High-dose insulin therapy: is it time for U-500 insulin?
OBJECTIVE
To provide an overview of U-500 regular insulin action, review published clinical studies with U-500 regular insulin, and offer guidance to practicing endocrinologists for identifying patients for whom U-500 regular insulin may be appropriate.


METHODS
This review has been produced through a synthesis of relevant published literature compiled via a literature search (MEDLINE search of the English-language literature published between January 1969, and July 2008, related to U-500, insulin resistance, concentrated insulin, high-dose insulin, insulin pharmacokinetics, and diabetes management) and the authors' collective clinical experience.


RESULTS
The obesity epidemic is contributing to an increase in the prevalence of type 2 diabetes, as well as to increasing insulin requirements in insulin-treated patients. Many of these patients exhibit severe insulin resistance, manifested by daily insulin requirements of 200 units or greater or more than 2 units/kg. Delivering an appropriate insulin volume to these patients can be difficult and inconvenient and may be best accomplished with U-500 regular insulin by multiple daily injections or with continuous subcutaneous insulin infusion, rather than with standard U-100 insulin. Implementation of U-500 regular insulin in patients previously on other insulin formulations is described with a treatment algorithm covering dosage requirements ranging from 150 to more than 600 units per day on the basis of the authors' experience.


CONCLUSIONS
Regimen conversion of appropriately selected patients from high-dose, U-100 insulin to U-500 regular insulin therapy on the basis of the recommendations presented in this article may potentially result in improved glycemic control and lower cost.
Lane
Wendy S
WS
Mountain Diabetes and Endocrine Center, Asheville, North Carolina 2880, USA. mountaindiabetes@msn.com
Cochran
Elaine K
EK
Jackson
Jeffrey A
JA
Scism-Bacon
Jamie L
JL
Corey
Ilene B
IB
Hirsch
Irl B
IB
Skyler
Jay S
JS
D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage*; D007332:Insulin Infusion Systems; D016896:Treatment Outcome
D007004:Hypoglycemic Agents; D007328:Insulin