Chronic intermittent intravenous insulin therapy (CIIIT) is a technique for delivering variable-dosage insulin to diabetic patients with the goal of improved long-term glycemic control. Through an unknown mechanism, it is postulated to induce insulin-dependent hepatic enzymes to suppress glucose production. There are three main sites of insulin-mediated glucose homeostasis that must function in a coordinated fashion to maintain euglycemia: 1. insulin secretion by the pancreas; 2. glucose uptake, primarily in the muscle, liver, gut, and fat; and 3. hepatic glucose production. For example, in the fasting state, when insulin levels are low, the majority of glucose uptake is non-insulin mediated. Glucose uptake is then balanced by liver production of glucose, critical to nourish vital organs, such as the brain. However, after a glucose challenge, insulin binds to specific receptors on the hepatocyte to suppress glucose production. Without this inhibition, as can be seen in diabetic patients, marked hyperglycemia may result. Different classes of diabetic drug therapy target different aspects of glucose metabolism. Various insulin secretagogues (i.e., sulfonylureas) function by increasing the pancreatic secretion of insulin; thiazolidinediones (i.e., pioglitazone [Actos®]; and rosiglitazone [Avandia®]) function in part by increasing glucose uptake in the peripheral (principally skeletal) tissues; and biguanides (i.e., metformin) function by decreasing hepatic glucose production. While patients with type-2 diabetes may be treated with various combinations of all three of the above classes of drugs, patients with type-1 diabetes, who have no baseline insulin secretion, receive exogenous insulin therapy with or without additional drug therapy with thiazolidinediones or metformin. Large-scale randomized studies have established that tight glucose control is associated with a decreased incidence of microvascular complications of diabetes (i.e., nephropathy, neuropathy, and retinopathy). Currently, the American Diabetics Association recommends a target hemoglobin A1c (HbA1c) concentration of less than 7%.
Chronic intermittent intravenous insulin therapy (CIIIT) also referred to outpatient intravenous insulin therapy (OIVIT), hepatic activation, or metabolic activation, and/or pulsatile intravenous insulin therapy, involves delivering insulin intravenously over a 6- to 7-hour period in a pulsatile fashion using a specialized pump controlled by a computerized program that adjusts the dosages based on frequent blood glucose monitoring. The pulses are designed to deliver a higher, more physiologic concentration of insulin to the liver than is delivered by traditional subcutaneous injections. This higher level of insulin is thought to more closely mimic the body’s natural levels of insulin as they are delivered to the liver. It is hoped that this therapy ultimately results in improved glucose control through improved hepatic activation. CIIIT is typically delivered once weekly as outpatient therapy.
Any FDA approved insulin infusion pump can be used for the purposes of CIIIT. Infusion pumps have received U.S. Food and Drug Administration (FDA) marketing clearance through the 510(k) process, as they are determined to be substantially equivalent to predicate devices for the delivery of intravenous medications.