CLOSED LOOP SYSTEM IN TYPE 1 DIABETES MANAGEMENT COMPARISON WITH PRAMLINTIDE Vs EXENATIDE

Diabetes complications can be minimized or forestalled with the use of intensive insulin management. In the post-Diabetes Control and Complications Trial (DCCT) era, diabetologists around the globe are engaged in developing better methods of improving glycemic control in patients with type 1 diabetes mellitus (T1DM). To achieve the DCCT-recommended glycemic and hemoglobin A1C (HbA1c) goals, in addition to physicians, engineering and pharmaceutical companies are augmenting our ability to improve control by innovative compounds and technologies such as continuous glucose monitoring. Despite these substantial advances, hyper- and hypoglycemia continue to be problematic in the management of T1DM, especially in children.

Current T1DM management involves checking blood glucose pre-prandially and once at bedtime (4 times/day), and making insulin dose adjustments based on these 4 blood glucose measurements. This approach is woefully inadequate. Post-meal hyperglycemia is missed, and low blood glucose is undetected until the patient has symptomatic hypoglycemia. Moreover, we depend on patients to make appropriate dose modifications to basal rates of insulin when on the pump, without the guidance of adequate blood glucose measurements. The continuous glucose monitoring system (CGMS) is increasingly studied as a tool to examine glucose trends, and is helping to combat inadequate self-monitoring. However, the CGMS still relies on the patient's ability to make accurate insulin dose adjustments based on glucose readings. To address this issue the closed loop system is now under investigation.

The closed loop system is developed to closely emulate physiologic insulin delivery. The algorithm was developed by modeling beta cells and validated by hyperglycemic clamp studies using the subcutaneous site for measurement of blood glucose and insulin delivery. The algorithm is known as the external Physiologic Insulin Delivery (ePID). Current studies suggest that basal requirements are detected accurately, and the algorithm responds effectively. However, meal related elevation in blood glucose remains a challenge, as when blood glucose levels begin to rise and are seen in the subcutaneous glucose sensor signal, it is already too late to administer insulin in a way that will effectively minimize the postprandial glucose peak. Improvements in the ePID algorithm have been studied to improve the postprandial response with some success, but require user intervention for best results, and despite that glucose excursions fail to normalize in the post-prandial period. It is likely that further improvements in postprandial glycemia will be limited with insulin monotherapy. Besides insulin there are other dysregulated hormones such as glucagon and amylin, which contribute to post-prandial hyperglycemia.

The autoimmune destruction of insulin-secreting beta cells of the pancreas is presumed to cause T1DM. In addition to insulin, other hormones such as glucagon and amylin play a role in normalizing glucose excursions. Failure of glucagon suppression results in immediate postprandial hyperglycemia, and a loss of glucagon response to hypoglycemia results in late postprandial hypoglycemia. Despite the increasing use of subcutaneous continuous insulin administration and newer insulin analogs, insulin replacement remains imperfect, and glucose excursions are inadequately controlled in diabetes. This suggests that other factors, in addition to diet and insulin management, may need to be addressed if postprandial glucose excursions are to be normalized in T1DM.

The recent discovery of the hormone amylin has enhanced our understanding of postprandial glucose homeostasis. Patients with T1DM have deficiencies of both insulin and amylin. Amylin, a 37-amino acid polypeptide hormone, is co-secreted from the pancreatic beta cells in conjunction with insulin in response to nutrient stimuli. Amylin, in the immediate postprandial period, may mediate part of its effect by suppressing glucagon secretion, resulting in the suppression of hepatic glucose production and the slowing of gastric emptying.