Cutaneous Carbonyl Stress Linked to Nerve Dysfunction and Neuropathy Risk in Recent-Onset Type 2 Diabetes: Study

Endogenous carbonyl stress contributes to the formation of advanced glycation end products (AGEs), which are considered potential targets for preventing or treating diabetic sensorimotor polyneuropathy (DSPN). To explore this, Gidon J. Bönhof, Department of Endocrinology and Diabetology, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany, and colleagues aimed to investigate cutaneous carbonyl stress, oxidative stress, immune cell activity, and endothelial cell damage in early type 2 diabetes compared to individuals with normal glucose tolerance (NGT) by utilizing novel cutaneous biomarkers.

For this purpose, the researchers included 160 individuals recently diagnosed with type 2 diabetes (≤12 months) and 144 individuals with normal glucose tolerance from the baseline cohort of the German Diabetes Study. Nerve function was evaluated using electrophysiological assessments, quantitative sensory testing, and clinical evaluations. Skin biopsies were taken to examine intraepidermal nerve fiber density, AGEs autofluorescence, argpyrimidine area, and endothelial cell area. Additionally, skin autofluorescence was measured noninvasively using the AGE reader. A subgroup of 80 type 2 diabetes patients was reassessed after five years to monitor long-term changes.

Based on the study, the researchers reported the following findings:

• After adjusting for sex, age, HbA1c, LDL cholesterol, and BMI, argpyrimidine area was higher in recent-onset type 2 diabetes (17.5 ± 18.8%) compared to those with normal glucose tolerance (NGT) (11.7 ± 12.7%).
• AGEs autofluorescence showed an inverse correlation with nerve conduction, such as peroneal motor nerve conduction velocity (r = −0.346), in type 2 diabetes.
• AGEs autofluorescence was positively correlated with AGE reader measurements in type 2 diabetes (r = 0.358) but showed no such correlation in NGT.
• Higher baseline AGEs autofluorescence and lower endothelial cell area predict worsening of clinical and neurophysiological outcomes over five years.

The study showed that markers of cutaneous AGEs were linked to neurophysiological deficits in recent-onset type 2 diabetes and predicted their progression over five years, highlighting the role of carbonyl stress in the early development of diabetic sensorimotor polyneuropathy.

"Prospective analyses highlighted that cutaneous AGEs and reduced endothelial integrity may predict declining nerve function, supporting the role of carbonyl stress in the development and progression of DSPN and identifying it as a potential therapeutic target," the researchers concluded.

Reference:

Gidon J. Bönhof, Alexander Strom, Tobias Jung, Kálmán B. Bódis, Julia Szendroedi, Robert Wagner, Tilman Grune, Michael Roden, Dan Ziegler; Cutaneous Carbonyl Stress Is Associated With Nerve Dysfunction in Recent-Onset Type 2 Diabetes. Diabetes Care 2024; dc241799. https://doi.org/10.2337/dc24-1799