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, 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 2
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 16 th President of the United States 3
Diabetes is a growing problem 40.7 Africa 66.7 15.9 Europe 183.3 58.0 158.8 628.6 Middle East & North Africa 424.9 82.0 38.7 millions millions North America & Caribbean 45.9 South & Central America 62.0 26.0 151.4 82.0 Soutth East Asia 42.3 Western Pacific 2017 2045 *Numbers expressed in millions 4 Source: Diabetes Atlas , 8th ed. http://www.diabetesatlas.org/resources/2017-atlas.html (accessed 23 Oct 2018)
Age distribution of those with diabetes X 2 The number of older adults with diabetes is expected to double over the next 5 years 2 1 in 4 people in residential care have diabetes 2 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 5
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 adults 1 1 Thunander M et al. Diabetes Res Clin Pract 82:247 – 255, 2008 6
Subdivisions within type Adult onset type 1 diabetes more likely to have detectable c-peptide 1 As a result they usually have • Better clinical outcomes 2 • Less hypoglycaemia 2 Shorter burden of disease 1 Merger SR Diabet Med 30:170-178 2013: 2 DCCT Research group, Ann Intern Med 128:517 – 523, 1998 7
So what? They’re just a bit older… 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 8
Mortality and weight in older adults In-hospital mortality vs BMI in young elderly vs. very elderly 25 In-hospital mortality, % 65−80 y In younger patients 20 >80 y higher body weight 15 is a poor prognostic 10 indicator 5 In older patients the 0 converse is true <22 22−26 >26−30 >30 Body mass index, kg/m 2 In hospital mortality vs. BMI in young elderly vs. very elderly 9 Kamel and Iqbal. Arch Intern Med. 2001;161:1459.
HbA 1c differs for older adults Possible explanation 9.0 75.0 Younger adults <65 years HbA 1c by age Older adults >65 years HbA 1c (mmol/mol) 8.0 63.9 Older vs younger adults HbA 1c (%) 7.0 53.0 6.0 42.1 Lower red blood cell (RBC) CROSSOVER count 1 0.0 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 Treatment period 2 (week) Treatment period 1 (week) FPG by age 153 8.5 144 8.0 Decreased secretion of FPG (mg/dL) FPG (mmol/L) 135 7.5 EPO due to decline in 126 7.0 renal function 1 117 6.5 108 6.0 99 5.5 5.0 90 CROSSOVER 4.5 0 16 32 16 32 0 Titration period 1 Maintenance period 1 Titration period 2 Maintenance period 2 Treatment period 2 (week) Treatment period 1 (week) EPO, erythropoietin; Hb, haemoglobin; HbA 1c , glycated haemoglobin 10 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
What is Old… WHO – someone Chronological vs Office of National whose age has passed Statistics in the UK – physiological vs the median life functional age 65yrs expectancy at birth • UK – 81.2yrs • In Africa – 50-55yrs • Latin America – 60yrs 11
Age vs. Frailty… Both of these actors are the same age 12
Mortality of 75+ year old those who survive 6 months stratified by Frailty status 1.00 0.75 Fit 0.50 Mild Frailty 0.25 Moderate Frailty Severe Frailty 0.00 0 2 4 6 8 10 Follow-up (Years) analysis time 13 Data on File of Mazoli, J, Strain, WD et al from CPRD database
The frail, elderly patient with diabetes Older persons with diabetes are at higher risk than those without diabetes of: Usual complications of diabetes… Ageing and Diabetes CV disease, cancer and all cause morbidity/ mortality 14 Cukierman T, et al. Diabetologia. 2005;48(12):2460-9
The frail, elderly patient with diabetes Older persons with diabetes are at higher risk than those without diabetes of: Usual complications of diabetes… But Also Functional disability Ageing Functional Falls and and disability and fractures Geriatric syndromes: depression Diabetes depression CV disease, cancer and all cause morbidity/ mortality 15 Cukierman T, et al. Diabetologia. 2005;48(12):2460-9
The frail, elderly patient with diabetes Older persons with diabetes are at higher risk than those without diabetes of: Cognitive dysfunction Usual complications of diabetes… But Also Functional disability Ageing Functional Falls and and disability and fractures Geriatric syndromes: depression Diabetes depression Geriatric syndromes: cognitive impairment CV disease, cancer and all cause morbidity/ mortality 16 Cukierman T, et al. Diabetologia. 2005;48(12):2460-9
The frail, elderly patient with diabetes Older persons with diabetes are at higher Cognitive Cognitive risk than those without diabetes of: dysfunction dysfunction Usual complications of diabetes… But Also Functional disability Ageing Functional Falls and and disability and fractures Geriatric syndromes: depression Diabetes depression Geriatric syndromes: cognitive impairment CV disease, cancer and all cause Cognitive dysfunction should be added to the list of the morbidity/ complications of diabetes, along with retinopathy, neuropathy, mortality nephropathy and cardiovascular disease. 17 Cukierman T, et al. Diabetologia. 2005;48(12):2460-9
Pathophysiology ‒ diabetes and dementia Insulin Absence of ApoE4 resistance allele Reduced Cerebrovascular C-peptide ischemic event Hyperglycaemic Cognitive Cognitive Hypoglycaemia microvascular dysfunction dysfunction in diabetes injury ApoeE4, apolipoprotein E4; 18 Adapted from Kodl, et al. Endocrinol Rev 2008; 29:494 – 511
Hypoglycaemia and dementia 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 Adjusted for Age Additionally, adjusted Hypoglycaemia and risk of incident dementia cases a No. of No. of (as time scale) Hypoglycaemia and risk of incident dementia cases a Additionally adjusted for 7-year HbA1c level, hypoglycaemic dementia BMI, Race/Ethnicity, for comorbidities c diabetes treatment and episodes b (n) Adjusted for Age Additionally, adjusted cases education, sex, and duration years of insulin use No. of No. of (as time scale) BMI, for 7-year HbA 1c level, of diabetes hypoglycaemic dementia Race/Ethnicity, education, Additionally adjusted diabetes treatment and episodes b (n) cases sex, and duration of diabetes for comorbidities c 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 Hazard ratio (95% CI) a Analyses combined using Cox proportional hazard models; b The 1 or more group was compared with 0 and 1, 2 and 3 or more groups were simultaneously compared to 0; c Adjustment made using a comorbidity composite scale, BMI=body mass index; CI=confidence interval; HbA 1c =haemoglobin A 1c 19 Whitmer et al. JAMA 2009; 301:1565 – 572
Relationship between glucose and risk of dementia Risk of incident dementia associated with average glucose level over the preceding 5 years among participants without diabetes Patients without Diabetes Hazard Ratio Average Glucose Level for Dementia 2.00 (95% Cl) 1.80 Participants without diabetes 1.60 95 mg/dl 0.86 (0.77-0.97) 1.40 100 mg/dl 1.00 Hazard ratio 1.20 105 mg/dl 1.10 (1.03-1.17) 1.00 110 mg/dl 1.15 (1.05-1.27) 0.80 115 mg/dl 1.18 (1.04-1.33) p value 0.01 0.60 90 95 100 105 110 115 120 5-years Mean Glycemia (mg/dl) 20 Crane PK et al., N Engl J Med 2013; 369:540-548
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