Patients with type 2 diabetes on intensive lipid lowering therapy may be at an increased risk for developing secondary neuropathies, based on the results of a recent study.
A common metabolic comorbidity among patients with type 2 diabetes is dyslipidemia; other secondary complications that result from uncontrolled diabetes include retinopathy, kidney disease, and neuropathy. Elevated serum cholesterol increases the risk of cardiovascular events through plaque ruptures, thus typically prompting treatment with lipid lowering agents such as the statin class of medications. Previous studies have found an association between low serum cholesterol levels and an increased incidence of nerve lesions in patients with type 2 diabetes. This leads researchers to question which moving factor contributes to the development of new lesions in nerve tissue in patients with type 2 diabetes, in order to determine if aggressive lipid lowering therapies are potentially harmful in certain patient populations
A recent prospective cohort study conducted out of Germany and published in the Journal of the American Medical Association had this exact question in mind as the researchers were developing their trial design; their objective was to determine the association between serum cholesterol and development of nerve lesions in patients with type 2 diabetes. After screening a total 256 potential candidates, only 100 patients with type 2 diabetes with and without already diagnosed diabetic neuropathy were eligible to be enrolled into this study; participants were excluded if they had a significant medical history of lumbar surgery, any relevant disc herniation, possessed any risk factors for neuropathic developments, or had an estimated glomerular filtration rate of less than or equal to 60 mL/min.
Patients enrolled underwent magnetic resonance imaging of the right leg to determine the incidence of diabetic neuropathy; patients were required to meet neuropathy deficit or symptom score threshold of five or greater and have abnormal conduction in two or greater nerves to confirm diagnosis. Two tailed t tests were used to compare outcomes between patients with type 2 diabetes who already had a diagnosis of secondary diabetic neuropathy (n = 64) and those who had yet to develop it (n = 36) at baseline. Pearson correlation coefficients were calculated to determine associations between neuropathic findings and other study outcomes.
On average, patients enrolled were 64.6 years old and male with a BMI of 30, HbA1c of 7.23% and normal kidney function. Statistically significant positive correlations were found between reduced tibial and peroneal nerve conduction velocities and diagnosed diabetic neuropathy (r = 0.32 and 0.30, respectively). Significant correlations were also found between incidence of diabetic neuropathy and both total serum cholesterol and serum low density lipoprotein cholesterol (LDL-C) values, but not high density lipoprotein cholesterol (HDL-C). On average, patients who had diabetic neuropathy had 22.31 mg/dL lower total serum cholesterol and 26.17 mg/dL lower LDL-C. Total serum LDL-C was positively correlated most significantly with tibial compound muscle action potential (r = 0.44). No other significant correlations were found between diagnosis of diabetic neuropathy and other baseline characteristics and clinical labs.
Similar to the results previously mentioned, significant negative correlations were found between reduced nerve conduction velocities and muscle action potentials of the tibial and peroneal nerves and an increase in lipid equivalent lesion loads. Correlations failed to be demonstrated between outcomes within the sural nerve. Lipid equivalent lesion loads were also significantly negatively correlated with total serum cholesterol levels (r = -0.41), LDL-C levels (r = -0.33) and HDL-C levels (r = -0.30). Magnetic resonance imaging results from a total of 8 sural nerve readings were missing from the study and not included within primary analysis due either severe patient obesity resulting in impaired recording or severe nerve damage that developed during the study period, offering a possible explanation for the lack of correlations found compared to those of the tibial and peroneal nerves.
In conclusion, through cross sectional analysis, the researchers found a significant association between low serum cholesterol levels, especially LDL-C and an increased amount of nerve lesions and peripheral nerve swelling in patients with type 2 diabetes. The results of this study warrant future longitudinal trials with similar designs to determine which exact causes increase patient risk for developing diabetic neuropathy.
- Reduced cholesterol levels, especially LDL-C, were observed to be significantly associated with decreased conduction velocities and action potential of nerves in patients with type 2 diabetes.
- Data from 100 total patients enrolled into this study was obtained prospectively and analyzed cross sectionally to determine correlations.
- Providers should consider the possible increased risk of neuropathy in patients with type 2 diabetes on intensive lipid lowering therapy.
Reference for “Intensive Lipid Lowering Linked To Neuropathy”:
Jende JME, Groener JB, Rother C, et al. Association of serum cholesterol levels with peripheral nerve damage in patients with type 2 diabetes. JAMA Network Open 2019; 2(5):e194798. DOI: 10.1001/jamanetworkopen.2019.4798
Adam Chalela B.S., PharmD Candidate, USF College of Pharmacy Class of 2020