Association of diabetic foot ulcers with chronic vascular diabetic complications in patients with type 2 diabetes

ContextDiabetes mellitus is a common disease which is prevalent globally, presenting with chronic complications and constitutes a major risk to the patient. Diabetic foot ulcers are the single biggest risk factor for non-traumatic lower limb amputations in persons with diabetes. We aimed to screen for the chronic vascular diabetic complications in patients with diabetic foot ulcers (DFUs) and to assess the association of diabetic foot ulcers with these complications in the study group.Subjects and methodsThis cross-sectional study included 180 type 2 diabetic patients (aged 30–70 years) with diabetic foot ulcers who attended the Outpatient Clinic of Diabetes in Alexandria Main University Hospital. Full diabetic foot examination was done to all study subjects. DFUs were assessed using University of Texas Diabetic Wound Classification System. HbA1c, LDL-C, serum creatinine, and urinary albumin creatinine ratio (ACR) were measured for all study subjects. Estimated glomerular filtration rate (eGFR) was calculated using CKD-EPI equation. Fundus examination was done for all study subjects.ResultsThe prevalence of diabetic kidney disease (DKD) and diabetic retinopathy (DR) was 86.1% and 90% respectively among the study group. 86.7% of patients had neuropathic DFUs, 11.1% of them had ischemic DFUs and 2.2% had neuro-ischemic DFUs. Regarding diabetic peripheral neuropathy (DPN) and peripheral arterial disease (PAD) as risk factors for developing DFU, the prevalence of both of them respectively was 82% and 20% among the study group. There was statistically significant association between both DKD, DR and peripheral neuropathy. There was also statistically significant association between both DKD, DR and peripheral arterial disease (PAD).ConclusionChronic vascular diabetic complications are common among type 2 diabetic patients with diabetic foot ulcers. There is statistically significant association between these complications and diabetic peripheral neuropathy (DPN) and peripheral arterial disease (PAD).     

Depression and Incident Diabetic Foot Ulcers: A Prospective Cohort Study

Objective

To test whether depression is associated with an increased risk of incident diabetic foot ulcers.

Methods

The Pathways Epidemiologic Study is a population-based prospective cohort study of 4839 patients with diabetes in 2000-2007. The present analysis included 3474 adults with type 2 diabetes and no prior diabetic foot ulcers or amputations. Mean follow-up was 4.1 years. Major and minor depression assessed by the Patient Health Questionnaire-9 were the exposures of interest. The outcome of interest was incident diabetic foot ulcers. We computed the hazard ratio and 95% confidence interval (CI) for incident diabetic foot ulcers, comparing patients with major and minor depression with those without depression and adjusting for sociodemographic characteristics, medical comorbidity, glycosylated hemoglobin, diabetes duration, insulin use, number of diabetes complications, body mass index, smoking status, and foot self-care. Sensitivity analyses also adjusted for peripheral neuropathy and peripheral arterial disease as defined by diagnosis codes.

Results

Compared with patients without depression, patients with major depression by Patient Health Questionnaire-9 had a 2-fold increase in the risk of incident diabetic foot ulcers (adjusted hazard ratio 2.00; 95% CI, 1.24-3.25). There was no statistically significant association between minor depression by Patient Health Questionnaire-9 and incident diabetic foot ulcers (adjusted hazard ratio 1.37; 95% CI, 0.77-2.44).

Conclusion

Major depression by Patient Health Questionnaire-9 is associated with a 2-fold higher risk of incident diabetic foot ulcers. Future studies of this association should include better measures of peripheral neuropathy and peripheral arterial disease, which are possible confounders or mediators.     

The war in Ukraine and diabetic foot care: Challenges,recommendations

AimsA number of reports have illustrated the barriers that the war in Ukraine puts to diabetes care. While their recommendations are valuable for glycemic control and the prevention or early detection of life - threatening diabetes complications, such as hypoglycemia and ketoacidosis, the discourse on diabetic foot is limited. This letter emphasizes the implications of the war in diabetic foot care and discusses potential solutions.MethodsThe authors searched peer – reviewed and grey literature to identify records related to the prevalence of diabetic foot in Ukraine and the standards of care before and after the invasion of Ukraine.ResultsThousands of people in Ukraine sustain diabetic foot ulcers and, thus, are at high risk for lower limb amputations due to the limited access to healthcare services in the country. If not addressed, disability associated with chronic ulcers and amputations can severely affect individual and public health in Ukraine. Strengthening primary and remote care, educating people on self – care and providing adequate supplies for the management of diabetic foot have a major potential to prevent amputations, disability and death.ConclusionsProviding adequate diabetic foot care in Ukraine and other regions tormented by armed conflicts is vital for the health of the local population and the potential of the affected countries to recover after the crisis.     

Operative versus non-operative treatment in diabetic dry toe gangrene

Background and aimDiabetic foot is a major comorbidity of diabetes, with 15–25% of diabetic patients developing diabetic foot ulcer during their lifetime. Other major diabetic foot complications include cellulitis, abscess, wet gangrene, dry gangrene, and necrotizing fasciitis. Dry gangrene involves tissue necrosis due to chronic ischemia whereby the tissue becomes numb, dry, wrinkled, and dead. Although diabetic foot complications have been extensively studied in literature, there is limited data on the management of dry gangrene.MethodsWe report a case series of 12 patients with diabetes-related dry gangrene in the toes, initially planned to be managed conservatively with autoamputation.ResultsOne patient had an autoamputation, while eight patients underwent surgical amputations (six major amputations, two minor amputations) for better clinical outcomes. Two patients died, while no change was observed in one patient even after 12 months of follow-up.ConclusionManaging diabetic dry toe gangrene by waiting for autoamputation may lead to worse clinical outcomes and should be practiced cautiously on a case-by-case basis. Early surgical intervention should be opted to improve patients’ quality of life.     

Reduction of Gangrene and Amputations in Diabetic Renal Transplant Patients: the Role of a Special Foot Clinic

This 4-year prospective study investigated the reasons for high levels of gangrene and major amputation in diabetic renal transplant patients and whether regular mutli-disciplinary foot care could reduce morbidity. All foot lesions were documented and investigated in 50 diabetic patients, mean age 49.2 ± 11.0 (SD) years, duration of diabetes 25.3 ± 9.0 years, time since renal transplantation 60.2 ± 35.1 months, who attended a special foot clinic monthly for education, vascular and neurological assessment, podiatry and footwear. Foot lesions included: neuropathic ulcers, ischaemic ulcers, traumatic lesions, Charcot's arthropathy, pathological fracture. Treatment included antibiotics, podiatry, footwear, and angioplasty or distal bypass where appropriate. Only 13 patients were deemed ischaemic but peripheral neuropathy was a very common finding (mean VPT 24.8 ± 12.9 V). Gangrene and major amputations showed a decrease on previous years and healing times for lesions were similar to those previously reported in diabetic patients without renal transplants. The majority of foot lesions, both in soft tissue and bone, were related to neuropathy and trauma and responded well to optimal foot care within the renal unit. Gangrene and major amputations were usually preventable.     

The potential of transdermal nitric oxide treatment for diabetic peripheral neuropathy and diabetic foot ulcers

The Center for Disease Control (CDC) estimates that 29 million Americans have diabetes, and 70% of diabetic patients develop diabetic peripheral neuropathy [1,2]. Up to 27% of the direct medical cost of diabetes may be attributed to DPN [3]. A 2013 article from the American Diabetes Association reported a $176 billion direct medical cost of diabetes in 2012 [4]. DPN patients often suffer from shooting and burning pain in their distal limbs and a severe loss of sensation. Diabetic foot ulcers, infections, and amputations may follow. Currently available treatments: tricyclic antidepressants, anticonvulsants such as gabapentin and pregabalin, serotonin and norepinephrine reuptake inhibitor, duloxetine, topical 5% lidocaine (applied to the most painful area) can manage painful symptoms but do not address the underlying pathologies of DPN and diabetic wound ulcers. A combination of pain-reducing medications can provide relief when individual medications fail, and opioids such as tramadol and oxycodone may be administered with these medications to reduce pain [5]. Due to the prevalence of diabetes, DPN, and diabetic foot ulcers, and because of the lack of available effective treatments to directly address the pathology contributing to these conditions, novel treatments are being sought. Our hypothesis is that a deficiency of nitric oxide synthase in diabetic patients leads to a lack of vascularization of the peripheral nerves, which causes DPN; and this could be treated with vasodilators such as nitric oxide. In this paper, the mechanisms of DPN are reviewed and analyzed to elucidate the potential of a transdermal nitric oxide application for the treatment of DPN and diabetic wound ulcers by increasing vasodilation.     

糖尿病周围神经病变和血管病变对糖尿病足溃疡的相互作用及相关性探讨

目的 探讨糖尿病足溃疡（DFU）发生的危险因素,分析糖尿病周围神经病变（DPN）和糖尿病血管病变（PAD）与DFU的相互作用.方法 选取T2DM患者278例,按其是否合并DFU分成糖尿病足溃疡组（DFU,102例）和糖尿病非足溃疡组（NDFU,176例）,回顾性分析两组生化特征和并发症情况.采用Logistic回归分析DFU发生的危险因素,并通过相对超额危险度比（RERI）,归因比（AP）和相互作用指数（S）评价DPN与PAD的相加相互作用.结果 与NDFU组比较,DFU组HbA1c和纤维蛋白原（FIB）水平,DR、DPN和PAD发生率均升高,血红蛋白（Hb）、血白蛋白（Alb）、TC和LDL-C降低（P＜0.05）.Logistic回归分析显示,DFU相关影响因素有：HbA1 c、DPN、PAD、Hb、Alb和FIB（OR分别为1.41、3.66、3.00、0.98、0.79和2.51）.DPN和PAD对DFU的相加相互作用指标RERI、AP和S分别为3.45（95％CI：1.22～8.56）、0.29（95％CI：0.02～0.58）和1.45（95％CI：1.03～4.96）.结论 血糖控制欠佳、合并DPN和PAD、营养不良及FIB代谢失衡是DFU发生的主要危险因素.DPN和PAD对DFU存在相加相互作用,同时患有DPN和PAD可增加DFU的患病风险.     

Prevalence and risk factors for diabetic neuropathy and painful diabetic neuropathy in primary and secondary healthcare in Qatar

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.     

Decreasing Incidence of Major Amputation in Diabetic Patients: a Consequence of a Multidisciplinary Foot Care Team Approach?

The purpose of this retrospective study was to evaluate the changes in diabetes-related lower extremity amputations following the implementation of a multidisciplinary programme for prevention and treatment of diabetic foot ulcers in a 0.2 million population with a 2.4 % prevalence of diabetes. All diabetes-related primary amputations from toe to hip from 1 January 1982 to 31 December 1993 were included. In 294 diabetic patients, 387 primary major (above the ankle) or minor (through or below the ankle) amputations were performed, constituting 48 % of all lower extremity amputations. The annual number of amputations at all levels decreased from 38 to 21, equalling a decrease of incidence from 19.1 to 9.4/100 000 inhabitants (p = 0.001). The incidence of major amputations decreased by 78% from 16/1 to 3.6/100 000 inhabitants (p<0.001). The absolute number of amputations with a final level below the ankle showed no increase, but their proportion increased from 28 to 53 % (p<0.001) and the reamputation rate decreased from 36 to 22 % (p<0.05) between the first and last 3-year period. Thus, a substantial long-term decrease in the incidence of major amputations was seen as well as a decrease in the total incidence of amputations in diabetic patients. Seventy-one per cent of the amputations were precipitated by a foot ulcer. These findings indicate that a multidisciplinary approach plays an important role to reduce and maintain a low incidence of major amputations in diabetic patients     

Clinical outcome of diabetes patients hospitalized with foot ulcers, Dar es Salaam, Tanzania.

AIMS: To determine the prevalence rate, clinical features, risk factors, and clinical outcome of foot ulcers in diabetes patients admitted to Muhimbili National Hospital, Dar es Salaam, Tanzania. METHODS: A prospective cohort study of newly hospitalized, adult diabetes patients with foot ulcers was conducted during January 1997 to December 1998 (study period). Detailed clinical and epidemiological data were recorded for each patient, followed by a comprehensive physical examination. Clinical outcome was documented. RESULTS: Of 627 diabetes patients evaluated during the study period, 92 (15%) had foot ulcers. Of these 92 patients, 30 (33%) were selected for surgery (minor and major amputations); the rest were managed conservatively. Patients who underwent surgery were more likely than those who did not to have gangrene (P < 0.001) or neuropathy (P < 0.01). On stratification by severity of ulcers, patients with Wagner score > or = 4 were significantly more likely than those < 4 to have neuroischaemic foot lesions (P < 0.001) or delayed presentation to hospital (P < 0.001). The overall mortality rates for amputees and non-amputees were similar (29%); the highest in-patient mortality rate (54%) was observed among patients with severe (Wagner grade > or = 4) ulcers who did not undergo surgery. CONCLUSIONS: Diabetic foot ulcers are associated with significant morbidity and mortality in Tanzania. Mortality rates among patients with severe ulcers remain high despite surgery. Thus, surgery undertaken during the less severe stages of ulcers may improve patient outcome. Education of patients should underscore the importance of foot care and consulting a doctor during the early stages of foot ulcer disease.     

The distribution and severity of diabetic foot disease: a community study with comparison to a non-diabetic group.

A surveillance programme was undertaken to identify all diabetic patients with foot disease in a defined population with the same age and sex structure as that of the UK. Of 1150 diabetic patients identified, 1077 were reviewed either at home or in hospital. The presence of foot deformity, amputation, and foot ulceration was determined. The site, depth, and duration of ulcers were recorded and any previous ulceration noted. All feet with ulcers were X-rayed. A non-diabetic comparison group of 480 age- and sex-matched individuals were also examined by the same observer. The prevalence of past or present foot ulceration was 7.4 (95% CI 5.8-9.0)% in diabetic patients and 2.5 (95% CI 1.1-3.9)% in the non-diabetic group, yielding an odds ratio of 2.94 (95% CI 1.58-5.48) (p less than 0.001) for the occurrence of foot ulceration in diabetic patients. Of the ulcers found on examination, 39.4% were neuropathic, 24.2% were vascular, and 36.4% were mixed. Multiple logistic regression analysis of selected variables revealed that duration of diabetes, absent light touch, impaired pain perception, absent dorsalis pedis pulse, and the presence of any retinopathy were significant predictors of the presence of foot ulcers. The prevalence of amputation in diabetic patients was 1.3 (95% CI 0.6-2.0)%, but there were no amputations in the non-diabetic group.     

Wound healing effects of dipeptidyl peptidase-4 inhibitors: An emerging concept in management of diabetic foot ulcer—A review

ObjectiveDipeptidyl peptidase-4 (DPP-4) inhibitors have a well-known effect on glycaemic control in patients with diabetes but little is known on their wound healing role in this group of population. This paper reviews the effects of DPP-4 inhibitors on wound healing of diabetic foot ulcers.MethodsPublished data on effects and mechanism of DDP-4 inhibitors on wound healing were derived from Medline, PubMed and Google Scholar search of English language literature from 1994 to 2014 using the key words such as “DPP-4 inhibitors”, “endothelial healing” “diabetes” and “chronic ulcers”.ResultsDPP-4 inhibitors show a potential benefit in processes of wound healing in diabetic chronic foot ulcers. The enzyme inhibitors promote recruitment of endothelial progenitor cells and allow the final scaffolding of wounds. Furthermore DPP-4 inhibitors augment angiogenesis and have widespread effects on optimising the immune response to persistent hypoxia in chronic diabetes wounds.ConclusionDPP-4 inhibitors show promise in the local wound healing of diabetic foot ulcers in addition to its already established glycaemic control. In the light of high rate of amputations due to non-healing ulcers with profound psychological and economical liability, more investigations on the usefulness of DPP-4 inhibitors in the high risk diabetes population are needed.     

Prevalence of peripheral neuropathy in patients with diabetes: A systematic review and meta-analysis

AimsWe aimed to determine pooled prevalence of diabetic peripheral neuropathy (DPN) in patients with diabetes and to explore the impacts of research variables on prevalence estimates.MethodsA systematic search was performed in PubMed, EMBASE, The Cochrane Library and Scopus from onset up to July 2018 to identify articles investigating the prevalence of DPN. Random-effects models were used to calculate the pooled prevalence of DPN. The heterogeneity of the study was estimated with the I² statistic. The publication bias was described by Egger’s test and funnel plot.ResultsA total of 29 studies with a total of 50,112 participants were included in this meta-analysis. The results showed that the pooled prevalence of DPN was 30% (95% confidence interval, CI 25–34%). The pooled prevalence of DPN among patients with type 2 diabetes mellitus was higher than patients with type 1 diabetes mellitus (31.5%, 95% CI 24.4–38.6% vs 17.5%, 95% CI 4.8–30.2%). The pooled prevalence of DPN of studies involving a mixed type of diabetes mellitus was 24.8% (95% CI 13.1–36.5%, I² = 99.1%).ConclusionsMedical staff should strengthen the evaluation and diagnosis of DPN. Moreover, they need to teach diabetic patients how to prevent this complication.     

The prevalence of clinical diabetic polyneuropathy in Spain: a study in primary care and hospital clinic groups

Summary A multiregional cross-sectional study of clinical diabetic polyneuropathy (DPN) was carried out among Spanish diabetes patients using a standard system for scoring symptoms and signs of polyneuropathy. The main patient sample comprised 2 644 patients (54.7 % women) aged 15–74 years (mean 57.2 ± 0.3 years), 86.9 % of whom had Type II (non-insulin-dependent) diabetes mellitus and 29.4 % were attending hospital clinics. Mean duration of diabetes since diagnosis was 10.2 ± 0.2 years. The prevalence of DPN was 22.7 % (95 % confidence interval 21.2–24.3 %) in the whole sample, 12.9 % (9.4–16.5 %) among patients with Type I (insulin-dependent) diabetes mellitus and 24.1 % (22.4–25.9 %) among patients with Type II diabetes; there was no significant difference in prevalence between men and women. Prevalence increased with age (from < 5 % in the 15- to 19-year-old age group to 29.5 % in the 70- to 74-year-old group) and with duration of diabetes since diagnosis (from 14.2 % among those with duration < 5 years to 44.2 % among those with duration > 30 years). In a supplementary sample of 161 diabetic patients aged 75 to 79 years (excluded from the main sample to prevent confusion between diabetes-induced and ageing-induced neuropathies), prevalence was 37.8 %. Ninety-three patients (3.3 %) had or had had foot ulcers and 21 of these 93 (0.7 %) had undergone amputation; 90.8 % of ulcerated patients had Type II diabetes, and 54 % had DPN (in most cases with loss of perception of vibration), as against a prevalence of DPN of 19.9 % among patients without ulcers. We conclude that nearly a quarter of Spanish diabetic patients have DPN; that over 90 % of DPN patients have Type II diabetes; that the prevalence of DPN increases with age and with the duration of the disease, and that the risk of foot ulcers among DPN patients is about three times the risk among diabetic patients without DPN. We accordingly emphasize the responsibility of primary care physicians to try to prevent diabetic foot lesions by early diagnosis of DPN. [Diabetologia (1998) 41: 1263–1269] Received: 10 March 1998 and in final revised form: 8 June 1998     

Contribution of diabetes to amputations in sub-Sahara Africa: A systematic review and meta-analysis

Diabetes related amputations remain a major global problem, with devastating complications. We critically appraised relevant literature to quantify the prevalence of diabetes related amputations in sub-Saharan Africa (SSA). An electronic search was performed using the EMBASE and PubMed databases until 2020. Twenty-four out of 834 studies retrieved were included. The pooled prevalence of diabetic-related amputations was 36.9% (95%CI: 32.9%–40.8%). Complications of diabetes related amputations included infection, anaemia, foot deformity and mortality. The study revealed a substantial contribution of diabetes to the burden of amputations in SSA and suggests the need for further studies to assess how to reduce the incidence of diabetes, reduce the incidence of and or delay the progression of macro and microvascular complications of diabetes in SSA.     

Geographic variation in Medicare spending and mortality for diabetic patients with foot ulcers and amputations

AimsThe purpose of this study was to identify the presence or absence of geographic variation in Medicare spending and mortality rates for diabetic patients with foot ulcers (DFU) and lower extremity amputations (LEA).MethodsDiabetic beneficiaries with foot ulcers (n=682,887) and lower extremity amputations (n=151,752) were enrolled in Medicare Parts A and B during the calendar year 2007. We used ordinary least squares (OLS) regression to explain geographic variation in per capita Medicare spending and one-year mortality rates.ResultsHealth care spending and mortality rates varied considerably across the nation for our two patient cohorts. However, higher spending was not associated with a statistically significant reduction in one-year patient mortality (P= .12 for DFU, P= .20 for LEA). Macrovascular complications for amputees were more common in parts of the country with higher mortality rates (P< .001), but this association was not observed for our foot ulcer cohort (P= .12). In contrast, macrovascular complications were associated with increased per capita spending for beneficiaries with foot ulcers (P= .01). Rates of hospital admission were also associated with higher per capita spending and increased mortality rates for individuals with foot ulcers (P< .001 for health spending and mortality) and lower extremity amputations (P< .001 for health spending, P= .01 for mortality).ConclusionsGeographic variation in Medicare spending and mortality rates for diabetic patients with foot ulcers and amputations is associated with regional differences in the utilization of inpatient services and the prevalence of macrovascular complications.     

Strategies to reduce severe diabetic foot infections and complications during epidemics (STRIDE)

AimsPatients with diabetes, including those with foot complications, are at highest risk for severe outcomes during the COVID-19 pandemic. Diabetic foot ulcers (DFU) present additional challenges given their superimposed risk for severe infections and amputations. The main objectives were to develop a triage algorithm to effectively risk-stratify all DFUs for potential complications, complying with social distancing regulations, preserving personal protective equipment, and to assess feasibility of virtual care for DFU.MethodsLongitudinal study during the COVID-19 pandemic performed at a large tertiary institution evaluating the effectiveness of a targeted triage protocol developed using a combined approach of virtual care, electronic medical record data mining, and tracing for rapid risk stratification to derive optimal care delivery methods. 2868 patients with diabetes at risk for foot complications within last 12 months were included and rates of encounters, hospitalizations, and minor amputations were compared to one year prior.ResultsThe STRIDE protocol was implemented in 1-week and eventually included 2600 patients (90.7%) demonstrating effective triage. During normal operations, 40% (938 of 2345) of all visits were due to DFUs and none were performed virtually. After implementation, 98% face-to-face visits were due to DFU, and virtual visits increased by 21,900%. This risk stratified approach led to similar low rates of DFU-related-hospitalization and minor amputation rates 20% versus 24% (p > 0.05) during and prior the pandemic, respectively.ConclusionsImplementation of STRIDE protocol was effective to risk-stratify and triage all patients with diabetic foot complications preventing increase in hospitalization and amputations while promoting both social and physical distancing.     

Glycemic profile variability: An independent risk factor for diabetic neuropathy in patients with type 2 diabetes

BackgroundImpaired glycemic control is a potential predictor for macro- and microvascular complications of diabetes, which could be recognized by glycemic variability. The aim of this 10-year prospective cohort study presented here is to gain a better understanding of the correlation between GV and diabetic peripheral neuropathy (DPN) as one of the most common complications of T2DM.MethodsSince February 2010, 1152 adult patients with T2DM have been followed-up. Baseline features, anthropometric measurements, and laboratory findings were collected and documented during ten years. The association between DPN incidence and glycemic profile variability was evaluated using cox regression analysis. The coefficient of variation of glycemic indices within subjects was calculated and compared using an independent sample t-test.ResultsIndividuals who developed neuropathy had significantly higher mean levels of glycemic indices (HbA1c, FBS, and 2hpp), urinary albumin excretion, mean creatinine levels, and a longer duration of diabetes. A significant positive correlation between incidence of DPN and glycemic profile variability (cv-FBS10 %, cv-FBS20 %, cv-2hpp20 %, cv-HbA1c5 % and cv-HbA1c10 %) was revealed. Results also showed that higher variability of FBS was associated with the higher risk of neuropathy incidence (HR: 12.29, p-value: 0.045), which indicates that glycemic profile variability is an independent risk factor for DPN in patients with T2DM.ConclusionVariability of glycemic profiles from a visit to visit, regardless of sustained hyperglycemia, was indeed a significant risk factor for DPN in diabetic type 2 patients. CV-FBS was the most critical glycemic variability indices for DPN development.