Low Serum Cholesterol Levels May Worsen Peripheral Nerve Damage in Type 2 Diabetes

Researchers examined the association between cholesterol metabolism and sciatic nerve alterations in T2D.

Lowering serum cholesterol levels in patients with type 2 diabetes (T2D) and diabetic polyneuropathy might result in more nerve lesions and peripheral nerve swelling, according to study results published in JAMA Network Open.

Researchers conducted this prospective cross-sectional study to examine the association between cholesterol metabolism and sciatic nerve alterations in patients with T2D. They used high-resolution magnetic resonance neurography to create 3-dimentional reconstructions of sciatic nerve hypointense lesions in the right legs of 100 adults with T2D (mean age, 64.6). Participants were measured for nerve diameter and lipid equivalent lesion load, diabetic polyneuropathy, and other clinical, serologic, and electrophysiologic data. Of the study cohort, 64 patients had diabetic polyneuropathy.

The researchers determined that lipid equivalent lesion load positively correlated with the sciatic nerve’s mean cross-sectional area (r = 0.44; P <.001), as well as the maximum length of a lesion (r = 0.71; P <.001).

Furthermore, lipid equivalent lesion load was negatively associated with levels of total serum cholesterol (r = -0.41; P <.001), high-density lipoprotein cholesterol (r = -0.30; P =.006), and low-density lipoprotein cholesterol (r = -0.33; P = .003).

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Total cholesterol and low-density lipoprotein cholesterol levels were positively correlated with nerve conduction velocities. As lipid equivalent lesion load increased, nerve conduction velocities decreased in the tibial (r = -0.33; P =.01) and peroneal nerves (r = -0.51; P <.001), and nerve conduction amplitudes of the tibial (r = -0.31; P =.02) and peroneal nerves (r = -0.28; P =.03) also decreased.

Study limitations included an inability to complete longitudinal analysis due to its cross-sectional design.

“Regarding novel therapies for treating dyslipidemia in patients with T2D,” the researchers said, “our results suggest that clinical trials of patients with very low serum cholesterol levels should be vigilant about the onset or deterioration of neuropathic symptoms.”

“Additional longitudinal studies on the role of cholesterol metabolism in [diabetic polyneuropathy] appear to be required to determine whether there is a critical threshold of serum cholesterol for an impairment of nerve regeneration,” they added.

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Jende JME, Groener JB, Rother C, et al. Association of serum cholesterol levels with peripheral nerve damage in patients with type 2 diabetes. JAMA Netw Open. 2019;2(5):e194798.