Healio
Healio
May 31, 2019
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Aggressive cholesterol lowering may contribute to diabetic polyneuropathy

Adults with type 2 diabetes may be susceptible to deteriorating nerve function and more prevalent nerve lesions when their serum cholesterol levels are decreased, regardless of whether they have diabetic polyneuropathy, according to findings published in JAMA Network Open.

Although lowering serum cholesterol levels is advised for adults with type 2 diabetes to treat dyslipidemia, lower levels are also associated with more peripheral nerve damage, according to study background.

“It has not yet been determined whether lowering serum cholesterol levels in patients with [type 2 diabetes] has a positive influence on the course of [type 2 diabetes diabetic polyneuropathy],” Felix T. Kurz, MD, of the department of neuroradiology at Heidelberg University Hospital in Germany, and colleagues wrote. “With regard to emerging therapies, such as protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors that promote an aggressive lowering of total serum cholesterol levels, it is crucial to understand whether a decrease in total serum cholesterol and LDL [cholesterol] levels is beneficial or potentially harmful for patients with [type 2 diabetes] with [diabetic polyneuropathy].”

Kurz and colleagues recruited 100 adults with type 2 diabetes (mean age, 64.6 years; 32% women; 36% with diabetic polyneuropathy) from the department of endocrinology at Heidelberg University Hospital between 2015 and 2018 for a prospective cohort study. Magnetic resonance neurography on the right leg was used to measure lipid equivalent lesions and nerve mean cross-sectional area. Nerve conduction velocities and compound muscle action potential were also recorded.

Negative associations between lipid equivalent lesion load and nerve conduction velocities were observed in both the tibial (P =. 01) and peroneal nerves (P < .001). Both nerves also exhibited a negative association between lipid equivalent lesion load and compound muscle action potential (P = .02 for tibial nerve; P = .03 for peroneal nerve). According to the researchers, lipid equivalent lesion load was also negatively associated with levels of serum cholesterol (P < .001), HDL cholesterol (P = .006) and LDL cholesterol (P = .003). Similarly, maximum lesion length and larger tibial nerve mean cross-sectional area were negatively associated with serum cholesterol levels (P < .001 for both) and with LDL cholesterol levels (P < .001 and P = .002, respectively), the researchers reported, adding that maximum lesion length was negatively correlated with nerve conduction velocities in the tibial (P = .002) and peroneal (P < .001) nerves as well as with compound muscle action potential in each nerve (P =.049 and P = .047, respectively). The correlations between tibial nerve mean cross-sectional area and nerve conduction velocities in the peroneal and tibial nerves (P < .001 for both) as well as with compound muscle action potential in each nerve (P < .001 and P = .001, respectively) were all negative.

“The findings are of importance for the understanding of the pathogenetic mechanisms underlying [diabetic polyneuropathy] in [type 2 diabetes] because the long-term dyslipidemia outcomes seen in humans cannot be properly reproduced in rodents owing to substantial differences in lipid metabolism,” the researchers wrote. “In light of emerging therapies for dyslipidemia in [type 2 diabetes], such as PCSK9 inhibitors that promote a more aggressive lowering of serum cholesterol levels, our results suggest that current clinical trials including patients with very low serum cholesterol levels should pay close attention to signs of neuropathic damage.” – by Phil Neuffer

Disclosures: Kurz reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

Sources/Disclosures

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Source:

Jende JME, et al. JAMA Netw Open. 2019;doi:10.1001/jamanetworkopen.2019.4798.