The Role of Epigenetics in the Development of Type 2 Diabetes
Epigenetics allows cells to control how different genes are turned on or off within each cell through epigenetic regulation.
Epigenetic changes play an integral role in all aspects of T2DM, from its risk and development to complications and insulin resistance and malfunction. They affect defective secretion of insulin as well.
Genetics
Ever since people first asserted that heredity played a pivotal role in developing type 2 diabetes, researchers have been on a search for genetic variants which increase its risk. This was only made possible due to advancements in human genetic studies and modern genomic technologies.
T2D’s heritability ranges between 30-70%; family history can be an effective predictor of risk, with twofold and threefold increased risks among siblings and first-degree relatives of individuals diagnosed with the condition respectively. More than 120 genetic loci have been linked with T2D or glucose and insulin concentrations among European and multiethnic populations.
These genetic loci may be explained through mechanisms involving epigenetic modifications, including DNA methylation and histone acetylation, that the body uses to regulate gene expression in response to environmental stimuli and can be passed down for multiple generations.
Environment
Epigenetics explains why, even though all cells in our bodies contain identical DNA sequences, each cell exhibits distinct appearance and behavior due to epigenetic influences.
Epigenetics refers to how our genes are activated or deactivated without altering their actual sequence, using chemical tags on chromosomes as signals to turn specific genes on and off in cells. Epigenetics can also change chromosome structures by relaxing their tight pack state and allowing access to genes within.
Recent advances in epigenetics have demonstrated how diet, environment, and lifestyle choices can alter gene expression – thus explaining many correlations researchers have noted between lifestyle factors and risk of diabetes (90). Epigenetic changes can occur in any cell type and can be passed along from mother to daughter cells as well as across generations; examples include DNA methylation, histone modification, chromatin remodeling and noncoding RNA production.
Lifestyle
Epigenetics refers to heritable changes that influence gene expression without altering DNA sequence itself. Such epigenetic changes can alter whether certain genes are turned “on” or “off”, and affect how much protein each gene produces.
Numerous approaches have been created for subclassifying type 2 diabetes using clinical features like HbA1c, BMI, lipid profiles and pancreatic autoantibodies. While studies using these features have demonstrated various associations with outcomes, their low to moderate quality of evidence limits their usefulness.
Recent advances in stratification models utilizing genetic or multi-trait information, using machine learning (ML) or other computational methods, have yielded reproducible type 2 diabetes subtypes linked to outcomes. They include process-specific or partitioned polygenic scores as well as muscle gene expression data from muscle tissues – taking advantage of rapidly expanding human genetic risk information and entering clinical practice for use.
Genetic Testing
Genetic testing involves the analysis of DNA or RNA, chromosomes, proteins or certain metabolites to detect any changes associated with heritable disorders. This can be accomplished directly examining DNA that makes up genes (direct testing), looking at markers co-inherited with disease-causing genes (linkage testing), assaying specific metabolites or proteins or even analyzing whole chromosomes directly (cytogenetic testing).
Recent epigenome-wide association studies have identified DNA methylation sites associated with type 2 diabetes and fasting glucose levels. These environmental markers may reflect changes to insulin secretion or metabolism that come with increased body weight.
Research also indicates that in-utero environments can alter epigenetic memory of genes, and this may contribute to T2D development. For instance, during 1944-1945 Dutch Famine caused metabolic changes that affected glucose metabolism and other risk factors later in life. It is essential that you consult a trained genetic counselor prior to undertaking genetic testing.
