{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T05:35:01Z","timestamp":1767591301349,"version":"3.48.0"},"reference-count":110,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"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. Neurol."],"abstract":"<jats:p>What Hyperglycemia Does to the Legs is quite devastating and ends with the tragic event of losing lower limbs. A patient with diabetic neuropathy (DN) may have both good and sensory loss. On one hand, there are symptoms like pain, sensitivity, tingling, cramping, and cold feet. On the other hand, there are negative symptoms, including sensory loss and delayed wound healing the cues back up this negative out comes (Sensory nerves are essential for healing wounds because they help regulate the immune system and encourage the movement of cells, the creation of growth factors, and the reproduction of cells). When sensory nerves are injured or cut off, there is a decline in neuropeptides and white blood cell presence, which slows down the healing process. This problem is especially seen in diabetic neuropathy, as the loss of sensory functions greatly affects the ability to heal wounds, Chronic wounds display high levels of inflammation, reduced activity of growth factors, and poor oxygen supply to tissues, which all lead to slow healing and the persistence of non-healing wounds. The development and progression of DN cannot be explained solely by elevated blood glucose levels. New evidence suggests that a naturally occurring reactive metabolite called MG (methylglyoxal) can enhance function by modifying neuronal ion channels involved in chemo sensing and action potential generation in nociceptive nerve endings. This modification occurs after Glo1 (glyoxalase I) levels are reduced. One possible reason for the development of DN is the effect of dicarbonyls on the neuronal compartment. Thus, there may be new and improved ways to treat DN if we focus on preventing the buildup and effects of MG.<\/jats:p>","DOI":"10.3389\/fneur.2025.1591279","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T05:30:19Z","timestamp":1767591019000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Hyperglycemic effects on limbs tingling and twisting sensations"],"prefix":"10.3389","volume":"16","author":[{"given":"Samaa Faez","family":"Khudhur","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,5]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1296","DOI":"10.1016\/j.neuron.2017.02.005","article-title":"New horizons in diabetic neuropathy: mechanisms, bioenergetics, and 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