Hidden biomarkers uncovered for diabetes early warning signs
Hidden biomarkers that could help identify the early warning signs of diabetes have been identified, which may offer access to greater personalized treatment approaches.
Scientists from the Indian Institute of Technology (IIT; Mumbai, India) Bombay have unearthed previously hidden blood biomarkers that could help identify early warning signs of diabetes, offering hope for a new wave of diabetes diagnoses in India. The study was published in the Journal of Proteome Research.
An estimated 101 million people are living with diabetes in India, and a further 136 million are classified as being prediabetic, making it one of India’s most widespread health challenges. Conventional diagnostic tests, such as measuring fasting glucose, HbA1c and creatinine levels, capture just a small portion of the complex biochemical disruptions underlying the disease and often fail to predict who is at highest risk. Because many cases are diagnosed late, complications affecting the eyes, kidneys, nerves, heart and brain are common.
“Type 2 diabetes is not just about high blood sugar. It disrupts amino acids, fats and other pathways in the body. Standard tests often miss this hidden activity, which may begin years before the onset of clinical symptoms,” explained Sneha Rana, a doctoral scholar at IIT Bombay.
The team at IIT Bombay set about to uncover the biochemical patterns that precede clinical symptoms using metabolomics. The study analyzed whole blood samples from 52 volunteers collected at Osmania General Hospital (Hyderabad, India) between June 2021 and July 2022. The group included 15 healthy individuals, 23 patients with type 2 diabetes, and 14 patients with diabetic kidney disease — kidney damage caused by diabetes via high blood sugar and high blood pressure.
Using liquid chromatography–mass spectrometry and gas chromatography–mass spectrometry, the researchers performed metabolite profiling of nearly 300 metabolites at once and identified 26 that differed significantly between healthy and diabetic participants. While some variations included well-known indicators such as glucose, cholesterol and 1,5-anhydroglucitol, the study also highlighted novel markers like valerobetaine, ribothymidine and fructosyl-pyroglutamate — compounds not previously associated with diabetes. They also identified two distinct subgroups among diabetic patients; one group appeared metabolically closer to healthy individuals, whereas the second showed major changes related to stress, inflammation and energy production.
“These markers could one day be used by doctors, just like cholesterol tests are used to assess heart disease risk. This means some patients may need more aggressive treatment, while others might benefit more from lifestyle changes,” noted Rakesh Sahay, researcher at Osmania Medical college (Hyderabad, India).
The researchers also found biochemical patterns that could help identify diabetic patients at risk of developing kidney complications. When comparing participants with diabetic kidney disease to other groups, the team observed a steady increase in seven metabolites, including sugar alcohols such as arabitol and myo-inositol, as well as ribothymidine and a toxin-like compound called 2PY, which accumulates in cases of kidney damage.
“This suggests that diabetes is a much broader metabolic disorder beyond just glucose dysregulation… The work has potential for clinical translation as a test could be developed based on dried blood spots made from finger pricks, and this is an ongoing work in our lab,” commented Pramod Wangikar, Professor at IIT Bombay.
Although the study involved a small sample size, the researchers plan to extend it to obtain data from a larger subset, with the aim of developing simple clinical tests that can diagnose diabetes earlier but also identify those at higher risk of complications.
