This section covers the definition, cause, consequences, and cure of diabetes.

Definition

Diabetes is a disease of carbohydrate metabolism defined by elevated blood sugar. Diabetes physiology is well understood. Elevated blood sugars are the result of greatly diminished secretion of the hormone insulin by pancreatic islets of Langerhans or by diminished response to insulin by the body coupled with somewhat diminished secretion of insulin. The first type of diabetes is named "Insulin-Dependent Diabetes Mellitus (IDDM)" and the second type is named "Non-Insulin-Dependent Diabetes Mellitus (NIDDM)."

Cause

The cause of IDDM is thought to be progressive and irreversible destruction of the islets by the diabetic's immune system. In the United States approximately 0.7% of the population will develop IDDM, most before age 25; hence the old name, "juvenile diabetes." At present there are 700,000 people with IDDM. All people with IDDM are treated with daily insulin injections, exercise, and diet; and with multiple daily blood glucose measurements.

The primary cause of NIDDM is thought to be "peripheral insulin resistance" (declining insulin sensitivity in the body, especially skeletal muscles) coupled with a secondary decline in insulin secretion by the islets of Langerhans. The root cause of insulin resistance is unknown. In the United States approximately 12% of the population will develop NIDDM, most after age 25; hence the old name, "adult diabetes." At present there are 16,000,000 people with NIDDM, most being undiagnosed. People with NIDDM are treated with exercise and diet; many take oral medication, some daily insulin injections, and some make blood glucose measurements. An estimated 700,000 people with NIDDM take insulin regularly.

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Consequences

Diabetes is associated with retinal, renal, neurological and cardiovascular complications. It causes 24,000 new cases of blindness annually. Diabetes is the leading cause of end-stage renal disease and increases the risk for cardiovascular disease fourfold. Many of the complications of diabetes are associated with breakdown of the microvasculature.

DCCT Study

These vascular-related complications are preventable through tight control of diabetes. The Diabetes Control and Complications Trial (DCCT) showed that sustained reduction in glucose levels result in striking risk reduction (Figure below). Even more dramatic reductions are expected from the near-perfect glycemia provided by the Islet Sheet.

A Cure for Diabetes

We believe that a therapy that produces euglycemia without risk of hypoglycemia is a cure for diabetes. There are four general approaches that might accomplish a cure for diabetes.

Pancreas and Islet Transplantation

Several hundred pancreas and islet transplants, all depending on immune suppression to prevent rejection of the implant, have taken place. Recently, the success rate of the islet procedure has been improving and may soon rival the success rate of kidney transplantation, over 80%. However, current immune suppression methods have side effects that rival the morbidity of diabetes. We see little likelihood of complication-free immune suppression in the near future.

Bio-Mechanical Devices

An artificial pancreas involving a glucose sensor, an insulin pump with a reservoir and a computer to determine the pump speed is one possibility. The chief difficulty with this approach has been that no glucose sensor is sufficiently sensitive, accurate and stable. If the device malfunctions, it may kill the diabetic.

Genetic and Cellular Engineering

In this approach cells, are engineered to evade the host immune system. This may be accompanied by specific immunosuppression. While promising, the rate of progress thus far indicates that complete immune evasion by bioengineered cells (in the absence of a physical barrier) will not be possible for many years.

Bio-artificial Pancreas

The bio-artificial pancreas has living, functional islets or cells in an artificial polymer matrix. This is the approach taken by Islet Sheet Medical.

The matrix can in principle be many different polymers; a common one, and the one favored by ISM, is alginate.

The cellular component can be primary islets of Langerhans (harvested with minimal damage from living donors or animals), cultured cell lines, or cultured genetically engineered cells.