The Diabetic Foot

1. The Diabetic Foot Syndrome

The diabetic foot syndrome (DFS) is the constellation of complications that arise in the foot of a person with diabetes from the convergence of:

• Peripheral neuropathy — sensory, motor, and autonomic.
• Peripheral arterial disease (PAD) — especially infra-popliteal, calcific.
• Foot deformity — from intrinsic-muscle wasting, AGE-stiffened collagen, prior trauma, prior CN.
• Skin / soft-tissue fragility — dry, non-sweating, AGE-glycated.
• Impaired immune response — especially when glycaemic control is poor.

The clinical end-points of DFS are ulceration, infection, Charcot neuroarthropathy, and amputation. These are tightly linked: ulceration is the gateway lesion (~25% lifetime risk in diabetics; Singh, Armstrong & Lipsky JAMA 2005), infection complicates ~half of ulcers, and major amputation follows in 14–24% of ulcers. Charcot is the proximate cause of a substantial fraction of ulcerations through its characteristic plantar prominences.

The IWGDF (International Working Group on the Diabetic Foot) has produced successive consensus guidelines (most recently 2023, the “IWGDF guidelines on the prevention and management of diabetes-related foot disease”) which now form the international standard. These integrate the risk stratification (section 8), screening cadence, and the modality-specific recommendations cited throughout this course.

2. Peripheral Neuropathy in Diabetes

Diabetic peripheral neuropathy (DPN) is a length-dependent, distal, symmetric, sensorimotor-and-autonomic neuropathy. Prevalence: ~50% of patients with diabetes over a lifetime; even higher (~70%) in long-duration insulin-treated patients (Pop-Busui et al., ADA Position Statement, Diabetes Care 2017).

Pathogenesis is multifactorial:

• Polyol pathway flux — intracellular sorbitol accumulation → osmotic and metabolic stress in Schwann cells and axons.
• AGE / RAGE signalling — oxidative stress, ROS, microvascular dysfunction.
• PKC activation — via diacylglycerol; vascular smooth-muscle and basement-membrane abnormalities.
• Hexosamine pathway — UDP-GlcNAc → aberrant O-GlcNAcylation of intracellular proteins.
• Mitochondrial dysfunction — impaired energy supply to long axons.
• Vasa nervorum disease — ischaemic component.

Clinically the typical “stocking-and-glove” distribution reflects the length-dependent vulnerability of the longest axons. The symptoms map differently to fibre size:

Importantly, painful and painless DPN coexist. About a third of DPN patients have positive (painful) symptoms — burning, allodynia, “walking on broken glass”. Two-thirds have purely negative symptoms (numbness alone), which is more dangerous because the patient does not seek care. The “painless” foot is the foot at risk.

3. Loss of Protective Sensation (LOPS)

The single clinically most useful concept is loss of protective sensation (LOPS): the level of sensory loss below which an unrecognised injury is likely to occur and progress. Brand and Birke (J Rehabil Res Dev 1986) operationalised it as inability to detect the 10 g (5.07) Semmes-Weinstein monofilament at standardised plantar test sites.

Crucially, LOPS is a threshold concept, not a measurement of “total” sensation. Once 10 g is missed, the foot is at risk regardless of whether smaller filaments would also be missed. LOPS is the inclusion criterion for nearly every foot-screening pathway and is the gateway to category 1 risk in the IWGDF system (section 8).

The relationship between sensation and ulceration / CN risk is sigmoid: below 10 g detection, risk rises sharply. Empirically, the annual ulceration risk in a LOPS+ foot is ~7–10% versus <1% in a LOPS− diabetic foot (Boulton et al., Lancet 1986; ADA Standards of Care).

4. The Semmes-Weinstein 5.07 Monofilament

The monofilament is a calibrated nylon fibre that buckles at a known load. The numbering follows Sidney Weinstein and Josephine Semmes (1962) as the base-10 logarithm of the force (in tenths of a milligram) required to bend it. The clinically important sizes:

The buckling-force relation is approximately\( F \;\approx\; 10^{(\text{filament number})}\,\text{milligrams} \), so the 5.07 filament buckles at \(10^{5.07} \approx 11{,}700\) mg \(\approx 10\) g.

Standard test (ADA / IWGDF protocol):

1. Patient supine, eyes closed, ambient quiet.
2. Demonstrate the filament on the patient’s arm or hand first.
3. Apply perpendicular to the skin until the filament buckles into a C-shape.
4. Hold for ~1.5 seconds; do not press onto a callus.
5. Patient reports “yes” or “no” for each application.
6. Test 4 plantar sites per foot: hallux pulp, plantar 1st, 3rd, 5th MT heads (some pathways add the heel and dorsum — total 10 sites). Two of three correct → intact at that site.
7. Insensitivity at ≥1 plantar site → LOPS positive.

The monofilament has reasonable test characteristics: sensitivity for ulceration prediction ~66–91%, specificity ~34–86% (Feng et al., meta-analysis, J Diabetes Complications 2009). It is markedly inferior at detecting early small-fibre neuropathy but very good at flagging the foot at risk.

5. Other Bedside Tests for Neuropathy

• 128 Hz tuning fork — vibration sense at the hallux interphalangeal joint or medial malleolus. Test along with patient’s detection of cessation. Loss correlates well with LOPS.
• Biothesiometer / VPT — vibration perception threshold; >25 V predicts ulceration (Young et al., Diabetes Care 1994). The gold-standard quantitative test.
• Achilles reflex — absent in >90% of advanced DPN.
• Pinprick & thermal sensation — test small-fibre integrity; abnormality often precedes monofilament loss.
• Ipswich Touch Test — the examiner lightly touches the toes for 1–2 seconds, patient identifies which is touched. Insensitivity at ≥2 sites → high risk. Validated equivalent to monofilament (Rayman et al., Diabetes Care 2011); ideal in resource-limited settings.
• Sudoscan / electrochemical skin conductance — non-invasive measure of sudomotor function; small-fibre.
• Skin biopsy with intra-epidermal nerve fibre density — research / specialist; gold standard for small-fibre neuropathy.
• Nerve conduction studies — large fibre; not routine for screening.

No single test perfectly captures all fibre types. The IWGDF and ADA recommend combining the 10 g monofilament with at least one other modality (commonly 128 Hz vibration or Ipswich Touch) at every annual exam. A foot is “at-risk neuropathic” if either modality is abnormal.

6. Peak Plantar Pressures

The mechanical correlate of the diabetic foot — and the bridge between neuropathy and CN — is the elevation of peak plantar pressure (PPP) at sites of structural prominence. PPP is measured by capacitive or resistive pressure mats during gait, in N·cm⁻².

• Normal foot — PPP at 1st MT head ~30–50 N·cm⁻².
• Neuropathic non-ulcerated — PPP often 70–100 N·cm⁻².
• Pre-ulcerative threshold — commonly cited at ≥70 N·cm⁻² (Veves et al., Diabetologia 1992).
• Charcot midfoot rocker-bottom — PPP at the new midfoot apex may exceed 200 N·cm⁻².

The mechanical drivers of elevated PPP in the neuropathic foot:

• Equinus contracture — tight Achilles drives forefoot loading. The lengthening of the gastrocnemius (Strayer or open-Z lengthening) reduces forefoot PPP and forms the basis of percutaneous Achilles tenotomy in offloading recalcitrant ulcers.
• Claw-toe / fat-pad migration — metatarsal heads exposed.
• Bony prominence after CN deformity — especially the rocker-bottom midfoot.
• Limited joint mobility — AGE-stiffened ankle/subtalar; reduced shock absorption.
• Reduced subcutaneous tissue compliance — AGE-glycated skin and fat.

The pressure–time integral (PTI)— integral of pressure over the stance phase — is a better predictor of ulceration than PPP alone, as a moderately elevated pressure sustained over a long stance time is more damaging than a transient peak. \( \mathrm{PTI} = \int_{t_0}^{t_1} P(t)\, dt \). Pressure-mapping insoles (F-Scan, Pedar) now allow ambulatory measurement and are used to calibrate offloading footwear and total-contact casts.

7. Peripheral Arterial Disease — The Other Half of DFS

CN tends to occur in well-perfused neuropathic feet. This is the second clinical pearl that distinguishes it from ulceration alone, which strongly correlates with PAD. But the same patient may have CN in one region while harbouring infrapopliteal PAD that affects healing of any superimposed ulcer.

• Ankle-brachial index (ABI) — ABI <0.9 = PAD; >1.3 = falsely elevated due to medial arterial calcification (Mönckeberg sclerosis), common in diabetes. ABI is therefore unreliable in many CN candidates.
• Toe-brachial index (TBI) — digital arteries are spared from medial calcification. TBI <0.7 = PAD. Generally preferred in diabetes.
• Toe pressure — absolute toe pressure <30 mmHg predicts non-healing.
• Transcutaneous oxygen tension (TcPO₂) — >40 mmHg favours healing; <30 mmHg is concerning.
• Pulse exam — absent dorsalis pedis or posterior tibial pulse warrants arterial workup, even in a CN-suspicious foot.
• Duplex / CTA / MRA — for revascularisation planning.

Diabetic PAD has a characteristic infrapopliteal predominance: the tibial and peroneal arteries are typically affected; the femoral and popliteal are often spared. Endovascular distal-revascularisation (often retrograde tibial-pedal access) is the modern standard. The 2019 Global Vascular Guidelines (Conte et al., J Vasc Surg) and the 2024 BEST-CLI trial defined the modern algorithm for chronic limb-threatening ischaemia.

8. The IWGDF Risk Stratification

The IWGDF risk-stratification system (most recent revision 2023; based on the earlier Bus, Lavery and Schaper categorisations) classifies the diabetic foot into five risk levels that drive the screening cadence:

Charcot history is itself a powerful risk marker, often placing the patient in category 3a regardless of whether ulceration has occurred. The risk-stratification system drives:

• Frequency of foot examination — yearly to monthly.
• Footwear prescription — off-the-shelf, accommodative, custom; depth shoe with custom insole; CROW boot in high-risk healed-CN feet.
• Education intensity — simple checklist vs. structured program.
• Specialist referral — podiatry, vascular, foot & ankle ortho.

The key concept is that the diabetic foot is a chronic-disease management problem, not an episodic acute-care problem. Multidisciplinary diabetic-foot clinics that integrate endocrinology, vascular, podiatry, infectious-disease, and orthopaedic foot & ankle reduce major amputation rates by 30–75% (Krishnan et al., Diabetes Care 2008; Mills et al., J Vasc Surg 2014).

9. Putting It Together — The Foot at Risk for Charcot

The foot at risk for CN is a recognisable composite:

• Long-standing diabetes (typically >10 years) with poor historical glycaemic control.
• LOPS by 5.07 monofilament or VPT >25 V, with absent ankle reflex.
• Dry, non-sweating skin, distended dorsal veins (autonomic small-fibre loss).
• Bounding (or apparently bounding) pulses, ABI normal or >1.3, but TBI may be borderline.
• Equinus contracture (Silfverskiöld test positive); claw toes; intrinsic-minus deformity.
• Plantar pressures elevated to >70 N·cm⁻² at MT heads or midfoot apex.
• Often: prior ulcer, prior contralateral CN, or recent revascularisation.

Onto this substrate falls a precipitant — a sprain, an unrecognised fracture, surgery, or simply a few weeks of poorly accommodated footwear. The next thing the patient (or, more likely, the clinician) notices is a warm, swollen foot. By then the cascade described in Part II is well underway, and the imaging features described in Part IV can begin to be read against the staging of Part V.

The clinical bottom line: every patient with diabetic neuropathy needs an annual foot exam that includes the 10 g monofilament, vibration testing, pulse palpation (ideally TBI), inspection for deformity and skin breakdown, and a skin-temperature comparison. Any unexplained warm/swollen unilateral foot in a neuropathic diabetic gets MRI and an offloading device the same day.