MTE 1 and 6
Transitional Care – Adult to Geriatrics
Jill Crandall, MD
Saturday, February 8, 2014
2:00 p.m. – 3:30 p.m. and 3:45 p.m. – 5:15 p.m.
More than 25% of the US population over age 65 has diabetes and another 30% has impaired glucose
regulation and thus, are at increased risk for diabetes. Diabetes in older adults is not only common, but is
distinctly heterogeneous, since it includes “survivors” of middle-age (or earlier) onset of diabetes as well
as those with incident diabetes in older age. The burden of complications and co-morbidities and the
complexity of medical management are generally much greater in the former. Further complicating the
care of older adults with diabetes are age-related changes in body composition, drug metabolism,
hypoglycemia awareness, cognition and physical function. In addition, psycho-social issues such as
financial status, availability of family and community support and patient preferences and goals all
require special consideration with older patients with diabetes.
This session will review some of the unique and challenging aspects of diabetes management (type 1 and
type 2) in older adults and provide a form for case discussions and review of current clinical guidelines.
Reference List:
1. Kirkman MS, Briscoe VJ, Clark N, et al. Diabetes in older adults (ADA Consensus Report).
Diabetes Care 2012;35:2650-64.
2. Huang ES, Zhang Q, Gandra N, et al. The effect of comorbid illness and functional status on the
expected benefits of intensive glucose control in older patients with type 2 diabetes: a decision
analysis. Annals Intern Med 2008; 149:11-19.
3. Schutt M, Fach EM, Seufert J, et al. Multiple complications and frequent severe hypoglycemia in
elderly and old patients with type 1 diabetes. Diab Med 2012;29:e176-179.
4. American Geriatrics Society Expert Panel on the Care of Older Adults with Diabetes Mellitus.
Guidelines abstracted from the American Geriatrics Society Guidelines for Improving the Care of
Older Adults with Diabetes Mellitus: 2013 update. J Am Ger Soc 2013;61:2020-2026.
Issues in diabetes care:
transition from adult to geriatrics
Jill P. Crandall, MD
Diabetes Research & Training Center
Institute for Aging Research
Albert Einstein College of Medicine
Disclosures:
none
Percent (%)
Prevalence of glucose intolerance by age category
(NHANES 2005-2006)
Cowie, et al. Diabetes Care 2009;32:287
Age
group
Diabetes=diagnosed and undiagnosed
Pre-DM=IFG, IGT or both
Factors leading to diabetes in older adults
Impaired mitochondrial function
Increased intramyocellular lipid
Increased systemic inflammation
Sarcopenia
Plasma glucose (mmol/L)
Heterogeneity of diabetes in older adults
2-hr
glucose
FPG
Diabetes Care 2003;26:61
Diabetes Care 2009;32:287
Heterogeneity of diabetes in older adults (>65 yrs)
middle age vs. older age onset (NHANES)
No DM
Middle age onset Elderly onset
P
(MA vs. E)
Age at diagnosis (years)
---
53 (0.7)
Fasting glucose (mg/dl)
105 (12)
HbA1c (%)
5.6 (0.02)
Oral DM medication
Insulin use
Retinopathy
72 (0.5)
<0.001
172 (11)
132 (6)
0.001
7.4 (0.1)
6.9 (0.2)
0.01
---
46%
68%
0.83
---
46%
10%
<0.001
---
39%
13%
< 0.001
History of any CVD
20%
36%
35%
0.82
Stroke
8%
14%
11%
0.60
CAD
14%
30%
28%
0.75
Peripheral neuropathy
21%
36%
37%
0.86
Selvin, et al. Diabetes Care 2006;29:2415
Contributions of Basal and Prandial Hyperglycemia to Total
Hyperglycemia in Older and Younger Adults with Type 2
Diabetes Mellitus
Journal of the American Geriatrics Society
Volume 61, Issue 4, pages 535-541, 21 MAR 2013 DOI: 10.1111/jgs.12167
http://onlinelibrary.wiley.com/doi/10.1111/jgs.12167/full#jgs12167-fig-0002
Diabetes and geriatric syndromes
Diabetes and geriatric syndromes
• Cognitive dysfunction
• Physical function impairment
• Falls and fractures
•
•
•
•
•
Polypharmacy
Depression
Vision & hearing problems
Chronic pain
Urinary incontinence
Diabetes and cognitive impairment
• Increased prevalence of cognitive impairment and dementia
in cross-sectional studies
• DM is established risk factor for cerebrovascular disease
• Depression is more common in diabetes, can be confused w/
dementia
• Hypoglycemia (iatrogenic) may affect cognitive function
• Hyperglycemia (even experimental) reduces performance on
cognitive tests
• Plausible mechanisms exist to explain association, both for
vascular (CVD risk factors) and Alzheimer’s dementia (AGEs)
Effect of diabetes on cognitive function changes
12- year follow-up of the Maastricht Aging Study
Baseline status
Non- DM
DM
Baseline DM
accelerated cognitive decline
(information-processing and
executive function)
Incident DM
Early decline in information
processing
Duration of DM exposure
important in development of
cognitive decline
Spauwen, et al. Diabetes Care 2012;36:1554.
Diabetologia 2005;48:2460
ACCORD Mind
- No effect of intensive therapy
on tests of cognitive function
- Small reduction in brain atrophy
with intensive therapy
5 point lower DSST score
increased risk of severe
hypoglycemia by 13%
Diabetes Care 2012;35:787
Lancet Neurology 2011;10:969
Response to hypoglycemia with aging:
non-diabetics
Older (n=7) age 65±3 vs. younger (n=7) age 23±2
Stepped hypoglycemic clamp (nadir 50 mg/dl)
Matyka, et al. Diabetes Care 1997;20:135
Response to hypoglycemia with aging:
diabetic subjects
With increasing age:
- Reduced intensity of hypoglycemic
symptoms, despite normal hormonal
response to hypoglycemia
- Evidence of greater hypoglycemia
induced cognitive impairment
Bremer, at al. Diabetes Care 2009;32:1513
Hypoglycemia detected by CGM in older
adults with poor glucose control
95% of
hypoglycemic
episodes
unrecognized by
symptoms or FS
glucose
Frequency,
duration & severity
of hypoglycemia
the same for those
with HbA1c < or >
9%
Arch Intern Med. 2011;171(4):362-364.
Hypoglycemia
Impaired
cognition
JAMA 2009; 310:1565
JAMA Int Med 6/13
Diabetes and physical disability
The Study of Osteoporotic Fractures
Predictors of disability
(9 yrs F/U)
•Baseline functional status
•BMI
•Age
•CHD
•Arthritis
•Vision impairment
HRR 1.76
1.76
1.53
1.80
1.98
1.42
(1.43-2.15) (1.37-2.25) (1.31-1.80) (1.40-2.30) (1.40-2.79) (1.23-1.65)
•Physical inactivity
Gregg, et al. Diabetes Care 2002;25:61
Diabetes and risk of falls
Women’s Health & Aging Study
Multivariate odds ratio
No
DM
DM
orals
DM
insulin
Any fall
1
1.35
1.45
Recurrent
falls
1
1.34
2.73
Volpato, et al. J Geron 2005;60:1539
Diabetes and fracture risk
Increased risk of falls
Bone density & quality
• Sensory loss due to
• BMD increased (T2DM)
neuropathy – postural
• Bone quality reduced
instability
– Impaired bone strength
(greater cortical porosity)
• Peripheral vascular
– Reduced bone turnover
disease
(osteocalcin down,
• Hypoglycemia
sclerostin up)
• Vision loss due to diabetic
– Bone accumulation of
retinopathy
AGEs ( brittleness)
– Increased ROS
• Impaired physical function
Curr Diab Rep 2013;13:411
Diabetes & Fractures
ARIC study
Fracture related hospitalizations
HR 1.74 (1.42-2.14)
Diabetes Care 2013;36:1153
For a given T score (or FRAX score),
women with DM had a higher risk of hip or
non-spine fracture than women without DM
of similar age.
Non-spine fractures in women
JAMA 2011;305:2184
Specific treatment considerations
weight and nutrition
pharmacology
Weight & body composition change with age
• Body composition
– Sarcopenic obesity  frailty
• Intentional and unintentional weight loss both
associated with:
– loss of muscle and bone mass
– risk of micronutrient deficiency
– increased mortality in observational studies
• Role of physical activity
– May protect from adverse changes in body
composition
•
•
•
•
Age 70 ±5, BMI 39± 5
Reduced calorie diet
Wt. loss goal 10%
Supervised exercise, 90’ tiw
Percent change from baseline
Control
Diet & exercise
p
0.4
9.2
.001
VO2 max
1.8
10.4
.02
Walking speed
-1.9
7.6
0.04
Knee flexion
1.1
25.5
.008
Single leg stand
-5.5
79.5
.04
Physical performance
Arch Int Med 2006; 166:860
Diabetes pharmacotherapy in older adults:
What is the same and what is different?
Same
• Drug efficacy similar
in most cases
• Side effect profiles
also similar
Different
• Less tolerance for hypoglycemia
risk
• Susceptibility to certain AEs
(fractures, CHF) greater in
elderly
• Non-pharmacological factors
may have greater importance
– Cost, ease of use, polypharmacy
Diabetes Clinical Trials in Older Adults
• Older adults are underrepresented in most RCT
• Few patients over age 70 or with significant comorbidities are enrolled
• Few trials designed to address age –related
differences in drug response
• Most evidence is from post-hoc sub-group
analysis
Factors influencing drug effects in older adults
Pharmacokinetics
• Changes in body
composition: Reduced
lean body mass, albumin
& body water; increased
fat mass
• Reduced renal function
• Decreased hepatic blood
flow and reduced function
of drug metabolizing
enzymes (*)
Pharmacodynamics
• Loss of “homeostatic
resilience”
• Polypharmacy and drug
interactions
• Specific age-related
metabolic defects
* Highly variable
Anti-diabetic medications: use in the elderly
•
•
•
•
•
•
•
Metformin
SU and glinides
TZDs
DPP-4 inhibitors
GLP1 agonists
Insulin
Other non-insulin meds (α-glucosidase inhibitors,
colesevelam, bromocriptine, pramlintide)
Does it work?
Is it safe?
Metformin failure and age
Kaiser-Permanente HMO
– Older patients more likely to achieve HbA1c < 8% in 1st year
of treatment
– In multivariable analysis, younger age was independent
predictor of metformin failure (HbA1c > 7.5% or 2nd drug)
– Each additional 10 years of age lowers risk of subsequent
metformin failure by 17%
– Mean age was ~ 58±12
Brown, et al. Diabetes Care 2010;33:501
Nichols, et al Diabetes Care 2006;29:504-09
Metformin safety in older adults
Study of metformin in adults age 70-88 yrs (n=24)
If CrCl 30-60 ml/min – 850 mg/day
If CrCl > 60 ml/min – 1,700 mg/day
After 2 months, metformin levels in therapeutic range and lactate not
elevated and did not differ by renal status
Int J Clin Pharmacol Ther Toxicol 1990;28:329
Additional considerations:
- Vitamin B12 deficiency
(Diabetes Care 2012;35:327)
- Weight loss
Lipska, et al. Diabetes Care 2011;34:1431
Sulfonylureas
• SU –hepatic metabolism, renal excretion
• Risk of hypoglycemia
relative risk of severe hypoglycemia ~1.3 for
patients age 65+, c/w ages 20-64
J Clin Epidemiol 1997;50:735
- Acute and chronic (12 weeks) dosing of glyburide at
doses up to 20 mg/day
- Mean age 69 (n=10) vs. 46 (n=10)
- Pharmacokinetics similar in both age groups
- Pharmacodynamics similar in both age groups
- Conclusion: age per se appears to have no influence on
pharmacokinetics/dynamics
Annals of Pharmacotherapy 1996;30:472
Sulfonylureas:
increased risk of hypoglycemia with glyburide
Incidence of severe hypoglycemia:
Glimepiride 0.86/1000 person-years
vs.
Glibenclamide 5.6/1000 person-years
Holstein,et al. Diabetes Metab Res
Rev 2001;17:467
Adjusted relative risk of severe hypoglycemia
among glyburide users, compared with glipizide
users: 1.9 (95% CI, 1.2 to 2.9)
Shorr et al. JAGS 1996
TZDs and fracture risk
DC 2008
Loke, et al. CMAJ 2009;180:32
Fracture risk with TZDs
• Fx risk mostly in women
• Distal limb fx most
common (humerus,
wrist); hip?
• Fx risk increases with
longer duration of
exposure
• Risk with pio (OR ~2.6)
similar to rosi (OR~ 2.4)
Diab Med 2011; 28:759
Arch Intern Med 2008;168:820-825
• Bone density reduced
(hip, spine)
• Markers of bone
formation reduced
• Evidence for decreased
osteoblast differentiation
• Increased bone marrow
fat
• Variable evidence for
increased osteoclast
activity
DPP-4 inhibitors
• 206 patients, mean age 72
(range, 65-96)
• Baseline HbA1c 7.8%
(range, 6.5-10.0)
• Sitagliptin 100 or 50 mg/day
Safety:
- Overall AEs and serious AEs
similar in active and placebo
groups
-No hypoglycemia AEs reported
-Drug related AEs in 10.8%
(active) and 8.7% (placebo)
Barzilai, et al. CMRO 2011;27:1049
GLP-1 agonists
• Pooled analysis of phase 3 trials
• Mean age 69 vs. 52 years
Liraglutide Liraglutide
1.8 mg
1.2 mg
>65
Placebo
< 65 > 65 < 65 > 65 < 65
Minor hypoglycemia (%)
15
13
4
8
9
8
SAEs (%)
4.1
3.9
7.6
4.8
5.1
4.9
Vomiting (%)
7.4
7.8
5.4
8.4
3.0
1.9
Withdrawn due to n/v (%)
9.7
4.9
3.7
4.2
0
0.2
Bode et al. Am J Geriatr Pharmacother 2011;9:423
Insulin
• Pharmacokinetics and pharmacodynamics of insulin
analogs similar in older vs. younger patients
• Main issues are:
–
–
–
–
Complexity of regimens
Ease of administration (syringe vs. pen)
Cost
Tolerance for hypoglycemia risk
Krones, et al. Diab Ob Metab 2007;9:754
Basal insulin + OHD vs. biphasic insulin
• ~130 patients, mean age 69
• OH failure (HbA1c 8.9%)
• Add glargine to SU + metformin
vs. 70/30
• Dose titration
Janka, et al. JAGS 2007;55:182
Type 1 diabetes in older adults
Compared with older patients with T2DM:
• Likely to have longer duration of DM,
therefore more complications
• More likely to have impaired hypoglycemia
counter-regulation and hypoglycemia
unawareness
• No therapeutic option to insulin –hpoglycemia
risk cannot be eliminated
Characteristics of older vs. younger
Type 1 DM patients
Age (years)
Diabetes duration (years)
HbA1c (%)
Severe hypoglycemia
(episodes/100 p-y)
BMI (kg/m2)
Diabetic retinopathy (%)
Age < 60
N=60,622
20
8
8.3
24
Age > 60
N=3987
70
28
7.6
40
22
8
27
45
0.4
0.3
24
9
7
12
MI (%)
Stroke (%)
Insulin pump use (%)
Schutt et al. Diabetic Medicine 2012;29:e176
Type 1 DM in the elderly
• Loosening glycemic targets alone not
sufficient to reduce risk of hypoglycemia
• Patient with declining cognitive ability needs
to transition care to family or health care
system
• Families and health care providers (e.g.,
visiting nurse, senior centers) may not be
familiar with complex treatment regimens
Treatment guidelines
for older adults with diabetes
American Diabetes Association
and Lilly Clinical Research Award:
Diabetes Care in Older Adult
Diabetes Care 2012;35:2650
Clinical and translational studies
focused on improving the evidence
base and understanding of the
goals, barriers, and effects of
treatments and interventions in older
adults with type 1 and type 2
diabetes
JAGS 2013;11:2020
Consensus recommendations
Screen older adults periodically for:
• Cognitive dysfunction
www.mocatest.org/
www.hospitalmedicine.org/geriresource/toolbox/mental_status
_page.htm
• Depression
PHQ-9
Geriatric Depression Scale
• Functional status & fall risk
Short Physical Performance Battery (SPPB)
Consensus recommendations
• Assess patients for hypoglycemia regularly
• Chose anti-hyperglycemic therapies carefully
– Consider polypharmacy
– Avoid glyburide, TZDs
– Metformin appropriate for many patients
• Individualize goals and re-assess frequently
• Assess burden of treatment (patient and caregivers)
• Screening and prevention for patients likely to
benefit
Individualization of glycemic targets
ADA 2012
Health status categories
to determine treatment goals
Healthy
-
Few co-existing illness
Intact cognition and
physical function
Longer remaining life
expectancy
Complex
intermediate
-
Multiple co-existing
chronic illnesses
ADL deficits (2+)
Mild-moderate cognitive
or physical impairment
Intermediate remaining
life expectancy; high
treatment burden;
hypoglycemia
vulnerability; fall risk
Very complex
poor health
-
Long term care facility –
end stage chronic disease
moderate to severe
cognitive impairment
Limited remaining life
expectancy makes
benefits uncertain
Diabetes Care 2012;35:2650
-
Treatment goals for older adults with diabetes
HbA1c
Healthy
Complex
intermediate
Very complex
poor health
< 7.5%
< 8.0%
Fasting
glucose
90-130
90-150
Treatment Goals
Bedtime
Blood
glucose pressure
90-150
< 140/80
100-180 < 140/80
< 8.5% 100-180
110-200
Lipids
Statin *
Statin *
< 150/90 Consider
benefit
* Statin unless contraindicated or not tolerated
Diabetes Care 2012;35:2650
Consensus recommendations for research questions
• What specific cellular and molecular mechanisms underline
the high rates of diabetes in older adults?
• How does aging affect trajectories of development of
micro/macro vascular complications?
• What are the mechanisms that link diabetes and cognitive
impairment?
• Comparative effectiveness studies of diabetes therapies in
older adults
• What is true incidence (and consequences)of hypoglycemia in
older adults?
• What is the evidence that intentional weight loss is beneficial
in overweight older adults with diabetes?
Diabetes Care 2012;35:2650
Additional resources
ASP Workshop on Diabetes Mellitus and
Cardiovascular Disease in Older Adults
http://www.im.org/AcademicAffairs/Aging
Cases for discussion
Ms Andrews, your 83-year-old patient, is proud. She walks daily,
watches her diet, and never misses her appointments. Her glycated
hemoglobin (HbA1c) level is 6.9%. As she readies to leave, you notice
her bruised arm. It is from one of her fainting spells, she says. After
asking a few more questions, you realize she has been having
hypoglycemic episodes, including at least 1 last week in which she lost
consciousness and needed her son’s assistance. Based on multiple
performance metrics, her care has been exemplary. But has your
treatment caused more harm than good?
Ms Andrews wants her life back; her fainting spells have limited her daily
walks and social visits, and she lives in fear of getting hurt and of losing
her independence. She now recognizes that hypoglycemia did not need
to be an obligatory consequence of her treatment. Her cognition is briefly
tested, and results suggest normal function. After discussing her options
using a decision aid (http://diabetesdecisionaid.mayoclinic.org), she
prefers a simpler insulin regimen to achieve an HbA1c level of about 8%
Lipska and Montori;JAMA Intern Med. 2013;173(14):1306-1307
Mr. F
•
•
•
•
82 yo man, h/o T2DM, insulin requiring for > 20 yrs
Well controlled on basal/bolus
Multiple co-morbidities (CAD, PVD, CKD 4, COPD)
Declining cognitive function
– Poor judgment re: insulin dosing
– Poor memory – skipping doses or double-dosing
– Declining impulse control- un-restrained eating
• Change of goals
• Shift in responsibility from pt. to wife
• Behavior management (limit access to food outside of
meal time)
Ms. Z
• 71 yo woman w/ new onset DM (BMI ~ 30); well
controlled on metformin, then SU for ~ 3 years
• Dramatic weight loss (intentional?), but gradual
worsening of glycemic control (HbA1c 6.8% to 9%)
•
•
•
•
Granddaughter w/ T1DM
antiGAD antibodies +++
C-peptide < 0.6
Dx: LADA
Ms. Z
• Did well on low-dose basal insulin, fixed dose
pre-meal aspart
• Gradual deterioration, glucose more variable,
volatile
• Multiple attempts to teach CHO counting
– By now she is 80 yrs old
– Pt. frustrated with poor control (A1c < 8%)
– Difficulty with new tasks
• Shift in goals: avoid extremes, accept less than
perfect glucose regulation
• CHO consistency, fixed doses, frequent monitoring
Ms. S
•
•
•
•
65 yo woman T2DM
Well controlled on SU
Regular exercise, vegetarian diet
Enrolled in LookAhead trial
• Increasing co-morbidities: spinal stenosis,
osteoarthritis, gout  unable to exercise, weight gain
• Economic stress  can’t afford fresh veggies,
preferred diet not feasible
• Glucose control deteriorates
Ms. S
• Now age 80
• Begins insulin, but unable to control glucose
• Lives alone, fearful of lows
• Co-pays mount, can’t afford pens, strips
• Focus on other medical conditions, does not
follow through on changes to insulin regimen
Ms. G
• 65 yo woman with cognitive impairment; lives
with similarly impaired sister
• Deteriorating glucose control on metformin
plus DPP4 inhibitor (HbA1c 8.5%)
• Patient & family goals:
– maintain independent living
– acceptable glycemic control
• Treatment focus: avoid hypoglycemia potential
• Options:
- acarbose
– TZD
– SGLT2 inhibitor
- bromocriptine
- colesevelam
Mr. M
• 90 yo man, h/o T2DM for ~ 5 years
• Did well on metformin, but d/c due to eGFR 30;
sitagliptin started
• Admitted with acute pancreatitis, DKA -> started on
insulin (glargine 60 units/day)
• Recurrent hypoglycemia, glargine dose reduced
• HbA1c 11%
• BMI 22
• Son administers insulin q HS, is away all day at work
• Diet: snacks on “SF” candies, cookies, puddings
Mr. M
Glargine
wt
am FS
pm FS
aspart
HS FS