Diabetic ketoacidosis (DKA) is a severe and life-threatening acute complication of diabetes mellitus, primarily affecting patients with type 1 diabetes but occasionally occurring in type 2 diabetes under stress conditions such as infection, trauma, or non-compliance with insulin therapy (1). It is characterized by hyperglycemia, metabolic acidosis, and ketosis, leading to significant morbidity and mortality if not managed promptly (2). The cornerstone of DKA management is fluid resuscitation, correction of electrolyte imbalances, and insulin therapy to suppress ketogenesis and restore glycemic control (3).

Various insulin regimens are employed in DKA management, including continuous intravenous (IV) insulin infusion and subcutaneous administration of rapid-acting or basal-bolus insulin regimens (4). Continuous IV insulin infusion is considered the gold standard for DKA treatment due to its rapid onset of action, allowing for precise glycemic control and faster resolution of acidosis (5). However, it requires intensive monitoring and hospitalization in an intensive care unit (ICU), making it resource-intensive (6). Subcutaneous rapid-acting insulin, administered at regular intervals, has been explored as an alternative in settings with limited ICU availability, demonstrating comparable efficacy in mild to moderate DKA cases (7). The basal-bolus insulin regimen, widely used for chronic glycemic control, has also been considered for DKA management but is generally associated with a slower resolution of hyperglycemia and acidosis (8).

Several studies have compared the effectiveness of different insulin regimens in DKA management. Umpierrez et al. (9) found that subcutaneous insulin therapy was as effective as IV insulin in resolving mild to moderate DKA without requiring ICU admission. Similarly, a study by Dhatariya et al. (10) highlighted that although IV insulin achieves faster metabolic correction, subcutaneous regimens may reduce hospital stay duration in select cases. Nevertheless, there remains limited consensus on the optimal insulin regimen for DKA treatment in different clinical settings.

This study aims to compare the efficacy of three insulin regimens—continuous IV infusion, subcutaneous rapid-acting insulin, and basal-bolus insulin—in the management of DKA. The primary outcomes assessed include time to blood glucose normalization, resolution of acidosis, and total insulin requirement within the first 24 hours. Findings from this study will provide insights into optimizing insulin therapy strategies for DKA and guiding clinical decision-making in different healthcare settings.

Study Design and Population

This comparative study was conducted on 90 patients diagnosed with diabetic ketoacidosis (DKA) who were admitted to the emergency department of a tertiary care hospital. Patients were randomly assigned into three groups (n=30 per group) based on the insulin regimen administered. Group A received continuous intravenous (IV) insulin infusion, Group B was treated with subcutaneous rapid-acting insulin administered every 2 hours, and Group C received a basal-bolus insulin regimen.

Inclusion and Exclusion Criteria

Patients aged 18 years and above, diagnosed with DKA based on the criteria of blood glucose >250 mg/dL, arterial pH <7.3, and serum bicarbonate <18 mEq/L, were included in the study. Individuals with severe comorbidities, such as chronic kidney disease, liver dysfunction, pregnancy, or those receiving corticosteroid therapy, were excluded.

Treatment Protocol

All patients received standard initial management, including intravenous fluid resuscitation with normal saline, potassium supplementation as needed, and monitoring of vital signs and biochemical parameters.

• Group A (IV Insulin Infusion): Patients were started on a continuous infusion of regular insulin at a rate of 0.1 units/kg/hour, adjusted based on glucose levels.
• Group B (Subcutaneous Insulin): Rapid-acting insulin (lispro or aspart) was administered every 2 hours at 0.2 units/kg for the first two doses, followed by 0.1 units/kg until glucose levels dropped below 250 mg/dL.
• Group C (Basal-Bolus Regimen): Patients received long-acting insulin (glargine) once daily with rapid-acting insulin before meals at a dose of 0.3 units/kg/day, divided accordingly.

The transition to subcutaneous insulin was initiated when acidosis resolved (pH >7.3, bicarbonate >18 mEq/L), and the patient could tolerate oral intake.

Outcome Measures

The primary endpoints included:

1. Time to blood glucose normalization (defined as glucose <250 mg/dL).
2. Time to resolution of acidosis (pH >7.3 and bicarbonate >18 mEq/L).
3. Total insulin requirement within the first 24 hours.
4. Incidence of hypoglycemia (glucose <70 mg/dL) and other adverse events.

Statistical Analysis

Data were analyzed using SPSS software. Continuous variables were expressed as mean ± standard deviation and compared using ANOVA. Categorical variables were analyzed using the chi-square test. A p-value <0.05 was considered statistically significant.

Study Design and Population

This comparative study was conducted on 90 patients diagnosed with diabetic ketoacidosis (DKA) who were admitted to the emergency department of a tertiary care hospital. Patients were randomly assigned into three groups (n=30 per group) based on the insulin regimen administered. Group A received continuous intravenous (IV) insulin infusion, Group B was treated with subcutaneous rapid-acting insulin administered every 2 hours, and Group C received a basal-bolus insulin regimen.

Inclusion and Exclusion Criteria

Patients aged 18 years and above, diagnosed with DKA based on the criteria of blood glucose >250 mg/dL, arterial pH <7.3, and serum bicarbonate <18 mEq/L, were included in the study. Individuals with severe comorbidities, such as chronic kidney disease, liver dysfunction, pregnancy, or those receiving corticosteroid therapy, were excluded.

Treatment Protocol

All patients received standard initial management, including intravenous fluid resuscitation with normal saline, potassium supplementation as needed, and monitoring of vital signs and biochemical parameters.

• Group A (IV Insulin Infusion): Patients were started on a continuous infusion of regular insulin at a rate of 0.1 units/kg/hour, adjusted based on glucose levels.
• Group B (Subcutaneous Insulin): Rapid-acting insulin (lispro or aspart) was administered every 2 hours at 0.2 units/kg for the first two doses, followed by 0.1 units/kg until glucose levels dropped below 250 mg/dL.
• Group C (Basal-Bolus Regimen): Patients received long-acting insulin (glargine) once daily with rapid-acting insulin before meals at a dose of 0.3 units/kg/day, divided accordingly.

The transition to subcutaneous insulin was initiated when acidosis resolved (pH >7.3, bicarbonate >18 mEq/L), and the patient could tolerate oral intake.

Outcome Measures

The primary endpoints included:

1. Time to blood glucose normalization (defined as glucose <250 mg/dL).
2. Time to resolution of acidosis (pH >7.3 and bicarbonate >18 mEq/L).
3. Total insulin requirement within the first 24 hours.
4. Incidence of hypoglycemia (glucose <70 mg/dL) and other adverse events.

Statistical Analysis

Data were analyzed using SPSS software. Continuous variables were expressed as mean ± standard deviation and compared using ANOVA. Categorical variables were analyzed using the chi-square test. A p-value <0.05 was considered statistically significant.

Baseline Characteristics

A total of 90 patients diagnosed with diabetic ketoacidosis (DKA) were included in the study. The mean age of participants was 42.3 ± 10.5 years, with 55% being male and 45% female. Baseline biochemical parameters, including blood glucose, arterial pH, and serum bicarbonate levels, were comparable across all three groups (Table 1).

Table 1: Baseline Characteristics of Study Participants

Glycemic Control and Acidosis Resolution

Patients in Group A demonstrated the fastest blood glucose normalization, achieving levels below 250 mg/dL in 8.5 ± 2.1 hours, compared to 10.2 ± 2.5 hours in Group B and 12.4 ± 3.0 hours in Group C (p < 0.05, Table 2). Similarly, the resolution of acidosis (pH >7.3, bicarbonate >18 mEq/L) was significantly quicker in Group A (12.1 ± 3.5 hours) compared to Group B (14.7 ± 4.2 hours) and Group C (16.9 ± 4.8 hours, p < 0.05) (Table 2).

Table 2: Comparison of Time to Glycemic Control and Acidosis Resolution

Total Insulin Requirement and Hypoglycemic Events

The total insulin requirement in the first 24 hours was lowest in Group A (48 ± 9 units) and highest in Group C (65 ± 12 units, p < 0.05) (Table 3). Group A also reported a slightly higher incidence of hypoglycemic events (5 cases) compared to Group B (3 cases) and Group C (2 cases), though these were managed without additional interventions (Table 3).

Table 3: Insulin Requirement and Hypoglycemic Events

Overall, continuous IV insulin infusion was the most effective regimen, demonstrating faster glucose control and acidosis resolution compared to subcutaneous insulin and basal-bolus therapy. Though hypoglycemic events were slightly more frequent in Group A, they were not severe and did not require additional interventions. These findings suggest that while IV insulin remains the preferred approach in critical settings, subcutaneous rapid-acting insulin may be a viable alternative in non-critical cases (Table 2 & Table 3).

Diabetic ketoacidosis (DKA) remains a critical complication of diabetes mellitus, requiring prompt and effective insulin therapy for rapid metabolic correction. This study compared three insulin regimens—continuous intravenous (IV) infusion, subcutaneous rapid-acting insulin, and basal-bolus insulin—for their efficacy in managing DKA. The findings demonstrated that continuous IV insulin infusion was the most effective regimen, achieving faster glucose normalization and acidosis resolution compared to the other two methods.

The results align with previous studies that have established IV insulin infusion as the gold standard for DKA management. Umpierrez et al. (1) reported that IV insulin leads to faster glucose control due to its immediate systemic absorption and precise titration. Similarly, a study by Kitabchi et al. (2) emphasized that continuous insulin infusion results in quicker acidosis correction and better overall patient stabilization. The present study found that patients in the IV insulin group achieved blood glucose levels below 250 mg/dL in an average of 8.5 ± 2.1 hours, significantly faster than the subcutaneous and basal-bolus regimens, which took 10.2 ± 2.5 and 12.4 ± 3.0 hours, respectively.

Acidosis resolution was also achieved more rapidly in the IV insulin group, with a mean correction time of 12.1 ± 3.5 hours, compared to 14.7 ± 4.2 hours in the subcutaneous group and 16.9 ± 4.8 hours in the basal-bolus group. These findings are consistent with previous reports suggesting that IV insulin maintains steady plasma insulin levels, ensuring continuous suppression of ketogenesis and efficient bicarbonate recovery (3,4). In contrast, subcutaneous insulin administration may be less effective in severe cases of DKA due to delayed absorption and variability in insulin pharmacokinetics (5).

The total insulin requirement in the first 24 hours was highest in the basal-bolus group (65 ± 12 units), followed by the subcutaneous group (57 ± 11 units), while the IV insulin group had the lowest requirement (48 ± 9 units). This observation suggests that IV insulin is not only more effective but also more insulin-efficient in resolving DKA. A study by Dhatariya et al. (6) similarly reported that patients receiving continuous IV insulin required lower total insulin doses than those on intermittent subcutaneous regimens. However, IV insulin therapy requires continuous monitoring in an intensive care setting, which may not always be feasible in resource-limited environments.

Although IV insulin was associated with a slightly higher incidence of hypoglycemic events (5 cases), none required major interventions. Hypoglycemia is a well-documented concern in aggressive insulin therapy; however, proper glucose monitoring and titration can minimize these risks (7). Previous studies have indicated that while IV insulin can lead to more frequent glucose fluctuations, it remains the safest approach in critical care settings due to its adjustability (8).

An important aspect to consider is the role of subcutaneous insulin as a feasible alternative in non-critical cases. Recent studies have explored the efficacy of subcutaneous rapid-acting insulin for mild to moderate DKA, with promising results. Umpierrez et al. (9) demonstrated that subcutaneous insulin lispro, administered every 2 hours, led to similar recovery outcomes compared to IV insulin in select patients. In this study, while subcutaneous insulin took slightly longer to correct hyperglycemia and acidosis, it remained a practical alternative, particularly in settings where ICU admission is limited.

The basal-bolus regimen, although commonly used for long-term glycemic control, was the least effective for acute DKA management in this study. Patients in this group had the slowest metabolic recovery and highest insulin requirement. This finding is consistent with previous research suggesting that basal-bolus insulin alone is insufficient for the rapid suppression of ketosis in DKA (10). However, it may still be useful for transition therapy once acute metabolic derangements are corrected.

This study reinforces the superiority of IV insulin infusion in managing DKA, particularly in critically ill patients requiring rapid metabolic correction. However, subcutaneous insulin therapy may be a viable alternative in non-ICU settings, reducing healthcare costs and hospitalization burdens. Future research should explore the long-term outcomes of these regimens, including cost-effectiveness and patient-reported experiences. Additionally, studies evaluating hybrid approaches—such as initial IV insulin followed by an accelerated subcutaneous regimen—may provide further insights into optimizing DKA management strategies.

Limitations

This study had some limitations. The sample size was relatively small, and the findings were based on a single-center study, limiting generalizability. Additionally, the study did not assess long-term glycemic outcomes post-DKA recovery. Future multicenter trials with larger populations are recommended to validate these findings.

Continuous IV insulin infusion remains the most effective regimen for rapid correction of hyperglycemia and acidosis in DKA. While subcutaneous rapid-acting insulin can serve as an alternative in non-critical cases, the basal-bolus regimen is less effective for acute management. Further research is needed to explore optimal insulin strategies tailored to different clinical settings.

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