Risk Of Diabetic Peripheral Neuropathy Research Articles

Metformin treatment and risk of diabetic peripheral neuropathy in patients with type 2 diabetes mellitus in Beijing, China.

Metformin treatment is associated with vitamin B12 deficiency, which is a risk factor for neuropathy. However, few studies have examined the relationship between metformin treatment and diabetic peripheral neuropathy (DPN), and the available findings are contradictory. We aimed to assess whether metformin treatment is associated with DPN in patients with type 2 diabetes mellitus (T2DM) in Beijing, China. All patients with newly diagnosed T2DM between January 2010 and September 2012 in the Medical Claim Data for Employees database were included. Metformin treatment was defined as any record of metformin prescription. The average daily dose of metformin during follow-up was calculated. DPN was defined as DPN admissions occurring after a diagnosis of T2DM in the database. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. Among 49,705 T2DM patients, 1,933 DPN events were recorded during a median follow-up of 6.36 years. The crude incidence rates were 7.12 and 3.91 per 1000 person-years for patients treated with metformin (N=37,052) versus those not treated (N=12,653). Patients treated with metformin had an 84% increased risk of DPN compared with patients not using metformin (HR, 1.84; 95% CI, 1.62, 2.10). The daily dose was positively associated with DPN risk (HR, 1.48; 95% CI, 1.46, 1.51; P for trend <0.001). The risk of DPN was 1.53-fold (1.30, 1.81) and 4.31-fold (3.76, 4.94) higher in patients with daily doses of 1.0-2.0g and >2.0g, respectively, than in patients who did not receive treatment. Patients aged less than 60 years had a higher risk of DPN (P<0.05 for interaction test). Among patients taking vitamin B12 at baseline, there was no increased risk of DPN in the metformin group (1.92: 0.79, 4.69). In Chinese patients with T2DM, metformin treatment was associated with an increased risk of DPN admission and this risk responds positively to the daily dose of metformin. In particular, metformin use was a major risk factor for DPN in younger patients. Concomitant use of vitamin B12 may avoid the increased risk of DPN associated with metformin use.

Aspartate aminotransferase/alanine aminotransferase ratio was associated with type 2 diabetic peripheral neuropathy in a Chinese population: A cross-sectional study.

Despite previous research that focused on aspartate aminotransferase/alanine aminotransferase ratio (AAR) as predictors of type 2 diabetes mellitus (T2DM) and cardiovascular disease, there has been limited research evaluating the association between AAR and diabetic microvascular complications. This study aimed to investigate the association of AAR with diabetic peripheral neuropathy (DPN). A total of 1562 hospitalized patients with T2DM were divided into four groups according to AAR quartiles. The relationship between AAR and DPN and related parameters was explored by the Spearman correlation coefficients, multivariable logistic regression analysis, and receiver operating characteristic (ROC) curves. Patients with higher AAR quartiles had higher levels of vibration perception threshold (VPT) and presence of DPN, and AAR was positively associated with VPT and presence of DPN independent of sex, age, body mass index, and diabetic duration (P<0.01 or P<0.05). Moreover, AAR remained significantly associated with a higher odds ratio (OR) of DPN (OR 2.413, 95% confidenceinterval[CI] 1.081-5.386, P<0.05) after multivariate adjustment. Additionally, the risk of presence of DPN increased progressively as AAR quartiles increased (all P for trend <0.01) in both male and female subjects, and the highest quartile of AAR of male and female subjects was respectively associated with 107.3% (95% CI: 1.386-3.101; P<0.01) and 136.8% (95% CI: 1.550-3.618; P<0.01) increased odds of DPN compared with the lower quartiles. Last, the analysis of receiver operating characteristic curves revealed that the best cutoff values for AAR to predict the presence of DPN were 0.906 (sensitivity: 70.3%; specificity: 49.2%; and area under the curve [AUC]: 0.618) and 1.402 (sensitivity: 38%; specificity: 81.9%; and AUC: 0.600) in male and female subjects, respectively. These findings suggest that the high AAR may be associated with the presence of DPN in Chinese patients with T2DM, and may be used as an additional indicator of risk of DPN.

Diabetic peripheral neuropathy in the outpatient department – a red-flag for associated risk factors and comorbidities

Objectives. To assess the characteristics of patients with type 2 diabetes mellitus (DM) and diabetic peripheral neuropathy (DPN) as compared to patients with type 2 DM without DPN in an ambulatory setting, given the pandemic size of DM and its challenge for the healthcare systems worldwide in the 21st century. From the chronic complications of DM, DPN has a major impact on the patient’s life quality. DPN risk factors are both modifiable and unmodifiable and represent either other comorbidities per se, or predisposing factors for various comorbidities that alter the patient’s prognosis. Material and Methods. We conducted a retrospective observational study with 112 patients with type 2 DM treated in an out-patient department, in order to assess the characteristics and associated comorbidities of DPN. The group characteristics are a mean age of 60.28±9.76 years; 62.5% males; 77.67% from urban settlement; a prevalence of DPN of 52.67%. Outcomes. In the statistical analysis, DPN significantly associated with duration of DM, the need for insulin-therapy, risk factors such as smoking or obesity; with other complications of DM such as retinopathy, chronic kidney disease, atherosclerotic cardiovascular disease or peripheral artery disease; with comorbidities such as heart failure; and with the level of HDL-cholesterol and eGFR. Conclusions. A patient with DPN is more prone to also present other microvascular complications of type 2 DM, such as chronic kidney disease, retinopathy and, respectively with macrovascular complications of type 2 DM, and with other comorbidities such as heart failure and obesity. Its easily available diagnosis in an ambulatory setting by quantitative sensory testing should offer to DPN the status of a good marker for the presence of other chronic complications or comorbidities in type 2 DM, prompting the patient’s screening and an adequate medical management.

Increased levels of serum adenosine deaminase and increased risk of diabetic peripheral neuropathy in type 2 diabetes.

BackgroundIncreased serum adenosine deaminase (ADA) levels have been shown to be involved in metabolic abnormalities and immune disequilibrium, which may in turn contribute to inflammatory diseases. This study aimed to determine whether increased serum ADA levels are related to diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes (T2D).MethodsThis study was part of a series exploring the potential risks for DPN. All patients received DPN assessment based on neuropathic symptoms, neuropathic signs, and nerve conduction studies to calculate the composite Z score of nerve latency, amplitude and conduction velocity (NCV). DPN was confirmed by both at least a presentation of neuropathic symptoms/signs and an abnormal nerve conduction index. Serum ADA levels were also synchronously detected.ResultsA total of 384 eligible patients with T2D were recruited for this study, and 24.5% (n=94) were determined to have DPN. Increases in serum ADA levels were closely associated with increases in composite Z score of latency (β=0.263, t=5.273, p<0.001) and decreases in composite Z score of amplitude (β=–0.126, t=–2.352, p=0.019) and NCV (β=–0.201, t=–3.841, p<0.001) after adjusting for other clinical covariates. Moreover, each 5 U/L increase in serum ADA levels was associated with a 1.781-fold increased adjusted odds ratio of having DPN (95% confidence interval: 1.271–2.495). Furthermore, the optimal cut-off value of serum ADA levels to discriminate DPN was ≥14.2 U/L (sensitivity=59.57%, specificity=75.52% and Youden index=0.351) after analysis by receiver operating characteristic curve.ConclusionsIncreased serum ADA levels may be a potential risk factor for DPN in patients with T2D.

High-normal serum carcinoembryonic antigen levels and increased risk of diabetic peripheral neuropathy in type 2 diabetes

BackgroundIncreased serum carcinoembryonic antigen (CEA) levels are reported to be associated with various metabolic and inflammatory diseases. This study assessed whether high-normal serum CEA is related to diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes (T2D).MethodsAll subjects received DPN assessment based on neuropathic symptoms, neuropathic signs, and nerve conduction studies to calculate composite Z scores of nerve latency, amplitude and conduction velocity (NCV). DPN was confirmed by both at least a presentation of neuropathic symptoms/signs and an abnormal nerve conduction index. Serum CEA levels and other clinical indices were also synchronously detected. Multivariable linear regression analyses were used to determine the independent effects of serum CEA levels on nerve conduction indices, multivariable logistic regression analyses were used to determine the independent impact of CEA levels on the risk of DPN, and receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic capability of CEA levels to discriminate DPN.ResultsWe ultimately recruited 402 eligible subjects with normal ranges of serum CEA for this study, and 25.4% (n = 102) were determined to have DPN. After adjusting for other clinical covariates, serum CEA levels were independently associated with the composite Z score for latency (β = 0.132, t = 2.330, p = 0.021), amplitude (β = − 0.164, t = − 2.838, p = 0.005) and NCV (β = − 0.210, t = − 3.662, p < 0.001). Moreover, the prevalence of DPN in the first, second, third and fourth quartiles of CEA level was 12.9%, 19.0%, 29.4% and 40.4%, respectively (p for trend < 0.001); the corresponding adjusted odds ratios and 95% CIs for DPN in CEA quartiles were 1, 1.47 (0.45–4.82), 1.72 (0.54–5.53) and 4.58 (1.39–15.06), respectively. Furthermore, the optimal cut-off value of high-normal serum CEA to discriminate DPN was ≥ 2.66 ng/mL, with a Youden index of 0.28, sensitivity of 66.67% and specificity of 61.00%.ConclusionsIncreased serum CEA levels within the normal range are closely linked to dysfunction of peripheral nerve conduction and the risk of DPN, and high-normal serum CEA levels are a potential risk factor for DPN in T2D.

Melatonin receptor gene polymorphisms as a risk factor in patients with diabetic peripheral neuropathy.

Oxidative stress plays an important role in the pathogenesis of diabetic peripheral neuropathy (DPN). Melatonin is one of the most powerful endogenous antioxidants and has anti-inflammatory properties. We investigated how the gene polymorphism of melatonin differs in patients with DPN compared to an healthy control group. A total of 54 diabetic peripheral neuropathy patients who applied to the Neurology outpatient clinic between 2020 and 2021, and 53 healthy controls comparable with the patient group in terms of age and gender were included in the study. Electromyography was performed and the melatonin gene polymorphism was analysed using the pyrosequencing method. Melatonin gene variants rs2119882, rs13140012, and rs10830963 were analysed in patients and controls. The rs2119882 (G allele) has a protective role, and rs13140012 polymorphism has a related 5-fold higher risk of DPN in the recessive model. Melatonin gene polymorphisms have been shown to be associated with DPN. This is the first and only study investigating the relationship between melatonin gene polymorphisms and DPN. Ethnicity is very important in genetic studies, and it will give us more information on the role of melatonin gene variantsin larger study groups of diabeticpatients of other ethnic origin.

467-P: The Relationship between Diabetic Peripheral Neuropathy and Metformin Treatment in Type 2 Diabetes Mellitus

Background: Metformin is the first-line therapy for the treatment of Type 2 diabetes mellitus (T2DM) . However, the use of metformin may lead to neuropathy by affecting the absorption of vitamin B12. Our objective was to explore the association between the application of metformin and diabetic peripheral neuropathy (DPN) . Methods: The multicenter randomized cross-sectional study was conducted in 13 hospitals in Beijing from October 2015 to April 2016. T2DM Patients were divided into confirmed DPN group, suspected DPN group and non-DPN group by the five physical examinations (Ankle reflex, acupuncture pain, temperature, vibration, and pressure) . Non-parametric Mann-Whitney test was used for the comparison between non-normally distributed variables between two groups. Chi-square test was used for the comparison of categorical variables. The risk factors of DPN in T2DM Patients were assessed using logistic regression. Results: Compared with patients without metformin, patients taking metformin were more likely to suffer from DPN and suspected DPN (P &amp;lt; 0.0for both) . Similar results were obtained after stratifying the data based on age, BMI, and HbA1c. It was shown that the application of metformin was a risk factor for DPN (OR = 5.06, 95%Cl: 3.90-6.56; P &amp;lt; 0.001) and suspected DPN (OR = 3.58, 95%Cl: 2.78-4.62; P &amp;lt; 0.001) in T2DM patients after the adjustment for age, BMI and HbA1c. In addition, prolonged application of metformin, increased cumulative and single doses would also be associated with the risk of DPN (P &amp;lt; 0.0for all) . Conclusion: The application of metformin was observed relate to DPN in T2DM patients. The vitamin B12 concentration and peripheral nerve function of T2DM patients with the application of metformin should be monitored. Disclosure Q.Pan: None. J.Luo: None. L.Guo: None. Funding National Key R&amp;D Program of China (2020YFC2009006)

Correlation between the accumulation of skin glycosylation end products and the development of type 2 diabetic peripheral neuropathy

BackgroundThe accumulation of advanced glycation end products (AGEs) occurring in skin tissues can be measured by AGE Reader. Here, we assessed the correlation between AGEs values and the development of type 2 diabetic peripheral neuropathy (DPN).MethodsThe basic clinical information of 560 patients with T2DM was collected through an electronic system. AGEs and diabetic complication risk score was measured by AGE Reader, a non-invasive optical signal detector. All of the participants were classified into 4 groups based on Dyck criteria: grade 0 (non-DPN group), grade 1 (early stage group), grade 2 (middle stage group) and grade 3 (advanced group). Pearson correlation analysis and Spearman correlation analysis were used to evaluate the correlation between AGEs and other indexes. The sensitivity and specificity of glycosylated products were evaluated by ROC curve.ResultsWith the increase of DPN severity, the accumulative AGEs showed an increasing trend. Significant differences (P = 0.000) of AGEs were found among grades 0, 1, 2, and 3 of DPN, and significant differences (P = 0.000) of AGEs were found between grades 1 and 3. There were significant differences in DPN risk score between grades 0, 1, 2, and 3, between grades 1, 2, and 3, and between grades 2 and 3 (P < 0.01 or P < 0.05). AGEs were positively correlated with age, blood uric acid, disease course, systolic blood pressure, the risk scores of the four major complications of diabetes, renal function indicators (serum creatinine, Cystatin C, homocysteine, the ratio of urinary albumin and creatinine, urinary microalbumin, α-microglobulin, urinary transferrin, urinary immunoglobulin), inflammatory indicators (white blood cell count, neutrophil count, neutrophil-to-lymphocyte ratio, C-reactive protein), and TCSS score. However, it was negatively correlated with BMI,fasting insulin, insulin 1–3 h postprandial, lymphocyte count, HOMA insulin resistance index and estimated glomerular filtration rate. The area under the AGEs cumulant and neuropathy risk score curve was 0.769 and 0.743, respectively. The confidence intervals were (71.2–82.6%) and (68.8–79.9%), respectively. The maximum Youden’s index of AGEs cumulant was 0.440, and the corresponding AGEs cumulant value was 77.65. The corresponding sensitivity and specificity were 0.731 and 0.709, respectively. Furthermore, the maximum Youden’s index of neuropathy risk score was 0.385, and the corresponding neuropathy risk score was 66.25. The corresponding sensitivity and the specificity were 0.676 and 0.709, respectively.ConclusionThe cumulative amount of skin AGEs can be used as the diagnostic index and the prediction and evaluation index of DPN severity. Moreover, the diabetic peripheral neuropathy risk score can predict the risk of DPN in patients with T2DM.

Correlation between Acylcarnitine and Peripheral Neuropathy in Type 2 Diabetes Mellitus.

Objective In patients with type 2 diabetes mellitus (T2DM), it is unknown whether acylcarnitine changes in the patient's plasma as diabetic peripheral neuropathy (DPN) occurs. The purpose of the present study was to investigate the correlation between acylcarnitines and DPN in Chinese patients with T2DM. Methods A total of 508 patients admitted to the First Affiliated Hospital of Jinzhou Medical University were included in this study, and all of whom were hospitalized for T2DM from January 2018 to December 2020. The diagnostic criteria for DPN were based on the 2017 Chinese Guidelines for the Prevention of Type 2 Diabetes. The contents of 25 acylcarnitine metabolites in fasting blood were determined by mass spectrometry. The measured acylcarnitines were classified by factor analysis, and the factors were extracted. To determine the correlation between acylcarnitines and DPN, binary logistic regression analysis was applied. Results Among the 508 T2DM patients, 270 had DPN. Six factors were extracted from 25 acylcarnitines, and the cumulative contribution rate of variance was 61.02%. After the adjustment for other potential confounding factors, such as other carnitines and conventional risk factors, Factor 2 was positively associated with an increased risk of DPN (OR: 1.38, 95% CI: 1.13-1.69). Factor 2 contained acetylcarnitine (C2), propionylcarnitine (C3), butylcarnitine (C4), and isovalerylcarnitine (C5). Conclusions Plasma levels of short-chain acylcarnitines (C2, C3, C4, and C5) were positively associated with DPN risk.

Association Between Serum Albumin Levels and Diabetic Peripheral Neuropathy Among Patients with Type 2 Diabetes: Effect Modification of Body Mass Index.

BackgroundThe role of serum albumin in the risk of diabetic peripheral neuropathy (DPN) remains unclear. This study aimed to explore the relationship between serum albumin level and DPN, and to examine any possible effect modifiers among patients with type 2 diabetes mellitus.MethodsThis cross-sectional study was conducted in Jiangxi, China, from May 2012 to December 2014. Serum albumin levels were determined in 523 subjects, and the association between serum albumin level and DPN was evaluated using linear regression models (odds ratio [OR] and corresponding 95% confidence interval [CI]).ResultsThere was a significant inverse association between serum albumin level (per 1 g/L increment, OR 0.95 [95% CI 0.92–0.98]) and the risk of DPN. Accordingly, when serum albumin was assessed as quartiles, a significantly lower risk of DPN was found in participants in quartile 4 (OR 0.49 [95% CI 0.25–0.95]), compared with those in quartile 1. Consistently, higher albumin levels (≥35 g/L) were associated with decreased odds for DPN (OR 0.36 [95% CI 0.17–0.74]) compared with lower levels. Furthermore, the albumin–DPN association was significantly stronger in patients with a relatively high body mass index (BMI; ≥24 kg/m2; OR 0.91 [95% CI 0.85–0.98]) than in those with a low BMI (<24 kg/m2; OR 0.99 [95% CI 0.94–1.04]; P for interaction = 0.042).ConclusionThese data suggest that serum albumin level could be a novel risk factor for DPN among patients with type 2 diabetes and relatively high BMI (>24 kg/m2).

Heart rate-corrected QT interval: A novel diagnostic biomarker for diabetic peripheral neuropathy.

Aims/IntroductionTo explore the relationship between heart rate‐corrected QT (QTc) interval and diabetic peripheral neuropathy (DPN), and whether QTc interval has diagnostic utility for DPN beyond nerve conduction velocity.Materials and MethodsA total of 965 patients with diabetes, including 473 patients with DPN and 492 patients without DPN, underwent standard 12‐lead electrocardiography and detailed assessments of peripheral neuropathy.ResultsPatients with DPN had longer QTc intervals than those without. Among participants, from the first to fourth quartile of QTc interval, the proportion of patients with DPN appreciably increased and the nerve conduction velocity obviously decreased (P for trend <0.001). The univariate and multivariate analyses showed that prolonged QTc interval was closely associated with increased risk of DPN (univariable odds ratio 1.112, 95% confidence interval 1.097–1.127, P < 0.001; multivariable odds ratio 1.118, 95% confidence interval 1.099–1.137, P < 0.001). Receiver operating characteristic analysis for the diagnosis of DPN showed a greater area under the curve for QTc interval of 0.894 than the median nerve motor conduction velocity of 0.691, median nerve sensory conduction velocity of 0.664 and peroneal nerve motor conduction velocity of 0.692. The optimal cut‐off point of QTc interval for DPN was 428.5 ms with sensitivity of 0.715 and specificity of 0.920 (P < 0.001). The combination of QTc interval and nerve conduction testing increased the area under the curve for the diagnosis of DPN (from 0.736 to 0.916; P < 0.001).ConclusionsQTc interval with 428.5 ms has more reliable diagnostic utility for DPN than nerve conduction velocity, and prolonged QTc interval is closely associated with an increased risk of DPN.

Association of Vitamin D Level with Diabetic Peripheral Neuropathy

Background: Diabetes mellitus causes a range of nerve damage referring to diabetic neuropathy. Diabetic neuropathy affects over 132 million individuals worldwide (about 1.9% of the population). Diabetes is the largest recognized cause of neuropathy in affluent countries, and the most prevalent consequence and reason for morbidity and mortality. The deficient vitamin D value is one of the newest considerations of the development of diabetes and peripheral neuropathy. Objective: the objective of this study was to compare vitamin D levels among Type 2 diabetes mellitus patients with/without diabetic peripheral neuropathy and to find an association of Vitamin D levels with diabetic peripheral neuropathy based on the Michigan Neuropathy Screening Instrument (MNSI) score at a tertiary care hospital, Peshawar. Method: A case-control study was conducted from August 2021 to October 2021 after taking approval from the ethical committee of Prime foundation Pakistan, Mercy Teaching Hospital Peshawar. Patients with type 2 diabetes were recruited and then divided into two groups using the purposive sampling technique. Type 2 diabetes with neuropathy included group A Patients (Cases), while type 2 diabetes without neuropathy included group B (Controls). Both groups had 49 study subjects each based on convenience. A physical examination was conducted to prove the diagnosis of diabetic peripheral neuropathy (DPN) using the Michigan Neuropathy Screening Instrument (MNSI). Patients screening positive on the MNSI (&gt;2 points out of a 10-point scale) were considered neuropathic. Serum vitamin D levels were assessed in both patients (cases) and controls using a hospital laboratory and labeled as Vitamin D sufficiency (more than 30ng/ml), Vitamin D deficiency (&lt;20 ng/ml), Higher Vitamin D (100 ng/ml) and vitamin D insufficiency (between 20 and 30 ng/ml). Results: A total of 98 subjects were enrolled in the study with a 1:1 ratio of cases and controls. Median age [57 (IQR 52-65) versus 55 (IQR=48-61), p&lt;0.001] and disease duration [10 (IQR=8-16) versus 7 (IQR=4-10), p&lt;0.001] were significantly different among cases and control. The proportion of patients with normal vitamin D levels was significantly lower in cases than in control (10.2% versus 67.3%, p&lt;0.001). On the multivariable regression model, vitamin D levels were found to be an independent predictor of DPN with a significantly lower risk of DPN among patients with normal vitamin D levels as compared to those who had vitamin d higher than 100 ng/ml (OR=0.19, 95% CI:0.001-0.282, p=0.004). Conclusion: Our study concluded that patients with Type 2 diabetes mellitus DPN have deficient levels of Vitamin D as assessed by Michigan Neuropathy Screening Instrument. Considerable risk of Diabetic peripheral neuropathy among patients having a deficiency of Vitamin D was proved.

Diabetic Peripheral Neuropathy Associated with Cardiovascular Risk Factors and Glucagon-Like Peptide-1 Concentrations Among Newly Diagnosed Patients with Type 2 Diabetes Mellitus

PurposeThis study was aimed at the prevalence, cardiovascular risk factors of diabetic peripheral neuropathy (DPN), and the relationship between DPN and fasting glucagon-like peptide-1 (fGLP-1) concentrations in newly diagnosed patients with type 2 diabetes mellitus (nT2D).MethodsA cross-sectional descriptive study was conducted from 2015 to 2020 with a population of 473 nT2D. Screening for DPN was based on the United Kingdom screening test. fGLP-1 was measured by enzyme-linked immunosorbent assay.ResultsThe prevalence of DPN was 26.6%, in which mild grade was 17.3%, moderate grade was 8.2% and severe grade was 1.1% in total. Age (OR = 1.73, 95% CI 1.12–2.67, p = 0.012), smoking (OR = 1.64, 95% CI 1.03–2.62, p = 0.037), poor control HbA1c (OR = 2.66, 95% CI 1.23–5.76, p = 0.01), 24-h urinary albumin (24hUA) (OR = 2.49, 95% CI 1.26–4.94, p = 0.007), and diabetic retinopathy (OR = 3.17, 95% CI 1.46–6.89, p = 0.002) significantly increased the risk for DPN. In multivariate logistic regression analysis, hypertension (OR = 2.96, 95% CI 1.16–7.55, p = 0.023), triglyceride (OR = 1.50, 95% CI 1.11–2.03, p = 0.009), albumin (OR = 0.85, 95% CI 0.75–0.95, p = 0.005), and fGLP-1 (OR = 0.79, 95% CI 0.67–0.93, p = 0.005) correlated with DPN. The fGLP-1 concentrations were reduced significantly in DPN (p < 0.001). In particular, male patients with DPN had a significantly lower fGLP-1 levels than those without DPN (p < 0.001).ConclusionThe prevalence of DPN among nT2D was 26.6%. Age, smoking, hypertension, HbA1c control, triglyceride, albumin, 24hUA, diabetic retinopathy were the associated risk factors of DPN, and fGLP-1 was negatively correlated with DPN (OR = 0.79, 95% CI 0.67–0.93, p = 0.005).

Risk Factors for Diabetic Peripheral Neuropathy in Adolescents and Young Adults With Type 2 Diabetes: Results From the TODAY Study.

Data related to diabetic neuropathy in youth with type 2 diabetes are limited. We examined the relationship of glycemic control, sex, race/ethnicity, BMI, and other type 2 diabetes-associated factors with the development of diabetic peripheral neuropathy (DPN) in youth with type 2 diabetes enrolled in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study. The Michigan Neuropathy Screening Instrument (MNSI) and a 10-g monofilament exam were performed annually. DPN was defined as a score (>2) on the MNSI-exam or combined MNSI-exam and MNSI-survey scores (exam >2 and/or survey ≥4), or monofilament exam (<8 of 10 correct responses) at two or more consecutive visits. Multivariable time-to-event models assessed the association of risk factors evaluated longitudinally with DPN events. A total of 674 participants (35% male), with a mean age of 14 years and diabetes duration <2 years at study entry, were evaluated annually over an average of 10.2 years. Male subjects had a significantly higher cumulative incidence of DPN than female subjects (38.5% vs. 27.2% via MNSI-exam, P = 0.002; 14.0% vs. 5.1% via monofilament exam, P = 0.01). Rates did not differ by race/ethnicity. Higher HbA1c and BMI were associated with higher DPN, by both MNSI and the monofilament test. In multivariable models, male sex, older age, and higher BMI were associated with MNSI-exam DPN risk. DPN was evident early in the course of youth-onset type 2 diabetes and increased over time. It was higher in male subjects and related to glycemic control. These findings raise concern for long-term development of neuropathy-related morbidity in youth with type 2 diabetes and the need to achieve improved glycemic control.

Decreased Physiological Serum Total Bile Acid Concentrations in Patients with Type 2 Diabetic Peripheral Neuropathy.

PurposeBile acids, amphipathic cholesterol metabolites, have been reported to have cytoprotective and neuroprotective effects in humans and animal models. The relationship of physiological serum total bile acid (TBA) levels with diabetic peripheral neuropathy (DPN), however, has not been determined. The purpose of this study was to investigate the relationship between physiological serum TBA and DPN.Patients and MethodsIn total, 856 patients with type 2 diabetes mellitus (T2DM) aged 20–89 years were enrolled in this cross-sectional study. Serum TBA was measured, and its relationship with DPN and other parameters was analyzed.ResultsT2DM patients with DPN had significantly lower serum TBA compared with those without (P<0.01). Serum TBA was negatively associated with glycated hemoglobin A1C, plateletcrit, fibrinogen, urine albumin-to-creatinine ratio, vibration perception thresholds, and prevalence of DPN, peripheral arterial disease, and diabetic foot ulceration after adjustment for age, sex, and body mass index (P<0.01 or P<0.05). A graded association with prevalence of DPN and increase in serum TBA quartiles was observed (P for trend <0.01), and there was an 48.2% decreased risk of DPN in the highest quartile of serum TBA versus the lowest quartile (95% CI 0.299–0.617; P=0.000) after multivariate adjustment. Receiver-operating characteristic analysis revealed that the optimal cutoff point of serum TBA to indicate DPN was 2.85 μmol/L (sensitivity 77.6% and specificity 45.6%).ConclusionThese findings suggest that lower physiological serum TBA level may be associated with the prevalence of DPN in T2DM patients and may be a potential biomarker for DPN.

An association between fibrinogen gene polymorphisms and diabetic peripheral neuropathy in young patients with type 1 diabetes.

In complex etiopathogenesis of diabetic peripheral neuropathy (DPN), hemostatic dysfunction and subclinical inflammation play a possible role. Fibrinogen is involved in both the hemostatic and inflammatory pathways, so we hypothesize that fibrinogen gene polymorphisms might be associated with DPN. A total of 127 young patients with type 1 diabetes (T1D) (average age, 18.5 ± 4.65years; average diabetes duration, 14.5 ± 2.26years) and 90 healthy controls were enrolled into the study. Basic biochemical and coagulation parameters were measured and gene polymorphisms of fibrinogen alpha (rs6050) and beta (rs1800790) were established. DPN was diagnosed in 38 diabetic patients by neurological examination. AA genotype and Aallele of rs1800790 polymorphism of fibrinogen beta were associated with increased risk of DPN (odds ratio [OR] 4.537, 95% confidence interval [95CI] 1.14-19.94, p = 0.019 and OR 1.958, 95CI 1.038-3.675, p = 0.029, respectively). No association was found between DPN and rs6050 gene polymorphisms. Plasma fibrinogen concentration significantly correlated with HbA1c (Spearman's correlation coefficient [r] = 0.54) and HDL cholesterol (r = -0.67). A allele and AA genotype of rs1800790 seem to be associated with DPN in young patients with T1D. Further studies are appropriate to elucidate the role of fibrinogen gene polymorphisms in the complex etiology of DPN.

Change in Urine Albumin-to-Creatinine Ratio and Risk of Diabetic Peripheral Neuropathy in Type 2 Diabetes: A Retrospective Cohort Study.

PurposeThis study aimed to assess association between change in urine albumin-to-creatinine ratio (UACR) and the risk of diabetic peripheral neuropathy (DPN) in type 2 diabetes mellitus.Patients and MethodsA retrospective study was performed, which included 185 individuals with type 2 diabetes. At baseline, and at two-year follow-up, we collected basic data, recorded symptoms and signs of DPN, measured biochemical indicators, composite motor nerve conduction velocity (composite MCV), and composite sensory nerve conduction velocity (composite SCV).ResultsChanges of composite SCV, MCV and TCSS among different changes in UACR in patients without DPN and with DPN were not significantly different. An increase in UACR ≥30% (OR 3.059, 95%; CI: 1.012–9.249) suggested a risk for new-onset DPN. Based on ROC curve analysis, the areas under the curve were 0.654 ± 0.066 for change of UACR levels in non-DPN patients.ConclusionChange in UACR and NCV was not related in patients without DPN and with DPN; change in UACR ≥30% suggested a risk for new-onset DPN.

Identification of two novel subgroups in patients with diabetes mellitus and their association with clinical outcomes: A two‐step cluster analysis

Aims/IntroductionThe aim of this study was to determine whether distinct subphenotypes of patients with type 2 diabetes in the European classification exist in Chinese populations, and to further establish novel subphenotypes more suitable for Chinese populations.Material and MethodsThe research retrospectively analyzed 5414 patients with type 2 diabetes from the National Clinical Research Center for Metabolic Diseases Diabetes Center in China, and a two‐step cluster analysis was carried out. First, we confirmed the European classification in Chinese populations by six parameters, including age at disease onset, body mass index, glycosylated hemoglobin, homeostatic model assessment 2 to estimate β‐cell function and insulin resistance, and glutamate decarboxylase antibodies. Furthermore, triglycerides and uric acid were added to refine the cluster analysis, and Cox regression was used to evaluate the risk of diabetic complications.ResultsJust three clusters were replicated in our cohort according to Emma Ahlqvist's European classification. When other variables were added to the cluster analysis, seven subgroups were identified, including five clusters of the European classification and two novel subgroups, namely, uric acid‐related diabetes and inheritance‐related diabetes. Compared with patients with inheritance‐related diabetes, patients with severe insulin‐resistant diabetes showed a higher risk of diabetic peripheral neuropathy, hypertension and chronic kidney disease, and the uric acid‐related diabetes subgroup showed a higher risk of coronary heart disease, cerebral vascular disease and end‐stage renal disease. Patients with severe insulin‐deficient diabetes showed a higher risk of diabetic retinopathy and diabetic foot than those with inheritance‐related diabetes. Furthermore, there were sex‐specific associations between subgroups and clinical outcomes. No significant difference was observed in the prevalence of cancer in each subgroup.ConclusionsSeven subgroups of type 2 diabetes were identified in Chinese populations, with distinct characteristics and disparate clinical outcomes. This etiology‐based stratification might contribute to the diagnosis and management of type 2 diabetes.

Relationship of serum vitamin D levels with diabetic microvascular complications in patients with type 2 diabetes mellitus.

Background:Vitamin D deficiency has been reported to be associated with diabetic microvascular complications, but previous studies have only focused on the relationship between vitamin D and specific complications. Therefore, we aimed to explore the relationship between vitamin D level and diabetic microvascular complications in general, including diabetic retinopathy (DR), diabetic nephropathy (DN), and diabetic peripheral neuropathy (DPN).Methods:This was a cross-sectional study of 815 patients with type 2 diabetes mellitus (T2DM). Clinical information and laboratory results were collected from the medical records. The relationship between vitamin D and the three diabetic microvascular complications was investigated.Results:The serum 25-hydroxyvitamin D (25 [OH] D) level of patients with DPN and/or DN was significantly lower than that of T2DM patients without any microvascular complications (P < 0.01). Univariate analysis showed that the 25 (OH) D level was related to DPN and DN, but not DR. After adjustment, the 25 (OH) D level was confirmed to be an independent protective factor for DPN (odds ratio [OR]: 0.968, P = 0.004]) and DN (OR: 0.962, P = 0.006). The prevalence of DPN and DN increased significantly as the serum 25 (OH) D levels decreased. Furthermore, patients with both DPN and DN had the lowest concentration of serum 25 (OH) D (P < 0.001), and the prevalence of macroalbuminuria increased more abruptly than that of microalbuminuria across the 25 (OH) D tertiles. Among the patients with vitamin D insufficiency, those with DPN presented more comorbid macroalbuminuria than those without DPN (15.32% vs. 4.91%; P = 0.001).Conclusions:Vitamin D deficiency is independently associated with higher risk of DPN and DN, but not DR, in T2DM patients. Further, it may be a potential predictor for both the occurrence and severity of DPN and DN.

Proinflammatory Cytokines Predict the Incidence of Diabetic Peripheral Neuropathy Over 5 Years in Chinese Type 2 Diabetes Patients: A Prospective Cohort Study

Aims: Inflammation has been implicated in the pathogenesis of diabetic peripheral neuropathy (DPN) as suggested in various cross-sectional studies. However, more convincing prospective studies in diabetes patients are scarce. Therefore, we aimed to evaluate whether proinflammatory cytokines could predict the incidence of DPN through a prospective study with a five-year follow-up. Methods: We followed up 315 patients with diabetes who did not have DPN, recruited from five community health centers in Shanghai in 2014, for an average of 5.06 years. Based on the integrity of blood samples, 106 patients were selected to obtain the proinflammatory cytokines. Plasma markers of proinflammatory cytokines at baseline included interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), and intercellular adhesion molecule 1 (ICAM-1). Neuropathy was assessed by MSNI at baseline and during follow-up. Results: Among the 106 randomly chosen patients, 63 developed DPN after 5.06±1.14 years of follow-up. The baseline plasma levels of TNF-α, IL-6, and ICAM-1 were higher in the neuropathic group (P<0.05). In multivariate models, increased plasma levels of TNF-α (hazard ratio, HR: 8.74 [95% confidence interval, CI: 1.05-72.68]; p <0.05) and ICAM-1 (HR 23.74 [95% CI 1.47-383.81]; p <0.05) were both associated with incident DPN, after adjusting for known DPN risk factors. Conclusions: Increased plasma levels of proinflammatory factors, especially TNF-α and ICAM-1, predicted the incidence of DPN over 5 years in Chinese diabetes patients, but larger longitudinal studies are required for confirmation. Funding Statement: The present study was supported by grants from the National Natural Science Foundation of China (81770807, to B Lu and 81800692, to LJ Ji), Shanghai Talent Development Fund Program (2018054, to B Lu), Shanghai Shenkang Hospital Developing Center Clinical Scientific and Technological Innovation Program (SHDC12016210, to B Lu), Shanghai Science and Technology Committee Program (17411961500, to S Zhang), Shanghai General Hospital Program of Chinese traditional and Western medicine combination (ZY(2018-2020)-FWTX-1002, to YM Li) and Shanghai Municipal Commission of Health and Family Planning Clinical Research Project (20184Y0318, to LJ Ji). Declaration of Interests: The authors declare that there is no conflict of interest. Ethics Approval Statement: The study was approved by the Human Investigation Ethics Committee of Huashan Hospital.