Type 2 diabetes is a chronic illness characterised by the presence of elevated blood glucose levels. It accounts for between 80 and 90% of diabetes cases and is one of the major cardiovascular risk factors. If not treated appropriately it can lead to very serious complications including strokes, heart attacks, neuropathy and blindness. Currently, glycated hemoglobin A1c is used as a measure of glycemic control and also as a diagnostic criterion for diabetes and does not identify the cause of Type 2 diabetes.
However, DNA methylation has been hypothesized as one of the crucial mechanisms mediating the relation between Type 2 diabetes and environmental exposures. Now, a study from researchers at the Hospital del Mar Medical Research Institute (IMIM) has identified an epigenetic mechanism implicated in the regulation of blood sugar. The team state that their results, replicated in two patient cohorts, could help to both identify patients at risk of developing diabetes and control treatment response, as well as generating possible future therapies for this disease.
Previous studies show that methylation is an epigenetic process which modifies DNA, altering the structure of a gene without modifying its basic sequence. Unlike genetics, where all the cells of a single organism share the same DNA that remains unchanged throughout life, epigenetics, and methylation in this case, the best studied epigenetic mechanism, is dynamic and adjusts according to lifestyle. It is a mechanism that can be associated with risk modulation in diverse pathologies, including diabetes. The current study reveals that the methylation of the TXNIP gene is associated with diabetes mellitus type 2 and, in particular, average blood glucose levels.
The current study analysed methylation in the blood samples of a cohort of 355 stroke patients using a state-of-the-art technique allowing them to study more than 450,000 methylation points in the genome. In addition, the group also compared the methylation profiles of diabetics and non-diabetics as well as their levels of glycosylated haemoglobin, a biomarker that indicates blood glucose levels over the past 3 months. Results show that in both analyses the TXNIP gene had a low-level of genomic methylation, known as hypomethylation, in patients with diabetes, especially in those with poor control over their glucose levels. Data findings show that in addition, computer simulations reveal that the hypomethylation position is located in a regulating region of the gene, which is why it has an effect on the expression.
The study was subsequently replicated in two cohorts from independent populations, with 167 and 645 patients respectively, confirming the relationship between TXNIP methylation, diabetes and glucose level dysfunction. The lab conclude that these findings could aid in the early detection of this disease as well as helping assess the effectiveness of both treatments and lifestyle changes that the patients can make to control it.
The team surmise that methylation of this gene could be used as an early biomarker of dysfunction in the control of glucose levels and are currently studying the implications and specific role of this gene in diabetes. For the future, the researchers state that this epigenetic marker could provide a possible therapeutic target for treating diabetes or controlling glucose concentrations.