Diabetes and insulin therapy in older people

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1 Hendra p /03/ :58 Page 1 Diabetes and insulin therapy in older people TIMOTHY J HENDRA Abstract Concerns about hypoglycaemia, plus lack of evidence of benefit, contributed to underutilisation of insulin for older people with type 2 diabetes in the past. Following the UKPDS it is clear that many elderly patients treated with diet and oral antidiabetic agents will develop beta-cell failure and will be at risk of worsening glycaemic control with reduced well-being unless insulin is considered. Following diabetes diagnosis, the mainstay of treatment will be dietary control and exercise together with management of cardiovascular risk factors. When glycaemic control deteriorates oral agents will be needed. However, whereas in the past insulin was seen as a last resort for older type 2 patients there is support for considering its early use in selected older people with preserved cognitive function and poor glycaemic control, as well as for frail older people with weight loss and poor quality of life. The regimens of choice may include a combination of basal insulin with oral agents or twice-daily combinations of premixed short and intermediate acting insulin. The development of insulin analogues with their associated reduced risk of hypoglycaemia may also herald a new era of insulin treatment for older people. Br J Diabetes Vasc Dis 2005;5:19 23 Key words: older people, early use of insulin, quality of life. Introduction Treatment for older people with diabetes differs from that in younger adults since the majority have type 2 disease and are at particular risk of macrovascular compared with microvascular complications. Treatment approaches therefore need to take particular account of cardiovascular risk factors 1 as well as glycaemic control, while recognising that quality of life is a fundamental management aim. The clinician should also be aware of the increasing prevalence of insulin resistance with normal ageing, 2 and the high prevalence of unknown diabetes in the elderly population. Correspondence to: Professor Timothy J Hendra Department of Geriatric Medicine, Brearley Wing, Northern General Hospital, Herries Road, Sheffield, S5 7AU, UK. Tel: +44 (0) ; Fax: +44 (0) Tim.Hendra@sth.nhs.uk Timothy J Hendra Specific clinical issues to consider when caring for an older person include: a. An increased likelihood of co-morbidities such as dementia, depression, poor mobility, and sensory deprivation which the patient and their carers may perceive as being more important than diabetes. b. Limitations on the older person s ability to recognise and deal with hypoglycaemia due to greater co-morbidity. c. The need to regularly review the aims of treatment as the patient ages. d. The increased involvement of formal and informal carers. e. Residential and Nursing Home residency. f. The different expectations and beliefs of older people. In the UK, the NSF For Older People and the NSF for Diabetes identify important standards for managing all older people as well as those with diabetes. These are timely in view of the changing demography that will result in a significant increase in the number of very old people (> 80 years) in society. The management of diabetes in older people at home and in care homes will always require a different approach to that for younger adults. 3,4 This article will focus on insulin treatment for the older person with type 2 diabetes and will reflect current trends of treating to target, and the early introduction of insulin, while emphasising that there will always be a trade-off between these therapeutic strategies and the need to avoid serious hypoglycaemia. VOLUME 5 ISSUE 1. JANUARY/FEBRUARY

2 Hendra p /03/ :58 Page 2 Abbreviations DSN diabetes specialist nurse HbA 1C glycated haemoglobin NICE National Institute for Clinical Excellence NPH neutral protamine Hagedorn NSF national service framework Figure 1. Possible schematic pathway for starting insulin in an older person Glycaemic targets not being met / Frequent infections / Recurrent hospital admissions with poor control Table 1. Possible barriers to the use of insulin Fear of needles Fear of hypoglycaemia Reluctance or inability to undertake capillary glucose monitoring Inability to use a pen device due to impaired manual dexterity, poor vision, or cognitive impairment Cultural issues resulting in stigmatisation Effect on place of residency Significant co-morbidity Social isolation Mixing oral therapy and insulin introduces complexity Perceptions that insulin is not effective in type 2 disease except as a last resort Aims of insulin treatment At the outset it is important to agree the goals of treatment with patients and carers especially with the latter if the patient is disabled and/or cognitively impaired. For some patients the goals of treatment can appropriately be set at relief of osmotic symptoms and preservation of well-being with the avoidance of intercurrent infections rather than trying to achieve tight glycaemic control. However, clinically important reductions in microvascular disease can be achieved with improved glycaemic control in type 2 diabetes. The United Kingdom Prospective Diabetes Study (UKPDS) 5 and Kumamoto 6 studies utilised a target HbA 1C level of 7.0% that may be unrealistic in the context of hypoglycaemic risk for many older people. The Steno-2 study 7 which includes treatment of macrovascular risk factors as well as glycaemic control, represents a multifactoral approach to managing diabetes that is appropriate for all older people in the context of a healthy ageing programme combining lifestyle and therapeutic interventions. Recommendations from the European Diabetes Working Party For Older People (available at suggest aiming for a target HbA 1C of % for subjects with single system involvement with the precise target depending upon existing cardiovascular disease, presence of microvascular complications, and ability to self-manage. For frail patients, or those with functional dependency, multisystem disease, or subjects in whom the risk of hypoglycaemia is high and symptom control paramount, then the target HbA 1C should be %. 8 From the UKPDS it is evident that in type 2 diabetes beta-cell Consider adding insulin to or in place of oral agents Assess: Cognition 12,13 Functional ability to perform ADL 14 Mood 15 Discuss treatment goals with patient and Refer to DSN or Practice Nurse: Review treatment goals Choice of regimen Monitoring Frequency of review Start insulin Review function deteriorates inexorably with time whether patients are treated intensively or conventionally. 9 In view of the increasing life expectancy of all older people it is reasonable to assume that many newly diagnosed type 2 patients in their late 60s and early 70s will live to be at risk of microvascular complications and experience beta-cell failure. Therefore, the value of early introduction of low-dose insulin in combination with oral agents in type 2 disease to achieve beta-cell rest is as relevant for older people as for younger adults. 10 Although it may be justifiably argued that the optimal strategy for the early addition of insulin to oral agents is yet to be determined, what is clear is that it is no longer acceptable to regard switching to insulin as the final last step when older people have poor glycaemic control associated with poor quality of life and/or weight loss. Weight gain and improved well-being are justifiable aims of starting insulin in older people. When to start insulin The indications for insulin are well known, as are the perceived barriers (table 1). In older people the use of insulin in the context of myocardial infarction and its possible role in acute stroke are 20 THE BRITISH JOURNAL OF DIABETES AND VASCULAR DISEASE

3 Hendra p /03/ :58 Page 3 Table 2. Insulin regimens Insulin Advantages Disadvantages Comments Once-daily intermediate/long Single injection that can be Will not produce satisfactory glycaemic Of value where sole aim is to relieve duration insulin given by formal/informal carer control when used alone without osmotic symptoms oral agents New insulin analogues (e.g. insulin glargine) may achieve better glycaemic control with less hypoglycaemic risk important to note. There are specific concerns that the introduction of insulin should not be unnecessarily delayed in older people with poor glycaemic control and weight loss because of concerns about the risk of hypoglycaemia. In particular, many older people may be receiving off-label triple therapy of a sulphonylurea, metformin and a glitazone when they could be started on either insulin to normalise their fasting glucose levels with oral agents or started on a twice-daily short/intermediate acting insulin mixture. 11 When considering insulin for an older person a comprehensive assessment of their cognitive and functional status, as well as their mood, should be undertaken (figure 1). Instruments that could be employed include the Abbreviated Mental Test score 12 and Folstein Minimental State Score 13 for cognitive function, the Barthel Index 14 for the ability to perform the activities of daily living, and the Hospital Anxiety and Depression Scale 15 to screen for mood disorder. Rehabilitation needs will be identified as well as deficiencies in cognitive function that may affect the patient s ability to recognise and deal with hypoglycaemia, use an insulin pen, or make their own adjustments to insulin dosage. Other psychological barriers, including fear of needles and the possible stigma of this treatment will need to be considered together with the educational needs of carers. 16 Having assessed the patients and agreed the goals of treatment (including glycaemic targets) insulin should then be started in the community with ready access to specialist help which in the UK is usually from hospital-based Diabetes Nurse Specialists but can be from appropriately trained (General) Practice Nurses. Reserved for situation where older person lives alone in community and injection needs to be given by district nurse/carer who visits once daily Twice-daily pre-mixed short/ Can achieve reasonably good Requires regular meal patterns With careful supervision can produce intermediate duration insulin glycaemic control a good balance of reasonably good Will not achieve normoglycaemia control without risk of or glycated haemoglobin < 7.0% hypoglycaemia in selected patients without significant risk of hypoglycaemia Basal/Bolus insulin regimen Can achieve near-normoglycaemia Expensive Suitable for selected motivated patients without cognitive Allows flexibility in meal times Regular capillary monitoring and multiple impairment injections will be unacceptable and/or impractical for many older patients Insulin plus oral medication Less weight gain than twice- Preferred for patients with daily mixtures poor control who remain overweight One injection a day Many older patients can perform capillary glucose monitoring and will employ pen devices despite failing eyesight and reduced manual dexterity due to arthritis. Choice of insulin The range of insulin regimens have differing roles and potential advantages for older people depending upon their individual circumstances and the aims of treatment (table 2). For many older people, although recognising the importance of controlling peak post-prandial glucose levels, it is appropriate to focus upon treating to normalise fasting glucose levels using long or intermediate acting insulins. The use of titration algorithms to increase insulin dosages in a stepwise manner with a view to holding HbA 1C levels < 7.0% may also be appropriate in some cases. 17 Twice-daily NPH insulin may be associated with better glucose control and patient satisfaction than once-daily ultralente, 18 while the combination of bedtime metformin with insulin prevents weight gain and is associated with reduced hypoglycaemia and better glycaemic control than other bed-time insulin regimens 19 (table 3). Insulin, well-being and cognitive function Many type 2 patients, irrespective of age, feel significantly improved within 72 hours of starting insulin. This could be related to an improvement in glycaemic control but may in part be due to other factors including possibly a direct effect of insulin on well-being. Over a longer period insulin produces sustained improvements in well-being, as measured by generic instruments, in selected older people whose baseline scores are well VOLUME 5 ISSUE 1. JANUARY/FEBRUARY

4 Hendra p /03/ :58 Page 4 Table 3. Author Studies of different insulin regimens in type 2 diabetic subjects Findings and mean age of patients Key messages Yki-Jarvinen et al. Combination of metformin and bedtime insulin (1999) 19 associated with less weight gain, improved glycaemic control and less hypoglycaemia compared to other insulin bedtime regimens in type 2 patients (ages years) Taylor et al. Twice-daily NPH insulin associated with better (2000) 18 glycaemic control, better treatment satisfaction and less hypoglycaemia compared to once-daily ultralente insulin (age 60 years) Schwartz et al. Insulin Mix 70/30 plus metformin as effective as (2003) 11 triple oral therapy in lowering HbA 1C. Triple oral therapy not as cost-effective (age 54 years) Riddle et al. Systematic titration of bedtime basal insulin plus (2003) 17 oral therapy can achieve 7% HbA 1C in most overweight type 2 patients with starting HbA 1C levels of %. Glargine produces less nocturnal hypoglycaemia compared to NPH insulin (ages years) below standardised norms for older people of the same age. 20 However, in patients with poor control whose baseline wellbeing scores are higher, the longer-term effects of insulin on well-being are less clear, 21 perhaps reflecting the multi-dimensional reliance of well-being upon other factors including patient-health worker contact, frequency of hypoglycaemia, comorbidity and social support. The possibility of a direct relationship between insulin and cognitive function is of note. Studies in Alzheimer s Disease demonstrated that increasing insulin levels while maintaining euglycaemia can improve memory, while increasing glucose levels with suppressed endogenous insulin, suggest an interesting but important relationship between memory, glucose metabolism and insulin sensitivity. 22 Insulin analogues Insulin aspart and insulin lispro may be associated with improvements in quality of life and treatment satisfaction, as well as small reductions in glycated haemoglobin in type 1 but not type 2 diabetes. 23 Insulin detemir and insulin glargine are longer acting analogues given twice or once daily and are associated with comparable glycaemic control to standard intermediate duration insulins but in addition may be associated with reduced frequency of nocturnal hypoglycaemia. Although current NICE (UK) guidelines do not recommend insulin glargine as a routine treatment option for type 2 diabetes, 24 the possible benefits in older people in terms of hypoglycaemia reduction may make this an attractive option for older people who live alone and who are starting insulin in combination with oral agents. 19,25 Future, less invasive, methods of insulin delivery have potential benefits for older people, 26 in particular a study of inhaled Older people with diabetes are a heterogenous group whose differing treatment needs require individual review and alteration as ageing occurs Starting insulin, either alone or in combination with oral therapy, can be associated with improved quality of life and better glycaemic control in selected older patients without the risk of significant hypoglycaemia Early introduction of basal insulin to control fasting glucose is appropriate for selected older people with type 2 diabetes Long-acting insulin analogues may have significant advantages in older people because of a lower risk of nocturnal hypoglycaemia preprandial insulin in type 2 patients via the AERx Insulin Diabetes Management System is encouraging. 27 Attitudes of patients towards starting insulin Despite education and counselling patients may not perceive the value and consequences of insulin in the same way as healthcare professionals. Patients often rank well-being or quality of life as the goal of switching to insulin above improvements in glycaemic control and avoidance of complications. 28 Attitudes will be affected by historical attitudes towards starting insulin as a failure on their part, concerns about how their relatives and friends will view the treatment, and the possibility that they will be alone in the community without support to cope with needles and the risk of hypoglycaemia. Interactions with other older people who have started insulin, and their relationship with the healthcare team may also be important. Older people are at particular risk of hypoglycaemia because of polypharmacy, poor renal function and the difficulties associated with glycaemic monitoring due to poor vision, cognitive impairment and impaired manual dexterity. 3 There is evidence that elderly patients, like many younger adults, are not good at recognising the symptoms of hypoglycaemia. In addition, the presence of limited mobility and impaired manual dexterity mean that many older people will also have difficulties in dealing with the consequences of hypoglycaemia even if they recognise that their glucose levels are low. Although insulin treatment places patients at particular high risk of hypoglycaemia, and of falls, there is also a hypoglycaemic risk associated with sulphonylureas. However, hypoglycaemia need not be a problem in older people starting insulin using basal/bolus and twice-daily mixtures of short/intermediate acting insulin if there is support from a DSN. 20,21 22 THE BRITISH JOURNAL OF DIABETES AND VASCULAR DISEASE

5 Hendra p /03/ :58 Page 5 Older women with diabetes have an increased risk of falling, partly because of the increased rates of known fall risk factors, and may benefit from interventions to prevent falls. 29 Hence the need for a falls assessment should be conducted when considering starting sulphonylurea or insulin in older people who are frail or who have joint disease or movement disorders. can be minimised by initial careful assessment of patient cognitive function, one-to-one education, and careful selection of treatment options and glycaemic targets at the outset. After that, annual review of hypoglycaemic risk, preferentially with carers or neighbours in the community, is essential. Conclusion The avoidance of hypoglycaemia remains an important goal from the physician s and patient s perspective in the management of diabetes in the older person. Long-acting insulin analogues such as insulin detemir or glargine can be introduced early with the aim of treating to fix fasting glucose levels in the older type 2 diabetic patient. These analogues may have advantages over the established isophane preparations, 30 and in the disabled frail elderly may provide better glycaemic control with a lower hypoglycaemic risk. References 1. Hendra TJ, Sinclair AJ. Improving the care of elderly diabetic patients: the final report of the St Vincent Joint Task Force for diabetes. Age Ageing 1997;26: Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults. Findings from the Third National Health and Nutritional Examination Study. JAMA 2002;287: Sinclair AJ, Turnbull CJ, Croxson SCM. Document of care for older people with diabetes. Postgrad Med J 1996;72: Sinclair AJ, Turnbull CJ, Croxson SCM. Document of diabetes care for residential and nursing homes. Postgrad Med J 1997;73: UK Prospective Diabetes Study (UKPDS) Group. 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Am J Med 2004;116(suppl 3A):3S-9S. 11. Schwartz S, Sievers R, Strange P et al. Insulin 70/30 Mix plus metformin versus triple oral therapy in the treatment of type 2 diabetes after failure of two oral drugs: efficacy, safety, and cost analysis. Diabetes Care 2003;26: Qureshi KN, Hodkinson HM. Evaluation of a ten-question mental test in the institutionalised elderly. Age Ageing 1974;3: Folstein MF, Folstein SE, McHugh PR. "Mini-mental state": a practical method for grading the cognitive state of patients for the clinician. J Psychiatry Res 1975;12: Collins C, Wade DT, Davies S, Horne V. The Barthel Index: a reliability study. Int Disabil Stud 1988;10: Herrmann C. International experiences with the Hospital Anxiety and Depression Scale a review of validation data and clinical results. J Psychosomatic Research 1987;42: Pop Bogatean M, Hancu N. People with type 2 diabetes facing the reality of starting insulin therapy: factors involved in psychological insulin resistance. 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Drug Ther Bull 2004;42: National Institute for Clinical Excellence. Guidance on the use of longacting insulin analogues for the treatment of diabetes- insulin glargine. December 2002(online). full_guidance.pdf. 26. Owens DR, Zinman B, Bolli G. Alternative routes of insulin delivery. Diabetic Med 2003;20: Hermansen K, Ronnemaa T, Petersen AH, Bellaire S, Adamson U. Intensive therapy with inhaled insulin via the AERx Insulin Diabetes Management System. Diabetes Care 2004;27: Taylor C, Towse K, Reza M et al. Transferring elderly patients to insulin: a prospective study of diabetes nurses physicians and patients perceptions. Pract Diab Int 2002;19: Schwartz AV, Hillier TA, Sellmeyer DE et al. Older women with diabetes have a higher risk of falls: a prospective study. Diabetes Care 2002;25: DeWitt DE, Hirsch IB. Outpatient insulin therapy in type 1 and type 2 diabetes mellitus. JAMA 2004;289: VOLUME 5 ISSUE 1. JANUARY/FEBRUARY