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

Abstract

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.

Keywords: OGTT; diabetes mellitus; glucose; insulin; type 2.

Conflict of interest statement

Competing interests: KMU reports support from Medtronic and 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 the National Institutes of Health during the conduct of the study, and other support from Bristol Myers Squibb and Pfizer, outside the submitted work. DJW reports grants from NIDDK which funded the 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, personal fees from Eli Lilly and Company, and personal fees from Intarcia, Janssen, Merck, Neurimmune, Novo Nordisk, and Pfizer, outside the submitted work. KJM reports grants from the 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, JIB, MAB, EVG, FI-B, JML, and PR have nothing to disclose. KMU and SEK are supported by funding from the US Department of Veterans Affairs.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Classification analysis of OGTT glucose response curve shapes by sex and race (A) and sex, race, BMI, waist to hip ratio, and duration of diabetes (B). In B, only sex and BMI remained as significant independent classifiers. The percentages within each column are shown on the plot. AA, African American; AI, American Indian; BMI, body mass index; OGTT, oral glucose tolerance test.

Figure 2

OGTT glucose response curve shape for the whole cohort classified as monophasic, biphasic, or continuous rise. Mean glucose (A), insulin (B), and C peptide (C) are depicted at each OGTT time-point separately for participants within each of the subgroups. Pointwise 95% CIs are drawn around the means at each time-point. OGTT, oral glucose tolerance test.

Figure 3

OGTT glucose response curve shapes stratified by sex: monophasic, biphasic, or continuous rise. Mean glucose (A women, D men), insulin (B women, E men), and C peptide (C women, F men) are depicted at each OGTT time-point separately for participants within each of the subgroups. Pointwise 95% CIs are drawn around the means at each time-point. OGTT, oral glucose tolerance test.