More than half of individuals with diabetes, mainly T2DM, are undiagnosed until severe complications appear. Even in diagnosed patients, the disease progression may be accelerated due to the lack of rigorous glycemic monitoring and the inability of screening methods to reflect glycemic status accurately. Traditional glycemic indicator, such as glucose and HbA1c, present several limitations that can lead to underdiagnosis and poor disease prognosis in people with T2DM. (3)

For example, HbA1c is not always a reliable measurement of average circulating glucose levels. The measurement value and life span of the HbA1c are proportional to the half-life of the red blood cell ranging from 90 to 120 days, hence, changes in the production rate or circulating life span of red blood cells will directly affect HbA1c levels. This association between the half-life of the red blood cell and HbA1c can result in overestimation and underestimation of the glycemic levels in the body. (1) (3)

Implementing successful and cost-effective strategies for systematic screening of diabetes mellitus is imperative to ensure early detection, lowering patients’ risk of developing life-threatening disease complications. Practical and effective diabetes screening, monitoring, and diagnosis approaches are essential to decrease the disease’s prevalence, prevent the onset of complications and improve the quality of life. (3)

Apart from glucose testing, there are additional biomarkers and several diagnostic criteria recommended by the American Diabetes Association (ADA) and the World Health to predict the risk of progression to diabetes. Therefore, identifying these new biomarkers and assay methods for diabetes mellitus to develop robust, non-invasive, painless, highly-sensitive, and precise screening techniques is essential.

Diabetes, prediabetes, and insulin resistance are characterized by a marker inflammatory state. Biochemical markers are elevated on the onset of T2DM and may further increase with disease progression. Therefore, several biomarkers, including markers of acute phase reactants and inflammatory markers can be used to detect the development and progression of diabetes, such as adiponectin,Retinol binding protein 4, Gamma-glutamyl transferase (GGT), and alanine transaminase (ALT), Leptin, etc. (4) (5)

Adiponectinis a protein hormone derived from the adipose tissue that exhibits insulin-sensitizing, anti-inflammatory, and anti-atherogenic properties. This independent predictor of diabetes is associated with the progression of diabetes and is inversely related to the risk of prediabetes. Especially, in men, lower levels of adiponectin were detected decades before the clinical diagnosis of type 2 diabetes. Similarly, it is a well-known fact that leptin, an adiposity hormone plays a key role in the regulation of energy homeostasis, but several studies have shown that leptin is also responsible for or driving hyperglycemia in states of uncontrolled insulin-deficient diabetes. (5)

Additionally, elevated levels of Gamma-glutamyl transferase (GGT), and alanine transaminase (ALT) can be used as important biomarkers for detecting the risk of diabetes. These markers of oxidative stress are early markers of abnormal triglyceride storage and lipolysis in insulin- sensitive tissues in the liver, which in turn can be dubbed as an early manifestation of conditions characterized by insulin resistance. On the other hand, although retinol-binding Protein 4 has been implicated in insulin resistance and prediabetes, the association between the biomarker and T2DM remains unclear. (1) (4)

Evidence from studies comparing the performance of new glycemic markers such as glycated albumin (GA), fructosamine (FA), and 1,5-anhydroglucitol (1,5-AHG) have shown that they provide independent clinical information and can improve the prognostic value of conventional markers. In addition, several studies have been conducted to evaluate novel biomarkers in conventional fluids such as blood and urine. These include THBS1, GPLD1, Acylcarnitine, and miRNA.However, to date, no biomarker studied so far is the perfect marker for all T2DM patients in all conditions. (1)

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