Relationship between Hyponatremia and Peripheral Neuropathy in Patients with Diabetes

Abstract

Objectives: Hyponatremia is a common complication of diabetes. However, the relationship between serum sodium level and diabetic peripheral neuropathy (DPN) is unknown. This study was aimed at investigating the relationship between low serum sodium level and DPN in Chinese patients with type 2 diabetes mellitus.

Methods: A retrospective study was performed on 1928 patients with type 2 diabetes between 2010 and 2018. The multivariate test was used to analyze the relationship between the serum sodium level and the nerve conduction function. A restricted cubic spline was used to flexibly model and visualize the relationship between the serum sodium level and DPN, followed by logistic regression with adjustment.

Results: As the serum sodium level increased, the prevalence of DPN had a reverse J-curve distribution with the serum sodium levels (69.6%, 53.7%, 49.6%, 43.9%, and 49.7%; P = 0.001). Significant differences existed between the serum sodium level and the motor nerve conduction velocity, sensory nerve conduction velocity, part of compound muscle action potential, and sensory nerve action potential of the participants. Compared with hyponatremia, the higher serum sodium level was a relative lower risk factor for DPN after adjusting for several potential confounders (OR = 0.430, 95%CI = 0.220-0.841; OR = 0.386, 95%CI = 0.198-0.755; OR = 0.297, 95%CI = 0.152-0.580; OR = 0.376, 95%CI = 0.190-0.743; all P < 0.05). Compared with low-normal serum sodium groups, the high-normal serum sodium level was also a risk factor for DPN (OR = 0.690, 95%CI = 0.526-0.905, P = 0.007). This relationship was particularly apparent in male participants, those aged <65 years, those with a duration of diabetes of <10 years, and those with a urinary albumin - to - creatinine ratio (UACR) < 30 mg/g.

Conclusions: Low serum sodium levels were independently associated with DPN, even within the normal range of the serum sodium. We should pay more attention to avoid the low serum sodium level in patients with type 2 diabetes mellitus.

Figure 1

Details of excluded patients.

Figure 2

Relationship between serum sodium level and diabetic peripheral neuropathy. Restricted cubic splines were used to flexibly model and visualize the relationship between the serum sodium level and DPN. The risk of DPN was relatively flat until around 140 mmol/L of the serum sodium level and then started to increase rapidly forward and afterward (P for nonlinearity <0.05) in all serum sodium groups, especially in male patients, those aged <65 years, and those with UACR < 30 mg/g. However, a nonlinear trend was not observed in normal serum sodium group and its subgroups. The average serum sodium level of 140 mmol/L serves as a reference.

Figure 3

Plot of diabetic peripheral neuropathy and serum sodium level. (a) All serum sodium group and normal serum sodium group. Adjusted for age, sex, duration of diabetes, BMI, systolic blood pressure, diastolic blood pressure, HbA1c, eGFR, serum kalemia, hypotensive drugs (β-blocker, CCB, ACEI, and ARB), statins, hypoglycemic drugs, insulin use, smoking, drinking, and hypertension. (b) Subgroup analysis of all serum sodium group and normal serum sodium group. Adjusted for hypotensive drugs (β-blocker, CCB, ACEI, and ARB), statins, hypoglycemic drugs, insulin using, smoking, and drinking.