Diagnosis and management of diabetes in older people

Diagnosis and management of diabetes in older people Anne Kilvert 1 MD, FRCP, Consultant Physician Charles Fox 1 BM, FRCP, Consultant Physician 1 Northampton General Hospital, Cliftonville, Northampton, UK Correspondence to: Dr Anne Kilvert, Consultant Diabetologist, Northampton General Hospital, Cliftonville, Northampton NN1 5BD, UK; email: Anne.Kilvert@ ngh.nhs.uk Abstract The incidence of diabetes has plateaued since 2004, although the prevalence continues to rise. The highest incidence is in people over the age of 70 years, most of whom have type 2 diabetes; a minority have type 1, which can present at any age. Type 1 diabetes may present more slowly in older people, a condition sometimes known as latent autoimmune diabetes in adults (LADA). Older people with diabetes have more than double the risk of cardiovascular disease compared to their non-diabetic peers, and the risk of diabetes-related major lower limb amputation is twice as high in those over 75 years compared with the 40 64 age group. Treatment targets for glycaemic control, blood pressure and cholesterol should be individualised in older people, taking into account factors such as functional status, life expectancy and comorbidities, including visual impairment. In some individuals the risk of adverse effects from medication (hypoglycaemia, postural hypotension) may outweigh the potential benefits. Treatment should be selected based on functional status and comorbidities, and changing circumstances such as declining renal function, declining appetite, weight loss or cognitive changes should prompt a medication review. Hypoglycaemia is a particular threat in this age group. There is a high prevalence of diabetes in care homes, which should have policies in place for screening for diabetes, the management of people with diabetes and training of staff. Copyright 2017 John Wiley & Sons. Practical Diabetes 2017; 34(6): 195 199 Key words older people; type of diabetes; treatment targets; hypoglycaemia; care homes Introduction Diabetes can present at any age but in older people the presence of other medical problems complicates its management. It is even difficult to define older as there is no direct link between chronological age and functional performance. We will take the accepted cut off of 65 years of age to mean older, with the important proviso that many people with diabetes in this age group are extremely fit and well and should be managed in the same way as their younger counterparts. Incidence of diabetes in older people Despite all the publicity about the increasing prevalence of type 2 diabetes, the incidence in the UK appears to have plateaued since 2004. The encouraging explanation for this paradox is that people with diabetes are living longer. The incidence data come from several sources which include the following. The Health Improvement Network (THIN), 1 which analysed more than 8 million electronic records from 550 GP practices, broadly representative of the UK population, between 2000 and 2013. The Scottish national diabetes register, which published data from 2004 to 2013. 2 THIN reported an overall rise in incidence of type 2 diabetes from 3.69 to 3.99 per 1000 person-years at risk (PYAR) in men and from 3.06 to 3.73 per 1000 PYAR in women. The peak incidence in 2004 coincided with the introduction of the quality outcomes framework (QOF), which may have encouraged the recording of new diagnoses. The Scottish study shows that the overall incidence of type 2 diabetes in Scotland has been stable between 2004 and 2013 at 4.88 per 1000 PYAR in men and 3.3 in women. Both UK and Scottish data show an increase in prevalence of type 2 diabetes from 2 3% to 5% over the PRACTICAL DIABETES VOL. 34 NO. 6 COPYRIGHT 2017 JOHN WILEY & SONS 195

study periods, probably because people are living longer. The THIN data show that the highest incidence of type 2 diabetes for both men and women is in the 70 79 age group at 12.7 and 10.3 per 1000 PYAR for men and women respectively, with the 60 69 and 80 89 age groups coming second and third. The Scottish data 3 show a similar picture: in both men and women the incidence rates were highest at 75 years, although both groups showed a slight decline in incidence over the course of the observation period. (Figure 1.) So we can be sure that people in their 7th, 8th and 9th decade are having to cope with a new diagnosis of type 2 diabetes. What about type 1 diabetes? Figures for the incidence of type 1 diabetes by age are difficult to establish, partly because the accuracy of the diagnosis is uncertain in older people. There is no doubt that classical type 1 diabetes can develop at any age 4 although the presentation in older people is often more gradual, leading to misdiagnosis as type 2 diabetes. Determining the type of diabetes in older people People diagnosed over the age of 65 years are likely to have type 2 diabetes but, as with all adults, the possibility of type 1 must be considered. Those with type 2 diabetes are usually overweight but overweight people may also develop type 1 diabetes, so weight is not an absolute discriminator. The classical presentation of type 1 diabetes rapid onset of severe symptoms, significant weight loss and ketonuria should raise suspicion of type 1 diabetes but this is not the norm in older patients. Type 1 diabetes in this age group frequently has a gradual onset of symptoms, only recognised as type 1 when oral medication fails to have an effect. 5 The term LADA (latent autoimmune diabetes in adults) has been used to describe people with the immunological characteristics of type 1 diabetes (anti-gad, insulin autoantibodies, islet cell antibodies) who do not require insulin within the first six months of diagnosis. 6 LADA is linked with other Men Incidence rate per 1000 person-years Ages: 14 12 10 8 6 4 75 years 65 years 55 years 45 years 2 2004 2006 2008 2010 2012 Year Figure1. Age-specific trends in incidence rates of type 2 diabetes among people in deprivation decile 5 in Scotland between 2004 and 2013. (Reproduced from: Read SH, et al. Diabetologia 2016; 59:2106 13) 2 autoimmune conditions within the spectrum of type 1 diabetes and shares a similar genetic profile. 7 There is debate about whether LADA is a separate entity or part of the spectrum of type 1 diabetes since the only feature which distinguishes it from type 1 is the delayed need for insulin. The UK Prospective Diabetes Study found that in a cohort of people aged 55 65 at the time of diagnosis of type 2 diabetes, 4% had islet cell antibodies and 7% had anti-gad antibodies. In this older cohort, antibody-positive individuals were phenotypically identical to those with type 2 diabetes but were more likely to require insulin within the first six years compared with their antibody-negative peers. 8 The messages are: Type 1 diabetes does not always present in a classical way in older people. Adults of all ages may develop more slowly progressive autoimmune type 1 diabetes, sometimes known as LADA. The possibility of type 1 diabetes should be considered in anyone who does not respond to oral therapy, particularly those who are not overweight at diagnosis. Incidence rate per 1000 person-years Women Ages: 14 12 10 8 6 4 75 years 65 years 55 years 45 years 2 2004 2006 2008 2010 2012 Year Prognosis Whether older people develop diabetes in middle age or later in life, they have more than double the risk of cardiovascular disease and end stage renal disease, compared with their non-diabetic peers. Retinopathy is more common in those who have had diabetes since middle age but, retinopathy apart, the increased risks associated with diabetes in the >65 years age group do not seem to be linked to duration of diabetes. This is probably because the other microvascular complications (nephropathy and peripheral neuropathy) are both associated with premature death, which has a greater impact on those diagnosed in middle age. 9 Although there is evidence that major amputation rates are decreasing overall in people with diabetes, the diabetic population aged over 75 years has twice the risk of a major lower limb amputation compared to the 40 64 age group. 10 Treatment targets As people age, additional factors must be considered when agreeing targets for glycaemia, blood pressure and cholesterol. The risks of polypharmacy increase and side 196 PRACTICAL DIABETES VOL. 34 NO. 6 COPYRIGHT 2017 JOHN WILEY & SONS

effects such as hypoglycaemia, dehydration, and postural hypotension can have serious consequences. Evidence on which to base targets is sparse, as many trials exclude older people and those with comorbidities. Targets need to be individualised, balancing potential benefits against the risks of tight glycaemic and blood pressure control; the risk of adverse effects restricts the treatment choice. Glycaemic targets What can we learn from the trials of the effect of glycaemic control on diabetes complications? The UKPDS provides good evidence for the medium- and long-term benefit of early tight control (HbA1c 53 59mmol/mol) but subsequent trials (ACCORD, ADVANCE and VADT), which recruited older people and targeted a lower HbA1c (<42 48mmol/mol), failed to show such clear benefits. The ACCORD trial was notorious for showing that tight glycaemic control was linked to higher mortality. The excess mortality was in the under 65 age group, but those over 75 had twice the number of hospital visits for severe hypoglycaemia. 11 An observational study of 72 310 people aged >60 years showed a U-shaped association between HbA1c and mortality, with the risk of diabetes complications or death rising when the HbA1c was above 64mmol/mol and mortality rising when the HbA1c fell below 42mmol/ mol. 12 No difference was detected between age groups 60 69, 70 79 and >80 years. Doubts raised by these studies have led the American Diabetes Association and the European Diabetes Working Party (EDWP) for Older People to caution against tight control and to advise taking functional state rather than chrono logical age into account when determining the target for an individual. It takes up to six years for the benefits of good control to emerge, so factors reducing life expectancy (advanced age, frailty and comorbidities) should be taken into account. Tight glycaemic control in older people carries its own risks of cardiovascular events and hypoglycaemia. The EDWP suggests a target HbA1c of 53 58mmol/mol for fit older people and 59 69mmol/mol for the frail. 13 However, even a target of 69mmol/ mol may be risky in frail patients, where the aim should be to avoid hypoglycaemia and symptomatic hyperglycaemia. It is essential to agree goals and management strategy with patients and/or carers. Blood pressure The evidence for lowering blood pressure comes from large trials, which included older people with diabetes, and benefit was seen within one year of starting treatment. The need to treat high systolic pressure is undisputed but the ideal target is not clear. Given that a low diastolic pressure is a risk factor for mortality in the elderly, and that over-zealous treatment increases the risk of postural hypotension and falls, individual risk should be taken into account. Evidence from a post hoc analysis of the VADT study suggests that the target systolic pressure should be less than 140mmHg but the diastolic should not be lower than 70mmHg. 14 Cholesterol Large trials of cholesterol lowering treatments have included people with diabetes and those aged >80 years. A meta-analysis of 14 trials of statin therapy in primary prevention included 18 686 people with diabetes and showed a 20% relative reduction in major adverse vascular outcomes in those under and over 65 years. 15 Similar outcomes have been demonstrated for secondary prevention and, as the effect is seen relatively rapidly (within one to two years), only those with limited life expectancy will fail to benefit. Treatment options Lifestyle Diet and exercise are the central pillars of lifestyle changes recommended to people newly diagnosed with diabetes but advice should be modified depending on functional status, not chronological age. For those who are fit and well, recommendations should be as for younger people. Advice should be adapted for those with disabilities. The normal ageing process leads to sarcopenia and an irreversible reduction in the number of neurones supplying the muscles; 16 older people with diabetes may have additional nerve damage due to neuropathy, which further reduces their activity. 17 A number of physiological and psychological factors cause people to slow down with age and when this process begins to interfere with normal daily living, it can be described as frailty. Although there is no universally agreed definition of frailty, it is a useful concept and approximately 10% of people aged 65 75 and 50% of those over 80 years meet this description. Frailty covers a wide range of conditions and, while its course is typically downhill, there is always an opportunity to reverse the process by increasing physical activity. Even people who have been sedentary throughout their lives can increase longevity and cognition by taking up an exercise programme in old age. 18,19 However, it appears that serious exercise is needed to make a difference: 45 minutes of moderate intensity exercise two to three times a week. 20 There seem to be no risks associated with programmes involving light or moderate exercise but intense exercise regimens carry a risk of one cardiovascular event per 100 years of vigorous activity. 21 Despite all the positive evidence, the uptake of formal activity programmes is low in older people, which reflects the difficulty of changing behaviour in this age group. Oral therapy and GLP-1 analogues The range of medication available for treatment of type 1 and type 2 diabetes in older people is the same as for younger age groups, but the choice may be limited by impaired renal function, risk of hypoglycaemia or inability to cope with complex regimens. As people age it is important to be on the lookout for changes which may require a change in treatment: Decline in renal function. Reduced or erratic nutritional intake (risk of hypoglycaemia). Weight loss (leading to reduction in insulin resistance). Cognitive or visual impairment (may lead to dosage errors). PRACTICAL DIABETES VOL. 34 NO. 6 COPYRIGHT 2017 JOHN WILEY & SONS 197

Older people taking sulphonylureas are at particular risk of hypoglycaemia and this may become chronic, presenting as confusion or cognitive impairment (case study 1). Those with cognitive impairment may forget to eat, increasing the risk of hypoglycaemia. An HbA1c below 53mmol/mol should raise the possibility of hypoglycaemia and this should prompt dose reduction or total withdrawal of the sulphonylurea. Higher HbA1c levels do not exclude the possibility of hypoglycaemia. Table 1 shows the treatment options and the modifications which may be required. Insulin Whether the person has type 1 or type 2 diabetes, the insulin regimen should be tailored to the needs of the patient and adapted if circumstances change. Age in itself is not a factor in determining the regimen; people who develop type 1 diabetes later in life can learn to manage a basal bolus regimen or even an insulin pump (case study 2). However, if functional status declines and cognition is impaired, the insulin regimen must be simplified and glycaemic targets relaxed. It is important to reassess the person s ability to manage their diabetes with this in mind. For people with frailty or comorbidities, a single daily insulin regimen, designed to avoid hyper- and hypoglycaemia, possibly supervised by a district nurse, may be safer than a combination of oral therapies. Residential and nursing homes There is increasing concern about the way diabetes is detected and managed in care homes. Diabetes UK produced practical guidelines for diabetes care in residential homes in 2010; 22 awareness and uptake of these guidelines were audited in 2014. 23 In the audit, 2043 out of 9000 care homes (23%) responded to a diabetes questionnaire. The prevalence of diabetes was surprisingly low at 10.4%, which suggests that they are not carrying out the recommended routine screening for diabetes, which would increase the prevalence to 20% or more. 24 The Case study 1: Ernest Aged 82 years. Living with wife in own home Type 2 diabetes on metformin 500mg bd and gliclazide 40mg od HbA1c 46mmol/mol Concern about his ability to cope at home; frequent falls and increasing confusion Admitted following a fall. Very confused Blood glucose 2.8mmol/L on admission Treated for hypoglycaemia but usual medication continued Fasting blood glucose 2 4mmol/L for next 3 days Gliclazide stopped. Fasting blood glucose rose to 7 8mmol/L Over next few days mobility improved and confusion resolved Discharged home to wife Diagnosis: chronic hypoglycaemia Message Sulphonylureas can cause unexplained confusion and frailty, which may be corrected by stopping the drug Medication Risks for older people Action Metformin DPP-4 inhibitors SGLT2 inhibitors Pioglitazone Case study 2: Felicity Impaired renal function increases risk of lactic acidosis Dose reduction required in impaired renal function (except linagliptin) Postural hypotension and dehydration Fluid retention and increased risk of heart failure. Increased fracture risk New diagnosis of diabetes aged 67 Body mass index 23kg/m 2 Failed to respond to oral therapy Anti-GAD positive. Diagnosis of type 1 diabetes (latent autoimmune diabetes in adults) Insulin commenced Changed from twice-daily mixture to basal bolus DAFNE course Blood glucose very labile with swings from high to hypo, causing great anxiety HbA1c 84mmol/mol Insulin pump approved Significant improvement in blood glucose control and confidence HbA1c 60mmol/mol with few hypos Message An insulin pump may transform lives at any age Reduce dose if egfr <50 and stop if <30 Reduce dose or change to linagliptin if the egfr <50 Do not use if egfr <60. Not recommended for people >75 years of age Do not use if risk of heart failure Sulphonylureas Hypoglycaemia Use short-acting sulphonylurea only (e.g. gliclazide). Look out for evidence of hypoglycaemia and reduce or stop if hypos identified GLP-1 agonists Do not use if impaired renal function Reduce dose if egfr <50 and stop if <30 Table 1. Therapeutic options (excluding insulin) for blood glucose lowering in elderly people 198 PRACTICAL DIABETES VOL. 34 NO. 6 COPYRIGHT 2017 JOHN WILEY & SONS

important findings of the audit were as follows: 47% were unaware of the Diabetes UK guidelines. 37% had no written policy for hypoglycaemia management. 65% had no policy for screening for diabetes. 63% had no designated staff member with responsibility for diabetes. 64% did not have a copy of the resident s annual diabetes review (i.e. poor communication with primary care). 33% did not provide staff with access to training in diabetes care Under pressure from professional organisations, the Care Quality Commission has produced guidance for those inspecting the quality of care for diabetes in care homes. 25 Sadly, residential homes are subject to increasing financial constraints and they will find it hard to achieve the high standards demanded by the CQC. Declaration of interests There are no conflicts of interest declared. References 1. Sharma M, et al. 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Key points The incidence of diabetes increases with age and peaks at 70 79 years Type 1 diabetes may present at any age Diabetes doubles the cardiovascular risk in older people Treatment targets and regimens need to take into account functional status and life expectancy Targets and medication need to be re-assessed in response to physical and cognitive changes Care homes should have policies in place to detect and manage diabetes in their residents 5. Kilvert A, et al. Insulin dependent diabetes in the elderly. Diabet Med 1984;1:115 8. 6. Tuomi T, et al. Antibodies to glutamic acid decarboxylase reveal latent autoimmune diabetes mellitus in adults with a non-insulin-dependent onset of disease. Diabetes 1993;42:359 62. 7. Cervin C, et al. Genetic similarities between latent autoimmune diabetes in adults, type 1 diabetes, and type 2 diabetes. Diabetes 2008;57:1433 7. doi: 10.2337/db07-0299 [accessed 27 February 2017]. 8. Turner R, et al. UKPDS 25: autoantibodies to isletcell cytoplasm and glutamic acid decarboxylase for prediction of insulin requirement in type 2 diabetes. UK Prospective Diabetes Study Group. Lancet 1997;350:1288 93. 9. Selvin E, et al. The burden and treatment of diabetes in elderly individuals in the U.S. Diabetes Care 2006;29:2415 9. 10. Li Y, et al. Declining rates of hospitalization for nontraumatic lower-extremity amputation in the diabetic population aged 40 years or older: U.S., 1988 2008. Diabetes Care 2012;35:273 7. 11. Miller ME, et al. The effects of baseline characteristics, glycaemia treatment approach, and glycated haemoglobin concentration on the risk of severe hypoglycaemia: post hoc epidemiological analysis of the ACCORD study. BMJ 2010;340:b5444. doi: https://doi.org/10.1136/bmj.b5444 [accessed 5 March 2017]. 12. Huang ES, et al. Rates of complications and mortality in older diabetes patients: The Diabetes and Aging Study. JAMA Intern Med 2014;174:251 8. 13. Sinclair AJ, et al. European Diabetes Working Party for Older People 2011 clinical guidelines for type 2 diabetes mellitus. Executive summary. Diabet Metab 2011;37(Suppl 3):S37 8. 14. Anderson RJ, et al. Blood pressure and cardiovascular disease risk in the Veterans Affairs Diabetes Trial. Diabetes Care 2011;34:34 8. 15. Baigent C, et al.; Cholesterol Treatment Trialists (CTT) Collaborators. Efficacy and safety of cholesterol-lowering treatment: prospective metaanalysis of data from 90 056 participants in 14 randomised trials of statins. Lancet 2005;366: 1267 78. 16. McPhee JS, et al. Physical activity in older age: perspectives for healthy ageing and frailty. Biogerontology 2016;17:567 80. 17. Zhao G, et al. Physical activity in U.S. older adults with diabetes mellitus: prevalence and correlates of meeting physical activity recommendations. J Am Geriatr Soc 2011;59:132 7. 18. Hamer M, et al. Taking up physical activity in later life and healthy ageing: the English longitudinal study of ageing. Br J Sports Med 2014; 48:239 43. 19. Lautenschlager NT, et al. Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: a randomized trial. J Am Med Assoc 2008;300:1027 37. 20. Forster A, et al. Is physical rehabilitation for older people in long-term care effective? Findings from a systematic review. Age Ageing 2010;39:169 75. 21. Powell KE, et al. Physical activity for health: what kind? How much? How intense? On top of what? Annu Rev Public Health 2011;32:349 65. 22. Diabetes UK. Good clinical practice guidelines for care home residents with diabetes. 2010. Available at: https://www.diabetes.org.uk/documents/about% 20Us/Our%20views/Care%20recs/Care-homes-0110. pdf [accessed 16 March 2017]. 23. Institute of Diabetes for Older People, Association of British Clinical Diabetologists. England-wide care home diabetes audit. Executive summary. 2014. Available at: http://bit.ly/1ry5yqp [accessed 16 March 2017]. 24. Taylor A. Diabetes care in care homes and for the housebound. J Diab Nursing 2003;7:384 6. 25. Fox C, Kilvert A. The state of diabetes care in residential homes. J Diab Nursing 2016;20:142 6. Visit our website The Practical Diabetes website carries a wide range of additional information in support of the journal. You can access the current issue online, search through back issues in our archive or download our growing collection of ABCD position statements. Find out more at www.practicaldiabetes.com PRACTICAL DIABETES VOL. 34 NO. 6 COPYRIGHT 2017 JOHN WILEY & SONS 199