Closed-loop therapy in older adults with type 1 diabetes: hypoglycaemia benefits and risk stratification

Abstract

We read with interest the Comment in The Lancet Healthy Longevity by Richard Pratley and Anna Casu questioning whether technology can improve the management of type 1 diabetes in older adults.1Pratley RE Casu A Can technology improve the management of older adults with type 1 diabetes? Yes, but….Lancet Healthy Longev. 2022; 3: e120-e121Summary Full Text Full Text PDF Scopus (2) Google Scholar Although the authors draw attention to important points, two key considerations warrant further reflection.The first is hypoglycaemia. Pratley and Casu highlight the importance of what they consider to be the first randomised closed-loop trial in older individuals, reported in the same issue.2Boughton CK Hartnell S Thabit H et al.Hybrid closed-loop glucose control compared with sensor augmented pump therapy in older adults with type 1 diabetes: an open-label multicentre, multinational, randomised, crossover study.Lancet Healthy Longev. 2022; 3: e135-e142Summary Full Text Full Text PDF PubMed Scopus (3) Google Scholar A caveat in their Comment is the absence of hypoglycaemia benefit with this new therapeutic technology. We agree with Pratley and Casu that hypoglycaemia prevention is a critically important area in the management of older adults. We therefore wish to highlight findings from the ORACL multicentre randomised trial, involving 30 older adults with type 1 diabetes and reported in 2021, demonstrating reduced hypoglycaemia with closed-loop therapy.3McAuley SA Trawley S Vogrin S et al.Closed-loop insulin delivery versus sensor-augmented pump therapy in older adults with type 1 diabetes (ORACL): a randomized, crossover trial.Diabetes Care. 2022; 45: 381-390Crossref PubMed Scopus (9) Google Scholar Using a first-generation closed-loop system (MiniMed 670G; Medtronic, Northridge, CA, USA), hypoglycaemia (<3·9 mmol/L) was reduced by median 0·5 percentage points (95% CI 0·3–1·1; p=0·0005) compared with sensor-augmented pump therapy in the ORACL trial; strikingly, there was a three-fold reduction in hypoglycaemia overnight with closed loop.The second is risk stratification when considering effects of diabetes technology among older adults. There is increasing awareness of the importance of risk assessment when considering treatment and clinical targets for older adults with type 1 diabetes.4Sinclair AJ Dunning T Dhatariya K et al.Clinical guidelines for type 1 diabetes mellitus with an emphasis on older adults: an Executive Summary.Diabet Med. 2020; 37: 53-70Crossref PubMed Scopus (18) Google Scholar Recommendations by Sinclair and colleagues specifically support the consideration of frailty, a state of increased vulnerability and low resilience to adverse health outcomes, in the routine delivery of diabetes care.5Sinclair A Bellary S Dhatariya KK Diabetes in older adults – time to include frailty as a care indicator.Diabet Med. 2021; 38e14560Crossref PubMed Scopus (2) Google Scholar In the ORACL trial, 20% of participants had mild cognitive impairment and one-third had impaired awareness of hypoglycaemia; none were frail or malnourished, although 20% were prefrail and 13% were at risk for malnutrition.3McAuley SA Trawley S Vogrin S et al.Closed-loop insulin delivery versus sensor-augmented pump therapy in older adults with type 1 diabetes (ORACL): a randomized, crossover trial.Diabetes Care. 2022; 45: 381-390Crossref PubMed Scopus (9) Google Scholar Risk assessments were limited in the older adult closed-loop trial report by Boughton and colleagues, reducing the clinical applicability of these results.2Boughton CK Hartnell S Thabit H et al.Hybrid closed-loop glucose control compared with sensor augmented pump therapy in older adults with type 1 diabetes: an open-label multicentre, multinational, randomised, crossover study.Lancet Healthy Longev. 2022; 3: e135-e142Summary Full Text Full Text PDF PubMed Scopus (3) Google Scholar We propose that studies involving older adults need to sufficiently characterise the cohort studied, including their clinical, cognitive, frailty, and functional status, to allow clinical contextualisation of results.In conclusion, discordant randomised trial evidence for closed-loop therapy effects on hypoglycaemia in older adults with type 1 diabetes warrants further examination. Whether differences in the cohorts studied, differences between closed-loop algorithms, or other factors contributed to the inconsistent hypoglycaemia effects remains to be determined. Moreover, detailed characterisation of older adult participants is paramount to interpretation of diabetes technology clinical trial results and their application to clinical practice. We read with interest the Comment in The Lancet Healthy Longevity by Richard Pratley and Anna Casu questioning whether technology can improve the management of type 1 diabetes in older adults.1Pratley RE Casu A Can technology improve the management of older adults with type 1 diabetes? Yes, but….Lancet Healthy Longev. 2022; 3: e120-e121Summary Full Text Full Text PDF Scopus (2) Google Scholar Although the authors draw attention to important points, two key considerations warrant further reflection. The first is hypoglycaemia. Pratley and Casu highlight the importance of what they consider to be the first randomised closed-loop trial in older individuals, reported in the same issue.2Boughton CK Hartnell S Thabit H et al.Hybrid closed-loop glucose control compared with sensor augmented pump therapy in older adults with type 1 diabetes: an open-label multicentre, multinational, randomised, crossover study.Lancet Healthy Longev. 2022; 3: e135-e142Summary Full Text Full Text PDF PubMed Scopus (3) Google Scholar A caveat in their Comment is the absence of hypoglycaemia benefit with this new therapeutic technology. We agree with Pratley and Casu that hypoglycaemia prevention is a critically important area in the management of older adults. We therefore wish to highlight findings from the ORACL multicentre randomised trial, involving 30 older adults with type 1 diabetes and reported in 2021, demonstrating reduced hypoglycaemia with closed-loop therapy.3McAuley SA Trawley S Vogrin S et al.Closed-loop insulin delivery versus sensor-augmented pump therapy in older adults with type 1 diabetes (ORACL): a randomized, crossover trial.Diabetes Care. 2022; 45: 381-390Crossref PubMed Scopus (9) Google Scholar Using a first-generation closed-loop system (MiniMed 670G; Medtronic, Northridge, CA, USA), hypoglycaemia (<3·9 mmol/L) was reduced by median 0·5 percentage points (95% CI 0·3–1·1; p=0·0005) compared with sensor-augmented pump therapy in the ORACL trial; strikingly, there was a three-fold reduction in hypoglycaemia overnight with closed loop. The second is risk stratification when considering effects of diabetes technology among older adults. There is increasing awareness of the importance of risk assessment when considering treatment and clinical targets for older adults with type 1 diabetes.4Sinclair AJ Dunning T Dhatariya K et al.Clinical guidelines for type 1 diabetes mellitus with an emphasis on older adults: an Executive Summary.Diabet Med. 2020; 37: 53-70Crossref PubMed Scopus (18) Google Scholar Recommendations by Sinclair and colleagues specifically support the consideration of frailty, a state of increased vulnerability and low resilience to adverse health outcomes, in the routine delivery of diabetes care.5Sinclair A Bellary S Dhatariya KK Diabetes in older adults – time to include frailty as a care indicator.Diabet Med. 2021; 38e14560Crossref PubMed Scopus (2) Google Scholar In the ORACL trial, 20% of participants had mild cognitive impairment and one-third had impaired awareness of hypoglycaemia; none were frail or malnourished, although 20% were prefrail and 13% were at risk for malnutrition.3McAuley SA Trawley S Vogrin S et al.Closed-loop insulin delivery versus sensor-augmented pump therapy in older adults with type 1 diabetes (ORACL): a randomized, crossover trial.Diabetes Care. 2022; 45: 381-390Crossref PubMed Scopus (9) Google Scholar Risk assessments were limited in the older adult closed-loop trial report by Boughton and colleagues, reducing the clinical applicability of these results.2Boughton CK Hartnell S Thabit H et al.Hybrid closed-loop glucose control compared with sensor augmented pump therapy in older adults with type 1 diabetes: an open-label multicentre, multinational, randomised, crossover study.Lancet Healthy Longev. 2022; 3: e135-e142Summary Full Text Full Text PDF PubMed Scopus (3) Google Scholar We propose that studies involving older adults need to sufficiently characterise the cohort studied, including their clinical, cognitive, frailty, and functional status, to allow clinical contextualisation of results. In conclusion, discordant randomised trial evidence for closed-loop therapy effects on hypoglycaemia in older adults with type 1 diabetes warrants further examination. Whether differences in the cohorts studied, differences between closed-loop algorithms, or other factors contributed to the inconsistent hypoglycaemia effects remains to be determined. Moreover, detailed characterisation of older adult participants is paramount to interpretation of diabetes technology clinical trial results and their application to clinical practice. SAM reports support for research from Medtronic, speaker honoraria from Eli Lilly, Roche, and Sanofi, and has served on an advisory board for Medtronic. ST reports non-financial support from Abbott Diabetes. Can technology improve the management of older adults with type 1 diabetes? Yes, but…Technology-based approaches aimed at improving health have permeated our lives. Today, smart phone applications, smart watches, activity trackers, and an ever-evolving ecosystem of biometric trackers are in routine use by millions of consumers worldwide. Nowhere have advances in technology been more impactful than in the field of diabetes. For example, intermittent finger-stick blood glucose testing is rapidly giving way to newer technologies such as continuous glucose monitoring. Full-Text PDF Open AccessHybrid closed-loop glucose control compared with sensor augmented pump therapy in older adults with type 1 diabetes: an open-label multicentre, multinational, randomised, crossover studyHybrid closed-loop insulin delivery is safe and achieves superior glycaemic control to SAP therapy in older adults with long duration of type 1 diabetes. Importantly this was achieved without increasing the risk of hypoglycaemia in this population with risk factors for severe hypoglycaemia. This suggests that hybrid closed-loop therapy is a clinically important treatment option for older adults with type 1 diabetes. Full-Text PDF Open AccessClosed-loop therapy in older adults with type 1 diabetes: hypoglycaemia benefits and risk stratification – Authors' replyWe thank Sybil McAuley and Steven Trawley for bringing the recently published results of the ORACL trial1 to our attention and apologise for not including their work in our recent Comment.2 In this study, they and their colleagues report that, relative to sensor-augmented pump therapy, a hybrid closed-loop insulin delivery strategy was associated with significant improvements in time in range measured by continuous glucose monitoring in older adults with type 1 diabetes. Moreover, and in contrast to the study of Charlotte Boughton and colleagues,3 they report small but significant decreases in hypoglycaemia with a hybrid closed-loop strategy. Full-Text PDF Open Access