Determinants of longitudinal change in insulin clearance: the Prospective Metabolism and Islet Cell Evaluation cohort

Objective To evaluate multiple determinants of the longitudinal change in insulin clearance (IC) in subjects at high risk for type 2 diabetes (T2D).Research design and methods Adults (n=492) at risk for T2D in the Prospective Metabolism and Islet Cell Evaluation cohort, a longitudinal observational...

Full description

Saved in:
Bibliographic Details
Main Authors: Christine Lee, Stewart B Harris, Anthony J Hanley, Philip W Connelly, Bernard Zinman, Ravi Retnakaran, Zhila Semnani-Azad, Luke W Johnston
Format: Article
Language:English
Published: BMJ Publishing Group 2019-05-01
Series:BMJ Open Diabetes Research & Care
Online Access:https://drc.bmj.com/content/7/1/e000825.full
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850109974865248256
author Christine Lee
Stewart B Harris
Anthony J Hanley
Philip W Connelly
Bernard Zinman
Ravi Retnakaran
Zhila Semnani-Azad
Luke W Johnston
author_facet Christine Lee
Stewart B Harris
Anthony J Hanley
Philip W Connelly
Bernard Zinman
Ravi Retnakaran
Zhila Semnani-Azad
Luke W Johnston
author_sort Christine Lee
collection DOAJ
description Objective To evaluate multiple determinants of the longitudinal change in insulin clearance (IC) in subjects at high risk for type 2 diabetes (T2D).Research design and methods Adults (n=492) at risk for T2D in the Prospective Metabolism and Islet Cell Evaluation cohort, a longitudinal observational cohort, had four visits over 9 years. Values from oral glucose tolerance tests collected at each assessment were used to calculate the ratios of both fasting C peptide-to-insulin (ICFASTING) and areas under the curve of C peptide-to-insulin (ICAUC). Generalized estimating equations (GEE) evaluated multiple determinants of longitudinal changes in IC.Results IC declined by 20% over the 9-year follow-up period (p<0.05). Primary GEE results indicated that non-European ethnicity, as well as increases in baseline measures of waist circumference, white cell count, and alanine aminotransferase, was associated with declines in ICFASTING and ICAUC over time (all p<0.05). There were no significant associations of IC with sex, age, physical activity, smoking, or family history of T2D. Both baseline and longitudinal IC were associated with incident dysglycemia.Conclusions Our findings suggest that non-European ethnicity and components of the metabolic syndrome, including central obesity, non-alcoholic fatty liver disease, and subclinical inflammation, may be related to longitudinal declines in IC.
format Article
id doaj-art-fde63e6e8b4a4166b8716d92dbf5e41a
institution OA Journals
issn 2052-4897
language English
publishDate 2019-05-01
publisher BMJ Publishing Group
record_format Article
series BMJ Open Diabetes Research & Care
spelling doaj-art-fde63e6e8b4a4166b8716d92dbf5e41a2025-08-20T02:37:57ZengBMJ Publishing GroupBMJ Open Diabetes Research & Care2052-48972019-05-017110.1136/bmjdrc-2019-000825Determinants of longitudinal change in insulin clearance: the Prospective Metabolism and Islet Cell Evaluation cohortChristine Lee0Stewart B Harris1Anthony J Hanley2Philip W Connelly3Bernard Zinman4Ravi Retnakaran5Zhila Semnani-Azad6Luke W Johnston7Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada1 Department of Epidemiology and Biostatistics, Schulich School of Medicine and Dentistry, Western University, London, Ontario, CanadaDepartment of Nutritional Sciences, University of Toronto, Toronto, Ontario, CanadaKeenan Research Centre for Biomedical Science, St Michael’s Hospital, Toronto, Ontario, CanadaUniversity of Toronto, Toronto, Ontario, CanadaMount Sinai Hospital, Toronto, Ontario, CanadaDepartment of Nutritional Sciences, University of Toronto, Toronto, Ontario, CanadaDepartment of Public Health, Aarhus Universitet, Aarhus, DenmarkObjective To evaluate multiple determinants of the longitudinal change in insulin clearance (IC) in subjects at high risk for type 2 diabetes (T2D).Research design and methods Adults (n=492) at risk for T2D in the Prospective Metabolism and Islet Cell Evaluation cohort, a longitudinal observational cohort, had four visits over 9 years. Values from oral glucose tolerance tests collected at each assessment were used to calculate the ratios of both fasting C peptide-to-insulin (ICFASTING) and areas under the curve of C peptide-to-insulin (ICAUC). Generalized estimating equations (GEE) evaluated multiple determinants of longitudinal changes in IC.Results IC declined by 20% over the 9-year follow-up period (p<0.05). Primary GEE results indicated that non-European ethnicity, as well as increases in baseline measures of waist circumference, white cell count, and alanine aminotransferase, was associated with declines in ICFASTING and ICAUC over time (all p<0.05). There were no significant associations of IC with sex, age, physical activity, smoking, or family history of T2D. Both baseline and longitudinal IC were associated with incident dysglycemia.Conclusions Our findings suggest that non-European ethnicity and components of the metabolic syndrome, including central obesity, non-alcoholic fatty liver disease, and subclinical inflammation, may be related to longitudinal declines in IC.https://drc.bmj.com/content/7/1/e000825.full
spellingShingle Christine Lee
Stewart B Harris
Anthony J Hanley
Philip W Connelly
Bernard Zinman
Ravi Retnakaran
Zhila Semnani-Azad
Luke W Johnston
Determinants of longitudinal change in insulin clearance: the Prospective Metabolism and Islet Cell Evaluation cohort
BMJ Open Diabetes Research & Care
title Determinants of longitudinal change in insulin clearance: the Prospective Metabolism and Islet Cell Evaluation cohort
title_full Determinants of longitudinal change in insulin clearance: the Prospective Metabolism and Islet Cell Evaluation cohort
title_fullStr Determinants of longitudinal change in insulin clearance: the Prospective Metabolism and Islet Cell Evaluation cohort
title_full_unstemmed Determinants of longitudinal change in insulin clearance: the Prospective Metabolism and Islet Cell Evaluation cohort
title_short Determinants of longitudinal change in insulin clearance: the Prospective Metabolism and Islet Cell Evaluation cohort
title_sort determinants of longitudinal change in insulin clearance the prospective metabolism and islet cell evaluation cohort
url https://drc.bmj.com/content/7/1/e000825.full
work_keys_str_mv AT christinelee determinantsoflongitudinalchangeininsulinclearancetheprospectivemetabolismandisletcellevaluationcohort
AT stewartbharris determinantsoflongitudinalchangeininsulinclearancetheprospectivemetabolismandisletcellevaluationcohort
AT anthonyjhanley determinantsoflongitudinalchangeininsulinclearancetheprospectivemetabolismandisletcellevaluationcohort
AT philipwconnelly determinantsoflongitudinalchangeininsulinclearancetheprospectivemetabolismandisletcellevaluationcohort
AT bernardzinman determinantsoflongitudinalchangeininsulinclearancetheprospectivemetabolismandisletcellevaluationcohort
AT raviretnakaran determinantsoflongitudinalchangeininsulinclearancetheprospectivemetabolismandisletcellevaluationcohort
AT zhilasemnaniazad determinantsoflongitudinalchangeininsulinclearancetheprospectivemetabolismandisletcellevaluationcohort
AT lukewjohnston determinantsoflongitudinalchangeininsulinclearancetheprospectivemetabolismandisletcellevaluationcohort