Too Much or Too Little? The Double Jeopardy of Subcutaneous Insulin Therapy in Diabetes.

Abstract

A quote variously attributed to either Woodrow Wilson or Winston Churchill describes golf as “an ineffectual attempt to put an elusive ball into an obscure hole with implements ill-adapted to the purpose.” There are many analogies with the challenges faced with insulin therapy in diabetes. In health, nondiabetic β-cells detect changes in ambient glucose, facilitated by signals from circulating hormones such as glucagon-like peptide 1 and perhaps neural signals (1), allowing insulin secretion to be altered appropriately. Critically, insulin is then released in an oscillatory fashion into the portal circulation so that the levels in the portal vein are approximately fourfold higher than those seen in systemic circulation (2). With exogenous insulin therapy in diabetes, this situation is fundamentally different. In addition to the significant clinical challenges of determining regimen and appropriate insulin doses and timing while allowing for factors such as pharmacokinetics and variability in absorption, exogenous insulin is delivered subcutaneously so that the usual ratio of portal-to-systemic insulin is lost. This means that the direct actions of insulin to suppress net hepatic glycemic output might be lessened and/or the peripheral actions of insulin to promote glucose disposal, particularly in skeletal muscle, might be increased. What are the implications of this for insulin therapy in diabetes, i.e., does this matter for patients and clinicians? In this issue of Diabetes , Gregory et al. (3) compared the differential effects …