Recent advances in the diagnosis and management of diabetic neuropathy

<p>The number of Diabetic Foot Ulcer (DFU) cases is growing due to the rising number of older persons in society and the increasing worldwide prevalence of diabetes mellitus (DM). Indeed, a DFU occurs in approximately 1 out of every 7 patients with DM. Clinical preventive and management interventions for DFU typically include the employment of multiple guideline-based interventions, with the goal of preventing the onset of DFU in the first place. The development of new and effective interventions in wound care generally remains an area of intense research interest, especially in DFU, where the search continues for evidence on high efficacy, yet cost effective interventions. This clinically focussed paper will present an overview of DFU, introduce some of the costs associated with DFU prevention and management in addition to including important treatment considerations. This paper also highlights the urgent need for more high quality robust clinical trial research to meet the expanding treatment needs of this growing patient population</p>

Foot Care

BackgroundNeuropathy is the most common microvascular complications among diabetic patients. Diabetic peripheral neuropathy (DPN) is the predominant variety which may associate with increased in mortality and morbidity among type 2 diabetes mellitus (T2DM).ObjectiveTo assess the prevalence of diabetic peripheral neuropathy and its correlation with risk factors among T2DM.MethodsThis was a cross-sectional retrospective study, data was collected from a previous cohort study conducted at the University Diabetes Center, King Saud University Medical City (KSUMC), King Saud University, Riyadh, Saudi Arabia. The data of T2DM patients were collected from case report form, included demographic data, history of chronic diabetes neuropathy, and laboratory reports. Statistical analysis includes Student`s t test, chi square test, and Pearson correlation and logistic regression were performed.ResultsA total of 430 patients with T2DM data was collected and analyzed, and of them 54% were females, with the mean age of 55.88 years. The prevalence of diabetic neuropathy among study participants were 40.2%, and 73.3% of them having the subtype polyneuropathy. The mean BMI; p = 0.006, FBS; p < 0.001, HbA1c; p < 0.001, cholesterol p = 0.001, LDL; p < 0.001, and triglyceride; p < 0.001 levels were a significantly higher among participants with diabetic neuropathy than without neuropathy. The male gender (Risk Ratio: 1.294, 95% CI:1.090, 1.536) p = 0.003, fasting blood glucose (Risk Ratio: 1.157, 95% CI:1.051, 1.273) p = 0.003 Cholesterol (Risk Ratio: 1.588, 95% CI:1.174, 2.147) p = 0.003, triglyceride (Risk Ratio: 1.290, 95% CI:1.086, 1.538), p = 0.004, and LDL (Risk Ratio: 1.299, 95% CI:1.073, 1.574), p = 0.007) were found to be significant risk factors for DPN.ConclusionDPN is highly prevalent among T2DM patients in Saudi Arabia. Poor glycemic control and hyperlipidemia were associated with significantly higher risk for DPN patients among T2DM.

AIMS: To determine the prevalence of painful diabetic neuropathy (PDN), to evaluate the composition and efficacy of pharmacotherapy and to develop a differential algorithm for symptomatic treatment of PDN.&#x0D; MATERIALS AND METHODS: 4494 outpatient subjects participated in this study. Severity of pain syndrome was assessed with DN4 question- naire (supplemented with NTSS-9 scale) and visual analogue scale (VAS). After initial examination, a pharmacological evaluation of treatment was performed.&#x0D; RESULTS: Based on our data, prevalence of diabetic neuropathy was estimated at 54%, with painful form reaching 6.4%. Median age was 57.2-12.1, duration of diabetes mellitus - 16.5-10.6 years. Type 1 / type 2 ratio equaled 32.4% : 67.6%, male/female - 29.7%: 70.3%. Median HbA1c level was 8.4?1.6%. Ratio of chronic/acute forms of neuropathy was 267 : 20. Pain severity (as measured by VAS) distribution was as following: 15.6% ? severe, 40.6% ? moderate, 12.3% - mild, and 31.3% ? no pain symptoms. We did not find PDN to be associated with any parameters but sensory deficit (NTSS-9 and NDS: r=0.4; p 0.001). 21% of patients with chronic painful neuropathy (CPN) demonstrated allodynia and hyperalgesia besides typical symptoms. 97.9% of patients were previously treated with "pathogenetic" agents, 2.1% received anticonvulsants; overall efficiency was estimated at 22%. Patients with CPN and allodynia did not respond to treatment with alpha-lipoic acid (ALA), but pregabalin was efficient. After the examination treatment composition was adjusted as follows: treatment was ceased in 23% of patients, 11.9% received ALA, 53.6% - anticonvulsants, and 11.5% - antidepressants; overall efficiency was estimated at 75%.&#x0D; CONCLUSION: Prevalence of PDN is relatively low. 15.6% of patients suffer from severe pain. Neuropathic pain intensity correlates only with sensory deficit and is not dependent on any other parameters. CPN consists of two forms with higher and lower intensity of pain symptoms. Symptomatic therapy is indicated in acute variant of PDN, but also in chronic cases accompanied with allodynia and hyperalgesia. ALA appears to be effective as an initial stage of management of moderate or mild CPN.

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Diabetic peripheral neuropathy is a common complication of diabetes. It presents as a variety of syndromes for which there is no universally accepted unique classification. Sensorimotor polyneuropathy is the most common type, affecting about 30% of diabetic patients in hospital care and 25% of those in the community. Pain is the reason for 40% of patient visits in a primary care setting, and about 20% of these have had pain for greater than 6 months. Chronic pain may be nociceptive, which occurs as a result of disease or damage to tissue with no abnormality in the nervous system. In contrast, neuropathic pain is defined as “pain arising as a direct consequence of a lesion or disease affecting the somatosensory system.” Persistent neuropathic pain interferes significantly with quality of life, impairing sleep and recreation; it also significantly impacts emotional well-being, and is associated with depression, anxiety, and noncompliance with treatment. Painful diabetic peripheral neuropathy is a difficult-to-manage clinical problem, and patients with this condition are more apt to seek medical attention than those with other types of diabetic neuropathy. Early recognition of psychological problems is critical to the management of pain, and physicians need to go beyond the management of pain per se if they are to achieve success. This evidence-based review of the assessment of the patient with pain in diabetes addresses the state-of-the-art management of pain, recognizing all the conditions that produce pain in diabetes and the evidence in support of a variety of treatments currently available. A search of the full Medline database for the last 10 years was conducted in August 2012 using the terms painful diabetic peripheral neuropathy, painful diabetic peripheral polyneuropathy, painful diabetic neuropathy and pain in diabetes. In addition, recent reviews addressing this issue were adopted as necessary. In particular, reports from the American Academy of Neurology and the Toronto Consensus Panel on Diabetic Neuropathy were included. Unfortunately, the results of evidence-based studies do not necessarily take into account the presence of comorbidities, the cost of treatment, or the role of third-party payers in decision-making. Thus, this review attempts to give a more balanced view of the management of pain in the diabetic patient with neuropathy and in particular the role of pregabalin.

Aims/IntroductionThis study determined the prevalence and risk factors for diabetic peripheral neuropathy (DPN) and painful DPN (pDPN) in patients with type 2 diabetes in primary healthcare (PHC) and secondary healthcare (SHC) in Qatar.Materials and MethodsThis was a cross‐sectional multicenter study. Adults with type 2 diabetes were randomly enrolled from four PHC centers and two diabetes centers in SHC in Qatar. Participants underwent assessment of clinical and metabolic parameters, DPN and pDPN.ResultsA total of 1,386 individuals with type 2 diabetes (297 from PHC and 1,089 from SHC) were recruited. The prevalence of DPN (14.8% vs 23.9%, P = 0.001) and pDPN (18.1% vs 37.5%, P < 0.0001) was significantly lower in PHC compared with SHC, whereas those with DPN at high risk for diabetic foot ulceration (31.8% vs 40.0%, P = 0.3) was comparable. The prevalence of undiagnosed DPN (79.5% vs 82.3%, P = 0.66) was comparably high, but undiagnosed pDPN (24.1% vs 71.5%, P < 0.0001) was lower in PHC compared with SHC. The odds of DPN and pDPN increased with age and diabetes duration, and DPN increased with poor glycemic control, hyperlipidemia and hypertension, whereas pDPN increased with obesity and reduced physical activity.ConclusionsThe prevalence of DPN and pDPN in type 2 diabetes is lower in PHC compared with SHC, and is attributed to overall better control of risk factors and referral bias due to patients with poorly managed complications being referred to SHC. However, approximately 80% of patients had not been previously diagnosed with DPN in PHC and SHC. Furthermore, we identified a number of modifiable risk factors for PDN and pDPN.

Gabapentin

Aims/IntroductionThis study determined the prevalence and risk factors for diabetic peripheral neuropathy (DPN), painful DPN and diabetic foot ulceration (DFU) in patients with type 2 diabetes in secondary healthcare in Qatar, Kuwait and the Kingdom of Saudi Arabia.Materials and MethodsAdults aged 18–85 years with type 2 diabetes were randomly enrolled from secondary healthcare, and underwent clinical and metabolic assessment. DPN was evaluated using vibration perception threshold and neuropathic symptoms and painful Diabetic Peripheral Neuropathy was evaluated using the Douleur Neuropathique 4 questionnaire.ResultsA total of 3,021 individuals were recruited between June 2017 and May 2019. The prevalence of DPN was 33.3%, of whom 52.2% were at risk of DFU and 53.6% were undiagnosed. The prevalence of painful DPN was 43.3%, of whom 54.3% were undiagnosed. DFU was present in 2.9%. The adjusted odds ratios for DPN and painful DPN were higher with increasing diabetes duration, obesity, poor glycemic control and hyperlipidemia, and lower with greater physical activity. The adjusted odds ratio for DFU was higher with the presence of DPN, severe loss of vibration perception, hypertension and vitamin D deficiency.ConclusionsThis is the largest study to date from the Middle East showing a high prevalence of undiagnosed DPN, painful DPN and those at risk of DFU in patients with type 2 diabetes, and identifies their respective risk factors.

Local sympathetic denervation in painful diabetic neuropathy.

Objective: Foot and ankle exercise has been advocated as a preventative approach in reducing the risk of foot ulceration. However, knowledge about the appropriate types and intensity of exercise program for diabetic foot ulcer prevention is still limited. The current study aimed to examine the effects of an eight-week mini-trampoline exercise on improving foot mobility, plantar pressure and sensation of diabetic neuropathic feet. Methods: Twenty-one people with diabetic peripheral neuropathy who had impaired sensation perception were divided into two groups. The exercise group received a foot-care education program plus an eight-week home exercise program using the mini-trampoline (n = 11); whereas a control group received a foot-care education only (n = 10). Measurements were undertaken at the beginning, at the completion of the eight-week program and at a 20-week follow-up. Results: Both groups were similar prior to the study. Subjects in the exercise group significantly increased the range of the first metatarsophalangeal joint in flexion (left: p = 0.040, right: p = 0.012) and extension (left: p = 0.013) of both feet more than controlled subjects. There was a trend for peak plantar pressure at the medial forefoot to decrease in the exercise group (p = 0.016), but not in the control group. At week 20, the number of subjects in the exercise group who improved their vibration perception in their feet notably increased when compared to the control group (left: p = 0.043; right: p = 0.004). Conclusions: This is a preliminary study to document the improvements in foot mobility, plantar pressure and sensation following weight-bearing exercise on a flexible surface in people with diabetic neuropathic feet. Mini-trampoline exercise may be used as an adjunct to other interventions to reduce risk of foot ulceration. A larger sample size is needed to verify these findings. This trial is registered with COA No. 097.2/55.

breakthrough pain is supported by moderate certainty evidence and can be used in the appropriate population. 4. For palliative therapies and the treatment of neoplastic pain, the evidence is still...

Diabetic polyneuropathy (DPN) is a serious complication of both type 1 and type 2 diabetes. The major clinical manifestations of DPN are neuropathic pain, diabetic foot (which is associated with ulcers, gangrene, and amputation), and autonomic neuropathy. Diabetic sensorimotor peripheral neuropathy (DSPN) is the most common form of DPN and affects approximately 50% of people with type 1 or 2 diabetes during their lifetime (1) . Despite its major clinical impact, DPN remains underdiagnosed and undertreated. To reduce the burdens of DPN, there is an urgent need to develop both novel diagnostic procedures that enable to improve the early detection of the disease and new treatments that address multiple mechanistic pathways (Figure) (2) .

Objective Although ample evidence exists on the association between vitamin D deficiency and diabetic peripheral neuropathy, only a few studies have distinguished between painful and painless forms. This study compared serum vitamin D levels in type 2 diabetes patients with and without painful neuropathy. Methods We enrolled 46 patients with diabetes (painless diabetic peripheral neuropathy, n = 15; painful diabetic peripheral neuropathy, n = 16; non-neuropathy, n = 15) and 15 healthy controls. Assessments included neurologic exams, Michigan Neuropathy Screening Instrument, electrophysiology, skin biopsy, and serum 25(OH)D measurements. Results The level of 25(OH)D was significantly lower in painful diabetic peripheral neuropathy (23.00 ± 7.97) patients versus controls (44.48 ± 6.77), non- diabetic peripheral neuropathy (31.22 ± 6.14) patients, and painless diabetic peripheral neuropathy patients (36.91 ± 6.22; P &lt; 0.01). Multivariate analysis identified vitamin D as an independent factor for painful diabetic peripheral neuropathy (P = 0.007). The 25(OH)D level was significantly correlated with sural amplitude (r = 0.377), peroneal amplitude (r = 0.434), vibration threshold (r = −0.393), and Michigan Neuropathy Screening Instrument score (r = −0.456). Conclusions Serum 25(OH)D levels were significantly lower in painful diabetic peripheral neuropathy, suggesting the potential role of vitamin D deficiency in the pathogenesis of diabetic peripheral neuropathy.

Diabetic peripheral neuropathy (DPN) is an important microvascular complication of diabetes mellitus (DM). It is a major contributor to foot ulceration and lower limb amputation in persons with DM and have also a significant negative effect on patient's quality of life. This meta-analysis reviews prevalence of DPN among patients with type 1 and 2 DM in Iran. Using PubMed and NLM Gateway (for MEDLINE), Institute of Scientific Information (ISI), and SCOPUS as the main international electronic data sources, and Iranmedex, Irandoc, and Scientific Information Database (SID), as the main domestic databases with systematic search capability, we systematically searched surveys, papers, and reports on the prevalence of DPN (between January 1991 to February 2013). Heterogeneity of reported prevalence’s between studies was assessed by the Chi-square-based Q test and due to heterogeneity; overall prevalence of DPN was estimated using random-effect meta-analysis model. We found 304 records; from them a total of 21 studies comprising 5540 diabetic patients were included. The prevalence of diabetic neuropathy (reported) from 16% to 87%. In overall the prevalence of DPN estimated 53% (95% CI: 41-65) by using random-effect. This study show that the prevalence of DPN seems very high among the population with diabetes in Iran and more than half of the patients with DM has any type of diabetic neuropathy.