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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 3 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. In the fasting state, when insulin levels are low, most glucose uptake into cells is non-insulin mediated. Glucose uptake is then balanced by liver production of glucose. 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.
Medications Used for Glucose Homeostasis in Diabetes
Diabetes is characterized by elevated blood glucose levels due to inadequate or absent insulin production (type 1 diabetes) or due to a state of increased hepatic glucose production, decreased peripheral glucose uptake, and decreased insulin secretion (type 2 diabetes).
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 3 of these classes of drugs, without or without additional insulin, patients with type 1 diabetes, who have no baseline insulin secretion, receive exogenous insulin therapy. Standard insulin management involves use of subcutaneous injection to mimic a physiologic insulin profile. Intravenous insulin is used in the acute inpatient setting for the management of hyperglycemic emergencies (ie, diabetic ketoacidosis).
Chronic Intermittent Insulin Therapy
Several forms of chronic intermittent insulin therapy in which insulin is delivered intravenously or into the peritoneal space have been evaluated.
Chronic intermittent intravenous insulin therapy (CIIIT)--also referred to as outpatient intravenous insulin therapy, pulsatile intravenous insulin therapy, hepatic activation therapy, or metabolic activation therapy--involves delivering insulin intravenously over a 3-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. CIIIT is principally designed to normalize the hepatic metabolism of glucose. In a 1993 article describing the development of the technique, Aoki and colleagues proposed that, in patients with type 1 diabetes, lower levels of insulin in the portal vein are associated with a decreased concentration of the liver enzymes required for hepatic metabolism of glucose. The authors state, “We reasoned that if the liver of an IDDM [insulin-dependent diabetes mellitus; ie, type 1 diabetes] patient could be perfused with near-normal concentrations of insulin during meals, the organ could be reactivated,” and proposed that intermittent intravenous pulsatile infusions of insulin administered once weekly while the patient ingests a carbohydrate meal will increase the portal vein concentrations of insulin, ultimately stimulating the synthesis of glucokinase and other insulin-dependent enzymes. 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 because it is delivered to the liver. The goal of this therapy is improved glucose control through improved hepatic activation.
CIIIT is typically delivered once weekly as outpatient therapy.
Any 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.
Chronic intermittent intravenous insulin therapy is considered investigational.
POLICY EXCEPTIONSFederal Employee Program (FEP) may dictate that all FDA-approved devices, drugs or biologics may not be considered investigational and thus these devices may be assessed only on the basis of their medical necessity.
This policy does not apply to use of intravenous insulin infusions in the inpatient setting (ie, for the treatment of diabetic ketoacidosis or diabetic hyperosmolar coma).
Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.
The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.
POLICY HISTORY5/2002: Approved by Medical Policy Advisory Committee (MPAC)
1/13/2004: Code Reference section updated, ICD-9 procedure code 99.17 deleted, ICD-9 diagnosis code range 250.00-250.93 listed separately
03/10/2006: Coding updated. CPT4 revisions added to policy
1/7/2009: Policy reviewed, no changes
04/26/2010: Policy statement unchanged. FEP verbiage added to the Policy Exceptions section. Added HCPCS code G9147.
10/21/2010: Policy reviewed; no changes.
09/23/2011: Policy reviewed. Policy description updated regarding techniques and devices; policy statement unchanged.
05/07/2013: Policy reviewed; no changes.
11/06/2013: Policy reviewed; no changes.
09/02/2014: Policy reviewed; description updated. Policy statement unchanged.
08/21/2015: Code Reference section updated for ICD-10.
10/28/2015: Policy description updated regarding diabetes and standard insulin management. Policy statement unchanged. Policy guidelines updated to state that this policy does not apply to use of intravenous insulin infusions in the inpatient setting (ie, for the treatment of diabetic ketoacidosis or diabetic hyperosmolar coma). Investigative definition updated.
03/30/2016: Policy description updated. Policy statement unchanged.
06/01/2016: Policy number added.
Blue Cross Blue Shield Association policy # 2.01.43
CODE REFERENCEThis may not be a comprehensive list of procedure codes applicable to this policy.