Diabetes and dementia: Addressing the needs of an overlooked population
Diabetes and dementia are on the rise. Projections for the UK suggest that by 2025, 5 million people will have diabetes (90% with type 2 diabetes) and 1 million people will have dementia. The UK government has singled out diabetes and dementia conditions independently as key areas to target moving forward. In addition, there is also a push to manage “multimorbidity” and deal with the complexities of an aging population. It is therefore surprising that the combination of diabetes and dementia is not attracting more attention among clinicians, researchers and policy makers.
Clinical research is still in the initial stages of unravelling the relationship between cognitive impairment and diabetes. However, there is epidemiological evidence indicating that people with diabetes are at twice the risk of developing dementia than those without diabetes. Given the early state of research it is unsurprising to find that a number of mechanisms have been postulated to account for the association between cognitive impairment and diabetes. The leading theories are summarized in the table below:
Proposed diabetes–dementia mechanistic links
Type 3 diabetes mellitus/Alzheimer’s disease
It could be argued that cognitive impairment should be among the recognized list of “diabetes complications”. Indeed, there is a gap in research for long-term diabetes trials to incorporate data on cognitive impairment into their outcomes. Data on glycated hemoglobin (HbA1c) and its link to cognitive impairment appears to support this assertion, as the English Longitudinal Study of Ageing demonstrated that increasing HbA1c is associated with cognitive decline. However, despite the epidemiological link between diabetes and cognitive impairment there is a paucity of data on managing both conditions, and as a result, a lack of guideline implementation.
The limited data on this comorbidity have led to current guidance being based on consensus statements and common sense approaches that focus on relaxing targets and avoiding hypoglycemia via the simplification of regimens. However, to date, there has not been a single study that has looked into the practical aspects of managing of patients with diabetes and dementia. Guidelines issued by organizations such as the American Diabetes Association (ADA), International Diabetes Federation (IDF) and various other working groups do not utilize robust evidence in practice. Rather, they rely on best practice discussion among specialists. It is therefore imperative that future trials are directed towards this area of diabetes care.
Focus of clinical care
There is a clear need for specific focus and understanding in this area due to the complexity of managing patients exhibiting both diabetes and dementia. As always, individualized care is key; however, there are similar trends that are common to patients with both conditions. For instance, a degree of cognitive decline can be expected as patients with diabetes approach old age. In line with these changes, diabetes self-management and awareness can become impaired, potentially leading to poorer adherence and greater reliance on carers/family, regardless of the type of diabetes or treatment employed.
While the focus of diabetes management in older adults tends to be based around the avoidance of hypoglycemia, care must be taken to ensure that medications are optimized, and HbA1c targets (even if lax) are achieved to avoid osmotic symptoms and complications, including hyperosmolar hyperglycemic state or diabetic ketoacidosis.
Guidance on managing patients with diabetes and dementia is mixed. Some larger societies such as the ADA and IDF have specific sections of guidance covering dementia; however, in the UK there is no specific guidance. Currently, there are two key documents that address the issue of diabetes and dementia: specifically the TREND-UK and Institute for Diabetes in Old People (IDOP) guidance. TREND-UK provides practical guidance on managing patients and a working group position statement has also looked at managing patients with both conditions. However, this has been superseded by the IDOP guidelines released in 2017, which deal with frailty in diabetes but also address dementia. A general recommendation given by all three organizations is to aim for an HbA1c between 7% and 8% (53–64 mmol/mol) with further relaxation in advanced and frailer cases (see table below). The focus is on hypoglycemia avoidance and improving life through the adoption of simpler regimens.
HbA1c target recommendations from leading organizations and working groups
International Diabetes Federation. Managing Older People With Type 2 Diabetes: Global Guideline (2012)
7–8% (53–64 mmol/mol)
7–8% (53–64 mmol/mol)
American Diabetes Association. Mild-moderate cognitive impairment (2019)
<8% (64 mmol/mol)
90–150 mg/dl (5–8.3 mmol/l)
100–180 mg/dl (5.5–10 mmol/l) bedtime
American Diabetes Association. Moderate-severe cognitive impairment (2019)
<8.5% (70 mmol/mol)
100–180 mg/dl (5.5–10 mmol/l)
110–200 mg/dl (6.1–11.6 mmol/l)
Reproduced with permission of the editors, British Journal of Diabetes: Management of diabetes and dementia. Puttanna A, Padinjakara N. British Journal of Diabetes 2017; 17: 93–99. doi:10.15277/bjd.2017.139
Practical management for healthcare teams
The first step toward achieving better outcomes in individuals with diabetes and dementia must be increased awareness and acknowledgement of this population and their complex care needs.
In teams that are better educated about diabetes and dementia, active case finding in both primary and secondary care becomes possible, enabling preventative measures to be taken rather than relying solely on reactive interventions. Within primary care, opportunities include assessing coded patients with both conditions, or placing specific focus on care home populations. In the secondary care setting, involvement of the dementia specialist team or nurse and/or the gerontology team allows for further case finding and liaison with diabetes teams. Patients with both diabetes and dementia need a focused and structured assessment, which should result in the production of an individualized management plan.
Determining glycemic target
Assessment must include: a recent HbA1c and/or recent blood sugar readings (depending on whether or not insulin has been prescribed); assessment of self-management skills; who the main carers are (if any); and, caloric intake. Further assessment of hypoglycemia risk, vascular and foot risk, and risk of other complications as well as trends in glycemic control will support the development of a management plan. A target HbA1c and glycemic range should be determined, which will vary in intensity depending on a patient’s life expectancy, self-care needs, comorbidities and expectations (including those of carers or family). It is important that in those with limited self-management skills, carers and family are involved and made aware of the plans.
Type 1 diabetes
Patients with type 1 diabetes can also benefit from assessment of insulin doses to avoid inappropriate dosing with variable caloric intake. With irregular eating patterns, insulin administration may need to be delayed or reduced depending on the amount eaten. This is a developing area with further research needs. Though not specifically for those with cognitive impairment, recent articles have suggested management considerations for the frail older adult with type 1 diabetes.
Medication choice in Type 2 diabetes
Patients with type 2 diabetes and dementia need appropriate medication regimens, which should focus on simplification and lower hypoglycemia risk as these individuals are a particularly vulnerable group. The balance between reducing risk and hyperglycemia can prove tricky and the risk of rebound hyperglycemia must be considered when de-intensification is considered.
To date, no medication has demonstrated a definite benefit in terms of cognitive improvement in patients with established dementia. However, pioglitazone and some glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown potential in cognitive impairment. Current management should address the previously mentioned issues together with the side effect profile and safety of each class of medications. The table below provides an overview of benefits and risks of each medicine class in patients with diabetes and dementia.
Benefits of use
Risks of use
Low risk hypoglycaemia, well tolerated
Risk in renal impairment (dehydration), gastrointestinal side effects, comorbidities can limit use
Quick glucose stabilisation, relatively well tolerated
Increased risk of hypoglycaemia, especially if comorbidities, risk of heart failure
Useful but limited glycaemic control
Long-term effects (cardiovascular/bladder/fracture risk)
Rapid insulin promoting action, useful in erratic eaters, possible lower risk hypoglycaemia
Limited availability, cost
Benefit especially in renal impairment, low risk hypoglycaemia
Moderate glycaemic improvement
Low risk hypoglycaemia, good glycaemic improvement
Weight loss may not be ideal, satiety effects not ideal, gastrointestinal side effects, cost benefit, may not be effective at late stage
Good glycaemic improvement but avoid
Risk of dehydration, UTIs/thrush and confusion, comorbidities limit use
UTI=urinary tract infection. Reproduced with permission of the editors, British Journal of Diabetes: Management of diabetes and dementia. Puttanna A, Padinjakara N. British Journal of Diabetes 2017; 17: 93–99. doi:10.15277/bjd.2017.139
Despite the knowledge that there is a link between both conditions, there are still limited clinical data regarding management of people with diabetes and dementia. This is partly being addressed by the DIADEM project in the West Midlands.
The impact of medication and diabetes management on cognitive function and risks of medications in those with cognitive dysfunction need to be further investigated. There is some work with GLP-1 RAs on patients with cognitive impairment, however we will have to wait before large-scale studies include cognitive performance as part of their data collection, despite the fact that this is sorely needed.