Diabetes

Diabetes is a group of diseases that affects how the body uses and breaks down blood sugar. A diabetic patient has elevated blood sugar levels, which can lead to serious health complications.

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A NYSCF Public Outreach Panel
on diabetes and stem cell research
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There are three common forms of diabetes, namely type 1, type 2, and gestational diabetes. As an aggregate, 25.8 million children and adults in the United States have either undiagnosed or diagnosed diabetes, representing over 8% of the population.

In type 1 diabetes, the immune system attacks insulin-producing beta cells in the pancreas. With fewer beta cells to respond, less insulin is secreted to breakdown sugar, leading to chronically elevated blood sugar levels. If left untreated, type 1 diabetes is fatal. 

Type 2 diabetes is characterized by insulin resistance, in which the pancreas fails to produce insulin sufficiently or cells fail to use insulin correctly. Sugar cannot enter cells, where it is needed, and it instead builds up in the blood. If left untreated, type 2 diabetes can also be life-threatening.

Other forms of diabetes include monogenic diabetes, in which a genetic mutation causes diabetes, gestational diabetes, which occurs during pregnancy, and other disease-related forms of diabetes.

Generally diabetes can be managed through a combination of dietary changes, increased exercise, and insulin or related mediations. There is, however, no cure to this disease. Diabetes increases risk of highly morbid complications, including blindness, cardiovascular damage and disease, kidney damage, and lower-limb amputation.

With NYSCF support, scientists have made tremendous progress in developing therapeutic strategies and identifying drug candidates for all forms of diabetes.

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egli

NYSCF Senior Research Fellow Dr. Dieter
Egli works with stem cells to model diabetes

How can stem cell research help us find better treatments and cures for diabetes?

Stem cells provide a living window onto diabetes. Researchers at the NYSCF Research Institute derive actual beta cells affected in this disease from patients’ skin samples. These cells mature, get sick, and die off in a dish as in a patient. We can, for the first time, scrutinize what goes wrong on a cellular level that leads to what goes wrong in a patient.

In 2011, Dieter Egli, PhD, a NYSCF – Robertson Investigator, and Scott Noggle, PhD, the Director of the NYSCF Laboratory and the NYSCF – Charles Evans Senior Research Fellow for Alzheimer’s Disease, published a paper in Nature that significantly changed how patient-specific cells may be derived: the NYSCF team reprogrammed an adult cell into a pluripotent stem cell from patients with type 1 diabetes by combining the adult cells with unfertilized donor oocytes. Thereby, they generated patient-specific stem cells that could differentiate into beta cells to potentially transplant and replace damaged or diseased cells in diabetic patients without immune rejection.

This research was heralded as the "#1 Medical Breakthrough" of 2011 by Time magazine, and was covered in the press, including The New York TimesCNN, and The Economist, among other outlets. Currently, the NYSCF diabetes research team is working to move this significant advance forward and to develop cell therapies to treat all forms of diabetes.

Significant effort has also been placed on understanding why beta cells are attacked by the body’s own immune system in type 1 diabetes. The initial events that lead to beta cell loss remain unclear. However, by examining single genetic mutations at a time, scientists are able to observe how disruptions in one part of the chain have important downstream effects. Through genetic manipulations, they can compare stem cell-derived beta cells from these patients with healthy controls to identify drugable targets

To reach this goal, NYSCF scientists have been creating stem cells from patients with monogenic forms of diabetes, most recently from patients with type 2 maturity onset diabetes of the young (MODY). They achieved an important proof of concept that these stem cell-derived beta cells can accurately reflect the features of this genetic disease in a dish. They corrected the responsible genetic mutation and artificially controlled the maturation of these cells into beta cells progenitors. As a necessary proof-of-concept, they transplanted these stem cell-derived beta cells into mice, which restored insulin levels to those seen in healthy patients. 

Capitalizing on the NYSCF Global Stem Cell Array, NYSCF scientists generate patient-specific beta cells through advanced stem cell techniques. Coupled with the medical histories of patients, these cells serve as an incredibly powerful tool to increase our understanding and to find treatments for this autoimmune disease.

At the NYSCF Research Institute, scientists have the expertise and the newest technology to model the disease using human stem cells, which helps researchers investigate this problem and bring us closer to a cure.


Further Reading:

Diabetes on Wikipedia

American Diabetes Association

National Institutes of Health: National Diabetes Information Clearinghouse

New York Times Health Guide on Diabetes

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