. Introduction The global trend of Diabetes Mellitus (DM) is worrying. The total number of people with DM is projected to continue increasing. By 2030, the overall incidence of DM is expected to rise to 578 million (10.2%), and by 2045, it will rise to 700 million (10.9%). DM also contributes to global NCD deaths, having been identified as the fourth most common cause of NCD death at around 1.6 million [1]. DFU is one of the commonest diabetic complications. It is characterised as the ulceration or destruction of foot tissues caused by neuropathy or peripheral arterial disease (PAD) among people with DM [2]. The International Diabetic Federation reported the global prevalence of DFU to be 6.3%, but it could range up to 14% [3–5]. The prevalence of DFU in Malaysia has generally ranged from 5–10%, but in a study conducted in 2018, the prevalence of DFU reached as high as 42% among diabetic patients in Kuala Lumpur [6,7]. D. G. Armstrong et al. found that the most significant risk factor for a DFU was a healed DFU [8]. DFU was the leading cause of LLA, and 85% of poorly healed DFU cases ended in LLA because the neuropathy and PAD persisted and readily caused another ulcer if proper foot care was not established [8,9]. Furthermore, Zhang et al. reported that 25% of diabetic patients would develop diabetic foot ulcers in their lifetime [4]. In their study in 2007, D. G. Armstrong et al. reemphasised the significant impact of DFU and LLA on the mortality rate. Their 5-year mortality data revealed that overall LLA led to a higher 5-year mortality rate compared to all cancers combined. The 5-year mortality with major LLA was 56.6%, and minor LLA led to 46.2% mortality. Hence, they concluded that both DFU and LLA were independent risk factors for premature mortality [10
Hyperglycaemic states causes two things
1. -> increased action of aldose reductase and sorbitol dehydrogenase -> causing glucose conversion – sorbitol and fructose.
sorbitol and fructose -> causing decrease in synthesis of nerve cell myoinositol (required for normal neuron conduction)
At the same time, the conversion of glucose causes the depletion of nicotinamide adenine dinucleotide phosphate stores. (necessary for detoxification of reactive oxygen species and synthesis of nitric oxide). ->increased the oxidative stress and vasoconstriction -> ischemia
2. Abnormal glycation of nerve cell proteins and inappropriate activation of protein kinase C -> causes nerve dysfunction and ischemia
-Damage to innervation of the intrinsic foot muscles leads to imbalance between flexion and extension of the affected foot.
-causing anatomic deformities -> abnormal bony prominences and pressure points -> skin breakdown -> ulceration
- For example is the claw toe deformity: increased pressure is placed on the dorsal and plantar aspects of the deformity. Secondly is the Charcot atropathy (the rocker bottom deformity leads to increased pressure on the plantar midfoot).
Autonomic system dysfunction, with impaired microvascular thermoregulation and anhidrosis
-reduces sweat and oil gland functionality -> skin not moisturized and becoming dry easily -> friction and tears and skin breakdown -> ulceration
Sensory
-patient unable to detect insult from trauma to lower extremities. Wound go unnoticed and progressively worsen
sensory loss involving Type A myelin fibers causes a loss of proprioception, pressure sensation, vibratory perception
Destruction of the type C sensory fibers leads to an inability to appreciate painful stimuli
As a result of these impaired sensations, the diabetic patient can experience repetitive foot trauma, including blister formation or even metatarsal bone fracture, without an appreciation of foot discomfort.
Ischemia from peripheral vascular disease
-Contribute up to 50% of cases of DFU.
-Common affected arteries are the tibial and peroneal arteries.
“Persistent hyperglycemic state ->endothelial cell dysfunction and smooth cell abnormalities”
“Decrease in endothelium-derived vasodilators -> vasoconstriction”
“Thromboxane A2 increases -> vasoconstriction platelet aggregation agonist ->plasma hypercoagulability.
atherosclerosis
The immune system of a patient with diabetes is much weaker than the healthy people
hyperglycemic state causes an elevation of pro-inflammatory cytokines and impairment of polymorphonuclear cell functions like chemotaxis, adherence, phagocytosis and intracellular killing
The immune system is compromised by lowered leukocyte activity, inappropriate inflammatory response and the disruption of cellular immunity (inhibition of fibroblast proliferation and impairment of the basal layer of keratinocytes, reducing epidermal cell migration)
Leukocyte phagocytosis was significantly reduced in patients with poorly controlled diabetes, and improvement of microbiocidal rates was directly correlated with correction of hyperglycemia. Decreased chemotaxis of growth factors and cytokines, coupled with an excess of metalloproteinases, impede normal wound healing by creating a prolonged inflammatory state.
