Self-reported Fatigue: Relationships with Physical Function and Oxygen Uptake in Leg Osteoarthritis and Type 2 Diabetes

Mobility Research Center (MRC)1; Department of Physical Medicine and Rehabilitation, University of Michigan2 ; Geriatrics Center and Division of Geriatric Medicine3 University of Michigan Hospitals;

VA Ann Arbor Health Care System Geriatric Research Education and Clinical Center (GRECC)4

Acknowledgments: National Institute on Aging; National Center for Medical Rehabilitation Research; American College of Rheumatology Research and Education

Foundation; VA Office of Research and Development (Rehab R&D and Medical Research Services)

Susan Murphy ScD, OTR1,2,4

Neil Alexander MD1,3,4

Presentation

Part I: Older women with leg osteoarthritis

A. Daily pain and fatigue, in relation to physical activity

B. Behavioral intervention to reduce barriers to PA and increase symptom control

Part II: Task-specific oxygen uptake and self-reported fatigue in older adults

A. As predictors of mobility performance

B. In Type 2 diabetes mellitus

Symptoms and Physical Activity in Women with OA

• 60 women (40 with knee or hip OA, 20 controls)

• Mean age 64 + 8 years• 5 day home assessment

– Actiwatch-S measured physical activity; recorded symptoms 6 times/day

– Pain/fatigue measured on scale of (0- none to 4-extremely severe)

– Fatigue defined as “tiredness or weariness”

Part I A: Clinical Research Questions

• How do pain and fatigue symptoms manifest in daily routines?

• How do pain and fatigue symptoms impact physical activity?

Pain in Women with OA and Controls (data depicted as means + SE)

0

0.5

1

1.5

2

2.5

1 3 5 7 9 11 13 15 17 19 21 23 25 27 29

All Timepoints over 5 days

Pa

in 0

-4

control

OA

Day 1 Day 2 Day 3 Day 4 Day 5

Fatigue in Women with OA and Controls (data depicted as means + SE)

0

0.5

1

1.5

2

2.5

1 3 5 7 9 11 13 15 17 19 21 23 25 27 29

All Timepoints over 5 days

Fa

tig

ue

0-4

control

OA

Day 1 Day 2 Day 3 Day 4 Day 5

Momentary Within-Day Symptoms by WOMAC Physical Disability

0

0.5

1

1.5

2

2.5

Low WOMAC Physical Disability High WOMAC Physical Disability

Sy

mp

tom

Se

ve

rity

Pain

Fatigue

Dependent Variable: Physical Activityβ

estimateStandard

Error P value

Fatigue -30.08 6.21 <.0001

Pain 16.86 8.36 .04

Age -2.43 1.79 .18

Geriatric Depression Scale -7.52 5.40 .17

Daily Medication Use -2.07 14.50 .89

Timed Up and Go Test -14.30 6.00 .02

Summary and Conclusions • For women with mildly painful OA, momentary

fatigue may increase more disproportionately through the day than pain, particularly in those with higher disability (more pain)

• Increased momentary fatigue is associated with decreased physical activity

• Increased pain is associated with increased physical activity

• Interventions to increase physical activity and manage symptoms in leg osteoarthritis may need a better emphasis on fatigue

Murphy SL et al. Arthritis Rheum 2008

Part 1 B: Behavioral Intervention• Current exercise programs for OA limited in their

link to activity or environmental context, nor are they designed to reduce individual barriers to PA and improve symptom control

• Hypothesis: Compared to those randomized to group exercise

and health education, can group exercise plus activity strategy training (AST, an OT approach) more effectively improve pain, fatigue, and physical activity?

• Design:– 1 month intervention with 2 and 4 month

boosters– 6 month follow-up

Baseline Characteristics

EX + ED

(n=26)EX + AST

(n=28)

P

value

Age (years) 74.8 (7.3) 75.8 (7.1) .65

No. of women (%) 22 (85) 26 (93) .33

BMI (kg/m2) 30.0 (4.8) 30.1 (6.5) .98

No. of chronic conditions 1 (1.2) 1.5 (1.4) .17

No. of painful joints 4.6 (2.1) 4.4 (2.1) .79

(Murphy SL et al, Arthritis Rheum, in press)

EX+ED EX+AST

Pain and Fatigue Symptoms in OA PatientsPre and Post Intervention

0

2

4

6

8

PRE POST

fatigue

pain

Fatigue - Brief Fatigue Inventory, severity subscale; Pain – WOMAC pain subscale

Pain (time) p<0.005

Fatigue (time x group) p<0.05

Trend for fatigue to decrease in AST and increase in ED

Daily Peak Activity

600

640

680

720

760

Pre-Intervention Post-Intervention

Act

ivit

y C

ou

nts

EX+ED EX+AST

Activity counts – collected via wrist-worn accelerometry (Actiwatch, MiniMitter-Respironics)

Trend for peak activity to increase in AST and decrease in ED

(time x group) p<0.05

Summary and Conclusions

• Compared to controls. participants in a group exercise plus activity strategy training designed to reduce individual barriers to PA and improve symptom control had:– Reductions in pain– Reductions in fatigue– Improvements in peak physical activity

Part II: Task-specific oxygen uptake and self-reported fatigue in older adults

• Global question: How does aerobic function relate to: – mobility performance?– symptoms of exertion and fatigue?

• A: Analysis of peak V02 versus submaximal oxygen kinetics in predicting mobility performance.

• B: In Type 2 diabetics, analysis of VO2 during peak GXT, submax, and six minute walk (6MW) in predicting perceived exertion (RPE) and fatigue

Background and Significance

• Age- and disease-associated declines in aerobic capacity (VO2 Max) contribute to functional disability in older adults.

• Standard VO2 measures may be limited

– Max VO2 (e.g. max treadmill) is difficult to achieve in older adults

– Peak VO2 is frequently reported

Background and Significance (2)

• The aerobic demands of many ADL’s are submaximal

• Measures of submaximal (vs maximal or peak) aerobic fitness might:– Be easier and safer to perform, especially

for frail older adults– Better predict functional ability

0

0.1

0.2

0.3

0.4

0.5

0.6

Oxy

gen

Con

sum

ptio

n (L

/min

)

0 120 240 360 480 600 720 840

Time (sec)

Oxygen Debt

Oxygen Deficit

Exercise

Kinetics Of Oxygen Uptake

Oxygen Kinetics in Healthy Older Woman

0 180 360 540 720 900

Time (seconds)

Healthy Woman

RestWalking (1.0 mph) Recovery

(63.7 mL)

(944.1 mL)

0

200

400

600

800

1000O

xyg

en

Up

take (

mL

/min

)O2 Deficit

O2 Debt

Oxygen Kinetics in Healthy and Mobility Impaired Older Women

0 180 360 540 720 900

Time (seconds)

Healthy Woman

RestWalking (1.0 mph) Recovery

(63.7 mL)

(944.1 mL)

0

200

400

600

800

1000

Oxyg

en

Up

take (

mL

/min

)

O2 Deficit

O2 Debt

0 180 360 540 720 900

Time (seconds)

Mobility Impaired Woman

RestWalking (1.0 mph) Recovery

(873.0 mL)

(1734.4 mL)

0

200

400

600

800

1000

Oxyg

en

Up

take (

mL

/min

)

O2 Deficit

O2 Debt

Mean (SEM) Comparisons: Aerobic Unimpaired (n=21) vs Impaired (n=20)

Unimpaired Impaired

Age (yrs) 76 (1) 82 (1)*

Peak VO2 (ml/kg/min) 24 (1) 14 (1)*

TCdeficit (s) 23 (3) 58 (9)*

TCepoc (s) 40 (7) 57 (7)

Get up + Go (s) 12 (1) 20 (2)*

6-min-walk (m) 415 (17) 286 (27)*

*p<0.05

(Alexander, J Gerontol, 2003)

Tcdeficit => Initial oxygen deficitTcepoc => Excess post-exercise oxygen

consumption

Peak VO2 and Oxygen Kinetics versus Functional Performance: Unimpaired Old

Task Peak VO2 tcdeficit tcEPOC

Peak VO2 0.62** 0.29

GUG 0.48* 0.58* 0.06

GUG x 3 0.55* 0.60** 0.13

Bag Carry 0.29 0.22 0.59**

Six Min Wk 0.45* 0.31 0.15

** p<0.01; * p<0.05 (Alexander, J Gerontol, 2003)

Peak VO2 and Oxygen Kinetics versus Functional Performance: Impaired Old

Task Peak VO2 tcdeficit tcEPOC

Peak VO2 0.11 0.49*

GUG 0.21 0.10 0.42

GUG x 3 0.41 0.02 0.33

Bag Carry 0.35 0.07 0.53*

Six Min Wk 0.62** 0.18 0.64**

** p<0.01; * p<0.05 (Alexander, J Gerontol, 2003)

Summary and Conclusions• Older adults with aerobic impairment have:

– Slowed submaximal oxygen kinetics– Poor functional mobility performance

• Measures of submaximal oxygen kinetics correlate as highly with functional mobility performance as Peak VO2 measures, particularly for impaired old during post-exercise recovery.

• Submaximal VO2 kinetics may be more useful than Peak VO2 in estimating the contribution of aerobic function to mobility impairment.

Type 2 Diabetics[Enrolled in RCT ex program, age >60, n=56 [27 female]

Mean (SD) Range

Age (years) 70.4 (5.7) 60-83

BMI 33.6 (5.9) 24-50

EPESE total 1.0 (1.2) 0-6.0

BFI (global) 2.0 (1.8) 0-7.3

BFI (severity) 2.9 (2.2) 0-8.3

6MW dist (feet) 1264.5 (229.6) 660-1960

Comf Gait Sp (m/s) 1.2 (0.2) 0.8-1.5

Oxygen Uptake (VO2) Measurements

Three tasks:Graduated treadmill

(traditional peak)Submaximal treadmill

(1 MPH)Six minute walk

Self Report Measurements

During exercise task:• Rated Perceived Exertion (RPE): How hard

you worked– Range 6-20; 11=fairly light; 13=somewhat

hard; 15=hard; 17=very hard• Fatigue: How much fatigue you had

– 0=No fatigue; 10=Fatigue as bad as could be

0

5

10

15

20

25

Peak VO2 During TaskSubmax6MWGXT

Mean(SD)

OxygenUptake

(ml/kg/min)

*

*

*

0

5

10

15

20

Post-Task Rate of Perceived Exertion (RPE)

Submax6MWGXT

Mean(SD)RPE

Score

0

5

10

15

20

25

Peak VO2 During TaskSubmax6MWGXT

Mean(SD)

OxygenUptake

(ml/kg/min)

*

*

*

0

1

2

3

4

5

6

7

8

Fatigue Post-TaskSubmax6MWGXT

Mean(SD)

FatigueScore

*

*

*

Self-reported task-specific fatigue is not related to general fatigue

Post-task fatigue rating GXT Submax 6MW BFI global 0.12 0.18 -0.04 BFI severity 0.12 0.07 -0.11 Submax fatigue 0.52* 0.50* 6MW fatigue 0.39* 0.50* GXT fatigue 0.52* 0.39*

Non-peak task-related fatigue may better relate to usual mobility function

Post-task fatigue rating GXT Submax 6MW BFI global 0.12 0.18 -0.04 BFI severity 0.12 0.07 -0.11 EPESE 0.14 0.32* 0.16 TUG 0.28* 0.31* 0.16 Comf Gait Sp -0.25 -0.32* -0.22 6MW dist -0.14 -0.47* -0.32*

Task specific self-reported fatigue relates more to VO2 kinetics than peak VO2

Post-task fatigue rating GXT Submax 6MW Peak GXT VO2 -0.12 Peak Submax VO2 -0.04 Peak 6MW VO2 -0.05 Submax Tc deficit 0.15 Submax Tc EPOC 0.34* 6MW Tc deficit 0.33* 6MW EPOC 0.39*

Summary and Conclusions

In this group of relatively functional older adult Type 2 diabetics:

• Peak VO2 and post-task fatigue increase with task demand

• Self-reported task-specific fatigue is not related to general fatigue

• Non-peak task-related fatigue may better relate to usual mobility function

• Task specific self-reported fatigue relates more to VO2 kinetics than peak VO2

Discussion

• Measures acquired during submaximal exercise tests, including 6MW, as opposed to peak GXT, are better indicators of physical function, and likely fatigue.

• Future studies should consider:– Whether these relationships hold true for

other models of disability and fatigue (such as in non-cardiac disease, high baseline fatigue)

– What the underlying physiological link is between subjective fatigue and objective measures of oxygen utilization

MRC faculty/collaborators, staff and students/fellows Faculty Staff Students/Fellows

N. Alexander W. Champoux D. Adamo B. Schulz

J. Ashton-Miller D. Channer A. Beg C. Smeesters

C. Blaum R. Cleland M. Branch J. Sprague

A. Chang R. Goswami C. Cao D. Thelen

D. Dengel B. Grincewicz S. Carlos J. Ulbrich

D. Fry-Welch J. Grunawalt H. Chen L. Wojcik

A. Galecki M. Hofmeyer J. Dean

B. Giordani R. Keller K. DeGoede

K. Gretebeck J. Kemp-Rowe N. Gallagher

M. Gross J. Medell A. Goldberg

K. Guire T. Moore M. Gu

A. Kuo T. Morrow M. Hernandez

J. Liang M. Nabozny D. Koester

S. Murphy E. Pear K. Kozak

L. Nyquist D. Scarpace J. Light

C Persad D. Strasburg C. Luchies

A. Schultz D. Wilson M. Montagnini

N. Shepard J. Nnodim

P. Vaitkevicius

L. Yao

Area B = VO2(SS)/k

Area A

k=VO2(SS)/O2 deficit

or

k= 0.693/t1/2

Calculation Of Oxygen Uptake Kinetics

Whipp, JAP 30:261-263, 1971

Onset of Work

Time (min)

VO

2 (m

L/m

in)

Mono-exponential Model of Oxygen Uptake Kinetics

VO2=VO2(steady-state)(1-e-(kt))

VO2 is VO2 above baseline at time t

VO2 is steady state increase in VO2

• k is the rate constant of the reaction with the dimension of t-1