Dysregulated Asprosin Concentrations in Prediabetes and Type 2 Diabetes: A Comparative Analysis

Organization: Ramnath Prasad Institute of Higher Education, Patna, Bihar, India.

Corresponding Author and Principal Investigator: Dr. Sudeep Kumar, Department of Biochemistry, Ramnath Prasad Institute of Higher Education, Patna, Bihar, India. Email:

Date: July 12, 2025

1. Executive Summary:

Type 2 Diabetes Mellitus (T2DM) and its precursor, prediabetes, represent a significant and escalating health challenge in India, placing immense strain on healthcare systems and individual well-being. Early identification and intervention are crucial to mitigate the progression of these metabolic disorders. This proposal seeks CSR funding to expand upon groundbreaking research conducted at the Ramnath Prasad Institute of Higher Education, which has identified asprosin, a fasting-induced adipokine, as a potential early biomarker for metabolic deterioration in prediabetes and T2DM. Our preliminary cross-sectional study revealed progressively dysregulated asprosin concentrations from normoglycemia to prediabetes and overt T2DM, implicating its utility in early diagnosis and potentially as a therapeutic target. This project aims to conduct further longitudinal studies and expanded research to elucidate the causal role of asprosin in glucose dysregulation and its utility in diabetes risk stratification within the Indian context. The findings will pave the way for novel preventive strategies and therapeutic interventions, aligning directly with corporate social responsibility initiatives focused on public health, particularly in combating non-communicable diseases.

2. Introduction and Problem Statement:

Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance, relative insulin deficiency, and chronic hyperglycemia. Prediabetes, an intermediate state of glycemic dysregulation, is a critical window for early intervention to prevent or delay the onset of T2DM. Understanding the molecular and hormonal changes during the transition from normoglycemia to prediabetes and then to overt diabetes is essential for identifying early biomarkers and therapeutic targets.

Asprosin, a fasting-induced glucogenic adipokine, was identified in 2016 as a C-terminal cleavage product of profibrillin (FBN1 gene product). It plays a significant role in glucose homeostasis by stimulating hepatic glucose release via the G protein-CAMP-PKA pathway and also influences appetite regulation through hypothalamic pathways. Emerging evidence suggests that its dysregulation may contribute to the pathogenesis of metabolic disorders like prediabetes and T2DM. Recent studies have shown elevated circulating asprosin levels in individuals with obesity and T2DM, linking it to insulin resistance and glucose intolerance. Furthermore, some evidence indicates that asprosin concentrations might be altered in the prediabetic state even before clinical diabetes is diagnosed.

However, comparative data on circulating asprosin levels across different glycemic states remain limited, and findings regarding asprosin levels in prediabetes have been inconsistent. These discrepancies underscore the need for focused comparative analyses of asprosin concentrations across the glycemic spectrum. Investigating asprosin's dysregulation in prediabetes and T2DM can offer insights into its potential as an early biomarker for metabolic derangements and a target for therapeutic modulation. Given the high prevalence of diabetes in India, research into early detection and prevention mechanisms is of paramount importance.

3. Project Goal and Objectives:

Goal: To elucidate the role of asprosin as an early biomarker for metabolic deterioration and a potential therapeutic target in prediabetes and type 2 diabetes within the Indian population, contributing to improved early intervention strategies.

Objectives:

• To conduct comprehensive longitudinal studies tracking asprosin levels in individuals progressing from normoglycemia to prediabetes and T2DM, assessing its predictive value for diabetes progression.

  
  

• To expand the sample size to allow for robust subgroup analysis based on critical demographic factors such as sex, age, and BMI categories, which were limitations in the preliminary study.

  
  

• To investigate postprandial asprosin dynamics, considering its regulation by nutritional status, to gain additional insights into its role in glucose metabolism.

  
  

• To contribute to the standardization of asprosin quantification methods, enhancing inter-study comparability and ensuring reliable data for future research and clinical applications.

  
  

• To explore the adipose tissue-asprosin axis more thoroughly, particularly in the context of visceral fat distribution, as asprosin levels have been linked with BMI.

  
  

• To facilitate the translation of research findings into practical clinical applications for diabetes risk stratification and preventive strategies.

4. Methodology:

Building upon our initial cross-sectional study that included 440 adult participants (80 normoglycemic controls, 200 prediabetic subjects, and 160 patients with T2DM), this project proposes the following expanded methodology:

• Longitudinal Study Design: We will recruit a new cohort of individuals, including normoglycemic and prediabetic subjects, and follow them over a period of 2-5 years. Regular monitoring of glycemic parameters (fasting glucose, HbA1c), insulin, lipid profile, anthropometric measurements (BMI, waist circumference), and serum asprosin levels will be performed at predefined intervals (e.g., every 6-12 months). This will enable us to observe the progression of asprosin levels in relation to the development of prediabetes and T2DM.

  
  
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  Expanded Sample Size and Subgroup Analysis: The sample size will be significantly increased to allow for detailed subgroup analyses, addressing previous limitations concerning sex, age, and BMI categories. This will help us understand how asprosin dysregulation varies across different demographic groups and body compositions.

  
  

• Postprandial Asprosin Dynamics: In a subset of participants, we will conduct oral glucose tolerance tests (OGTTs) with serial asprosin measurements to assess its postprandial dynamics. This will provide valuable insights into how asprosin responds to nutrient intake and its potential role in post-meal glucose regulation.

  
  
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  Advanced Biochemical Analysis: Serum asprosin will continue to be quantified using enzyme-linked immunosorbent assay (ELISA). We will also incorporate additional markers for inflammation (hs-CRP) and insulin resistance (HOMA-IR, TyG Index).

  
  
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  Adipose Tissue Analysis (Pilot Study): In a small, consenting sub-cohort, we aim to explore the relationship between visceral fat distribution and asprosin levels, potentially through imaging techniques (e.g., DEXA scan) or correlation with waist circumference.

  
  
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  Data Analysis: Statistical analysis will involve repeated measures ANOVA for longitudinal data, and correlation analyses (Pearson correlation) to assess the relationship between asprosin and various metabolic parameters. Predictive models will be developed to evaluate asprosin's utility in predicting diabetes onset. A p-value < 0.05 will be considered statistically significant.

  
  
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  Ethical Considerations: The study protocol will be approved by an Institutional Ethics Committee, and informed written consent will be obtained from all participants, ensuring confidentiality.

  
  

5. Expected Outcomes and Impact:

This research is expected to yield several significant outcomes with substantial impact on public health in India:

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  Early Biomarker Identification: The study will firmly establish asprosin's potential as an early biomarker for identifying individuals at high risk for diabetes progression, allowing for timely preventive strategies.

  
  
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  Improved Diabetes Risk Stratification: By understanding the patterns of asprosin dysregulation across the glycemic spectrum, clinicians can better stratify individuals based on their diabetes risk, leading to more targeted interventions.

  
  
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  Novel Therapeutic Targets: The elucidation of asprosin's causal role in glucose dysregulation could open new avenues for therapeutic modulation, including lifestyle interventions or pharmacotherapy aimed at normalizing asprosin levels. Animal studies have already shown promising results with asprosin neutralization.

  
  
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  Contribution to Global Knowledge: The findings will address inconsistencies in previous research and contribute significantly to the global understanding of asprosin's role in metabolic disorders, particularly in a large and diverse population like India's.

  
  

• Capacity Building: This project will strengthen research infrastructure and expertise in metabolic research at the Ramnath Prasad Institute of Higher Education, fostering a new generation of scientists equipped to tackle public health challenges.

• Public Health Benefits: Ultimately, the project aims to contribute to reducing the burden of prediabetes and T2DM in India by facilitating earlier diagnosis, more effective prevention strategies, and potentially new treatment approaches.

6. Budget (Summary - Detailed budget available upon request):

The requested CSR funding will primarily cover:

• Personnel costs (research assistants, statisticians)

• Reagents and consumables for biochemical assays (ELISA kits, glucose, HbA1c, insulin, lipid profile, hs-CRP, etc.)

• Equipment maintenance and calibration

• Data management and statistical software

• Participant recruitment and follow-up incentives

• Publication and dissemination costs

• Contingency

7. Conclusion:

The rising prevalence of prediabetes and T2DM in India necessitates urgent and innovative approaches for early detection and intervention. Our preliminary research has strongly indicated the potential of asprosin as a critical player in metabolic dysregulation. With CSR funding, we can expand this vital research through robust longitudinal studies and comprehensive analyses, moving closer to establishing asprosin as a reliable early biomarker and a viable therapeutic target. This project aligns perfectly with CSR objectives focused on improving public health outcomes and fostering scientific advancement, offering a tangible return on investment through healthier communities and a reduced burden of chronic disease in India. We are confident that this research will significantly contribute to the ongoing efforts to combat the diabetes epidemic and improve the quality of life for millions.