RT Journal Article SR Electronic T1 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 JF BMJ Open Diabetes Research & Care JO BMJ Open Diab Res Care FD American Diabetes Association SP e002264 DO 10.1136/bmjdrc-2021-002264 VO 9 IS 1 A1 Kristina M Utzschneider A1 Naji Younes A1 Neda Rasouli A1 Joshua I Barzilay A1 Mary Ann Banerji A1 Robert M Cohen A1 Erica V Gonzalez A1 Faramarz Ismail-Beigi A1 Kieren J Mather A1 Philip Raskin A1 Deborah J Wexler A1 John M Lachin A1 Steven E Kahn A1 , YR 2021 UL http://drc.bmj.com/content/9/1/e002264.abstract AB 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.The Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) is being conducted with funding from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). This manuscript is based on the baseline (pretreatment) data from the 5047 participants enrolled into the study. These baseline data will be archived with the NIDDK data repository and will be available for sharing with other investigators upon publication. In accordance with the NIH Public Access Policy, we continue to provide all manuscripts to PubMed Central including this manuscript. GRADE has provided the protocols to the public through its public website (https://grade.bsc.gwu.edu/ancillary-study-info). GRADE abides by the NIDDK data sharing policy and implementation guidance as required by the NIH/NIDDK (https://repository.niddk.nih.gov/studies/grade).