Frailty, older people and type 2 diabetes

Type 2 diabetes is one of the most common chronic conditions in older adults, and the number of people over the age of 70 with diabetes is growing worldwide. For example, of the 2.6 million people in the UK with diabetes, at least half are over 65 years old (Diabetes UK, 2010). The prevalence of diabetes in the adult general population is 4.1%, whereas it is more than 10% among people over the age of 65 years (Diabetes UK, 2010). The prevalence approaches 25% in care home residents, who represent people who may require more care and management of comorbidities (Sinclair et al, 2001).

Frailty
Frailty is a condition characterised by reduction in physiological reserve and ability to resist physical or physiological stressors. Frailty is defined based on the presence of three or more of the following: weight loss, weakness, decreased physical activity, exhaustion and slow gait speed. People with diabetes aged 65 and over are more likely to be frail than older adults without diabetes (Abdelhafiz et al, 2015). Around 11% of people with diabetes over the age of 65 are classified as frail (Abdelhafiz et al, 2015).

The biological processes that underlie frailty are still unclear and are likely to be complex and multifactorial. However, sarcopenia is known to be a central component of frailty, and is more common in people with diabetes than people without diabetes (Jang, 2016). The relationship between frailty and hypoglycaemia is likely to be bi-directional (Abdelhahiz et al, 2015). Hypoglycaemia can lead to frailty, and frailty is a risk factor for hypoglycaemia in older people with diabetes.

There are various indexes and scales to classify and diagnose frailty (e.g. Clinical Frailty Scale or CHSA 9-point Scale). The simple FRAIL scale (Box 1) is quick to complete and seems to be as sensitive and specific as other scales (Abdelhafiz, 2015). Some authorities recommend that it be used to screen all people over the age of 70 years for frailty.

Glycaemic targets for older people
Many guidelines on the management of type 2 diabetes do not provide specific guidance for older people; however, the International Diabetes Federation (IDF) produced a global guideline in 2013, solely for the management of people with diabetes over the age of 70: IDF Global Guideline for Managing Older People with Type 2 Diabetes. The guideline recommends relaxing strict glycaemic control in the presence of comorbidities (such as functional dependency, dementia and frailty) to a HbA_1c up to 70 mmol/mol (8.5%; IDF, 2013). This is to reduce the risk of hypoglycaemia, which can lead to confusion and an increased risk of falls and fractures. Hypoglycaemic events can also lead to a higher risk of mortality following hospital admission, and some people may also experience permanent neurological damage. The guideline distinguishes several functional categories of older people with diabetes, and gives specific management recommendations for each category (Table 1). The NICE (2015) guideline on type 2 diabetes also recommends relaxation of glycaemic targets in the presence of frailty and dementia.

Hypoglycaemia in older people
The true prevalence of hypoglycaemia among older people is unknown. Most studies that have tried to address this question rely on the recall of hypoglycaemic episodes by participants. Accurate recall of hypoglycaemia is notoriously difficult in any age group, and none more so than in an older population (Hope and Strain, 2013). For epidemiological purposes, “severe” hypoglycaemia is usually defined as that requiring external assistance for treatment. Episodes of severe hypoglycaemia can also be corroborated with documentary evidence from ambulance services, if the emergency services are required. The difficulties in accurate patient recall of hypoglycaemia episodes was addressed by a carefully designed prospective observational study over 9–12 months in the UK (UK Hypoglycaemia Study Group, 2007). Participants were required to return a data-collection sheet every time they experienced a severe hypoglycaemia episode.

Careful monitoring for hypoglycaemia is required during the treatment of diabetes with insulin and/or sulfonylureas, particularly in the older population. The UK Hypoglycaemia Study Group (2007) found that annual prevalence of sulfonylurea-associated severe hypoglycaemia was 7%, a prevalence similar to that observed in people with type 2 diabetes treated with insulin for <2 years. The prevalence of severe hypoglycaemia among people with type 2 diabetes who had received insulin treatment for >5 years was 25%, and it was 46% in those with long-standing type 1 diabetes (>15 years).

Older people may not experience the typical symptoms of hypoglycaemia, and may have a reduced awareness of the initial sympathetic symptoms (i.e tremor, shaking, sweating) associated with developing hypoglycaemia. Hence, there is less time before the later symptoms of neuroglycopenia occur, such as confusion and decreased conscious level (Matyka et al, 1997). Neurological symptoms such as slurred speech, light-headedness and unsteadiness, in addition to the neuroglycopenic symptoms, tend to be more common in older people with hypoglycaemia than in younger people (Hepburn et al, 1993). These symptoms can be misattributed by people with diabetes or by healthcare professionals to other presentations common in older age. As such, hypoglycaemia in older people may present, for example, as “off legs”, infection, acute confusion, mini-stroke, stroke, fits, or even simply “ageing”. Therefore, it is useful to check that older patients are aware of the symptoms of hypoglycaemia and know how to treat it.

Hypoglycaemia, and the associated fear of hypoglycaemia, affects mental health, quality of life and often contributes to depression; depression itself can be a symptom of hypoglycaemia (Hope and Strain, 2013). The hypoglycaemia can also affect socialisation, activities of daily living, learning and self-care capacity (Barendse et al, 2012).

Treatment considerations
Older people are at an increased risk for adverse medicine-related events due to age-related changes in pharmacokinetics (especially renal elimination) and pharmacodynamics (increased sensitivity).

NICE (2015) guidelines recommend that metformin therapy is the initial monotherapy of choice in treating type 2 diabetes. However, the British National Formulary (BNF; 2009) advises caution in the use of metformin in people with renal impairment, heart failure, hepatic impairment or in those at risk of tissue hypoxia. Sulfonylurea therapy used to be the only first-line glucose-lowering option recommended (NICE, 2009), if metformin was contra-indicated, and as older people with type 2 diabetes are more likely to have renal or hepatic impairment and heart failure, sulfonylurea therapy among older people can be a fairly common occurence. As a result, low HbA_1c in older people on sulfonylurea therapies can be common. A primary care survey of nearly 4000 patients with type 2 diabetes aged 70 years or older found that of those who were on insulin or sulfonylurea therapies, nearly 30% had an HbA_1c of 53 mmol/mol (<7%), and 12% had an HbA_1c of 48 mmol/mol (<6.5%; Hambling et al, 2016). The latest NICE (2015) guideline for type 2 diabetes now recommends that drugs other than sulfonylurea can be used as monotherapy if metformin is contraindicated or not tolerated.

Reducing polypharmacy may be considered among older people with diabetes, if appropriate. In a study of residents with diabetes in nursing homes in Coventry, 63 residents (84%) were being prescribed four or more medications (for diabetes and cardiovascular disease). A total of 15% were on sulfonylurea monotherapy and 24% were on metformin plus sulfonylurea (Gadsby et al, 2011). Regular medication review undertaken in this group has the potential to reduce costs, minimise adverse drug reactions and increase health gain.

Cognitive impairment and dementia
Individuals with dementia have a degree of cognitive impairment that has led to significant memory problems, a degree of disorientation, or a change of personality and who are unable to self care. Physically, they may be relatively well. Dementia is a chronic condition that is becoming ever more prevalent with the ageing population, and there is growing recognition that it may develop earlier in people with diabetes than people without diabetes (Sinclair et al, 2013). There also appears to be an increased risk of dementia in people who have had episodes of severe hypoglycaemia (Hope and Strain, 2013). In addition, people with dementia or cognitive impairment who have diabetes and are treated with insulin or sulfonylurea may be more likely to develop hypoglycaemia than those without dementia. This is often due to confusion following drug regimens and taking extra doses, or being given medications regularly by carers when the individual has not eaten. The relationship between dementia and diabetes, therefore, is also likely to be bi-directional (Yaffe et al, 2013).

Screening for cognitive impairment in primary care using a simple quick test, such as the Mini Cog test, has been shown to be a practical and appropriate cognitive screen for older people with diabetes. The Mini Cog test can be easily integrated into the annual diabetes review of older people to help identify those who may benefit from extra assistance with their management.

Practical action points

• Stop sulfonylurea therapy in an older person with a low HbA_1c (<53 mmol/mol [7%]) and review with a further HbA_1c test in 3–6 months. If additional glucose-lowering therapy is felt to be necessary, consider using an agent with a low propensity to cause hypoglycaemia, such as a dipeptidyl-peptidase-4 inhibitor at appropriate dose for renal function.
• Review agreed glycaemic control targets and see if in the presence of comorbidities a higher HbA_1c target should be used in line with IDF (2013) guidelines.
• Exempt the older person from the Quality and Outcomes Framework glycaemic target clinical indicator (in England, Wales and Northern Ireland).
• Consider screening for frailty (e.g. FRAIL Scale) and cognitive impairment (e.g. Mini Cog) at the diabetes annual review for all people aged 70 years and over.
• Consider the case scenario in Box 2. Is this a familiar scenario? What would you do?

Conclusion
Hypoglycaemia (both mild and severe) is a significant problem in older people with type 2 diabetes on sulfonylurea or insulin therapy. It increases risks of falls, fractures, hospitalisation and death, but as hypoglycaemia in older people can be difficult to recognise, it needs a high index of suspicion. Many with HbA_1c levels indicative of “good” control may be at significant risk. It is good practice to review all frail, older people and those with dementia who have type 2 diabetes to consider whether they may be over-treated and to stop sulfonylurea therapy if hypoglycaemia is felt to be a significant risk.