Can islet cell transplantation protect against low blood glucose levels?

This study examined the effect of islet transplantation on  hypoglycemia in type 1 diabetes patients.

A normal pancreas produces both insulin and glucagon. These hormones perform opposite functions: insulin decreases blood glucose levels while glucagon increases them when they become too low. Patients with type 1 diabetes mellitus, however, lack the islet cells that produce insulin. Without insulin, the glucose taken in from food cannot be broken down, leading to high levels of glucose in the blood stream. This can damage nerves, blood vessels, and various organs.

Therefore, type 1 diabetes patients must add insulin to the body, usually through injections. However, the use of injections in the management of diabetes can cause hypoglycemia (dangerously low blood sugar levels), a complication which may be life threatening. When a healthy patient faces hypoglycemia, glucagon and adrenaline signal to the liver and kidneys to increase glucose production, while the muscles secrete lactate, which the liver uses in glucose production. In diabetic patients who don’t secrete glucagon, however, this glucose counter-regulatory system does not function properly.

A new treatment option for type 1 diabetes is the transplantation of islet cells from a healthy donor pancreas. Previous studies have found that while islet transplantation improves insulin and glucagon functioning, they do not reach normal levels, and patients still experience episodes of hypoglycemia. The current study examined glucose counter-regulatory functioning following hypoglycemia in islet transplantation patients.

This study included 36 patients: 24 type 1 diabetics, 12 of whom underwent islet transplantation, and 12 non-diabetic control patients. Patients completed two experimental sessions. In one session their glucose, adrenaline, lactate, and other hormones were measured under normal circumstances, and in the second session levels were measured as they underwent a controlled hypoglycemic episode.

Glucose counter-regulation (the sum of processes that protect against the development of hypoglycemia and restore normal glucose levels should hypoglycemia occur) was improved in islet transplanted patients (7.8μmol kg−1 min−1) versus non-islet transplanted patients (0.3μmol kg−1 min−1) but was still 45% lower than in controls (14.1 μmol kg−1 min−1).

During hypoglycemia, increased glucose production accounted for 49% of counter-regulation in islet transplanted patients versus 60% in controls. Decreased glucose disposal accounted for 39% of counter-regulation in islet transplanted patients versus 36% in controls.

Lactate gluconeogenesis (the production of glucose from lactate, a chemical compound in the body) increased during hypoglycemia in islet transplanted patients and control subjects, accounting for 70% of the increased glucose production in islet transplanted patients and 20% of the increased glucose production in control subjects.

During hypoglycemia, glucose counter-regulatory hormones increased in islet transplanted patients and control subjects. Glucagon levels in islet transplanted patients reached 30% of those seen in control subjects. Adrenaline levels in islet transplanted patients reached 25% of those send in control subjects. 

When comparing glucose production during the two sessions, hypoglycemia led to an 80% glucose increase in islet transplanted patients, a 236% increase in control patients, and glucose decreased in non-transplanted diabetics.

This study concluded that islet transplantation improved the response to hypoglycemia through increases in lactate secretion and glucose production. However, patients with transplanted islets do not improve to the level of non-diabetics.