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

[email protected]

@DocStrain

mailto:[email protected]

2

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

https://www.healthamplifier.org/

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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)

http://www.diabetesatlas.org/resources/2017-atlas.html

5

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

http://www.statcan.gc.ca/pub/82-625-x/2012001/article/11659-eng.htm

6

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…

9

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

10

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



Ageing and

Diabetes



But Also

Functional disability

Geriatric syndromes: depression


morbidity/mortality

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Falls andfractures



Ageing and

Diabetes



But Also



Geriatric syndromes: cognitive impairment


morbidity/mortality

Cognitivedysfunction

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Falls andfractures



Ageing and

Diabetes



But Also



Geriatric syndromes: cognitive impairment


morbidity/mortality

Cognitive dysfunction should be added to the list of the complications of diabetes, along with retinopathy, neuropathy,

nephropathy and cardiovascular disease.



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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


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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

type 1 diabetes in older adults: identifying the challenge · 2020-06-21 · cv disease, cancer and...

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