Review

Diabetes in older people: new insights and remaining

challenges
Alan Sinclair, Trisha Dunning, Leocadio Rodriguez-Maas

Diabetes in ageing communities imposes a substantial personal and public health burden by virtue of its high
prevalence, its capacity to cause disabling vascular complications, the emergence of new non-vascular complications,
and the eects of frailty. In this Review, we examine the current state of knowledge about diabetes in older people
(aged 75 years) and discuss how recognition of the eect of frailty and disability is beginning to lead to new
management approaches. A multidimensional and multidisciplinary assessment process is essential to obtain
information on medical, psychosocial, and functional capabilities, and also on how impairments of these functions
could limit activities. Major aims of diabetes care include maintenance of independence, functional status, and
quality of life by reduction of symptom and medicine burden, and active identication of risks. Linking of therapeutic
targets to individual functional status is mandatory and very tight glucose control is often not necessary. Hypoglycaemia
remains an important avoidable iatrogenic event. Quality diabetes care in older people remains an important
challenge for health professionals.

Introduction
Chronic diseases have the greatest eect of any disease
type in older adults aged 75 years. Management strategies
are often based on evidence from younger populations of
patients and on a single disease, and cannot adequately
support the physician to manage the complexity of illness
in older people. When diabetes occurs in later life, the
treatment plan needs continued surveillance, a highly
skilled balancing act of competing priorities by the
physician, a good appreciation of age-related physiological
and metabolic changes, and true implementation of the
so-called individualised approach to care.1
Ample evidence of the economic, social, and health
burden of diabetes in older people exists,2,3 along with
increased awareness that diabetes lowers the chances of
successful ageing, increases functional limitation, and
impairs quality of life.4 Diabetes in ageing individuals
can be a substantial chronic disorder,5 and is often
overlooked in older people residing in institutions;6 this
susceptible group has special characteristics and needs.7
However, there has been a renewed call for action8 and
international clinical guidelines on adult diabetes have
acknowledged the unique characteristics of older people
with the disorder.912
In this Review, we examine the current state of
knowledge about diabetes in older people (75 years) and
the emergence of new clinical complications (mood
disorder, dementia, and falls) that need additional
specialist care. We also discuss how recognition of the
eect of frailty and disability is beginning to lead to new
management approaches.13 All aspects of care should be
linked to processes that increase patient safety, which is
often compromised by inappropriate treatment choices,
overly strict glucose targets, and suboptimum specialist
follow-up.9,14
We recognise that older people with diabetes can span
four decades (aged 6090 years and older) and are not a
homogeneous group. Their cognitive and physical status
varies widely, and they often have complex health and

social needs. We therefore dened older people as those

aged 75 years and older because the risks of comorbid
illness, frailty, and dependency begin to sharply increase
after this age.15

Nature of diabetes in old age

Epidemiology and public health burden
The rate of diagnosed and undiagnosed diabetes increases
with age, but this increase reaches a plateau or starts to fall
after age 85 years.16 More than 25% of people over 65 years
of age have diabetes, and about 50% have prediabetes,12
although the signicance and clinical relevance of
prediabetes diagnosis in ageing populations has not yet
been shown. Most older people with diabetes have type 2
diabetes,17 accounting for more than 90% of older patients
and 75% of those given insulin.18 Prevalence of type 1
diabetes from 6080 years of age is about 03% for women
and 04% for men in England and Wales (gure 1).19 In the
USA, one in ve new cases of diagnosed diabetes occurs in
those aged 65 years and over.20 During a 10 year period
(19942004), the annual incidence of new diabetes cases in
the USA increased by 23%, and prevalence increased by
62%, in those aged 65 years and older.3 An analysis of a 5%
sample of Medicare beneciaries in the USA aged 67 years
or older between 1994 and 200116 showed that the highest
increase in annual incidence of new cases of diabetes was
seen in non-white groups (eg, Hispanics and non-Hispanic
blacks), and was greatest for Asians (68% increase).
In the UK, people with diabetes have a higher risk of
dying than those without diabetes at all ages younger than
80 years, and the risk is higher in women than in men,
with the hazard ratio of death for those between 6079 years
of age at 191 for men and 253 for women.21 Authors of a
systematic review22 of mortality associated with diabetes
showed lower mortality at older than younger age, and
suggested that short life expectancy in these individuals
(because of their advanced age) would be associated with
low risk of developing vascular complications and,
consequently little eect on clinical outcome and mortality.

www.thelancet.com/diabetes-endocrinology Published online November 24, 2014 http://dx.doi.org/10.1016/S2213-8587(14)70176-7

Lancet Diabetes Endocrinol 2014

Published Online
November 24, 2014
http://dx.doi.org/10.1016/
S2213-8587(14)70176-7
Diabetes Frail, Hampton
Lovett, Droitwich,
Worcestershire, UK
(Prof A Sinclair FRCP); Centre for
Nursing and Allied Health
Research at Deakin University,
VIC, Australia, and Barwon
Health, VIC, Australia
(Prof T Dunning PhD); and
Department of Geriatrics,
Hospital Universitario de
Getafe, Getafe, Madrid, Spain,
and School of Health Sciences,
Universidad Europea de
Madrid, Madrid, Spain
(Prof L Rodriguez-Maas MD)
Correspondence to:
Prof Alan Sinclair, Diabetes Frail,
Hampton Lovett, Droitwich,
Worcestershire WR9 0QH, UK
sinclair.5@btinternet.com

Review

prevalence is predicted to increase, mainly due to

increased numbers of older people.24
Roughly 3540% of diabetes-related costs are associated
with management of vascular complications, mainly
cardiovascular disease and nephropathy, and admission
to hospital,25,26 but additional costs, such as
institutionalisation, increase the nancial burden in older
people with diabetes. Any restriction of activities of daily
living creates a three-times increase in costs compared
with costs of those who are independent, and admission
to a care home creates a nine-times increase in costs.27,28

Female
Male

90
8589
8084
7579
7074
6569

Age group (years)

6064
5559
5054
4549
4044
3539

Pathophysiology and diagnosis

3034

Insulin secretion seems to decrease with age, with

substantially diminished -cell sensitivity and acute insulin
response to glucose.29 Insulin resistance in older people
seems to predominate in skeletal muscle, whereas hepatic
glucose output seems to be almost unaected, unlike in
younger patients. Under mixed meal and glucose injection
test conditions, insulin resistance in older people is related
to both visceral and total fat, although aerobic tness and
leg strength can minimise dierences in insulin action
between younger and older people.30 Overall, these ndings
suggest that the biological ageing eect on glucose
metabolism is an interplay between decreased insulin
secretion and increased insulin resistance.30
Some of the most striking dierences between the
pathophysiology of type 2 diabetes in older and younger
adults is the presence of insulin resistance in the absence
of obesity, which could be linked to increased fat
accumulation in muscle and liver tissue, and
mitochondrial dysfunction in skeletal muscle.31 Studies
using the glucose tolerance test and both hyperglycaemic
and euglycaemic clamp tests show that type 2 diabetes in
older lean individuals is associated with a marked
impairment in glucose-induced insulin secretion,32
whereas in older obese people with type 2 diabetes, the
main decit seems to be a marked resistance to insulinmediated glucose disposal.32
A dierent set of risk factors for type 2 diabetes, through
two key underlying mechanisms of insulin resistance or
-cell dysfunction, operates for older adults compared
with younger adults.33 For example, increased adiposity
and obesity were associated with a lower risk of diabetes
preceded predominantly by -cell dysfunction in older
people than in younger people, whereas dietary score (a
quality measure of diet based on factors such as intake of
trans fat and bre, and glycaemic indices of food) and
alcohol consumption were inversely associated with risk
of diabetes preceded predominantly by insulin resistance
in older people but not in younger people.33 This
dierence suggests the existence of pathophysiological
subtypes in older adults with type 2 diabetes. Further
support for this view comes from a study of Japanese
men and women aged 4079 years,34 in which obesity
conferred a lower risk for diabetes in people aged
6079 years than for people aged 4059 years.

2529
2024
1519
1014
59
04
10

08

06

04

02

02

04

06

08

10

Type 1 diabetes prevalence (%)

B
90
8589
8084
7579
7074
6569

Age group (years)

6064
5559
5054
4549
4044
3539
3034
2529
2024
1519
1014
59
04
20

15

10

10

15

20

Type 2 diabetes prevalence (%)

Figure 1: Prevalence of dierent age groups of male and female patients with (A) type 1 and (B) type 2
diabetes in England and Wales in 2011
Reproduced with permission of the Health and Social Care Information Centre.19 Copyright 2013. All rights reserved.

An ageing population aects a societys health because

of increased numbers of people and more years lived with
disability. Diabetes exacerbates this burdenit is ranked
as the seventh highest cause of years of life lost and the
eighth highest cause of disability-adjusted life years in
western countries, and the 14th highest worldwide cause
of disability-adjusted life years.23 In 2010, diabetes
accounted for 19% of worldwide disability-adjusted lifeyears, an increase of more than 60% from 1990. Diabetes
2

www.thelancet.com/diabetes-endocrinology Published online November 24, 2014 http://dx.doi.org/10.1016/S2213-8587(14)70176-7

Review

Type 2 diabetes in older people can be asymptomatic or

insidious, and atypical manifestations can be present.
Frequent health-care contact for other medical
comorbidities in the absence of diabetes-related symptoms also reveals incidental cases of diabetes through
subsequent testing for diabetes. For example, diabetes
can present as urinary incontinence, falls, and cognitive
or behavioural disturbances. International guidelines for
diabetes in older people recommend opportunistic
diabetes screening for at-risk individuals, such as during
general health checks and on admission to hospital or a
care home.10,35
Three factors have been identied that increase the
value of screening for diabetes: older than 55 years of
age, systolic blood pressure of 130 mm Hg or higher, or
a BMI higher than 35 kg/m,36 which shows that in older
people obesity should not be the only reason to screen
for diabetes. No agreement exists on the best screening
test for diabetes in people aged 55 years and older. A
choice of methods is available: HbA1c, fasting blood
glucose concentration, and the oral glucose tolerance
test, with each having dierent sensitivities and
specicities. In this regard, fasting blood glucose
concentration is often normal in early-onset diabetes,
and high values seem to identify risk proles for
cardiovascular disease and mortality dierent to positive
results using other tests.37 The oral glucose tolerance
test, however, can present practical diculties, is often
inconvenient, and can be unrealistic. Diagnosis of
diabetes in older people can be made using HbA1c
measurement, assuming usual assay quality assurance
is adhered to and other confounding factors are
considered, such as diabetes of very recent onset, acute
hospital admission, chronic renal failure, vitamin B12
deciency anaemia, disorders of decreased erythropoiesis, chronic disease of rheumatoid arthritis, and
aspirin usage, all of which can change the ability of
HbA1c to diagnose diabetes.

Complications
Older people with diabetes are at a higher risk of
microvascular and macrovascular diseasesuch as
ischaemic heart disease, peripheral artery disease, stroke,
heart failure, and chronic kidney disease18,38than
younger people, and these complications tend to occur
earlier after diabetes diagnosis.39 These complications
threaten independence, self-care capacity, and quality of
life.12,40 Increased duration of diabetes and advancing age
independently predict morbidity and mortality rates in
older people with this disease,41 with cardiovascular and
hypoglycaemic episodes being the most frequent nonfatal events.
Risk scores for cardiovascular disease have been tested
in well established cohorts of older people, but they have
low predictive capacity for cardiovascular events in
people with diabetes older than 85 years.42,43 The 2013
International Diabetes Federation global guideline stated

that all people with diabetes aged 60+ years are

considered at high cardiovascular risk and application of
a risk equation is unnecessary.10

Frailty and disability

Ageing is associated with a decrease in the eect of a
single disease on mortality risk. Although older people
with diabetes have a high rate of comorbidity,44 the
increased risk of dying due to diabetes itself diminishes
with increasing age and becomes nearly irrelevant in
those older than age 80 years.45
Type 2 diabetes has an increasing eect on functional
autonomy as patients become older, resulting in a change
in management focus from the traditional major aim
of prolonging life and avoiding life-threatening complications to extending disability-free life expectancy.
Disability and its main modiable risk factor, frailty,4648
are two main predictors of adverse outcomes in older
peopleincluding death, admission to hospital, permanent institutionalisation, falls, and additional disability.46
By contrast with disability, which is dicult to reverse,49
frailty is a dynamic process with broad opportunities for
intervention to delay or avoid disability.50,51
Frailty is a state of increased vulnerability to minor
stressors, leading to diculties in maintenance of
homoeostasis, which increases the risk of adverse
outcomes (disability, falls, and death). Frailty has a higher
predictive power for adverse outcomes such as disability
and death than does comorbidity in people older than
80 years.48 Practical ways of detecting and measuring
frailty exist.10,46
Diabetes has previously been suggested to be a model
of frailty,52 and signicantly increases the risk of frailty
(odds ratio [OR] 118127),53 mobility disability
(OR 171), instrumental activities of daily living disability
(an adverse change in activities that allow independent
living, such as housework, money management, and
grocery shopping; OR 165), and activities of daily living
disability (diculties with self-care; OR 182).54,55
Additionally, macrovascular complications are powerful
predictors of progression of frailty in older adults with
diabetes (OR 184).56 However, diabetic comorbidities,
such as hypertension and cardiovascular and cerebrovascular disease, only explain 38% of the excess risk in
women and 16% in men.57
Long-duration diabetes increases the loss of skeletal
muscle mass and function, both of which play a pivotal
pathophysiological role in frailty, sarcopenia, and disability,58 and lead to a reduction in mobility and gait
speed. Sarcopenia is emerging as a key pathophysiological
event in lower limb dysfunction in diabetes.58 Attenuation
of these eects on muscle mass and function has been
reported in treatment with insulin sensitisers.58 Insulin
resistance can aggravate lower limb dysfunction,59 further
worsening the increased intramyocellular fatty acid
metabolites caused by the reduced mitochondrial activity
that accompanies muscle ageing.

www.thelancet.com/diabetes-endocrinology Published online November 24, 2014 http://dx.doi.org/10.1016/S2213-8587(14)70176-7

Review

Emerging areas
Mood disturbance
Diabetes is associated with a two-times increase in the risk
of depression, and more than a quarter of older people
with diabetes have depression symptoms and mood
disturbances;60,61 yet, these symptoms are not routinely
examined for. In older adults, the presence of both diabetes
and depression can synergistically increase the risk of
negative health outcomes, including mortality, disability,
and complications.62 In a meta-analysis of 16 studies with a
mean follow-up of 6 years in patients with diabetes and a
mean age range of 6276 years, the presence of depression
was associated with increases in all-cause mortality (hazard
ratio 146, 95% CI 129166) and cardiovascular mortality
(1.39, 111173).63 Another meta-analysis64 showed an
association between depression and poor glucose control
in people with diabetes, but did not provide specic data
on older people. However, in a dierent study,65 depression
was associated with high postprandial glucose concentrations (but not fasting glucose concentrations or
HbA1c) in people with diabetes aged older than 65 years.
Randomised controlled trials66,67 have shown the ecacy
of pharmacotherapy, cognitive behavioural therapy, and
stepped collaborative care for major depressive disorder,
although specic studies in older people with diabetes are
scarce. A primary care intervention trial consisting of
treatment adherence programmes, drug review, serotonin
reuptake inhibitor treatment, and personal psychotherapy
versus usual care showed a halving of risk of death in
older adults (mean age 71 years) with diabetes and
depression, with a median follow-up of 52 months.68
Exercise training has shown conicting results on quality
of life and symptoms of depression in type 2 diabetes,
and specic studies in older people are scarce.69

Cognitive impairment and delirium

Diabetes is associated with mild cognitive impairment
and brain cortical changes in older people,70 which cause
Patient-related
Life expectancy (total and active)
Functional and cognitive status
Comorbidity prole
Risk of hypoglycaemia
Social support and family
dynamics

Disease-related
Time of evolution of diabetes
(duration)
Vascular complication prole
Mobility limitation and falls rate
Eect on quality of life and
health status

Treatment options
Adapt treatment regimes to highest health gain
in varying categories of patients
Balance risk of hypoglycaemia with vascular
risk-reducing glucose targets
Implement hospital-avoidance strategies
Reduce risk of institutionalisation
Use non-drug strategies to increase and
maintain functional status

Figure 2: Factors aecting clinical decision-making and treatment options

for older people with diabetes

diculties in performing instrumental activities of daily

living.71 Mental and motor slowing and decreased
measures of attention and executive functioning have
also been shown in people with diabetes.72 Diabetes and
dementia are highly prevalent long-term disorders that,
irrespective of any linked associations or cause, frequently coexist in older people. Both hyperglycaemia and
hypoglycaemia seem to increase the risk of dementia.73,74
Type 2 diabetes is associated with both major subtypes of
dementia, with about a 25-times increased risk of
incident vascular dementia and a 15-times increased
risk of Alzheimers disease.75 Case nding is often poor
for cognitive impairment in medical settings and for
diabetes in mental health settings, and structured care
policies are absent, highlighting the need for best clinical
practice in this area.76
Delirium is also a severe life-threatening and functionthreatening disorder in older people, and diabetes is one
of the main risk factors for its development in acute
medical illnesses77 (such as diabetic ketoacidosis, stroke,
and heart failure) in surgical procedures,78 and in
palliative care scenarios.79 Preventive strategies in older
patients include early detection (within 2 h) of
postoperative delirium; cautious use of drugs, such as
benzodiazepines, steroids, and antihistamines; prompt
treatment of infections, particularly urinary tract
infections; eective management of constipation; and
avoidance of hypoglycaemia.

Falls
Although routine diabetes care rarely includes a falls risk
assessment, older people with diabetes are at high risk of
falls.8082 Risk factors for people with diabetes include
polypharmacy, muscle weakness, previous stroke, motor
and sensory neuropathy, poor glycaemic control,
hypoglycaemia, insulin use, cognitive dysfunction,
orthostatic hypotension, and visual impairment.12,83,84 Low
HbA1c (<53 mmol/mol; <70%) has been associated with
an increased risk of falls and hip fracture in frail older
people).85,86 Insulin treatment is associated with an
increased risk of falls.87 Fall reduction in people with
diabetes needs a multifactorial intervention approach,
and there is strong evidence of a benet in older people.88
Measurement of gait velocity and ankle muscle strength
can help identify people at risk of falling,88 and gait,
balance, and strength training might reduce the risk of
falls for people with diabetes.89,90

Functional assessment
Assessment of older people with diabetes should be a
multidimensional and multidisciplinary process.10
Authors of meta-analyses have shown substantial
benets (improved health status and quality of life,
detection of unmet needs, less functional decline, fewer
admissions to nursing homes, and some reduction in
mortality in those aged less than 80 years) from use
of a structured assessment procedure known as

www.thelancet.com/diabetes-endocrinology Published online November 24, 2014 http://dx.doi.org/10.1016/S2213-8587(14)70176-7

Review

comprehensive geriatric assessment.91,92 Functional

status can dictate the screening, preventive, diagnostic,
and therapeutic approach to the patient, including
therapeutic targets. Validated instruments are available
for use in older people with diabetes (appendix).
Functional measures (including cognition) have been
incorporated into assessment of risk of death within
410 years in older populations,93 and such methods
could have future roles in planning of diabetes care in
frail older people.

Treatment and medicinal management

Strategies
Diabetes management is often suboptimum in older
people, especially in those living in care homes.94,95
Diabetes management strategies for high-functioning
older people with diabetes who have a long life expectancy
are similar to those for younger people, but such
strategies are unlikely to be safe for frail individuals.
A risk minimisation care plan should be developed that
suits the individuals functional status, optimises their
quality of life, maintains their independence for as long
as possible, and then enables a dignied death.96 Because
older people are at high risk of toxic eects of medication
due to altered renal and liver function, polypharmacy,
drugdrug interactions, and adverse events, a quality use
of medicines97 approach should be adopted to medicine
decision making,11,96 although this approach can be
complex (gure 2). Quality use of medicines is the safe
and judicious use of medicines by the general public,
while ensuring that all medicines used are eective,
which means that they should have a quantiable benet
to the patients health, quality of life, or both. Clinicians
should adopt appropriate targets for treatment according
to the individual functional status of their patients
(table 1).10,11,12,96

Glucose-lowering medicines and blood glucose targets

Intensive glucose-lowering treatment in type 2 diabetes
has shown only slight benets in adults of all ages,98 but
with a high potential for adverse events (including
increased mortality risk). In observational studies, an
HbA1c concentration greater than 64 mmol/mol (>80%)
is associated with impairments of mobility and activities
of daily living,99 walking diculties, and incident
frailty.100 A U-shaped relation between HbA1c concentration and mortality has been reported in a study of
older adults (aged 60 years) with diabetes in the USA,101
which supported setting an HbA1c target of
<64 mmol/mol (<80%), with the caution that an HbA1c
concentration of <42 mmol/mol (<60%) was associated
with increased mortality risk. Similar ndings were
reported previously in a retrospective cohort study.102
These observations provide a rationale for setting
dierent HbA1c targets for older people depending on
age and functional level. Abandoning HbA1c targets is
entirely reasonable in some older people, such as those

of very advanced age (>80 years) with frailty, residents of

nursing homes, and those with a life expectancy of less
than 2 years.
Although there are few randomised clinical trials of
glucose-lowering in older people with diabetes, the need
for individualised care has been recognised.1 According
to the International Diabetes Federation, 510 mmol/L
is a safe random glucose range for older people, but
615 mmol/L might be safer for older people at a high
risk of hypoglycaemia and with increased susceptibility.10
An HbA1c target of 5364 mmol/mol (7080%) is
suitable for functionally independent older people with a
reasonable life expectancy. A target of up to 69 mmol/mol
(85%) is appropriate for frail older people and those
with dementia and a life expectancy of less than
10 years.10
Several major international guidelines provide
comprehensive guidance on management of diabetes in
older people,9,10,12 including the setting of metabolic
targets (table 1). We have proposed an algorithm that
places an obligation on the clinician to tailor treatment to
characteristics of the patient, the likelihood of
hypoglycaemia, the presence or not of frailty, and life
expectancy (gure 3). Metformin can be an eective rstline choice of treatment, even in frail older patients with
diabetes,9,10 but a cautious approach is necessary in
patients with renal impairment (table 2).
Few major age-related restrictions on the choice of
glucose-lowering drugs exist, but treatment decisions
should include a review of several factors (table 2).
Dipeptidyl peptidase 4 (DDP-4) inhibitors are eective
in older people,105 and they have been shown to be
reasonably safe.106,107 Barnett and colleagues,106 in a
randomised, double-blind, phase 3 study in people aged
70 years and over, showed that linagliptin lowered
glucose eectively and safely and was well tolerated.
Strain and colleagues107 had similar ndings with
vildagliptin, and eorts were made to adjust
individualised targets according to frailty status.
Independent or
robust

Frail or mild
disability

Moderate or
severe disability
or cognitive
impairment

See Online for appendix

End of life

HbA1c
concentration

Range 775%
Range 78%
(5359 mmol/mol) (5364 mmol/mol)

<85%
Avoid symptomatic
(<69 mmol/mol) hyperglycaemia

Systolic/diastolic
blood pressure

<140/90 mm Hg

<140/90 mm Hg

<150/90 mm Hg Avoid short-term lifethreatening blood pressure

levels

LDL cholesterol

<2 mmol/L;
individualised in
people aged 80
years

Individualise

Not necessary

Not necessary

>1 mmol/L

Individualise

Not necessary

Not necessary

HDL cholesterol
Data from references.

10,14,15

Table 1: Suggested targets for dierent cardiovascular risk factors according to functional status in older
people with type 2 diabetes

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Review

Glucagon-like peptide 1 receptor agonists are

recommended as third-line treatment options in the
International Diabetes Federation global guideline.10
However, gastrointestinal side-eects and weight loss
can be problematic in frail underweight individuals.108,109
Long-term data for sodium/glucose cotransporter 2
Initial clinician assessment

Vascular
complications
prole

Physical function,
frailty, and
cognition
Comorbidities or drugs

Consideration of findings
Total or active life expectancy
Risk of complications
Competing risks
Need for carer or social support
Hypoglycaemia and adverse drug
reaction risk
Definition of functional categories
Independent,
robust

Frail

Physical or
cognitive
impairment

End of life

Focus on disease
Focus on function

Individualised management of patient

Nutrition, physical activity and exercise, drugs, and
level and coordination of care

Figure 3: Management of diabetes in older people based on comprehensive

assessment and individualised treatment

Drug class

Comment

Age-related fall in renal

function

Metformin,
sulfonylurea, or
DPP-4 inhibitor

Avoid sulfonylureas in susceptible older patients. Little

adjustment needed for DPP-4 inhibitor treatment. Stop
metformin when eGFR is <30 mL/min.

Thiazolidinedione-linked
increase in risk of heart
failure, fractures,103 and
bladder cancer

Thiazolidinedione
(pioglitazone)

Contraindicated in bladder cancer, or a history of bladder

cancer. Do not use in heart failure (stages IIV) or a history
of heart failure. Assess benet to risk ratio in those with a
falls or fractures or osteoporosis history104

Frailty

GLP-1 receptor
agonists

Assess potential eect of weight loss with GLP-1 receptor

agonist treatment

Carer support

Insulin or GLP-1
receptor agonist

Ensure sucient carer or family support is available to

manage administration and monitoring of each regimen

Risk of hypoglycaemia

Sulfonylureas or
insulin

Be cautious in frail and cognitively impaired dependent

patientsuse lowest eective dose, maintain random
glucose concentrations above 7 mmol/L, and aim for an
HbA1c concentration near to the upper limit of 85%
(<69 mmol/mol). Avoid long acting sulfonylureas

DPP-4=dipeptidyl peptidase 4. eGFR=estimated glomerular ltration rate. GLP-1=glucagon-like peptide 1.

Table 2: Factors aecting treatment decisions on the use of glucose-lowering treatment for older adults
with diabetes

inhibitors are not available. They seem to be well

tolerated in older people, and weight loss (reported in
earlier clinical trials) is roughly 30% in those aged
65 years and over.110 In this study, no serious cases or
discontinuations due to urinary tract infections occurred
in those aged 65 years and older, but clinicians need to
monitor patients very closely for this adverse eect
because it can lead to delirium, metabolic decompensation, and admission to hospital. Reduced renal
function and risk of genitourinary infections need to be
considered in older people.10
Standard adult insulin regimens need more surveillance
and monitoring in older people because of the increased
risk of hypoglycaemia. A regimen consisting of a basal
insulin plus metformin or DDP-4 inhibitor is sensible for
frail, disabled, or cognitively impaired older people, for
whom the target HbA1c concentration is less than
69 mmol/mol (<85%) and the risk of hypoglycaemia is
very high.9,10,111,112 Addition of the DDP-4 inhibitor
linagliptin to a basal insulin regimen does not seem to
greatly increase incidence of hypoglycaemia or weight
gain in older people with diabetes.113

Hypoglycaemia
Hypoglycaemia is an under-recognised medicine-related
adverse event in older people, and is often misattributed
to other disorders. Autonomic symptoms are diminished
and symptom intensity is low overall in older people.114 In
non-diabetic individuals, advancing age itself could also
be associated with mild attenuation of blood glucose
recovery and slight reductions in counter-regulatory
responses to hypoglycaemia.114
Risk of severe hypoglycaemia tends to be higher in
people with either near-normal (HbA1c <42 mmol/mol;
<60%) or very poor glycaemic control (>75 mmol/mol;
>90%),115 and in those with dementia and renal
impairment.116 Patients with macroalbuminuria and
those with a long duration of type 2 diabetes, even when
renal function is normal, are at high risk of severe
hypoglycaemic episodes.117 Recent admission to hospital
and polypharmacy are also strong predictors of
hypoglycaemia in older adults.118
Insulin and sulfonylureas carry a high risk of hypoglycaemia, which in turn increases the risk of acute and
long-term cognitive changes to delayed and working
memory,119,73 serious falls, myocardial infarction,120 and
death.121 Repeated hypoglycaemia is also likely to be a risk
factor for frailty.122 In those aged 80 years and older with
diabetes, hypoglycaemia might account for up to one in
ve admissions to hospital.116 Many older patients given
insulin can be frail or have visual or cognitive issues.
Therefore, adjustment of insulin dose based on within-day
and day-to-day glucose uctuation, and education about
insulin adjustment on sick days (days when a patient with
diabetes has any illness or might just have symptoms of
nausea or gastrointestinal upset), are likely to be more
important in older adults to prevent hypoglycaemia.

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Review

Nutrition and activity

End-of-life care

A challenge in older people with diabetes is to avoid

malnutrition, and restrictive diets have not shown major
benets in adults up to 75 years of age.123 Many older
people with diabetes are decient in essential amino
acids, vitamins, and trace elements; therefore,
supplements might be indicated that can aect medicine
transport and drug eectiveness and safety.124 However,
doses of these supplements often need to be modied in
end-stage renal failure and dialysis, making nutritional
assessment mandatory.125 Wound healing after surgery
and pressure and venous ulcers increase the amount of
protein needed. Authors of one report have recommended varying daily protein intake to maintain and
regain lean body mass and functionfor adults aged
65 years and older, a range of 1012 g protein per kg of
bodyweight per day is recommended, whereas for those
with acute or chronic disease, a range of 1215 g per
kg of bodyweight per day is recommended.126 Physical
activity, including exercise, is essential to preserve
muscle mass, promote strength and balance, contribute
to glycaemic control, improve mobility, and prevent
falls,127 and could be particularly important in those with
long-duration diabetes who might have additional lower
quadricep muscle strength.128

Planning for palliative and end-of-life situations should

be incorporated into annual diabetes complication
screening processes.35,139 Management of existing complications to treat pain, promote comfort and quality of
life, and prevent unnecessary admissions to hospital is
essential.35,139 The HbA1c target needs to be individualised
according to expected survival time, but this target is not
relevant in the terminal stage.35,139 A joint management
approach between the palliative care and diabetes teams
is essential, and should support advanced care planning.
This planning should not be seen as an activity only
undertaken near to the time of death, but as an
opportunity to plan for other events along the declining
path of health, such as the need for admission to hospital
or management of intercurrent infection. At all times,
the wishes of the individual and their family, and their
advanced care plan should be considered.

Special considerations
Care homes
Diabetes is a highly prevalent chronic disease in care
home residents,129 and a high prevalence of detected
and previously undetected diabetes occurs in mental
health care homes.130 Residents have high levels of
comorbidity, disability, and frailty, and a shortened
survival,94,131 and are at risk of substantial polypharmacy.132
They exhibit important management problems,
including nutritional deciency, weight loss, increased
risk of hypoglycaemia, high infection rates, and leg and
foot ulceration.133 Management should focus on safety,
comfort, maintenance of quality of life, and preventive
care to reduce hypoglycaemia. Maintenance of
functional status and avoidance of unnecessary
admission to hospital for diabetes-related issues are
important, along with support for care sta from
community-based specialist teams.134
Little clinical trial evidence is available about this
patient population. An early dietary replacement study135
(changing diabetic diets to standard diets) in a small
sample of care home residents did not lead to any
deterioration in glycaemic control, and in a US-based
study,136 optimisation of glycaemic control did not reduce
the rate of pneumonia in long-term residents. Authors
of a small underpowered study137 showed that an
approach involving education of care sta led to an
improvement in mood and quality of life of residents,
and sta gained diabetes knowledge. National guidance
on management of diabetes in care homes is available in
some countries.96,138

Future research
Many research questions about diabetes in older people
are unanswered.1 The American Diabetes Association
American Geriatrics Society Consensus Report12
established a non-exhaustive list of 23 clinically relevant
priority research questions. Future research questions
have been identied in the panel, and these questions
address issues such as inclusion in clinical trials of older
people with the range of comorbidity and frailty
encountered in clinical practice, and development and
implementation of risk stratication models that report
harms and benets according to risk strata. Some of
these issues are addressed in a large EU-funded
randomised controlled clinical trial being done in seven
countries (the MID-Frail Study)140 that aims to assess the
eectiveness of a multimodal intervention (adjustment
of clinical targets to those suitable for older populations,
an exercise program based on strength exercise, and an
educational programme designed to avoid malnutrition
and hypoglycaemia) in 1800 frail or prefrail (those with
risk factors for frailty) people older than 70 years of age
with type 2 diabetes. The study is the rst major study to
focus on the eects of treatment on functional outcomes
in diabetes. The rst results will be available at the end
of 2016.

Conclusion
In this Review, we have provided evidence that diabetes
has a profound health-related societal eect on ageing
communities. The personal health burden is substantial;
for example, diabetes diagnosed at age 60 years reduces
quality-of-life years by 111 years in men and 138 years in
women.141 Although we have shown in this Review the
need for clinicians to develop new skills in functional
assessment and management, meaningful progress
towards high-quality care for older people with diabetes
needs a major change in attitudes and clinical behaviour
by health and social care sta. This change has to be

www.thelancet.com/diabetes-endocrinology Published online November 24, 2014 http://dx.doi.org/10.1016/S2213-8587(14)70176-7

Review

Panel: Future research questions and how to address them

What are the roles of frailty and sarcopenia in functional decline in older patients
with diabetes?
Examination of the interplay between frailty, sarcopenia, and vascular or non-vascular
comorbid illness in diabetes
Testing of the rapid FRAIL scale* in people with diabetes
How can personalised support systems and assistive technology be applied in
routine clinical practice?
Feasibility/pilot assessments of electronic decision support tools (aids)
Randomised clinical trials of eectiveness in patient empowerment, treatment
satisfaction, and reduction of cardiovascular risk and admission to hospital
How can clinical trial-based evidence about older patients with type 2 diabetes be
improved?
Randomised clinical trials in older people (aged 75 years) to examine benets of
glycaemic control using outcome measures such as predisability or disability,
incidence of dementia, frailty, quality of life, mood level, hypoglycaemia, and rates of
admission to hospital
Demonstration of likely benets in many dierent types of older people with diabetes,
including those who are frail, who are care home residents or housebound, who have
dementia, and who are at the end of their life
Inuence government bodies, medical charities, and major pharmaceutical companies
to participate in trials
What evidence is needed to inuence commissioners of clinical diabetes services?
Health economic analyses of interventions using study designs that allow relevant and
appropriate cost comparisons
Analytical methods that account for biases such as confounding due to comorbid
illness
*FRAIL scale: Fatigue: are you fatigued? Resistance: do you have diculty walking up one ight of steps? Aerobic: are you unable
to walk at least one block? Illness: do you have more than ve illnesses? Loss of weight: have you lost more than 5% of your
weight in the past 6 months?142

Search strategy and selection criteria

We identied references for this Review through searches of
PubMed and Medline for articles published from Jan 1, 1990,
to May 31, 2014, using the terms elderly, aged, older
people, geriatric, clinical trial, care homes, functional
evaluation, and frailty in combination with the term
diabetes. After we reviewed the abstracts yielded by the
initial search, we identied 1232 publications that formed the
basis of this Review. References from these databases were
supplemented by the databases from the guideline
development work of the European Diabetes Working Party
for Older People9 and the International Diabetes Federation
Global Guideline on Older People with Type 2 diabetes
Working party,10 and personal databases. We have also cited
several book chapter references from books we felt would be
of interest to the reader.

underpinned by a shift in focus from specic diabetes

management to comprehensive functional assessment,
individualised metabolic targeting, and a responsibility of
the clinician to plan for optimum patient safety and quality
8

of life. This shift will need clinicians to recognise diabetes

as a model of predisability (frailty), meaning that future
intervention strategies could lead to better functional
outcomes. A new research culture in diabetes in older
people is needed (panel). We hope that the next decade is
remembered for invention, innovation, and discovery in
the arena of diabetes in older people.
Contributors
All authors contributed equally to the conception, structure, and writing
of the manuscript, and preparation of tables and gures.
Declaration of interests
We declare no competing interests.
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