Table 1.

Advantages and disadvantages of prevention strategies for diabetic neuropathy. DFUs, diabetic foot ulcers; DN, diabetic neuropathy; QoL, quality of life; T1DM, type 1 diabetes; T2DM, type 2 diabetes.

Prevention Strategy	Indication(s)	Intervention Types	Level of Evidence	Advantages	Disadvantages
Glycemic control	To reduce the risk of DN	Pharmacological: - Insulin - Antidiabetic medicines Nonpharmacological: - Lifestyle modifications - Pancreas transplant - Bariatric surgery	High-quality—all intervention types that enhance glycemic control for at least 12 months [70]	-Glycemic control reduces the risk of DN in T1DM (significant) and in T2DM (not significant) [70] -Glycemic control can be readily assessed with flash glucose monitors (FreeStyle Libre) and continuous glucose monitoring -Guidelines recommend that individualized glycemic targets are based on shared decision making [71,72,73,74,75,76]	-Enhanced glycemic control does not significantly reduce the risk of DN in T2DM [70] -Risk associated e.g., hypoglycemic episodes, side effects of anti-diabetic medications, treatment-induced neuropathy and potentially other acute neuropathies [77,78,79]
Lifestyle modifications	To reduce the risk of DN, to prevent progression of DN, to reduce cardiometabolic factors	Nonpharmacological: - Supervised exercise programs e.g., ∘ endurance training ∘ sensorimotor training ∘ combined endurance and strength training ∘ resistance training ∘ balance training ∘ combined balance and gait training/whole-body vibration/resistance training ∘ whole-body vibration ∘ physiotherapy/rehabilitation -Diet -Counselling	Moderate-quality—supervised exercise programs for DN and DFUs in people with diabetes [80,81] Low-quality—supervised exercise programs for DN in people with prediabetes [82], diet and counselling for DN in people with diabetes	-Endurance training may significantly reduce the risk of DN [83] - Supervised exercise programs may improve DN outcomes [80] ∘ endurance training may reduce neuropathic pain and may improve nerve conduction, symptoms, vibration perception threshold, blood glucose levels, daily function, arterial blood flow, QoL and relationships ∘ sensorimotor training may improve balance and mobility ∘ combined endurance and strength training may improve small fiber function and mobility ∘ balance training may reduce pain, tingling, anxiety, depression, concerns about falling, blood inflammatory markers and may improve QoL, mobility, trunk strength, function and blood glucose levels ∘ balance training combined with either gait training, whole-body vibration and resistance training may improve mobility, balance, vibration perception and gait and may reduce concerns about falling ∘ whole body vibration may improve mobility, balance, posture, blood glucose levels and lower limb strength ∘ physiotherapy/rehabilitation may improve mobility, balance and stability and may reduce fall risk -Supervised exercise programs can be personalized -Supervised exercise programs may reduce the risk of DFUs [81] -Diabetes and diet counselling may improve glycemic control and promote weight loss [84,85] -Counselling may also facilitate compliance with exercise programs -Lifestyle modifications provide a holistic approach	-The effects of resistance training on DN outcomes are inconclusive [80] -Patient compliance with supervised exercise programs is often low -There is a lack of infrastructure and resources to provide supervised exercise regimens in public healthcare systems -Long-term behavior change is challenging -Socioeconomic determinants of health may complicate behavior change -The availability of services is low, and the effectiveness of low-contact programs is uncertain (e.g., internet-delivered resources)
Footcare	To reduce the risk of further foot complications	Pharmacological: -Antibiotics Nonpharmacological: -Referral to multidisciplinary footcare services -Patient education on footcare -Offloading -Debridement -Revascularization	Low-quality—referral to multidisciplinary footcare services, patient education on footcare	-Footcare ensures regular risk assessment of ulceration and opportunity to modify abnormal risk factors -Referral to multidisciplinary footcare services may reduce the risk of amputation severity, mortality rates and length of hospital stay [86] -A multidisciplinary footcare team with surgical and infection expertise may provide optimal limb salvage treatment [87] -Footcare includes patient education and self-management	-Footcare has no bearing on DN risk -Multidisciplinary footcare services often underperform [88] -There is insufficient evidence to determine if educational strategies reduce the incidence of DFUs and amputations [89] -Patient compliance with self-footcare is often low