Genetic risk score for moderate obesity-related diabetes linked to future coronary disease
By Sasha Ellery BM BCh
A high polygenic risk score for moderate obesity-related diabetes (MOD) is associated with the development of diabetes and coronary artery disease (CAD), a large prospective study published in Diabetes Care finds.
Using 24,025 participants from the Malmö Diet and Cancer cohort, the investigators tested whether polygenic risk scores for five adult-onset diabetes subtypes predicted incident diabetes and CAD. Over a median of 24 years’ follow up, 17.1% of participants developed diabetes and 16.0% developed CAD. All five subtype scores were associated with incident diabetes, but only the MOD subtype score was independently associated with incident CAD.
Associate Professor Milan Piya, Head of Department for the Macarthur Diabetes, Endocrinology and Metabolism Service at Campbelltown and Camden Hospitals, Sydney, said, ‘While findings from this study are interesting, this classification of different types of type 2 diabetes [used in the study] is from a predominantly European population and is not widely used in clinical practice here in Australia… MOD fits best with the traditional view of type 2 diabetes related to obesity and insulin resistance.’
Associate Professor Piya added that the polygenic risk score the researchers used was not available in Australia outside possible research settings. ‘So it will be a few years before they would be available for use by GPs in Australia.’
Participants in the highest tertile of the MOD score had a 10% higher risk of CAD than those in the lowest tertile, and Kaplan-Meier analysis showed that those in the highest tertile also had lower CAD-free survival.
‘This study goes back 24 years, so in that time we have seen a much more widespread use of statins, tighter blood pressure targets as well as use of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, which all reduce cardiovascular disease risk,’ Associate Professor Piya told Endocrinology Today. ‘So the effect size of 1.1 does not seem that large in this context with so many other variables that may influence the outcome.’
Mendelian randomisation suggested a possible causal effect of MOD on certain cardiovascular outcomes, including CAD, any stroke, any ischaemic stroke and myocardial infarction.
The authors said the findings supported using genetic factors to identify people at risk of developing diabetes and CAD, which could allow earlier preventive measures and potentially more intensive monitoring. They also noted important limitations, including incomplete clinical subtyping data and the predominantly European ancestry of the study population.
‘GPs should universally be treating people with type 2 diabetes as high risk [for CAD] and adopting prevention care including screening for CAD, cholesterol lowering and blood pressure lowering medications, as well as improving blood glucose control,’ Associate Professor Piya said. He added that there were some exceptions for aggressively treating type 2 diabetes for CAD prevention, such as if the patient was older and frail, and if the treatment side effects outweighed the benefits.