Kristina M Utzschneider1, Naji Younes2, Neda Rasouli3, Joshua Barzilay4, Mary Ann Banerji5, Robert M Cohen6, Erica V Gonzalez7, Kieren J Mather8, Faramarz Ismail-Beigi9, Philip Raskin10, Deborah J Wexler11, John M Lachin2, Steven E Kahn12. 1. VA Puget Sound Health Care System and University of Washington, Seattle, WA, United States of America. Electronic address: grademail@bsc.gwu.edu. 2. The Biostatistics Center, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Rockville, MD, United States of America. 3. University of Colorado, Denver, Denver, CO, United States of America. 4. Kaiser Permanente of Georgia, Duluth, GA, United States of America. 5. State University of New York (SUNY), Downstate Medical Center, Brooklyn, NY, United States of America. 6. University of Cincinnati and Cincinnati VA Medical Center, Cincinnati, OH, United States of America. 7. Baylor College of Medicine, Houston, TX, United States of America. 8. Indiana University, Indianapolis, IN, United States of America. 9. Case Western Reserve University School of Medicine, Cleveland, OH, United States of America. 10. University of Texas - Southwestern Medical Center, Dallas, TX, United States of America. 11. Diabetes Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States of America. 12. VA Puget Sound Health Care System and University of Washington, Seattle, WA, United States of America.
Abstract
AIMS: Evaluate the relationship between measures of glycemia with β-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 β-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 β-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 β-cell dysfunction in adults with early T2DM treated with metformin alone. Efforts to improve glycemia should focus on interventions aimed at improving β-cell function. This Trial is registered in Clinicaltrials.gov as NCT01794143. Published by Elsevier Inc.
AIMS: Evaluate the relationship between measures of glycemia with β-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 β-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 β-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 β-cell dysfunction in adults with early T2DM treated with metformin alone. Efforts to improve glycemia should focus on interventions aimed at improving β-cell function. This Trial is registered in Clinicaltrials.gov as NCT01794143. Published by Elsevier Inc.
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