A potential microRNA biomarker identified for diabetes in the Indian population

Debaleena Basu

A recent study has identified microRNAs that are potential biomarkers for diabetes. At least one of them is specific to the Indian population.

In search of a micro (RNA) solution to a macro disease (diabetes)
In search of a micro (RNA) solution to a macro disease (diabetes)  (Photo: Muthuswamy Balasubramanyam)

Diabetes, a disease involving impaired glucose metabolism, has assumed epidemic proportions due to its high prevalence worldwide. India is estimated to have more than sixty-two million diabetic patients, making it one of the epicentres of the global epidemic. The numbers are predicted to increase exponentially in the coming decades. Worryingly, the age of onset of diabetes in Indians is decreasing, indicating that in the coming years, a substantial section of India’s youth will be suffering from the disease. However, research on diabetes in India has been insufficient, making it difficult to formulate an adequate national response.

Scientific efforts worldwide have focussed on finding biomarkers that can aid screening and early detection of diabetes. Indians comprise the Asian Indian Phenotype’, which refers to a gamut of biochemical and clinical peculiarities in the South Asian population that predisposes it to the disease. This makes direct extrapolation of data obtained from western populations to Indians difficult. This motivated a research group from Madras Diabetes Research Foundation (MDRF) to conduct a recent study focussed on finding a biomarker for diabetes specifically tailored for the Indian population.

The most promising biomarkers should be robust and clinically translatable”, explained Muthuswamy Balasubramanyam, a senior scientist at the foundation and one of the principal investigators of the study. Circulatory microRNAs, small pieces of non-coding RNAs floating in the bloodstream, satisfy both these conditions — they are remarkably stable and require only a blood sample for testing — thus being ideal for large-scale clinical use. MicroRNAs are also known to be master regulators of gene function, affecting a variety of physiological processes. Research has shown that the level of circulating microRNAs changes consistently in various pathophysiologies like cancer and cardiovascular diseases, but little is known about its role in diabetes, especially in the Indian context.

Aiming to identify circulating microRNAs that could serve as biomarkers for diabetes, the investigators recruited three groups of subjects for the study: diagnosed Type 2 Diabetes Mellitus (T2DM) patients, subjects with normal glucose metabolism (NGT: Normal Glucose Tolerance) and those with pre-diabetic state of Impaired Glucose Tolerance (IGT). Blood glucose level was measured in all the participants to confirm the grouping. Candidate microRNAs were searched after characterizing the microRNA profile for each participant. We found that four microRNAs had different serum levels in IGT and T2DM patients compared to control NGT subjects”, said Balasubramanyam. Levels of two of these microRNAs were also similarly altered in diet-induced diabetic mice, providing further support towards their potential usability as a diabetes biomarker.

Interestingly, among the altered microRNAs , miR-128 has never been described in previous diabetes studies and appears to be specific for the Indian population”, said Balasubramanyam. Considering that miR-128 has been earlier reported as a biomarker of cognitive impairment and that there exists a neurological component in the etiology of type 2 diabetes, Balasubramanyam speculated that miR-128 could be the connecting link for the cognitive dysfunction and/​or depression associated with metabolic diseases like diabetes. miR-128 was further positively correlated with cholesterol both in prediabetic subjects and in diet-induced diabetic mice, suggesting that its increased level might be associated with the development of altered lipid level associated with T2DM. 

The results, though preliminary, are exciting because miRNAs are considered to have tremendous potential as non-invasive biomarkers for the screening, monitoring and diagnosis of a disease. The group plans to conduct long-term studies to elucidate the connection of these microRNAs with diabetes to facilitate their use as biomarkers in future. The day might come when a simple blood test would reveal the microRNA profile, facilitating pre-emptive screening of at-risk people. Effective prevention and management can then start right away, before the onset of the disease, which in turn, would lead to a reduction of the burden diabetes imposes on the in Indian nation and society at large.

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