Association of Serum Cholesterol Levels With Peripheral Nerve Damage in Patients With Type 2 Diabetes

Abstract

Importance: 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.

Objective: To investigate whether there is an association between serum cholesterol levels and peripheral nerve lesions in patients with T2D with and without DPN.

Design, setting, and participants: 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.

Exposures: 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.

Main outcomes and measures: The primary outcome was lesion load and extension. Secondary outcomes were clinical, serologic, and electrophysiologic findings.

Results: 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.

Conclusions and relevance: 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.

Figure 1.. Segmentation of Sciatic Nerve Hypointense Lesions in a T2-Weighed, Fat-Suppressed Sequence and Subsequent Processing of Image Factors

A, Typical acquired image at the thigh level. Red box indicates the sciatic nerve. B-D, Examples of different amounts of nerve lesions and clinical factors for 3 different patients at different clinical diabetic polyneuropathy stages. B, No polyneuropathy (neuropathy symptom score [NSS] = 0, neuropathy deficit score [NDS] = 5, total serum cholesterol [SC] level = 220 mg/dL [to convert to millimoles per liter, multiply by 0.0259). C, Moderate polyneuropathy (NSS = 4, NDS = 6, total SC = 167 mg/dL). D, Severe polyneuropathy (NSS = 6, NDS = 7, total SC = 40 mg/dL). E-G, Three-dimensional reconstructions of nerve lesions (red) and vital nerve volume (yellow) for the 3 patients with type 2 diabetes in panels B through D. E, No polyneuropathy (patient in B): few nerve lesions. F, Moderate polyneuropathy (patient in C): moderate amount of nerve lesions. G, Severe polyneuropathy (patient in D): extensive nerve lesions. Additional details about statistical correlations of lesion load or length are in the Results section.

Figure 2.. Magnetic Resonance Neurography Sciatic Nerve Findings in Correlation With Serum Cholesterol Levels

A, Total serum cholesterol (SC) level vs lipid equivalent lesion (LEL) load. SC level decreased linearly as a function of LEL load (in percentage of nerve tissue) as SC (LEL) = −1.28 mg/dL (%) × LEL + 211.5 mg/dL. B, SC level vs maximum lesion length (MLL). SC level decreased linearly as a function of MLL as SC (MLL) = −4.32 g/dL 1/m × MLL+ 242.50 mg/dL. C, SC level vs mean cross-sectional area (MCA). SC level decreased linearly as a function of the MCA as SC (MCA) = −0.45 × 10³ g/dL 1/m² × MCA + 248.40 mg/dL.