PMID- 33752962 OWN - NLM STAT- MEDLINE DCOM- 20220113 LR - 20230610 IS - 1873-460X (Electronic) IS - 1056-8727 (Print) IS - 1056-8727 (Linking) VI - 35 IP - 5 DP - 2021 May TI - Association of glycemia with insulin sensitivity and beta-cell function in adults with early type 2 diabetes on metformin alone. PG - 107912 LID - S1056-8727(21)00086-6 [pii] LID - 10.1016/j.jdiacomp.2021.107912 [doi] AB - AIMS: Evaluate the relationship between measures of glycemia with beta-cell function and insulin sensitivity in adults with early type 2 diabetes mellitus (T2DM). METHODS: This cross-sectional analysis evaluated baseline data from 3108 adults with T2DM <10 years treated with metformin alone enrolled in the Glycemia Reduction Approaches in Diabetes. A Comparative Effectiveness (GRADE) Study. Insulin and C-peptide responses and insulin sensitivity were calculated from 2-h oral glucose tolerance tests. Regression models evaluated the relationships between glycemic measures (HbA1c, fasting and 2-h glucose), measures of beta-cell function and insulin sensitivity. RESULTS: Insulin and C-peptide responses were inversely associated with insulin sensitivity. Glycemic measures were inversely associated with insulin and C-peptide responses adjusted for insulin sensitivity. HbA1c demonstrated modest associations with beta-cell function (range: r - 0.22 to -0.35). Fasting and 2-h glucose were associated with early insulin and C-peptide responses (range: r - 0.37 to -0.40) as well as late insulin and total insulin and C-peptide responses (range: r - 0.50 to -0.60). CONCLUSION: Glycemia is strongly associated with beta-cell dysfunction in adults with early T2DM treated with metformin alone. Efforts to improve glycemia should focus on interventions aimed at improving beta-cell function. This Trial is registered in Clinicaltrials.gov as NCT01794143. CI - Published by Elsevier Inc. FAU - Utzschneider, Kristina M AU - Utzschneider KM AD - VA Puget Sound Health Care System and University of Washington, Seattle, WA, United States of America. Electronic address: grademail@bsc.gwu.edu. FAU - Younes, Naji AU - Younes N AD - The Biostatistics Center, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Rockville, MD, United States of America. FAU - Rasouli, Neda AU - Rasouli N AD - University of Colorado, Denver, Denver, CO, United States of America. FAU - Barzilay, Joshua AU - Barzilay J AD - Kaiser Permanente of Georgia, Duluth, GA, United States of America. FAU - Banerji, Mary Ann AU - Banerji MA AD - State University of New York (SUNY), Downstate Medical Center, Brooklyn, NY, United States of America. FAU - Cohen, Robert M AU - Cohen RM AD - University of Cincinnati and Cincinnati VA Medical Center, Cincinnati, OH, United States of America. FAU - Gonzalez, Erica V AU - Gonzalez EV AD - Baylor College of Medicine, Houston, TX, United States of America. FAU - Mather, Kieren J AU - Mather KJ AD - Indiana University, Indianapolis, IN, United States of America. FAU - Ismail-Beigi, Faramarz AU - Ismail-Beigi F AD - Case Western Reserve University School of Medicine, Cleveland, OH, United States of America. FAU - Raskin, Philip AU - Raskin P AD - University of Texas - Southwestern Medical Center, Dallas, TX, United States of America. FAU - Wexler, Deborah J AU - Wexler DJ AD - Diabetes Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States of America. FAU - Lachin, John M AU - Lachin JM AD - The Biostatistics Center, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Rockville, MD, United States of America. FAU - Kahn, Steven E AU - Kahn SE AD - VA Puget Sound Health Care System and University of Washington, Seattle, WA, United States of America. CN - GRADE Research Group LA - eng SI - ClinicalTrials.gov/NCT01794143 GR - UL1 TR000445/TR/NCATS NIH HHS/United States GR - UL1 TR002529/TR/NCATS NIH HHS/United States GR - UL1 TR000439/TR/NCATS NIH HHS/United States GR - P30 DK020541/DK/NIDDK NIH HHS/United States GR - UL1 TR002378/TR/NCATS NIH HHS/United States GR - P30 DK020572/DK/NIDDK NIH HHS/United States GR - UL1 TR002345/TR/NCATS NIH HHS/United States GR - P30 DK017047/DK/NIDDK NIH HHS/United States GR - UL1 TR002548/TR/NCATS NIH HHS/United States GR - U34 DK088043/DK/NIDDK NIH HHS/United States GR - UL1 TR002537/TR/NCATS NIH HHS/United States GR - P30 DK092926/DK/NIDDK NIH HHS/United States GR - UL1 TR002535/TR/NCATS NIH HHS/United States GR - P30 DK072476/DK/NIDDK NIH HHS/United States GR - P30 DK079626/DK/NIDDK NIH HHS/United States GR - UL1 TR001409/TR/NCATS NIH HHS/United States GR - U01 DK098246/DK/NIDDK NIH HHS/United States GR - UL1 TR001449/TR/NCATS NIH HHS/United States GR - UL1 TR002489/TR/NCATS NIH HHS/United States GR - U54 GM104940/GM/NIGMS NIH HHS/United States GR - UL1 TR001108/TR/NCATS NIH HHS/United States GR - UL1 TR002243/TR/NCATS NIH HHS/United States GR - I01 BX005831/BX/BLRD VA/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20210317 PL - United States TA - J Diabetes Complications JT - Journal of diabetes and its complications JID - 9204583 RN - 0 (Blood Glucose) RN - 0 (C-Peptide) RN - 0 (Glycated Hemoglobin A) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 9100L32L2N (Metformin) SB - IM MH - *Blood Glucose MH - C-Peptide MH - Cross-Sectional Studies MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Glycated Hemoglobin MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Insulin/blood MH - *Insulin Resistance MH - Insulin-Secreting Cells/*physiology MH - *Metformin/therapeutic use MH - Randomized Controlled Trials as Topic PMC - PMC8048071 MID - NIHMS1685667 OTO - NOTNLM OT - Beta-cell function OT - Glucose tolerance OT - Glycemic control OT - Insulin sensitivity OT - Type 2 diabetes COIS- Declaration of competing interest The writing group reports the following as relevant conflicts of interest: KMU reports support from Medtronics, personal fees from Novo Nordisk, outside the submitted work; NR reports grants and other support from Novo Nordisk, outside the submitted work; RMC reports grants from National Institutes of Health during the conduct of the study; other support from Bristol Myers Squibb and Pfizer, outside the submitted work; DJW reports grants from an NIDDK funded trial during the conduct of the study; and other support from Novo Nordisk, outside the submitted work. SEK reports grants from NIH during the conduct of the study; personal fees from Boehringer Ingelheim, Eli Lilly, Intarcia, Janssen, Merck, Novo Nordisk, and Pfizer, outside the submitted work. KJM reports grants from National Institutes of Health during the conduct of the study; and at the time of publication. KJM is an employee of Eli Lilly and Company. Data collection, analysis, and preparation of the manuscript occurred prior to this employment and were independent of Eli Lilly and Company. NY, JB, MAB, EVG, FIB, JML, and PR have nothing to disclose. KMU and SEK are supported by funding from the United States Department of Veterans Affairs. EDAT- 2021/03/24 06:00 MHDA- 2022/01/14 06:00 PMCR- 2022/05/01 CRDT- 2021/03/23 06:10 PHST- 2020/12/21 00:00 [received] PHST- 2021/02/17 00:00 [revised] PHST- 2021/03/06 00:00 [accepted] PHST- 2021/03/24 06:00 [pubmed] PHST- 2022/01/14 06:00 [medline] PHST- 2021/03/23 06:10 [entrez] PHST- 2022/05/01 00:00 [pmc-release] AID - S1056-8727(21)00086-6 [pii] AID - 10.1016/j.jdiacomp.2021.107912 [doi] PST - ppublish SO - J Diabetes Complications. 2021 May;35(5):107912. doi: 10.1016/j.jdiacomp.2021.107912. Epub 2021 Mar 17.