Mismatch between HbA1c and time in range targets among older adults with type 1 diabetes

International diabetes societies unanimously recommend individualisation of HbA1c targets for older adults with diabetes to account for frailty and functional status.1Draznin B Aroda VR Bakris G et al.13. Older adults: standards of medical care in diabetes—2022.Diabetes Care. 2022; 45: S195-S207PubMed Google Scholar, 2Imran SA Agarwal G Bajaj HS Ross S Targets for glycemic control.Can J Diabetes. 2018; 42: S42-S46Summary Full Text Full Text PDF PubMed Scopus (49) Google Scholar, 3Holt RIG DeVries JH Hess-Fischl A et al.The management of type 1 diabetes in adults. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).Diabetes Care. 2021; 44: 2589-2625Crossref PubMed Scopus (159) Google Scholar, 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 (27) Google Scholar Although the specific implementation of these recommendations differs by the various societies, in general, HbA1c targets are successively increased for older adults with increasing frailty or functional dependence (table).TableSummary of HbA1ctarget recommendations by different organisations for older adultsDiabetes UKDiabetes CanadaAmerican Diabetes AssociationAmerican Diabetes Association–European Association for the Study of DiabetesPatient populationType 1 diabetesDiabetesDiabetesType 1 diabetesNon-frail<70 years old: 6·5–7·0%;≥70 years old: 7·0–7·5%<7·0%<7·0–7·5%..Mild frailty7·0–7·5% or 8%7·1–8·0%<8·0%..Substantial frailty7·5–8·5%7·1–8·5%<8·0%<8% if reduced life expectancy or harms outweigh risks Open table in a new tab In 2019, continuous glucose monitoring (CGM) targets were published as the International Consensus on Time in Range, which has since been widely adopted. For older adults, a time in range (3·9–10·0 mmol/L)] target of more than 50% and a time below range (<3·9 mmol/L) target of less than 1% are recommended.5Battelino T Danne T Bergenstal RM et al.Clinical targets for continuous glucose monitoring data interpretation: recommendations from the International Consensus on Time in Range.Diabetes Care. 2019; 42: 1593-1603Crossref PubMed Scopus (1703) Google Scholar To date, these recommendations are the sole guidance for CGM targets pertaining to older adults. However, as noted by Steven Trawley and colleagues in The Lancet Healthy Longevity,6Trawley S Ward GM Vogrin S et al.Glucose profiles of older adults with type 1 diabetes using sensor-augmented pump therapy in Australia: pre-randomisation results from the ORACL study.Lancet Healthy Longev. 2022; (published online Nov 18)https://doi.org/10.1016/S2666-7568(22)00266-5Summary Full Text Full Text PDF PubMed Scopus (2) Google Scholar there is a mismatch between recommended HbA1c and CGM targets for older adults. Although HbA1c targets are individualised, CGM targets for older adults are applied uniformly to all older adults, and do not consider frailty or functional status. As CGM use becomes increasingly common within older populations, evidence-based CGM targets for older adults are required. Trawley and colleagues compared 2 weeks of CGM data among older adults with type 1 diabetes during the run-in phase for the Older Adult Closed Loop (ORACL) diabetes technology trial with the recommended CGM targets for older adults.6Trawley S Ward GM Vogrin S et al.Glucose profiles of older adults with type 1 diabetes using sensor-augmented pump therapy in Australia: pre-randomisation results from the ORACL study.Lancet Healthy Longev. 2022; (published online Nov 18)https://doi.org/10.1016/S2666-7568(22)00266-5Summary Full Text Full Text PDF PubMed Scopus (2) Google Scholar 24 (80%) of the 30 participants were non-frail, six (20%) were pre-fail, and none were frail. Ten (33%) of 30 participants had impaired hypoglycaemia awareness. The median time in range was 71% (IQR 64–79) and the time below range was 2% (1–3). Only seven (23%) of 30 participants met the recommended time below range target of less than 1%. Participants who used predictive low glucose alerts spent less time in hypoglycaemia. The authors conclude that the recommended time in range target of more than 50% for all older adults (equating to an HbA1c of 8·3%) is inappropriately low for non-frail older adults, and they argue that CGM targets for older adults should be individualised on the basis of frailty status and method of insulin delivery.6Trawley S Ward GM Vogrin S et al.Glucose profiles of older adults with type 1 diabetes using sensor-augmented pump therapy in Australia: pre-randomisation results from the ORACL study.Lancet Healthy Longev. 2022; (published online Nov 18)https://doi.org/10.1016/S2666-7568(22)00266-5Summary Full Text Full Text PDF PubMed Scopus (2) Google Scholar, 7Vigersky RA McMahon C The relationship of hemoglobin A1C to time-in-range in patients with diabetes.Diabetes Technol Ther. 2019; 21: 81-85Crossref PubMed Scopus (259) Google Scholar The authors also highlight that reducing the time below range in older adults could be accomplished through use of low-glucose alerts and more accurate mealtime insulin doses, since most hypoglycaemia occurred within 4 h of insulin boluses. It is important to note some limitations of this analysis. The sample size is small and comprised of non-frail older adults. Furthermore, all participants used insulin pump therapy at baseline, and received education and training on sensor-augmented pump therapy before CGM data collection. Thus, the results have limited generalisability to older adults with functional impairment or frailty, and those not using sensor-augmented pump therapy. In the WISDM study, in which older adults with type 1 diabetes were randomly assigned to CGM or standard blood glucose monitoring, only 108 (53%) of 203 participants used insulin pump therapy and 32 (16%) had clinically significant cognitive impairment.8Pratley RE Kanapka LG Rickels MR et al.Effect of continuous glucose monitoring on hypoglycemia in older adults with type 1 diabetes: a randomized clinical trial.JAMA. 2020; 323: 2397-2406Crossref PubMed Scopus (145) Google Scholar In participants randomly assigned to CGM, the time below range was 3% (IQR 2–5) and time in range was 63% (SD 13),8Pratley RE Kanapka LG Rickels MR et al.Effect of continuous glucose monitoring on hypoglycemia in older adults with type 1 diabetes: a randomized clinical trial.JAMA. 2020; 323: 2397-2406Crossref PubMed Scopus (145) Google Scholar which are higher and lower, respectively, than in the ORACL population.6Trawley S Ward GM Vogrin S et al.Glucose profiles of older adults with type 1 diabetes using sensor-augmented pump therapy in Australia: pre-randomisation results from the ORACL study.Lancet Healthy Longev. 2022; (published online Nov 18)https://doi.org/10.1016/S2666-7568(22)00266-5Summary Full Text Full Text PDF PubMed Scopus (2) Google Scholar The optimal time below range threshold for older adults, and whether this differs from the general adult population, is unknown. All older adults with type 1 diabetes might be at an increased risk of severe hypoglycemia, since ageing is associated with an impaired glucagon response and reduced hypoglycemia awareness.9Bremer JP Jauch-Chara K Hallschmid M Schmid S Schultes B Hypoglycemia unawareness in older compared with middle-aged patients with type 2 diabetes.Diabetes Care. 2009; 32: 1513-1517Crossref PubMed Scopus (243) Google Scholar, 10Matyka K Evans M Lomas J Cranston I Macdonald I Amiel SA Altered hierarchy of protective responses against severe hypoglycemia in normal aging in healthy men.Diabetes Care. 1997; 20: 135-141Crossref PubMed Scopus (179) Google Scholar The analysis by Trawley and colleagues6Trawley S Ward GM Vogrin S et al.Glucose profiles of older adults with type 1 diabetes using sensor-augmented pump therapy in Australia: pre-randomisation results from the ORACL study.Lancet Healthy Longev. 2022; (published online Nov 18)https://doi.org/10.1016/S2666-7568(22)00266-5Summary Full Text Full Text PDF PubMed Scopus (2) Google Scholar was not designed to evaluate whether a more stringent time below range threshold, such as less than 1%, leads to less clinically significant or severe hypoglycaemia than the more liberal threshold of less than 4% recommended for the general adult population. Studies with larger sample sizes and longer durations of follow-up are required to identify the optimal time below range threshold for both frail and non-frail older adults. A so-called hierarchical approach to CGM targets for older adults might be prudent, in which achievement of the time below range target is first prioritised, followed by maximising the time in range, but without sacrificing greater time below range. Trawley and colleagues have highlighted the mismatch between HbA1c and CGM targets for older adults.6Trawley S Ward GM Vogrin S et al.Glucose profiles of older adults with type 1 diabetes using sensor-augmented pump therapy in Australia: pre-randomisation results from the ORACL study.Lancet Healthy Longev. 2022; (published online Nov 18)https://doi.org/10.1016/S2666-7568(22)00266-5Summary Full Text Full Text PDF PubMed Scopus (2) Google Scholar CGM targets must be updated to align with HbA1c target recommendations, and individualised based on frailty, functional status, and use or non-use of sensor-augmented pump therapy or closed-loop systems. Further studies should be done to clarify the optimal time below range thresholds among frail and non-frail older adults, to minimise the risks of clinically significant or severe hypoglycaemia in the older adult population. I am supported by a Sunlife Financial New Investigator Award from the Banting & Best Diabetes Center. I am grateful to Bruce Perkins for reviewing the first draft of this Comment and providing feedback. Glucose profiles of older adults with type 1 diabetes using sensor-augmented pump therapy in Australia: pre-randomisation results from the ORACL studyUsing sensor-augmented pumps after multidisciplinary education, this group of older adults without frailty achieved a time in range far exceeding minimum consensus recommendations. However, the current stringent hypoglycaemia recommendations for all older adults were not met. Predictive low alerts could reduce hypoglycaemia, particularly overnight. Investigation into the effectiveness of CGM-based targets that consider frailty, functional status, and diabetes therapies for older adults is warranted. Full-Text PDF Open Access

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