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Introduction
Case Study
Glycaemic targets
Hypoglycaemia
Microvascular complications of diabetes
Cardiovascular risk prevention
Specific medication
Specific drugs for type 2 diabetes
Other important factors
Conclusion
References
Introduction
This review, using a clinical case scenario, aims to give a comprehensive overview of some of the problems associated with managing diabetes in older patients. These include blood glucose management and glycaemic targets, hypoglycaemia, cardiovascular risk protection, medication use and microvascular disease. Using consideration of all these matters, the clinician can have a sound foundation to assist with clinical decision making.
Case study
An 83-year-old female with a background history of vascular dementia who is being treated with insulin for her type 2 diabetes presents to the accident and emergency department after being found unconscious at her nursing home. When the paramedics arrived it was discovered that she was hypoglycaemic with a capillary blood glucose reading of 1.8 mmol/L. She was successfully treated with a bolus of intravenous glucose. By the time she arrived at the hospital her conscious level had improved and her blood glucose reading had normalised to 6.3mmol/L. On review, the admitting team established that she had been suffering with diarrhoea and vomiting for the last two days with reduced oral intake. Her insulin had been administered the morning of admission at her usual dose (she was taking a twice daily pre-mixed preparation of insulin). The diagnosis was insulin-induced hypoglycaemia in the context of a viral gastroenteritis. Her hypoglycaemia and gastroenteritis were managed in hospital and she was discharged back to her nursing home on a once daily preparation of insulin, which was solely a ‘long-acting’ preparation upon the advice of the attending diabetes specialist nurse.
This case highlights one of the many challenges faced by clinicians managing all patients but specifically elderly persons with diabetes. Diabetes, worryingly, is showing an increasing trend worldwide. It is thus imperative that all clinicians have familiarity and confidence in dealing with patients who suffer with the illness. The rate of newly diagnosed diabetes exponentially increases with age but tends to plateau after age 85 years with approximately 25% of people over the age of 65 suffering from the condition.1 Because of the high prevalence of comorbidities, there are many factors to consider in order to safely manage this cohort of patients.2
Glycaemic targets
Traditionally, diabetes-related research has championed intensive management of hyperglycaemia with the aim to achieve lower haemoglobin A1C (HbA1c) concentrations. This is paramount as lowering the HbA1c is associated with reduction of both micro- and macro-vascular complications of diabetes. Reduction in blood glucose readings generally also prevents dangerous emergencies associated with diabetes-hyperosmolar hyperglycaemic state and diabetic ketoacidosis. These conditions carry a high mortality rate and every effort to prevent their development is crucial. Consistent hyperglycaemia can lead to osmotic symptoms that can pre-dispose to fluid and electrolyte disturbances.
It is important to note that the larger and most reliable studies advocating the lowering of HbA1c were conducted exclusively in patients under the age of 65 years.3, 4 There are however studies that have specifically looked at an older group of patients with greater burden of preexisting cardiovascular disease and these have stressed caution with intensive glucose control especially given the risk of hypoglycaemia. One study highlighting this risk has shown a ‘U- shaped’ relationship between HbA1 and mortality in patients with diabetes aged ≥60 years.5
The ACCORD study showed increased mortality with intensive glycaemic management in the elderly6 while other studies have shown an overall nonbeneficial role in reducing cardiovascular mortality when intensive blood glucose management is sought despite there being a reduction in diabetes-related nephropathy.7, 8 This is essential when considering what our traditional HbA1C targets are. To reduce the risk of complications the optimal HbA1c is considered to be less than 7% (or 53mmol/mol).
The European Diabetes Working Party for Older People 2011 Clinical Guidelines for Type 2 Diabetes aims to suggest achievable and safe glycaemic targets in those over the age of 70. In patients who are free of major comorbid disease a target HbA1c of 7–7.5% (53–59mmol/mol) should be sought, while those with frailty (significant comorbidity, care home resident and with high risk of hypoglycaemia) this target should be relaxed to 7.6–8.5% (60–69mmol/mol). Below those age groups, and in the absence of disabling comorbidity, the HbA1c target should be intensified for the reasons highlighted above.
It is vital to stress that the studies alluded to above have shown a correlation with duration of diabetes and ability to prevent both morbidity and mortality. The UKPDS, a landmark study in diabetes, in its 10 year follow up study showed a “legacy effect” for treating hyperglycaemia, suggesting that starting with intensive therapy at diagnosis led to better long term outcomes, thus encouraging urgency in treating newly diagnosed diabetics. The aforementioned studies, which showed less beneficial outcomes, were carried out in patients with established diabetes for several years. This leads to the conclusion that addressing glycaemia at a later course in the disease process is less beneficial. This is key because the commonest age range for a new diagnosis of diabetes is 45–649 and hence if diabetes is treated early, the long term success will be better.
Hypoglycaemia
Hypoglycaemia can be an extremely debilitating symptom, as well as carrying potentially dangerous consequences with it. Older patients in general may be more prone to severe hypoglycaemia compared to younger persons possibly as a result of less severe warning symptoms.10 Not surprisingly, the risk is inversely proportionate to the level of glycaemic control with patients with an HbA1c of ≤6.0% (42 mmol/mol) being at the highest risk.5 The choice of medication influences the development of a low blood glucose with insulin and sulfonylureas carrying the highest risk. Older patients are more likely to have concurrent renal disease,11 which in itself is an independent risk factor for medication induced hypoglycaemia.12
Hypoglycaemia can cause significant psychological distress as well as negatively affect the general confidence of the elderly patient.13 It is also associated with other forms of serious morbidity, for example, precipitating events such as cerebrovascular and myocardial ischaemia alongside significant physical injury.14 Therefore it is vital that every effort is made to prevent hypoglycaemic events, such as relaxing blood glucose targets, exercising caution with the dosage of medication, as well as educating both patients and their carers both on prevention and treatment of hypoglycaemia. Those with impaired ability to self-manage or communicate symptoms of hypoglycaemia should have a particular focus on preventative measures.
Microvascular complications of diabetes
Older people are more likely to suffer with crippling effects of the microvascular complications of diabetes. Eye disease, renal disease and foot disease all carry unique problems associated with them, but they all share in common a devitalising effect on an individual. All of these complications are more likely to occur with a longer duration of diabetes.15 People with visual disturbance16 or foot disease17 are more likely to suffer with falls. Foot disease can also lead to debilitating foot amputation, which also has a higher prevalence in the over 50 age group.
Diabetes-related renal disease is one of the important and common conditions requiring dialysis. Nephropathy in its own right signifies greater cardiovascular risk, but it is paramount to think about the implications of dialysis and the issues surrounding that such as frequent hospital visits, infections (both with peritoneal and haemodialysis), depression, impaired quality of life and mortality.
In an older person with diabetes, it is thus imperative to consider pre-existing complications and their impact as well as screen for and prevent any further complications. This further adds to the case of individualised care.
Cardiovascular risk prevention
Diabetes as a disease entity is a major risk factor for the development of cardiovascular disease.18 Though optimisation of glycaemic control is essential, the other facets for preventing cardiovascular disease need to be managed appropriately especially given that increasing age is a compelling risk factor for cardiovascular mortality and morbidity.19 Issues such as hypertension need to be treated effectively, but careful consideration should be given to adverse events related to over-treatment, such as hypotension-related syncope and falls. Lipid lowering therapy should be used where appropriate as this has a key role in improving cardiovascular outcomes, even in the elderly.20, 21 This benefit has also got to be weighed against the risk of sideeffects that are potentially related to drug treatment such as myalgia, which can affect quality of life.21
Other factors, such as encouragement of exercise and healthy diet as well as smoking cessation should continue to be promoted, where appropriate.
Aspirin use for prevention of cardiovascular disease is an area that has been debated extensively. There is no doubt that aspirin confers a net benefit in secondary prevention in those with established cardiovascular disease.22 Its role in primary prevention is questionable because of the increased bleeding risk associated with the drug. There is insufficient evidence to advocate for the use of aspirin in people with diabetes for the sake of primary prevention in individuals who would otherwise be at low risk for cardiovascular disease.23 Thus, by inference, a careful assessment considering the risk of cardiovascular disease should be balanced against the bleeding risk before prescribing aspirin as a prophylactic life prolonging measure.
Specific medication
There needs to be a prudent approach when considering medication use in the elderly. Within the scope of diabetes there is now a plethora of options with regards to pharmaceutical management. Arguably, there is a role for every type of anti-hyperglycaemic agent, but that role must be clearly defined and the drug choice made on the basis of a careful individual care plan with a focus on shared decision making. The choice of treatment should take into account factors such as hypoglycaemia, renal function, drug interactions with other medication (in a group of patients often on polypharmacy), side-effects, contraindications, ease of use for the patient, storage issues and patient choice.
Specific drugs for type 2 diabetes
Metformin
Metformin should be considered as the first-line oral anti-diabetic drug in elderly patients with type 2 diabetes.24 The advantages include metformin being effective and lowering diabetes related end-points including reduction in cardiovascular and all-cause mortality.4 It is generally welltolerated, does not cause hypoglycaemia (when used as monotherapy) and has a favourable cost. However, it must be used with caution in the elderly considering the potential for gastro-intestinal side effects as well as the risk of lactic acidosis in endorgan dysfunction, in particular renal disease.25
Sulfonylureas
Sulfonylureas are generally considered as secondline therapy for type 2 diabetes, even in the elderly.24 As with metformin, this class of drug is generally well tolerated but by far the most important concern is the predisposition towards hypoglycaemia.
The risk of hypoglycaemia is particularly problematic with longer-acting sulfonylureas such as glibenclamide.26, 27 This risk of hypoglycaemia is enhanced in those with kidney disease28 and in those using combination therapy with other antidiabetic agents.29
Dipeptidyl Dipeptidase 4 (DPP-IV) inhibitors
Dipeptidyl Dipeptidase 4 (DPP-IV) inhibitors provide a useful choice as these, like metformin, are not individually causally linked with hypoglycaemia and have been shown to enhance insulin sensitivity.30 The other advantage this class of drug confers is the relative safety in renal dysfunction.31 There are also studies that show that DPP-IV inhibitors are both effective and well tolerated in the elderly.32 The cost of these drugs must be borne-in-mind and as such this can prove to be a limiting factor.
Glucagon like peptide (GLP) 1 agonists
Glucagon like peptide (GLP) 1 agonists can be considered in the elderly, but must be used with caution. These drugs need to be delivered by injection with the frequency of drug, depending on preparation, varying between twice daily and once weekly. This flexibility can be useful especially if the ability of the individual to self-administer such medication is in doubt. As with other antihyperglycaemic agents, they need to be used with caution in those with renal disease.33 The other important considerations include their effect on weight (these drugs generally promote weight loss which is not always desirable in the elderly), as well as their potential adverse gastro-intestinal side-effects.34 This limits their use in frail and underweight patients, but could be useful in obese patients. The cost of these drugs, as with DPP-IV inhibitors, can also be an obstacle.
Sodium glucose co-transporter 2
Sodium glucose co-transporter 2 (SGLT-2) inhibitors are a new and interesting class of drugs. They work by promoting renal excretion of glucose by lowering the renal threshold for glycosuria. Certain drugs within the class have been shown to be effective within the elderly population and are generally safe.35 This benefit must be weighed against the potential side effects which include increased pre-disposition towards urinary tract infections and genital mycotic infections, which can be a significant concern in the elderly.35 The cost of these drugs is also a factor that needs to be evaluated carefully before choosing them. As with GLP-1 agonists, they also promote weight loss, albeit to a lesser extent, which can be either advantageous or disadvantageous depending on the individual.
Thiozolinediones
Thiozolinediones improve insulin sensitivity however their use has been limited because of increased risk of fluid retention and therefore the potential for worsening heart failure, weight gain and the development of oedema, increased fracture risk, and concerns over malignancy of the bladder.36
Insulin
The use of insulin should always be considered carefully, especially when used with other antidiabetic medications with an emphasis on ‘situationspecific’ decisions. Despite the obvious concern of hypoglycaemia, it must be stressed that when indicated, insulin therapy should not be delayed.24 Elderly people are at higher risk of visual impairment and more likely to have joint disease,37 which can influence specific insulin delivery devices making these elements of care requiring utmost attention.
Other important factorsn
Older people with diabetes are more likely to suffer with cognitive impairment than those without the condition.38 Cognitive impairment in turn makes the management of both hyper and hypoglycaemia more challenging. Depression is also more common in people with diabetes.39 Diabetes is an important cause of physical disability and the effects of this are further translated into ill consequences of both physical and mental health. People with diabetes are also more likely to require hospital admission with longer hospital stays even if the admission was not primarily linked to the diabetes itself.40
Conclusion
Diabetes in the over 50 age group is definitely a challenging condition to manage. There are many different components of the disease itself and its treatment that require a comprehensive assessment. The role of shared decision making with full involvement of patients and their carers cannot be stressed enough and more importantly, care should be personalised for each individual. There should also be a focus on multidisciplinary team working as this unique patient group provides a challenge that requires a holistic approach.
Conflict of interest: none declared
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