Research to Identify and Correctly Treat Rare Forms of Diabetes

Dr. Louis Philipson
Louis Philipson, MD, PhD

The vast majority of diabetes cases—both type 1 and type 2—are polygenic diseases, meaning that more than one gene contributes to risk of and progression to diabetes. However, some very rare forms of diabetes, distinct from type 1 or type 2 diabetes, are caused by single gene mutations. These forms of diabetes account for an estimated 1-5 percent of all cases of diabetes and are called "monogenic" diabetes.

Beginning in the early 1990s scientists started to identify particular single gene mutations as the causative factor in neonatal diabetes—diabetes that appears in newborns up to about 6-9 months of age. In part because neonatal monogenic diabetes is rare, these individuals are often misdiagnosed as having type 1 diabetes and are treated with insulin. However, because the single gene mutations that cause the disease don't necessarily result in total insulin deficiencies like type 1 diabetes, oral medications like sulfonylureas can sometimes be used to better manage diabetes in patients with monogenic diabetes. The correct diagnosis of monogenic diabetes is critical to manage these patients appropriately, and can make a significant impact in the lives of the patients who are correctly diagnosed.

However, the study of rare diseases can be especially difficult, in part because of the challenge in identifying sufficient numbers of patients to study. With funding from the American Diabetes Association, Dr. Louis Philipson created the first registry for individuals with monogenic diabetes. Using web-based technologies, the University of Chicago Monogenic Diabetes Registry allows for the successful recruitment of a relatively large number of patients with monogenic diabetes who are providing great insight into our understanding of these sub-types of diabetes, and how best to treat them. Data can be efficiently collected and maintained in a secure and confidential manner. Now DNA from people diagnosed with diabetes in the first several months of life can be tested for known mutations. If a defined mutation is confirmed, these patients may be able to transition from insulin therapy to sulfonylurea, an oral medication, to effectively manage their diabetes.

The more we learn about links between genetics and diabetes through biomedical research, the better able we are to develop and deploy the correct treatment regimen to treat individuals based on their specific genetic make-up. Because of the work of individuals like Dr. Philipson, we now know that individuals who have been diagnosed with diabetes as infants are more likely to have monogenic diabetes, and that they should be tested at a center that specializes in monogenic diabetes. Importantly, the genetic test is required to diagnose these forms of diabetes; patients who suspect they might have monogenic diabetes are strongly advised not to change their medication regimen in the absence of a verified diagnosis that warrants a change. Insulin therapy is essential to all individuals with type 1 diabetes—and even those individuals with monogenic diabetes who may be candidates for transition from insulin therapy to oral medication must do so under the care and guidance of their physician to ensure a safe transition.

Insulin remains a life-saving medication, allowing people with type 1 diabetes and with complicated type 2 diabetes to live long, healthy and productive lives.

See the American Diabetes Association's FAQs on monogenic diabetes (PDF).

Monogenic diabetes and the work of Dr. Louis Philipson was highlighted in a documentary film that recently aired on a Chicago-based PBS affiliate.

  • Last Reviewed: March 19, 2015
  • Last Edited: August 10, 2015

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