation exceeds 70% at 5 years for all patients with diabetes. [5
Previous studies have reported several factors that affect mortality after LEA [6
]. Beyaz et al. reported that mortality could be predicted by the duration of insulin use, age, sex, and renal insufficiency after below-knee amputation [6
]. Moreover, Costa et al. reported that old age, major amputation, and low hemoglobin levels are risk factors for death in patients with diabetic foot ulcers [7
Sarcopenia is an aged related condition that involves multiple risk factors, and is associated with function decline, frailty, and other poor health outcomes [11
]. Sarcopenia is defined as the loss of skeletal muscle mass and strength with aging and contributes to both physical disability and mobility limitations [13
]. In addition to aging, many chronic diseases are also associated with sarcopenia [12
]. A few recent studies have shown that sarcopenia affects the outcomes including mortality of abdominal surgery, as well as solid organ cancer surgery [14
]. Frailty that reduced homeostatic reserves has been studied with sarcopenia. When sarcopenia and frailty accompany, physical function impairment may eventually occur [17
Among chronic diseases, diabetes is one of the significant contributors to the exacerbation of sarcopenia [17
]. The Health, Aging, and Body Composition Study revealed that diabetes is associated with rapid loss of skeletal muscle strength and mass [18
]. The prevalence of sarcopenia is as high as 15% in patients with type 2 diabetes [19
]. Sarcopenia can cause a functional disability such as ambulation limitation after LEA, which is thought to be closely related to mortality.
However, the association between sarcopenia and mortality rate after LEA remains unclear. In addition, to the best of our knowledge, no study has investigated the effect of sarcopenia on postoperative outcomes including survival rate after LEA. If sarcopenia affects mortality after LEA, the presence of sarcopenia may be a predictor of the prognosis of LEA in patients with diabetic foot.
Therefore, the objective of this study was to evaluate the relationship between sarcopenia and mortality after LEA. The hypothesis was that sarcopenia affects the mortality of LEA.
To the best of our knowledge, this study is the first to analyze the relationship between survival after LEA and sarcopenia. The findings of this study showed that the mortality rate due to LEA in patients with sarcopenia was higher than that in patients without sarcopenia. These results indicate that preventing sarcopenia in diabetic patients is important to maintain high survival rates. For the same reason, the presence of sarcopenia can be a predictor of the outcome of LEA.
According to previous studies, the 5-year mortality rate after LEA was reported to be 39–80% [4
], and in our study, the 5-year mortality rate of all patients was 52.7%, similar to other studies. However, the 5-year mortality rate of patients with sarcopenia was only 60.7%, while the 5-year mortality rate of patients without sarcopenia was 36.4%. Even after adjusting for all other variables in the multivariate analysis, age, presence of cardiac disease and sarcopenia was an independent predictor for mortality in patients with LEA for diabetic foot. In previous studies [6
], the mortality rate was found to increase with higher amputation levels. Evans et al. [26
] reported that the 2-year survival rate of forefoot/midfoot amputation group was 80%, while that of below knee amputation group was only 48%. However, in our study, the difference in mortality rate between patients who underwent minor amputation and those who underwent major amputation was 10.5%, whereas the difference in mortality rate according to the presence of sarcopenia was 24.3%. It means that mortality rates were significantly higher in sarcopenia patients regardless of the amputation level. And this suggests that the prevention or management of sarcopenia, regardless of amputation level, can be important to improve survival outcomes after LEA.
The known risk factors for survival after LEA are older age, male sex, long-term insulin use, and low hemoglobin level [6
]. In our study, multivariate analysis was performed on factors that differed according to demographics such as age, sex, height, and weight, but only old age was found to have a significant effect. We also analyzed the relationship between laboratory results such as creatinine, HbA1c and fasting glucose level and survival rate, but no significant differences in survival rates were observed. There was no significant difference in preoperative creatinine level between sarcopenia and non-sarcopenia group, which is very valuable in that the presence of sarcopenia has a significant effect on survival, regardless of end-stage renal disease. It is not rejected by study by Wukich et al. [27
] that end-stage renal disease affects survival. In our study, age, presence of cardiac disease and sarcopenia is an important independent predictor.
In a study of 414 type 2 diabetic patients aged 65 years and older, the risk for low muscle mass was 2–4 times higher in diabetic patients than in the control group [28
]. It is known that comorbidities such as increased insulin resistance, higher cardiovascular risk factors, renal failure, peripheral neuropathy, and decreased muscle quality also influence prognosis [29
]. However, this study showed that among patients with diabetes, the prognosis of patients with sarcopenia may be worse for the first time. Many patients with diabetic foot ulcer have relatively reduced activity, and their willingness and strength to walk especially after LEA becomes worse. On the basis of the findings of this study, we propose active rehabilitation and gait exercise training for patients with diabetic foot disease. In addition, our findings provide that efforts to improve muscle strength may increase the survival rate of patients with diabetic foot.
Although the survival rate is important, it is important to determine the treatment strategy of the patients, as well as the difference in functional activity among the surviving patients. Evans et al. [26
] showed a difference in survival rates between below knee amputation group and forefoot/midfoot amputation group, but 64% were able to walk and the two groups were identical. This is contradictory to the general idea that functioning will drop when amputate at higher levels. This can be a hopeful message for patients who have undergone high level amputation. Wukich et al. [30
] reported a significant improvement of SF-36 (Short Form 36) and FAAM score after major amputation compared with before amputation. However, the functional score was not included in this retrospective study.
This study has some limitations. First, there may have been selection bias because only those patients who underwent LEA and had CT data were included. Second, the amputation level was varied. However, we believe that our attempt to categorize amputation has the advantage of reflecting the overall progress of the patients. Third, in this study, only the muscle volume of L3 level was used as a diagnostic criterion, although the method of diagnosing sarcopenia is very diverse. Fourth, an analysis of the factors affecting the outcomes after LEA should include the presence of peripheral artery disease and evidence of infection. However, not all of the patients were not performed vascular study in this study and no available data about evidence of wound infection. Further study is therefore needed. Fifth, this study was retrospective in nature. Therefore, in addition to measuring the skeletal muscle index using CT, there was no investigation of muscle strength and performance, which is a recent diagnostic criterion for sarcopenia. Future prospective studies may be needed to investigate the relationship between muscle function and survival. Lastly, there was no preoperative and final follow up functional score such as FAAM score.