The Diabetic Foot

Pathophysiology of the Diabetic Foot

The diabetic foot is characterised by a pathophysiological triad of peripheral neuropathy, peripheral arterial disease, and immunosuppression. Each component independently and synergistically predisposes to ulceration, infection, and amputation.

Peripheral Neuropathy in Diabetes

Sensorimotor Neuropathy: Loss of pain, temperature, pressure, vibration, and proprioception sensation. Without protective pain sensation, patients fail to recognise trauma (minor pressure, friction, or thermal injury) and develop ulcers unknowingly. The classic diabetic foot ulcer occurs at pressure points (metatarsal heads, heel, dorsal toes) precisely because areas of high pressure go unnoticed without sensation. Motor Neuropathy: Wasting of intrinsic foot muscles (interossei, lumbricals) occurs from denervation. These small muscles normally maintain balance between plantar flexors and dorsiflexors of the toes. Intrinsic muscle wasting leads to claw toe and hammer toe deformities (hyperextension at metatarsophalangeal joints, flexion at interphalangeal joints). Prominent metatarsal heads protrude abnormally and bear excessive pressure during walking. The normal fat pad under the metatarsal heads (which cushions pressure) migrates distally with intrinsic muscle loss, leaving metatarsal heads unprotected. Abnormal pressure distribution increases further with gait disturbances. Result: new ulceration develops at these prominent areas. Autonomic Neuropathy: (1) Loss of sweating → dry, fissured skin → breaks in skin barrier → portal of entry for bacteria. (2) Arteriovenous (AV) shunting in the dermal microvasculature: autonomic neuropathy causes unopposed vasodilation via loss of normal sympathetic vasoconstriction. AV shunts form, allowing blood to bypass the capillary network. Result: the foot appears warm with bounding pulses and distended dorsal veins — it looks well-perfused clinically. However, capillary blood flow is reduced (blood flows preferentially through AV shunts rather than capillaries) → tissue oxygen delivery is severely impaired → “warm ischaemic foot paradox” — clinically warm foot with actual tissue hypoxia and poor wound healing. (3) Neuropathic cachexia — loss of protective motor function, atrophy of foot muscles, weakness.

Peripheral Arterial Disease in Diabetes

Accelerated atherosclerosis: Diabetics develop peripheral arterial disease 10–20 years earlier than non-diabetics. Hyperglycaemia, dyslipidaemia, hypertension, smoking, and inflammation all accelerate atherogenesis. Distribution pattern is distinctive: Unlike non-diabetic PAD, which affects aortoiliac and femoropopliteal segments first (proximal vessels), diabetic PAD predominantly affects tibial and peroneal arteries (distal/infrapopliteal vessels). This distribution makes revascularisation more challenging — distal vessels are smaller and harder to access for bypass grafting or angioplasty. Bilateral disease is very common in diabetics. Medial calcification (Mönckeberg’s sclerosis): Diabetics develop extensive calcium deposition in the medial layer of medium and small arteries (not atherosclerotic plaque; medial calcification is distinct from intimal atherosclerotic calcification). This creates “railroad-track” appearance on X-ray. Medial calcification does NOT cause significant stenosis or occlusion by itself, but it makes vessels incompressible (stiff). This is clinically important because incompressible vessels cannot be compressed by the blood pressure cuff during ABPI measurement. Result: ABPI falsely elevated (>1.2, which normally indicates either normal vessels or measurement error). In diabetics with medial calcification, ABPI is unreliable for assessing perfusion. Solution: Use Toe-Brachial Index (TBI) instead of ABPI in diabetics. Toe arteries (digital arteries) are less affected by medial calcification than larger vessels, making TBI more reliable. Normal TBI ≥0.7; critical ischaemia TBI <0.3; intermediate 0.3–0.7. Microangiopathy: Basement membrane thickening of capillaries occurs due to increased collagen IV and laminin deposition. Thickened basement membrane impairs diffusion of oxygen and nutrients to tissues, and impairs leucocyte migration from blood into tissue → reduced wound healing, increased infection susceptibility.

Immunosuppression in Diabetes

Hyperglycaemia impairs multiple components of innate and adaptive immunity: (1) Neutrophil chemotaxis: reduced ability of neutrophils to migrate to infected sites. (2) Phagocytic killing: reduced oxidative burst, impaired bacterial killing. (3) Complement activation: reduced complement-mediated bacteria opsonisation and destruction. (4) T-cell function: impaired T-cell proliferation and cytokine production. (5) Result: Poor wound healing, increased susceptibility to infection, difficulty clearing biofilm, delayed recognition and treatment of infection. Biofilm formation by polymicrobial organisms in diabetic foot infections is particularly problematic — bacteria become sequestered in biofilm matrices protected from antibiotics and immune cells. Hyperglycaemia also impairs fibroblast proliferation and VEGF signalling → reduced angiogenesis and granulation tissue formation → impaired wound healing.

Summary: The Pathophysiological Triad