Lowri H Thomas,1 Philip MS Evans,2 Atul Kalhan2
1 Cardiff University School of Medicine, Cardiff University, Cardiff, UK
2 Department of Diabetes and Endocrinology, Royal Glamorgan Hospital, Llantrisant, UK
Address for correspondence: Professor Atul Kalhan
Department of Diabetes and Endocrinology, Royal Glamorgan Hospital, Cwm Taf Morgannwg University Health Board, Ynysymaerdy, Llantristant CF27 8XR, UK
Telephone: 01443 443443 ext.3665
E-mail: atul.kalhan@wales.nhs.uk
https://doi.org/10.15277/bjd.2021.290
Background: The management of type 2 diabetes mellitus (T2DM) in frail older adults is made challenging by the impact of physical and cognitive decline on self-monitoring of blood glucose (BG), administration of medications, especially injectable therapies, and risk of hypoglycaemia.
Aims and objectives: (1) To revisit the prevalence of hypoglycaemia in adults with T2DM living in aged-care facilities; (2) to evaluate the impact of simplification of T2DM treatment on quality of life (QOL), morbidity and mortality in this population; and (3) to identify higher risk older adults in whom simplification of therapy will be most appropriate.
Methods: MEDLINE was searched using the following concept areas: aged-care facilities, T2DM, anti-diabetic therapies, morbidity, mortality and QOL. Results (and additional literature identified by citation checking) were screened and assessed against pre-defined eligibility criteria. Standardised structures for extracting, appraising and reporting the literature were used.
Results: Hypoglycaemia is common in adults with T2DM in aged-care facilities. Glycated haemoglobin (HbA1c) needs to be interpreted cautiously in this cohort, with additional capillary BG monitoring needed to identify individuals at risk of hypo- or hyperglycaemia. Simplification of T2DM treatment can reduce morbidity and mortality in frail older adults.
Conclusion: In residents of aged-care facilities, simplification of T2DM treatment can help deliver optimal individualised patient-centred care and improve QOL.
Br J Diabetes 2021;21:11-19
Key words: type 2 diabetes mellitus, aged-care facilities, frailty, dementia
Type 2 diabetes mellitus (T2DM) is a significant global healthcare issue – a challenge intensified by our ageing population.1 By 2030, 5.5 million people in the UK will have T2DM,2 affecting 17% of those aged over 75 years.3
For older adults with T2DM, co-morbidities, polypharmacy and decreased functional reserve equates to greater personal and economic burden of disease: older adults are disproportionally affected by disease complications and hypoglycaemia, which can further impair quality of life (QOL) and accentuate physical and cognitive dependence.4
The global prevalence of T2DM in aged-care facilities (including residential and nursing homes) is estimated at 25–33%.4 Compared with age- and sex-matched controls, residents with T2DM experience accelerated physical and cognitive decline with increased hospital admissions, rapid acquisition of the frail phenotype and reduced life expectancy.4 Paradoxically, intensive glycaemic control, especially hypoglycaemia, is known to contribute to this decline.4 The International Diabetes Federation (IDF) recommends a glycated haemoglobin (HbA1c) of 53–64 mmol/mol in functionally dependent older adults, with lenience to <70 mmol/mol in individuals with frailty or dementia.5 This less intensive glycaemic target aims to balance vascular benefits against the risk of hypoglycaemia in older adults.5 HbA1c represents the average glycaemic control over an 8–12-week period and is not an ideal parameter for evaluating day-to-day fluctuation in blood glucose (BG) levels. Additionally, anaemia, haemoglobinopathies and renal impairment are relatively more common amongst older adults, resulting in a less reliable marker of glycaemic control in this cohort.
Hypoglycaemia is common and under-recognised in residents of aged-care facilities.4 This may reflect the dynamic nature of diabetes: disease and age-related changes to body composition, renal and hepatic dysfunction, reduced nutrition and cognitive impairment result in an increased risk of hypoglycaemia and an impaired ability to respond to lower BG levels. A re-evaluation of glycaemic targets and simplification of treatment can mitigate the risks posed by intensive therapeutic regimens.
Over the last decade, novel oral glucose-lowering therapies have offered simplified treatments and additional cardiovascular and renovascular benefits.6 However, long-term data outcomes on their safety and efficacy in frail older adults are still to be robustly established.
We aimed to evaluate hypoglycaemia prevalence and HbA1c levels as semi-quantitative evidence of overtreatment in residents of aged-care facilities. In addition, we carried out a retrospective review of the literature to evaluate the impact of simplification of T2DM treatment on morbidity, mortality and QOL in this population. Finally, we suggest a possible approach to identify higher risk older adults in whom simplification of therapy will be most appropriate.
Searching the literature
In April 2020 the MEDLINE database was searched using text word and subject heading functions. The search incorporated the following concept areas: aged-care facilities, T2DM, anti-diabetic therapies, simplification of therapy, morbidity, mortality and QOL. Aged-care facilities include both residential and nursing homes. Appendix 1 (online at www.bjd-abcd.com) details the full search strategy used.
Selecting the literature
Results and additional literature identified through citation checking were screened by title and abstract to exclude literature clearly irrelevant to review. Thereafter, full-text articles were assessed against the following pre-defined eligibility criteria.
Inclusion criteria:
Exclusion criteria:
Extracting, appraising and reporting the literature
Data extraction was guided by the Cochrane Collaboration’s template for data extraction.7 The Critical Appraisal Skills Programme checklists8 were used to guide appraisal while the write-up of this review was supported by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist.9
The search strategy yielded 88 results. Following screening by title and abstract, 27 records clearly irrelevant to review were excluded. The remaining 61 full-text articles were assessed for eligibility against the criteria detailed above. Of these, 43 records were excluded. These included 15 records not reflective of review focus, 13 literature reviews, guidelines, opinions or editorials, 10 inaccessible records, and 5 non-English studies (see Figure 1). The remaining 18 studies are included in this review.
We identified 18 studies which evaluated the prevalence of hypoglycaemia and the need for simplification in residents with T2DM in aged-care facilities (see Table 1).10–27 Based on a retrospective analysis of data from 10 observational studies, our systematic review suggests that hypoglycaemia remains common: hypoglycaemia was reported in 6.6–43%,10,11,13,14,16,18,19,24,26,27 clearly identifying it as a preventable factor contributing to increased morbidity and mortality in this cohort.
We could identify only three studies which evaluated a strategy for simplification of T2DM treatment in residents of aged-care facilities (see Table 2). Based on our meta-analysis, older adults with T2DM were more prone to experience hypoglycaemia at both ends of the HbA1c spectrum.10,13,14
Part A: Evaluating the need for simplification of T2DM treatment in residents of aged-care facilities
Management of T2DM in frail older adults poses special challenges as a reduction in functional capacity, development of co-morbidities, polypharmacy, cognitive decline and frailty warrants dynamic re-evaluation of glycaemic targets. The vascular benefits of intensive control need to be weighed against risks posed by hypoglycaemia, with focus on simplification of the therapeutic regimen and adaptation of an individualised approach.
Multiple observational and cross-sectional studies have investigated the prevalence of hypoglycaemia and used HbA1c as a marker of glycaemic control.10–28 We identified 16 studies (collectively involving 7,869 aged-care residents with T2DM) in which data on HbA1c were collected and compared to evaluate glycaemic control. Among these studies, the mean HbA1c was 51.9 mmol/mol (95% CI 52.0 to 51.8 mmol/mol); Figure 2). However, of the five studies reporting grouped values, HbA1c <53 mmol/mol was seen in 43–55%.14–16,19,22 With the IDF recommending a target HbA1c of 53–64 mmol/mol in functionally dependent older adults, with lenience to <70 mmol/mol in those frail or living with dementia,9 this suggests significant overtreatment of this population cohort.
Interestingly, higher HbA1c levels were also associated with an increased risk of developing hypoglycaemia,10,13,14 reflecting poor glycaemic control at both ends of the HbA1c spectrum. HbA1c is a poor marker of glucose variability and needs to be interpreted cautiously in older adults (especially those dependent on carers for nutrition and injectable therapy) due to their susceptibility to BG fluctuation. HbA1c levels can also be falsely high or low due to anaemia, polycythaemia or renal impairment, which become more prevalent with ageing. Andreassen et al19 found capillary BG measurements to have a broader reach in identifying older adults at risk of developing hypoglycaemia than HbA1c levels.
We identified 10 observational studies which have reported on the prevalence of hypoglycaemia in aged-care facility residents. The prevalence of hypoglycaemia based on these studies ranged from 6.6% to 60%,10,11,13,14,16,18,19,24,26,27 reflecting it to be a common and avoidable risk factor associated with increased morbidity in this age group. Indeed, of the 44 nursing homes approached by Hurley et al, 19% reported hypoglycaemic evens as “frequent” among its residents.28
Insulin therapy was commonly associated with the greatest risk of hypoglycaemia compared with other treatment modalities,10,11,13,14,16,24,27 highlighting this therapy as the most in need of review and simplification. An exception to this was a study by Abbatecola et al who observed a lower risk of severe hypoglycaemia associated with rapid and analogue insulin (OR 0.333, 95% CI 0.184 to 0.602 and OR 0.248, 95% CI 0.070 to 0.882, respectively) compared with sulfonylurea therapy (OR 8.8, 95% CI 4.2 to 18.2).18 This study also reported residents with dementia (18%) to be especially vulnerable to developing severe hypoglycaemia compared with residents without dementia (8%).18 Multiple other studies have reported an increased risk of sulfonylurea-induced hypoglycaemia in residents with dementia.16,18
Part B: Simplification of T2DM treatment in residents of aged-care facilities
There is limited literature exploring simplification of T2DM treatment in this population. We identified three such studies which provide a regimen for simplification of T2DM management in residents of aged-care facilities. These studies showed marked heterogeneity in population selection, intervention used for simplification and reported outcomes, making direct comparison non-viable. For example, Sjoblom et al explored different strategies for simplification including switching insulin to oral antidiabetic drugs, cessation of insulin <20 units and halving of insulin >20 units.21 Dharmarajan et al explored simplifying insulin regimens from sliding scale (SS) to basal bolus (BB).15 A study by Umpierrez et al was the only one to compare basal insulin (glargine) with DPP4 inhibitor (linagliptin) monotherapy.11
Of the two studies reporting BG levels, both showed reduced glycaemic variability with simplified treatment. For example, compared with baseline, linagliptin monotherapy resulted in significantly lower mean daily BG.11 A 34% absolute risk reduction in residents affected by hypoglycaemia was also demonstrated when compared with those receiving insulin.11 Similarly, Dharmarajan et al demonstrated significantly lower fasting BG in those on BB insulin regimens compared with SS.15 Here, there were no significant differences in the incidence of hypoglycaemia, although data collection for this occurred over a three-day period only.15
Two of the studies used HbA1c to report the impact of simplification on glycaemic control. Although Sjoblom et al reported a 7 mmol/mol mean HbA1c increase, the 6-month post-intervention mean remained low at 40 mmol/mol.21 When compared with insulin therapy, linagliptin showed no significant difference in HbA1c at 6 months.11 In addition, simplification caused no significant changes to all-cause hospital admissions11,21 or mortality.21
Our systematic review of the literature provides further evidence to support a well-formed consensus: residents with T2DM in aged-care facilities are often subject to intensive glycaemic control and hypoglycaemia. In older adults with T2DM, intensive glycaemic control, especially hypoglycaemia, contributes to accelerated physical and cognitive decline, hospital admissions, frailty and reduced life expectancy.4 Although limited by scarcity of randomised controlled trials, this review suggests that simplification of T2DM treatment can effectively reduce hypoglycaemia risk without compromising glycaemic control in this population.11,15,21 Additionally, simplification may also benefit QOL by reducing tablet, injection and BG monitoring burden for both residents and carers.29
Part C: Identification of residents most likely to benefit from simplification of T2DM treatment
Identifying aged-care facility residents most likely to benefit from simplification of therapy has not received much focus. Evaluating glycaemic control in this cohort is challenging as factors such as cognitive impairment, frailty, reduced functional reserve and depression may make self-monitoring of BG and reporting of osmotic symptoms difficult.
HbA1c measurement remains a relatively insensitive tool to screen those at risk of developing hypoglycaemia.10,13,14 Capillary BG monitoring should supplement HbA1c monitoring in identifying older adults most vulnerable to develop hypoglycaemia. Short- or medium-term continuous glucose monitoring in aged-care facility residents deemed at high risk of hypoglycaemia offers a pragmatic approach and a far more comprehensive reflection of glycaemic control.
The number of antidiabetic prescriptions has not been observed to show correlation with hypoglycaemia risk.12 Care is needed to avoid cessation of insulin in those with type I diabetes mellitus or Latent Autoimmune Diabetes of Adulthood (LADA). As such, further work is needed to explore whether an insulinopenic phenotype as suggested by history, low or low-normal body mass index, previous diabetic ketoacidosis, presence of anti-GAD or anti-islet cell antibodies or strong personal history of autoimmune conditions correctly identifies those with insulin dependency. Similarly, preserved urinary C-peptide:creatinine can give biochemical reassurance of residual pancreatic β cell function and confidence to simplify diabetic treatment.
Selecting a safe and individualised regimen for simplification remains integral in delivering biological, not chronological, patient-centred care – a principal central to all discussions in this review.
In summary, simplification of treatment should be considered in most residents with T2DM living in aged-care facilities, especially in the presence of dementia and frailty. Treatment regimens need to be individualised with simplification of the insulin regimen and/or switching to oral glucose-lowering medications wherever possible. At the time of writing this review, the COVID-19 pandemic reminds us that keeping our older adults with diabetes safe, reducing their dependence on caregivers for administration of tablets, injections and BG monitoring, is far more important now than it has been ever before.
Conflict of interest None.
Funding None.
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