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Year : 2020  |  Volume : 3  |  Issue : 2  |  Page : 58-69

Chinese guidelines for diagnosis and treatment of diabetic foot

Department of Vascular Surgery, Xuanwu Hospital Affiliated to Capital Medical University, Beijing, China

Date of Submission02-Mar-2020
Date of Decision20-Mar-2020
Date of Acceptance24-Mar-2020
Date of Web Publication09-Jul-2020

Correspondence Address:
Dr. Gu Yongquan
Department of Vascular Surgery, Xuanwu Hospital Affiliated to Capital Medical University, Beijing 100053
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/VIT.VIT_10_20

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How to cite this article:
Yongquan G. Chinese guidelines for diagnosis and treatment of diabetic foot. Vasc Invest Ther 2020;3:58-69

How to cite this URL:
Yongquan G. Chinese guidelines for diagnosis and treatment of diabetic foot. Vasc Invest Ther [serial online] 2020 [cited 2020 Aug 11];3:58-69. Available from: http://www.vitonline.org/text.asp?2020/3/2/58/289238

As one of the serious chronic complications leading to disability and death of diabetic patients in China, diabetic foot features a high incidence rate, difficult treatment, and huge cost for treatment. At present, the guidelines formulated by the International Working Group for Foot Disease and the American Diabetic Foot Group are mainly referred to in China. However, due to the characteristics of China's diabetic foot, the China International Exchange and Promotive Association for Medical and Health Care and the Expert Committee on Diabetic Foot Disease of Chinese Chapter of International Union of Angiology organized the national experts on diabetic foot to draft the Chinese Guidelines for Diagnosis and Treatment of Diabetic Foot.

  Concept of Diabetic Foot and High-Risk Foot Top

Diabetic foot: Distal neuropathy of lower extremity and/or foot ulcer and/or deep tissue damage from vasculopathy at different degrees, which all are caused by diabetics, with or without infection. Diabetic high-risk foot: Diabetic patients do not have foot ulcer but have peripheral neuropathy, no matter whether they have foot deformity or peripheral arterial disease or a history of foot ulcer or amputation of lower extremity or toe.

  Epidemiology Of Diabetic Foot And Lower Extremity Arterial Disease Top

Foreign data show that diabetes patients accounted for 40%–60% of all nontraumatic amputations of lower extremity, and 85% of diabetes-related lower distal amputations occurred after foot ulcer. The incidence of foot ulcer was 4%–10% among diabetic patients. According to the data of multicenter studies in China, the proportion of lower extremity arterial lesions is 19.5% in patients with diabetes of over 50 years old in China.[1] Single-center studies showed that the proportion of lower extremity arterial lesions was 35.4% in patients with diabetes of over 60 years old.[2]

The incidence of new ulcer in 1 year was 8.1% in diabetic patients and 31.6% in diabetic patients with foot ulcer.[3]

  Clinical Manifestations Of Diabetic Foot Top

Manifestations of neuropathy

The skin of the affected extremity is dry and free of perspiration, and the patient has tingling, causalgia, numbness, hypoesthesia, or anesthesia at the extremities and also sock-like changes, and has the feeling of stepping on cotton wadding when walking.

Manifestations of lower extremityischemia

The patient has skin malnutrition, amyotrophy, dry skin with poor elasticity, decreased skin temperature, pigmentation, and decreased or disappeared arterial pulsation at the extremity, and may have intermittent claudication symptoms of the lower limbs. With the progress of the lesions, the patient may suffer from rest pain, gangrene at the toe end, and ulcer at the compression part of the heel or metatarsophalangeal joint, and some patients may have limb infection.

  Auxiliary Examination Of Diabetic Foot Top

Nervous system examination

Diabetic peripheral neuropathy (DPN) can be diagnosed with the following methods. However, peripheral neuropathy caused by other causes must be excluded. (1) Test method with 10 g nylon wire: As a relatively simple one for sensory nerve, this method requires a piece of special nylon wire which can produce 10 g pressure by bending by 45°. Before the examination, the nylon wire is usually used in the palm or forearm of the patient for 2–3 times to allow him/her to feel the normal feeling of 10 g pressure produced by the nylon wire. The test should be carried out on both feet. The pressure time should be 2–3 s on each examination point and not be too long; the examination site should avoid callosum, blister, ulcer surface, and the like. It is suggested that 10 points should be tested in the abdomens of the first, third, and fifth toes; the heads of the first, third, and fifth metatarsals; the core of the foot; the lateral sides of the foot palm; and between the first and second metatarsals of the both heel and dorsum of the foot. If a patient has two or more points with sensory abnormalities, he/she is regarded as abnormal one. (2) Vibration sense: This is a semi-quantitative examination on the sense of deep tissue. First, the handle of a tuning fork which is vibrating is placed at the mastoid of the patient to let him/her feel the vibration of the fork, and then at the bony protuberances of the two feet for comparative examination, including the first medial metatarsophalangeal joint, and medial and lateral malleolus. (3) Ankle reflex, algesia, and thermesthesia: These three methods can also be used in the diagnosis of DPN. (4) Nerve conduction velocity (NCV) was considered as the “gold standard” for the diagnosis of DPN in the past.[4] Usually, when there are two or more NCV slowdowns, DPN can be considered to occur in combination with other symptoms and signs, and auxiliary examinations.

Examination of vascular disease

(1) Physical examination: The vascular lesions of lower extremities are examined through palpation of femoral artery, dorsal arteries of foot and/or posterior tibial artery; through Buerger test to understand the situation of lower extremity ischemia. (2) Examination of skin temperature: Infrared examination of skin temperature is a simple and practical method to evaluate local blood supply. It is best to use temperature difference to judge blood supply to limbs. (3) Blood pressure: ratio of ankle artery to brachial artery: Also known as ankle brachial index (ABI), it reflects the blood circulation of limbs. Its normal value is 0.9–1.3. 0.71–0.89 means mild ischemia, 0.4–0.7 means moderate ischemia, and <0.4 means severe ischemia. Patients with severe ischemia are prone to suffer from gangrene of the legs (toes). If the systolic pressure of ankle artery is too high, for example, it is higher than 200 mmHg or ABI is higher than 1.3, it should be highly suspected that the patient has calcification of lower extremity artery. Some patients with a normal ABI value may have a false-negative result, which can be corrected with treadmill exercise test or toe brachial index measurement. (4) Transcutaneous oxygen pressure (TcPO2): A person has the normal value of TcPO2>40 mmHg on the back of the foot; if there is TcPO2<30 mmHg, it indicates that the peripheral blood supply is insufficient, the foot is prone to ulcer, or the existing ulcer is difficult to heal; if there is TcPO2<20 mmHg, the foot ulcer is almost impossible to heal. (5) Vascular imaging examinations, including color Doppler ultrasound, computed tomography angiography (CTA), magnetic resonance angiography (MRA), and digital subtraction angiography (DSA). Color Doppler examination of blood vessels is noninvasive and simple and can be used to know the status of atherosclerotic plaques and whether there is stenosis or occlusion of arteries. It is suitable for the large-scale screening of vascular diseases. CTA and MRA feature clear imaging and can show whether there is stenosis or occlusion of blood vessels, but their accuracy is lower than that of DSA. DSA is still the “golden standard” for the diagnosis of lower extremity vascular diseases and can accurately show the status of arterial occlusion and the establishment of arterial collateral circulation and play an important role in the selection of treatment options.

  Diagnosis Of Diabetic Foot Top

Diagnosis of diabetic lower extremity angiopathy

Diagnosis basis: (1) It is in accordance with the diagnosis of diabetes; (2) It has clinical manifestations of lower extremity ischemia; (3) Auxiliary examination indicates lower extremity angiopathy, with ABI <0.9 at rest or ABI >0.9 at rest, but lower extremity discomfort occurs at exercise, ABI is reduced by 15%–20% after treadmill exercise test or imaging indicates vascular stenosis.

Diagnosis of diabetic peripheral neuropathy

A patient has a clear history of diabetes, neuropathy at or after the diagnosis of diabetes, and also clinical manifestations of lower extremity neuropathy. If there are two or more abnormalities in the following five examinations, DPN is diagnosed: (1) Abnormal thermesthesia; (2) Hypoesthesia or an aesthesia of foot in nylon wire examination; (3) Abnormal pallesthesia; (4) Ankle areflexia; and (5) Slowdown of two or more NCVs. Other diseases should be excluded in this diagnosis such as cervical and lumbar lesions (nerve root compression, spinal stenosis, and cervical and lumbar degenerative changes), cerebral infarction, Guillain–Barre syndrome, and severe arteriovenous diseases (vein embolism and lymphangitis). It is also necessary to identify the neurotoxic effects of drugs, especially chemotherapeutics, and the damage to nerve caused by metabolic toxicants from renal insufficiency.

Diagnostic stratification of DPN:[5],[6],[7] (1) Definite diagnosis: A patient has symptoms or signs of distal symmetric polyneuropathy and abnormal nerve conduction; (2) Clinical diagnosis: A patient has the symptoms of distal symmetric polyneuropathy and one positive sign, or no symptoms but two or more positive signs; (3) Suspected diagnosis: A patient has symptoms of distal symmetric polyneuropathy but no sign; and (4) Subclinical diagnosis: A patient has no symptoms or signs of distal symmetrical polyneuropathy, but only abnormal nerve conduction.

Diabetic foot infection

According to the scope of infection and clinical manifestations, diabetic foot infection below the ankle of a diabetes patient can be classified into mild, moderate, and severe,[7] as shown in [Table 1].
Table 1: International Working Group on Diabetic Foot/Infectious Disease Society of America classification of diabetic foot infection

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Type and grade of diabetic foot

The manifestations of diabetic foot include infection, ulcer, and gangrene. According to the etiology, ulcer can be divided into nervous, ischemic, and neuro-ischemic ulcer. Gangrene can be divided into three types: wet gangrene, dry gangrene, and mixed gangrene in terms of its nature. It helps to choose a reasonable treatment plan and judge prognosis to correctly classify and grade diabetic foot patients before treatment.

Classification according to the cause of ulcer

(1) Neuropathic ulcer: Patients with neuropathic ulcer usually have numbness, abnormal sensation, and dry skin, but the skin temperature is normal and the pulse of dorsal foot artery is good. The patients with severe disease can develop into neuroarthropathy (Charcot's disease); (2) Neuro-ischemic ulcer: Patients have peripheral neuropathy and peripheral vascular disease at the same time, and diabetic foot patients are mostly of this kind. In addition to the symptoms of neurogenic ulcer, patients also have the cold sensation of the lower limbs, intermittent claudication, rest pain, and etc.; weakened or disappeared pulse of the dorsal foot artery; the reduced skin temperature of the foot; and less bleeding in the wound surface during debridement and dressing change; and (3) Ischemic ulcer: This kind of patients have no peripheral neuropathy, but mainly ischemic changes, which is rare, so diagnosis can be made only after peripheral neurogenic lesions should be excluded according to the symptoms, signs, and related examinations.

Classification according to the nature of gangrene

(1) Wet gangrene: There are relatively more diabetes patients with wet gangrene, who have often local redness, swelling, pyrexia, pain, dysfunction, etc., and severe cases are often accompanied by toxaemia or septicemia or other clinical manifestations; (2) Dry gangrene: Patients with dry gangrene have local dry tissue gangrene, generally without infection; and (3) Mixed gangrene: Mixed gangrene is a little more common than dry gangrene, and accounts for 15.2% of diabetic foot gangrene, and the disease is often combined with infection.

Grading of diabetic foot

Wagner grading and Texas grading are widely accepted clinically at present. However, due to complex illness conditions of diabetic foot, the vasculopathy, neuropathy, infectious degree, and soft tissue and bone destruction differ a lot, and thus any grading method is not perfect in this aspect.

Wagner grading

This grading method was first proposed by Meggitt in 1976, and promoted by Wagner later.[8] It is the most widely used grading method clinically and in scientific research at present, as shown in [Table 2].
Table 2: Wagner grades of diabetic foot

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Texas grading

Proposed by Lavery et al. of Texas San Antonio University, the United States[9] [Table 3], Texas grading method is used to evaluate diabetic foot ulcer and gangrene from two aspects, i.e., pathological degree and etiology, so that it better reflects the situation of wound infection and ischemia, and is better than Wagner grading method in evaluating the severity of wound and predicting the prognosis of limbs.
Table 3: Texas grades of diabetic foot

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Domestic grading method

In 1995, Li Shiming from the General Hospital of Air Force classified diabetic foot into 0–5 grades according to the degree of pathological changes based on the development law of infection; pathophysiology; anti-infection ability of body tissues; and the nature, scope, and depth of gangrene. Grade 0: Patients have no open lesions on skin. It is often manifested as insufficient blood supply to the extremities, cool skin, cyanosis or pallor, numbness, and dullness or loss of sensation. In addition, patients have tingling or causalgia on extremities, and often have the manifestations of high-risk foot such as toe or foot deformity. Grade 1: Patients have open lesions on the skin of extremities, and also superficial ulcers caused by blisters, blood blisters, corns or calluses, frostbite or scald, and other skin lesions, but the lesions have not yet affected deep tissues. Grade 2: Patients have infectious lesions invading deep muscle tissue. Patients have usually mild cellulitis, multiple purulent foci and sinus tract, or widen infection of the extensor space, resulting in penetrating ulcer or gangrene of the pelma and dorsum of the foot and more purulent secretion. There is focal dry gangrene on the skin foot or toe, but no destruction of tendon or ligament. Grade 3: Patients have tissue damage of tendon and ligament, a large purulent cavity formed by cellulitis, increased purulent secretion and necrotic tissue, dry gangrene with foot or a few toes, and bone destruction which is not obvious. Grade 4: Patients have bone destruction resulted from severe infection, osteomyelitis, bone joint destruction or pseudarthrosis, Charcot's arthropathy, and severe wet or dry gangrene or necrosis with some feet or toes. Grade 5: Patients have infection or ischemia with most or all of the feet, leading to severe wet or dry gangrene, blackening of the extremities, and dry cadaver, which often affect ankle joint and crus. Generally, large amputation is used. It should be noted that this grading method has certain limitations and does not take into account the factors of ischemia, but it is understandable in the current environment because the ischemic factors were not the main factors for Chinese patients, and the understanding of diabetic foot also had certain limitations in the medical community at that time. As the first grading method proposed by Chinese scholars, it has been recognized and used by peers all over China.

  Treatment Of Diabetic Foot Top

Prevention and treatment objectives and strategies of diabetic foot

Prevention and treatment objectives of diabetic foot: To prevent the progress of systemic atherosclerotic disease, prevent the occurrence of cardiovascular and cerebrovascular events, and reduce the mortality of diabetic foot patients; to prevent ulcer and diabetic gangrene caused by ischemia, prevent amputation or reduce the amputation plane, and improve the lower extremity function of patients with intermittent claudication. Prevention and treatment strategies of diabetic foot: first-level prevention: To prevent or delay the occurrence of neuropathy and peripheral vascular disease; second-level prevention: To relieve symptoms and delay the progress of neuropathy and peripheral vascular disease; third-level prevention: To reconstruct blood circulation, comprehensively treat ulcer, and reduce amputation rate and the incidence of cardiovascular events.

Internal medical treatment of diabetic foot

Diabetic foot can be divided into the following three types: nervous type, ischemic type, and neuro ischemic type. It has been found from research that the main type of diabetes is mixed type in China, followed by ischemic type, while the proportion of pure nervous type is lower than that of the former two types.[10] For neuropathy, in addition to the treatment of neuropathy, it is important to reduce the pressure of the affected limb, and local debridement can promote the healing of ulcer;[11] for ischemic lesions, drug treatment, exercise, and reconstruction of blood flow of the lower limb can be used to achieve a certain effect;[12],[13] even for mixed lesions, if the blood flow is improved, the neuropathy can also be relieved partially.

Good metabolism management

For diabetic foot patients, we should actively control blood glucose by firstly choosing insulin,[10] and fully control blood glucose (glycosylated hemoglobin <7%), and at the same time reduce the incidence of hypoglycemia as much as possible to reduce the incidence of foot ulcer and infection, and then decrease the risk of amputation.[14] However, because diabetic foot patients are often older and they have more comorbidities and complications, we should not blindly emphasize the control of glycosylated hemoglobin in patients whose glycosylated hemoglobin is below 7%. In this case, we should refer to the individual control goal recommended by the Expert Consensus on the Control Targets of Glycosylated Hemoglobin in Chinese Adult Type-2 Diabetes formulated by the Endocrinology Branch of the Chinese Medical Association.[15] For diabetic foot with hypertension, the blood pressure should be controlled below 130/80 mmHg; for diabetic foot with abnormal lipid metabolism, statins should be given to control the level of LDL cholesterol below 2.6 mmol/l; for diabetic foot with lower extremity arterial disease, the level of LDL cholesterol should be controlled below 1.8 mmol/l; if there is no clinical taboo, a low dose of aspirin (75–150 mg/day) should be given.[16]

Exercise rehabilitation treatment of lower extremities

If patients with ischemic or neuro-ischemic diabetic foot have intact skin of the foot, exercise can improve the walking distance and walking time of those with intermittent claudication.[17] Compared with placebo or routine nursing, exercise rehabilitation treatment under supervision can significantly improve the maximum walking distance, painless walking distance, and 6-min walking distance of patients with lower extremity arterial disease,[18] and at the same time, it can also significantly improve the motor function indexes of patients with lower extremity arterial disease, such as distance score, speed score, and ladder score mentioned in Walking Impairment Questionnaire. It is a safe and effective treatment to enhance walking exercise that can improve the motor tolerance and motor function of patients with ischemic or neuro-ischemic diabetic foot, and not increase the incidence of adverse events.[18]

Drug treatment

Vasodilator therapy with drugs

At present, the vasodilators used clinically include lipomicrosphere alprostadil injection, beraprost sodium, cilostazol, salgrel hydrochloride, buflomedil, and pentoxifylline.

As a powerful phosphodiesterase - inhibitor, cilostazol was recommended as a first-line drug for the treatment of intermittent claudication by the Trans-Atlantic Collaboration in 2007.[19] In the treatment of diabetic foot, cilostazol can not only inhibit platelet aggregation to prevent thrombosis, but also increase the blood flow of narrow artery and improve the ischemic state of the affected limb through vasodilation/expanding blood vessels.[20] The application of cilostazol can significantly delay the occurrence of amputation in diabetic patients,[18] and also improve the situation of arterial ischemia in diabetic foot patients.[21] Studies have shown that the treatment with cilostazol (100 mg, twice a day) for 24 weeks can effectively prevent diabetic foot ulcer;[22] after 8 weeks of treatment with cilostazol (100 mg, twice a day), the transcutaneous partial oxygen pressure, intermittent claudication, and coldness and algesia of limbs are significantly improved in patients with Type 2 diabetic lower limb ischemia, which is better than aspirin.[23] The adverse reactions of cilostazol mainly include headache, diarrhea, abnormal stool, dizziness, and palpitation, but the symptoms are mild and tolerable. The serious adverse events of cilostazol include cardiovascular events whose mortality rate is not increased compared with placebo, but the long-term effectiveness is not clear.[24] The recommended dose of cilostazol is 50–100 mg/time, twice a day.

As a multitarget circulatory improver, salgrel hydrochloride has specific antagonistic effect on platelet and 5-hydroxytryptamine-2 receptor of vascular smooth muscle, thus inhibiting platelet aggregation caused by 5-hydroxytryptamine-2 receptor and also vasoconstriction and proliferation of smooth muscle cells, and also improves the deformability of red blood cells, collateral circulation, and microcirculation disorders. Salgrel hydrochloride is recommended for the treatment of ischemic symptoms such as ulcer, pain, and cold sensation caused by chronic arterial occlusive disease, and is effective especially in the treatment of rest pain. The recommended dose of salgrel hydrochloride is 100 mg/time, three times/day.

Among the prostaglandins, lipomicrosphere alprostadil has the best efficacy and tolerance. A meta-analysis showed that prostaglandin E1 significantly increased walking distance compared with placebo, and the walking ability of patients kept increasing even after discontinuation of treatment.[25] According to the degree of pathological changes of patients, the dose of lipomicrosphere alprostadil injection is recommended to be 10 μg/time through intravenous injection or intravenous drip, 1–2 times/day, and the course of treatment is 14–21 days. The treatment with beprost sodium can improve the subjective symptoms of the lower limbs of patients with diabetic peripheral vascular disease, such as burning sensation, cold sensation, edema, exertional pain, acupuncture pain, and sensory abnormality.[26] Therefore, beprost sodium can effectively improve the symptoms of patients with intermittent claudication.[27]

As a nonselective phosphodiesterase inhibitor, pentoxifylline is the first drug approved by the FDA (in 1984) for the treatment of intermittent claudication. It can inhibit the activity of platelet phosphodiesterase, increase the level of cyclic adenosine phosphate,[28] and thus decrease the level of adenosine diphosphate, inhibit platelet adhesion and aggregation, reduce blood viscosity, and prevent thrombosis;[29] at the same time, it can stimulate vascular endothelial cells to release prostaglandins, inhibit the synthesis of endothelin in endothelial cells, and then play the role of vasodilator.[28] In addition, pentoxifylline can reduce the transcription level of tumor necrosis factor-alpha and inhibit the expression of inflammatory factors.[30]

Tongsaimai tablet (capsule) can promote the repair of vascular endothelial cells, the establishment of collateral circulation, the improvement of hemodynamics, and thus the improvement of blood microcirculation. Clinical evidence showed that tongsaimai tablet can improve the symptoms of intermittent claudication and rest pain; eliminate numbness, pain, and swelling of lower limbs; and improve the ABI ratio and TcPO2 of patients.

Antiplatelet drug treatment

For diabetic foot patients, clopidogrel is an antiplatelet drug with indications. Compared with aspirin, antiplatelet therapy with clopidogrel and aspirin can significantly reduce all-cause mortality and cardiovascular events, but slightly increase the risk of severe bleeding.[31] In addition, dual antiplatelet therapy of combining clopidogrel with aspirin can significantly reduce the event of major amputation after vascular reconstruction of the lower extremity.[32] Therefore, clopidogrel is currently recommended as another treatment option for patients who are intolerant or allergic to aspirin. What's more, treatment with aspirin or aspirin combined with dipyridamole can significantly improve the patency rate of the grafted vascular prosthesis in patients with diabetic foot after vascular bypass surgery. However, this effect was not found at any time point in the autologous venous transplantation, but found at all time points in the artificial blood vessel transplantation, covering 12 months after transplantation.[24] Compared with aspirin, aspirin combined with clopidogrel has no significant difference in the patency rate of all vascular grafts at 24 months after transplantation, and there is no significant difference in the incidence of amputation or death between groups, while aspirin combined with clopidogrel does not increase the risk of major or fatal bleeding, but increases the total risk of bleeding, including mild and moderate bleeding.[33]

Anticoagulants (heparin, low-molecular-weight heparin, and oral anticoagulants)

At present, there is no clear evidence to support the use of anticoagulant therapy in the intermittent claudication stage of prediabetic foot.[34] However, some studies have confirmed that the application of rivaroxaban, a new oral anticoagulant, can effectively reduce the incidence of limb ischemia events in patients with peripheral arterial disease.[35] Compared with aspirin alone, the combination of rivaroxaban (2.5 mg, twice a day) and aspirin can significantly reduce the incidence of major adverse events, such as severe limb ischemia events requiring intervention and amputations above the foot caused by vascular causes in the limbs of patients with peripheral arterial disease, by up to 46%. At the same time, the combined therapeutic regimen can reduce major amputation events by 70%. Moreover, compared with aspirin, treatment with rivaroxaban alone (5 mg, twice a day) can significantly reduce the incidence of major adverse events in limbs by 33%.[36] At the same time, compared with aspirin alone, the combination of rivaroxaban (2.5 mg, twice a day) and aspirin can significantly reduce the incidence of major cardiovascular events by 28%.[37] Compared with aspirin alone, combination of rivaroxaban (2.5 mg, twice a day) and aspirin can significantly reduce the risk of re-amputation and re-vascular intervention in patients with peripheral arterial disease who have already major adverse events of limbs.[38] Compared with aspirin alone,[39] the combination of low-molecular-weight heparin and aspirin can significantly reduce the rate of vascular occlusion/restenosis (up to 85%) in patients with diabetic foot who underwent intravascular minimally invasive therapy (balloon dilatation and stent implantation), while batroxobin combined with aspirin can significantly reduce the rate of vascular restenosis and not significantly increase bleeding or adverse events of other digestive tracts in patients with diabetes. In the initial treatment of acute limb ischemia, there was no significant difference between the initial operation and thrombolysis for limb salvage or death at 30 days, 6 months, or 1 year thereafter, but the incidence of stroke in the initial thrombolysis group (1.3%) was significantly higher than that in the initial operation group (0%), and the corresponding incidence of massive hemorrhage in the groups was 8.8% and 3.3%, respectively[40] and the corresponding incidence of embolism at the distal end of the lesion in the groups was 12.4% and 0%, respectively; therefore, in patients with acute limb ischemia, there was no significant difference in limb salvage or death between the initial surgical treatment and thrombolytic treatment, but the initial thrombolytic treatment would increase the risk of limb ischemia and bleeding complications. The above-mentioned drug therapies only delay the development of mild-to-moderate lower extremity arterial ischemic lesions, which is the basis of diabetic foot treatment, but most of the patients with severe lower extremity ischemia cannot achieve the purpose of improving symptoms and preserve limbs. Therefore, percutaneous intervention or surgical treatment is needed for the patients with severe ischemia for whom conventional internally medical treatment is ineffective.

Surgical treatment for vascular reconstruction

Surgical treatment for blood flow reconstruction is necessary for patients with severe ischemia for whom the therapeutic effect of systemic drugs is unsatisfactory.

Endovascular interventional therapy of lower extremity artery

Endovascular interventional therapy of lower extremity artery includes percutaneous transluminal angioplasty (mainly refers to common/drug-coated balloon angioplasty), stenting angioplasty based on balloon dilatation, or direct intra-arterial stent-assisted angioplasty, as well as various volume reduction operations commonly used at present. As a minimally invasive method, it can be used as the first choice, especially when the patient is old and weak or cannot tolerate artery bypass surgery with other diseases.[41],[42],[43] Indications for endovascular interventional therapy of lower extremity artery: Rutherford Grade 3 or above and Fontaine Stage II-b or above. The current evaluation indicators include subjective indicators and objective ones. The former includes the improvement of subjective symptoms, such as the degree of pain easement or relief, and the improvement of coldness sensation of limbs; the latter include ABI, the healing of ulcer surface, and the reduction of amputation plane. For diabetic patients with lower limb ischemia, it is considered as a clinical success as long as one of the indexes above is improved. After endovascular interventional therapy, the recovery of blood flow of the target blood vessel is regarded as a technical success.

Bypass grafting of lower extremity artery

The common methods for bypass grafting of lower extremity artery involve superior and inferior knee bypass. The specific operating method depends on the experience of the operator and the vascular conditions of the patient. The indications of arterial bypass grafting are as follows: (1) There is a better arterial outflow tract at the distal end of the lower extremity; (2) The patient has better physical quality and can tolerate the operation. Evaluation on curative effect: The evaluation indexes are basically the same as those for endovascular interventional treatment of lower extremity artery. It is regarded as a technical success as long as the distal blood supply of anastomosis is improved.

Angiogenes is therapy

Also known as therapeutic angiogenesis, angiogenesis therapy mainly increases the substrate of vascular growth factor by supplementing the number of endothelial stem progenitor cells so as to achieve better effect of angiogenesis. It can be said that it is a physiological strengthening therapy for the treatment of ischemic diseases. Now, stem cell transplantation cannot be used as a routine method for the treatment of diabetic lower extremity vascular disease, although domestic and foreign studies have reported that stem cell transplantation has a certain effect on lower extremity vascular disease.[44],[45],[46],[47] At present, stem cell transplantation includes autogenous and allogeneic transplantation, and autogenous stem cell transplantation has been widely used and achieved good results in China. Currently, there are three sources of autologous stem cells: bone marrow, peripheral blood, and improved bone marrow. Autologous stem cells have at least two advantages: (1) There is no immune rejection and (2) there is no ethical problem related to embryonic stem cells. Allogeneic stem cells are still at the preclinical or clinical research stage.

Perioperative management

No matter which therapeutic method is used, we should pay attention to the perioperative management with the main measures involved as follows: (1) Anticoagulant therapy: For diabetic patients with lower extremity ischemia, most of them are in hypercoagulable state. Anticoagulant therapy can be used to prevent thrombosis, especially after the reconstruction of the blood supply of inferior genicular artery or the treatment of poor outflow tract of distal extremity artery; (2) Antiplatelet therapy: Antiplatelet therapy belongs to routine application; (3) Vasodilator: Vasodilator belongs to routine application; (4) Defibrillation therapy: Defibrillation therapy can be applied if the fibrinogen of patients with foot disease is higher than normal; (5) Application of vasoactive drugs: Vasoactive drugs represented by Diosmin can not only promote venous blood return and reduce injury from reperfusion after arterial reconstruction, but also promote wound healing.[48],[49],[50]

Wound treatment for diabetic foot

Preconditions for promoting wound healing

At the same time of wound treatment, we need to actively carry out the treatment of systemic conditions, including blood glucose control, anti-infection, metabolic regulation, lower extremity revascularization, and nutritional support (including correction of anemia and hypoalbuminemia).

Nonsurgical treatment

(1) Palliative debridement: Under the premise of avoiding active bleeding and excessive loss of healthy tissue, tissue scissors or ultrasonic water scalpels can be used to remove clear necrotic tissue during dressing changes so as to shorten the time of self-dissolvable debridement, reduce the chance of infection, and improve the drainage of deep tissue, but it is necessary to preserve the ecological tissue. For wet gangrene or according to the location of wound, which is helpful to mixed gangrene with severe infection, even if the general physical or medical conditions do not allow large-scale debridement, decompression should be done as early as possible to make drainage unobstructed; (2) Dressing change on wound: Dressing change on wound can be carried out in outpatient department, and its frequency can be determined according to the degree of wound infection and the amount of exudation; (3) Dressing on wound: Dressing on wound should be selected according to different stages of wound, for example, if the wound has the main manifestation of infection, disinfectants such as iodophor can be used alone to enhance the frequency of dressing change; if the necrotic tissue of the wound has been dissolved off and the granulation tissue of the basement has begun to proliferate, the combination of disinfectant and bactericidal drugs and growth-promoting ones can be used for binding up and dressing change; (4) Dressing selection: Priority should be given to dressings with combined functions such as sterilization, active adsorption or drainage of exudate, keeping the wound moderately wet, and anti-adhesion, or multiple single-functional and cost-effective wound dressings can also be flexibly selected according to the conditions of the wound. (5) Negative pressure drainage technology of wound: It can effectively improve the drainage of wound, accelerate the dissolution-off of necrotic tissue and the proliferation of granulation tissue, but hospitalization is needed. For diabetic foot, especially for the wound surface of toes, we should pay attention to avoiding a too high pressure setting and also the compression injury of adjacent toes caused by the improper covering and fixation of negative pressure material and sticking film. For wound with thicker secretion, the drip negative-pressure suction technology can be used with the immersion and washing treatment with normal saline and silver ion solution under negative pressure, which have antibacterial function and growth factors which can promote wound healing; for wound without effective control of infection, continuous closed negative-pressure suction should be used with caution; (6) Biotherapy: Autogenous bone marrow stem cells or peripheral blood stem cells can be chosen for stem cell therapy. Multipoint injection of calf muscle is helpful for promoting the establishment of collateral circulation and improving the distal ischemic condition of the ischemic limbs. Topical therapy with autologous platelet-rich plasma gel can effectively improve the proliferation ability of local granulation tissue in ischemic wounds, but it should be applied to relatively sterile wound surface after debridement. The inferior genicular artery; Maggot therapy can be used to accelerate the removal of necrotic tissue on the wound and shorten the course of treatment, but medical maggots should be used; (7)Application of decompression orthoses: In the process of treatment and prevention of recurrence after recovery, professional orthoses such as decompression insole and diabetic foot shoes should be selected timely avoid the deepening and recurrence of wound; (8) Physical therapy: Physical therapy and systemic hyperbaric oxygen therapy are helpful to improve the inflammation and microcirculation of wound and promote wound healing.

Surgical treatment

Surgical treatment methods such as debridement or skin grafting should be carried out timely according to the conditions of the wound and whole body of the patient so as to effectively remove the necrotic tissue; close the wound as soon as possible; shorten the course of treatment significantly; and avoid the complications such as disused muscular atrophy, osteoporosis, deep-vein thrombosis, and cardiopulmonary function decline of lower extremities caused by long-term dressing change.

Surgical timing

On the premise that the whole body conditions permit, debridement should be carried out as early as possible to remove the necrotic tissue of the wound; if the proliferation of granulation tissue of the wound has covered with deep tissues such as bones and tendons, skin grafting should be carried out timely when conditions permit to avoid the problems of edema and aging of granulation tissue of the wound and a too long course of treatment.

Indications of wound debridement

(1) Definite gangrene of toes, pelma of foot and limbs; (2) Wound surface at the acute inflammatory stage of necrotizing fasciitis; (3) Wound surface with the abscess of plantar fascia and myolemma space; (4) Wound surface with infective sinus ducts; (5) Wound surface with exposed and inactivated deep tissues such as tendons and bones, which is difficult to be removed by dressing change; (6) Wound surface with a large amount of necrotic tissue remains; and (7) Wound surface with the granulation tissue hyperplasia at the base and without deep tissue exposed, which is difficult to heal through dressing change within 1 month.

Selection of surgical method

We should give priority to simple surgical plans with small secondary injury as far as possible so as to strive to solve complex problems with simple methods. (1) Tourniquet: It is recommended to use tourniquet with caution for patients with severe stenosis or occlusion of the inferior genicular artery; (2) Debridement: Attention should be paid to the damage to deep tissue so as to avoid the sandwich necrosis of muscle tissue and osteofascial compartment syndrome, and ensure the smooth drainage after operation; it is recommended to remove the long-term exposed tendon tissue due to the infection or injury of tendinous membrane through multiple debridement operations and also the residual end of the dead bone as much as possible It should be removed as much as possible and the surrounding soft tissue should be preserved as much as possible; (3) Suture: For wound with small scope of infection and without residual dead cavity, one-stage tension-free suture can be performed after debridement, but is not recommended for wound with inflammatory swelling of the surrounding tissue and obvious insufficiency of blood supply; (4) Skin grafting: if the wound base meets the conditions of skin grafting, the wound should be closed as soon as possible. It is suggested to choose the blade-thick skin grafting in priority. For special parts such as joints and negative key points, it is suggested to adopt the middle thick skin grafting through perforating, and it is not necessary to choose the free skin grafting; (5) Skin flap transplantation: Because many lower limbs of diabetic patients suffer from different degrees of ischemic lesion of blood vessels simultaneously, the risk of skin flap transfer and transplantation is high. For wound with exposed tendon and bone, if the patient's systemic conditions are good and the patient has not arterial occlusion, it is recommended to use skin flaps for transferring and coverage, which can effectively increase the wound healing rate and reduce the recurrence rate of ulcer in the later stage. In this case, on the premise of detailed examination and evaluation of blood vessels in the surgical site before operation, the operation plan should be formulated, and the selection sequence should be vicinal skin flap and in situ or distal pedicled perforator flap in turn because free skin flap needs to sacrifice the main blood vessels for anastomosis, and the risk is very high, so it is not recommended to use; (6) Amputation/toe amputation: Amputation can be carried out for patients whose necrotic limb infection is life-threatening, whose blood supply cannot be reconstructed, whose wound is difficult to heal, whose pain is difficult to bear, and who is difficult to afford long-term nonsurgical treatment but strongly requires amputation because of poor family economic situations; (7) Selection of amputation plane: the amputation plane can be generally determined according to the patient's systemic conditions, local blood supply, and injury, so as to maintain the function of the affected limb as much as possible in the case of primary healing of the stump. At present, the most widely used method clinically is to use the measurement with the transcutaneous oxygen partial pressure, which can also be combined with the vascular imaging examination. When the transcutaneous oxygen partial pressure of the tissue is <20 mmHg, it indicates that the amputation stump cannot heal; when more than 40 mmHg, it indicates that the healing risk of the amputation stump is significantly reduced; when between the two, there is a possibility of healing and it is necessary to supplement and improve the treatment with arterial perfusion method.

To give full play to the advantages of external medicine and external treatment of Chinese traditional medicine, different debridement timings and methods should be chosen for the local treatment of diabetic foot according to different pathological types of diabetic foot gangrene.[51],[52],[53]

For wet gangrene, in principle, local debridement should be carried out sooner rather than later. Mainly seen in diabetic foot gangrene (tendon degeneration necrosis-tendon gangrene), it is characterized by redness, swelling, and protrusion of the dorsum of foot and pelma of foot and toe-plantar area, by pressing which, there may be wave motion or have been broken, rotten tendons are exposed, exudates are dirty and stinky, and the drainage is not smooth. In this case, the signs of ischemia are not obvious, so it is advisable to treat with heat-clearing method as soon as possible. In the acute stage, local redness, swelling, causalgia, and pain are more obvious, so incision and drainage are the main method. It is not suitable to perform large-scale and thorough debridement in order to prevent gangrene from spreading and expanding, systemic infection from being induced, and life from being endangered. When the condition of the systemic and local circulation and microcirculation is improved, the foot infection is basically controlled, and the disease condition is relatively stable, debridement can be performed on the wound in a larger range, the degenerated and necrotic tendons and necrotic tissues can be removed, the effective drainage can be maintained, and at the same time, the infection control can be strengthened, and the systemic circulation and microcirculation can be improved, so as to prevent the spread and expansion of ulcer.

Dry gangrene is mainly seen in vascular occlusion and ischemia type diabetic foot. In principle, local debridement should be carried out later rather than earlier to keep dry gangrene stable. Attention should be paid to local disinfection and keeping dry. After the boundary between necrotic tissue and healthy tissue becomes clear and local collateral circulation is established basically, local resection can be performed on the necrotic tissue. As a result, the necrotic tissue is removed and the wound surface is exposed. The section of bone should be shorter than that of the soft tissue. If the blood supply is improved well, the necrotic tissue can also be resected and sutured. The incision near the border can be used for toe (finger) resection and suturing or hemipodectomy and suturing.

Nibbling debridement method: When the wound surface of diabetic foot gangrene is rotten and not clean, the infection of diabetic foot is basically controlled, the disease condition is relatively stable, and gangrene is relatively limited, the method of “nibbling” is adopted to gradually remove the necrotic tissue.

External application of traditional Chinese medicine: After routine basic treatment and debridement, external application of traditional Chinese medicine can improve the symptoms of diabetic foot such as ulcer area, swelling, numbness, pain, and skin color. (1) At the early stage of the disease, namely, inflammatory necrosis stage, the patient suffers from dampness, heat, and high poison; local redness and swelling; ulcerated surface; purulent cavity; filthy and smelly smell; and rotten flesh and broken tendons. It is suitable to mainly clear away heat and detoxify and eliminate putrefaction, in combination with external hoop therapy,[54] for which Ruyi Jinhuang Powder is selected as the prescription. Compound Cortex Phellodendri Liquid can be added to wound cleaning;[55],[56] Jiuyi Pellet can be selected for wound cleaning. After wound cleaning, gauze strip applied with Jiuyi Pellet or soaked with Compound Cortex Phellodendri Liquid can be selected to put into the sinus tract for drainage and external application. (2) At the middle stage of the disease, namely, granulation hyperplasia stage, the patient suffers from struggle between evils and good, less secretion on the wound surface, light odor, and gradually red granulation. It is suitable to mainly eliminate the putrefaction and generate muscle, and apply Red Ointment and Jingwanhong Ointment externally.[57],[58] (3) At the late stage of the disease, namely, skin-generating stage of scars, the poison is removed, the good is strengthened, the wound surface is clean, and the granulation is tender red. It is suitable to generate muscle and skin, with muscle-generating Yuhong ointment for the prescription,[59] which is applied on the wound after debridement.

Members of the expert group participating in the discussion of the guidelines

Gu Yongquan (Department of Vascular Surgery, Xuanwu Hospital Affiliated to Capital Medical University); Ran Xingwu (Department of Endocrinology, West China Hospital of Sichuan University); Yang Caizhe (Department of Endocrinology, Characteristic Medical Center of Air Force); Ju Shang (Department ofVascular Surgery, Dongzhimen Hospital Affiliated to Beijing University of Traditional Chinese Medicine); Liu Peng (Department of Vascular Surgery, China-Japan Friendship Hospital); Li Xiaoqiang (Department of Vascular Surgery, Gulou Hospital, Nanjing, Jiangsu Province); Jiang Yufeng (Department of Wound Repair, Special Medical Center of Strategic Support Force); Hao Daifeng (Third Department of Post-burning Plastic Surgery and Wound Repair Center of Fourth Medical Center, the PLA General Hospital); Guo Lianrui (Department of Vascular Surgery, Xuanwu Hospital Affiliated to Capital Medical University); Zhou Huimin (Department of Endocrinology, First Hospital Affiliated to Hebei Medical University); Han Huimin (Department of Endocrinology, Daqing City Fourth Hospital, Heilongjiang Province); Liu Jinyu (Key Laboratory of Pathobiology of the Ministry of Education, Jilin University); Zhou Qiuhong (Department of Endocrinology, Xiangya Hospital Affiliated to Central South University); Li Binghui (Liyuan Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology); Zhao Jichun (Department of Vascular Surgery, West China Hospital of Sichuan University); Cao Yemin (Shanghai Integrated Hospital of Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine); Zhou Huimin (Department of Endocrinology, First Hospital Affiliated to Hebei Medical University); Lv Bonan (Department of Vascular Surgery, Hebei People's Hospital); Hao Tianzhi (Department of Rehabilitation and Reconstruction, Beijing Chaoyang Emergency Rescue Center of Integrated Traditional Chinese and Western Medicine); Gu Jianping (Department of Vascular Intervention, NanjingFirst Hospital, Jiangsu Province); Chen Guoping (Department of Vascular Intervention, NanjingFirst Hospital, Jiangsu Province); Zhang Lan (Department of Vascular Surgery, Renji Hospital Affiliated to School of Medicine of Shanghai Jiaotong University); Ma Liren (Department of Peripheral Blood Vessels, Pingdingshan Hospital of Traditional Chinese Medicine, Henan Province); Wu Shibai (Department of Endocrinology, Characteristic Medical Center of Air Force); Guo Pingfan (Department of Vascular Surgery, First Hospital Affiliated to Fujian Medical University); Chen Dejie (Department of Vascular Surgery, Xiangyang Central Hospital, Hubei Province); Ji Donghua (First Hospital Affiliated to Dalian Medical University);Li Fanqiang (Diagnosis and Treatment Center for Diabetic Foot of Taiyuan Second People's Hospital, Shanxi Province); Wang Fujun (Department of Endocrinology, Fourth Hospital of Hebei Medical University); Cui Fengqin (Department of Endocrinology, Handan Central Hospital, Hebei Province); Sun Baohua (Department of Vascular Surgery, Jinan Fourth People's Hospital, Shandong Province); Chen Huating (Department of Wound Repair, Liyuan Hospital of Tongji Medical College of Huazhong University of Science and Technology); Chen Jun (Department of Endocrinology, XiaoshanFirst People's Hospital, Zhejiang Province); Yang Jie (Department of General Surgery, Chancheng District Central Hospital, Foshan City, Guangdong Province); Cui Wenjun (Department of Vascular Surgery, Fifth Hospital Affiliated to Zhengzhou University); Yu Huafeng (Department of Endocrinology, Anshan Group General Hospital); Huang Pingping (Hematology Hospital, Institute of Hematology of Peking Union Medical College, Chinese Academy of Medical Sciences); Liu Yong (Department of Vascular Surgery, Hospital Affiliated to Southwest Medical University) Wang Aiping (Department of Endocrinology, Air Force Hospital, the PLA Eastern Theater Command).

Financial support and sponsorship

Fund “Climbing the peak” Program of Talent Training Plan of Beijing Medical Administration Bureau (DFL2015801) and Capital Special Research Project for Health Development (2016-1-2012).

Conflicts of interest

There are no conflicts of interest.

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  [Table 1], [Table 2], [Table 3]


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