Abstract
Lowering serum cholesterol levels is a well-established treatment for dyslipidemia in patients with type 2 diabetes (T2D). However, nerve lesions in patients with T2D increase with lower serum cholesterol levels, suggesting that lowering serum cholesterol levels is associated with diabetic polyneuropathy (DPN) in patients with T2D. To investigate whether there is an association between serum cholesterol levels and peripheral nerve lesions in patients with T2D with and without DPN. This single-center, cross-sectional, prospective cohort study was performed from June 1, 2015, to March 31, 2018. Observers were blinded to clinical data. A total of 256 participants were approached, of whom 156 were excluded. A total of 100 participants consented to undergo magnetic resonance neurography of the right leg at the Department of Neuroradiology and clinical, serologic, and electrophysiologic assessment at the Department of Endocrinology, Heidelberg University Hospital, Heidelberg, Germany. Quantification of the nerve's diameter and lipid equivalent lesion (LEL) load with a subsequent analysis of all acquired clinical and serologic data with use of 3.0-T magnetic resonance neurography of the right leg with 3-dimensional reconstruction of the sciatic nerve. The primary outcome was lesion load and extension. Secondary outcomes were clinical, serologic, and electrophysiologic findings. A total of 100 participants with T2D (mean [SD] age, 64.6 [0.9] years; 68 [68.0%] male) participated in the study. The LEL load correlated positively with the nerve's mean cross-sectional area (r = 0.44; P < .001) and the maximum length of a lesion (r = 0.71; P < .001). The LEL load was negatively associated with total serum cholesterol level (r = -0.41; P < .001), high-density lipoprotein cholesterol level (r = -0.30; P = .006), low-density lipoprotein cholesterol level (r = -0.33; P = .003), nerve conduction velocities of the tibial (r = -0.33; P = .01) and peroneal (r = -0.51; P < .001) nerves, and nerve conduction amplitudes of the tibial (r = -0.31; P = .02) and peroneal (r = -0.28; P = .03) nerves. The findings suggest that lowering serum cholesterol levels in patients with T2D and DPN is associated with a higher amount of nerve lesions and declining nerve conduction velocities and amplitudes. These findings may be relevant to emerging therapies that promote an aggressive lowering of serum cholesterol levels in patients with T2D.
Highlights
Distal symmetric diabetic polyneuropathy (DPN) is one of the most severe complications of diabetes, affecting approximately 200 million patients worldwide, with increasing prevalence leading to high morbidity and rising health care costs.[1]
The lipid equivalent lesion (LEL) load was negatively associated with total serum cholesterol level (r = −0.41; P < .001), high-density lipoprotein cholesterol level (r = −0.30; P = .006), low-density lipoprotein cholesterol level (r = −0.33; P = .003), nerve conduction velocities of the tibial (r = −0.33; P = .01) and peroneal (r = −0.51; P < .001) nerves, and nerve conduction amplitudes of the tibial (r = −0.31; P = .02) and peroneal (r = −0.28; P = .03) nerves
The findings suggest that lowering serum cholesterol levels in patients with type 2 diabetes (T2D) and DPN is associated with a higher amount of nerve lesions and declining nerve conduction velocities and amplitudes
Summary
Distal symmetric diabetic polyneuropathy (DPN) is one of the most severe complications of diabetes, affecting approximately 200 million patients worldwide, with increasing prevalence leading to high morbidity and rising health care costs.[1]. Inpatient magnetic resonance neurography (MRN) at 3.0 T is a noninvasive method that allows for an exact qualitative and quantitative analysis of nerve damage in different neuropathies.[7,8,9] Recent results from an MRN study[10] in patients with DPN have shown that a decrease in serum high-density lipoprotein cholesterol (HDL-C) levels is associated with an increase in fat-equivalent lesions of the sciatic nerve and an increase in clinical symptom severity These nerve lesions occurred more frequently in patients with T2D compared with patients with T1D.10. Low serum cholesterol levels are associated with neuropathic symptoms and impair nerve regeneration after axonal damage in neurons of the central and peripheral nervous systems.[13,14,15,16,17] This association was mainly attributed to an insufficient supply of cholesterol to neurite tips and adjacent Schwann cells of regenerating axons as a consequence of a decrease in lipoproteins.[14,18,19,20,21] 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,[16] it is crucial to understand whether a decrease in total serum cholesterol and LDL-C levels is beneficial or potentially harmful for patients with T2D with DPN
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