We are well aware of the conventional predictors for type 2 diabetes. Besides non-modifiable factors such as age, gender, ethnic background and family history of disease, modifiable factors include BMI, waist circumference, blood pressure, cholesterol levels and lifestyle choices (smoking, diet, exercise…). They all appear in classical calculators for diabetes risk assessment and have been used in the medical practice for many years.
But what about new emerging risk factors and predictors?
In recent years, the rapid advancements in human genetics have led to the discovery of thousands of genetic variants associated with all kinds of diseases. So type 2 diabetes should not be an exception, right?
In his presentation at the Expert Forum on diabetes, Vincent Mooser, Professor, Head Clinical Chemistry CHUV at the University of Lausanne, highlighted that type 2 diabetes is highly heritable. Meta-analysis of multiple twin studies including over 35,000 same-sex twins revealed a high heritability for type 2 diabetes of 72% across the cohorts. Additionally, genome-wide association studies (GWAS), large observational studies to identify genes involved in traits and human disease, revealed over 100 genetic variants associated with type 2 diabetes.
To the surprise of scientists, only roughly 10% of the heritability could be accounted for by these variants. In order to find the “missing heritability,” scientists have been pursuing fine-mapping of the whole genome in order to identify additional low-frequency variants with large effect size for the disease. However, none of those identified seem to play a significant role in predisposition to type 2 diabetes (see also the interview we did with Professor Mooser during the Expert Forum on diabetes).
As highlighted during the presentation of Francisco Verdeguer, Assistant Professor at the Department of Molecular Mechanisms of Disease at the University of Zurich, the missing genetic heritability may partially be concealed at another layer of our genome – the epigenetic level. Different epigenetic mechanisms have been shown to regulate the temporal and spatial control of genes as a response to environmental stresses, without changing the underlying genetic code. There is a growing body of literature suggesting an important role for epigenetics as a molecular link between environmental factors and type 2 diabetes, but more studies are needed to dissect its role in the pathogenesis of the disease and its complications.
Despite the current absence of explicit type 2 diabetes "driver gene(s)", it is too early to disregard the value of genetic research to the individual. It has been suggested that an alternative clinical use of genetic information is determining whether genetic testing may affect a person’s behaviour and thus modify the risk of developing diabetes. In fact, the big promise of direct-to-consumer (DTC) genetic testing provider offering disease predisposition testing is that insights into personal genetic information could encourage individuals to take a more proactive role in their health care.
Studies from the US Diabetes Prevention Program (DPP) showed that carriers of the most significant genetic marker associated with type 2 diabetes risk who underwent lifestyle modifications (low-fat diet, exercise, and behaviour modification) can reduce their risk of type 2 diabetes development by 80% compared to participants not engaged in preventive lifestyle interventions.
Given that the risk of developing type 2 diabetes is highly dependent on modifiable factors, notably diet, lack of exercise and obesity, acting on these is probably the most promising way in order to reduce one's type 2 diabetes disease burden significantly.
To conclude, although genetic variants identified so far may be limited in their ability to predict type 2 diabetes, some people will be actually more worried about their genetic risk rather than their lifestyle. Using genetic information could motivate a high-risk individual to improve his/her behaviour, and in turn help to prevent the eventual onset of the disease. On the other hand, news that one has above-average genes may indeed be counterproductive by demotivating those with lower genetic risk from engaging in healthy behaviours.
Watch our summary video if you would like to know more about the other presentations and sessions during our Expert Forum on diabetes.
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