Background and Objectives: Diabetic peripheral neuropathy (DPN) is a common and debilitating complication of obesity and type 2 diabetes (T2D) affecting up to 50% of patients with long-standing disease. While chronic hyperglycemia plays a central role in its pathogenesis, intensive glycemic control provides only partial protection, suggesting the involvement of additional metabolic pathways. The primary objective of this systematic review was to evaluate the role of lipid metabolism disturbances and advanced lipidomic alterations in the development and progression of DPN in patients with obesity and T2D. Secondary objectives included identifying specific lipid species associated with DPN and exploring their potential pathophysiological and clinical implications. Methods: This systematic review included 8 studies that met the inclusion criteria and was conducted according to PRISMA guidelines and registered in PROSPERO/2026/CRD420261288920. Study quality was assessed using the Newcastle–Ottawa Scale. Results: Large population-based cohorts reported a consistent association between hypertriglyceridemia and DPN prevalence, with triglyceride levels >204 mg/dL associated with an approximately 40% increased risk. Lipidomic analysis revealed alterations in acylcarnitine, sphingolipids, and phospholipids. However, the evidence remains limited and heterogeneous, and neuropathy-specific outcomes were insufficiently evaluated in interventional studies. Conclusions: Lipid metabolism disturbances, particularly hypertriglyceridemia and specific lipidomic alterations, may contribute to DPN beyond the effects of hyperglycemia. Although not yet clinically actionable, lipidomic alterations may represent promising future biomarkers and therapeutic targets in DPN. However, the current evidence is limited by heterogeneity and predominantly observational designs. Further well-designed longitudinal and interventional studies are needed to clarify causal relationships and clinical relevance.

Background: Diabetes Mellitus (DM) is frequently associated with diabetic peripheral neuropathy (DPN) and cardiovascular diseases (CVD). The aim of this study is to assess the relationship between DPN symptoms, vitamin B12 level, and autonomic neuropathy in DM patients with high and very high CV risk or established CVD. Material and Methods: A cross-sectional analysis of 164 patients from the Outpatient DM Department of Suceava County Hospital from September 2025 was performed. The clinical, paraclinical, and demographic data were collected, including Toronto Clinical Neuropathy Score (TCNS), Sudoscan, Orthostatic Hypotension (OH), and B12 level. Results: In total, 65.9% of patients had DPN; the mean HbA1c was 8.22% ± 1.74. No significant correlation was obtained between autonomic neuropathy (Sudoscan) and DPN severity (p = 0.163) or between vitamin B12 and DPN (p = 0.6). Vitamin B12 was associated with CV risk assessed with Sudosan (p = 0.04). OH had limited diagnostic significance for autonomic dysfunction. Conclusions: No strong link was detected between B12 levels and DPN; thus, it cannot be considered a predictive marker. Objective DPN screening remains essential. Sudoscan is practical and non-invasive in assessing autonomic neuropathy, but only when combined with TCNS may it increase the DPN screening and risk stratification in high-CV-risk populations with DM.

Background and Objectives: Peripheral neuropathy (PNP) is a frequent and debilitating complication among patients with diabetes mellitus (DM) and other metabolic conditions, substantially affecting morbidity, functional status, and quality of life. Identifying predictors of PNP is essential for optimizing early diagnostic strategies and improving long-term management outcomes. The aim of this study was to determine the predictive factors of PNP in a cohort of patients with DM. Materials and Methods: A cross-sectional study including 117 patients diagnosed with DM assessed for PNP was conducted. All patients were evaluated clinically and biologically. PNP was clinically assessed using the Toronto Clinical Scoring System (TCSS) score and sudomotor function by Sudoscan. Results: The patients included were mostly males with type 2 DM and metabolic syndrome phenotypes. Moreover, the patients with PNP were much older than those without PNP (65 [57–69] vs. 59.50 [46–68] years, p = 0.008), with a longer duration of DM (10 [6–15.50] vs. 5.5 (2–14] years, p = 0.019), and associated autonomic diabetic neuropathy (χ² = 24.382, p < 0.001). Furthermore, TCSS and Sudoscan were correlated with a history of PNP, especially Sudoscan, which showed a very good discriminative ability for diabetic neuropathy diagnosis (AUC = 0.816). In a multivariable logistic regression including age, DM duration, and HbA1c, age was independently associated with PNP, with each additional year increasing the odds of neuropathy by approximately 6% (OR = 1.06, 95% CI 0.02–1.09, p = 0.002). When age was excluded, DM duration showed a borderline association with PNP (OR = 1.055, CI95% 0.997–1.117), suggesting potential overlap between these variables. Adding sudomotor assessment to the initial model improved the model performance (AUC 0.70–0.72). Conclusions: Age emerged as the main independent predictor of diabetic neuropathy, highlighting the role of cumulative metabolic exposure in the development of neural damage. Moreover, sudomotor assessment may have a complementary role in PNP assessment.