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. We also completed and published the results of a clinical protocol investigating the effects of oral vitamin C on insulin sensitivity and endothelial function in type 2 diabetes. Finally, we have an active animal protocol to validate QUICKI in rodents.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Intramural Research (Z01)
Project #
1Z01AT000003-05
Application #
7296794
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2006
Total Cost
Indirect Cost
Name
Complementary & Alternative Medicine
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Chen, Hui; Karne, Rajaram J; Hall, Gail et al. (2006) High-dose oral vitamin C partially replenishes vitamin C levels in patients with Type 2 diabetes and low vitamin C levels but does not improve endothelial dysfunction or insulin resistance. Am J Physiol Heart Circ Physiol 290:H137-45
Karne, Rajaram J; Chen, Hui; Sullivan, Gail et al. (2005) Letter re: Limited accuracy of surrogates of insulin resistance during puberty in obese and lean children at risk for altered glucoregulation. J Clin Endocrinol Metab 90:4418-9; author reply 4419
Chen, Hui; Sullivan, Gail; Quon, Michael J (2005) Assessing the predictive accuracy of QUICKI as a surrogate index for insulin sensitivity using a calibration model. Diabetes 54:1914-25
Karne, Rajaram J; Chen, Hui; Quon, Michael J (2004) Diagnosing insulin resistance by simple quantitative methods in subjects with normal glucose metabolism. Diabetes Care 27:1247-8; author reply 1249
Campia, Umberto; Sullivan, Gail; Bryant, Melissa B et al. (2004) Insulin impairs endothelium-dependent vasodilation independent of insulin sensitivity or lipid profile. Am J Physiol Heart Circ Physiol 286:H76-82
Bakalov, Vladimir K; Cooley, Margaret M; Quon, Michael J et al. (2004) Impaired insulin secretion in the Turner metabolic syndrome. J Clin Endocrinol Metab 89:3516-20
Chen, Hui; Sullivan, Gail; Yue, Lilly Q et al. (2003) QUICKI is a useful index of insulin sensitivity in subjects with hypertension. Am J Physiol Endocrinol Metab 284:E804-12
Quon, Michael J (2002) QUICKI is a useful and accurate index of insulin sensitivity. J Clin Endocrinol Metab 87:949-51
Mather, K J; Hunt, A E; Steinberg, H O et al. (2001) Repeatability characteristics of simple indices of insulin resistance: implications for research applications. J Clin Endocrinol Metab 86:5457-64
Quon, M J (2001) Limitations of the fasting glucose to insulin ratio as an index of insulin sensitivity. J Clin Endocrinol Metab 86:4615-7