June 03, 2019
By Marilynn Larkin
NEW YORK (Reuters Health) - Low serum cholesterol levels in people with type 2 diabetes were associated with diabetic polyneuropathy in a cross-sectional study.
"The key point of our study is that low levels of total serum cholesterol and low-density lipoprotein cholesterol are associated with a higher amount of nerve damage detected by high-resolution MRI of the sciatic nerve in patients with type 2 diabetes," Dr. Felix Kurz of Heidelberg University Hospital told Reuters Health by email. "The results were independent of patients' age, disease duration, glycemia or kidney function."
"This was very surprising to us, since we had expected lower levels of serum cholesterol and, in particular, LDL cholesterol to be beneficial for patients with type 2 diabetes," he noted. "Instead, our results now indicate that lowering serum cholesterol in type 2 diabetes is likely to impair nerve regeneration and, therefore, is potentially harmful in diabetic neuropathy."
"We therefore plan to investigate the role of lipid-lowering drugs such as statins or the newly developed PCSK9-inhibitors in the development of diabetic polyneuropathy in future studies," he said.
Dr. Kurz and colleagues conducted a single center, cross-sectional study of 100 patients with type 2 diabetes (mean age 65, 68% men) who underwent magnetic resonance neurography of the right leg and clinical, serologic and electrophysiologic assessments. Using advanced imaging tools, the team quantified the diameter of various nerves and the lipid equivalent lesion (LEL) load.
As reported online May 31 in JAMA Network Open, the LEL load correlated positively with a nerve's mean cross-sectional area - i.e., swelling (coefficient of correlation = 0.44) and the maximum length of a lesion (r = 0.71). For example, in patients with neuropathy, the mean LEL load in vital nerve tissue was 19.67%; the maximum length of a lesion was 63.47 mm and the mean cross-sectional area of the tibial nerve was 142.20 mm.
By contrast, in those without neuropathy, the mean LEL load in vital nerve tissue was 10.03%; the maximum length of a lesion was 50.07 mm and the mean cross-sectional area of the tibial nerve was 122.20 mm.
Further, the LEL load was negatively associated with total serum cholesterol level (r = −0.41), high-density lipoprotein cholesterol (r = − 0.30), low-density lipoprotein cholesterol (r = − 0.33), nerve conduction velocities of the tibial (r = − 0.33) and peroneal (r = − 0.51) nerves, as well as nerve conduction amplitudes of the tibial (r = − 0.31) and peroneal (r = − 0.28) nerves.
Summing up, the authors state, "The findings suggest that lowering serum cholesterol levels in patients with T2D and (diabetic polyneuropathy) is associated with a higher amount of nerve lesions and declining nerve conduction velocities and amplitudes."
Dr. Robert Rosenson, Professor of Medicine (Cardiology) at the Icahn School of Medicine at Mount Sinai in New York City, noted several limitations to the observational study. "The lipid changes associated with diabetic peripheral neuropathy are consistent with insulin resistance. It is possible that patients with diabetic peripheral neuropathy have more severe insulin resistance as an underlying mechanism," he said in an email to Reuters Health.
Further, he said, the study did not include "background medications that may influence lipid levels and insulin sensitivity and lacked an intervention to support the hypothesis."
"Future studies should consider prespecified measures of diabetic peripheral neuropathy," he said. "It is important to state that these adverse events were not reported in phase II, IIIA or IIIB clinical outcome trials with PCSK9 inhibitors."
JAMA Netw Open 2019.(c) Copyright Thomson Reuters 2019. Click For Restrictions - https://agency.reuters.com/en/copyright.html