Frailty and Dysglycaemia in Older Adults with Type 2 Diabetes on Insulin Therapy: The HARE Continuous Glucose Monitoring Study

Background: Glucose management can be difficult in frail older adults with type 2 diabetes (T2D) on insulin therapy. As no study has examined the interrelationship between frailty, dysglycaemia and mortality, we used continuous glucose monitors (CGMs) to prospectively profile insulin-requiring frail and borderline frail older adults with T2D, explored circulating metabolic factors that influenced it, and determined the prognostic value of CGM metrics. Methods: This was a multi-centre, prospective, observational study using weeklong real-time CGMs (Medtronic iPro2) between August 2018 and October 2019. 28,608 hours of CGM recordings were compiled from 215 community-living T2D patients (mean age 74·7 years) on long-term insulin therapy, and analysed according to Advanced Technologies & Treatments for Diabetes 2019 standardised metrics. Frailty index was computed, and comprehensive frailty assessments and serum metabolic profiling were performed. Association and regression analyses were adjusted for age, sex, comorbidities, renal function, and insulin and anti-diabetic drug regimens. Survival analysis and proportional hazard modelling were performed. Findings: Incremental frailty was associated with older age, higher HbA1c, worse renal function, and past history of stroke. Decreased ‘time in range’ (TIR) and increased ‘time above range’ (TAR) metrics were strongly correlated with increased frailty and hyperglycaemia, whereas overall TBR was not different between frailty levels. Insulin and anti-diabetic drug regimen did not significantly affect regression estimates. Reduced serum albumin level was identified as a determinant of hyperglycaemia/dysglycaemia. Importantly, increased Level 2 TAR (glucose >13·9 mmol/L) was predictive of mortality (median follow-up 2·3 years) that was explainable by frailty. Each 1% increment of Level 2 TAR was associated with a 1·9% increase in mortality hazard. Interpretation: In insulin-requiring older adults with T2D, incremental frailty was associated with increased dysglycaemia and hyperglycaemia rather than hypoglycaemia. Mortality hazard was increased with prolonged severe hyperglycaemia. Funding: Health and Medical Research Fund (HMRF no.15162161), Food & Health Bureau, The Government of the Hong Kong SAR of China.Declaration of Interest: Ronald CW Ma received research funding from AstraZeneca, Bayer, Boehringer Ingelheim, Medtronic, Novo Nordisk, Pfizer, Sanofi and Tricida Inc. for carrying out clinical trials, speaker honorarium or consultancy in advisory boards. All proceeds have been donated to the Chinese University of Hong Kong to support diabetes research. All others have nothing to declare. Ethical Approval: HARE is a multicentre, prospective, observational study approved by the institutional review board of The Chinese University of Hong Kong–New Territories East Cluster (CUHK-NTEC) Clinical Research Ethics Committee (CREC study no. 2017.702).