Year: 2004
Abstract Number: 664-P
Authors: ELIZABETH J. MURPHY, SCOTT M. TURNER, KRISTEN LAPRADE, RICHARD A. NEESE, DRINA I. BOBAN, MARC K. HELLERSTEIN
Institutions: Emeryville, CA; Berkeley, CA; San Francisco, CA
Results: Resistance of tissues to the actions of insulin (insulin resistance, or IR) is an increasingly prevalent condition and a major risk factor for type 2 diabetes, cardiovascular disease, cancer and other diseases. The absence of a reliable, clinically practical diagnostic test for IR has hampered early detection, evaluation of interventions and attempts to classify IR as a disease. We have developed a simple in vivo assay of whole body glycolytic disposal of glucose, based on the release of deuterium from oral ²H-glucose to body water (²H-OGTT). This method is now technically feasible because of advances in ultra-sensitive analytic techniques for measuring ²H20 enrichments, including isotope ratio-massspectrometry (MS) and cycloidal MS. Body ²H2O enrichments are measured from saliva or plasma. Inclusion of 15g of [6,6-²H2] glucose (82.4 mmol) in a 75g standard OGTT to lean control human subjects resulted in linear increases in ²H2O production from ca. 25 mmol (2hr) to 40-50 mmol (4hr, e.g. representing ca. 160 d in a 70 kg lean subject). This corresponds to 60% recovery of administered ²H2-glucose as body ²H2O. Subjects with obesity/ hyperinsulinemia or frank impaired glucose tolerance showed lower ²H20 production (30-40 mmol ²H2O at 4 hr). Lean subjects receiving HIV-protease inhibitor treatment (known to induce peripheral insulin resistance) also showed markedly reduced ²H20 production (20-30 mmol ²H2O at 4 hr). Plasma glucose enrichment can also be measured as an index of endogenous glucose production, i.e. hepatic insulin resistance. Reproducibility in individuals over time, use of lower amounts of ²H-glucose, correlation with glucose clamps, and the effects of insulin-sensitizing agents are under investigation. In summary, an out-patient test that does not require an IV line or blood draws, is based on well-understood physiologic actions of insulin, and is simple and inexpensive, may be available for diagnosis and monitoring of IR. Further work is required for validation.
Category: Clinical Therapeutics/New Technology - Treatment of Insulin Resistance
| Related Content: | |  |