According to the authors, large nerve fibre dysfunction related to diabetes, as measured by vibration perception threshold, is strongly linked with a high risk of foot ulceration. It also predicts amputation and mortality even in young type 1 diabetes patients and is associated with increased cardiovascular (CV) risk.
Because of the established strong association between lower extremity neuropathy and diabetic foot lesions, death related to diabetic foot problems (including ulceration) has been used as an estimate of mortality associated with peripheral neuropathy.
Patients with large fibre neuropathy also have evidence of small fibre neuropathy including autonomic neuropathy, which is associated with increased mortality from CV disease, particularly sudden cardiac death. Peripheral autonomic neuropathy (smallfibre) is associated with the development of foot ulcerationin diabetic subjects.
Neuropathy is also closely linked to calcification of vascular smooth muscle, a process thought to be mediated by receptor activator of nuclear factor kappa B ligand (RANK-L)/osteoprotegerin signalling pathway implicated in coronary and periphera lvascular disease.
Vascular calcification in diabetic neuropathy may be a significant factor in increased CV risk in neuropathic ulcerated patients independent of autonomic neuropathy and cardiac denervation. The rapeutic options targeting these emerging pathways may help modulate macro vascular complications and have a beneficial effecton cardiovascular outcomes in this population of diabetes patients.
Neuropathy may also be a marker of associated nephropathy, which is a well-established risk factor for CV death. Microalbuminuria, an independent predictor of progressive nephropathy, is associated with endothelial damageand reflects atherosclerotic disease and vascular dysfunction and has also been shown to be strongly associated with the development of diabetic foot ulcers in type 2 diabetic patients. Patients with diabetic nephropathy have a high frequency of autonomic neuropathy and both factors are associated with and contribute independently to the risk of silent ischaemia.
Cardiac autonomic neuropathy is also an independent risk factor for CV morbidity and mortality in type 1 diabetic patients with nephropathy. Moreover, survival after amputation is lower in diabetic patients with chronic kidney disease and those on dialysis and this may be related to the severity of neuropathy amongst other comorbidities in these patients.
Some of the excess mortality has also been thought to be due to uncontrolled sepsis. Foot infection with Staphylococcus aureus, which is a very common offender in DFUs, increases the mortality rate 2.6 times compared to those without Staphylococcus infection. It is postulated that Staphylococcus aureus could increase the risk of mortality through a cytokine response, which might cause plaque rupture and subsequent death from myocardial infarction.
Minimising the risk of DFUs
The risk of mortality due to DFUs can be minimised by preventative measures. The UK National Institute of Health Care Excellence, recommends the following:
1. Assess the risk of developing a DFU.When examining the feet of a person with diabetes, remove their shoes, socks, bandages and dressings, and examine both feet for evidence of the following risk factors: Neuropathy (use a 10g monofilament as part of a foot sensory examination), limb ischaemia, ulceration, callus, infection and/or inflammation, deformity, gangrene and Charcot arthropathy.
2. Use ankle brachial pressure index in line with the NICE guideline on lower limb peripheral arterial disease. Interpret results carefully in people with diabetes because calcified arteries may falsely elevate results.
3. Assess the person’s current risk of developing a diabetic foot problem or needing an amputation using the following risk stratification:Low risk (no risk factors present except callus alone), moderate risk (deformity, neuropathy or non-critical limb ischaemia) and high risk (previous ulceration, previous amputation, on renal replacement therapy, neuropathy and non-critical limb ischaemia together, neuropathy in combination with callus and/or deformity or non-critical limb ischaemia in combination with callus and/or deformity), active diabetic foot problem (ulceration, spreading infection, critical limb ischaemia, gangrene or suspicion of an acute Charcot arthropathy, an unexplained hot, red, swollen foot with/without pain.
4. For people who are at low risk of developing a diabetic foot problem, continue to carry out annual foot assessments, emphasise the importance of foot care, and advise them that they could progress to moderate or high risk.
5. Refer people who are at moderate or high risk of developing a diabetic foot problem to the foot protection service.
6. Newly referred patients should be assessed as follows: Within two and four weeks for people who are at high risk of developing a diabetic foot problem, six to eight weeks for people who are at moderate risk of developing a diabetic foot problem.
7. For people at moderate or high risk of developing a diabetic foot problem, the following action is recommended: Assess the feet, give advice about, and provide, skin and nail care of the feet, assess the biomechanical status of the feet, including the need to provide specialist footwear and orthoses, assess the vascular status of the lower limbs, liaise with other healthcare professionals about the person’s diabetes management and risk of CV disease.
8. Depending on the person’s risk of developing a diabetic foot problem, carry out reassessments at the following intervals: Annually for people who are at low risk, frequently (for example, every three to six months) for people who are at moderate risk, more frequently (for example, every one to two months) for people who are at high risk, if there is no immediate concern and very frequently (for example, everyone to two weeks) for people who are at high risk, if there is immediate concern. Consider more frequent reassessments for people who are at moderate or high risk, and for people who are unable to check their own feet.
9. People in a hospital who are at moderate or high risk of developing a diabetic foot problem should be given a pressure redistribution device to offload heel pressure. On discharge, they should be referred or notified to the foot protection service.
Offer one or more of the following as standard care for treating DFUs:
- Control of foot infection
- Control of ischaemia
- Wound debridement
- Wound dressings.
Proper prevention and management strategies can prevent the development of DFUs and decrease the high risk of mortality associated with the condition.