Type I Diabetes – New therapies and potential cures

Diabetes | May 14, 2014 | Author: The Super Pharmacist

Type I Diabetes – New therapies and potential cures

Not too long ago, insulin regimens required multiple daily injections. People with diabetes would have to take multiple blood sugar readings throughout the day and adjust the dose of their short-acting insulin to meet their individual requirements. This would mean large fluctuations of insulin and glucose (peaks and troughs) circulating in their blood. Too much insulin would result in hypoglycaemia while too little insulin could cause different complications, such as diabetic ketoacidosis.

Basal insulin

Newer, longer-acting insulins have reduced the need for multiple daily injections. For example, insulin glargine is a human insulin analogue that has been modified to delay absorption into the body. As a result, there is essentially no peak in insulin throughout the day. One or two injections provide enough insulin coverage to last throughout an entire day. Other basal insulins, such as insulin detemir and insulin degludec, provide similar coverage. These forms of insulin still carry some risk of hypoglycaemia, especially when administered during certain times of day.1 However, they are quite effective at controlling blood glucose and result in excellent haemoglobin A1C levels.2

Insulin pumps

Insulin PumpInsulin injections may be completely avoidable with the use of an insulin pump. An insulin pump is a computerized device, usually worn on the waist, that supplies insulin through a small tube or catheter. The catheter is placed under the skin into the subcutaneous fat and held in place with an adhesive. The pump delivers insulin continuously to cover basal insulin requirements. At the user's discretion, the pump can be programmed to provide additional amounts of insulin to cover periods of increased blood glucose, e.g., at mealtime. An insulin pump is not an artificial pancreas—the patient still must take blood glucose readings and administer sufficient amounts of insulin throughout the day. However the pump does eliminate the need to make subcutaneous injections, since the catheter is always present.

Sensor-augmented insulin pumps

Sensor-augmented insulin pumps take insulin pumps one step further. These devices function the same way as traditional insulin pumps except they also take blood glucose measurements. This eliminates (or at least reduces) the need for both insulin injections and finger sticks. The device greatly improves haemoglobin A1C levels in patients with poorly controlled type I diabetes.3 Patients and physicians can use the information derived from blood glucose monitoring software to optimize insulin regimens.

Automated closed-loop insulin pumps aka the artificial pancreas

The newest insulin pump technology (still under development) is the artificial pancreas. Researchers refer to the artificial pancreas as the automated closed-loop insulin pump. This pump measures circulating blood glucose levels and calculates the type and dose of insulin that is best for the patient. It then automatically administers the insulin, similar to the function of a healthy pancreas. In type I diabetes clinical trials, the artificial pancreas was better able to maintain optimal blood glucose levels then finger stick testing and injections.4,5 The device also reduced the incidence of night-time hypoglycaemia. Other devices administer both insulin and glucagon (glucagon can be thought of as the opposite of insulin), which also improved blood glucose levels and reduced hypoglycaemic events.6

Transplantation

The cells within the pancreas that control insulin and glucagon secretion are called islet cells. Abnormalities in these cells are the chief cause of type I diabetes. Presumably if one could transplant healthy islet cells (or even a whole pancreas) in a person with type I diabetes, the transplant would regulate glucose levels (effectively curing diabetes). Trials are currently underway to test different approaches to islet cell transplantation.7 The current barrier to this research approach is that transplants of these cells require long-term immunosuppression. It should be possible to transplant cells that do not provide an immune response.

Immunotherapy

Type I diabetes is an autoimmune disease, thus a reasonable therapeutic approach is to provide immunotherapy to block autoimmune destruction of pancreatic islet cells. While there have been several clinical trials using both antigen-specific antibodies and immune system-modulating drugs, these treatments are either too toxic or do not provide long-term protection for islet cells.8 Nevertheless, a substantial research effort in this area is still underway.

Stem cell therapy

There are numerous approaches being tested that take advantage of stem cell technology in the treatment of type I diabetes.9 In broad terms, researchers are pursuing two approaches. In one approach, scientists are attempting to reprogram pancreatic cells using gene therapy to become fully functional islet cells capable of secreting insulin and glucagon. In another approach, they are surgically removing cells from patients with type I diabetes, converting them to functional islet cells, and then transplanting them back into the patient. Compared to the other treatment options, stem cell therapy for type I diabetes is in its relative infancy. While it has great potential to cure type I diabetes, large clinical trials are likely several years away.

References

  1. Hamann A, Matthaei S, Rosak C, Silvestre L. A randomized clinical trial comparing breakfast, dinner, or bedtime administration of insulin glargine in patients with type 1 diabetes. Diabetes Care. Jun 2003;26(6):1738-1744.
  2.  Mavrogiannaki AN, Migdalis IN. Long-acting basal insulin analogs: latest developments and clinical usefulness. Ther Adv Chronic Dis. Nov 2012;3(6):249-257.
  3.  Bergenstal RM, Tamborlane WV, Ahmann A, et al. Effectiveness of Sensor-Augmented Insulin-Pump Therapy in Type 1 Diabetes. New England Journal of Medicine. 2010;363(4):311-320.
  4.  Hovorka R, Kumareswaran K, Harris J, et al. Overnight closed loop insulin delivery (artificial pancreas) in adults with type 1 diabetes: crossover randomised controlled studies. BMJ. 2011;342:d1855.
  5.  Phillip M, Battelino T, Atlas E, et al. Nocturnal glucose control with an artificial pancreas at a diabetes camp. N Engl J Med. Feb 28 2013;368(9):824-833.
  6. Haidar A, Legault L, Dallaire M, et al. Glucose-responsive insulin and glucagon delivery (dual-hormone artificial pancreas) in adults with type 1 diabetes: a randomized crossover controlled trial. CMAJ. Mar 5 2013;185(4):297-305.
  7. Jamiolkowski RM, Guo LY, Li YR, Shaffer SM, Naji A. Islet transplantation in type I diabetes mellitus. Yale J Biol Med. Mar 2012;85(1):37-43.
  8. Chen W, Xie A, Chan L. Mechanistic basis of immunotherapies for type 1 diabetes mellitus. Transl Res. Apr 2013;161(4):217-229.
  9.  Wagner RT, Lewis J, Cooney A, Chan L. Stem cell approaches for the treatment of type 1 diabetes mellitus. Transl Res. Sep 2010;156(3):169-179.

 

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