A Non-Invasive Surrogate Test of OGTT to Screen for Pre-diabetes

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DESCRIPTION (provided by applicant): The long-term objectives of this proposal are to develop an inexpensive, totally non-invasive surrogate test for the 2-h oral glucose tolerance test (2-h OGTT) for the purpose of identifying individuals with pre-diabetes for preventive purposes. We believe that such a test can be developed based on oral administration of a 75-g 13C-labeled glucose solution administered according to the current American Diabetes Association protocol followed by the measurement of the area under the curve (AUC) for breath CO2 isotopic enrichment. Because this test measures the combined effects of impairments in both glucose and lipid oxidation during an OGTT protocol, it: (i) is more sensitive than the current 2-h OGTT, and (ii) correlates strongly with the 2-h OGTT blood glucose. And because it relies solely on collecting breath samples, it is totally non-invasive and thus ideal for screening purposes involving large numbers of individuals. Our preliminary data demonstrate that this is a good surrogate test for the 2-h OGTT, but in order to proceed further we need to first establish its intra- and inter-individual variability as a function of worsening glucose tolerance. During Phase-I funding cycle (the current application), we will conduct a protocol in 20 men and women whose glycemia ranges from normoglycemic to diabetic according to standard 2-h OGTT blood glucose for the purpose of establishing intra- and inter-individual variability of the proposed test at different values of 2-h OGTT. During a subsequent Phase-II funding cycle, we plan to conduct appropriate protocols in order to: (i) establish the strength of the correlation between this surrogate test and the 2-h OGTT, and (ii) investigate whether this approach can be used to predict development of impaired glucose tolerance for preventive purposes. During Phase-III and with non-SBIR funds, we will: (i) establish a central facility to manufacture the relevant test kits, and (ii) develop collaborative relations with selected diabetes research centers in order to demonstrate its applications and make the test available to the community. PUBLIC HEALTH RELEVANCE: Type 2 diabetes mellitus (T2DM) is a serious chronic disease affecting millions of people globally. Prevention/delay of onset of diabetes is considered an important issue in diabetes management and requires the ability to select individuals early in the course of progression (pre-diabetes) before onset of clinical symptoms. Current diagnosis of pre-diabetes is based on either fasting plasma glucose or 2-hour plasma glucose after administration of an oral glucose tolerance test (OGTT). These two methods identify different subsets of pre-diabetics and are both necessary for selection of at-risk individuals. Use of oral glucose tolerance test has been discouraged by the American Diabetes Association because of its limitations related to cost, convenience, and repeatability. We propose to develop a totally non-invasive surrogate test for the 2-h OGTT based on breath sampling after administration of a standard dose of glucose labeled with the non- radioactive stable isotope 13C6-glucose.