Can We Predict The Risk Of Diabetes?

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​Diana Juvinao-Quintero, PhD

Predicting who will develop diabetes mellitus, specifically type 2 diabetes (T2D), would greatly enhance the ability to care for people and help reduce risk. How far are we from being able to accurately predict the onset of diabetes? 

Current reports from the Centers for Disease Control and Prevention (CDC) estimate that around 34.2 million Americans have T2D, with differences by race and ethnicity (non-Hispanic Black and Hispanic Americans have higher rates). T2D is characterized by a failure of beta-cells in the pancreas to produce enough insulin to compensate for the progressive loss of sensitivity to insulin in peripheral tissues, often related to excess weight. While obesity is a strong predictor of T2D (80-85% risk prediction), not all individuals with obesity develop T2D.
 
Genetic characteristics might help to improve predictions. Specifically, researchers have explored whether regulatory markers of DNA that influence how genes are expressed might help. DNA provides the genetic blueprint for how the body and many diseases develop; this DNA can be modified when people are exposed to the environment. These modifications are known as epigenetic markers, and they are believed to play an important role in explaining the risk of complex diseases like T2D. Epigenetic markers can be modified by changes in the environment associated with disease risk, like smoking, diet, pollutants, among others, and they are also under partial genetic control. Currently, the most studied epigenetic signature is DNA methylation or the addition of a methyl (CH3) group to one of the molecules in DNA (Figure 1). DNA methylation can influence activation or inactivation of the expression of the nearby gene; information on these patterns of methylation might help improve our ability to predict risk for developing T2D.

For instance, the strongest DNA methylation marker in blood associated with T2D across different ethnic groups (Europeans, Indians, Arabs, etc.) has been found in one specific gene which role is in regulating insulin secretion in pancreatic beta-cells, the synthesis of glucose in the liver, and the uptake of glucose from peripheral tissues. Furthermore, by using a predictive score combining the effect of 5 DNA methylation sites associated with future risk of T2D identified in a prospective multi-ethnic cohort study, researchers were able to determine ethnic differences in the risk of T2D revealed by DNA methylation. In this study, the authors found that Indians had a 3.51% higher future risk of T2D compared to Europeans after adjusting for common clinical risk factors.
 
Overall, the discovery of new molecular markers to predict T2D incidence and progression is a promising field of study. These markers may add to more traditional ways to predicting risk. The aim is to use these markers in the early detection, allowing for possibly earlier prevention and treatment of T2D, especially in populations at higher risk of developing the disease. Epigenetic markers have the advantage of being modifiable either by lifestyle or using medication, but before including them as clinical biomarkers, we need to assess their replicability across different populations, and evaluate their causal role in the disease.