I. Peripheral neuropathy
Loss of protective sensation due to peripheral neuropathy is the most important and common complication leading to foot ulcers. The prevalence of peripheral neuropathy in those with diabetic extremities god 25 years or more is 50%. In the DCCT study, 39% of diabetic patients entering the trial had neuropathy at the time of the trial with lesions primarily of multiple symmetric sensorimotor neuropathy. Approximately 10% of patients with diabetes were found to have pre-existing neuropathy, with clinical signs of disease progression. Reports from the United Kingdom indicate that the prevalence of diabetic neuropathy increases with age, reaching 44.2% at the age of 70 to 90 years. In general, 60% of diabetic foot ulcers have only peripheral neuropathy, 20% have only peripheral vasculopathy, and 20% have both peripheral neuropathy and vasculopathy. It has also been reported that 62% of diabetic foot ulcers have neuropathy as the primary causative agent, 13% have peripheral vasculopathy, and 25% are mixed. Even in cases of amputation, there are both separate and mixed causative pathologies. Some data show that 46% of diabetic foot amputation cases are mainly ischemic lesions, 59% are infections, 61% are neuropathies, 81% are wounds that do not heal, 84% are ulcers, 55% are gangrene, and 36% originate from minor trauma, infection, and amputation (36% of which are skin ulcers due to wearing inappropriate shoes). This shows that the combined effect of multiple factors leads to amputation.
(i) Sensory neuropathy
In patients with diabetic foot lesions due to peripheral neuropathy, although sensation is diminished or even absent, foot neuropathy can cause patients to have abnormal sensation and clinical nociception. In this way nociception and sensory loss are not two unrelated states and can coexist. The loss of sensation caused by peripheral neuropathy makes the patient lose self-protection mechanisms and vulnerable to external injury, and it is difficult to detect early and seek timely medical attention when foot lesions appear, even in the case of existing foot ulcers, the patient can still walk without pain, resulting in worsening ulcers and bacterial infections. When a painful painless ulcer that is already infected appears, it suggests worsening of the infection, and although the ulcer indicates that there may be no change, the infection may penetrate into the deeper tissues of the foot.
(ii) Motor neuropathy
Foot deformities due to peripheral neuropathy often lead to ulcers. In diabetic patients, motor neuropathy can lead to impaired proprioception, atrophy and weakness of the interosseous muscles within the foot, and muscle imbalance, resulting in structural damage to the foot, such as hammertoes, claw-like toes, and arch collapse. These deformed toes develop toe ulcers under the combined increased pressure from shoes or insoles, which may be related to thinning or displacement of the fat pad under the first metatarsal head. Toes and under the first metatarsal head are susceptible to callus formation, ulceration and infection, which can lead to osteomyelitis or even amputation. This change in the point of application, where the weight application point is shifted to the toe head, is the main factor leading to typical penetrating plantar ulcers.
(iii) Plantar neuropathy
Diabetic plantar neuropathy has various side effects, arteriovenous shunts that increase skin surface temperature, distal limb ischemia, increased tarsal bone resorption, and sometimes edema. In addition, the foot is sweat-free and prone to skin cracking, creating conditions for bacterial invasion, leading to infection and the formation of ulcers, including plantar ulcers, diabetic neuropathy at the end of the foot into osteoarthropathy with multiple structural destruction, Charcot foot. Peripheral neuropathy leads to sensory deficits in the foot, and repetitive stimulation of the sensory deficit area can induce ulcer development. Eighty percent of diabetic patients with foot ulcers have neuropathy, so peripheral neuropathy is an important factor in the development of ulcers. Long-term local irritation can lead to callus, which increases the local pressure by about 30%, and the increase in local pressure can lead to necrosis or even ulceration of the callus. Ulcers often occur where the callus is thick and under heavy pressure, such as the metatarsal heads, especially the palmar side of the first metatarsal head. If the ulcer appears on the lateral side of the foot, it is often due to wearing inappropriate shoes, and local ischemia and pressure produce ulcers. In contrast, ulcers on the back of the foot are often due to trauma.
II. Peripheral vascular lesions
The incidence of peripheral arteriopathy in diabetic patients is high, with early onset, rapid progression and severe disease, and the lesions mostly involve the distal limb extremities, especially below the knee. Although revascularization surgery confirms that the importance of microangiopathy in diabetic foot lesions is not as important as once expected, ischemia due to vascular lesions can potentially worsen the atrophic lesions of the diabetic foot.
In terms of the composition of the atherosclerotic platelet, diabetic and non-diabetic patients are almost identical, both consisting of fatty deposits, smooth muscle cells, monocytes, macrophages and calcifications. However, the difference between diabetic and non-diabetic patients is that diabetic patients develop atherosclerosis earlier and progress faster, and the onset is similar in men and women, with no significant gender difference; another difference is the site of the lesioned vessels, which are often below the bifurcation of the anterior tibial, posterior tibial and peroneal arteries in diabetic patients, while non-diabetic patients often involve proximal vessels, such as the femoral artery, iliac artery and aorta.
The main risk factors for the development of peripheral vascular disease in diabetic patients are genetic factors, the course of diabetes and diabetes itself. Other risk factors are smoking, abnormal lipid metabolism, hypertension, hyperglycemia, and obesity (especially central obesity). And these factors are treatable. Among them, smoking is the main factor. This is because smoking can cause vasospasm and increased blood clotting in addition to atherosclerosis. It also affects wound healing and increases the risk of infection. Recent studies have shown that insulin resistance or hyperinsulinemia is also an independent factor in atherogenesis. This is particularly important in patients with type 2 diabetes. Glycation end-products are another important factor in accelerating atherosclerosis. Glycation end-products induce a series of reactions upon binding to receptors on endothelial cells and macrophages, contributing to excessive stromal proliferation and local thrombosis. When macrophage secretory glycation end products come into contact, they can release cytokines that damage endothelial cells and induce platelet formation. In addition, the cross-linking of collagen fibers increases the sclerosis of the vessel wall. The hypercoagulable state of diabetes and thrombosis are also important factors.
The causes of diabetic toe gangrene formation are.
(1) Thrombosis on the basis of atherosclerosis.
(2) Microthrombosis secondary to infection.
The clinical features of diabetic foot lesions with predominantly neuropathy are.
(1) The degree of sensory deficit is disproportionate to the extent of the secret lesion;
(2) thickening of the glial layer, cracking and ulcer formation, especially the formation of ulcers on the bottom of the foot;
(3) Atrophy of the muscles in the foot, deformation of the foot and toes;
(4) Loss or diminution of tactile, pain and vibration sensations in the foot, and loss of tendon reflexes;
(5) Wet temperature of the foot, venous congestion and edema may occur;
(6) The dorsal arterial pulse of the foot is present, and there is no clinical manifestation of foot ischemia.
The clinical features of foot ischemic lesions with mainly peripheral small artery lesions are.
(1) localized painful lesions, black dry gangrene, lesions may be limited to the toes or heel, and may be accompanied by extensive superficial infection;
(2) Low foot temperature, pallor of the foot when the foot is elevated, and bruising of the area under pressure;
(3) Atrophy and wasting of the foot, thickening of the toenails, and sparse sweat hair;
(4) Weak or absent peripheral arterial pulsation;
(5) Slow filling of peripheral veins, often greater than 15 seconds;
(6) Other clinical symptoms of ischemic lesions may be present;
(7) Mildly diminished or normal sensory nerves and tendon reflexes.