Tan Tock Seng Hospital’s novel approach to address cardiovascular risks in Type 2 diabetes, with support from the Tanoto Foundation Medical Research Fund

Cardiovascular disease (CVD) remains the leading cause of mortality and morbidity in patients with type 2 diabetes mellitus (T2DM). Patients with diabetes are two-to-four-times more likely to suffer from atherosclerotic cardiovascular disease (ASCVD) — a specific form of CVD caused by the buildup of plaque in the arteries, which can lead to heart attacks and strokes — compared to individuals with no diabetes. Furthermore, ASCVD events tend to occur a decade earlier in diabetes patients. In Singapore alone, about 23 people die from CVD, heart disease and stroke every day, with CVD accounting for over 30% of all deaths in 2023 (Singapore Heart Foundation).

Studies show that one in five Singaporeans has one or more risk factors for CVD, such as hypertension, high cholesterol, diabetes (commonly known as the ‘three highs’), smoking, and obesity. The combination of these risk factors can increase the baseline risk of a heart attack by more than three times (National Heart Centre Singapore). Despite the advancements in cardiometabolic care, evidence-based interventions to manage low-grade inflammation, remain inefficient.

Colchicine, a low cost-effective generic medication costing around S$0.26 a day, has long been recognized for its anti-inflammatory properties in treating gout by targeting the inflammation pathway through neutrophils. While it is currently employed for secondary prevention of ASCVD, Associate Professor Rinkoo Dalan, Senior Consultant from the Department of Endocrinology at  Tan Tock Seng Hospital (a healthcare institution of the National Healthcare Group), is embarking on a novel journey to explore colchicine’s potential in primary prevention for patients with T2DM.

This groundbreaking research seeks to uncover whether this humble medication can play a vital role in safeguarding the heart health of high-risk individuals. Associate Professor Dalan’s interdisciplinary team, comprising of clinicians, engineers, and immunologists, sets out to confirm these promising findings and refine its benefits using a precision medicine approach, by first identifying the specific patients who stand to gain the most from this innovative treatment.

Associate Professor Dalan said, “Understanding and mitigating cardiovascular risks is critical for the long-term health of diabetes patients. One of the gaps in cardiometabolic risk management is inefficient evidence-based interventions to manage low-grade inflammation. Through the support of the Tanoto Foundation Medical Research Fund (MRF), our research team will be investigating the potential of Colchicine as a low-cost solution to reduce cardiovascular risk for type 2 diabetes patients.”

Colchicine’s potential to prevent ASCVD stems from its ability to inhibit neutrophil-driven inflammation, a key factor in cardiovascular events for diabetes patients. By targeting low-grade inflammation, Associate Professor Dalan’s team hopes to reduce the cardiovascular risks associated with T2DM in a cost-effective manner.

Precision medicine is a key component of Associate Professor Dalan’s research, focusing on tailoring treatment to the specific biological characteristics of each patient. Instead of a one-size-fits-all approach, precision medicine enables clinicians to develop therapies that are more personalized and effective by accounting for individual variations. In this case, her team aims to identify specific T2DM patients who have a higher risk of cardiovascular events due to their unique inflammatory profile, particularly neutrophil-driven inflammation.

To achieve this, Associate Professor Dalan’s research will develop a clinical-friendly microfluidics blood testing workflow and define a novel inflamed “neutrophil signature panel” to identify T2DM patients with higher risk of ASCVD. The research will culminate in a Phase II randomized controlled trial to study the impact of colchicine on subclinical atherosclerosis (arterial health) in T2DM patients stratified by neutrophil biomarkers.

The findings from this study will pave the way for the potential use of colchicine in patients T2DM within Singapore’s diverse multi-ethnic population, complementing existing risk factor-based therapies.

Associate Professor Dalan remarks, “The MRF is providing us not only with financial resources, but also other invaluable support to build up this study. It allows us to conduct a randomized controlled trial within our population to evaluate whether Colchicine truly fulfils the purpose that we hypothesize it does.”

She adds, “Through this funding, we are able to establish collaborations between multiple institutions in a multidisciplinary manner, involving scientists, endocrinologists, rheumatologists, immunologists, and ophthalmologists. This shared mission of delaying and preventing cardiovascular disease in patients with diabetes brings us all together. The fund also helps us to train the younger generation of clinical scientists to embark on studies aimed at this common mission.”

Looking ahead, Associate Professor Dalan’s team envisions that using Colchicine at an early stage in patients with diabetes may help arrest the inflammatory processes that lead to cardiovascular disease. The next steps will involve exploring how early intervention with Colchicine can reduce long-term cardiovascular risks in this vulnerable group, with the ultimate goal of integrating this approach into routine clinical practice for diabetes management.