Managing Diabetic Foot Ulcers Using Chinese Medicine
Chinese medicine (CM) has been used in China and other Asian countries for thousands of years and has proven effective in the treatment of many chronic diseases and conditions, including diabetic foot ulcer (DFU). This article describes the literature addressing DFU and discusses a comprehensive approach for treating DFU with CM. Many of the substances mentioned are not common in Western medicine; they are presented to underscore the training and skill necessary to utilize an alternative/holistic approach to DFU care.A DFU is one of the most common complications associated with diabetes mellitus (DM).1 More than 194 million people suffer from DM worldwide,2 and within the population of people with DM, the prevalence of foot ulcers ranges from 4% to 10%.3 Foot ulceration may lead to infections and lower extremity amputations, which are major causes of patient disability and often result in substantial morbidity, extensive periods of hospitalization, and mortality,4 as well as economic burden.5 An amputation occurs every 30 seconds throughout the world,6 and 85% of amputations are preceded by an ulcer.7 The situation promises to worsen in the future as the incidence of foot ulcers increases with the ever-growing global prevalence of type 2 diabetes, particularly in developing countries.8,9 DFUs are complex and require a multidisciplinary approach. The fundamental basics in the healing of DFUs include adequate perfusion, debridement, infection control, and pressure mitigation.4 However, no one approach has been found to guarantee an ideal outcome for healing a DFU. Chinese medicine (CM) has been used in China and other Asian countries for thousands of years and has proven to be an effective therapy in variety of diseases. Now it also has gained great popularity in other parts of the world and attracted interest from the scientific research community. Based on a unique theoretical system and accumulated clinical experiences, CM, which accounts for approximately 40% of all healthcare delivered in China,10 has developed a specific and systematic understanding of DFU and provided a comprehensive therapeutic tool for treating the wounds.
Recognition of DFU in CM
CM has its own specific physiology and pathology. According to ancient CM theory, the causes and mechanism of DFU (CM does not have a name for the condition; equivalently, DM is called tuo ju, xue bi, and jin ju) are complex and mostly qi and yin deficiency are involved. The major pathogenic factors in the CM approach include xue yu (blood stasis, obstruction of local blood circulation), shi zhuo (damp turbidity, ulcers with profuse exudate), and re du (heat toxin—ie, infection). The treatment of DFU using CM should take both clinical manifestation (symptoms) and major causes (underlying etiology) into account. Similar to Western approaches, CM treatment efforts are designed to increase the patient’s quality of life, limit DFU complications, salvage limbs, and improve DFU grades. A comprehensive CM approach to DFU care includes individualized endotherapy with Chinese herbal formulas, topical treatment, and acupuncture.11
DFU Stage-specific Treatment
Chinese herbal formula is always regarded as the primary therapy and applied quite widely in clinical practice for almost all kinds of diseases. The underlying idea of traditional CM is the holistic concept of the Yin-Yang balance in the body that strives for harmonization. Orally administered Chinese herbal formulas comprise several components that can help the body reinforce the healthy qi and eliminate the pathogenic factors according to CM therapeutic protocols. Because each prescription is highly individualized, many CM herbal substances for DFU can be utilized. Thus, it is difficult to cover all prescriptions completely in this paper; however, clinically, DFU can be categorized by stages and treated accordingly. The most commonly applied prescriptions are addressed in this paper. Ischemia before ulceration. In this stage, the ulceration has not occurred, and prompt intervention using CM can prevent ulceration. The major pathogeneses in this stage are identified in CM as qi deficiency and blood stasis based on the following manifestations: acroaesthesia (numbness in the limb extremities); feeling cold; pale, withered, or darkened skin; intermittent claudication; pain that worsens at night; cold limbs; fatigue; decreased dorsal pedis artery pulse; pale, white-coated tongue; and abnormal pulse. Some of the symptoms or signs are addressed in biomedicine, while more clinical symptoms or signs, such as qi deficiency and blood stasis, are the focus of CM and these clinical manifestations are the basis for CM diagnosis. The treatment principle is to replenish qi and stimulate blood flow to unblock Yang and diffuse the impediment. The most frequently prescribed medicines are classical herbal formulas described in CM books and include bu yang huan wu decoction to replenish qi and stimulate blood flow; huangqi guizhi five-herb decoction to unblock Yang and diffuse the impediment; and modified congeneric formulae based on changes of some symptoms. Typical Chinese herbal formulae are presented in Table 1. The herbal medicine names mentioned in the table refer to the sliced herbal materials (yin pian), and those materials are commonly used for decoction in CM and can be provided in general Chinese medicine clinics over world. All the Chinese medicine injections mentioned are approved drugs by Station Food and Drug Administration (SFDA); they are commonly used in most Chinese hospitals and can be found in Chinese drug stores. DFU with ulceration. When the patient presents with a DFU, with or without infection, the major pathogenesis is recognized as yin deficiency and blood stasis in CM, with retained re du (heat toxin). Manifestations include acroaesthesia; scorching hot pain that is worse at night; ulceration in the extremities; ulcer exudate; dry mouth and difficulty swallowing; agitation; insomnia; dry stool; discolored urine; decreased pulse in the dorsal pedis artery; dark purple tongue, lack of tongue coating, or yellow tongue coating; and stringy, rapid, fine pulse or slippery, rapid, fine pulse. The treatment principle is to nourish yin and activate blood to clear the heat and remove toxin. The most frequently used prescriptions include zeng ye decoction to nourish yin; and si miao yong an decoction to activate blood to clear the heat and remove toxin. A sample formula is presented in Table 2. DFU in a terminal stage with severe gangrene. This stage is considered the most complicated. The primary pathogenesis includes deficiency of both yin and yang and stasis and stagnation due to heat toxin, manifested as fatigue; acratia; cold pain in the low back and knees; acroaesthesia; cold and pain worse at night; dry mouth and difficulty swallowing; limb puffiness/swelling; burning in the chest, palms, and soles; nonhealing ulcers in the acra; enlarged tongue; white or yellow fur; and decreased, weak, fine, or rapid pulse. The treatment principles are to nourish yin and assist yang, promote the local blood circulation, and remove toxin. The medicines most often applied based on the changes of symptoms and signs include di huang yin zi decoction to improve the gangrene, nourish yin, and assist yang; er xian decoction to promote the local blood circulation and remove toxin; si miao yong an decoction to activate blood to clear the heat and remove toxin; and a modified congeneric formulae are. An example of a core formula is presented in Table 4.
DFU Stage-specific Topical Treatment
Topical treatment for DFU with CM is easy to facilitate. Topical treatment is intended to prevent ulceration in the early stages, promote ulcer drainage, promote wound healing of the gangrene, and reduce the amputation rate. Common topical treatment methods are listed in Table 5. The sliced herbal medicines (yin pian) listed in the table can be found in most Chinese medicine clinics.
Acupuncture will help promote the blood circulation in the affected extremities to recover sensation and motor function by unblocking the meridian, activating collaterals, and regulating whole body function. Acupoints including ST36 (Zusanli), GB34(Yanglingquan), BL39(Weizhong), SP6 (Sanyinjiao), BL60 (Kunlun), KI3 (Taixi), SP10 (Xuehai) often are used to treat DFU. Ear points applied include AH6 (Jiaogan), AT4 (Pizhixia), CO10 (Shen, kidney), CO12 (Gan, liver), CO13 (Pi, spleen), CO14 (Fei, lung), and CO15 (Xin, heart).
Clinical Studies in the Treatment of Diabetic Foot Ulcers
CM treatment has been used for DFU care for thousands of years. The therapeutic effect is recognized mostly through clinical experience. However, over the past decades, an increasing number of researchers has focused on exploring the mechanism of CM for DFU. Some wound healing-enhancing formulae and active components such as Radix Astragali, Radix Rehmanniae, Rhizoma Alismatis and Rhizoma Atractylodis Macrocephalae have proven effective in enhancing fibroblast viability,12 modifying tissue glucose homeostasis effect in vitro,13 and promoting DFU healing in rats through the processes of tissue regeneration, angiogenesis, and inflammation control.2,14 This research provides scientific support for the use of CM for treating DFU. Clinical trials also have been conducted to assess the effectiveness and safety of CM or integrative CM and modern treatment for DFU. Some randomized, controlled trials (RCTs) underscore the value of CM in treating DFU. A study15 of 57 patients with chronic diabetic foot ulcers of Wagner's ulcer grade 1 to 3 involving the topical CM compound tangzu yuyang ointment (TYO) plus standard wound therapy (SWT) showed the addition of CM was more effective (and had few side effects) than using only SWT in the management of chronic DFU after 24 weeks treatment. In another RCT15 involving 72 cases, danggui sini decoction (used for nourishing blood to warm meridians, which has positive effect on decreasing the plasma level of advanced glycation end products in patients with Wagner grade 0 DFU due to blood stasis or/and kidney yang deficiency syndrome) was shown to improve clinical symptoms in patients with DFU of Wagner grade 0 and showed therapeutic effects on diabetes complicated by vascular disease. Another RCT16 conducted on 63 patients concluded integrated Chinese and Western medicine (ICWM) treatment for DFU was better than using Western medicine alone and emphasized the value of individualized CM treatment. A preliminary clinical study in 30 patients,17 using CM and simple debridement as an alternative to amputation, was shown to successfully salvage limbs in 35 of 40 legs. A case report18 encourages further research into the treatment of DFU with CM. A patient with severe DFU (Wagner IV grade) was cured after treatment using a holistic multidisciplinary approach (ie, a combination of traditional CM and Western medicine, surgical management, education for diabetic foot care, and psychological counseling); this patient may otherwise have had foot amputation and/or sepsis. In the authors’ clinical practice, a severe case of DFU (Wagner IV grade) also was treated successfully with integrative CM and modern medicine therapy.
According to the holistic characteristics of CM theory, the targets of treatment are concentrated on traditional CM patterns (syndrome or Zheng) rather than diseases. CM intervention includes multiple, interactive, personalized measures, and outcomes tend to depend on whether the body’s harmony is restored. This makes efficacy assessment using RCTs difficult.19 Furthermore, blinding topically applied CM products is difficult; thus, it is challenging to design a cogent RCT to assess efficacy and safety of CM for DFU objectively. Therefore, a meta-analysis aimed to assess the effectiveness and safety of CM as an adjunctive method to standard therapy for patients with DFU may be a way to determine the effectiveness and safety of CM as an adjunctive therapy for treating DFU. However, at this juncture, a firm conclusion could not be reached because of the poor quality of the included trials. Although the quality of previous clinical trials involving CM used in the treatment of DFU need to be improved, more good-quality clinical trials in this topic are currently ongoing under financial support of Ministry of Science and Technology of China. The authors believe that more solid evidence could be collected to show the efficacy of CM in the treatment of DFU. Further high-quality trials are justified.20
CM, as either independent or adjunctive therapy for DFU treatment, can be an effective and safe approach. Studies that yield more clinical evidence should be developed, especially regarding topical product research.
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Yunyu Huang (Department of Nutritional Department, Dongzhimen Hospital, Beijing), Miao Jiang (China Academy of Chinese Medical Sciences, Beijing,), Chi Zhang (China Academy of Chinese Medical Sciences, Beijing,), Yuming Guo (China Academy of Chinese Medical Sciences, Beijing,), and Aiping Lu (China Academy of Chinese Medical Sciences, Beijing; and E-institute of Shanghai Municipal Education Commission, Shanghai TCM University, Shanghai) For more information, email Dr. Lu: email@example.com. This research was sponsored partly by the projects from the National Science Foundation of China (Project Nos. 30825047 and 30902003), National Eleventh Five Year Support Plan (Project No. 2006BAI04A10), the Innovative Methodology Project supported by MOST of China (2008IM020900), and E-institutes of Shanghai Municipal Education Commission (No. E03008).