{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T12:24:34Z","timestamp":1766147074647,"version":"3.48.0"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"\n Background<\/jats:title>\n \n Apolipoprotein E (ApoE) affects lipid metabolism and was associated with type 2 diabetes mellitus (T2DM) complications, including diabetic peripheral neuropathy (DPN). Despite improved glycemic control, DPN prevalence continues to rise, indicating mechanisms beyond hyperglycemia. We assessed the association between\n APOE<\/jats:italic>\n genotypes and DPN susceptibility in patients with T2DM, focusing on dyslipidemia-linked pathways underlying neuropathy susceptibility distinct from glycemic effects.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n The case-control study included 908 Lebanese patients with T2DM (382 with DPN, 526 without) and 695 healthy controls who underwent multimodal DPN assessment (NCS, QST, and MNSI).\n APOE<\/jats:italic>\n genotyping was performed by PCR-RFLP analysis. Logistic regression models were applied to examine the associations between\n APOE<\/jats:italic>\n variants and higher odds of DPN.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n T2DM patients showed significantly higher frequencies of\n \u03f52<\/jats:italic>\n and\n \u03f54<\/jats:italic>\n alleles than controls. Among T2DM patients, those with DPN had significantly higher\n \u03f52<\/jats:italic>\n allele frequency and lower \u03f53 allele frequency. At the genotype level,\n \u03f53<\/jats:italic>\n \/\n \u03f53<\/jats:italic>\n genotype demonstrated lower odds of DPN, while\n \u03f52\/\u03f53<\/jats:italic>\n ,\n \u03f52\/\u03f54<\/jats:italic>\n , and\n \u03f53\/\u03f54<\/jats:italic>\n were significantly associated with increased odds after adjustment for traditional risk factors. When pooled by allele,\n \u03f52<\/jats:italic>\n -containing genotypes (\n \u03f52\/\u03f53<\/jats:italic>\n +\n \u03f52\/\u03f54<\/jats:italic>\n ; OR (95% CI) = 1.86 [1.38\u20132.51], and\n \u03f54<\/jats:italic>\n -containing genotypes (\n \u03f53\/\u03f54<\/jats:italic>\n +\n \u03f54\/\u03f54<\/jats:italic>\n +\n \u03f52\/\u03f54<\/jats:italic>\n ; OR (95% CI) = 1.62 [95% CI = 1.08\u20132.44]) showed high odds of DPN. Lipid profiles varied by genotype:\n \u03f54<\/jats:italic>\n -containing genotypes displayed atherogenic patterns (elevated total cholesterol and triglycerides, reduced HDL) and were associated with a 1.6-fold higher odds of DPN, while\n \u03f52-<\/jats:italic>\n containing genotypes showed increased total cholesterol and LDL among DPN patients. Genotype-specific clinical correlations were genotype-specific:\n \u03f53<\/jats:italic>\n \/\n \u03f53<\/jats:italic>\n was associated with retinopathy and hypertension but protective against nephropathy, while\n \u03f53<\/jats:italic>\n \/\n \u03f54<\/jats:italic>\n correlated with diabetic complications and dyslipidemia, and\n \u03f54<\/jats:italic>\n \/\n \u03f54<\/jats:italic>\n linked to a higher BMI.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n APOE<\/jats:italic>\n genetic variants, especially\n \u03f54<\/jats:italic>\n -containing genotypes, are associated with DPN susceptibility among Lebanese T2DM patients, independent of traditional risk factors including glycemic control. These population-specific findings require validation in prospective cohorts before clinical use but indicate potential value for\n APOE<\/jats:italic>\n genotyping in DPN precision-risk models.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fendo.2025.1738873","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T12:22:23Z","timestamp":1766146943000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Apolipoprotein E genotypes are associated with diabetic peripheral neuropathy in Lebanese adults with type 2 diabetes: a case-control 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