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Charting the evolution of diabetes research and care: from epidemiology to precision medicine: PLOS Medicine 15th Anniversary

In celebration of our 15 Year Anniversary, Academic Editor Ronald CW Ma highlights advancements published in PLOS Medicine in diabetes research and care, including improved precision medicine.  


Happy 15th Birthday to PLOS Medicine! I still remember reading about the PLOS journals and the idea of making science accessible to all back when PLoS was first launched. It is amazing how far the Open Access movement has developed, how far that idea has advanced and how scientific publishing has been revolutionized. Congratulations PLOS Medicine on this important milestone!

Among the many articles that I have enjoyed reading in PLOS Medicine over the years, I would like to highlight two for sharing with other readers on this special occasion.

1) Event Rates, Hospital Utilization, and Costs Associated with Major Complications of Diabetes: A Multicountry Comparative Analysis

This paper by Philip Clarke and colleagues from the ADVANCE Collaborative Group, published back in 2010, highlighted the significant economic burden of diabetes and rates of hospitalization resulting from diabetes co-morbidities, using data from the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) study, a landmark multi-centre trial on the treatment of diabetes conducted in 20 countries. Within the ADVANCE trial settings, the study demonstrated important differences in the rates of hospitalization for different diabetes complications in different regions of the world (Asia, Eastern Europe, and established market economies such as Australia, New Zealand and Canada), mirroring epidemiological observations of comparative higher nephropathy rates, higher stroke risk, and lower risks of coronary artery disease among Asians (mostly from Chinese centres in this particular trial) with type 2 diabetes, thereby highlighting the heterogeneity of risk of diabetes complications (and costs) in different populations.

This study also provided important tools to facilitate estimation of healthcare expenditure associated with diabetes in different healthcare settings. At the time of the study, it was estimated that the average annual per capita health expenditure was approximately 216 international dollars in China, and 698 international dollars in Russia, but that the annual hospital costs for people with diabetes experiencing major macrovascular complications such as coronary or cerebrovascular events would be around four and ten times these average per capita expenditures. Perhaps not fully appreciated at the time was the significant burden associated with hospitalization with heart failure, which is a topic of much current interest in relation to recent advances in the treatment of type 2 diabetes.

Although the work was focused on evaluating the economic burden of diabetes in different parts of the world, this work can be considered as an important example of early attempts to “deconstruct” the heterogeneity of type 2 diabetes. As the diabetes epidemic continues unabated, the healthcare burden of diabetes complications has become a major concern globally.



2) Type 2 diabetes genetic loci informed by multi-trait associations point to disease mechanisms and subtypes: A soft clustering analysis

The second article, by Jose Florez and colleagues, utilized a state-of-the-art multi-omics approach to use available genetic and epigenomic data to probe the issue of heterogeneity of diabetes.  The authors showed that identified genetic loci linked to diabetes can be segregated according to underlying biological mechanisms which can be used to classify individuals, to provide a way forward for individualized diagnosis, monitoring and treatment. The study highlighted the potential role of genetic variants related to the beta cell, pro-insulin, obesity, lipodystrophy and liver/lipid traits in accounting for different patient characteristics, as well as long-term diabetes outcomes.

What was particularly interesting is the “soft-clustering” approach adopted by the authors, which did not require genetic variants to fit into only one pathway, or for individuals to be classified to have diabetes due to only one specific pathophysiological defect, but instead, for individuals to be identified to have scores in each of the above-mentioned categories, and thereby accepting that individuals may have developed diabetes with different contribution from the different underlying pathophysiology.  The use of such genetic risk scores may be useful in selecting the most appropriate therapies for individualized care in the future.

Over the last 15 years, the global burden of diabetes has more than doubled, from less than 200 million people affected back in the early 2000’s to now more than 422 million people affected globally (with the majority in LMICs). These 2 articles represent important advances in our understanding of type 2 diabetes over the last decade. Whilst the ADVANCE study was a landmark study that generated much interest, the Clarke paper highlighted much of the burden of diabetes complications, and our lack of understanding regarding the heterogeneity in risk of diabetes complications. Together with the Action to Control Cardiovascular Risk in Diabetes (ACCORD) and Veterans Affairs Diabetes Trial (VADT) studies, these landmark studies, published between 2008-2010, have highlighted the potential dangers of hypoglycaemia, and heralded the debate and call for more individualized treatment in type 2 diabetes, and contributed to the American Diabetes Association (ADA) and European Association for the Study of Diabetes (EASD) to propose in their joint position statement on management of hyperglycaemia in type 2 diabetes in 2012 to move away from a “one-size-fit-all” approach to treatment, but instead adopt a treatment strategy that is more tailored to individual patient profile, disease duration, co-morbidities and expectations. This represented a major watershed moment in the evolution of diabetes research and care.

With recent advances in genomic medicine and the genetics of type 2 diabetes, some of which have been reported in PLOS Medicine, the era of precision medicine in diabetes is very much here to stay. We, as diabetes researchers and clinicians caring for people with diabetes, look forward to further advances in our understanding of how best to treat individuals with diabetes based on their underlying genetics, pathophysiology, and needs, and to improving outcomes for people with diabetes.

Congratulations again PLOS Medicine and we look forward to the next 15 years of exciting advances!



Ronald Ma is Professor and Head of Division of Endocrinology and Diabetes at the Department of Medicine and Therapeutics, The Chinese University of Hong Kong, and co-lead of the Chinese University of Hong Kong-Shanghai Jiao Tong University Joint Research Centre in Diabetes Genomics and Precision Medicine. He is a member of the Executive Board, Asian Association for the Study of Diabetes (AASD), and member of the editorial board of PLOS Medicine.

Acknowledgement: RCWM acknowledge support from the Hong Kong Research Grants Council Research Impact Fund (R4012-18).



Image Credit: stevepb, Pixabay (CC0)

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