University of Oulu

Erik Fung, Leong-Ting Lui, Lei Huang, King Fai Cheng, Gloria H W Lau, Yi Ting Chung, Behzad Nasiri Ahmadabadi, Suyi Xie, Jenny S W Lee, Elsie Hui, Wing Yee So, Joseph J Y Sung, Irwin King, William B Goggins, Queenie Chan, Marjo-Riitta Järvelin, Ronald C W Ma, Elaine Chow, Timothy Kwok, Characterising frailty, metrics of continuous glucose monitoring, and mortality hazards in older adults with type 2 diabetes on insulin therapy (HARE): a prospective, observational cohort study, The Lancet Healthy Longevity, Volume 2, Issue 11, 2021, Pages e724-e735, ISSN 2666-7568, https://doi.org/10.1016/S2666-7568(21)00251-8

Characterising frailty, metrics of continuous glucose monitoring, and mortality hazards in older adults with type 2 diabetes on insulin therapy (HARE) : a prospective, observational cohort study

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Author: Fung, Erik1,2,3,4,5; Lui, Leong-Ting1,2,3; Huang, Lei1,2,3;
Organizations: 1Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
2Gerald Choa Cardiac Research Centre and CARE Programme at Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
3Laboratory for Heart Failure and Circulation Research, Li Ka Shing Institute of Health Sciences, Prince of Wales Hospital, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
4CUHK Medical Centre, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
5Department of Epidemiology and Biostatistics, MRC Centre for Environment and Health, School of Public Health, Imperial College London, London, UK
6Department of Medicine and Geriatrics, Alice Ho Miu Ling Nethersole Hospital and Tai Po Hospital, Hong Kong Special Administrative Region, China
7Department of Medicine and Geriatrics, Shatin Hospital, Hong Kong Special Administrative Region, China
8Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
9Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
10Department of Computer Science and Engineering, Faculty of Engineering, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
11School of Public Health, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
12Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland
13Unit of Primary Health Care, Oulu University Hospital, Oulu, Finland
14Department of Life Sciences, College of Health and Life Sciences, Brunel University London, UK
15Laboratory for Molecular Epidemiology in Diabetes, Li Ka Shing Institute of Health Sciences, Prince of Wales Hospital, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
16Phase I Clinical Trial Centre, CUHK, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.7 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2022020217325
Language: English
Published: Elsevier, 2021
Publish Date: 2022-02-02
Description:

Summary

Background: To our knowledge, no previous study has examined the inter-relationship between frailty, dysglycaemia, and mortality in frail older adults with type 2 diabetes who are on insulin therapy. We used continuous glucose monitors (CGMs) to profile this patient population and determine the prognostic value of CGM metrics. We hypothesised that incremental frailty was associated with increased hypoglycaemia or time below range (TBR).

Methods: HARE was a multicentre, prospective, observational cohort study with mortality hazard analysis carried out in four hospitals in Hong Kong. Eligible participants were community-living adults aged 70 years and older; had had type 2 diabetes for 5 years or more; were on insulin therapy; were frail; and were not hospitalised at the time of frailty assessment and CGM recording. Glucose control was characterised according to the Advanced Technologies and Treatments for Diabetes 2019 international consensus clinical targets. Frailty index was computed, and comprehensive frailty assessments and targeted serum metabolic profiling were performed. The Jonckheere-Terpstra test for trend was used to analyse frailty index tertiles and variables. Inter-relationships between CGM metrics and frailty, glycated haemoglobin A1c (HbA1c), and serum albumin were characterised using adjusted regression models. Survival analysis and Cox proportional hazard modelling were performed.

Findings: Between July 25, 2018, and Sept 27, 2019, 225 participants were recruited, 222 of whom had CGMs fitted and 215 of whom had analysable CGM data (190 were frail, 25 were not frail). Incremental frailty was associated with older age, greater HbA1c, worse renal function, and history of stroke. Eight of 11 CGM metrics were significantly associated with frailty. Decreased time in range (TIR; glucose concentration 3·9–10·0 mmol/L) and increased time above range (TAR) metrics were strongly correlated with increased frailty and hyperglycaemia, whereas TBR metrics were marginally or not different between frailty levels. Glucose-lowering agents did not significantly affect regression estimates. In patients with HbA1c of 7·5% or more, reduced serum albumin was associated with level 2 TAR (glucose concentration >13·9 mmol/L) and dysglycaemia. During a median follow-up of 28·0 months (IQR 25·3–30·4), increased level 2 TAR was predictive of mortality explainable by frailty in the absence of detectable interaction. Each 1% increment of level 2 TAR was associated with 1·9% increase in mortality hazard.

Interpretation: In older adults with type 2 diabetes who are on insulin therapy, incremental frailty was associated with increased dysglycaemia and hyperglycaemia rather than hypoglycaemia. Mortality hazard was increased with severe hyperglycaemia. Future clinical studies and trials targeting actionable CGM metrics highlighted in this study could translate into improved care and outcomes.

Funding: Health and Medical Research Fund, Food and Health Bureau, The Government of the Hong Kong Special Administrative Region of China.

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Series: The Lancet. Healthy longevity
ISSN: 2666-7568
ISSN-E: 2666-7568
ISSN-L: 2666-7568
Volume: 2
Issue: 11
Pages: e724 - e735
DOI: 10.1016/S2666-7568(21)00251-8
OADOI: https://oadoi.org/10.1016/S2666-7568(21)00251-8
Type of Publication: A1 Journal article – refereed
Field of Science: 3142 Public health care science, environmental and occupational health
3111 Biomedicine
Subjects:
Funding: Health and Medical Research Fund, Food and Health Bureau, The Government of the Hong Kong Special Administrative Region of China.
Copyright information: © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license.
  https://creativecommons.org/licenses/by-nc-nd/4.0/