Low Serum Sodium Associated With Peripheral Diabetic Neuropathy in Type 2 Diabetes

Low serum sodium levels are independently associated with diabetic peripheral neuropathy (DPN), even within the normal serum sodium range, in patients with type 2 diabetes (T2D), according to results of a retrospective study published in Journal of Diabetes Research.

Currently, literature on the relationship between DPN and serum sodium levels is limited.

In the current cross-sectional study, researchers sought to clarify this association to inform early screening among patients with T2D.

Patients with T2D were enrolled from a single medical center between 2010 and 2018. Diabetes diagnosis was made based on World Health Organization (WHO) criteria, and hypertension was defined as a systolic blood pressure of 140 mmHg or higher or a diastolic blood pressure of 90 mmHg or higher. Corrected blood sodium levels were calculated based on blood glucose level.

Somatic neuropathy symptoms were documented; they included numbness, burning, deep aching, and unsteadiness in walking. Neurologic examinations were completed and neurologic score and reflex score, and sensory function score were recorded. In addition, patients underwent a nerve conduction study.

The study cohort included 1928 patients with T2D (mean age, 60.10 years; 1053 men) enrolled from the Endocrinology and Neurology Department at the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China. Within the cohort, 1530 had normal serum sodium levels, 342 had hypernatremia, and 56 presented with hyponatremia. In addition, a total of 960 participants were diagnosed with DPN.

Patients were divided into 3 groups based on diagnostic criteria (hyponatremia, hypernatremia, and normal serum sodium); the normal serum sodium group was further subdivided into 3 tertiles.

Significant changes were observed in terms of sex, body mass index (BMI), smoking status, drinking history, and use of diuretics and oral hypoglycemic drugs.

Regarding nerve conduction function, the researchers found that the motor and sensory nerve conduction velocity and ulnar and sural-nerve sensory nerve action potential (SNAP) increased with an increase in serum sodium levels. Tibial and peroneal-nerve compound muscle action potential, as well as superficial peroneal-nerve SNAP, increased, and then decreased. Among patients with normal serum sodium levels, those in the low-normal vs high normal tertile had a lower mean corpuscular volume, ulnar-nerve sensory conduction velocity (SCV), and superficial peroneal-nerve SCV.

Risk for DPN was “relatively flat” up to a serum sodium level of 140 mmol/L (95 mg/dL), during which the risk rapidly increased in all serum sodium groups — particularly among men aged younger than 65 years and those with urine albumin-to-creatinine ratio (UACR) less than 30 mg/g.

In a whole-group analysis, the researchers divided patients into 5 groups based on serum sodium levels. Results of multiple logistic regression analyses showed that hyponatremia was associated with DPN, after adjusting for multiple factors including age, sex, diabetes duration, BMI, blood pressure, hemoglobin A1c, and estimated glomerular filtration rate; use of hypotensive or hypoglycemic drugs or insulin; and smoking, drinking, and hypertension. Across all serum sodium groups, no significant relationship was detected between subgroups of participants aged 65 years and older or with a UACR of at least 30 mg/g.

A fully adjusted logistic regression analysis in the normal serum sodium group showed that a high-normal serum sodium level was a “relatively lower” risk factor for DPN (odds ratio, 0.690; 95% CI, 0.526-0.905; P =.007). This relationship was particularly notable among men, participants aged younger than 65 years, those with a duration of diabetes less than 10 years, and those with a UACR less than 30 mg/g.

Study limitations included the small number of patients with hyponatremia, the lack of recorded sodium intake and vitamin B levels, and an inability to determine if the relationship between DPN and hyponatremia “reflected a direct effect of hyponatremia, a surrogate marker for underlying comorbidities or reason for DPN, or both.”

“Since even minor serum sodium disturbances are associated with mortality, patient outcomes can be significantly improved by frequently monitoring electrolytes and discontinuing drugs with adverse effects, when necessary,” the researchers concluded. “Further studies are needed to understand the factors leading to this prognostic relationship and the potential benefit from therapeutic strategies aimed at this metabolic disturbance.”

Reference

Zhang Y, Li C, Huang L, et al. Relationship between hyponatremia and peripheral neuropathy in patients with diabetes. J Diabetes Res. Published online August 20, 2021. doi:10.1155/2021/9012887