Type 1 diabetes in older adults: identifying the challenge · 2020-06-21 · CV disease, cancer and...
Transcript of Type 1 diabetes in older adults: identifying the challenge · 2020-06-21 · CV disease, cancer and...
Type 1 diabetes in older adults: identifying the challenge
David Strain, Diabetes and Vascular Research Centre
University of Exeter Medical School, UK
@DocStrain
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Conflict of interest
I have received speaker honoraria, conference sponsorship, unrestricted educational grants and/or attended meetings (i.e. had free dinner) sponsored by:
Astra Zeneca, Bayer, Boehringer Ingelheim, Bristol Myer Squib, Colgate Palmolive, Eli Lilly, Glaxo SmithKline, Janssen, Lundbeck, Menarini, Merck, Napp, Novartis, Novo Nordisk, Pfizer, Sanofi Aventis, Servier, Takeda
I currently hold research grants from
Astra-Zeneca, Bayer, Colgate Palmolive, Novartis, Novo Nordisk & Takeda
Half of the honoraria I receive are diverted directly to https://www.healthamplifier.orgsupporting medical services and education in one of the poorest communities in Tanzania
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Disclaimer
I would never allow a scientist to partake in my government – Give them a new piece of information and they are liable to change their mind
“ “Abraham Lincoln
16th President of the United States
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Diabetes is a growing problem
15.9
58.0
38.7
45.9
26.082.0
158.8
424.9 millions
40.7
66.7
82.0
62.0
42.3
151.4
183.3
Africa
Europe
Middle East & North Africa
North America & Caribbean
South & Central America
Soutth East Asia
Western Pacific
628.6 millions
2017 2045
*Numbers expressed in millionsSource: Diabetes Atlas, 8th ed. http://www.diabetesatlas.org/resources/2017-atlas.html (accessed 23 Oct 2018)
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Age distribution of those with diabetes
1. Canadian Community Health Survey 2011 (accessed at http://www.statcan.gc.ca/pub/82-625-x/2012001/article/11659-eng.htm)
2. Sinclair AJ et al. Diabetes Care 2001 Jun;24(6):1066-8
1 in 4 people in residential care have
diabetes2
X2The number of older adults with diabetes is expected to
double over the next 5 years2
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The (mis) perceptions
Type 2 diabetes is a disease of the elderly
Type 1 diabetes is a disease of the young
Up to 25% of people with type 1 diabetes are diagnosed as adults1
1 Thunander M et al. Diabetes Res Clin Pract 82:247–255, 2008
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Subdivisions within type
Adult onset type 1 diabetes more likely to have detectable c-peptide1
As a result they usually have
• Better clinical outcomes2
• Less hypoglycaemia2
Shorter burden of disease
1Merger SR Diabet Med 30:170-178 2013: 2DCCT Research group, Ann Intern Med 128:517–523, 1998
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Little person gets bigger
It’s just about size!
Fundamental changes in physiology
Kidneys, liver, heart, brain, autonomic nervous system, endocrine system, all start to fail
So what? They’re just a bit older…
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Mortality and weight in older adults
In younger patients higher body weight is a poor prognostic indicator
In older patients the converse is true
Kamel and Iqbal. Arch Intern Med. 2001;161:1459.
In hospital mortality vs. BMI in young elderly vs. very elderly
In-hospital mortality vs BMI in young elderly vs. very elderly
25
20
15
10
5
0
<22 22−26 >26−30 >30
Body mass index, kg/m2
In
-ho
sp
ital
mo
rta
lity
, % 65−80 y
>80 y
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EPO, erythropoietin; Hb, haemoglobin; HbA1c, glycated haemoglobin
1. Wu L et al. PLoS ONE 2017;12(9): e0184607.; 2. Yau CK et al. J Am Geriatr Soc 2012;60(7):1215–21
HbA1c differs for older adultsPossible explanation
Older vs younger adults
Lower red blood cell (RBC) count1
Decreased secretion of EPO due to decline in
renal function1
Older adults >65 years
Younger adults <65 years9.0
8.0
7.0
6.0
0.0
0 8 12 16 20 24 28 32 12 16 20 24 28 32
Titration period 1 Maintenance period 1 Titration period 2 Maintenance period 2
Hb
A1c (
%)
Hb
A1c (m
mo
l/mo
l)
75.0
63.9
53.0
42.1
0.0CROSSOVER
Treatment period 1 (week) Treatment period 2 (week)
153
144
135
126
117
108
99
90
00 16 32 16 32
Titration period 1 Maintenance period 1 Titration period 2 Maintenance period 2
Treatment period 1 (week) Treatment period 2 (week)
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
4.5
FP
G(m
g/d
L) F
PG
(mm
ol/L
)
CROSSOVER
HbA1c by age
FPG by age
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What is Old…
• UK – 81.2yrs• In Africa – 50-55yrs• Latin America – 60yrs
Chronological vs
physiological vs
functional age
Office of National
Statistics in the UK –
65yrs
WHO – someone
whose age has passed
the median life
expectancy at birth
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Age vs. Frailty…
Both of these actors are the same age
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Mortality of 75+ year old those who survive 6 months stratified by Frailty status
Data on File of Mazoli, J, Strain, WD et al from CPRD database
0.0
00.2
50.5
00.7
51.0
0
0 2 4 6 8 10analysis time
efi_c = fit efi_c = mild frailty
efi_c = moderate frailty efi_c = severe frailty
Kaplan-Meier survival estimates
Fit
Mild Frailty
Moderate Frailty
Severe Frailty
Follow-up (Years)
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CV disease,cancer and all cause
morbidity/mortality
The frail, elderly patient with diabetes
Cukierman T, et al. Diabetologia. 2005;48(12):2460-9
Ageing and
Diabetes
Older persons with diabetes are at higher risk than those without diabetes of:
Usual complications of diabetes…
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Functionaldisability anddepression
Falls andfractures
The frail, elderly patient with diabetes
Cukierman T, et al. Diabetologia. 2005;48(12):2460-9
Ageing and
Diabetes
Older persons with diabetes are at higher risk than those without diabetes of:
Usual complications of diabetes…
But Also
Functional disability
Geriatric syndromes: depression
CV disease,cancer and all cause
morbidity/mortality
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Functionaldisability anddepression
Falls andfractures
The frail, elderly patient with diabetes
Cukierman T, et al. Diabetologia. 2005;48(12):2460-9
Ageing and
Diabetes
Older persons with diabetes are at higher risk than those without diabetes of:
Usual complications of diabetes…
But Also
Functional disability
Geriatric syndromes: depression
Geriatric syndromes: cognitive impairment
CV disease,cancer and all cause
morbidity/mortality
Cognitivedysfunction
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Functionaldisability anddepression
Falls andfractures
The frail, elderly patient with diabetes
Cukierman T, et al. Diabetologia. 2005;48(12):2460-9
Ageing and
Diabetes
Older persons with diabetes are at higher risk than those without diabetes of:
Usual complications of diabetes…
But Also
Functional disability
Geriatric syndromes: depression
Geriatric syndromes: cognitive impairment
CV disease,cancer and all cause
morbidity/mortality
Cognitive dysfunction should be added to the list of the complications of diabetes, along with retinopathy, neuropathy,
nephropathy and cardiovascular disease.
Cognitivedysfunction
Cognitivedysfunction
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Pathophysiology ‒ diabetes and dementia
ApoeE4, apolipoprotein E4; Adapted from Kodl, et al. Endocrinol Rev 2008; 29:494 –511
Cognitive dysfunction in diabetes
Hypoglycaemia
Cerebrovascular ischemic event
Insulin resistance
Absence of ApoE4 allele
ReducedC-peptide
Hyperglycaemic microvascular
injury
Cognitivedysfunction
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Hypoglycaemia and dementia
Hypoglycaemia and risk of incident dementia casesaNo. of hypoglycaemic episodesb (n)
No. ofdementia
cases
Adjusted for Age(as time scale)
BMI, Race/Ethnicity, education, sex, and duration
of diabetes
Additionally adjusted for comorbiditiesc
Additionally, adjusted for 7-year HbA1c level, diabetes treatment and
years of insulin use
1 or more 250
1 150
2 57
3 of more 43
0.5 1.5 2.5 3.5 4.5 0.5 1.5 2.5 3.5 4.50.5 1.5 2.5 3.5 4.5
No. of hypoglycaemic episodesb (n)
No. ofdementia
cases
Adjusted for Age(as time scale) BMI,
Race/Ethnicity, education, sex, and duration of diabetes
Additionally adjusted for comorbiditiesc
Additionally, adjusted for 7-year HbA1c level, diabetes treatment and
years of insulin use
A longitudinal cohort study from 1980–2007 of 16,667 patients with a mean age of 65 years and type 2 diabetes who were
members of an integrated health care delivery system in northern California
Hazard ratio (95% CI)
Hypoglycaemia and risk of incident dementia casesa
a Analyses combined using Cox proportional hazard models; bThe 1 or more group was compared with 0 and 1, 2 and 3 or more groups were simultaneously compared to 0; cAdjustment made using a comorbidity composite scale, BMI=body mass index; CI=confidence interval; HbA1c=haemoglobin A1c
Whitmer et al. JAMA 2009; 301:1565–572
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Relationship between glucose and risk of dementia
Crane PK et al., N Engl J Med 2013; 369:540-548
Risk of incident dementia associated with average glucose level over the preceding 5 years
among participants without diabetes
Average Glucose Level
Hazard Ratio
for Dementia
(95% Cl)
Participants without diabetes
95 mg/dl 0.86 (0.77-0.97)
100 mg/dl 1.00
105 mg/dl 1.10 (1.03-1.17)
110 mg/dl 1.15 (1.05-1.27)
115 mg/dl 1.18 (1.04-1.33)
p value 0.01
2.00
1.80
1.60
1.40
1.20
1.00
0.80
0.60
90 95 100 105 110 115 120
Patients without Diabetes
5-years Mean Glycemia (mg/dl)H
azard
ratio
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Risk of incident dementia associated with average glucose level over the preceding 5 years
among participants with diabetes
Relationship between glucose and risk of dementia
CI, confidence interval
Crane PK et al., N Engl J Med 2013; 369:540-548
Average Glucose Level
Hazard Ratio
for Dementia
(95% Cl)
Participants with diabetes
150 mg/dl 1.10 (0.92-1.30)
160 mg/dl 1.00
170 mg/dl 1.01 (0.92-1.12)
180 mg/dl 1.15 (0.98-1.34)
190 mg/dl 1.40 (1.12-1.76)
p value 0.002
90 95 100 105 110 115 120
Patients with Diabetes
5-years Mean Glycemia (mg/dl)
2.00
1.80
1.60
1.40
1.20
1.00
0.80
0.60
Hazard
ratio
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The physiology of hypos – older patients
Zammitt NN, Frier BM. Diabetes Care 2005;28:2948–61
Normal glucose suppresses insulin at 4.6 mmol/L
Glucagon (3.8±0.3 mmol/L)
Adrenaline (epinephrine) (3.7±0.3 mmol/L)
Growth hormone (3.2 mmol/L)
Cortisol (3.0 mmol/L)
Neurotransmitters (2.4 mmol/L)
Normal physiological homeostasisGlucose falls
Glucose rises
2.8 mmol/L
1.9 mmol/L
1.6 mmol/L
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Symptoms of hypoglycaemia are non-specific in older people
Deary IJ et al. Diabetologia 1993;36:771–77; Jaap AJ et al. Diabet Med 1998;15:398–401
Autonomic:
Palpitations
Sweating
Anxiety
Neuroglycopenic:
Fatigue Irritability
Confusion Dizziness
Drowsiness Coma
Particularly in older people:
Unsteadiness
Light-headedness
All these are also common in older people without diabetes
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Managing elderly patients is complicated by
– Multiple co-morbidities,
– Increased risk from the complications of treatment
– Reduced life expectancy, therefore reduced return
Treatment should focus on reducing risk of side effects and improving symptoms
Take Home messages