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Background: To identify the relationship between BMI or lipid metabolism and diabetic neuropathy using a Mendelian randomization (MR) study. Methods: Body constitution-related phenotypes, namely BMI (kg/m2), total cholesterol (TC), and triglyceride (TG), were investigated in this study. Despite the disparate origins of these data, all were accessible through the IEU OPEN GWAS database (https://gwas.mrcieu.ac.uk/). Instrumental variables and F-statistics for each exposure-outcome pair were determined in weighted mode, weighted median, MR-Egger and Inverse-Variance Weighted (IVW) MR analyses. The p-value threshold was consistently set at 5.00E−08, following established methodology. The preliminary analysis utilized the IVW method to explore potential causal relationships between body constitution-related phenotypes and diabetic neuropathy. Inverse variance weighting, a technique amalgamating random variables, assigns weights inversely proportional to each variable's variance, commonly used for merging findings from independent studies. The weighted median method provides a causal estimate even when up to 50% of the instruments are invalid, enhancing robustness. The weighted mode method identifies the most common causal effect, reducing bias when some instruments exhibit horizontal pleiotropy. The Wald ratio method was utilized to calculate exposure-outcome effects, employing a range of methodologies to ensure result accuracy across different scenarios. This study addresses the critical gap in understanding the causal relationship between BMI, lipid metabolism, and diabetic neuropathy (DN). Employing a MR approach, it highlights BMI as a predictive factor for DN progression, providing insights into potential risk management strategies. Results: IVW analysis showed that BMI (P = 0.033, OR = 2.53, 95% CI 1.08–5.96) and triglycerides level (P = 0.593, OR = 1.11, 95% CI 0.77–1.60) were positively associated with the initiation of DN, indicating that the values of BMI and triglycerides are potentially the risk factors in DN development. Additionally, TC was negatively associated with the DN (P = 0.069, OR = 0.72, 95% CI = 0.50–1.03).The forest plot of advanced analysis between BMI and DN relationship indicated a positive correlation between increasing BMI and the risk of DN. In addition, it is evident that with the increase in BMI, the risk of diabetic polyneuropathy also rises. This research demonstrates a positive association between BMI and DN risk (P = 0.033, OR = 2.53, 95% CI = 1.08–5.96). However, no significant correlation was observed between triglycerides (P = 0.593) or total cholesterol (P = 0.069) and DN development, underscoring the complex interplay between lipid metabolism and DN. Conclusion: This research demonstrates a positive association between the risk of DN and BMI, while no significant correlation exists between TG or TC and the development of DN. These results imply that BMI may serve as a predictive factor for the progression of DN. [ABSTRACT FROM AUTHOR]

Aim: The present study aimed to determine the prevalence and predictors of DPN in newly diagnosed T2DM patients., Background: Diabetic Peripheral Neuropathy (DPN) is the most common and debilitating complication of Type 2 Diabetes Mellitus (T2DM)., Methods: Newly diagnosed T2DM patients visiting the outpatient department were recruited. Detailed demographic parameters, histories, physical examinations, and biochemical investigations were carried out. Patients were screened for DPN using the Diabetic Neuropathy Symptom (DNS) score, the revised Disability Neuropathy Score (NDS), Vibration Perception Threshold (VPT) using a biosthesiometer, and the 10 g SW Monofilament Test (MFT)., Results: A total of 350 newly diagnosed T2DM patients (mean age 46.4±13.6 years) were included. The prevalence of DPN was found to be 34% using the combined DNS and NDS scores. VPT was moderately impaired in 18.3% and severely impaired in 12% patients, while MFT revealed a loss of protective sensation in 35.4% patients. After logistic regression analysis, DPN was significantly associated with increasing age (OR 1.08, 95%CI 1.06-1.11), increasing HbA1C levels (OR 1.23, 95%CI 1.05-1.42), increasing TSH levels (OR 1.23, 95%CI 1.05-1.44), presence of hypertension (OR 2.78, 95%CI 1.51-5.11), and reduced BMI (OR 0.9, 95%CI 0.84- 0.99). The sensitivity and specificity of detecting DPN by combining VPT and MFT were 91.6% and 84.2%, respectively., Conclusion: The prevalence of DPN was high even in newly diagnosed T2DM and associated significantly with increasing age, HbA1C levels, TSH levels, hypertension, and reduced BMI. Earlier screening for DPN, along with aggressive control of glycemia, blood pressure, and hypothyroidism, may be beneficial., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)