Diabetes and older people

The population of people aged over 50 years is increasing progressively. People are living longer and the incidence and prevalence of diabetes increases with age. Ageing not only makes diabetes more likely, but diabetes accelerates biological ageing and the onset of other pathologies.

A study in Portsmouth, published in 2009, looked at a sample of 15,095 community-dwelling people aged 75 years and over. Type 2 diabetes and associated health problems were identified using self-reporting, GP records, drug histories, and urine and blood measurements. 1177 people were identified as having type 2 diabetes, giving an overall prevalence in this community of 7.8%, 9.4% for men and 6.8% for women. The age, sex and smoking adjusted odds ratios for various health problems, comparing people with and without diabetes, were proteinuria 1.7, chronic kidney disease stage 4 or 5 1.5, angina 1.3, myocardial infarction 1.5, cerebrovascular events 2.2, low vision 1.6, and foot ulceration 1.7.¹

To prevent these complications, clearly early identification and careful management of people who develop type 2 diabetes is paramount. We have seen a great increase in obesity and sedentary lifestyles, and in the US among older adults aged 65 years or older, 10.9 million people (26.9%) had diabetes in 2010.²

Eight years earlier in Memphis, a cohort of 3,075 well functioning people aged 70-79 years were studied. The prevalence of diagnosed and undiagnosed diabetes was 15.6 and 8% respectively among all participants. The number needed to screen was 10.6. In the multivariate analysis, compared to people without diabetes, those with undiagnosed diabetes were more likely to be men and were more likely to have a history of higher BMI, a larger waist circumference and hypertension. The number needed to screen was lowest in men (9.1), people with hypertension (8.7), people in the highest BMI quartile (6.9) and those with the largest waist circumference (6.8). The conclusions were that in approximately one-third of older people with diabetes, the condition remains undiagnosed. Screening may be more efficient among men and in people with hypertension, high BMI and a large waist circumference.³

Diabetes UK is currently promoting the diabetes risk score calculator (www.diabetes.org.uk/Riskscore), for the general public. However we need to be alert to the individuals at risk when we see them in our routine clinics. There have been numerous risk scores developed recently and these have been the subject of a systematic review in the BMJ.⁴ QDScore, UK is now widely available to health professionals for use in clinical practice. Prevention of diabetes is the “Holy Grail”.

We have made great strides in reducing the risk of both the traditionally recognised microvascular complications (retinopathy, nephropathy and neuropathy), and the macrovascular complications (coronary heart disease, stroke and peripheral vascular disease), but we need to be aware that as diabetes increasingly becomes a disease of older people, we will see less well recognised complications increase, such as cognitive disorders and physical disability, falls, fractures etc. For society these outcomes will have a direct impact on caregivers. The need for care home facilities and a loss of independence has a direct impact on quality of life, and is very expensive.

The guidelines for quality of care in diabetes are based primarily on research conducted among middle-aged populations and their appropriateness in the face of complex complications related to ageing often provides us with clinical dilemmas.

Although NICE provides helpful guidelines for the management of type 2 diabetes,⁵ there are only a few guidelines specifically designed for older people. The most useful is the European Diabetes Working Party for Older people 2011.⁶

The rationale for high quality diabetes care for older people is that screening and early diagnosis may prevent progression of undetected vascular complications, improvement of metabolic control will reduce cardiovascular risk, and improved screening for maculopathy and cataracts will reduce visual impairment and blind registrations. An integrated approach to the management of peripheral vascular disease and foot disorders will reduce the amputation rate and improved primary care and specialist follow-up will reduce hospital admission rates.

Goals for diabetes management in older adults should be set according to the motivation of the individual, the comorbidities, and the presence of complications, resources and support systems available, and the life expectancy of each individual.⁷

For older patients with type 2 diabetes with single system involvement, free of other major comorbidities, a target HbA1c of 7% or less should be aimed for. For those who are frail, dependent, have multisystem disease, are in care homes, including those with dementia where hypoglycaemia risk is high and symptom control and avoidance of hypoglycaemia is paramount, the target HbA1c should be less than 8%.

Recent trials show that aiming for effective glucose control with even lower targets may not always be beneficial and has important implications for older people. In the ACCORD,⁸ ADVANCE⁹ and VADT¹⁰ trials there was a lack of cardiovascular outcome benefit despite HbA1c levels of 6.4%, 6.4% and 6.9% respectively in the intensive arms. There was also increased mortality in the intensive arm of the ACCORD trial, which was terminated early.⁷ The longer term results of the UKPDS trial has shown a sustained benefit in microvascular outcomes and the emergence of cardiovascular benefit despite the early loss of glycaemic differences, suggesting a metabolic memory for good control in the early years.¹¹

We therefore need to focus on very good glycaemic control in the early years, and a more relaxed approach in later years and in those with cardiovascular comorbidities. Enhancement of blood pressure and lipid control should continue throughout.

There was an excellent review of glucose lowering therapies in older adults by KS Kim et al, in the Diabetes and Metabolism Journal 2012.¹²

Metformin is recommended as first line drug therapy for the management of diabetes in most current guidelines because it has proven efficacy in lowering blood glucose, a low risk of hypoglycaemia and low cost.¹³ Its use may be limited in older adults because of comorbidities such as renal insufficiency, hepatic insufficiency or heart failure. Metformin should be avoided in those with an eGFR of less than 30mL/min.¹²

Sulphonylureas (SUs) are cheap and effective, especially when used in combination with metformin. However, hypoglycaemia, particularly in older adults with impaired renal or hepatic function, or a poor oral intake, is a significant side effect. Glibenclamide should be avoided in older adults because it increases the risk of hypoglycaemia. A dipeptidyl peptidase-4 (DPP-4) inhibitor can be used instead of a sulphonylurea when the latter poses an unacceptable risk of hypoglycaemia. Another alternative in this situation is a meglitinide, which may cause less hypoglycaemia than sulphonylureas in those with reduced renal function. However, the need for frequent dosing and high cost tends to limit their use in the NHS.¹²

Incretin-based therapy, either DPP-4 inhibitors or glucagon-like peptide-1 (GLP-1), may be a good choice for older adults with diabetes, because of their proven efficacy, hypoglycaemia is rare unless used with SUs,  tolerability is good apart from nausea and they often lead to weight loss.¹²

Treatment with DDP-4 inhibitors in older adults with diabetes has been associated with a low risk of hypoglycaemia and they do not cause weight increase.¹⁴

There have been no studies specifically designed for older adults with diabetes using the two GLP-1 receptor agonists, exenatide and liraglutide, but there have not been any significant differences in their efficacy and safety between elderly and younger patients.¹⁵

The thiazolidinediones (TZDs) improve insulin sensitivity and reduce hepatic glucose production in the liver. They do not increase the risk of hypoglycaemia and have a more durable action in controlling hyperglycaemia than metformin or sulphonylureas. Precautions need to be taken however, since pioglitazone has recently been linked to an increased risk of bladder cancer.¹⁶ Because these drugs cause weight gain and fluid retention leading to oedema, they should not be used in patients with heart failure NYHA class III or IV.¹² Caution also needs to be observed in patients with bone loss who are at increased risk of fracture, particularly elderly women.^17,18

In older adults, the use of alpha-glucose inhibitors (AGIs) is restricted by their gastrointestinal side effects, and need for frequent dosing,¹² which leads to poor concordance.

Insulin is the most effective anti-hyperglycaemic agent, which can reduce HbA1c by 1.5-3.5%. Insulin therapy is frequently required by older adults with type 2 diabetes, due to the progressive decline of beta cell function with increasing age. Barriers to its use include the cost of monitoring, risk of hypoglycaemia, need for injections, and the complex nature of its administration.¹²  Long-acting basal insulin analogues may be preferable in older adults with diabetes, because of the reduced risk of hypoglycaemia compared to intermediate-acting (Neutral Protamine Hagedorn (NPH)) insulin.¹⁹  These insulins can be used alone or combined with metformin or sulphonylureas.⁶ Rapid-acting insulin, or premixed insulin, can be used if necessary.

In addition to glycaemic control, intensive therapy targeting hypertension, dyslipidemia and microalbuminuria can be effective at preventing cardiovascular morbidity in patients with type 2 diabetes. In the STENO-2 study, intensive treatment aspirin, plus angiotensin receptor antagonists, statins, fibrates and treatment for hypertension as necessary, reduced the risk of cardiovascular and microvascular events by about 50% compared with conventional therapy.²⁰

The publication of the diabetes subgroup of the Heart Protection Study (HPS)²¹ and the Collaborative Atorvastatin Diabetes Study (CARDS)²² have had a major influence on guidelines for the management of diabetes. CARDS was the first randomised controlled trial of statin therapy in patients with diabetes. 2,838 people with type 2 diabetes were randomised to receive either atorvastatin 10mg per day or placebo. Patients were between 40-75 years of age and had at least one of the following risk factors for CVD: hypertension, current cigarette smoking, retinopathy or albuminuria. Patients were excluded if they had clinical CVD, a baseline LDL level >4.12mmol/l or high triglycerides >6.78mmol/l. The primary endpoint was a composite of time to first acute coronary event, fatal or non-fatal stroke and coronary revascularisation. The trial was terminated two years earlier than expected because the pre-specified stopping rule for efficacy had been met. Atorvastatin reduced LDL cholesterol levels by 40% versus baseline, corresponding to an absolute reduction of 1.2mmol/l. There was a 37% reduction in the primary endpoint (p=0.001)²² and a 50% reduction in non-haemeorrhagic stroke (p=0.024).²³

A subsequent analysis of the diabetes subgroup of the Anglo Scandinavian Cardiac Outcomes Trial (ASCOT)²⁴ used a secondary endpoint of major cardiovascular events and procedures to assess the potential benefit of statin treatment (atorvastatin 10mg). There was a 23% reduction associated with statin therapy versus placebo (p=0.036). Importantly in ASCOT, blood pressure (BP) was extremely well controlled, with a mean systolic BP of 134mmHg,²⁵ showing the benefit of statin therapy over and above good blood pressure control.

This data, including the meta-analysis by the CTT collaboration,²⁶ has influenced national guidelines, leading to targets of 4 and 2mmol/l for total and LDL cholesterol respectively.⁵  The US National Cholesterol Education (NCEP) guidelines²⁷ and European ESC/EAS guidelines²⁸ have gone one step further than NICE by recommending a target LDL cholesterol <1.8mmol/l in patients with diabetes and established CVD. The US approach to hypertriglyceridaemia (triglycerides >2.2mmmol/l), which affects many patients with diabetes, is to target LDL cholesterol first then use non-HDL cholesterol as a secondary target for treatment with a goal of 0.8mmol/l higher than the LDL goal.²⁹

Modern diabetes care systems for older people requires an integrated approach with attention to early detection. Time needs to be spent on good patient education and a multidimensional approach to weight, glucose, blood pressure and lipid control, with an emphasis on prevention of diabetes and its complications. Management of uncomplicated cases is straightforward, but in the presence of comorbidities there is an increase in complexity which leads to difficult clinical decision making, with an emphasis on avoiding hypoglycaemia.

Conflict of interest: none declared

References

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