European Journal of Cardiovascular Medicine

Diabetes mellitus is a chronic metabolic disorder characterized by persistent hyperglycemia, which is associated with long-term damage, dysfunction, and failure of various organs, especially the eyes, kidneys, nerves, heart, and blood vessels [1]. Insulin therapy remains a cornerstone in the management of diabetes, particularly for type 1 diabetes and advanced type 2 diabetes, where oral antidiabetic agents are insufficient to achieve glycemic control [2]. Among the therapeutic options available, premixed insulin formulations such as Human Mixtard 30 and Human Mixtard 50 have been widely used due to their convenience in mimicking natural insulin secretion, thus improving compliance and overall diabetes management [3].

Premixed insulins, combining intermediate-acting and short-acting insulin, offer a balance between controlling postprandial glucose spikes and maintaining basal insulin levels. Human Mixtard 30 (30% short-acting insulin and 70% intermediate-acting NPH insulin) and Human Mixtard 50 (50% short-acting insulin and 50% intermediate-acting NPH insulin) are specifically designed to address the dual needs of basal and prandial insulin coverage [4]. These formulations are particularly beneficial for patients who have difficulty managing complex insulin regimens or those who have demonstrated poor glycemic control on basal or mealtime insulin alone [5].

Recent studies have emphasized the efficacy and safety of premixed insulin regimens in achieving targeted glycemic levels, with a significant reduction in HbA1c, suggesting their potential in reducing the risk of diabetes-related complications [6]. However, the comparative effectiveness of different ratios of premixed insulins in real-world clinical settings remains under-explored. Moreover, the choice between different premixed insulin formulations often depends on individual patient profiles, including lifestyle, meal patterns, and sensitivity to insulin [7]. This study aims to compare the effectiveness of Human Mixtard 30 and Human Mixtard 50 in improving glycemic control among poorly controlled insulin-requiring diabetics.

Study Design

This was a retrospective observational study.

Study Setting

The study was conducted at the Veer Surendra Sai Institute of Medical Sciences and Research (VIMSAR), Burla, Sambalpur, Odisha. This tertiary care teaching hospital serves as a regional referral center, providing a diverse patient population for the study.

Participants
A total of 100 poorly controlled insulin-requiring diabetic patients were included in this study. Participants’ data were sourced from outpatient and inpatient medical records maintained at VIMSAR.

Inclusion and Exclusion Criteria

Inclusion criteria consisted of adult patients (18 years and older) diagnosed with poorly controlled diabetes requiring insulin therapy, with complete medical records during the study period. Exclusion criteria included patients on non-insulin therapies, those with incomplete or missing data, individuals with known secondary causes of hyperglycemia (such as Cushing’s syndrome), and those with end-stage renal or hepatic failure.

Bias
To minimize selection bias, all eligible patients meeting the inclusion criteria during the study period were included without additional screening. Information bias was reduced by cross-checking data entries from multiple sources (inpatient and outpatient records). Measurement bias was addressed by standardizing all recorded parameters and ensuring consistent units and definitions across data entries.

Data Collection

Data were extracted from the hospital’s electronic and paper-based medical records. Variables collected included age, sex, baseline HbA1c, daily insulin doses, insulin regimen (Mixtard 30 vs. Mixtard 50), and follow-up HbA1c values. Additional data points such as body weight, lipid profiles, and adverse events were also recorded.

Procedure
Once eligible patients were identified, their medical records were reviewed in chronological order. Data were systematically recorded in a structured format. Each patient’s baseline HbA1c value, insulin regimen at initiation, and subsequent follow-up values were noted. Adverse events, if any, were documented and categorized.

Statistical Analysis

Statistical analysis was performed using SPSS version 23.0. Descriptive statistics such as means and standard deviations were calculated for continuous variables, while categorical variables were presented as frequencies and percentages. The paired t-test was used to compare pre- and post-intervention HbA1c levels. Chi-square tests were applied for categorical variables to examine differences between groups. Statistical significance was set at p < 0.05.

The study assessed 100 participants, 50 of whom were treated with Human Mixtard 30 and 50 with Human Mixtard 50. The mean age of participants was 58 years (SD = 10 years), with a gender distribution of 40% female and 60% male. The baseline HbA1c for the entire cohort was 9.2% (SD = 1.5%).

Table 1: Participant Demographics and Baseline Characteristics

The statistical analysis revealed a significant reduction in HbA1c from baseline to the study end point in both groups. The Human Mixtard 30 group showed a reduction to 7.8% (SD = 1.2%, p < 0.001), while the Human Mixtard 50 group decreased to 7.5% (SD = 1.1%, p < 0.001).

Table 2: HbA1c Levels Before and After Treatment

A comparative analysis between the two insulin regimens showed no significant difference in the reduction of HbA1c (p = 0.202). Both groups also reported similar rates of hypoglycemia as an adverse event, with 12% in the Mixtard 30 group and 10% in the Mixtard 50 group (p = 0.739).

Table 3: Adverse Events Reported

The study evaluated the effectiveness of two insulin regimens, Human Mixtard 30 and Human Mixtard 50, in managing poorly controlled diabetes in 100 participants. The findings revealed a significant improvement in glycemic control with both insulin types. Initially, the mean HbA1c level across all participants was 9.2%. After the intervention, participants on Human Mixtard 30 experienced a decrease in HbA1c to 7.8%, and those on Human Mixtard 50 saw a reduction to 7.5%. Both reductions were statistically significant (p < 0.001), indicating a robust response to insulin therapy.

Importantly, the study found no significant difference in the effectiveness of the two insulin regimens in lowering HbA1c levels (p = 0.202), suggesting that both formulations are similarly effective in controlling blood sugar levels. This equivalence is particularly relevant for clinical practice, as it allows flexibility in prescribing based on factors other than efficacy, such as patient preference, availability, or cost considerations.

The safety profiles of the two regimens were also comparable, with similar rates of hypoglycemia reported (12% for Human Mixtard 30 and 10% for Human Mixtard 50; p = 0.739). This similarity in adverse events underscores the comparable safety of these insulin types when used under clinical supervision. Overall, the results support the use of either Human Mixtard 30 or Human Mixtard 50 in the clinical management of poorly controlled insulin-requiring diabetes. The study highlights the importance of individualized treatment plans and provides evidence that can guide the choice between these two commonly used insulin regimens.

The role of soluble insulin receptors in metabolic syndrome has been highlighted in recent studies. Hiriart-Urdanivia et al. (2020) demonstrated that an increase in soluble insulin receptors in the bloodstream could serve as an early indicator of metabolic syndrome. Their research showed that hyperinsulinemic rats exhibited significantly higher levels of soluble insulin receptors compared to controls, suggesting a compensatory mechanism in response to metabolic dysfunction [8]. The impact of diabetes on liver glycogen metabolism was investigated by Daneshnia et al. (2022), who studied streptozotocin-induced diabetic rats. They found that total liver glycogen decreased by approximately 39% in diabetic rats, with a more pronounced reduction in the acid-soluble glycogen fraction. These findings indicate that diabetes significantly alters glycogen storage and utilization, potentially affecting metabolic control in insulin-dependent diabetics [9].

Another important aspect of metabolic regulation involves leptin receptors. Ali and Rasool (2023) examined the effects of metformin on plasma levels of soluble leptin receptors (sOB-R) in type 2 diabetes and metabolic syndrome patients. Their study reported a significant increase in sOB-R levels following metformin treatment, with levels rising from 7.82 ng/mL to 10.19 ng/mL in type 2 diabetes patients, indicating that metformin may enhance leptin sensitivity and metabolic regulation [10]. The hepatokine FNDC4 has been implicated in insulin sensitization. Georgiadi et al. (2021) identified GPR116 as a receptor for FNDC4 in white adipose tissue. Their research demonstrated that FNDC4 binding to GPR116 enhanced insulin signaling and glucose uptake in adipocytes. Supplementation with FNDC4 improved glucose tolerance and reduced inflammatory markers in prediabetic mice, suggesting a novel target for improving insulin sensitivity in metabolic disorders [11].

The relationship between insulin dosing and meal composition was explored by Toschi et al. (2024) in individuals with type 1 diabetes. They found that low-glycemic index meals required more insulin compared to high-glycemic index meals. Additionally, the carbohydrate-to-insulin ratio varied significantly depending on the fat and carbohydrate content of meals, emphasizing the importance of personalized insulin dosing strategies for optimizing glycemic control [12]. Palmiotti et al. (2024) assessed the effects of lifestyle-induced weight loss on insulin resistance and bile acid composition in obese individuals. While glycemic control improved following weight loss, they observed no significant changes in bile acid ratios, suggesting that insulin sensitivity improvements may not directly influence bile acid metabolism [13].

The study conclusively demonstrates that both Human Mixtard 30 and Human Mixtard 50 are effective in significantly reducing HbA1c levels in poorly controlled insulin-requiring diabetics, with no significant difference in their efficacy. The safety profiles of both insulin formulations were also found to be comparable, with similar rates of hypoglycemia reported. These findings support the continued use of either insulin regimen depending on patient-specific factors such as preference, accessibility, and cost. This research enriches the body of evidence suggesting that premixed insulins are a viable option for managing complex cases of diabetes, offering flexibility and simplicity in treatment protocols.

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