PMID- 27407117 OWN - NLM STAT- MEDLINE DCOM- 20171024 LR - 20220410 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 39 IP - 9 DP - 2016 Sep TI - Standardized Mixed-Meal Tolerance and Arginine Stimulation Tests Provide Reproducible and Complementary Measures of beta-Cell Function: Results From the Foundation for the National Institutes of Health Biomarkers Consortium Investigative Series. PG - 1602-13 LID - 10.2337/dc15-0931 [doi] AB - OBJECTIVE: Standardized, reproducible, and feasible quantification of beta-cell function (BCF) is necessary for the evaluation of interventions to improve insulin secretion and important for comparison across studies. We therefore characterized the responses to, and reproducibility of, standardized methods of in vivo BCF across different glucose tolerance states. RESEARCH DESIGN AND METHODS: Participants classified as having normal glucose tolerance (NGT; n = 23), prediabetes (PDM; n = 17), and type 2 diabetes mellitus (T2DM; n = 22) underwent two standardized mixed-meal tolerance tests (MMTT) and two standardized arginine stimulation tests (AST) in a test-retest paradigm and one frequently sampled intravenous glucose tolerance test (FSIGT). RESULTS: From the MMTT, insulin secretion in T2DM was >86% lower compared with NGT or PDM (P < 0.001). Insulin sensitivity (Si) decreased from NGT to PDM ( approximately 50%) to T2DM (93% lower [P < 0.001]). In the AST, insulin secretory response to arginine at basal glucose and during hyperglycemia was lower in T2DM compared with NGT and PDM (>58%; all P < 0.001). FSIGT showed decreases in both insulin secretion and Si across populations (P < 0.001), although Si did not differ significantly between PDM and T2DM populations. Reproducibility was generally good for the MMTT, with intraclass correlation coefficients (ICCs) ranging from approximately 0.3 to approximately 0.8 depending on population and variable. Reproducibility for the AST was very good, with ICC values >0.8 across all variables and populations. CONCLUSIONS: Standardized MMTT and AST provide reproducible and complementary measures of BCF with characteristics favorable for longitudinal interventional trials use. CI - (c) 2016 by the American Diabetes Association. FAU - Shankar, Sudha S AU - Shankar SS AD - Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN. FAU - Vella, Adrian AU - Vella A AD - Division of Endocrinology, Diabetes & Metabolism, Mayo Clinic College of Medicine, Rochester, MN. FAU - Raymond, Ralph H AU - Raymond RH AD - R-Squared Solutions, Skillman, NJ. FAU - Staten, Myrlene A AU - Staten MA AD - Kelly Government Solutions for National Institute of Diabetes and Digestive and Kidney Diseases, Rockville, MD. FAU - Calle, Roberto A AU - Calle RA AD - Pfizer, Cambridge, MA, and Groton, CT. FAU - Bergman, Richard N AU - Bergman RN AD - Cedars-Sinai Diabetes and Obesity Research Institute, Los Angeles, CA. FAU - Cao, Charlie AU - Cao C AD - Takeda Development Center Americas, Deerfield, IL. FAU - Chen, Danny AU - Chen D AD - Pfizer, Cambridge, MA, and Groton, CT. FAU - Cobelli, Claudio AU - Cobelli C AD - Department of Information Engineering, University of Padova, Padova, Italy. FAU - Dalla Man, Chiara AU - Dalla Man C AD - Department of Information Engineering, University of Padova, Padova, Italy. FAU - Deeg, Mark AU - Deeg M AD - Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN. FAU - Dong, Jennifer Q AU - Dong JQ AD - Pfizer, Cambridge, MA, and Groton, CT. FAU - Lee, Douglas S AU - Lee DS AD - Pfizer, Cambridge, MA, and Groton, CT. FAU - Polidori, David AU - Polidori D AD - Janssen Research & Development, San Diego, CA. FAU - Robertson, R Paul AU - Robertson RP AD - Pacific Northwest Diabetes Research Institute, Seattle, WA Division of Endocrinology, Departments of Medicine and Pharmacology, University of Washington, Seattle, WA. FAU - Ruetten, Hartmut AU - Ruetten H AD - Sanofi, Paris, France. FAU - Stefanovski, Darko AU - Stefanovski D AD - University of Pennsylvania, Philadelphia, PA. FAU - Vassileva, Maria T AU - Vassileva MT AD - Foundation for the National Institutes of Health, Bethesda, MD. FAU - Weir, Gordon C AU - Weir GC AD - Joslin Diabetes Center, Boston, MA. FAU - Fryburg, David A AU - Fryburg DA AD - ROI Biopharma Consulting, East Lyme, CT dfryburg@roibiopharma.com. CN - Foundation for the National Institutes of Health beta-Cell Project Team LA - eng SI - ClinicalTrials.gov/NCT01454973 SI - ClinicalTrials.gov/NCT01663207 SI - ClinicalTrials.gov/NCT01663207 GR - P30 DK036836/DK/NIDDK NIH HHS/United States GR - R01 DK078646/DK/NIDDK NIH HHS/United States PT - Journal Article DEP - 20160712 PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 0 (Blood Glucose) RN - 0 (Insulin) RN - 94ZLA3W45F (Arginine) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Adult MH - *Arginine MH - Blood Glucose/*metabolism MH - Case-Control Studies MH - Diabetes Mellitus, Type 2/diagnosis/*metabolism MH - Female MH - Glucose MH - Glucose Tolerance Test MH - Humans MH - Insulin/*metabolism MH - *Insulin Resistance MH - Insulin Secretion MH - Insulin-Secreting Cells/*metabolism MH - Male MH - *Meals MH - Middle Aged MH - National Institutes of Health (U.S.) MH - Prediabetic State/diagnosis/*metabolism MH - Reference Standards MH - Reproducibility of Results MH - United States PMC - PMC5001146 EDAT- 2016/07/14 06:00 MHDA- 2017/10/25 06:00 PMCR- 2017/09/01 CRDT- 2016/07/14 06:00 PHST- 2016/05/05 00:00 [received] PHST- 2016/06/15 00:00 [accepted] PHST- 2016/07/14 06:00 [entrez] PHST- 2016/07/14 06:00 [pubmed] PHST- 2017/10/25 06:00 [medline] PHST- 2017/09/01 00:00 [pmc-release] AID - dc15-0931 [pii] AID - 0931 [pii] AID - 10.2337/dc15-0931 [doi] PST - ppublish SO - Diabetes Care. 2016 Sep;39(9):1602-13. doi: 10.2337/dc15-0931. Epub 2016 Jul 12.