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©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
Age at diagnosis of type 2 diabetes and cardiovascular risk factor profile: A pooled analysis
Mary M Barker, Francesco Zaccardi, Emer M Brady, Gaurav S Gulsin, Andrew P Hall, Joseph Henson, Zin Zin Htike, Kamlesh Khunti, Gerald P McCann, Emma L Redman, David R Webb, Emma G Wilmot, Tom Yates, Jian Yeo, Melanie J Davies, Jack A Sargeant
Mary M Barker, Francesco Zaccardi, Emer M Brady, Joseph Henson, Zin Zin Htike, Kamlesh Khunti, David R Webb, Emma G Wilmot, Tom Yates, Melanie J Davies, Jack A Sargeant, Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester LE5 4PW, United Kingdom
Gaurav S Gulsin, Gerald P McCann, Jian Yeo, Department of Cardiovascular Sciences, Glenfield Hospital, University of Leicester, Leicester LE3 9QP, United Kingdom
Andrew P Hall, The Hanning Sleep Laboratory, University Hospitals of Leicester NHS Trust, University of Leicester, Leicester LE5 4PW, United Kingdom
Joseph Henson, Gerald P McCann, Emma L Redman, David R Webb, Tom Yates, Melanie J Davies, Jack A Sargeant, National Institute for Health Research, Leicester Biomedical Research Centre, Leicester LE5 4PW, United Kingdom
Kamlesh Khunti, Emma L Redman, Melanie J Davies, Leicester Diabetes Centre, University Hospitals of Leicester NHS Trust, Leicester LE5 4PW, United Kingdom
Kamlesh Khunti, National Institute for Health Research, Applied Research Collaboration East Midlands, Leicester LE5 4PW, United Kingdom
Emma G Wilmot, Department of Diabetes, University Hospitals of Derby and Burton NHS Foundation Trust, Derby DE22 3NE, United Kingdom
Author contributions: Davies MJ and Sargeant JA generated the study idea; Barker MM, Zaccardi F, Henson J, Yates T and Sargeant JA prepared and conducted the analysis; Barker MM, Zaccardi F, Davies MJ and Sargeant JA interpreted the analysis and drafted the manuscript, with clinical and/or academic input from co-authors; all authors reviewed and approved the final manuscript.
Supported by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (NIHR201165), as well as by the NIHR Leicester Biomedical Research Centre and the NIHR Applied Research Collaboration East Midlands.
Institutional review board statement: All studies included in the pooled dataset used for this analysis gained full ethical approval (CODEC: 16/WM/0457; EXPEDITION: 08/H0407/8; LYDIA: 13/WM/0311; DIASTOLIC: 15/WM/0222; PREDICT: 17/WM/0192).
Informed consent statement: All participants included in the studies provided written informed consent.
Conflict-of-interest statement: Barker MM, Zaccardi F, Brady EM, Gulsin GS, Hall AP, Henson J, Htike ZZ, McCann GP, Redman EL, Webb DR and Yeo J report no conflicts of interest. Khunti K has acted as consultant, advisory board member and speaker for Abbott, Amgen, Astrazeneca, Bayer, NAPP, Lilly, Merck Sharp and Dohme, Novartis, Novo Nordisk, Roche, Berlin-Chemie AG/Menarini Group, Sanofi-Aventis, Servier, Boehringer Ingelheim, EACME grants from Boehringer Ingelheim, AstraZeneca, Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Merck Sharp & Dohme. Yates T and Sargeant JA are supported by the NIHR Leicester BRC and have received project funding in the form an investigator-initiated grant from AstraZeneca. EGW has received personal fees from Abbott Diabetes Care, Dexcom, Eli lilly, Insulet, Medtronic, Novo Nordisk, Sanofi Aventis. Davies MJ has acted as consultant, advisory board member and speaker for Novo Nordisk, Sanofi, Lilly and Boehringer Ingelheim, an advisory board member and speaker for AstraZeneca, an advisory board member for Janssen, Lexicon, Servier and Gilead Sciences Ltd and as a speaker for Napp Pharmaceuticals, Mitsubishi Tanabe Pharma Corporation and Takeda Pharmaceuticals International Inc. She has received grants in support of investigator and investigator initiated trials from Novo Nordisk, Sanofi-Aventis, Lilly, Boehringer Ingelheim, AstraZeneca and Janssen.
Data sharing statement: Data included in this pooled analysis will be made available, after publication, to anyone upon reasonable request to the corresponding author.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Jack A Sargeant, PhD, Research Associate, Diabetes Research Centre, University of Leicester, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, United Kingdom.
jack.sargeant@leicester.ac.uk
Received: May 28, 2021
Peer-review started: May 28, 2021
First decision: June 24, 2021
Revised: July 8, 2021
Accepted: February 10, 2022
Article in press: February 10, 2022
Published online: March 15, 2022
Processing time: 290 Days and 22.5 Hours
BACKGROUND
The diagnosis of type 2 diabetes (T2D) in younger adults, an increasingly common public health issue, is associated with a higher risk of cardiovascular complications and mortality, which may be due to a more adverse cardiovascular risk profile in individuals diagnosed at a younger age.
AIM
To investigate the association between age at diagnosis and the cardiovascular risk profile in adults with T2D.
METHODS
A pooled dataset was used, comprised of data from five previous studies of adults with T2D, including 1409 participants of whom 196 were diagnosed with T2D under the age of 40 years. Anthropometric and blood biomarker measurements included body weight, body mass index (BMI), waist circumference, body fat percentage, glycaemic control (HbA1c), lipid profile and blood pressure. Univariable and multivariable linear regression models, adjusted for diabetes duration, sex, ethnicity and smoking status, were used to investigate the association between age at diagnosis and each cardiovascular risk factor.
RESULTS
A higher proportion of participants diagnosed with T2D under the age of 40 were female, current smokers and treated with glucose-lowering medications, compared to participants diagnosed later in life. Participants diagnosed with T2D under the age of 40 also had higher body weight, BMI, waist circumference and body fat percentage, in addition to a more adverse lipid profile, compared to participants diagnosed at an older age. Modelling results showed that each one year reduction in age at diagnosis was significantly associated with 0.67 kg higher body weight [95% confidence interval (CI): 0.52-0.82 kg], 0.18 kg/m2 higher BMI (95%CI: 0.10-0.25) and 0.32 cm higher waist circumference (95%CI: 0.14-0.49), after adjustment for duration of diabetes and other confounders. Younger age at diagnosis was also significantly associated with higher HbA1c, total cholesterol, low-density lipoprotein cholesterol and triglycerides.
CONCLUSION
The diagnosis of T2D earlier in life is associated with a worse cardiovascular risk factor profile, compared to those diagnosed later in life.
Core Tip: The diagnosis of type 2 diabetes (T2D) in younger adults, an increasingly common public health issue, is associated with a higher risk of cardiovascular complications and mortality, which may be due to a more adverse cardiovascular risk profile in individuals diagnosed at a younger age. This analysis demonstrates the adverse effect of younger diagnosis of T2D on cardiovascular risk factors, highlighting the need for targeted multifactorial age-appropriate interventions in order to improve the cardiovascular risk factor profile of younger adults with T2D and reduce their subsequent risk of cardiovascular complications and mortality.
