Globally diabetes is now one of the most common non-communicable diseases. The prevalence of diabetes is 10.1 crores (1), as per Indian Council of Medical Research – India Diabetes (ICMR INDIAB) study published in 2023. Persons with diabetes are at increased risk for chronic complications which may affect many organ systems and responsible for the associated morbidity and mortality with the disease. As the disease progresses, patients are at higher risk for the development of various complications including metabolic imbalances, blood vessels degeneration, effect on electrolyte concentration and offset of the proportion of electrolytes.

In diabetic people osmotic fluid changes brought on by hyperglycemia affects body's electrolyte concentration and causes electrolyte imbalance. If water movement transports intracellular electrolytes to the extracellular space, it may have a dilutional effect, by lowering extracellular electrolyte concentrations or increasing extracellular concentrations, especially in an insulin-deficient state (2). The relationship between blood glucose and electrolytes is complex and electrolyte imbalance may affect the course of diabetes and its management.

Moreover, diabetic nephropathy which is one of the complications of diabetes is characterized by impaired renal function can lead to electrolyte imbalance, as elevated blood sugar damages the nephrons, thereby altering electrolyte absorption and reabsorption. Diabetic patients frequently develop different types of subclinical electrolyte disorders. As fasting blood glucose rises, serum electrolytes namely sodium, potassium and chloride become deranged. Most encountered electrolyte abnormality being hyponatremia, however disturbances in potassium, chloride, calcium and magnesium are also not uncommon. Potassium is a crucial marker in diabetic nephropathy. So monitoring of serum electrolytes in diabetic patients may be helpful in preventing chronic irreparable complications. Number of studies have shown the association between electrolytes level and hyperglycemia (3,4). Hence, we determined to study the pattern of electrolytes in patients with diabetes mellitus and to compare the electrolyte levels in controlled and uncontrolled diabetes mellitus based on the glycemic status.

A prospective cross-sectional study was conducted in the department of Biochemistry, S.V. Medical College, Tirupathi after obtaining approval from institutional ethics committee.  A total of 79 participants with type 2 diabetes attending medicine OPD were enrolled. A written well-informed consent is collected from all the participants of the present study.

Inclusion criteria: Patients of both genders aged between 35 to 65yrs diagnosed as diabetes mellitus attending medical OP at SVRRGGH hospital, Tirupati.

Exclusion criteria: Patients with Type 1 diabetes mellitus, renal or hepatic failure, malabsorption syndrome, Cushing’s and Addison’s disease, on diuretics, ACE inhibitors and steroids. Pregnant women with gestational diabetes.

Sample size:

Sample size was calculated as 79 by using formula 4pq/d² considering the confidence interval equal to 95% with precision of 10% and prevalence of electrolyte imbalance as 83% according to a study conducted by Eshetu et al (5).

Four milliliters (4.0 mL) of venous blood were collected using standard phlebotomy technique in a serum tube for electrolyte estimation and in an EDTA vial for HbA1c analysis. The blood was allowed to clot at room temperature for 20-30 minutes, followed by centrifugation at 2000 RPM for 15 minutes. The supernatant serum was preserved at -20°C until further analysis was performed.  Serum electrolytes sodium, potassium and chloride were analyzed by using indirect ion selective electrode in ST 200 Pro electrolyte analyzer. Glycated hemoglobin was estimated based on immunoturbidimetry method by using commercially available kits in Transasia fully automated analyzer.

Statistical analysis:

The Kolmogorov-Smirnov test will be performed to test the normality of data distribution. Data obtained will be expressed as mean ± standard deviation for continuous variables and as frequency (number [%]) for categorical variables. Independent t-tests will be used to determine the mean difference for normally distributed data. The data collected will be entered in Microsoft excel and analyzed in SPSS software.

Table 1: Baseline characteristics and parameters of study participants

Table 2: Comparison of serum electrolyte levels in controlled and uncontrolled diabetes patients

Table 3: Correlation of HbA1c with Serum electrolytes

Fig 1: Bar diagram showing comparison of serum sodium, serum potassium, serum chloride and HbA1c levels among controlled and uncontrolled diabetes mellitus patients.

Electrolyte disturbances are common in patients with diabetes mellitus, particularly those with poor glycemic control. Understanding the pattern of electrolyte disturbances in diabetic patients is crucial for managing and preventing complications such as cardiovascular events, neurological issues, and kidney dysfunction, which are often exacerbated by these imbalances.

In the present study, serum sodium levels were significantly lower in uncontrolled diabetes patients (128.7 ± 7.2) compared to controlled patients (134.5 ± 3.76, p = 0.0018). This result aligns with several other studies investigating electrolyte disturbances in diabetes mellitus. Eshetu et al.⁶ similarly observed reduced serum sodium in uncontrolled diabetes, attributing it to osmotic diuresis induced by hyperglycemia, which leads to increased renal sodium excretion. Gupta et al.⁷ also found a significant reduction in serum sodium levels in diabetic patients with poor glycemic control, supporting the notion that hyperglycemia-induced renal dysfunction plays a key role in these imbalances. These consistent findings across studies suggest that sodium disturbances are a common feature of poorly controlled diabetes, highlighting the importance of monitoring electrolyte levels in such patients to avoid complications.

The present study also found elevated serum chloride levels in uncontrolled diabetes (109.5 ± 5.9) compared to controlled diabetes (106 ± 3.89, p = 0.0342). This observation is consistent with previous research, including studies by Banerjee et al.⁸  and Kumar et al.⁹, who reported higher chloride concentrations in poorly controlled diabetes. The increase in chloride levels may be a compensatory mechanism to maintain electrical neutrality as sodium levels decrease due to osmotic diuresis. Furthermore, a positive correlation between serum chloride and HbA1c (r = 0.38) in this study suggests that hyperglycemia influences chloride retention. In this context, the kidneys may retain chloride ions to balance sodium loss, as described by Banerjee et al.⁸. These findings underscore the role of chloride in the compensatory response to sodium depletion during episodes of hyperglycemia.

In contrast, the present study did not find a significant difference in serum potassium levels between controlled and uncontrolled diabetes (p = 0.7882), which is at odds with some other studies that report changes in potassium concentrations with poor glycemic control. Singh et al.¹⁰ found that potassium levels were significantly elevated in uncontrolled diabetes, likely due to insulin resistance, which impairs the cellular uptake of potassium. However, the present study's findings may be explained by the exclusion of patients with renal impairment, as potassium disturbances are more commonly observed in those with diabetic nephropathy (Gupta et al.⁷) Additionally, the relatively short duration of diabetes in the study cohort (mean duration = 5.03 ± 3.95 years) may have reduced the likelihood of significant potassium disturbances, which tend to be more pronounced in long-standing diabetes or cases with severe metabolic disturbances.

Moreover, Li et al.¹¹ and Yadav et al.¹² also observed that potassium levels in diabetic patients often remain within normal ranges unless there is significant renal dysfunction or long-term poor glycemic control. This further suggests that the absence of significant potassium imbalances in the current study might be due to the relatively early stage of diabetes in the patient population and the absence of comorbidities that could exacerbate potassium disturbances.

In conclusion, this study highlights the significant impact of glycemic control on electrolyte disturbances in type 2 diabetes mellitus patients, particularly concerning sodium and chloride levels. Uncontrolled diabetes was associated with lower sodium and higher chloride levels, consistent with osmotic diuresis and renal dysfunction. Although no significant changes in potassium levels were observed, other studies suggest potassium disturbances become more pronounced in long-standing or renal-compromised diabetes. Monitoring serum electrolytes in diabetic patients is crucial to preventing complications, and future research should focus on the underlying mechanisms contributing to these disturbances, particularly in patients with prolonged disease duration.

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