One of the most important metabolic actions of insulin is to promote increased glucose uptake and utilization by the body. Impairment of this action of insulin (insulin resistance) has been associated with many common diseases such as diabetes, obesity, hypertension, and dyslipidemias. Currently, the """"""""gold standard"""""""" method for measuring insulin sensitivity in vivo is the hyperinsulinemic euglycemic glucose clamp. This is a very labor intensive test that requires continuous infusions of insulin and glucose and multiple blood samples. An alternative method involves mathematical modeling of an intravenous glucose tolerance test (requires 30 blood samples over 3 hours). The purpose of this project is to develop a reliable method for measuring insulin sensitivity in vivo that is as accurate as currently available methods but simpler to implement. We discovered that the majority of the information needed to accurately estimate insulin sensitivity is contained in the fasting insulin and glucose levels and defined a Quantitative Insulin-sensitivity Check Index (QUICKI) defined as QUICKI = 1/(log (fasting glucose) + log (fasting insulin)). We performed hyperinsulinemic euglycemic glucose clamps as well as intravenous glucose tolerance tests on normal volunteers and groups of patients with diabetes, hypertension, or obesity and found that QUICKI was much more highly correlated with the glucose clamp than minimal model estimates of insulin sensitivity. Thus, we have devised a simpler method for determining insulin sensitivity in vivo that is suitable for studying large populations.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Intramural Research (Z01)
Project #
1Z01HL003609-05
Application #
6541703
Study Section
Cell Biology Integrated Review Group (CB)
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2001
Total Cost
Indirect Cost
Name
U.S. National Heart Lung and Blood Inst
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Wanant, S; Quon, M J (2000) Insulin receptor binding kinetics: modeling and simulation studies. J Theor Biol 205:355-64
Katz, A; Nambi, S S; Mather, K et al. (2000) Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab 85:2402-10
Cardillo, C; Nambi, S S; Kilcoyne, C M et al. (1999) Insulin stimulates both endothelin and nitric oxide activity in the human forearm. Circulation 100:820-5
Stickle, D F; Reynolds, M A; Morris, M D et al. (1999) Dynamic changes in plasma proinsulin/insulin ratio during insulin secretion influence correlation between radioimmunoassay (RIA) and IMX measurements of insulin. Clin Chim Acta 284:1-13