Cutting Edge: Biomarker can predict pre-diabetes years before diagnosis

With Type 2 diabetes becoming increasingly common in the younger population, there is a push for identifying high-risk sections early on. While a patient’s glucose levels have been the gold standard for detecting pre-diabetes and diabetes, a recent report has explored the potential of a new marker for identifying the condition: microRNA. These are essentially small molecules which regulate the expression of genes in response to prevailing environmental factors (nutrition, metabolism, stress etc).
Collaborative research between scients at the Diabetes Unit of KEM Hospital and Research Centre, Pune, and Western Sydney University, Australia, suggests that circulating levels of microRNAs measured during childhood might help predict pre-diabetes at a later age. The findings of the study have been published recently in the Journal of Developmental Origins of Health and Disease.

“This is the first report of longitudinal changes in circulating microRNAs as biomarkers of metabolic disease in later life. This preliminary discovery was done on small numbers and needs to be confirmed in larger numbers and other populations” Dr C S Yajnik, Director, Diabetes Research Unit KEM Hospital told The Indian Express.
The research was done using archived blood samples at the bio-bank of the Pune Maternal Nutrition Study, a birth cohort now in its 30th year. This study examined 710 families around Pune spanning three generations to track the development of diabetes.
Previous research had shown that 30% of the participants in the study who had pre-diabetes at 18 years of age, had higher glucose levels at 6 years and at 12 years of age compared to those who had normal glucose levels at 18 years.
Pre-diabetes is a stage where the patient’s glucose levels are higher than normal but lower than diabetic levels. Screening for pre-diabetes is usually done for high-risk groups such as individuals who have a family hory of diabetes (especially in parents) or those who are overweight/obese. The simple test measures a patient’s blood glucose, either on an empty stomach or after a glucose drink.
Considering the importance of early detection of pre-diabetes, researchers were also keen on looking for additional biomarkers to improve the accuracy of diagnosis and provide details about molecular mechanisms involved in the condition. In the last few decades, the number of people with pre-diabetes has rapidly increased all over the world, including India. A survey across India (Comprehensive National Nutrition Survey 2017) showed surprisingly high numbers of children and adolescents with pre-diabetes, without any apparent risk factors.
“Hence the finding of specific signatures of microRNAs in the blood years before pre-diabetes is diagnosed, is exciting. It may have interesting implications,” Dr Yajnik said, adding “The molecular mechanisms involved in these complex processes are called ‘epigenetic’, which act over and above the role of genetic factors. One of the important epigenetic mechanisms is microRNAs. MicroRNAs produced in one tissue can circulate in the blood and control the function of dant organs and systems”
The scients are excited about their preliminary findings and are now preparing to measure these markers in the remaining samples in the Pune cohort. “There are more than 700 families in the study and we have measured and reported only on a small number, as a proof of the principle. Many hundred samples are still waiting to be measured. This will happen over a period of time. We are excited that microRNAs may not only be markers of future trouble but also point towards epigenetic mechanisms involved in the process. That could guide us in prevention and treatment”, said Dr Yajnik.

The Australian scients — Dr Anand Hardikar and Dr Mugdha Joglekar, both originally from Pune — are specials in microRNA research and supervised the measurements during the study. Dr Mahesh Karandikar from DY Patil Medical College, Pune, also helped in the measurements.
The Pune Maternal Nutrition Study was started in collaboration with professors David Barker and Caroline Fall who had made an interesting observation in the UK that persons born with smaller birth weight had higher risk of diabetes later in life. This was a novel explanation which could explain the situation in India because Indian babies are the smallest in the world, and diabetes has assumed epidemic proportions in the country. Undernutrition of the ba in the womb affects its growth and development, creates smaller organs and systems and predisposes them to diabetes later in life if their lifestyle is not good.