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AMY1 gene copy number correlates with glucose absorption and visceral fat volume, but not with insulin resistance
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Barber, Thomas M., Bhatti, Ahsan A., Elder, Patrick J. D., Ball, Sarah P., Calvez, Ronan, Ramsden, David B., Cuthbertson, Dan J., Pfeiffer, Andreas F., Burnett , David and Weickert , Martin (2020) AMY1 gene copy number correlates with glucose absorption and visceral fat volume, but not with insulin resistance. Journal of Clinical Endocrinology and Metabolism, 105 (10). e3586-e3596. doi:10.1210/clinem/dgaa473 ISSN 0021-972X.
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Official URL: https://doi.org/10.1210/clinem/dgaa473
Abstract
Background
The human amylase gene (AMY1) has broad copy number (CN) variation that may associate with BMI.
Methods
DNA was extracted from urine (n=74) and serum (n=6) samples (‘ProFiMet’ cohort), and buccal (n=17) samples (Oral Starch Challenge [OSC] cohort), and assessed for AMY1 CN by droplet digital PCR. Association of AMY1 CN with comprehensive markers of metabolic status (ProFiMet cohort) were analysed with Pearson Correlation Coefficients (CC). For the healthy, euglycemic OSC cohort, glycemic response to OSC was analysed with independent-sample t-tests (subgroups: high AMY1 CN 9-12, n=10; low AMY1 CN 4-6, n=7).
Results
There were significant inverse correlations of AMY1 CN with total visceral fat volume (CC -0.33; P=0.004), and positive correlations of AMY1 CN with oral glucose insulin sensitivity score (OGIS [derived from OGTT], CC 0.26; P=0.02), serum HDL-cholesterol (CC 0.325; P=0.003), and serum adiponectin (CC 0.249; P=0.026). Linear regression multivariate analysis (adiponectin as dependent variable), showed independent association of adiponectin with AMY1 CN (Beta=0.29; P=0.03). There were no significant associations between AMY1 CN and clamp-derived M-value, homeostasis model assessment of insulin resistance (IR), hepatic endogenous glucose production, fecal floral signature or macronutrient dietary preference. Delta (mean) change in blood glucose concentration (fasting to 30-min post-OSC), was significantly greater in the high vs low AMY1 CN subgroups (mean 1.7mmol/l [SEM 0.6] vs 0.9mmol/l [SEM 0.9] respectively; p=0.016).
Conclusions
High AMY1 CN associates with favourable metabolic profile (lower visceral fat volume; higher serum adiponectin; enhanced glucose absorption following oral glucose and OSC), but not with whole-body or hepatic IR.
Item Type: | Journal Article | ||||||||
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Subjects: | Q Science > QP Physiology R Medicine > RC Internal medicine |
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Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Library of Congress Subject Headings (LCSH): | Amylases, Obesity , Metabolism -- Disorders, Insulin resistance , Glucose -- Metabolism, Glucose -- Absorption and adsorption | ||||||||
Journal or Publication Title: | Journal of Clinical Endocrinology and Metabolism | ||||||||
Publisher: | The Endocrine Society | ||||||||
ISSN: | 0021-972X | ||||||||
Official Date: | October 2020 | ||||||||
Dates: |
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Volume: | 105 | ||||||||
Number: | 10 | ||||||||
Page Range: | e3586-e3596 | ||||||||
DOI: | 10.1210/clinem/dgaa473 | ||||||||
Status: | Peer Reviewed | ||||||||
Publication Status: | Published | ||||||||
Reuse Statement (publisher, data, author rights): | This is a pre-copyedited, author-produced version of an article accepted for publication in Journal of Clinical Endocrinology and Metabolism following peer review. The version of record Thomas M Barber, Ahsan A Bhatti, Patrick JD Elder, Sarah P Ball, Ronan Calvez, David B Ramsden, Dan J Cuthbertson, Andreas F Pfeiffer, David Burnett, Martin O Weickert, AMY1 gene copy number correlates with glucose absorption and visceral fat volume, but not with insulin resistance, The Journal of Clinical Endocrinology & Metabolism, , dgaa473, is available online at: https://doi.org/10.1210/clinem/dgaa473 | ||||||||
Access rights to Published version: | Restricted or Subscription Access | ||||||||
Date of first compliant deposit: | 23 July 2020 | ||||||||
Date of first compliant Open Access: | 22 July 2021 | ||||||||
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