Noninvasive Insulin-Delivery Systems
Options and Progress to Date William T. Cefalu
University of Vermont College of Medicine, Burlington, Vermont
Since its discovery, insulin has been the mainstay of treatment for patients with type I diabetes. For patients with type 2 diabetes, we have traditionally relied on the oral agents, and these pharmaceutical agents have served us well. With the various drug classes now available, the oral agents address the pathophysiological abnormalities recognized to be present in the patient with type 2 diabetes. Specifically, oral hypoglycemic agents such as the sulfonylureas depend on insulin production by (3 cells and can markedly increase meal secretion of insulin. The biguanides, i.e., metformin, and the more recently introduced thiazolidinediones improve glycemic control by decreasing hepatic glucose production and sensitiz- -g ing the peripheral tissues to insulin. Nevertheless, the mode of action for diese |
two classes of drugs also depends on adequate endogenous insulin production or |
on exogenous insulin. In addition, the results of long-term prospective studies have demonstrated that the natural history of type 2 diabetes suggests a progres- ?
sive disease in which multiple therapies may be required to achieve glycemic a control. In this regard, the combination of drugs from the various classes has |
shown additive benefits to improve diabetic control, and combination oral therapy a
may be considered a routine approach in the management of type 2 diabetes. However, with the progressive nature of the disease, and the failure of combination oral therapy to adequately control the patient, insulin has emerged as a more viable treatment option much earlier in the disease process in patients with type 2 diabetes.
Type 2 diabetes, as discussed in detail in other chapters of this book, can be considered a disease in which a "relative" insulin deficiency exists at any given level of insulin resistance. Essentially, type 2 diabetes presents when the pancreas fails to compensate for the increased insulin demand and this failure to adequately compensate results in hyperglycemia. It has been observed that patients with type 2 diabetes will develop progressive insulin deficiency during the course of their disease. As a result, exogenous insulin may be required to achieve glyccmic control for most patients at some point, either as monotherapy or in combination. The European Diabetes Policy Group has suggested guidelines for diabetes care that recommend using insulin in type 2 diabetic patients with HbAlc levels >7.5%. It may be because of these suggested guidelines that the use of insulin in patients with type 2 diabetes appears to be more widely accepted in Europe than in the United States at this time. The National Institutes of Health has estimated, however, that in the United States approximately 40% of patients with type 2 diabetes currently receive exogenous insulin therapy.
The benefits of insulin therapy, although well established for type 1, have also become important in the management of patients with type 2 diabetes when one considers the benefits of improved glycemic control in both types of diabetes (for review, see Chapter 1). The Diabetes Control and Complications Trial demonstrated conclusively that the risk of microvascular complications (e.g., retinopathy, nephropathy, neuropathy) can be reduced significantly in patients with type
1 diabetes with tight glycemic control. Evidence for a benefit of improved glycemic control in type 2 patients was provided by the United Kingdom Prospective Diabetes Study. This study confirmed that in patients with type 2 diabetes, improved glycemic control significantly reduced the number of microvascular complications, as well as offering some indications of a favorable effect on macrovas-cular disease. Thus, when adequate glycemic control is not achieved in the type
2 diabetic patient, as determined by failure to achieve the target HbA k level with traditional oral therapies, it is appropriate to consider exogenous insulin administration. In the effort to achieve glycemic control, exogenous insulin ther- ^
apy can be considered the "gold standard" because die dose can be titrated to h achieve the desired glycemic target. ^
It can be argued that the benefits obtained by achieving good glycemic control with insulin therapy outweigh any theoretical or unsubstantiated risks. 5
However, both physicians and patients have concerns about the safety and ad- J
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Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...