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Microvascular complications, affecting small blood vessels, can lead to serious conditions such as kidney failure, painful nerve damage, and vision loss. Early detection and effective treatment of these issues are vital for improving patient outcomes and reducing healthcare expenses. Thus, this study aimed to assess diabetic microvascular complications among adults with type 2 diabetes in Adama, central Ethiopia. An institutional-based cross-sectional study was conducted among 381 adult type 2 diabetes patients. A computer-generated simple random sampling method was used to select study participants. Data were collected using a structured data extraction checklist. The collected data were entered into Epi info version 7.2 and exported to SPSS version 27 for processing and analysis. Binary logistic regression was employed to model the association between diabetic microvascular complications and explanatory variables. An adjusted odds ratio (AOR) with a 95% confidence interval (CI) was used to estimate the strength of association, and statistical significance was proclaimed at a p-value < 0.05. The prevalence of diabetic microvascular complications was 21.8% (95% CI: 17.8-25.6) with diabetic neuropathy being the most common (16.8%), followed by diabetic retinopathy (4.2%), and diabetic nephropathy (2.9%). Poor glycemic control (AOR = 2.00, 95% CI: 1.01-3.98), and a history of hypertension (AOR = 2.36, 95% CI: 1.39-4.00) were positively associated with the development of diabetic microvascular complications. Conversely, being aged 41-60 years (AOR = 0.35, 95% CI: 0.18-0.68) was negatively associated with the development of these complications. About one in five patients developed at least one diabetic microvascular complication. Age, poor glycemic control, and a history of hypertension were associated with the development of these complications. Therefore, intervening to improve glycemic control and manage hypertension is crucial in preventing the onset of diabetic microvascular complications., (© 2024. The Author(s).)

Several studies have investigated whether sarcopenia is associated with diabetic microvascular complications, but very few have examined associations between sarcopenia and cardiovascular autonomic neuropathy (CAN) in patients with type 2 diabetes mellitus (T2DM). Therefore, we investigated associations of muscle strength (handgrip strength [HGS]) and mass (appendicular skeletal muscle mass index [ASMI]) and CAN in patients with T2DM. We enrolled 342 patients in this retrospective, cross-sectional study. Cardiovascular reflex tests were used to assess CAN according to Ewing's protocol. Relative HGS was determined after normalizing absolute HGS to body weight (HGS/body weight [kg]). We defined low HGS and low ASMI according to a consensus report of the Asian Group for Sarcopenia. Logistic regression analyses were carried out to assess the associations between relative HGS or ASMI quartiles and the presence of CAN in patients with T2DM. The prevalence rates of CAN, low HGS, and low ASMI in the study subjects were 34.8%, 17.3%, and 18.7%, respectively. Low HGS was significantly more prevalent in patients with CAN than those without CAN (23.5% vs. 13.9%, p = 0.025). The CAN scores were significantly and negatively correlated with relative HGS but not with ASMI. Relative HGS was negative correlated with age, glycated hemoglobin, fasting plasma glucose, hsCRP, body mass index, and HOMA-IR and positively correlated with ASMI. The prevalence of CAN gradually increased with decreasing quartile of relative HGS (28.4% in Q4, 31.8% in Q3, 34.2% in Q2, and 45.3% in Q1, p = 0.02 for trend). Multivariable-adjusted prevalence ratios (PRs) for CAN, determined by comparing the first, second, and third quartiles with the fourth quartile of relative HGS, were 4.4 with a 95% confidence interval (95% CI) of [1.1 to 17.3]), 2.3 (95% CI [0.8 to 6.9]), and 1.2 (95% CI [0.4 to 3.7]), respectively. The prevalence of CAN and the PRs (95% [CI]) for CAN based on ASMI were not statistically significant. Our findings suggest that low muscle strength rather than low muscle mass was significantly associated with the presence of CAN. Therefore, HGS testing could help identify patients who would benefit from screening for earlier diagnosis of CAN., (© 2024. The Author(s).)

Purpose: The main study goal is to assess the relationship between adherence to the mediterranean diet (MD) and the presence of diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes mellitus (T2DM)., Methods: Observational pilot study of 174 patients diagnosed with T2DM. Sociodemographic and anthropometric variables, physical activity, smoking habits, blood biochemical parameters and comorbidities were recorded. The presence of alterations in sensitivity to pressure, pain, thermal and vibration was explored. Good MD adherence was a score  ≥  9 the 14-point MD adherence questionnaire (MEDAS-14)., Results: The study population consisted of 174 patients (61.5% men and 38.5% women), with a mean age of 69.56 ± 8.86 years; 19% of these patients adhered to the MD. The score obtained in the MEDAS-14 was higher in patients who did not present alterations in sensitivity to pressure (p = 0.047) or vibration (p = 0.021). The patients without diabetic peripheral neuropathy were more likely to comply with the MD and had a higher score on the MEDAS-14 (p = 0.047). However, multivariate analysis showed that only altered sensitivity to pressure was associated with adherence to the MD (altered sensitivity OR = 2.9; 95%CI 1.02-8.22; p = 0.045)., Conclusions: Although the patients with DPN had lower scores on the MEDAS questionnaire and therefore poorer adherence to the mediterranean diet, the only parameter significantly associated with the MD was that of sensitivity to pressure (monofilament test)., (© 2024. The Author(s).)

Purpose: To explore variations in systemic and ocular parameters among patients with diabetes, both with and without diabetic peripheral neuropathy (DPN) and to identify sensitive indicators for DPN diagnosis., Methods: Ninty-five patients with type 2 diabetes mellitus (T2DM) were involved in this cross-sectional study, including 49 without DPN and 46 with DPN. Ocular parameters were obtained using optical coherence tomography angiography (OCTA) and corneal confocal microscopy (CCM)., Result: Patients with DPN presented with significantly higher HbA1c (p < 0.05) and glycated albumin (GA, p < 0.01) levels, increased prevalence of diabetic retinopathy (DR, p < 0.05), and lower serum albumin (ALB, p < 0.01) and red blood cell (RBC, p < 0.05) levels. Ocular assessments revealed reduced corneal nerve fiber length (CNFL, p < 0.001) and enlarged foveal avascular zone (FAZ) area (p < 0.05) in DPN group. Logistic regression analysis indicated a significant association of presence of DR, RBC, GA, ALB, CNFL and DPN (p < 0.05, respectively). In the binary logistic regression for DPN risk, all three models including the presence of DR and CNFL exhibited the area under the curve (AUC) exceeding 0.8., Conclusion: The study establishes a strong correlation between ocular parameters and DPN, highlighting CCM's role in early diagnosis. Combining systemic and ocular indicators improves DPN risk assessment and early management., (© 2024. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Background: Oxidative stress is a risk factor for distal sensorimotor polyneuropathy (DSPN). Selenoprotein P is a protein with antioxidant properties but has not been investigated in the context of DSPN. This study aimed to assess the associations between selenoprotein P and DSPN in people without and with type 2 diabetes (T2D)., Methods: Cross-sectional and prospective analyses were based on 1053 (including 217 with T2D) and 513 participants (including 79 with T2D), respectively, aged 61-82 years from the population-based KORA F4 survey. DSPN at baseline (KORA F4) and in the follow-up survey KORA FF4 was defined based on the Michigan Neuropathy Screening Instrument. Serum levels of full-length selenoprotein P were quantified by ELISA. Associations between selenoprotein P and prevalent or incident DSPN were estimated using logistic regression analysis adjusting for multiple confounders., Results: Selenoprotein P levels were not associated with prevalent DSPN in the total sample. However, there was a significant interaction by diabetes status. Higher levels of selenoprotein P were associated with lower odds of prevalent DSPN in individuals without T2D (fully adjusted model: OR 0.825 [95 % CI 0.682, 0.998], p = 0.0476), but not in those with T2D (OR [95 % CI] 1.098 [0.829, 1.454], p = 0.5132; p interaction  = 0.0488). Selenoprotein P levels were not associated with incident DSPN over a follow-up of 6.5 years., Conclusion: In individuals without T2D from the older general population, lower selenoprotein P levels were associated with a higher prevalence of DSPN. Whether the antioxidant properties of selenoprotein P are responsible for the observed associations remains to be elucidated in future research., Competing Interests: Declaration of competing interest All authors declare that there are no conflicts of interest in connection with this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Diabetes mellitus (DM) is associated with increased risk of morbidity and premature mortality due to its various complications. In an Indian study, the prevalence of diabetic peripheral neuropathy (DPN) in type 2 diabetic subjects was shown to be 29.2%. There is increasing evidence that a deficiency of nerve growth factor (NGF) in diabetes, as well as the calcitonin gene-related peptide (CGRP), may also contribute to the development of DPN. The aim of the current study was to evaluate nerve growth factor levels with neuropathy in type 2 DM., Materials and Methods: Forty healthy controls and 40 patients with type 2 DM were recruited; they were asked to report to Dept. of Physiology for initial history taking, general examination and neuropathy examination. A total of 5 mL of blood was collected for neurotrophic factor estimation as well as glycemic profile estimation., Results: The brain-derived neurotrophic factor (BDNF) values were significantly lower in the DM group whereas the insulin levels were also quite high in DM. The hot thresholds for both the upper limb and lower limb were greater in the DM group suggesting the impending neuropathy. Similarly, the Michigan scores were also greater in the DM group. The neuropathy parameters especially the Michigan A and B and the hot thresholds were positively correlated with duration of DM and glucose profile., Conclusion: The neurotrophic factors especially BDNF are drastically reduced in DM patients and are negatively associated with neuropathy, and hence, BDNF can be utilized as a therapeutic target to treat and prevent neuropathy., (© 2024. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Hyperglycemia in type 2 diabetes leads to diabetic peripheral neuropathy (DPN) and neuropathic pain, yet the association between glycemic variability and painful DPN remains insufficiently evidenced. To address this, we conducted a prospective longitudinal cohort study involving adult type 2 diabetes patients at a medical center. DPN was identified using the Michigan Neuropathy Screening Instrument (MNSI), and neuropathic pain was assessed with the Taiwan version of the Douleur Neuropathique 4 (DN4-T) questionnaire. At baseline in 2013, all participants were free of DPN and were re-evaluated in 2019 for the development of painful DPN. We measured visit-to-visit glycemic fluctuations using the coefficient of variation (CV) of fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c). Patients were stratified into tertiles according to their FPG-CV and HbA1c-CV. Among the 622 participants, 267 developed DPN during the six-year follow-up. Following matching of age and sex, 210 patients without DPN and 210 with DPN (including 26 with neuropathic pain) were identified. Our findings revealed a significant association between high FPG-CV and painful DPN, with the highest tertile showing an adjusted odds ratio of 2.82 (95% confidence interval 1.04-7.64) compared to the lowest tertile. On the contrary, HbA1c-CV did not show a significant association with the risk of painful DPN. Our study indicates that higher FPG-CV is associated with an increased risk of painful DPN, supporting the role of glycemic variability in the development of painful DPN., (© 2024. The Author(s).)

Background: Cardiovascular autonomic neuropathy (CAN) is known to affect patients with diabetes mellitus (DM) and cause adverse renal outcomes. We aimed to analyze the association between CAN and diabetic kidney disease (DKD)., Method: We enrolled 254 DM patients (mean age, 56.7 ± 15.2 years; male: female ratio, 1.17:1) with 19 (7.5%) type 1 DM patients and 235 (92.5%) type 2 DM patients. All patients had undergone cardiovascular autonomic function tests between January 2019 and December 2021 in a tertiary hospital in Korea. Cardiovascular autonomic neuropathy was categorized as normal, early, or definite after measuring three heart rate variability parameters. Diabetic kidney disease refers to a persistently elevated urinary albumin-creatinine ratio (uACR ≥30 mg/g) or reduced estimated glomerular filtration rate (eGFR <60 mL/min/1.73 m 2 ). Logistic and Cox regression analyses were performed., Results: Patients with elevated uACR (n=107) and reduced eGFR (n=32) had a higher rate of definite CAN. After adjusting for covariates, definite CAN was associated with elevated uACR (OR=2.4, 95% CI 1.07-5.36) but not with reduced eGFR (OR=3.43, 95% CI 0.62-18.90). A total of 94 patients repeated uACR measurements within 2 years (mean follow-up, 586.3 ± 116.8 days). Both definite and early CAN were independent risk factors for elevated uACR (HR=8.61 and 8.35, respectively; both p <0.05). In addition, high-density lipoprotein cholesterol, ACE inhibitors/angiotensin receptor blockers and glucagon-like peptide-1 receptor agonists were independent protective factors for elevated uACR (HR=0.96, 0.25, and 0.07, respectively; all p <0.05)., Conclusion: Cardiovascular autonomic neuropathy is a potential indicator of DKD. Comprehensive management of DKD in the early stages of CAN may prevent microalbuminuria., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cho, Lim, Kwon, Chung, Moon, Yoon and Won.)

Aims/introduction: To investigate risk factors for diabetic peripheral neuropathy (DPN) and to explore the connection between insulin-like growth factor-1 (IGF-1) and DPN in individuals with type 2 diabetes., Materials and Methods: A total of 790 patients with type 2 diabetes participated in a cross-sectional study, divided into two groups: those with DPN (DPN) and those without DPN (non-DPN). Blood samples were taken to measure IGF-1 levels and other biochemical markers. Participants underwent nerve conduction studies and quantitative sensory testing., Results: Patients with DPN exhibited significantly lower levels of IGF-1 compared with non-DPN patients (P < 0.001). IGF-1 was positively correlated with the average amplitude of both motor (P < 0.05) and sensory nerves (P < 0.05), but negatively correlated with the vibration perception threshold (P < 0.05). No significant difference was observed between IGF-1 and nerve conduction velocity (P > 0.05), or the temperature detection threshold (P > 0.05). Multivariate regression analysis identified diabetes duration, HbA 1c , and the low levels of IGF-1 as independent risk factors (P < 0.001). Receiver operating characteristic analysis determined that at 8 years duration of diabetes, 8.5% (69.4 mmol/mol) HbA 1c and 120 ng/mL IGF-1, the optimal cut-off points, indicated DPN (P < 0.001)., Conclusions: A reduction of IGF-1 in patients with DPN suggests a potential protective role against axon injury in large fiber nerves of type 2 diabetes patients., (© 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background: Previous studies have shown that increasing body mass index (BMI) was associated with decreased hypoglycemia in type 2 diabetes, but it remains uncertain whether this finding could be applied to patients with and without cardiac autonomic neuropathy (CAN)., Methods: The study included 7789 participants with type 2 diabetes from action to control cardiovascular risk in diabetes (ACCORD) trail. CAN was defined as SDNN < 8.2 ms and RMSSD < 8.0 ms. Obesity was defined as BMI ≥ 30 kg/m 2 . Outcomes were identified as severe hypoglycemia requiring any assistance (HAA) or requiring medical assistance (HMA). We assessed the association between obesity and severe hypoglycemia in type 2 diabetes with or without CAN using COX regression models adjusted for baseline characteristics., Results: Over a median follow-up of 4.7 years, a total of 893 participants developed HAA and 584 participants developed HMA. Compared with non-obesity, obesity was associated with lower risk of severe hypoglycemia (HAA: hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.38-0.68, P < 0.001; HMA: HR 0.57, 95% CI 0.40-0.82, P = 0.002) in CAN present group, but not in CAN absent group (HAA: HR 0.98, 95% CI 0.83-1.16, P = 0.830; HMA: HR 0.97, 95% CI 0.79-1.19, P = 0.754). Similarly, increasing BMI was associated with reduced severe hypoglycemic events in participants with CAN, but not in participants without CAN., Conclusions: CAN modifies the association between obesity and hypoglycemia in type 2 diabetes. Type 2 diabetic individuals with CAN who are under weight control should pay attention to hypoglycemic events., Trial Registry: http://www., Clinicaltrials: gov . Unique identifier: NCT00000620., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Bariatric surgery leads to considerable weight loss and improved glycaemic control and seems to have a favourable impact on diabetes related foot complications (DFC)., Objectives: To assess the effect of bariatric surgery on diabetes related foot complications in patients with type 2 diabetes and determine whether DFC symptoms are improved after bariatric surgery., Methods: We searched MEDLINE, Embase and Cochrane Central Register of Controlled Trials. The primary outcome was the presence of DFC after bariatric surgery. The secondary outcome was the improvement of DFC after bariatric surgery among patients who already had DFC before surgery., Results: There were nine studies showing the presence of DFC post bariatric surgery and six detailing the changes in DFC post bariatric surgery. Bariatric surgery was not associated with a lower risk of developing or worsening DFC compared to conventional medical treatment based on 4 randomised control trials (IR 0.87, 95 % CI, 0.26, 2.98), while from observational studies was associated with 51 % lower risk of DFC (IR 0.49, 95 % CI, 0.31, 0.77). Bariatric surgery was associated with improvement in diabetic neuropathy assessment parameters including toe tuning fork score, self-reported neuropathy symptoms, neuropathy symptom score, and neuropathy symptom profile., Conclusion: Bariatric surgery led to a greater reduction in developing or worsening DFC among patients with type 2 diabetes compared to medical treatment in observational studies, but not among RCTs. Bariatric surgery was associated with improvements in diabetic neuropathy related assessment parameters and symptoms. Bariatric surgery could be a promising treatment for patients with type 2 diabetes who are at high risk of DFC., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: To evaluate the determinants of orthostatic hypotension (OH) in type 2 diabetes (T2D) and the usefulness of Δheart rate (HR)/Δsystolic blood pressure (SBP), index of cardiac baroreflex function, in identifying neurogenic OH., Methods: In 208 participants with T2D, we diagnosed early cardiovascular autonomic neuropathy (CAN) and confirmed CAN according to 1 and 2 HR-based cardiovascular reflex tests (HR-CARTs). Through OH test we defined OH as SBP falls of ≥20 and ≥30 mm Hg with supine SBPs of <140 and ≥140 mm Hg, respectively. In participants with OH, we used the lying-to-standing and OH test and its diagnostic accuracy for neurogenic OH (as OH plus confirmed HR-CAN)., Results: OH was present in 25 participants and associated with lower HR-CART scores, higher glycosylated hemoglobin level, the presence of CAN, retinopathy, and peripheral vascular disease, the absence of hypertension, and physical activity (all, P < .05) but not with interfering drugs and β-blockers. In a multiple logistic regression, HR-CAN was the main determinant of OH (odds ratio, 4.74) with physical activity and hypertension (odds ratios, 0.16 and 0.23; R 2  = 0.22). ΔHR/ΔSBP had a good diagnostic accuracy for neurogenic OH (area under the receiver operating characteristic curve, 0.816 ± 0.087) and, at the cutoff of 0.5 bpm/mm Hg, a sensitivity of 100% and specificity of 63.2%., Conclusion: CAN remains the primary determinant of OH in T2D but does not explain all its variance. The index ΔHR/ΔSBP may represent a useful clinical tool to identify neurogenic OH., Competing Interests: Disclosure The authors have no conflicts of interest to disclose., (Copyright © 2024 AACE. Published by Elsevier Inc. All rights reserved.)

Previous studies have revealed that thyroid hormone (TH) levels are associated with the risk of diabetic peripheral neuropathy (DPN) in euthyroid patients with type 2 diabetes mellitus (T2DM). However, the relationship between TH sensitivity, a complementary method for assessing thyroid function, and DPN remains unclear. This study aimed to investigate the correlation between DPN and TH sensitivity in euthyroid patients with T2DM. Exactly 708 euthyroid adults with T2DM were retrospectively enrolled. The FT3/FT4 ratio was used to estimate peripheral TH sensitivity. Central TH sensitivity was assessed using the Thyrotroph T4 Resistance Index (TT4RI), Thyroid-Stimulating Hormone Index (TSHI), Thyroid Feedback Quantile-based Index (TFQI), and Parametric TFQI (PTFQI). DPN was assessed using neurologic symptoms, signs, and nerve conduction velocity tests. The relationship between DPN and TH sensitivity was examined using logistic regression analysis. We observed that an elevated FT3/FT4 ratio was associated with DPN (OR = 1.36, 95%CI: 1.13-1.63, p = 0.0012). For each standard deviation (SD) increase in the TT4RI, TSHI, TFQI, and PTFQI, the OR of DPN was 0.80 (95%CI: 0.68-0.94, p = 0.0078), 0.72 (95%CI: 0.60-0.86, p = 0.0002), 0.69 (95%CI: 0.58-0.83, p < 0.0001), and 0.69 (95%CI: 0.58-0.82, p < 0.0001), respectively. These results suggested that reduced central and peripheral TH sensitivity is associated with a decreased risk of developing DPN., (© 2024. The Author(s).)

Background: Observational studies and clinical trials have implicated polyunsaturated fatty acids (PUFAs) in potentially safeguarding against diabetic microvascular complication. Nonetheless, the causal nature of these relationships remains ambiguous due to conflicting findings across studies. This research employs Mendelian randomization (MR) to assess the causal impact of PUFAs on diabetic microvascular complications., Methods: We identified instrumental variables for PUFAs, specifically omega-3 and omega-6 fatty acids, using the UK Biobank data. Outcome data regarding diabetic microvascular complications were sourced from the FinnGen Study. Our analysis covered microvascular outcomes in both type 1 and type 2 diabetes, namely diabetic neuropathy (DN), diabetic retinopathy (DR), and diabetic kidney disease (DKD). An inverse MR analysis was conducted to examine the effect of diabetic microvascular complications on PUFAs. Sensitivity analyses were performed to validate the robustness of the results. Finally, a multivariable MR (MVMR) analysis was conducted to determine whether PUFAs have a direct influence on diabetic microvascular complications., Results: The study indicates that elevated levels of genetically predicted omega-6 fatty acids substantially reduce the risk of DN in type 2 diabetes (odds ratio (OR): 0.62, 95% confidence interval (CI): 0.47-0.82, p = 0.001). A protective effect against DR in type 2 diabetes is also suggested (OR: 0.75, 95% CI: 0.62-0.92, p = 0.005). MVMR analysis confirmed the stability of these results after adjusting for potential confounding factors. No significant effects of omega-6 fatty acids were observed on DKD in type 2 diabetes or on any complications in type 1 diabetes. By contrast, omega-3 fatty acids showed no significant causal links with any of the diabetic microvascular complications assessed., Conclusions: Our MR analysis reveals a causal link between omega-6 fatty acids and certain diabetic microvascular complications in type 2 diabetes, potentially providing novel insights for further mechanistic and clinical investigations into diabetic microvascular complications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Liu, Gu, Shen, Zhou and Luo.)

Objectives: To determine how plasma fibrinogen levels impact the severity of microvascular complications in people with type 2 diabetes while focussing on the molecular mechanisms of fibrinogen's role in such complications., Methods: The analytical, cross-sectional study was conducted from September 2022 to March 2023 at the Department of Medicine, Mardan Medical Complex and Teaching Hospital, Khyber Pakhtunkhwa, Pakistan, and comprised adult patients of either gender who had been diagnosed with type 2 diabetes and microvascular complications. Each patient was subjected to an evaluation of microvascular complications, including diabetic retinopathy, nephropathy and neuropathy, using validated diagnostic criteria and clinical examinations. Data was analysed using SPSS 26., Results: Of the 174 patients 97(%) were males and 77(%) were females. Retinopathy was found in 57(32.7) patients with median age 53 years (interquartile range: 46-63 years). Nephropathy was found in 55(31.6%) subjects with median age 54 years (interquartile range: 50-61 years). Neuropathy was found in 62(35.6%) patients with median age 53 years (interquartile range: 48-58 years). Diabetic neuropathy was significantly associated with elevated plasma fibrinogen levels and various biomarkers, such as creatinine, urea, fasting blood glucose, glycated haemoglobin and estimated average glucose (p<0.05). Diabetic retinopathy was significantly linked with higher levels of fibrinogen, which manifested through symptoms, like floaters or dark spots, impaired colour vision, difficulty seeing at night, blurred or fluctuating vision and vision loss (p<0.05). Diabetic nephropathy and the progression of its severity was significantly associated with increased fibrinogen levels, as well as markers, like albuminuria, creatinine, urea, fasting blood glucose, glycated haemoglobin and estimated average glucose (p<0.05)., Conclusions: Elevated plasma fibrinogen levels in patients with type 2 diabetes significantly correlated with increased microvascular complications, underscoring the importance of monitoring and managing fibrinogen levels to mitigate diabetes-associated vascular pathologies.

Background and Study Aims: Nonalcoholic fatty liver disease is the most prevalent chronic liver disease globally and is linked to augmented susceptibility to type 2 diabetes mellitus (DM), cardiovascular disease, and microvascular complications inherent to DM, such as nephropathy, neuropathy, and retinopathy. The fibrosis-4 (FIB-4) scoring system, a noninvasive tool, is useful for predicting the extent of liver fibrosis across diverse pathologies. This study aimed to assess the potential predictive role of FIB-4 scores in microvascular complications associated with diabetes., Patients and Methods: The medical records of patients with type 2 DM admitted to our endocrinology clinic between February 2019 and December 2020 were retrospectively evaluated. Parameters including demographic attributes, fasting blood glucose, glycated hemoglobin, aspartate aminotransferase, alanine aminotransferase, thrombocyte levels, and microvascular complications were recorded. The FIB-4 score was computed, and patients were categorized based on these scores (<1.3 and ≥ 1.3)., Results: The analysis included 312 patients with a median age of 60 (50-68 years); 39.7 % were men. The median duration of diabetes was 10 years (5-20 years), and the median FIB-4 score was 0.93 (0.63-1.34). Neuropathy, nephropathy, and retinopathy were observed in 50.6 %, 31.4 %, and 34 % of the patients, respectively. Although the FIB-4 score did not differ significantly between patients with and without neuropathy or retinopathy, patients with nephropathy exhibited higher FIB-4 scores. Notably, patients with FIB-4 scores ≥ 1.3 demonstrated a significantly higher prevalence of nephropathy. Logistic regression analysis demonstrated that higher FIB-4 scores were significantly associated with an increased risk of nephropathy., Conclusion: The FIB-4 score is a cost-effective and straightforward tool with potential applicability in predicting nephropathy in individuals with type 2 DM., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.)

Currently, there are more than 10 million patients with diabetes mellitus in Japan. Therefore, the need to explore the pathogenesis of diabetes and the complications leading to its cure is becoming increasingly urgent. Pathological examination of pancreatic tissues from patients with type 2 diabetes reveals a decrease in the volume of beta cells because of a combination of various stresses. In human type 2 diabetes, islet amyloid deposition is a unique pathological change characterized by proinflammatory macrophage (M1) infiltration into the islets. The pathological changes in the pancreas with islet amyloid were different according to clinical factors, which suggests that type 2 diabetes can be further subclassified based on islet pathology. On the other hand, diabetic peripheral neuropathy is the most frequent diabetic complication. In early diabetic peripheral neuropathy, M1 infiltration in the sciatic nerve evokes oxidative stress or attenuates retrograde axonal transport, as clearly demonstrated by in vitro live imaging. Furthermore, islet parasympathetic nerve density and beta cell volume were inversely correlated in type 2 diabetic Goto-Kakizaki rats, suggesting that diabetic peripheral neuropathy itself may contribute to the decrease in beta cell volume. These findings suggest that the pathogenesis of diabetes mellitus and diabetic peripheral neuropathy may be interrelated., (© 2024 The Author(s). Pathology International published by Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

Aims/introduction: Deficiency of neurotropic factors is implicated in diabetic neuropathy (DN). Netrin-1 is a neurotropic factor, but its association with DN has not been explored. We have assessed the association between serum netrin-1 levels and early diabetic neuropathy assessed by quantifying corneal nerve fiber loss using corneal confocal microscopy., Materials and Methods: A total of 72 participants with type 2 diabetes, without and with corneal nerve fiber loss (DN- n = 42, DN+ n = 30), and 45 healthy controls were studied. Serum netrin-1 levels were measured by enzyme-linked immunosorbent assay, and corneal nerve morphology was assessed using corneal confocal microscopy., Results: Corneal nerve fiber density, branch density, fiber length and serum netrin-1 levels were significantly lower in the DN- and DN+ groups compared with controls (P < 0.001). Netrin-1 levels correlated with corneal nerve fiber length in the DN+ group (r = 0.51; P < 0.01). A receiver operating characteristic curve analysis showed that a netrin-1 cut-off value of 599.6 (pg/mL) had an area under the curve of 0.85, with a sensitivity of 76% and specificity of 74% (P < 0.001; 95% confidence interval 0.76-0.94) for differentiating patients with and without corneal nerve loss., Conclusions: Serum netrin-1 levels show a progressive decline with increasing severity of small nerve fiber damage in patients with diabetes. Netrin-1 could act as a biomarker for small nerve fiber damage in DN., (© 2024 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Purpose: Few studies have investigated the association between smoking and microvascular complications in the Asian population with type 2 diabetes mellitus (T2DM). We aimed to investigate the relationship between smoking status and microvascular complications in Korean patients with T2DM., Materials and Methods: From the Korean National Diabetes Program cohort, we included 2316 Korean male with T2DM who had baseline clinical information available, including their smoking status, and underwent diabetic complication studies., Results: Compared to non-smokers, current smokers had higher odds of any-microvascular complications [adjusted odds ratio (aOR) 1.45, 95% confidence interval (CI) 1.07-1.97, p =0.016]. The odds of neuropathy were significantly higher; however, the odds of retinopathy were significantly lower in current smokers than in nonsmokers (all p <0.05). Among those who underwent repeated complication tests after 3 years, the risk of newly developed retinopathy was significantly increased in ex-smokers [aOR 3.77 (95% CI 1.61-8.87), p =0.002]. Within ex-smokers, long smoking duration and smoking cessation within the recent 5 years were associated with an increased risk of newly developed retinopathy (all p <0.05)., Conclusion: Male smokers had higher odds of having overall diabetic microvascular complications, including neuropathy. However, the odds of having retinopathy were significantly lower among current smokers. More attention and research are needed regarding the increased risk of retinopathy development in ex-smokers who have recently stopped smoking after a long history of smoking., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2024.)

Background: The white blood cell count to mean platelet volume ratio (WMR) is considered a promising inflammatory marker, and its recognition is increasing. Inflammation is closely related to metabolic diseases such as diabetes and its complications. However, there are currently no reports on the correlation between WMR and type 2 diabetic peripheral neuropathy (DPN). This study aims to explore the correlation between WMR and DPN in type 2 diabetes patients. By understanding this association, we hope to provide a theoretical basis for preventing DPN through the improvement of inflammatory responses., Methods: This was a cross-sectional study involving 2515 patients with T2DM. Logistic regression analysis was conducted to assess the associations between WMR and DPN. Finally, the receiver operating characteristic curve (ROC curve) was employed to evaluate the predictive efficacy of WMR for DPN., Results: Patients in higher WMR quartiles exhibited increased presence of DPN. Additionally, WMR remained significantly associated with a higher odds ratio (OR) of DPN (OR 4.777, 95% confidence interval [CI] 1.296-17.610, P < 0.05) after multivariate adjustment. Moreover, receiver operating characteristic curve analysis indicated that the optimal cutoff value for WMR in predicting DPN presence was 0.5395 (sensitivity: 65.40%; specificity: 41.80%; and area under the curve [AUC]: 0.540)., Conclusions: In patients with T2DM, WMR was significantly increased in DPN and independently associated with an increased risk of DPN presence in Chinese patients. This suggests that WMR may serve as a useful and reliable biomarker of DPN, highlighting the importance of paying more attention to T2DM patients with high WMR to further prevent and reduce the development of DPN and related unfavorable health outcomes., (© 2024. The Author(s).)

Background: Diabetic peripheral neuropathy (DPN) is the most dominant cause of neuropathy worldwide, and there has been no specific treatment until now. The aim of the current study was to assess the probable protective effect of empagliflozin in type 2 diabetics who are suffering from DPN., Methods: Fifty eligible type 2 diabetes mellitus (T2DM) cases with diabetic peripheral neuropathy were recruited in this study and classified into 2 groups. Group I (n=25) (control group) received placebo tablets once daily. Group II (n=25) (empagliflozin group) received empagliflozin 25mg once daily for three months. Empagliflozin efficacy was evaluated using electrophysiological studies, and HbA1c levels, the brief pain inventory short-form item (BPI-SF) score, the diabetic neuropathy symptom (DNS) score, the atherosclerotic cardiovascular disease (ASCVD) risk score, and the serum levels of neuron-specific enolase (NSE), malondialdehyde (MDA) and calprotectin (Calpro), lipid profile, and random blood glucose level (RBG)., Results: After three months, comparing the results of the empagliflozin arm to the control arm showed a significant improvement in the electrophysiological studies and a significant decrease in the BPI-SF score and the mean serum levels of NSE and MDA. However, no significant difference was determined in HbA1c, Calpro, lipid profile, and RBG levels. In addition, the DNS and ASCVD risk scores were not significantly different. The NSE and MDA levels were significantly negatively correlated with the electrophysiological parameters. However, the BPI-SF score showed a non-significant difference., Conclusions: Empagliflozin may be a promising neuroprotective and therapeutic agent for diabetic peripheral neuropathy. Trial registration Identifier: NCT05977465., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)

The prevalence of overactive bladder (OAB) is known to be higher in patients with type 2 diabetes (T2DM). However, few studies have examined specific risk factors contributing to its progression among diabetes mellitus (DM) patients, so this study aimed to investigate the risk factors specific to diabetes mellitus that influence overactive bladder in the Syrian population. This cross-sectional study was conducted at four endocrinology centers in four Syrian provinces: Damascus, Aleppo, Homs, Hama, and Latakia. The study was comprised of patients who had been diagnosed with both T2DM and OAB and had visited these centers from February 2020 to January 2023. The Arabic version of the Overactive Bladder Symptom Score (OABSS) scale was used to categorize the participants based on the severity score into two groups: the mild OAB group and the moderate-severe OAB group. A logistic analysis was conducted to assess the risk factors associated with the OAB among patients with diabetes. Among the 153 patients diagnosed with both DM and OAB, significant distinctions were found between the two groups concerning the severity of overactive bladder, age, duration of diabetes, symptomatic diabetic peripheral neuropathy (DPN), and ankle reflex (P < 0.05). Furthermore, a multivariate analysis revealed that age (OR 1.48, 95% CI 0.89-2.19), duration of diabetes (OR 1.94, 95% CI 0.53-2.23), and symptomatic DPN (OR 2.74, 95% CI 1.39-4.13) independently acted as risk factors for the advancement of OAB. The severity of OAB in Syrian patients with diabetes is closely associated with the severity of DM. Factors such as age, duration of diabetes, and symptomatic DPN are independent predictors of the severity of OAB. Patients who experience symptomatic DPN are at an increased risk of developing OAB., (© 2024. The Author(s).)

Background: The evidence supporting a connection between elevated serum uric acid (SUA) levels and diabetic peripheral neuropathy (DPN) is controversial. The present study performed a comprehensive evaluation of this correlation by conducting a systematic review and meta-analysis of relevant research., Method: PubMed, Web of Science (WOS), Embase, and the Cochrane Library were searched for published literature from the establishment of each database to January 8, 2024. In total, 5 cohort studies and 15 cross-sectional studies were included, and 2 researchers independently screened and extracted relevant data. R 4.3.0 was used to evaluate the included literature. The present meta-analysis evaluated the relationship between SUA levels and the risk of DPN in type 2 diabetes (T2DM) by calculating the ratio of means (RoM) and 95% confidence intervals (CIs) using the method reported by JO Friedrich, and it also analyzed continuous outcome measures using standardized mean differences (SMDs) and 95% CIs to compare SUA levels between DPN and non-DPN groups. Funnel plot and Egger's test were used to assess publication bias. Sensitivity analysis was conducted by sequentially removing each study one-by-one., Results: The meta-analysis included 20 studies, with 12,952 T2DM patients with DPN and 16,246 T2DM patients without DPN. There was a significant correlation between SUA levels and the risk of developing DPN [odds ratio (OR) = 1.23; 95% CI: 1.07-1.41; p = 0.001]. Additionally, individuals with DPN had higher levels of SUA compared to those without DPN (SMD = 0.4; 95% CI: -0.11-0.91; p < 0.01)., Conclusion: T2DM patients with DPN have significantly elevated SUA levels, which correlate with a heightened risk of peripheral neuropathy. Hyperuricemia (HUA) may be a risk indicator for assessing the risk of developing DPN in T2DM patients., Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42024500373., Competing Interests: Author JG was employed by the company Amazon. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Zhang, Li, Zhao, Wei, Shi, Yang, Fan, Zhao, Zhu, Du, Guo and Cao.)

Background: Microvascular complications are long-term complications that affect small blood vessels, usually developed in diabetes, and are primary causes of end-stage renal disease, several painful neuropathies, and blindness. Thus, this study aimed to determine diabetic microvascular complications and factors associated with them among patients with type 2 diabetes., Methods: An institution-based cross-sectional study was conducted among 378 type 2 diabetes patients. The presence of at least one diabetic microvascular complications diagnosed by physicians and found on the record was considered to have microvascular complications. The data was collected by reviewing the medical records of T2DM patients who were on follow-up from January 1, 2012, to December 31, 2021. The collected data was entered into EpiData version 3.1 and analyzed by Stata version 14. Bivariate and multivariable logistic regression were used to identify statistically significant risk factors for diabetic microvascular complications at p-value < 0.05., Results: Patients with type 2 diabetes mellitus had a prevalence of diabetic microvascular complications of 26.5% (95% CI: 22.0%, 30.9%). Diabetic neuropathy was the highest (13.2%), followed by diabetic nephropathy (12.4%), and diabetic retinopathy (6.4%). Increasing age, poor glycemic control, hypertension comorbidity, anemia, positive proteinuria, a longer duration of type 2 diabetes mellitus, and hypercholesterolemia were significantly associated factors with diabetic microvascular complications., Conclusion: Diabetic microvascular complications were highly prevalent. Therefore, the study suggests that interventional strategies should be taken for poor glycemic control, hypertension comorbidity, anemia, positive proteinuria, and hypercholesterolemia to control the development of diabetic microvascular complications in patients with type 2 diabetes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Merid, Getahun, Esubalew and Gezahegn.)

Distal sensorimotor polyneuropathy (DSPN) is the earliest detectable and the most frequent microvascular complication in diabetes mellitus. Several studies have previously demonstrated correlations between cardiovascular risk factors in diabetic patients and independent risk factors for diabetic neuropathy. Our objective was to retrospectively analyze data from diabetic patients in the North-East region of Hungary who underwent neuropathy screening at the Diabetic Neuropathy Center, University of Debrecen, between 2017 and 2021. We aimed to investigate the correlations between cardiovascular risk factors and microvascular complications among patients with DSPN. The median age of the patients was 67 years, 59,6% were female, and 91,1% had type 2 diabetes. The prevalence of DSPN among the study subjects was 71.7%. A significantly longer duration of diabetes (p<0.01) was noted in patients with DSPN. Those with DSPN demonstrated a significantly higher HbA1c level (p<0.001) and a greater frequency of insulin use (p = 0.001). We observed a significantly elevated albumin/creatinine ratio (p<0.001) and a significantly lower eGFR (p<0.001) in patients with DSPN. Diabetic retinopathy exhibited a significantly higher prevalence in patients with DSPN (p<0.001). A higher prevalence of myocardial infarction (p<0.05), ischemic heart disease (p<0.001), peripheral arterial disease (p<0.05) and a history of atherosclerosis (p<0.05) was observed in patients with DSPN. In a multivariate logistic regression analysis, the following factors were independently associated with the presence of DSPN: higher HbA1c (OR:2.58, 95% CI:1.89-3.52, p<0.001), age (OR:1.03, 95% CI:1.01-1.05, p = 0.006), albumin/creatinine ratio above 3 mg/mmol (OR:1.23, 95% CI:1.06-1.45, p = 0.008), retinopathy (OR:6.06, 95% CI:1.33-27.53, p = 0.02), and composite cardiovascular endpoint (OR:1.95, 95% CI:1.19-3.19, p = 0.008). Our study revealed that age, elevated HbA1c levels, significant albuminuria, retinopathy, and cardiovascular complications may increase the risk of DSPN. Further investigation of these associations is necessary to understand the impact of patient characteristics during the treatment of diabetic neuropathy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Pető et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aims: We recently reported that genetic variability in the TKT gene encoding transketolase, a key enzyme in the pentose phosphate pathway, is associated with measures of diabetic sensorimotor polyneuropathy (DSPN) in recent-onset diabetes. Here, we aimed to substantiate these findings in a population-based KORA F4 study., Materials and Methods: In this cross-sectional study, we assessed seven single nucleotide polymorphisms (SNPs) in the transketolase gene in 952 participants from the KORA F4 study with normal glucose tolerance (NGT; n = 394), prediabetes (n = 411), and type 2 diabetes (n = 147). DSPN was defined by the examination part of the Michigan Neuropathy Screening Instrument (MNSI) using the original MNSI > 2 cut-off and two alternative versions extended by touch/pressure perception (TPP) (MNSI > 3) and by TPP plus cold perception (MNSI > 4)., Results: After adjustment for sex, age, BMI, and HbA1c, in type 2 diabetes participants, four out of seven transketolase SNPs were associated with DSPN for all three MNSI versions (all p ≤ 0.004). The odds ratios of these associations increased with extending the MNSI score, for example, OR (95% CI) for SNP rs62255988 with MNSI > 2: 1.99 (1.16-3.41), MNSI > 3: 2.27 (1.26-4.09), and MNSI > 4: 4.78 (2.22-10.26); SNP rs9284890 with MNSI > 2: 2.43 (1.42-4.16), MNSI > 3: 3.46 (1.82-6.59), and MNSI > 4: 4.75 (2.15-10.51). In contrast, no associations were found between transketolase SNPs and the three MNSI versions in the NGT and prediabetes groups., Conclusions: The link of genetic variation in transketolase enzyme to diabetic polyneuropathy corroborated at the population level strengthens the concept suggesting an important role of pathways metabolising glycolytic intermediates in the evolution of diabetic polyneuropathy., (© 2024 The Author(s). Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)

Background: Diabetic peripheral neuropathy (DPN), the very prevalent microvascular complication of type 2 diabetes mellitus (T2DM), severely threatens the quality of life of diabetic patients. Thus, prevention of DPN is extremely important for public health, and the identification of potential biomarkers may help with early prevention. Our work determined the association between phase angles (PhAs) and the risk of DPN in T2DM patients., Materials and Methods: This cross-sectional study recruited 697 T2DM patients from the Third Affiliated Hospital of Soochow University. All patients were divided into the non-diabetic peripheral neuropathy group and diabetic peripheral neuropathy group, and the DPN group was further divided into low, medium, and high diabetic foot ulcer risk groups according to vibration perception threshold results. Using univariate and multivariate logistic regression analyses continuously, the relationship between PhAs (arms, legs, trunk, and whole body) and the risk of DPN were evaluated. Further analysis was conducted on different subgroups of the study population., Results: After adjusting for the potential covariates, multivariate logistic regression analyses indicated that PhAs of the arms, legs, and whole body correlated inversely with the risk of DPN. However, the PhA of the trunk had no significant correlation with DPN. According to the stratified subgroup analysis, the negative association between PhA of the whole body and the risk of DPN remained significant in the sex and BMI group except for participants with BMI ≥ 28 kg/m²., Conclusions: For the first time, PhAs were acknowledged to be independently associated with DPN. Further exploration is needed to explain the findings., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Continuous glucose monitoring (CGM)-derived metrics have been used to accurately assess glycemic variability (GV) to facilitate management of diabetes mellitus, yet their relationship with diabetic peripheral neuropathy (DPN) is not fully understood. We performed a systematic review and meta-analysis to evaluate the association between GV metrics and the risk of developing DPN. Nine studies totaling 3,649 patients with type 1 and type 2 diabetes mellitus were included. A significant association was found between increased GV, as indicated by metrics including standard deviation (SD) with OR and 95% CI of 2.58 (1.45-4.57), mean amplitude of glycemic excursions (MAGE) with OR and 95% CI of 1.90 (1.01-3.58), mean of daily difference (MODD) with OR and 95% CI of 2.88 (2.17-3.81) and the incidence of DPN. Our findings support a link between higher GV and an increased risk of DPN in patients with diabetes. These findings highlight the potential of GV metrics as indicators for the development of DPN, advocating for their inclusion in diabetes management strategies to potentially mitigate neuropathy risk. Longitudinal studies with longer observation periods and larger sample sizes are necessary to validate these associations across diverse populations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Diabetic peripheral neuropathy (DPN) is the most prevalent complication of diabetes, and has been demonstrated to be independently associated with cardiovascular events and mortality. This aim of this study was to investigate the subclinical left ventricular (LV) myocardial dysfunction in type 2 diabetes mellitus (T2DM) patients with and without DPN., Methods: One hundred and thirty T2DM patients without DPN, 61 patients with DPN and 65 age and sex-matched controls who underwent cardiovascular magnetic resonance (CMR) imaging were included, all subjects had no symptoms of heart failure and LV ejection fraction ≥ 50%. LV myocardial non-infarct late gadolinium enhancement (LGE) was determined. LV global strains, including radial, circumferential and longitudinal peak strain (PS) and peak systolic and diastolic strain rates (PSSR and PDSR, respectively), were evaluated using CMR feature tracking and compared among the three groups. Multivariable linear regression analyses were performed to determine the independent factors of reduced LV global myocardial strains in T2DM patients., Results: The prevalence of non-infarct LGE was higher in patients with DPN than those without DPN (37.7% vs. 19.2%, p = 0.008). The LV radial and longitudinal PS (radial: 36.60 ± 7.24% vs. 33.57 ± 7.30% vs. 30.72 ± 8.68%; longitudinal: - 15.03 ± 2.52% vs. - 13.39 ± 2.48% vs. - 11.89 ± 3.02%), as well as longitudinal PDSR [0.89 (0.76, 1.05) 1/s vs. 0.80 (0.71, 0.93) 1/s vs. 0.77 (0.63, 0.87) 1/s] were decreased significantly from controls through T2DM patients without DPN to patients with DPN (all p < 0.001). LV radial and circumferential PDSR, as well as circumferential PS were reduced in both patient groups (all p < 0.05), but were not different between the two groups (all p > 0.05). Radial and longitudinal PSSR were decreased in patients with DPN (p = 0.006 and 0.003, respectively) but preserved in those without DPN (all p > 0.05). Multivariable linear regression analyses adjusting for confounders demonstrated that DPN was independently associated with LV radial and longitudinal PS (β = - 3.025 and 1.187, p = 0.014 and 0.003, respectively) and PDSR (β = 0.283 and - 0.086, p = 0.016 and 0.001, respectively), as well as radial PSSR (β = - 0.266, p = 0.007)., Conclusions: There was more severe subclinical LV dysfunction in T2DM patients complicated with DPN than those without DPN, suggesting further prospective study with more active intervention in this cohort of patients., (© 2024. The Author(s).)

Background: This study explored the correlation between pancreatic islet α cell function, as reflected by the plasma glucagon levels, and Diabetic Peripheral Neuropathy (DPN) in patients with Type 2 Diabetes Mellitus (T2DM)., Methods: A total of 358 patients with T2DM were retrospectively enrolled in this study and divided into the Non-DPN (NDPN) group (n = 220) and the DPN group (n = 138). All patients underwent an oral glucose tolerance test to detect levels of blood glucose, insulin and glucagon, and the Area Under the Curve (AUC) for Glucagon (AUCglu) was used to estimate the overall glucagon level. The Peripheral Nerve Conduction Velocity (PNCV), Amplitude (PNCA) and Latency (PNCL) were obtained with electromyography, and their Z scores were calculated., Results: There were significant differences regarding the age, disease duration, serum levels of alanine aminotransferase, aspartate aminotransferase, urea nitrogen, high-density lipoprotein, and 2h-C peptide between these two groups (p < 0.05). The NDPN group had higher glucagon levels at 30, 60 and 120 min and AUCglu (p < 0.05). The Z-scores of PNCV and PNCA showed an increasing trend (p < 0.05), while the Z-score of PNCL showed a decreasing trend (p < 0.05). The glucagon levels were positively correlated with PNCV and PNCA, but negatively correlated with PNCL, with Gluca30min having the strongest correlation (p < 0.05). Gluca30min was independently related to PNCV, PNCL, PNCA and DPN, respectively (p < 0.05). The function of pancreatic α islet cells, as reflected by the plasma glucagon level, is closely related to the occurrence of DPN in T2DM patients., Conclusion: Gluca30min may be a potentially valuable independent predictor for the occurrence of DPN., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier España, S.L.U.)

Diabetic peripheral neuropathy (DPN) is a common complication of type 2 diabetes mellitus (T2DM) that causes peripheral and autonomic nervous system dysfunction. Dysregulation of miRNAs plays a crucial role in DPN development. However, the role of miR-503-5p in DPN remains unknown. Herein, T2DM mice (db/db) were used as a DPN model in vivo, and astrocytes isolated from db/db mice were induced with high glucose levels as a DPN model in vitro. MiR-503-5p expression was analyzed using qRT-PCR. GFAP, MCP-1, and SEPT9 protein levels were analyzed using western blotting and immunofluorescence. Luciferase assays were performed to investigate the interaction between miR-503-5p and SEPT9. We found that miR-503-5p expression decreased in the spinal cord of DPN model mice and astrocytes treated with high glucose (HG). The db/db mice displayed higher body weight and blood glucose, lower mechanical withdrawal threshold and thermal withdrawal latency, and higher GFAP and MCP-1 protein levels than db/m mice. However, tail vein injection of agomiR-503-5p remarkably reversed these parameters, whereas antigomiR-503-5p enhanced them. HG markedly facilitated GFAP and MCP-1 protein expression in astrocytes, whereas miR-503-5p mimic or inhibitor transfection markedly blocked or elevated GFAP and MCP-1 protein expression, respectively, in astrocytes with HG. SEPT9 was a target of miR-503-5p. In addition, SEPT9 protein levels were found to be elevated in db/db mice and astrocytes treated with HG. Treatment with agomiR-503-5p and miR-503-5p mimic was able to reduce SEPT9 protein levels, whereas treatment with antigomiR-503-5p and miR-503-5p inhibitor led to inhibition of the protein. Furthermore, SEPT9 overexpression suppressed the depressing effect of miR-503-5p overexpression in astrocytes subjected to HG doses. In conclusion, miR-503-5p was found to alleviate peripheral neuropathy-induced neuropathic pain in T2DM mice by regulating SEPT9 expression., (© 2024. The Author(s).)

Objective: Meteorin-like (Metrnl), a secreted myokine, is a newly discovered neurotrophic factor. The aim of this study was to determine if there is a correlation between the Metrnl level and diabetic peripheral neuropathy (DPN)., Methods: The investigation was conducted on a sample of 80 patients with type 2 diabetes mellitus (T2DM) and 60 healthy controls. The T2DM patients were categorized into two subgroups based on skin biopsy: the DPN subgroup (n = 20) and the diabetes without neuropathy subgroup (n = 60)., Results: The T2DM groups had higher serum Metrnl concentrations compared with the controls. The serum Metrnl concentration was significantly lower in the DPN group than in T2DM patients without neuropathy. Logistic regression analysis demonstrated a notable correlation between serum Metrnl and DPN (OR: 0.997, 95% CI: 0.995-1.000, P < 0.05). Serum Metrnl level was negatively correlated with age and SBP after a simple logistic regression analysis., Conclusion: Serum Metrnl concentration is independently correlated with DPN., (© 2024. The Author(s).)

Background: Diabetic vascular complications share common pathophysiological mechanisms, but the relationship between diabetes-related macrovascular complications (MacroVCs) and incident diabetic microvascular complications remains unclear. We aimed to investigate the impact of MacroVCs on the risk of microvascular complications., Methods and Results: There were 1518 participants with type 1 diabetes (T1D) and 20 802 participants with type 2 diabetes from the UK Biobank included in this longitudinal cohort study. MacroVCs were defined by the presence of macrovascular diseases diagnosed after diabetes at recruitment, including coronary heart disease, peripheral artery disease, stroke, and ≥2 MacroVCs. The primary outcome was incident microvascular complications, a composite of diabetic retinopathy, diabetic kidney disease, and diabetic neuropathy. During a median (interquartile range) follow-up of 11.61 (5.84-13.12) years and 12.2 (9.50-13.18) years, 596 (39.3%) and 4113 (19.8%) participants developed a primary outcome in T1D and type 2 diabetes, respectively. After full adjustment for conventional risk factors, Cox regression models showed significant associations between individual as well as cumulative MacroVCs and the primary outcome, except for coronary heart disease in T1D (T1D: diabetes coronary heart disease: 1.25 [0.98-1.60]; diabetes peripheral artery disease: 3.00 [1.86-4.84]; diabetes stroke: 1.71 [1.08-2.72]; ≥2: 2.57 [1.66-3.99]; type 2 diabetes: diabetes coronary heart disease: 1.59 [1.38-1.82]; diabetes peripheral artery disease: 1.60 [1.01-2.54]; diabetes stroke: 1.50 [1.13-1.99]; ≥2: 2.66 [1.92-3.68]). Subgroup analysis showed that strict glycemic (glycated hemoglobin <6.5%) and blood pressure (<140/90 mm Hg) control attenuated the association., Conclusions: Individual and cumulative MacroVCs confer significant risk of incident microvascular complications in patients with T1D and type 2 diabetes. Our results may facilitate cost-effective high-risk population identification and development of precise prevention strategies.

Purpose: Sudomotor dysfunction is considered as one of the earliest manifestations of diabetic peripheral neuropathy. We aimed to investigate the association between sudomotor dysfunction non-invasively detected by the SUDOSCAN device and diabetic retinopathy (DR) in patients with type 2 diabetes., Methods: A total of 2010 patients admitted to a tertiary hospital located in Shanghai were included from March 2020 to September 2023. Sudomotor function was assessed by the SUDOSCAN device, and sudomotor dysfunction was defined as feet electrochemical skin conductance (FESC) <60 μs. Fundus radiography was used for DR assessment, which was graded according to the severity, specifically: (1) non-DR; (2) mild nonproliferative DR (NPDR); (3) moderate NPDR/vision-threatening DR (VTDR)., Results: Among the enrolled 2010 patients, 525 patients had sudomotor dysfunction; 648 were diagnosed with DR, which was equivalent to 32.2% of all patients. Patients with sudomotor dysfunction had a significantly higher prevalence of DR, compared to those with normal sudomotor function (40.8% vs. 29.2%, P < 0.05). After controlling for confounding factors including HbA1c, sudomotor dysfunction was significantly associated with any DR (odd ratio [OR] = 1.57, 95% CI 1.26-1.96). When FESC was considered as a continuous variable, the multivariable-adjusted OR of DR was 1.29 (95% CI 1.17-1.42) for per 1-SD decrease in FESC. Furthermore, multinomial logistic regression revealed significant associations between sudomotor dysfunction and all stages of DR (mild NPDR: OR = 1.40, 95% CI 1.11-1.78; moderate NPDR/VTDR: OR = 2.35, 95% CI 1.60-3.46)., Conclusions: Sudomotor dysfunction was significantly associated with DR in patients with type 2 diabetes., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Spexin is a novel peptide hormone and has shown antinociceptive effects in experimental mice. This study is aimed at evaluating the association of serum spexin level with diabetic peripheral neuropathy (DPN) and related pain in a Chinese population. Methods: We enrolled 167 type 2 diabetes mellitus (T2DM) including 56 patients without DPN (non-DPN), 67 painless DPN, and 44 painful DPN. Serum spexin was measured using ELISA. Logistic regression models were performed to analyze the independent effects of spexin on prevalence of DPN and painful DPN. In streptozotocin (STZ)-induced diabetic mice, mechanical pain threshold was measured using electronic von Frey aesthesiometer. Human peripheral blood mononuclear cells (PBMCs) were isolated and further stimulated with lipopolysaccharide without or with spexin. The gene expression was assayed by qPCR. Results: Compared with non-DPN, serum spexin level decreased in painless DPN and further decreased in painful DPN. The odds of DPN was associated with low spexin level in T2DM, which was similar by age, sex, BMI, and diabetes duration, but attenuated in smokers. The odds of having pain was associated with decreased spexin level in DPN, which was similar by age, sex, smoking status, and diabetes duration, but attenuated in normal weight. Furthermore, we observed that mechanical pain threshold increased in spexin-treated diabetic mice. We also found that lipopolysaccharide treatment increased the mRNA level of TNF- α , IL-6, and MCP-1 in human PBMCs, while spexin treatment prevented this increase. Conclusions: These results suggested that spexin might serve as a protective factor for diabetes against neuropathology and pain-related pathogenesis., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Ying Liu et al.)

Background: Insulin resistance is associated with chronic complications of diabetes, including diabetic peripheral neuropathy (DPN). Estimated glucose disposal rate (eGDR), calculated by the common available clinical factors, was proved to be an excellent tool to measure insulin resistance in large patient population. Few studies have explored the association between eGDR and DPN longitudinally. Therefore, we performed the current study to analyze whether eGDR could predict the risk of DPN., Methods: In this prospective study, 366 type 2 diabetes (T2DM) subjects without DPN were enrolled from six communities in Shanghai in 2011-2014 and followed up until 2019-2020. Neuropathy was assessed by Michigan Neuropathy Screening Instrument (MSNI) at baseline and at the end of follow-up., Findings: After 5.91 years, 198 of 366 participants progressed to DPN according to MNSI examination scores. The incidence of DPN in the low baseline eGDR (eGDR < 9.15) group was significantly higher than in the high baseline eGDR (eGDR ≥ 9.15) group (62.37% vs. 45.56%, p = .0013). The incidence of DPN was significantly higher in patients with sustained lower eGDR level (63.69%) compared with those with sustained higher eGDR level (35.80%). Subjects with low baseline eGDR (eGDR < 9.15) had significantly higher risk of DPN at the end of follow-up (odds ratio = 1.75), even after adjusting for other known DPN risk factors., Conclusions: The 5-year follow-up study highlights the importance of insulin resistance represented by eGDR in the development of DPN in T2DM. Diabetic patients with low eGDR are more prone to DPN and, therefore, require more intensive screening and more attention., (© 2023 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Introduction: This study aimed to assess and compare the prevalence of diabetes complications between men and women with Type 2 diabetes (T2D), as well as how gender relates to these complications., Methods: In this cross-sectional study, complications of diabetes, including coronary artery disease (CAD), retinopathy, neuropathy and diabetic kidney disease (DKD), were evaluated in 1867 participants with T2D. Additionally, baseline characteristics of the individuals, including anthropometric measurements, metabolic parameters and the use of dyslipidaemia drugs and antihyperglycaemic agents, were assessed. Gender differences in complications were examined using the chi-squared test. Multivariate logistic regression was employed to investigate the relationship between gender and T2D complications, with and without adjusting for the characteristics of the studied population., Results: In the studied population, 62.1% had at least one complication, and complications were 33.5% for DKD, 29.6% for CAD, 22.9% for neuropathy and 19.1% for retinopathy. The prevalence of CAD and neuropathy was higher in men. However, DKD and retinopathy were more prevalent among women. Odds ratios of experiencing any complication, CAD and retinopathy in men compared with women were 1.57 (95% CI: 1.27-2.03), 2.27 (95% CI: 1.72-2.99) and 0.72 (95% CI: 0.52-0.98), respectively, after adjusting for demographic factors, anthropometric measures, metabolic parameters and the consumption of dyslipidaemia drugs and antihyperglycaemic agents., Conclusion: The prevalence of diabetes complications was significantly higher in men with diabetes, highlighting the need for better treatment adherence. CAD was associated with the male gender, whereas retinopathy was associated with the female gender. Men and women with diabetes should be monitored closely for CAD and retinopathy, respectively, regardless of their age, diabetes duration, anthropometric measures, laboratory findings and medications., (© 2024 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

Background: Clinical studies have shown that diabetic peripheral neuropathy (DPN) has been on the rise, with most patients presenting with severe and progressive symptoms. Currently, most of the available prediction models for DPN are derived from general clinical information and laboratory indicators. Several Traditional Chinese medicine (TCM) indicators have been utilised to construct prediction models. In this study, we established a novel machine learning-based multi-featured Chinese-Western medicine-integrated prediction model for DPN using clinical features of TCM., Materials and Methods: The clinical data of 1581 patients with Type 2 diabetes mellitus (T2DM) treated at the Department of Endocrinology of the First Affiliated Hospital of Anhui University of Chinese Medicine were collected. The data (including general information, laboratory parameters and TCM features) of 1142 patients with T2DM were selected after data cleaning. After baseline description analysis of the variables, the data were divided into training and validation sets. Four prediction models were established and their performance was evaluated using validation sets. Meanwhile, the accuracy, precision, recall, F1 score and area under the curve (AUC) of ROC were calculated using ten-fold cross-validation to further assess the performance of the models. An explanatory analysis of the results of the DPN prediction model was carried out using the SHAP framework based on machine learning-based prediction models., Results: Of the 1142 patients with T2DM, 681 had a comorbidity of DPN, while 461 did not. There was a significant difference between the two groups in terms of age, cause of disease, systolic pressure, HbA1c, ALT, RBC, Cr, BUN, red blood cells in the urine, glucose in the urine, and protein in the urine (p < 0.05). T2DM patients with a comorbidity of DPN exhibited diverse TCM symptoms, including limb numbness, limb pain, hypodynamia, thirst with desire for drinks, dry mouth and throat, blurred vision, gloomy complexion, and unsmooth pulse, with statistically significant differences (p < 0.05). Our results showed that the proposed multi-featured Chinese-Western medicine-integrated prediction model was superior to conventional models without characteristic TCM indicators. The model showed the best performance (accuracy = 0.8109, precision = 0.8029, recall = 0.9060, F1 score = 0.8511, and AUC = 0.9002). SHAP analysis revealed that the dominant risk factors that caused DPN were TCM symptoms (limb numbness, thirst with desire for drinks, blurred vision), age, cause of disease, and glycosylated haemoglobin. These risk factors were exerted positive effects on the DPN prediction models., Conclusions: A multi-feature, Chinese-Western medicine-integrated prediction model for DPN was established and validated. The model improves early-stage identification of high-risk groups for DPN in the diagnosis and treatment of T2DM, while also providing informative support for the intelligent management of chronic conditions such as diabetes., (© 2024 John Wiley & Sons Ltd.)

Objective: Diabetic peripheral neuropathy frequently occurs and presents severely in individuals suffering from type 2 diabetes mellitus, representing a significant complication. The objective of this research was to develop a risk nomogram for DPN, ensuring its internal validity and evaluating its capacity to predict the condition., Methods: In this retrospective analysis, Suqian First Hospital's cohort from January 2021 to June 2022 encompassed 397 individuals diagnosed with T2DM. A random number table method was utilized to allocate these patients into two groups for training and validation, following a 7:3 ratio. By applying univariate and multivariable logistic regression, predictive factors were refined to construct the nomogram. The model's prediction accuracy was assessed through metrics like the ROC area, HL test, and an analysis of the calibration curve. DCA further appraised the clinical applicability of the model. Emphasis was also placed on internal validation to confirm the model's dependability and consistency., Results: Out of 36 evaluated clinicopathological characteristics, a set of four, duration, TBIL, TG, and DPVD, were identified as key variables for constructing the predictive nomogram. The model exhibited robust discriminatory power, evidenced by an AUC of 0.771 (95% CI: 0.714-0.828) in the training cohort and an AUC of 0.754 (95% CI: 0.663-0.845) in the validation group. The congruence of the model's predictions with actual findings was corroborated by the calibration curve. Furthermore, DCA affirmed the clinical value of the model in predicting DPN., Conclusion: This research introduces an innovative risk nomogram designed for the prediction of diabetic peripheral neuropathy in individuals suffering from type 2 diabetes mellitus. It offers a valuable resource for healthcare professionals to pinpoint those at elevated risk of developing this complication. As a functional instrument, it stands as a viable option for the prognostication of DPN in clinical settings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Luo, Long, Cheng, Xu and Li.)

Background: We explore the effect of suboptimal glycemic control on the incidence of diabetic peripheral neuropathy (DPN) in both non-elderly and elderly patients with type 2 diabetes mellitus (T2DM)., Methods: A 6-year follow-up study (2013-2019) enrolled T2DM patients aged >20 without DPN. Participants were classified into two groups: those below 65 years (non-elderly) and those 65 years or older (elderly). Biochemical measurements, including glycated hemoglobin (HbA1C), were recorded regularly. DPN was diagnosed using the Michigan Neuropathy Screening Instrument examination. The outcome was DPN occurrence in 2019., Results: In 552 enrollments (69% non-elderly), DPN occurred in 8.4% non-elderly and 24.0% elderly patients. A higher initial HbA1C level was significantly linked with a higher risk of future DPN in the non-elderly group (adjusted odds ratio [AOR] 1.46, 95% CI 1.13-1.89, p=0.004). In comparison, HbA1c at the end of the study period was not associated with DPN in the non-elderly group (AOR 1.17, 95% CI 0.72-1.90, p=0.526). In the elderly group, no statistical relationship was found between HbA1C levels and DPN, either in 2013 or in 2019., Conclusion: Suboptimal glycemic control at baseline, rather than at the end of the study period, predicts an increased risk of future DPN in individuals with T2DM under age 65. This correlation is not seen in elderly patients. Therefore, we recommend implementing enhanced glycemic control early in middle-aged T2DM patients and propose individualized therapeutic strategies for diabetes in different age groups., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Pai, Lin, Lee, Chen and Chang.)

Background: The systemic immuno-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) are widely used and have been shown to be predictive indicators of various diseases. Diabetic nephropathy (DN), retinopathy (DR), and peripheral neuropathy (DPN) are the most prominent and common microvascular complications, which have seriously negative impacts on patients, families, and society. Exploring the associations with these three indicators and diabetic microvascular complications are the main purpose., Methods: There were 1058 individuals with type 2 diabetes mellitus (T2DM) in this retrospective cross-sectional study. SII, NLR, and PLR were calculated. The diseases were diagnosed by endocrinologists. Logistic regression and subgroup analysis were applied to evaluate the association between SII, NLP, and PLR and diabetic microvascular complications., Results: SII, NLR, and PLR were significantly associated with the risk of DN [odds ratios (ORs): 1.52, 1.71, and 1.60, respectively] and DR [ORs: 1.57, 1.79, and 1.55, respectively] by multivariate logistic regression. When NLR ≥2.66, the OR was significantly higher for the risk of DPN (OR: 1.985, 95% confidence interval: 1.29-3.05). Subgroup analysis showed no significant positive associations across different demographics and comorbidities, including sex, age, hypertension, HbA1c (glycated hemoglobin), and dyslipidemia., Conclusion: This study found a positive relationship between NLR and DN, DR, and DPN. In contrast, SII and PLR were found to be only associated with DN and DR. Therefore, for the diagnosis of diabetic microvascular complications, SII, NLR and PLR are highly valuable., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Wang, Jia, Wang, Wang, Diao, Ou, Ma and Yang.)

BACKGROUND Diabetic peripheral neuropathy (DPN) is a prevalent complication affecting over 60% of type 2 diabetes patients. Early diagnosis is challenging, leading to irreversible impacts on quality of life. This study explores the predictive value of combining HbA1c and Neutrophil-to-Lymphocyte Ratio (NLR) for early DPN detection. MATERIAL AND METHODS An observational study was conducted at the First People's Hospital of Linping District, Hangzhou spanning from May 2019 to July 2020. Data on sex, age, biochemical measurements were collected from electronic medical records and analyzed. Employing multivariate logistic regression analysis, we sought to comprehend the factors influencing the development of DPN. To assess the predictive value of individual and combined testing for DPN, a receiver operating characteristic (ROC) curve was plotted. The data analysis was executed using R software (Version: 4.1.0). RESULTS The univariate and multivariate logistic regression analysis identified the level of glycated hemoglobin (HbA1C) (OR=1.94, 95% CI: 1.27-3.14) and neutrophil-to-lymphocyte ratio (NLR) (OR=4.60, 95% CI: 1.15-22.62, P=0.04) as significant risk factors for the development of DPN. Receiver operating characteristic (ROC) curve analysis demonstrated that HbA1c, NLR, and their combined detection exhibited high sensitivity in predicting the development of DPN (71.60%, 90.00%, and 97.2%, respectively), with moderate specificity (63.8%, 45.00%, and 50.00%, respectively). The area under the curve (AUC) for these predictors was 0.703, 0.661, and 0.733, respectively. CONCLUSIONS HbA1c and NLR emerge as noteworthy risk indicators associated with the manifestation of DPN in patients with type 2 diabetes. The combined detection of HbA1c and NLR exhibits a heightened predictive value for the development of DPN.

Introduction: Diabetic peripheral neuropathy is the most common complication of diabetes producing metabolic disruptions in the peripheral nervous system. Alteration in the predictable nature of tendon reflexes is the most common indicator suggesting the possibility of diabetic neuropathy. Evaluation of tendon reflexes is a part of various clinical scoring systems that assess neuropathy. The conventional reflex grading scales are subjective, lack temporal data, and have high inter-rater variability. Hence, an indigenous quantification tool was developed to evaluate the tendon reflexes in order to assess diabetic peripheral neuropathy., Materials and Methods: A cross-sectional study was carried out in 140 healthy volunteers and 140 patients with type 2 diabetes. The mean age of controls and diabetics (49.1 ± 8.9, 50.7 ± 7.5) years, weight (66.9 ± 9.4, 69.8 ± 11.5) kilograms and BMI (24.5 ± 3.8, 26.1 ± 4.7), respectively. All of them are subjected to evaluation of tendon reflexes using the reflex quantification tool comprised of surface mechanomyography and electrogoniometry that can provide various static and dynamic variables of tendon reflex., Results: The dynamic variables such as reflex amplitude, muscle velocity and angular velocity were significantly low in diabetic patients (p: <0.001) whereas latency and duration (p: <0.001) were prolonged. Furthermore, no significant difference was observed in the application of tendon striking force (p: 0.934) among the participants., Conclusion: The current study demonstrates that the proposed reflex quantification tool provides several dynamic variables of patellar tendon reflex, which are significantly affected and altered in diabetic patients suggesting the involvement of peripheral neurons., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Research Trust of DiabetesIndia (DiabetesIndia) and National Diabetes Obesity and Cholesterol Foundation (N-DOC). Published by Elsevier Ltd. All rights reserved.)

Background: Diabetic peripheral neuropathy (DPN) is a prevalent complication of type 2 diabetes mellitus (T2DM). A comprehensive understanding of DPN's causal factors is pivotal for effective prevention and treatment, but the precise clinical pathogenesis remains unclear., Objective: To investigate the correlation between blood selenium (Se) levels and DPN in T2DM patients and analyze factors contributing to lesion development., Methods: We selected 51 patients with DPN and 57 with T2DM alone between June 2021 and August 2022. Blood glucose, lipid, and Se levels were assessed. Electromyographic evoked potentials measured motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) in DPN patients., Results: DPN patients exhibited lower Se, MNCV, and SNCV compared to DM patients, with higher glucose and lipid levels (P < .05). Logistic regression analysis identified age (95%CI 1.256-9.631), disease duration (95%CI 2.160-11.816), fasting blood glucose (95%CI 2.160-11.816), and HbA1c (95%CI 1.064-7.632) as independent risk factors for DPN in T2DM, while Se (95%CI 0.324-1.126) emerged as an independent protective factor (P < .05)., Conclusions: Blood selenium levels and DPN are closely related, with selenium emerging as a significant factor in DPN occurrence among T2DM patients.

Background: Diabetic peripheral neuropathy (DPN) contributes to disability and imposes heavy burdens, while subclinical DPN is lack of attention so far. We aimed to investigate the relationship between vitamin D and distinct subtypes of subclinical DPN in type 2 diabetes (T2DM) patients., Methods: This cross-sectional study included 3629 T2DM inpatients who undertook nerve conduction study to detect subclinical DPN in Zhongshan Hospital between March 2012 and December 2019. Vitamin D deficiency was defined as serum 25-hydroxyvitamin D (25(OH)D) level < 50 nmol/L., Results: 1620 (44.6%) patients had subclinical DPN and they were further divided into subgroups: distal symmetric polyneuropathy (DSPN) (n=685), mononeuropathy (n=679) and radiculopathy (n=256). Compared with non-DPN, DPN group had significantly lower level of 25(OH)D (P < 0.05). In DPN subtypes, only DSPN patients had significantly lower levels of 25(OH)D (36.18 ± 19.47 vs. 41.03 ± 18.47 nmol/L, P < 0.001) and higher proportion of vitamin D deficiency (78.54% vs. 72.18%, P < 0.001) than non-DPN. Vitamin D deficiency was associated with the increased prevalence of subclinical DPN [odds ratio (OR) 1.276, 95% confidence interval (CI) 1.086-1.501, P = 0.003] and DSPN [OR 1. 646, 95% CI 1.31-2.078, P < 0.001], independent of sex, age, weight, blood pressure, glycosylated hemoglobin, T2DM duration, calcium, phosphorus, parathyroid hormone, lipids and renal function. The association between vitamin D deficiency and mononeuropathy or radiculopathy was not statistically significant. A negative linear association was observed between 25(OH)D and subclinical DSPN. Vitamin D deficiency maintained its significant association with subclinical DSPN in all age groups., Conclusions: Vitamin D deficiency was independently associated with subclinical DSPN, rather than other DPN subtypes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sun, Yang, Zhu, Ma, Li, Zhang, Liu, Fan, Zhang, Xu, Xu, Gao, Dong, Xia and Bian.)

Objectives: Hyperglycaemia-induced inflammation plays a vital role in the development of diabetic peripheral neuropathy (DPN). Recent evidences had reported the involvement of the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) in diabetic experimental models. So, this pilot study aimed to evaluate serum NF-κB levels in DPN patients., Methods: We recruited 50 T2DM patients, of which 25 were T2DM with neuropathy and 25 were T2DM without neuropathy. In all the participants peripheral neuropathy was diagnosed based on Total neuropathy score (TNS). Serum NF-κB levels were measured by ELISA., Results: We observed that the serum NF-κB levels were higher in DPN patients in comparison to T2DM patients without neuropathy. On spearman correlation, a positive correlation was found between serum NF-κB levels and TNS in the DPN group (r=0.741, p<0.001). The regression model shows the TNS to be an independent determinant of serum NF-κB levels after adjustment for potential confounders like age, duration of diabetes, and HbA1C (B=81.34; p<0.001)., Conclusions: NF-κB activation plays a key role in promoting inflammation which is associated with the progression of DPN. In this respect, the study of NF-κB levels in serum may be an additional diagnostic marker for DPN., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

The variability in diabetes risk factors, such as uric acid and lipids, may influence the development of complications. This study aimed to investigate the influence of such variability on the occurrence of diabetic complications. A retrospective analysis of electronic medical records was conducted with type 2 diabetic patients who received treatment at a tertiary care hospital in Chengdu, Sichuan Province, between 2013 and 2022. The risk factor variability is presented as the standard deviation (SD). The associations between the variability and complications were examined using a binary logistic regression model. The study included 369 patients with type 2 diabetes. The findings revealed that outpatient special disease management served as a protective factor against the development of complications [OR = 0.53, 95% confidence interval (CI) (0.29-0.10)], particularly for the prevention of diabetic peripheral neuropathy [OR = 0.51, 95% CI (0.30-0.86)]. Variability in total cholesterol (TC-SD) was found to be a risk factor for the development of complications [OR = 2.42, 95% CI (1.18-4.97)] and acted as a risk factor for diabetic peripheral vasculopathy [OR = 2.50, 95% CI (1.25-5.02)]. TC-SD is a risk factor for the occurrence of diabetic peripheral neuropathy and diabetic peripheral vasculopathy, whereas outpatient special disease management functions as a protective factor against complications and diabetic peripheral neuropathy. Thus, in addition to glycaemic control, the regulation of lipid levels should be emphasized, particularly among patients without outpatient special disease management, to delay the onset of complications., (© 2024. The Author(s).)

This study aimed to determine the efficacy of assessing the severity of diabetic polyneuropathy (DPN) in patients with untreated diabetes. Seventy-two patients with untreated type 2 diabetes who were hospitalized for glycemic control were enrolled and divided into the following two groups: patients who had no prior diagnosis and patients who were unattended or had discontinued treatment. Electrophysiological criteria consistent with Baba's classification were used to diagnose and assess the severity of DPN. The patients were divided into three subgroups: no DPN (stage 0), mild DPN (stage 1), and moderate or more-severe DPN (stages 2-4). Intergroup comparisons were performed for the clinical characteristics and the results of the nerve conduction studies. Twenty-two (30%), 25 (35%), and 25 (35%) patients were categorized into the no DPN, mild DPN, and moderate or more-severe DPN subgroups, respectively. The number of patients who were unattended or had discontinued treatment in the moderate or more-severe DPN subgroup was significantly higher than that in the no DPN subgroup. The patients in the moderate or more-severe DPN subgroup had an increased risk of developing diabetic retinopathy and nephropathy, with odds ratios of 19.5 and 11.0 for advanced stages of retinopathy and nephropathy, respectively. Thus, the assessment of the severity of DPN could aid in the prediction of the risk of developing diabetic complications in patients with untreated diabetes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Horinouchi, Deguchi, Mukai, Ijuin, Kawamoto and Nishio.)

Aims/introduction: This prospective cohort study aims to identify the optimal measure of glycated hemoglobin (HbA1c) variability and to explore its relationship with the development of new diabetic sensorimotor polyneuropathy (DSPN) in individuals with type 2 diabetes mellitus, building upon previous cross-sectional studies that highlighted a significant association between HbA1c visit-to-visit variability and DSPN., Materials and Methods: In a prospective study, 321 participants diagnosed with type 2 diabetes mellitus underwent comprehensive clinical assessments, neurophysiologic studies, and laboratory evaluations at enrollment and follow-up. Various indices, including HbA1c standard deviation (HbA1c SD), coefficient of variation (HbA1c CV), HbA1c change score (HbA1c HVS), and average real variability (HbA1c ARV), were employed to calculate the visit-to-visit variability HbA1c based on 3 month intervals. The investigation focused on examining the associations between these indices and the development of new DSPN., Results: The average follow-up duration was 16.9 ± 6.9 months. The Cox proportional hazards model identified age (P = 0.001), diabetes duration (P = 0.024), and HbA1C ARV (P = 0.031) as the sole factors associated with the development of new DSPN. Furthermore, the cumulative risk of developing DSPN over 1 year demonstrated a significant association with HbA1C ARV (P = 0.03, log-rank test)., Conclusions: Apart from age and diabetes duration, HbA1c variability emerged as a robust predictor for the occurrence of new DSPN. Among the various measures of HbA1c variability evaluated, HbA1c ARV demonstrated the highest potential as a reliable indicator for anticipating the onset of new DSPN., (© 2024 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background: This study aimed to evaluate the characteristics of bone metabolism and fracture risk in the type 2 diabetes mellitus (T2DM) patients with distal symmetric polyneuropathy (DSPN)., Methods: A total of 198 T2DM individuals were recruited from January 2017 to December 2020. Patients with DSPN were evaluated by strict clinical and sensory thresholds. Biochemical parameters and bone mineral density (BMD) were measured. The BMD, bone turnover markers, and probability of fracture were compared between two groups, and the factors related to BMD and probability of hip fracture in 10 years were further explored., Results: Compared with type 2 diabetes mellitus without distal symmetric polyneuropathy (T2DN-) patients, type 2 diabetes mellitus with distal symmetric polyneuropathy (T2DN+) patients had lower level of cross-linked C-telopeptide (CTX) (0.32 ± 0.19 vs 0.38 ± 0.21 ng/mL, p = 0.038) and higher level of bone-specific alkaline phosphatase (BALP) (15.28 ± 5.56 vs 12.58 ± 4.41 μg/mL, p = 0.003). T2DN+ patients had higher BMD of lumbar L1-L4 (1.05 ± 0.19 vs 0.95 ± 0.37, p = 0.027) and higher probability of hip fracture (0.98 ± 0.88 vs 0.68 ± 0.63, p = 0.009) as compared to T2DN- individuals. Univariate correlation analysis showed that BALP level (coefficient (coef) = -0.054, p = 0.038), CTX level (coef = -2.28, p = 0.001), and hip fracture risk (coef = -1.02, p < 0.001) were negatively related to the BMD of L1-L4. As for the risk of hip fracture evaluated by WHO Fracture Risk Assessment Tool (FRAX), age (coef = 0.035, p < 0.001), use of insulin (coef = 0.31, p =0.015), and levels of BALP (coef = 0.031, p = 0.017) and CTX (coef = 0.7, p = 0.047) were positively related to the risk of hip fracture. Multivariate regression analysis showed that CTX level (coef = -1.41, p = 0.043) was still negatively related to BMD at the lumbar spine., Conclusion: This study indicates that T2DM patients with DSPN have special bone metabolism represented by higher BALP level and lower CTX level which may increase BMD at the lumbar spine., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024, the Chinese Medical Association.)