Taken from www.diabetes.org:

Diabetes is a disease in which the body does not produce or properly use insulin. Insulin is a hormone that is needed to convert sugar, starches and other food into energy needed for daily life. The cause of diabetes continues to be a mystery, although both genetics and environmental factors such as obesity and lack of exercise appear to play roles.

There are 23.6 million children and adults in the United States, or 7.8% of the population, who have diabetes. While an estimated 17.9 million have been diagnosed with diabetes, unfortunately, 5.7 million people (or nearly one quarter) are unaware that they have the disease.

In order to determine whether or not a patient has pre-diabetes or diabetes, health care providers conduct a Fasting Plasma Glucose Test (FPG) or an Oral Glucose Tolerance Test (OGTT). Either test can be used to diagnose pre-diabetes or diabetes. The American Diabetes Association recommends the FPG because it is easier, faster, and less expensive to perform.

With the FPG test, a fasting blood glucose level between 100 and 125 mg/dl signals pre-diabetes. A person with a fasting blood glucose level of 126 mg/dl or higher has diabetes.

In the OGTT test, a person's blood glucose level is measured after a fast and two hours after drinking a glucose-rich beverage. If the two-hour blood glucose level is between 140 and 199 mg/dl, the person tested has pre-diabetes. If the two-hour blood glucose level is at 200 mg/dl or higher, the person tested has diabetes.

Major Types of Diabetes

Type 1 diabetes
Results from the body's failure to produce insulin, the hormone that "unlocks" the cells of the body, allowing glucose to enter and fuel them. It is estimated that 5-10% of Americans who are diagnosed with diabetes have type 1 diabetes.

Type 2 diabetes
Results from insulin resistance (a condition in which the body fails to properly use insulin), combined with relative insulin deficiency. Most Americans who are diagnosed with diabetes have type 2 diabetes.

Gestational diabetes
Immediately after pregnancy, 5% to 10% of women with gestational diabetes are found to have diabetes, usually, type 2.

Pre-diabetes
Pre-diabetes is a condition that occurs when a person's blood glucose levels are higher than normal but not high enough for a diagnosis of type 2 diabetes. There are 57 million Americans who have pre-diabetes, in addition to the 23.6 million with diabetes.

Making Progress Possible:  Research Review

(From the 2008 Diabetes Research Institute Foundation Annual Report)

From providing the seed funding for jumpstarting new research ideas to ensuring the continuation of promising research projects, the Diabetes Research Institute Foundation plays a major role in supporting the Institute’s multidisciplinary program.  Below is a summary of the progress made last year by DRI scientists in such cutting-edge areas as stem cell research, tissue engineering, nanotechnology and other cell-based therapies that are made possible through the generous donations to the Foundation.

REPROGRAMMING A PERSON’S OWN CELLS

The DRI’s stem cell team has developed a new approach to reprogram adult stem cells by “turning back the clock.”  Building upon research that demonstrated that a person’s own skin cells can be returned to an undifferentiated state, similar to that of an embryonic stem cell, the DRI is testing the same concept but using a much safer approach.  The reprogramming of the skin cells resulted when four master genes were inserted using retroviruses, which have numerous safety concerns.  DRI researchers are using protein transduction technology, which offers most of the advantages with none of the drawbacks.  The stem cell team has already used protein transduction technology to differentiate early stem cells into mature cell types.  This is the first attempt to apply the same principle to the opposite goal—reprogram adult cells into stem cells.  Armed with this preliminary data, the researchers have been awarded a grant from the National Institutes of Health to fully explore the potential of this technology.

SCIENTESTS IDENTIFY KEY STEPS FOR BETA CELL DEVELOPMENT

Scientists have determined that embryonic stem cells proceed through five developmental stages in order to become—or differentiate into—insulin producing cells.  At each stage, a “developmental switch” needs to be turned on to drive the cell down the intended path.  The key is to be able to insert these developmental switches, or signals, safely into the cell.  Using the protein transduction technology described above, DRI scientists have successfully tested four of these signals for their ability to induce pancreatic cell differentiation and a fifth is currently undergoing preliminary studies.  In addition to using embryonic stem cells, the research team has expanded the study to include other cell types, such as cord blood and amniotic fluid.

While embryonic stem (ES) cells hold great promise for curing diabetes and other diseases, their use poses certain risks to patients. B y their very nature, embryonic stem cells continue to divide and multiply, and if left unchecked, can form tumors called teratomas.  Unless safety mechanisms are put in place to prevent the occurrence of tumors, human embryonic stem approaches will not be clinically applicable.  DRI researchers are working to genetically modify ES cells with specific “suicide genes” that will be selectively activated in 1) cells that differentiate into tissues other than pancreatic insulin-producing  cells; and 2) cells that continue to divide after differentiation.  This double fail-safe mechanism is designed to ensure maximum safety for the clinical use of these cells.  The DRI is currently in the process of establishing a collaboration with the prestigious Roslin Institute in Scotland to deliver these genes using a technology called “gene targeting.”

NOVEL AGENTS AIMED AT REPLACING HARSH DRUGS

The DRI’s drug discovery team has been focusing on identifying and developing new small molecules to prevent the rejection of transplanted insulin-producing cells as well as thwart the autoimmune attach that initially destroyed these cells in the patient’s pancreas.  It is well known that these immune responses cannot occur without a cell-to-cell signaling called costimulatory interaction.  In particular, researches have been taking a close look at the CD40-CD154 pathway, which has shown to be important for promoting successful islet transplantation.  Effectively blocking this pathway would induce transplantation tolerance and prevent the recurrence of autoimmunity.  Although it was thought that small molecules would not block this interaction, it has become clear that they can.  THE DRI’s druge discovery team has now obtained proof-of-principle evidence that small molecules can effectively inhibit the critical CD40-CD154 interaction, which might provide new clinical therapies in many areas.

SCIENTISTS DISOVER NANOTECHNOLOGY AND ENGINEERING TECHNIQUES TO PROTECT ISLETS

The DRI’s tissue engineering team is working on a number of new approaches to protect transplanted cells from the recipient’s strong immunological and inflammatory responses while providing the critical nutrients needed to sustain healthy function.  The primary focus is on the use of alternative transplantation sites and new biomaterials to house these cells.  Initial studies have domenstrated that long-term restoration of blood sugar control can be reproducibly achieved after transplantation of islets into a prevascularized (filled with blood vessels) device in an experimental model.  By combining nanotechnology and advanced engineering principles, the team is now working to make a number of improvements to the device, including:  improving its physical structure; developing a “bioactive scaffold” that will house the islets and prevent them from clumping together; delivering anti-rejection drugs within the device instead of throughout the entire body; adding several factors that enhance the supply of oxygen to the encased islets; emitting nano-sized drugs that will reduce inflammation at the transplant site; and containing “helper cells” that enhance islet survival and function.

KEY SIGNALS DIRECT BETA CELL GROWTH

The DRI’s Molecular Biology team recently identified an important “master regulator” found in pancreatic islets.  These tiny genes create signals called microRNAs (miRNA) that regulate key biological functions, such as cell proliferation (growth) and the transformation of stem cells into adult cells.  The team discovered that a group of these signals miR-7, appeared in the islets in disproportionately higher numbers—200-fold greater in pancreatic islets as compared to the non-islet tissue of the organ.  The researchers believe that miR-7 has a very early, crucial role in the development of islet cells as well as in maintaining their insulin-producing function.  They are testing approaches to see if modifying the amount of miR07 could represent a novel way to generate insulin-producing cells.  The team is currently performing studies to define the role of miR-7 in the developing mouse pancreas.  These studies will help identify how genes regulate islet development and provide tools for new treatment strategies to cure diabetes.

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