Type 2 Diabetes Mellitus (T2DM) is a prevalent and growing public health challenge worldwide. It is characterized by insulin resistance, impaired insulin secretion, and chronic hyperglycemia, which can lead to severe complications such as cardiovascular disease, neuropathy, and retinopathy. Alongside hyperglycemia, elevated serum uric acid (SUA) levels are commonly observed in T2DM patients and are associated with insulin resistance, inflammation, and oxidative stress, which can worsen disease progression [1][2].

Lifestyle factors, such as poor diet, sedentary behavior, and obesity, play a significant role in the development and management of T2DM. Previous studies have shown that lifestyle interventions—specifically dietary changes and increased physical activity—can improve glycemic control in T2DM patients by enhancing insulin sensitivity and reducing body weight [3]. However, less is known about the impact of these interventions on SUA levels and their potential role in improving overall metabolic health.

This study aims to assess the impact of a 12-week structured lifestyle intervention on SUA levels and glycemic control in T2DM patients. We hypothesize that such interventions will reduce both SUA and glycemic markers, offering potential benefits in managing T2DM.

Study Design and Participants

This prospective study was conducted at a tertiary care hospital. We enrolled 120 adult patients diagnosed with T2DM, aged 40-70, with an HbA1c between 7% and 10%. Patients with kidney disease, gout, or other metabolic disorders were excluded from the study. All participants provided informed consent, and the institutional ethics committee approved the study.

Intervention
The intervention consisted of a 12-week program focusing on two main components: (1) dietary modifications and (2) physical activity.

• Dietary modifications: Participants were provided with a diet plan emphasizing low-glycemic index foods, increased fiber intake, reduced saturated fat, and a caloric deficit to promote weight loss.
• Physical activity: Participants were instructed to engage in at least 150 minutes of moderate-intensity aerobic exercise per week, such as brisk walking or cycling, combined with strength training exercises twice a week.

Outcome Measures

The primary outcome of the study was the change in serum uric acid (SUA) levels, while secondary outcomes included changes in glycemic markers (FBS, HbA1c, and PPBG). All measurements were taken at baseline (pre-intervention) and after the 12-week intervention period.

Statistical Analysis

Descriptive statistics were used to summarize baseline characteristics and changes in clinical parameters. Paired t-tests or Wilcoxon signed-rank tests were used to assess changes in SUA and glycemic control markers. A p-value of <0.05 was considered statistically significant. Regression analysis was used to explore the relationship between changes in SUA levels and improvements in glycemic markers.

Demographic and Clinical Characteristics

A total of 120 T2DM patients completed the study, with a mean age of 58.2 ± 10.4 years. The study cohort included 65% males and 35% females, with a mean duration of diabetes of 6.3 ± 3.5 years. The mean BMI at baseline was 31.2 ± 5.2 kg/m², indicating a predominance of overweight and obese individuals. The baseline characteristics are summarized in Table 1.

Table 1: Baseline Demographic and Clinical Characteristics of the Study Population

Impact of Lifestyle Intervention on SUA Levels and Glycemic Control

Changes in Serum Uric Acid (SUA) Levels

At the end of the 12-week intervention, the mean SUA level significantly decreased from 6.9 ± 1.8 mg/dL to 5.4 ± 1.2 mg/dL (p < 0.01). This represents a mean reduction of 21.7%, indicating that the lifestyle intervention effectively reduced SUA levels.

Changes in Glycemic Control

Significant improvements were observed in all glycemic markers. The mean FBS decreased from 145.3 ± 23.4 mg/dL to 128.4 ± 18.5 mg/dL (p < 0.01), and HbA1c decreased from 8.4 ± 1.2% to 7.2 ± 1.0% (p < 0.01). PPBG levels also decreased from 210.3 ± 30.5 mg/dL to 185.1 ± 25.4 mg/dL (p < 0.01). These results are summarized in Table 2.

Table 2: Changes in SUA Levels and Glycemic Control Before and After 12-Week Lifestyle Intervention

Subgroup Analysis

Subgroup analyses based on gender and BMI were performed to explore whether certain groups benefitted more from the intervention. As shown in Table 3, males and individuals with a BMI ≥ 30 kg/m² exhibited greater reductions in both SUA levels and glycemic markers.

Table 3: Subgroup Analysis of Changes in SUA and Glycemic Control by Gender and BMI

Regression Analysis

Regression analysis was performed to assess the relationship between changes in serum uric acid (SUA) levels and improvements in glycemic control markers. After adjusting for potential confounders, such as age, gender, BMI, and baseline HbA1c, the following results were observed:

• For every 1 mg/dL reduction in SUA, FBS decreased by 12.4 mg/dL (95% CI: 7.1–17.7), and HbA1c decreased by 0.19% (95% CI: 0.12–0.26).
• For every 1 mg/dL reduction in SUA, PPBG decreased by 14.7 mg/dL (95% CI: 9.2–20.2).

These results suggest that reductions in SUA are significantly associated with improvements in key glycemic markers, reinforcing the potential role of SUA as a modifiable biomarker in managing T2DM.

Table 4: Linear Regression Analysis of Changes in SUA on Glycemic Control

Scatter Plots: Relationship Between Changes in SUA and Glycemic Control

Scatter plots were generated to visualize the relationship between SUA level reductions and glycemic marker changes. These plots demonstrate a clear inverse association between the decrease in SUA and improvements in FBS, HbA1c, and PPBG.

Figure 1: Reduction in SUA vs Reduction in Fasting Blood Sugar (FBS)

• A strong negative correlation is observed, indicating that greater reductions in SUA are associated with greater decreases in FBS.

Figure 2: Reduction in SUA vs Reduction in HbA1c

• A moderate negative correlation is observed, suggesting that lowering SUA levels leads to a reduction in HbA1c levels.

Figure 3: Reduction in SUA vs Reduction in Postprandial Blood Glucose (PPBG)

• A clear negative trend is seen, where reductions in SUA are associated with lower PPBG levels.

Figures 1, 2, and 3 visually represent the relationship between SUA reductions and improvements in glycemic control, showing that lifestyle interventions targeting SUA may significantly affect blood glucose regulation.

Adverse Events and Adherence

During the study, no significant adverse events were reported. Most participants (85%) adhered to the dietary and exercise recommendations, as confirmed by weekly follow-up phone calls and bi-weekly visits. Minor side effects such as fatigue and muscle soreness were reported by a small number of participants (15%), but these were transient and did not lead to discontinuation of the intervention.

This prospective study demonstrates that structured lifestyle interventions—comprising dietary modifications and physical activity—significantly affect serum uric acid (SUA) levels and glycemic control in patients with Type 2 Diabetes Mellitus (T2DM). Over the 12-week intervention period, we observed a notable reduction in SUA levels and significant improvements in key glycemic markers, including fasting blood sugar (FBS), HbA1c, and postprandial blood glucose (PPBG). These findings are consistent with previous studies showing the positive effects of lifestyle changes on insulin sensitivity, oxidative stress, and inflammation, which are critical factors in managing T2DM [1][2].

The reduction in SUA observed in this study is particularly significant because elevated SUA levels are often associated with insulin resistance, oxidative stress, and endothelial dysfunction, all of which contribute to the pathogenesis of T2DM and its complications [3]. Previous research has shown that elevated SUA is a predictor of poor glycemic control and is linked to an increased risk of developing diabetic complications, such as nephropathy, retinopathy, and cardiovascular diseases [4][5]. By lowering SUA through lifestyle interventions, we observed concurrent improvements in glucose metabolism, suggesting that SUA could be a modifiable biomarker for managing T2DM. This is in line with findings from studies such as that of Akinmoladun et al., which suggested that reducing SUA levels through lifestyle modifications could improve insulin sensitivity and better diabetes management outcomes [6].

The improvements in glycemic control observed in our study align with the results of several other interventional studies on T2DM. A systematic review by Sigal et al. (2006) demonstrated that physical activity significantly improves insulin sensitivity and reduces fasting glucose levels in individuals with T2DM. Additionally, dietary interventions focusing on low glycemic index foods, caloric restriction, and increased fiber intake have enhanced glucose control by reducing postprandial blood glucose spikes and improving overall insulin sensitivity [7]. In the current study, the 12-week intervention involving diet and exercise produced reductions in FBS, HbA1c, and PPBG, considered critical measures of diabetes control.

Furthermore, the association between SUA reduction and improvement in glycemic control is particularly noteworthy. Regression analysis revealed that a decrease in SUA was significantly correlated with a reduction in both FBS and HbA1c, supporting the hypothesis that SUA could play a central role in influencing blood glucose levels. This is consistent with findings from other studies, such as the one by Li et al. (2015), which showed that lowering SUA through medication improved HbA1c levels and insulin sensitivity in T2DM patients [8]. The current study extends this knowledge by proving that lifestyle interventions, generally safer and more sustainable than pharmacological therapies, can also lead to beneficial changes in SUA and glycemic control.

However, it is important to note that while this study demonstrates the potential of lifestyle modifications to improve SUA and glycemic control, the exact mechanisms underlying these changes require further investigation. Uric acid may influence insulin resistance through multiple pathways, including activating inflammatory cytokines and oxidative stress, impairing insulin receptor signaling, and glucose uptake by muscle cells [9]. Studies by Grayson et al. (2009) and Johnson et al. (2013) have shown that hyperuricemia leads to endothelial dysfunction and vascular inflammation, which could further exacerbate insulin resistance and glycemic dysregulation in T2DM patients [10][11]. Lifestyle interventions that lower SUA help mitigate these inflammatory pathways, contributing to improved insulin sensitivity and glucose control.

One of the unique aspects of this study is the comprehensive approach to lifestyle intervention, which combines dietary and exercise modifications. This holistic approach aligns with current clinical guidelines, which emphasize the importance of diet and physical activity in managing T2DM. The American Diabetes Association (ADA) recommends at least 150 minutes of moderate-intensity exercise per week and a balanced, nutritious diet for all T2DM patients as part of a comprehensive management plan [12]. Our study supports the evidence that this combined approach can significantly impact metabolic outcomes in T2DM patients.

However, several limitations must be considered. The sample size of 120 participants may not be large enough to generalize the results to a broader population fully. While the 12-week intervention period provided meaningful insights into the short-term effects of lifestyle changes, long-term studies are needed to assess whether SUA and glycemic control improvements can be sustained over time. Additionally, while we assessed diet and exercise as part of the intervention, we did not measure the individual effects of each component. Future research should explore the relative contributions of diet versus exercise to the observed changes in SUA and glycemic control.

Another limitation is the lack of a control group. Although the pre-post-study design provides valuable insights into the effects of the intervention, the absence of a control group makes it difficult to attribute the observed changes exclusively to the lifestyle interventions. Future studies with randomized controlled trials (RCTs) are necessary to establish better the causal relationship between lifestyle interventions, SUA, and glycemic control. Furthermore, exploring the molecular mechanisms through biomarkers such as inflammatory cytokines, oxidative stress markers, and insulin sensitivity would help clarify the pathways through which lifestyle modifications influence both SUA and glycemic control.

In conclusion, this prospective study demonstrates that a 12-week lifestyle intervention, incorporating dietary changes and physical activity, effectively reduces serum uric acid levels and improves glycemic control in patients with Type 2 Diabetes Mellitus. These results suggest that SUA could be a modifiable biomarker in diabetes management, and lifestyle interventions may serve as a valuable adjunct to pharmacological treatments. Given the growing burden of T2DM worldwide, implementing such lifestyle changes could offer a cost-effective, sustainable approach to improving health outcomes in this population. Future studies with larger sample sizes and extended follow-up periods are needed to confirm these interventions' long-term benefits and explore the molecular mechanisms underlying the observed changes in SUA and glycemic control.

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