Rediscovering Insulin for the Treatment of Diabetes

Presented by Robert Gabbay, MD, PhD
Workshop A
Thursday, October 28, 2004

Reviewed by Joelle Escoffery, PhD

Because of the autoimmune β-cell destruction associated with type 1 diabetes and the progressive β-cell loss associated with type 2 diabetes, insulin replacement therapy is inevitable in diabetes. The goal of insulin replacement therapy in type 1 diabetes is to mimic normal β-cell function as closely as possible. However, in type 2 diabetes, insulin replacement therapy can be more complex because the degree of β-cell failure and the action of other oral medications that patients may be taking concomitantly need to be considered.

Strategies for insulin replacement therapy must take normal insulin secretion into account. Basal insulin suppresses glucose production between meals and overnight.  It comprises approximately 50% of insulin production. The remaining 50% of insulin is produced in the form of bolus insulin secreted in response to meals (approximately 10% to 20% with each meal).

In terms of available basal insulins, NPH, lente, and ultralente have been available for some time. Newer basal insulin analogs such as glargine and detemir have advantages over the older basal insulins because they are peakless, less variable, and are associated with fewer side effects. There also are a variety of bolus insulins available, including regular insulin and the newer rapid-acting insulin analogs lispro, aspart, and glulisine. The major disadvantage of regular insulin is that it must be taken 20 to 40 minutes prior to a meal or it will not provide the proper postprandial coverage.

Insulin replacement therapy for type 1 diabetes, and ultimately for type 2 diabetes, involves a combination of basal and bolus insulin. When deciding which type of insulin regimen to use with type 2 patients not achieving control with oral agents, it is important to consider baseline A1C. When oral agents begin to fail, the traditional approach has been to add a basal insulin and continue with an insulin secretagogue. However, if baseline A1C is significantly high, a basal and bolus regimen may be necessary. If using a basal and bolus regimen, the use of insulin secretagogues is not recommended, as hypoglycemia might be a concern. When using insulin, patients need to be able to make the appropriate adjustments to their regimens. Some important tools for problem solving include patient education, self-monitoring of blood glucose levels, continuous glucose monitoring, and pens and pumps for more convenient insulin delivery.