Thierry PEPERSACK MD PhD CHU St Pierre, Brussels

Interuniversitary Cursus of the Belgian Society of Gerontology & Geriatrics, January 24, 2015

Prevalence & age

•  Prevalence increases with aging

•  Industrialized countries: –  10% after 65 yrs

–  20% after 80 yrs

– >2/3 of hospitalized diabetics are > 65 yrs old.

Harris MI, Flegal KM, Cowie CC, Eberhardt MS, Goldstein DE, Little RR, et al. Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults. The Third National Health and Nutrition Examination Survey, 1988-1994. Diabetes care. 1998 Apr;21(4):518-24

Type 2 diabetes

•  “diabète de maturité” •  “diabète gras”

Is Age “Changing diabetes?”

Meneilly GS. Diabetes in the Elderly. In: Morley JE (ed). MedicalClinics of North America – Geriatric Medicine. Philadelphia, PA: Elsevier Saunders; 2006;90:909-923 Chang A, Halter JB. Aging and insulin secretion. Am J Physiol Endocrinol Metab 2002; 284: E7–E12, 2003; 10.1152/ajpendo.00366.

•  High prevalence of undiagnosed diabetics

•  2/3 of old diabetics do not present over

weight

Harris et al. Diabetes 1987;36:513 Meneilly et al. Diabetes Care 19;1320

Prevalence & age

Diagnosis & age

•  Diagnostic criteria unchanged but

•  age leads some specificities in terms of:

– Risk of some complications (hyperosmolarity,

hypoglycemia, etc.)

– Therapeutic choices

– Monitoring modalities

Metabolism & age

•  The « classic» pattern of type 2 diabetes of the middle-age, compared to normal weigth- , age- and sex- matched controls

Arner et al 1991, Meneilly et al 1996

Metabolism & age

Metabolic studies for old (80 yrs) lean or obese diabetics

•  Metabolic pattern differs from middle-age diabetics !

Arner et al 1991, Meneilly et al 1996

Metabolism & age

Constratsly from middle age-diabetics: !  Fasting hepatic glucose production is normal

in lean or obese old diabetics! •  Fasting hepatic glucose production measured

after radioactive glucose infusion

Arner et al 1991, Meneilly et al 1996

Metabolism & age

Constratsly from middle age-diabetics: !  Fasting hepatic glucose production is normal in

lean or obese old diabetics! "  Like young diabetics, old lean diabetics

present a marked decreased of insulin production induced by glucose infusion

HOMA

Hermans MP, Pepersack TM, Godeaux LH, Beyer I, Turc AP. Prevalence and Determinants of Impaired Glucose Metabolism in Frail Elderly Patients: The Belgian Elderly Diabetes Survey (BEDS). J Gerontol A Biol Sci Med Sci. 2005 Feb;60(2):241-7.

Plots of individual values for all subjects (n=98) of HOMA insulin sensitivity (%S; log scale) versus HOMA beta-cell function (%B; log scale). Symbols depict subjects with normal glucose tolerance (NGT; n=86; open circles), impaired fasting glycaemia (IFG; n=5; filled squares), and diabetes mellitus (n=8; open triangles).

Arner et al 1991, Meneilly et al 1996

Metabolism & age

Constratsly from middle age-diabetics: 1.  Fasting hepatic glucose production is normal in

lean or obese old diabetics! 2.  Like young diabetics, old lean diabetics present

a marked decreased of insulin production 3.  And Insulin resistance is moderate in old lean

diabetics –  Measured by euglycaemic clamp

Glucose metabolism & age: summarize Age is changing diabetes!

The main disorders for old diabetics: •  Lean:

–  Insulin secretion deficit •  Obese:

–  Insulin Resistance

Susceptibility of the olders ?

In view of the risk of hypoglycaemia…

Age is changing diabetes

Old Diabetics: prevalence and severity of hypoglycaemias ↑ (Stepka 1993)

# Lack of education (Thomsen 1991) # Lack of awareness of the signs and symptoms # Atypical presentation (cognitive but no OS signs) # Hormones changes: •  Glucagon > epinéphrine, GH, cortisol •  ↓ glucagon and GH responses to hypo in old

healthy subjects and in old diabetics (Meneilly et al 1994)

Hypoglycaemia

Henderson et al. Hypoglycaemia in insulin-treated Type 2 diabetes: frequency, symptoms and impaired awareness.. Diabetic Medicine 2003

Susceptibility of the olders ?

•  Awareness of the symptoms –  CNS disorders, cognitive disorders, autonomous, drugs

•  Malnutrition –  Glycogene reserve

•  Contra regulation hormones •  Atypical presentation

–  Geriatric syndromes: confusion, falls, dizziness, incontinence, functional disorders

# Prevention of hypoglycaemia is a vitally issue

Diabetes Care 2011:34(5);1164-70

JAMA. 2009;301(15):1565-1572

Malnutrition of the elderly

Pepersack T, Corretge M, Beyer I, Namias B, Andr S, Benoit F, et al. Examining the effect of intervention to nutritional problems of hospitalised elderly: a pilot project. The journal of nutrition, health & aging. 2002;6(5):306-10 Pepersack T. Outcomes of continuous process improvement of nutritional care program among geriatric units. The journals of gerontology. 2005 Jun;60(6):787-92 Pepersack T. Nutritional problems in the elderly. Acta Clin Belg 2009;64:85-91.

Functional dependence of the elderly •  Hospitalized subjects

N=655 age:83(7) yrs

Pepersack T, Beyer I et al. Arch Public Health 1999

>60% need help to eat

sarcopenia

Pepersack T. For an operational definition of cachexia. Lancet Oncology 2011: 12(5): 423-4.

Clinical presentation

Severity of acute complications

1.  acido-cetosis

•  co-morbidity whorst the pronosis

•  Need more insulin, longer stabilisation

•  Increased mortality –  22% for older versus 2% for younger

Malone JAGS 1992;40:1100

Severity of acute complications

2.  Hyperosmolar – Exclusively in the elderly –  pathologenesis:

!  light or unknown diabetes "  precipitating factors (infarct, stroke, infection,

drugs) $  insidious installation (days, weeks)

–  Instuporation –  Major dehydration (% thirst, ADL, etc)

– Mortality 50%

Cardio vascular risk factors

•  Tobacco •  Stress •  Sedentarity •  Diabetes •  Hypertension •  Hypercholesterolemia •  Obesity

•  Familial •  …

•  Late Diagnosis (10 yrs) & specific complications: –  retinopathy

–  glomerulopathy

– Neuropathy

•  Causal rule of hyperglycemia...

Ocular complications

•  Cataract: •  after 70 yrs similar prevalence than for non

diabetics •  Rule of diabetes more marked for youngers

•  Retinopathy: •  >25% après 75 ans •  Olders with more maculopathies than vasculo-

proliferatives changes presentation

Micro-anevrism

retinopathy

Renal complications

Increased risk in olders : !  high prevalence of hypertension "  physiological age-related decrease of GFR $  increased risk of urinary infection (bladder

obstruction) # Increased risk of acute renal impairment # Avoid X-ray contrast products, biguanides

Kimmelstiel Wilson

Diabetic nephropathy

Dx 2 6 10 20 30 years

Microalbuminuria prevalence (type 2)

Diabetic Neuropathy

Several presentation: –  poly, mono -neuropathy, autonomus

–  High prevalence of: •  Proximal amyotrophic form

•  Cachectic, pseudoneoplasic forms

–  Continence problems: •  Neurogenic bladder/prostate

–  Higher prevalence of vascular dementia and DAT...

Diabetic foot

•  arterial+ neuropathy •  worsened by:

– Static alterations – Aged-related osteo articular changes

Infectious complications

Immunodepression if bad gly control – Cholecystitis –  candidosis –  tuberculosis – External malignant otitis

Morley et al 1991

Geriatric problems

•  Hypodypsia

•  Anorexia

•  % visual acuity

•  % ADL

' +4-8 drinks/d

' Screen for weight loss

' stylo, loupes

' orthesis, meals on

wheels

Morley et al 1991

Geriatric problems

•  % physical activity

•  % GFR, liver

•  % Cognitive

•  depression

'  exercise program

'  % drugs dosis

' pensum, rehabilitation?

' Early screening and

treatment

Morley et al 1991

Geriatric problems

•  % barorecept.

•  Polypharmacy

•  Polypathology

•  poverty

' Orthostatic hypotension

' limitation, information

' priorities

' Social assessment

Treatments

Hulka et al 1975

①  Sulfonylurea

•  Caution, start low dosis •  Caution: drugs with active metabolites excreted by

kidney •  Prefer

•  drugs with exclusive hepatic metabolisation •  Without active metabolites •  Short half-time, biodisponibility? …

•  Caution for interactions: –  β blockers, sulfamides, fibrates, NSAI, AVK

①  Sulfonylurea

•  Caution, start low dosis •  Caution: drugs with active metabolites excreted by

kidney •  Prefer

•  drugs with exclusive hepatic metabolisation •  Without active metabolites •  Short half-time, biodisponibility? …

•  Caution for interactions: –  β blockers, sulfamides, fibrates, NSAI, AVK

Research News Many older people may be overtreated for diabetes, US study findsBMJ 2015; 350 doi: http://dx.doi.org/10.1136/bmj.h188 (Published 14 January 2015)Cite this as: BMJ 2015;350:h188

②  Metformin

☺  No hypoglycemia, no weight gain (?)

)  lactic acidosis –  GFR

•  Avoird after 75 yrs?

–  *lactate •  Liver, cardiac impairment, BPCO, arteritis

•  Stop before surgical intervention, X-ray contrast products, stroke, …

•  Not indicated without obesity! (…)

③  Insulin

•  When FG > 200 mg/dl •  Represents β cell function deficit •  Most of case with 1 to 2 injections/d •  Get the help of caregivers (relatives, nurses,

etc.) •  Insulin is given to late in most of the cases...

Arguments to propose insulin in old lean diabetics

•  Metabolic – Catabolic state due to the loss of bêta-cell

function – Good insulin sensitivity

•  Prevention of the “geriatric syndromes” –  falls, malnutrition, “failure to thrive”, weigth

loss, sarcopenia, pain, etc. •  Known length of action helps for

hypoglycaemia prevention

④  others?

•  α-glucosidase inhibitors (acarbose®)

•  Glinides (novonorm®)

•  GLP-1 (Glucagon-like Peptide 1)

?

future

•  Vanadium •  Antilipolytic agents •  β3-adrenergic

agonists •  anti-TNF-α Ab

•  Retrospective analysis •  3300 Patients > 64 years

–  2204 nateglinide –  436 Metformine –  293 glyburide –  769 placebo

•  Nateglinide well tolerated and effective •  Lower risk of adverse effects (with and without RI)

Diabetes care 26:2075-2080,2003

Incretin effect •  GLP-1 is the main hormone responsible of the incretin effect

•  Rapid inactivation of GLP-1 by DPP-4 limits his effect

•  Therapeutic approaches :

①  Incretino-mimetics (GLP-1 analogs) : Byetta® SC ②  Increase the half-time of endogenous post prandial GLP-1

secretion : inhibitors of the DPP-4: Januvia® PO

Graydon and al J Clin Endocrinol Metab 90:6251-6256, 2005

Stafford S, Elahi D, Meneilly GD. Effects of dipeptityl dipetidase-4 inhibitor sitaglipti in older adults with type 2 diabetes mellitus. J Am Geriatr Soc 2011;59: 1148-9.

Education of the patient and the relatives

•  regularity of the meals, •  symptoms of the hypoglyceamia, •  effects of physical exercise on the gly

control •  technics for « resucrage » •  attitude in front of intercurrent disease •  etc.

Annual check for complications

•  Ophtalmo •  ECG •  Blood pression •  Foots exams

–  arteries, skin, nails, sensitivity

•  Myotatic reflexes •  GFR

–  Cockcroft •  microalbuminuria •  Urinary infection •  Thorax X-ray? •  TBC ID?

•  Holistic assessements – medical –  psycho-social –  functionnal –  environment

•  improve survival and maintain autonomy

Stuck AE et al. Lancet 1993;342:1032-36

College for Geriatrics

•  ADL I-ADL •  Mobility •  Cognition •  Depression •  Social •  Nutrition •  Pain •  Fragilité

•  Katz, Lawton •  Stratify •  Clock DT •  GDS, Cornell •  SOCIOS •  MUST •  VAS, INVD •  ISAR

Domains Scales Alerts/Procedures

#  Function (continence)

#  Falls #  Dementia, delirium #  Depression #  Complexity #  Malnutrition #  Pain #  Length of stay

Pepersack on behalf of the College for Geriatrics, 2005, access online www.geriatrie.be

% of screened geriatric problems

•  ADL I-ADL •  Incontinence •  Falls •  Cognition •  Depression •  Social •  Nutrition •  Pain

•  26% •  4% •  35% •  34% •  3% •  7% •  17% •  8%

#  89% #  60% #  46% #  68% #  49% #  50% #  65% #  43%

+  63%*

+  56%*

+  11%

+  34%*

+  46%*

+  43%*

+  48%*

+  35%*

*p<0.0001

Domains before: after: gain:

Pepersack on behalf of the College for Geriatrics, 2005, J Nutr Health Aging 2008

THOMs: age is changing diabetes

•  Specificity of the old lean diabetic •  Frailty of the geriatric patient:

–  Face to medical attitudes (confounding geriatric syndromes)

–  Face to complications (glucotoxicity, morbidity, hypoglycaemia)

–  Face to the delayed insulin treatment •  Find a treatment with optimal therapeutic index

–  Safe (immune, cancer, hypogly), –  Efficacy (gly, PPG, HbA1c)