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Shape of the OGTT glucose response curve: relationship with β-cell function and differences by sex, race, and BMI in adults with early type 2 diabetes treated with metformin

  • Utzschneider, Kristina M1, 2
  • Younes, Naji3
  • Rasouli, Neda4, 5
  • Barzilay, Joshua I6
  • Banerji, Mary Ann7
  • Cohen, Robert M8, 9
  • Gonzalez, Erica V10
  • Ismail-Beigi, Faramarz11, 12
  • Mather, Kieren J13
  • Raskin, Philip14
  • Wexler, Deborah J15
  • Lachin, John M3
  • Kahn, Steven E1, 2
  • Crandall, JP
  • 1 VA Puget Sound Health Care System Seattle Division, Seattle, Washington, USA , Seattle
  • 2 University of Washington, Seattle, Washington, USA , Seattle
  • 3 The George Washington University, Rockville, Maryland, USA , Rockville
  • 4 University of Colorado Denver School of Medicine, Aurora, Colorado, USA , Aurora
  • 5 VA Eastern Colorado Health Care System, Denver, Colorado, USA , Denver
  • 6 Kaiser Permanente of Georgia, Duluth, Georgia, USA , Duluth
  • 7 SUNY Downstate Medical Center, New York City, New York, USA , New York City
  • 8 University of Cincinnati, Cincinnati, Ohio, USA , Cincinnati
  • 9 Cincinnati VA Medical Center, Cincinnati, Ohio, USA , Cincinnati
  • 10 Baylor College of Medicine, Houston, Texas, USA , Houston
  • 11 Case Western Reserve University School of Medicine, Cleveland, Ohio, USA , Cleveland
  • 12 Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio, USA , Cleveland
  • 13 Indiana University School of Medicine, Indianapolis, Indiana, USA , Indianapolis
  • 14 The University of Texas Southwestern Medical Center, Dallas, Texas, USA , Dallas
  • 15 Massachusetts General Hospital, Boston, Massachusetts, USA , Boston
Published Article
BMJ Open Diabetes Research & Care
Publication Date
Sep 16, 2021
DOI: 10.1136/bmjdrc-2021-002264
PMID: 34531242
PMCID: PMC8449940
PubMed Central
  • 1506
  • 1873


Introduction The shape of the glucose curve during an oral glucose tolerance test (OGTT) reflects β-cell function in populations without diabetes but has not been as well studied in those with diabetes. A monophasic shape has been associated with higher risk of diabetes, while a biphasic pattern has been associated with lower risk. We sought to determine if phenotypic or metabolic characteristics were associated with glucose response curve shape in adults with type 2 diabetes treated with metformin alone. Research design and methods This is a cross-sectional analysis of 3108 metformin-treated adults with type 2 diabetes diagnosed <10 years who underwent 2-hour 75 g OGTT at baseline as part of the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE). Insulin sensitivity (homeostasis model of insulin sensitivity, HOMA2-S) and β-cell function (early, late, and total incremental insulin and C peptide responses adjusted for HOMA2-S) were calculated. Glucose curve shape was classified as monophasic, biphasic, or continuous rise. Results The monophasic profile was the most common (67.8% monophasic, 5.5% biphasic, 26.7% continuous rise). The monophasic subgroup was younger, more likely male and white, and had higher body mass index (BMI), while the continuous rise subgroup was more likely female and African American/black. HOMA2-S and fasting glucose did not differ among the subgroups. The biphasic subgroup had the highest early, late, and total insulin and C peptide responses (all p<0.05 vs monophasic and continuous rise). Compared with the monophasic subgroup, the continuous rise subgroup had similar early insulin (p=0.3) and C peptide (p=0.6) responses but lower late insulin (p<0.001) and total insulin (p=0.008) and C peptide (p<0.001) responses. Conclusions Based on the large multiethnic GRADE cohort, sex, race, age, and BMI were found to be important determinants of the shape of the glucose response curve. A pattern of a continuously rising glucose at 2 hours reflected reduced β-cell function and may portend increased glycemic failure rates. Trial registration number NCT01794143 .

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