Abstract
Objectives
In obese adults the shape of the glucose response curve during an oral glucose tolerance test (OGTT) predicts future type 2 diabetes. Patients with an incessant increase or monophasic curves have increased risk compared to those with biphasic curves. Since type 2 diabetes is associated with increased cardiometabolic risk, we studied whether differences in OGTT response curve are associated with differences in cardiometabolic risk factors in healthy adolescents across a wide body mass index (BMI) range.
Methods
Sixty-nine (33F/36M), white adolescents (age: 15.2 ± 1.7 years; BMI: 21.5 ± 4.7 kg/m2; mean ± SD) were studied. Risk factors measured included percent body fat, blood pressure, lipids, augmentation index, reactive hyperemia, endothelin 1, plasminogen activator 1, inflammatory markers (interleukin 6, c-reactive protein), insulin secretion, insulin sensitivity (Matusda index), and disposition index (DI).
Results
Thirty-two subjects had biphasic responses; 35 subjects had monophasic responses and two females had incessant increases. Sex did not affect the frequency of responses. Glucose area under the curve during OGTT was greater in those with a mono vs. biphasic curves (p=0.01). Disposition index was markedly lower in subjects with a monophasic curve than in those with a biphasic curve (3.6 [2.3–5.0] vs. 5.8 [3.8–7.6], median [25th, 75th%] p=0.003). Triglyceride to high-density lipoprotein cholesterol (HDL) ratio was higher in subjects with a monophasic curve (p=0.046).
Conclusions
The decreased disposition index indicates that in healthy adolescents a monophasic response to OGTT is due to decreased insulin secretion relative to the degree of insulin resistance present. This was not associated with differences in most other cardiometabolic risk markers.
Trial registration
Funding source: American Heart Association
Funding source: National Center for Advancing Translational Sciences
Award Identifier / Grant number: UL1TR001070
Acknowledgments
The authors thank the nursing staff at the Clinical Research Center at the Wexner Medical Center of The Ohio State University and the staff in the Section of Endocrinology at Nationwide Children’s Hospital for their support in this project.
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Research funding: The project was supported by a grant from the Great Rivers Affiliate of the American Heart Association and award number grant UL1TR001070 from the National Center for Advancing Translational Sciences. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Advancing Translational Sciences or the National Institutes of Health.
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Author contributions: RPH designed and oversaw performance of the study, performed statistical analysis, wrote, and approved the final manuscript. MMC helped perform the studies and reviewed the manuscript, DZ performed laboratory measurements and reviewed the manuscript, CYY helped design the study, oversaw laboratory measurements and reviewed the manuscript. All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
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Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication. The authors have no conflict of interest.
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Informed consent: Written informed assent from the subject and informed consent from a parent or guardian were obtained.
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Ethical approval: The protocol was approved by the Nationwide Children’s Hospital Institutional Review Board and registered on Clinical Trials.gov, NCT02821104.
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