Assessment of Novel Biomarkers for Early Diagnosis and Prognosis of Type 2 Diabetes Mellitus

Adam Kretowski^*
*Correspondence: Adam Kretowski, Department of Diabetes and Endocrinology, University of Michigan Health, MI, USA, Email:

Keywords

Type 2 diabetes mellitus • Biomarkers • Early diagnosis • Prognosis • Genetic markers • Proteomics • Metabolomics • Insulin resistance • Hyperglycemia • Personalized medicine

Introduction

Type 2 diabetes mellitus is a global health challenge, affecting millions and leading to significant morbidity and mortality. It is characterized by chronic hyperglycemia resulting from insulin resistance and β-cell dysfunction. Early diagnosis and prognosis are pivotal in preventing complications such as cardiovascular disease, neuropathy, and nephropathy. Traditional diagnostic methods, including fasting glucose levels and HbA1c measurements, are limited in their ability to predict disease onset and progression accurately. This review aims to explore novel biomarkers that have emerged from advances in genomics, proteomics, and metabolomics, providing a comprehensive overview of their potential in enhancing early diagnosis and prognosis of T2DM [1].

Literature Review

Proteomics involves the large-scale study of proteins, which are vital in understanding disease mechanisms. In T2DM, several protein biomarkers have been identified, such as adiponectin, C-Reactive Protein (CRP), and Sex Hormone-Binding Globulin (SHBG). Adiponectin levels are inversely correlated with insulin resistance, while elevated CRP levels indicate inflammation, a key component of T2DM pathology. SHBG has been linked to insulin sensitivity and risk of diabetes.

Type 2 diabetes mellitus is a prevalent chronic metabolic disorder characterized by insulin resistance, impaired insulin secretion, and hyperglycemia. It is associated with serious complications such as cardiovascular disease, neuropathy, nephropathy, and retinopathy, which contribute to significant morbidity and mortality worldwide. Early diagnosis and prognosis of T2DM are essential for effective management and prevention of these complications. Traditional diagnostic methods, including Fasting Plasma Glucose (FPG), Oral Glucose Tolerance Test (OGTT), and Glycated Hemoglobin (HbA1c), are effective but limited in predicting disease onset and progression. Recent advancements in omics technologies have led to the identification of novel biomarkers that could enhance early diagnosis and prognosis of T2DM. This review evaluates genetic, proteomic, and metabolomic biomarkers, discussing their potential roles and the clinical evidence supporting their use. Genetic predisposition plays a significant role in T2DM. Genome-Wide Association Studies (GWAS) have identified numerous genetic loci associated with T2DM. Notable genetic markers include variants in the TCF7L2, FTO, and SLC30A8 genes, which are linked to insulin secretion and β-cell function. These genetic markers offer insights into an individual's risk of developing T2DM and can guide preventive measures [2].

The TCF7L2 gene, located on chromosome 10q25, has been consistently associated with T2DM across various populations. Variants in TCF7L2 affect insulin secretion and glucose production, making it a strong genetic marker for T2DM. Studies have shown that individuals carrying risk alleles in TCF7L2 have a higher likelihood of developing T2DM, independent of traditional risk factors. The FTO gene, known for its association with obesity, also plays a role in T2DM. Variants in FTO are linked to increased body mass index (BMI), which is a significant risk factor for T2DM. The SLC30A8 gene encodes a zinc transporter involved in insulin granule function. Mutations in SLC30A8 can impair insulin secretion, thereby increasing the risk of T2DM. These genetic markers offer insights into an individual’s predisposition to T2DM, allowing for targeted preventive measures. However, the predictive power of single genetic variants is limited. Polygenic risk scores (PRS), which aggregate the effects of multiple genetic variants, have shown promise in improving risk prediction and are being explored for clinical application. Proteomics, the large-scale study of proteins, provides dynamic insights into disease mechanisms. In T2DM, several protein biomarkers have been identified that reflect the disease’s complex pathophysiology [3].

Adiponectin, a hormone secreted by adipose tissue, plays a critical role in regulating glucose levels and fatty acid breakdown. Lower adiponectin levels are associated with increased insulin resistance and higher risk of T2DM. Monitoring adiponectin levels could help identify individuals at risk for T2DM and track disease progression. C-reactive protein (CRP) is an inflammatory marker that has been linked to T2DM. Elevated CRP levels indicate systemic inflammation, a key component of T2DM pathogenesis. High CRP levels have been associated with insulin resistance and increased risk of cardiovascular complications in T2DM patients. Measuring CRP levels could aid in the early detection and management of T2DM [4].

Sex hormone-binding globulin has been identified as a potential biomarker for T2DM. Lower SHBG levels are associated with increased risk of T2DM, particularly in women. SHBG levels reflect insulin sensitivity and can provide insights into metabolic health. Proteomic profiling can reveal a wide array of protein changes associated with T2DM, offering potential for discovering novel biomarkers. However, the variability in protein expression due to genetic, environmental, and lifestyle factors poses a challenge for the standardization and clinical application of these biomarkers. Metabolomics involves the comprehensive analysis of metabolites, the small molecules involved in metabolism. Metabolomic profiling has identified several biomarkers associated with T2DM, offering insights into metabolic disturbances that precede clinical diagnosis.

Branched-Chain Amino Acids (BCAAs) such as leucine, isoleucine, and valine have been consistently linked to insulin resistance and T2DM. Elevated levels of BCAAs are found in individuals with insulin resistance and those at high risk of developing T2DM. These amino acids may disrupt insulin signalling pathways, contributing to metabolic dysregulation. Acylcarnitines, intermediates in fatty acid metabolism, have also been associated with T2DM. Higher levels of certain acylcarnitines are observed in insulin-resistant individuals and those with T2DM. These metabolites reflect mitochondrial dysfunction and impaired fatty acid oxidation, key features of T2DM pathophysiology. Specific lipid species, including ceramides and phospholipids, have been identified as biomarkers for T2DM. Dysregulated lipid metabolism is a hallmark of T2DM, and certain lipid profiles are indicative of increased disease risk. Lipidomics, a subfield of metabolomics, focuses on the comprehensive study of lipids and their role in T2DM. Metabolomic biomarkers provide a dynamic and integrative view of metabolic health, reflecting real-time physiological changes. However, like proteomics, variability in metabolite levels due to external factors must be addressed to ensure their reliability and clinical utility [5].

Discussion

The integration of novel biomarkers into clinical practice could revolutionize the early diagnosis and prognosis of T2DM. Genetic biomarkers allow for risk stratification and targeted prevention strategies. Proteomic and metabolomic biomarkers offer dynamic insights into disease progression and therapeutic response. Combining these biomarkers with traditional diagnostic methods could improve accuracy and provide a more comprehensive understanding of an individual's health status. Despite the promise of novel biomarkers, several challenges remain. Variability in biomarker levels due to genetic, environmental, and lifestyle factors can affect their reliability and reproducibility. Standardization of biomarker assays and validation in diverse populations are essential steps toward clinical implementation. Additionally, the high cost and complexity of advanced omics technologies may limit their accessibility in routine clinical settings [6].

Conclusion

Advances in genomics, proteomics, and metabolomics have identified novel biomarkers with significant potential for the early diagnosis and prognosis of T2DM. These biomarkers provide deeper insights into the disease's molecular underpinnings, enabling personalized medicine approaches. However, further research and validation are needed to overcome existing challenges and integrate these biomarkers into routine clinical practice. The future of T2DM management lies in leveraging these advancements to achieve earlier intervention, better disease monitoring, and improved patient outcomes.

Acknowledgement

None.

Conflict of Interest

None.

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