Great strides have been made recently in predicting who is most likely to develop type 1 diabetes, allowing researchers to identify the disease at the earliest stages of development and potentially intervene to preserve beta cell function at a much earlier stage and ultimately prevent onset of symptomatic diabetes.
Analyzing the database from the Diabetes Prevention Trial of Type 1 Diabetes (DPT1), Jay Sosenko, MD, Professor of Medicine and Epidemiology at the University of Miami, identified the variables that were most predictive of who would develop symptomatic type 1 diabetes and used them to create a “risk score.” These variables included BMI, age, fasting C-peptide levels, a measure of overall C-peptide production and a measure of overall glucose. The C-peptide and glucose measurements were obtained from oral glucose tolerance tests. Sosenko then applied the “DPT1 Risk Score” (DPTRS) to data from another study, known as the TrialNet Natural History Study (also known as the Pathway to Prevention Study). This is a large multicenter study which is sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and which also receives support from the American Diabetes Association and JDRF. The main objective of TrialNet is to delay or prevent the onset of type 1 diabetes in individuals at high risk (relatives of type 1 diabetes patients who have pancreatic autoantibodies) for the disease. The findings showed that the DPTRS was highly predictive of who would ultimately be diagnosed with symptomatic type 1 diabetes in TrialNet.
According to Dr. Sosenko the DPTRS can identify even those who have normal glucose tolerance but who are nonetheless at risk, in part because it takes age into account because glucose values in children, compared to adults, tend to be lower. Dysglycemia, which is currently used to identify high risk individuals, is based upon the glucose thresholds of adults and these thresholds might not be appropriate for children. In other words, an 8-year-old with a normal two-hour glucose level for an adult (for example, 135 mg/dl) could possibly be at higher risk than an adult with a higher level (for example, 150 mg/dl). If age isn’t also considered, a child at high risk could be missed.
The researchers found that once the DPTRS passed a certain threshold, individuals were highly likely to develop symptomatic type 1 diabetes.
A second study, The Environmental Determinants of Diabetes in the Young (TEDDY), is looking at population – based predictions of type 1 diabetes and potential triggers for the disease. The TEDDY study screened children at birth to identify those with the highest genetic risk of developing type 1 and is following those children for development of islet antibodies and diabetes. The study has enrolled 1,300 participants at each of six medical centers in Sweden, Finland, Germany, Georgia/Florida, Colorado and Washington, for a total of 8,600 participants. The researchers estimate that 400 of them will ultimately develop type 1 diabetes. So far, 150 participants have been diagnosed with type 1 diabetes.
At the same time, they are measuring environmental exposures for the children in the study so that they can ultimately make correlations between these exposures and who develops type 1 diabetes.
Not only will TEDDY help researchers to better understand what causes type 1 diabetes, it also provides clear direction into how to develop population-wide methods to predict type 1 diabetes in all children starting at birth.
