Type 1 diabetes in older adults: identifying the challenge David - - PowerPoint PPT Presentation

▶

Feb 28, 2023 230 likes •487 views

Type 1 diabetes in older adults: identifying the challenge David Strain, Diabetes and Vascular Research Centre University of Exeter Medical School, UK D.strain@Exeter.ac.uk @DocStrain Conflict of interest I have received speaker honoraria,

SLIDE 1

Type 1 diabetes in older adults: identifying the challenge

David Strain,

Diabetes and Vascular Research Centre University of Exeter Medical School, UK D.strain@Exeter.ac.uk @DocStrain

SLIDE 2 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.org supporting medical services and education in one of the poorest communities in Tanzania

SLIDE 3 3

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

SLIDE 4 4

Diabetes is a growing problem

15.9 58.0 38.7 45.9 26.0 82.0 158.8

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 millions Source: Diabetes Atlas, 8th ed. http://www.diabetesatlas.org/resources/2017-atlas.html (accessed 23 Oct 2018)

SLIDE 5 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

The number of older adults with diabetes is expected to double over the next 5 years2

SLIDE 6 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

SLIDE 7 7

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

SLIDE 8 8

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…

SLIDE 9 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 <22 22−26 >26−30 >30 Body mass index, kg/m2 In-hospital mortality, % 65−80 y >80 y

SLIDE 10 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 adults

Possible 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 years 9.0 8.0 7.0 6.0 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 HbA1c (%) HbA1c (mmol/mol) 75.0 63.9 53.0 42.1 0.0 CROSSOVER Treatment period 1 (week) Treatment period 2 (week) 153 144 135 126 117 108 99 90 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 FPG (mg/dL) FPG (mmol/L) CROSSOVER HbA1c by age FPG by age

SLIDE 11 11

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

SLIDE 12 12

Age vs. Frailty…

Both of these actors are the same age

SLIDE 13 13

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

0.00 0.25 0.50 0.75 1.00 2 4 6 8 10 analysis time Fit Mild Frailty Moderate Frailty Severe Frailty Follow-up (Years)

SLIDE 14 14

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…

SLIDE 15 15

Functional disability and depression Falls and fractures

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

SLIDE 16 16

Functional disability and depression Falls and fractures

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

SLIDE 17 17

Functional disability and depression Falls and fractures

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.

Cognitive dysfunction

SLIDE 18 18

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 Reduced C-peptide Hyperglycaemic microvascular injury

Cognitive dysfunction

SLIDE 19 19

Hypoglycaemia and dementia

Hypoglycaemia and risk of incident dementia casesa

No. of

hypoglycaemic episodesb (n)

No. of

dementia cases Adjusted for Age (as time scale) BMI, Race/Ethnicity, education, sex, and duration

f 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 4.5 0.5 1.5 2.5 3.5 4.5

No. of

hypoglycaemic episodesb (n)

No. of

dementia 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

SLIDE 20 20

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) Hazard ratio

SLIDE 21 21

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

SLIDE 22 22

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 homeostasis Glucose falls Glucose rises 2.8 mmol/L 1.9 mmol/L 1.6 mmol/L

SLIDE 23 23

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

SLIDE 24 24

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

SLIDE 25