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IDENTICAL TWINS SHARE THE SAME GENETIC MAKE-UP, YET DUE TO LIFESTYLE CHOICES NOT ALWAYS THE SAME DEVELOPMENT OF CHRONIC DISEASES SUCH AS TYPE 2 DIABETES (T2D). RESEARCHERS HAVE INVESTIGATED THE MOLECULAR MECHANISMS THAT INDUCE T2D VIA AN IDENTICAL TWIN STUDY, WITH THE AIM TO BETTER UNDERSTAND WHY ONE TWIN DEVELOPS THE DISEASE WHILE THE OTHER REMAINS HEALTHY.

T2D is generally characterized as a lifestyle disease, caused by excess body weight, an unhealthy diet, inactivity, and age. However, there is also a strong genetic component to T2D with the disease known to be heritable. Family studies show that first degree relatives (so a parent, sibling, or child) of a person with diabetes are three times more likely to develop T2D than individuals with no family history. Trying to figure out which aspects of the disease are down to nature, and which are down to nurture is an important aspect of diabetes research.

Identical twins can be an interesting way to study these facets of diabetes – they are said to share 100% of their DNA, yet when one twin has diabetes, the other’s risk to develop the disease is 3 in 4 at most. This shows that both genetics and lifestyle are being combined in the development of T2D. A research team in Sweden completed a study published last year in the journal Diabetes,which studied 14 sets of identical twins – each with one twin with T2D and one twin without, in the hope of identifying mechanisms behind the development of T2D.

The researchers focussed their attention on adipose or fat tissue. It is already known that fat tissue can release hormones and regulate metabolism within different organs of the body. The study wanted to find out if epigenetic changes in the DNA could lead to changes in gene expression in the fat tissue, which could then lead on to the development of T2D. DNA methylation was investigated at nearly 500,000 points within the DNA, and was found to alter the expression of different genes between the twins.

For the twin with diabetes, genes involved in inflammation were up-regulated and genes involved in the metabolism of fat and glucose (specifically carbohydrates, amino acids, and lipids) were down-regulated. What this means for the diabetic twin is that they cannot process fat as well as the unaffected twin, which leads to increased fat levels circulating in the blood and then increased uptake by organs such as the pancreas and liver. This then causes insulin resistance and the development of T2D. The research showed that DNA methylation was very similar between identical twins, which suggested strong hereditary; however, in 1,400 places there was a difference in DNA methylation between the twins. Researchers believe that this is due to lifestyle, which confirms that a genetic predisposition to the disease is combined with lifestyle factors during T2D development.

Another interesting and unique finding to this study was a change in the actual DNA sequence between the twins. Six cases were found where one twin had more or fewer copies of a certain DNA sequence, which is unusual given that identical twins are classed as having identical DNA. It is currently unknown how these genetic alterations affect T2D development, with further studies needed to investigate this new finding.

Understanding the basic mechanisms of why some people develop T2D and others don’t is important to help in prevention of the disease. The researchers behind this study confirmed their findings in an independent control cohort, which means that the results are also relevant for the general public. Crown Bioscience hopes that these findings lead to further studies which can help explain the different components of T2D. Crown Bioscience supports research into diabetes through our well-defined in vitro assays and through our in vivomodels available for translational sciences and drug discovery. Our in vivomodels include the world’s largest collection of well characterized naturally diabetic non-human primate models and our dyslipidemia models. Contact us today at busdev@crownbio.com to discover how we can transform your diabetes research.