Twin Study Reveals Epigenetic Factors for Type 2 Diabetes

Epigenetic scientists have been keen on studying twins, particularly identical twins, as they are the perfect subjects to gain insight into the effects of the environment on the genome, especially when it comes to diseases. Because identical twins share the same DNA, any differences they have that are environmentally induced most likely show up in their epigenome.

In a case where one identical twin has a disease, but the other does not, researchers can look at the twins’ environments for variances in the elements. Or, if both twins have a condition, they can look for shared genetic aspects. The data compiled from twin studies offer valuable insight into the molecular mechanisms of disease and the biological impact resulting from environmental factors.

To understand more about type 2 diabetes (T2D), a disease regarded as environmentally induced, scientists from Lund University in Sweden conducted a twin study where only one sibling had T2D. What they found was that an epigenetic change was involved in the development of the disease.

Epigenetics deals with the changes in gene functions that do not alter the DNA sequence. These changes, which are potentially reversible, are influenced by factors in the environment, such as diet, stress, and exercise, among other things. Epigenetic changes are regulated primarily through three main mechanisms: DNA methylation, histone modifications, and micro-RNA (miRNA).

Evidence from previous studies has shown that epigenetic modifications caused by the environment can disrupt metabolic homeostasis and lead to the onset of T2D. DNA methylation, which is the addition of a methyl group to DNA, decreases the accessibility of genes, blocking transcription factor binding and inhibiting gene expression. Moreover, changes in DNA methylation have also been associated with insulin resistance, a hallmark of T2D.

For the Lund study, the researchers recruited several pairs of monozygotic, or identical, twins in their sixties discordant of T2D. Of the siblings that had the disease, BMI measurement was somewhat higher than their twin. Fat biopsies taken from the pairs were analyzed for DNA methylation and miRNA – small single-stranded non-coding RNA molecules that regulate protein production in cells.

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The results showed that the miR-30 gene, which produces a specific miRNA, was downregulated in the T2D twins. Thus, they had lower levels of miRNA-30 in their fat tissues than their healthy twin. This pattern was also seen in the control group of unrelated participants with and without T2D.

“We were able to confirm our results in individuals with no twin siblings and this proves that our results are relevant to all people and not only to identical twins,” said Emma Nilsson, a Lund researcher and co-author of the study.

People with T2D have difficulty processing blood sugar because their cells do not respond to insulin correctly. This effect is called insulin resistance, and it causes a high level of sugar to build up in the blood impairing the body’s ability to use glucose for energy.

Additional tests were done to see if a reduced amount of miRNA-30 in cultured fat cells affected their ability to absorb glucose. The researchers found that lower amounts of miRNA-30 in the cells left them with a reduced capacity for taking up glucose.

“We see the same pattern in people with type 2 diabetes. The study is an importance piece of the puzzle in our work to understand the mechanisms behind type 2 diabetes,” said Nilsson. “The more pieces of the puzzle we find, the better the new drugs we can develop.”

While more research is needed, the data from this study and other similar ones could lead to alternate treatment options for T2D, especially since managing blood sugar levels through diet, exercise, and current medications is difficult for many patients. Plus, some of diabetes medications have negative side-effects as well as a high cost, disparately impacting the most vulnerable of patients – ethnic minorities and food-insecure individuals.

The researchers here believe their study could pave the way for newer, more effective therapies that involve using miRNA as an active drug component, something that is currently being done for other disease. “Clinical studies are already underway in which microRNA is being tested as a drug against cancer, for example,” adds Nilsson.

Source: E. Nilsson et. al. (2021). Differential DNA Methylation and Expression of miRNAs in Adipose Tissue From Twin Pairs Discordant for Type 2 Diabetes. Diabetes.

Reference: Twin study finds type 2 diabetes clues in epigenetic changes. Lund University. November 22, 2021.

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