diabetes-related microvascular and macrovascular

8/12/2019 Diabetes-Related Microvascular and Macrovascular

1/35

Diabetes-Related Microvascular and MacrovascularDiseases in the Physical Therapy SettingW Todd CadePHYS THER. 2008; 88:1322-1335.

Originally published online September 18,2008 doi: 10.2522/ptj.20080008

The online version of this article, along with updated information and services, can befound online at: http://ptjournal.apta.org/content/88/11/1322

Collections This article, along with others on similar topics, appearsin the following collection(s):

Cardiovascular/Pulmonary System: OtherDiabetesOther Diseases or Conditions

e-LettersTo submit an e-Letter on this article, click here or clickon"Submit a response" in the right-hand menu under"Responses" in the online version of this article.

E-mail alerts Sign up here to receive free e-mail alerts
http://http//ptjournal.apta.org/content/88/11/1322http://http//ptjournal.apta.org/content/88/11/1322http://ptjournal.apta.org/cgi/collection/cardiovascular_pulmonary_system_otherhttp://ptjournal.apta.org/cgi/collection/cardiovascular_pulmonary_system_otherhttp://ptjournal.apta.org/cgi/collection/cardiovascular_pulmonary_system_otherhttp://ptjournal.apta.org/cgi/collection/diabeteshttp://ptjournal.apta.org/cgi/collection/diabeteshttp://ptjournal.apta.org/cgi/collection/other_diseases_or_conditionshttp://ptjournal.apta.org/cgi/collection/other_diseases_or_conditionshttp://ptjournal.apta.org/letters/submit/ptjournal;88/11/1322http://ptjournal.apta.org/letters/submit/ptjournal;88/11/1322http://ptjournal.apta.org/subscriptions/etoc.xhtmlhttp://ptjournal.apta.org/subscriptions/etoc.xhtmlhttp://ptjournal.apta.org/cgi/collection/cardiovascular_pulmonary_system_otherhttp://ptjournal.apta.org/cgi/collection/diabeteshttp://ptjournal.apta.org/cgi/collection/other_diseases_or_conditionshttp://ptjournal.apta.org/letters/submit/ptjournal;88/11/1322http://ptjournal.apta.org/subscriptions/etoc.xhtmlhttp://http//ptjournal.apta.org/content/88/11/1322


2/35

Downloaded from http://ptjournal.apta.org/ by

guest on February 6, 2014
http://ptjournal.apta.org/http://ptjournal.apta.org/http://ptjournal.apta.org/


3/35

DiabetesSpecial Issue


4/35


5/35

WT

Cade,

PT, PhD,

is

Assistant

Professor

of

Physical

Therapy

and

Medicine,

Washington

Universit

y School

of

Medicine,

Campus

Bo

!"#$,

%%%%

&orest

Par'

Blvd, St

(ouis,

M)

*+#!

-USA./

Address

all

correspo

ndence

to Dr

Cade at0

cadet12

usm/2ust

l/edu/

3Cade

WT/

Dia4etes

5relatedmicrovas

cular

and

macrova

scular

diseases

in the

physical

therapy

setting/

Phys

Ther.

$##!6!!0

+$$7

++"/8

9 $##!AmericanPhysicalTherapy

Association

Diabetes-Relat

edMicrovascularand

M

acrovascular

Dise

ases inthe

PhysicalTherapy

SettingW Todd Cade

Physical therapists

commonly treat

people with

diabetes for a wide

variety of

diabetes-

associated

impairments,including those

from diabetes-

related vascular

dis-ease. Diabetes

is associated with

both

microvascular and

macrovascular

diseases affecting

several organs,

including muscle,

skin, heart, brain,and kidneys. A

common etiology

links the different

types of diabetes-

associated

vascular disease.

ommon risk

factors for

vascular disease in

people with

diabetes,

specifically type !diabetes, include

hyperglycemia,

insulin resistance,

dyslipidemia,

hypertension,

tobacco use, and

obesity.

"echanisms for

vascular disease in

diabetes include

the pathologic

effects of

advanced

glycation end

product


6/35

accumu

lation,

impaire

d

vasodil

atory

re-

sponse

attribut

able to

nitric

o#ide

inhibiti

on,

smooth

muscle

cell

dysfunc

tion,

over-

product

ion of

endot

helial

grow

th

facto

rs,

chro

nic

infla

mma

tion,

hemo

dyna

mic

dys-

regul

ation

,

impa

ired

fibrin

olyti

c ability, and

enhanced platelet

aggregation. It is

becoming

increasingly

important for

physical therapists

to be aware of

diabetes-related

vascular

complications as

more patients

present with

insulin resistance

and diabetes. $he

opportunities for

effective physical

therapy

interventions %such

as e#ercise& are

significant.

Post

a

Rapi

d

Resp

onse

or

find

The

Bott

om

L

i

ne

:

w

w

w

.

p

t

j

o

u

r

n

al

.

o

rg

+$$ f PhysicalTherapy :olume!! ;um4er

;ovem4er $##!

Downloaded

from

http://ptjournal.apta.org/ byguest onFebruary 6,2014
http://ptjournal.apta.org/http://ptjournal.apta.org/http://ptjournal.apta.org/http://ptjournal.apta.org/http://ptjournal.apta.org/http://ptjournal.apta.org/http://ptjournal.apta.org/


7/35

Diabetes-Related Microvascular and Macrovascular Diseases in Physical Therapy

Diabetes mellitus %D"& is aglobal health issue affecting children,

adolescents, and adults. According tothe 'orld (ealth )rgani*ation,

appro#imately + million peopleworldwide cur-rently have type ! D"%formerly called adult-onset diabetes&over /01 of people with diabetes have

this form. $he number of people withtype ! D" is estimated to dou-ble by

!2.+In the year !, death from

diabetes-associated complica-tionsaccounted for appro#imately 31 of

worldwide mortality.!Addi-tionally, the

economic burden of di-abetes in the4nited States in !!

was estimated to be 5+2! billion.2

Diabetes is a disease that is strongly

associated with both microvascular and

macrovascular complications, including

retinopathy, nephropathy, and

neuropathy %microvascular& and

ischemic heart disease, peripheral

vascular disease, and cerebrovascu-lar

disease %macrovascular&, result-ing in

organ and tissue damage in

appro#imately one third to one half of

people with diabetes.6 7ecause of the

progressive nature of the disease,

physical therapists will increasingly

encounter patients with prediabetes %ie,

impaired glucose tolerance or insulin

resistance&, early type ! D" without or

with only a few vascular complications,

and more advanced disease with

several vascular compli-cations. 8or

additional information describing the

epidemiology of these problems in

people with D", see the perspective

article by Deshpande et al0in this issue.

Diabetes-associated vascular alter-

ations include anatomic, structural, andfunctional changes leading to

multiorgan dysfunction.3 As physical

therapists increasingly become first-

line providers of treatment for mus-

culoskeletal and movement disorders in

people with diabetes, it will be im-

portant for clinicians to be keenly

aware of the underlying vascular defi-

cits in

conditions such

as diabetic neu-

ropathy,

retinopathy,

nephropathy,

andcardiovascular

and peripheral

vas-cular

diseases in their

treatment pro-

grams, even if

these conditions

are not the

reasons for

referral.

Addition-ally,

physical

therapists will

play an

important role

in the care of

people with

diabetes

because

numerous in-

terventions

provided by

physical ther-

apists %such as

therapeutic

e#ercise& can

assist in

alleviating

symptoms, slow

the metabolic

progression to

overt type !

D", and reduce

morbid-ity and

mortality

associated with

these

complications.9

:+

Diabetic

microvascular

%involving

small vessels,

such as

capillaries& and

macrovascular

%involving large

vessels, such asarteries and

veins&

complications

have similar

etiologic

characteristics.

hronic

hypergly-

cemia plays ama;or role in

the ini-tiation

of diabetic

vascular

complica-tions

through many

metabolic and

structural

derangements,

including the

production of

advanced

glyca-tion end

products

%AP?@&,

elevated

production of

reactive

o#ygen spe-

cies %)S,

o#ygen-

containing

mole-cules

that can

interact with

other

biomolecules

and result in

damage&, and

abnormalstimulation of

hemo-dynamic

regulation

systems %such

as the renin-

angiotensin

system

>AS@&.

$he ob;ectives

of this articleare to briefly

describe the

epidemiology

of, the

comorbidities

and risk factors

as-sociated

with, the

pathogenesisof, and the

physical

therapy

manage-ment

associated with

microvascular

and

macrovascular

complications

of diabetes. In a

significant

portion of the

article, the term

BdiabetesC in-

cludes both

type + D" and

type !

D", whichhave much thesame vas-cular

pathology andetiology.


8/35

Microvascular

omplications of DiabetesDiabetic Retinopathy

Diabetic retinopathy %D& is a micro-

vascular complication that can affect the

peripheral retina, the macula, or both

and is a leading cause of visual

disability and blindness in people withdiabetes.

+ $he severity of D ranges

from nonproliferative and

preproliferative to more severely

proliferative D, in which the abnor-

mal growth of new vessels occurs.++

$otal or partial vision loss can occur

through a vitreous hemorrhage or retinal

detachment, and central vi-sion loss can

occur through retinal vessel leakage and

subseuent mac-ular edema.+!

$he

prevalence of D increases with

prolonged duration of diabetes.+2 Instudies including peo-ple with both type

+ diabetes and type ! diabetes, after 2

years of di-abetes, most patients had

some form of D, and over half had

proliferative

D people

with type +

diabetes and

taking insulin

had the highest

preva-lence of

D, and people

with type !

diabetes

diagnosed after

age 2 had the

lowest

prevalence of

D.+6 :+3

Diabetic

retinopathy also

recently was

seen in

appro#imately

+1 of peoplewith insulin

resistance %pre-

diabetes& and

was associated

with the

presence of

hypertension

and a higher

body mass

inde#.+9

)ther

studies of D

showed

associationswith younger

age of onset,

tobacco use,

insulin

treatment,

abnormal

blood lipid %ie,

total

cholesterol,

low-density

lipoprotein

>EDE@, and tri-

glyceride&levels,

pregnancy,

renal disease,

elevated

homocysteine

lev-els,+

and a

diet high in fat

%$able&.+/ :!+

$he earliesthistological

marker of Dis the loss of

pericytes.!!

Peri-cytes areelongatedcontractile cellsthat wraparoundendothelialcells of small

vessels!2

and

assist inproviding

maintenance ofcapillary tone%ie, di-latationand

constriction&,!6

capillary

;ovem4er $##! :olume

!!;um4er Physical

Therapyf +$+

Downloaded from

http://ptjournal.apta.org/February 6, 2014
http://ptjournal.apta.org/http://ptjournal.apta.org/


9/35


Table!


10/35

treatment of balance and movement disorders because these

disorders fre-uently affect lower-e#tremity sensa-tion and

can cause lower-e#tremity pain in people with diabetes. Eoss

of lower-e#tremity sensation coupled

with impaired peripheral vascular

function can contribute to lower-

+$% f Physical Therapy :olume !!

;um4er

;ovem4er $##!Downloaded from

http://ptjournal.apta.

org/ by gueston February6, 2014
http://ptjournal.apta.org/http://ptjournal.apta.org/http://ptjournal.apta.org/http://ptjournal.apta.org/


11/35



12/35

$igure &!


13/35


$igure '!

Microaneurysms in dia4etic retinopathy/&rom the Slice of (ife collection, curated 4y

SuEanne Stensaas, University of Utah/

for DF include hyperglycemia,dura-tion of diabetes, age ofonset, tobacco use, dyslipidemia,

hypertension,3,3+

and obesity

%$able&.3!

Macrovascular

omplications ofDiabetesardiovascular disease %GD& is

the leading cause % 91& of death

in people with type !

diabetes.32,36

Peo-ple with

diabetes have a 6-fold-greater risk

for having a GD event than

people without diabetes after

controlling for traditional risk

factors for GD, such as age,

obesity, to-bacco use,

dyslipidemia, and hyper-tension.

30,33 $hese GD risk

factors are common in diabetes,

but data

suggest that

diabetes is an

indepen-dent

risk factor for

GD. People

with diabetes

also have a 0-

fold-greater

risk for a first

myocardial

infarction %"I&

and a !-fold-

greater risk for

a

Diabetes-related cardiac

autonomic neuropathy is

freuently underdiag-

nosed and can include

clinical ab-normalities

such as resting tachy-

cardia, e#ercise

intolerance, resting (

variability, slow (recovery after e#ercise,

orthostasis, BsilentC

myocardial

infarction, and

increased risk of

mortality.0+,0!

$he

prevalence of

diabetes-related

cardiac auto-nomic

neuropathy is

unclear and has been

reported to rangefrom +1 to /1,

depending on the

outcome

variable.2

! isk

factors

for

diabetes-

associate

d cardiac

neuropat

hy in-

clude

age,

obesity,

smoking,

poor

glycemic

control,

and

hyperten

sion

%$able&.02

ardiac

autono

mic

dysfunc

tion in

people

with

diabetes

has

been

asso-ciated

with

diabetic

cardiomy

opa-thy,

a topic

beyond

the scope

of this

article. In

brief,

peoplewith

diabetic


14/35

cardiomyopathy have

diastolic filling and

rela#ation abnormalities

fre-uently later

accompanied by sys-tolic

dysfunction and heart

failure. It is unclear

whether cardiac auto-nomic dysfunction

directly mediates diabetic

cardiomyopathy, because

many of the same

risk factors and

mechanisms

contribute to the

devel-opment of

both conditions.0+

Diabetic%ephropathy

Diabetic

nephropathy %DF& is

a seri-ous and

progressive

complication of both

type + D" and type

! D". $he first

manifestation of DF

is typicallymicroalbuminuria,

which progresses to

overt albuminuria%ie, increased

albumin levels in the

urine, indicat-ing

more severe renal

dysfunction& and

eventually to renal

failure06

and is the

leading cause of

end-stage re-nal

disease %=SD&.00

Appro#imately one

fourth of people withtype ! diabetes have

microalbuminuria or

a more advanced

stage of DF that

worsens at a rate of

!1 to 21 per year.03

)ther characteristic

features of DF

include thickening of

glomer-ular

basementmembranes %8ig. +&

and glomerular

hyperfiltration,

leading

to

mesangia

l %central

part of

the renal

glomerul

us&

e#tracell

ularmatri#

e#-

pansion

and

further

increases

in uri-

nary

albumin

e#cretion

09 andpro-gressing

to

glomerul

ar andtubular

sclerosis

and renal

failure.0,

0/ Eike

those for

D andPF, the

risk

factors

recurrent

"I than

people

who

previ-

ously had

an "I

but do

not have

diabetes.

$hese

data

suggest

that the

risk for

an "I in

people

who have

diabetes

but who

have nothad an

"I is

similar to

that in

people

without

diabetes

but with

a

previous

"I.39

8urther,people

with

diabetes

have a

poorer

long-

term

prognosi

s after an

"I,

including

an

increasedrisk for

congesti

ve heart

failure

and

death.3

=ven

people

withinsulin

resistan

ce %ie,

the

blunted

respons

e of

tissues

>such as

muscle,

fat, and

liver@ to

insulinthat

freuent

ly

precede

s type !

D"&

have an

increase

d risk

for

GD.3/

$raditionally,diabetesandGDwerelimited

primarily to'est-erni*ed

populations.

(owever, re-cent

evidencesuggeststhat theseconditions arerapidlyemerginginresource-limitedregionsof the

world,9

and

estimatesindicatethat 1of peoplewithdiabetes

world-wide willdie from

GD.9+

People

with

diabetes

%particula

rly type !

D"&

freuentl

y have

many

traditiona

l risk

factors

for GD,

in-

cluding

central

obesity,

dyslipide

mia %ie,

elevated

serumtriglyceri

de, EDE,+$* f PhysicalTherapy :olume!! ;um4er

;ovem

4er$##!

Downloaded from

http://ptjournal.apta.org/

guest on February 6,2014


15/35


and free fatty acid levels and low high-

density lipoprotein levels&, and

hypertension.9!

$he combination of

central adiposity, dyslipidemia, hy-

perglycemia, and hypertension in the

general population is termed Bmetabolicsyndrome.C

92$hese fac-tors, along with

the independent risk factor of diabetes,

can act both inde-pendently and

cumulatively over time to significantly

increase risk for GD. $he combination

of hypergly-cemia, insulin resistance,

dyslipide-mia, hypertension, and

chronic in-flammation can in;ure the

vascular endothelium, leading to

macrovascu-lopathy and GD in people

with type

! D".

96

erebrovascular Disease

Stroke is the third leading cause of death

in the 4nited States, after GD and

cancer,90and is an event very fa-miliar to

physical therapists. Diabetes is an

independent risk factor across all ages93

for stroke the risk in people with diabetes

is up to !- to 6-fold greater, more so in

white people and women.90,99:9/ Diabetes

is also a risk factor for sudden and

eventual death from stroke,,+and people

who have diabetes and who have a stroke

have more severe neurological deficits and

a poorer long-term

prognosis,0

and a higher incidence ofstroke recurrence than people with-out

diabetes.3

As in GD, the presence of diabetes

adversely affects the cerebrovascular

circulation by increasing the risk of

intracranial and e#tracranial %eg, ca-

rotid artery& atherosclerosis.9,

Peo-ple

with diabetes have an increasedincidence of traditional risk factors for

stroke, including hypertension,

dyslipidemia, heart failure, and atrial

fibrillation./

(owever, after these

factors are controlled for, diabetes

remains a strong predictor for stroke,

suggesting that the presence of diabetes

carries an independent risk for stroke

apart from the in-

creased

presence oftraditional risk

factors

%$able&.

As in otherdiabetes-relatedcompli-cations,hyperglycemiaappears to be asignificantfactor in stroke.(yper-

glycemia is asignificant

predictor offatal andnonfatal

stroke/

anddeath from

stroke./+

(yperinsulinemia %ie,elevated bloodinsulin levels&also appears to

be a risk factor

for stroke,/!,/2

although thisrelationship is

still unclear./6

$he presence ofD,

proteinuria,microalbuminuria, andhyperuricemia

%ie, elevatedblood uric acidlevels& areother diabetes-related factorsassociated with

an in-creasedrisk for stroke

%$able&./+,/0,/3

8inally,elevated bloodlevels ofchronicinflammatorymarkers are as-sociated withan increasedrisk for strokein people with

diabetes./9

Peripheral

(rteryDisease

urrently in

the 4nited

States, more

than 2.0million people

%African-

American

white (ispanicpeo-ple& with

diabetes have

peripheral

artery disease

%PAD&./

Peripheral

artery disease

is

characteri*ed

by occlusionof the lower-

e#tremity ar-

teries,//

which

can cause

intermittent

claudication

and pain,

especially

upon e#ercise

and activity,+

and which can

result infunctional

impairments++

and

disability.+!

Physical

therapists

freuently

encounter

people with

diabetes-related PAD

because ofthese

functional

impairments

and because of

common

events of more

severe PADH

foot ulceration

and lower-

e#tremity

amputation.+2

7ecause

people withdiabetes are +0times more

likely to have

lower-e#tremity

amputation

than people

without

diabetes,+6

physicaltherapists

freuently treat

people with

diabetes-related

amputations.

As the

incidence of

diabetes

increases,

physical

therapists willmore fre-

uently see,treat, and

prescribe e#-

ercise for these

people. An

elevated

awareness of

PAD is needed

among physical

therapists

because death

in people with

diabetes andPF is fre-

disability,!: 6


16/35

uently attributed to GD.+0

"ore-

over, lower-e#tremity amputation is

more common in people with dia-betesand PAD than in people with-out

diabetes but with PAD+3

these data

suggest that physical thera-pists shouldcarefully assess lower-e#tremity blood

flow %ie, peripheral pulses& and skinintegrity for all pa-tients with diabetes,

especially those with known PAD.

Peripheral artery disease, like the

aforementioned vascular diseases, is

related to the duration and severity of

diabetes.+3,+9

(yperglycemia, spe-

cifically, glycation hemoglobin, has

been shown to be an independent risk

factor for PAD.+

In addition to dia-

betes, other risk factors for PAD in-clude hypertension, tobacco use, obe-

sity %ie, waist-to-hip ratio&, elevated

serum fibrinogen levels, dyslipidemia, a

history of GD, and physical inactiv-ity

%$able&.+/,++

ommonMechanisms forMicrovascular

andMacrovascularDiseases inDiabetes)ne common

pathogenicmecha-nism for

microvasculardisease is

rooted in

chemicalreactions be-tween by-

products ofsugars and pro-

teins that occurover the course

of days to

weeks andeventually pro-

duceirreversible

cross-linkedpro-tein

derivatives

called A


17/35


$igure )!

Potentialmechanisms fordia4etes5associated

endothelialdysfunction/

AF@ advancedglycation end

products,


18/35

)ther mechanisms involved in mi-

crovascular disease include the P?

pathway %a family of multifunctional

en*ymes involved in signal transduc-

tion and gene e#pression of growth

factors and inflammatory signals+!6

that

may increase vascular perme-ability&

and the polyol pathway %the en*ymesaldose reductase and sorbi-tol

dehydrogenase, which cataly*e

reactions that can lead to sorbitol

accumulation-associated osmotic and

o#idative stress damage to the endo-

thelium+!0

& %8ig. 2&. Peripheral nerve

damage in DF, including neuronal

degeneration and impairment of re-

generation of thinly myelinated fi-bers,

is also mediated by A


19/35


$igure *!Potential mechanisms for dia4etes5associated vascular a4normalities/ ;) nitric oide, tPA5 tissue plasminogen activator5, PA?5

plasminogen activator inhi4itor5/BstickC to the

endothelialsurface.

+26

Insulin resistance

also can

contribute to a


20/35

decrease in F) production and the subseuent impaired

vasodila-tory response. In addition, insulin re-sistance can

lead to an increase in the release of free fatty acids from

adipose tissue+20

and stimulate the P? pathway, which can

directly and indirectly inhibit eF)S activity through

increased )S generation.+23

$he production of A


21/35

;ovem4er $##! :olume !! ;um4er

PhysicalTherapy f+$G

Downloaded from


February 6, 2014
http://ptjournal.apta.org/http://ptjournal.apta.org/http://ptjournal.apta.org/http://ptjournal.apta.org/http://ptjournal.apta.org/


22/35


over time to produce atheroma and

eventual atherosclerosis.9!

"any of the mechanisms for GD

appear to affect the cerebrovascula-ture

in a similar manner, but this theory isunder debate.

+66 (ow-ever, a uniue

effect of diabetes on neurons and glial

cells occurs dur-ing ischemia %such as

during a tran-sient ischemic attack or

stroke&. $his relationship has been

demonstrated through the relationship

between hyperglycemia and increased

intra-cellular acidosis.+60

Feuronal

intra-cellular acidosis occurs during an

ischemic event as a result of ele-vated

anaerobic metabolism, which leads to

neuron and glial cell dam-age.

+60,+63

Acidosis may induce intra-cellular

damage through )S genera-tion,

intracellular signaling disruption, and

activation of DFA-splitting en-

*ymes.+63

(yperglycemia also is asso-

ciated with increased levels of e#cita-

tory amino acids %eg, glutamate&, which

may induce neuronal cell death through

the activation of glutamate re-ceptors,

the influ# of e#cess calcium, and

mitochondrial %cell energy power-

house& in;ury.+63,+69

$his process may

lead to a poorer outcome of stroke in

people with diabetes.

Role of Physical Therapists

in Diabetes-Related

Microvascular and

Macrovascular DiseasesDiabetes-related comorbidities are

conditions that physical therapists will

encounter during the evaluation and

treatment of movement and functionaldisorders in people with diabetes.

7esides improving move-ment and

function, in general, phys-ical therapists

may improve the ual-ity of life for

people with diabetes and macrovascular

and microvascu-lar diseases through the

use of inter-ventions that address pain,

poor en-durance, obesity, and increased

risk for microvascular and

macrovascular diseases. Specifically,

the prescrip-

tion and

monitoring of

an individual-

i*ed e#ercise

program are

essential in a

management

program,

regard-less of

the severity of

diabetes. =#er-

cise therapy

may greatly

benefit many

patients with

diabetes by re-

ducing

hyperglycemia,

insulin resis-

tance,dyslipidemia,

and hyperten-

sion these

reductions may

translate into an

improved

vascular

disease risk

profile in

children,

adolescents,

and adults with

diabetes.+6 :+0

=#er-cise also

may aid in

weight loss,

spe-cifically,

loss of trunk

fat, and also

may improve

glycemic and

lipemic control

in people with

diabetes.+0+

Additionally,e#ercise may

improve

physical

function+0!

and

uality of life

in people with

diabetes.+02

au-tion

should be

observed in

patients who

haveproliferative

D, micro-

albuminuria,

and cardiac

autonomic

dysfunction

and who are

starting

aerobic

e#ercise

programs,

because

e#ercise,

particularly

resistance e#-

ercise,

increases

retinal blood

pres-sure,

reduces kidney

blood flow,

and stressesautonomic

control of (

and

contractility.+06

8or additional

in-formation

related to the

metabolic

effects of

e#ercise in

people with

D", seerelated articles

by $urcotte

and 8isher+00

and


23/35

improve markers of DF, specifically

decreasing microalbuminuria.+36

Peripheral artery disease is another

condition that physical therapists fre-

uently encounter in patients with

diabetes. $he clinical evaluation of PAD

in people with diabetes com-monlyinvolves palpating for periph-eral

arterial pulses, but this tech-niue has

been shown to have poor accuracy for

the determination of PAD.+30

$he ankle

brachial inde# %A7I&, a sensitive and

specific test for determining PAD,+33

is

performed by measuring systolic blood

pressure in the upper %brachial artery&

and lower %dorsalis pedis and posteriortibialis arteries& e#tremities with a hand-

held Doppler probe and divid-ing the

higher ankle systolic pressure by the

higher brachial artery pres-sure.+39 An

A7I of less than ./ is predictive of

PAD, and an A7I of less than .0 is

associated with impaired physical

function %such as walking distance&.+33

Although a

Doppler probe

is not

commonly used

in the physical

therapy setting,

clinics that

freuently treat

people with

diabetes-associated PAD

may benefit

from using this

relatively

ine#pen-sive

tool because it

may provide di-

agnostic and

treatment

monitoring

criteria. )therclinical testing

in pa-tients

with diabetes-associated PAD

may include

treadmill

testing+3

or

the 3-minute

walk test+3/

to

deter-mine

walking

capacity and

time toclaudication

and pain, ifpresent. Su-

pervised

e#ercise

training in

people with

PAD has been

shown to be

highly

beneficial in

terms of

walkingdistance and

time, time to

claudicationand pain, and

uality of

life+9,+9+

is

more effective

than

pharmacologic

therapy+9!

and

is considered to

be first-line

therapy in thetreatment of

PAD.+3

Accordingly,

physical thera-

pists are

becoming first-

line treatment

providers for

patients with

diabetes-related

PAD andshould be

strong ad-

vocates of

e#ercise

treatment for

these patients.

++# f Physical Therapy

:olume !!;um4er

;ovem4er $##!

Downloaded from


February6,2014


24/35


$he clinical evaluation and treatment of

DF, a common condition in the physical

therapy setting, reuire more specificity.

$he evaluation of diabetic PF in the

clinical setting in-volves a variety of

tests, which may include themeasurement of periph-eral %typically of

the lower e#trem-ity, such as the foot&

light touch and vibration sense as well

as nerve bi-opsy.+92

$he clinical

evaluation of vi-bration sense, a test

freuently used in the physical therapy

setting, is the strongest predictor of foot

insensitiv-ity ulceration.+96

=lectrophysiologic nerve conduction

testing, occasion-ally performed in

physical therapy clinics but more often

performed in physicians offices, is

considered to be the gold standard for

measuring nerve function.+90

Ferve

biopsy is not considered part of routine

clini-cal testing in DF however, skin

bi-opsy testing is becoming more fre-

uent in clinics. Skin biopsy testing is

minimally invasive and may pro-vide

important information, such as nerve

density and small-fiber neurop-athy,+93

and it may be useful in pre-dicting the

progression of the disease.+99

A newly

developed non-invasive techniue forassessing the presence of DF is corneal

confocal microscopy, with which the

density and length of the corneal nerve

have been shown to be strongly associ-

ated with lower-e#tremity nerve density

and which is gaining in pop-ularity.29

$hese clinical measure-ments also may

be used to assess the efficacy of specific

interventions, in-cluding medications,

e#ercise, and weight loss.

linical tests to evaluate diabetes-

associated cardiac autonomic neu-

ropathy include measurement of resting

(, e#ercise testing, mea-surement of

blood pressure in re-sponse to postural

changes %such as moving from a supine

position to a standing position&,

autonomic refle# testing, measurement

of !6-hour ( variability, spontaneous

barorefle#

sensitivity

testing, and

cardiac radio-

nuclide

imaging.0+

Several of these

tests, including( and blood

pres-sure

responses to

e#ercise and

pos-tural

changes, can be

performed in

the physical

therapy setting.

A rest-ing (

of + beats per

minute is

considered tobe tachycardia

in adults.

)rthostatic

hypotension is

defined as a

decrease of

greater than 2

mm (g in

systolic blood

pressure and a

decrease

greater than +mm (g in

diastolic blood

pressure in re-

sponse to a

change from a

supine position

to a standing

position.+9

Pa-

tients with

diabetes-

associated car-

diac autonomic

neuropathyhave a blunted

( response to

e#ercise %ie,

they do not

attain the age-

predicted

ma#imal (&

and a slow (

recovery after

peak e#ercise0!

the latter is

predictive ofGD and all-

cause mor-

tality.0!

Physical

therapists,

therefore, may

have to rely

more on the

patientsperceived

e#ertion than

on ( re-

sponses for

e#ercise

prescription.+9/

onclusionDiabetes is

associated

with both mi-

crovascular

and

macrovascular

dis-eases

affecting

numerous

organs, in-

cluding

skeletal

muscle, skin,

heart, brain,

and kidneys.

ommonpatho-genic

mechanisms

link the differ-

ent types of

diabetes-

associated vas-

cular disease

%such as GD

and PAD&.

ommon risk

factors for

vasculardisease in

diabetes

include

hypergly-

cemia, insulin

resistance,

dyslipide-mia,

hypertension,

tobacco use,

and obesity.

"echanisms

for

microvascular

dis-ease in

diabetes

include the

patho-logic

effects of A


25/35

overproduction of endothelial growth

factors, chronic inflammation, he-

modynamic dysregulation, impaired

fibrinolytic ability, and enhanced

platelet aggregation %clotting&. It is

becoming increasingly important for

physical therapists to be aware of

diabetes-related vascular complicationsas more patients present with insulin

resistance and type ! D". $he oppor-

tunities for effective physical therapy

interventions %such as e#ercise& are

significant.

This 2or' 2as supported 4y ;ational ?nsti5

tutes of =ealth grant ##%+%+A/

This article was submitted January 8 !""8

and was acce#ted May $ !""8.

D)?0 #/$"$$HptI/$##!###!

References1 'orld (ealth )rgani*ation. Diabetes facts.

Available atH httpHJJwww.who.intJmediacentreJfactsheetsJfs2+!JenJinde#.html. Accessed December +2, !9.

2 'orld (ealth )rgani*ation. Diabetesaction

now bookletHa life-threateningcondition.Available atHwww.who.intJdiabetesJ7))?E=$K($"EJenJinde#2.html.AccessedDecember +2,

!9.3 (ogan P, Dall

$, Fikolov P.=conomiccosts ofdiabetes in the4S in !!.Dia-betesCare.!2!3H/+9:/2!.

6 4?ProspectiveDiabetesStudy%4?PDS&.GIII. Studydesign,

progress andperfor-mance.Diabetologia.+//+26H99:/.

0 DeshpandeAD, (arris-(ayes ",

Schoot-man".=pidemiology of diabetesand diabetes-relatedcomplications. Phys Ther.!H+!06 :+!36.

3 ahman S,ahman $,Ismail AA,ashid A.Diabetes-associatedmacrovasculopa-thyHpathophysiology andpathogenesis.DiabetesObes Metab.!9/H939:9.

9 Davey Smith


26/35


10 ?nowler ', 7arrett-onnor =, 8owlerS=, etal. eduction in the incidence of type !diabetes with lifestyle interven-tion ormetformin.N Engl J Med.!!263H2/2: 62.

++(arding S. =#tracts from Bconcise clinicalevidenceCH diabetic retinopathy. BMJ.!22!3H+!2:+!0.

+!Sheet* "M, ?ing


27/35

2/"alik A, Fewrick P


28/35


02'itte D, $esfaye S, haturvedi F, et al. iskfactors for cardiac autonomic neu-ropathy intype + diabetes mellitus. Dia-betologia.!06H+36 :+9+.

06Drummond ?, "auer ". $he early natu-ralhistory of nephropathy in type + dia-betes, IIH

early renal structural changes in type +diabetes.Diabetes.!!0+H +0 :+09.

007renner 7", ooper "=, de eeuw D, et al.=ffects of losartan on renal and car-diovascularoutcomes in patients with type ! diabetes andnephropathy. N EnglJ Med. !+260H3+:3/.

03Adler AI, Stevens M, "anley S=, et al.Development and progression of ne-phropathyin type ! diabetesH the 4nited ?ingdomProspective Diabetes Study %4?PDS 36&.idney Int.!232H !!0:!2!.

098riedman =. Diabetic renal disease. InH ifkin(, Porte D Mr, eds. Ellenberg and %i")ins

Diabetes Mellit!s/ Theory and Practice. 6thed. Few Lork, FLH =lsevier+//H36 :9/.

0hen S, (ong S', Iglesias-de la ru* ", etal. $he key role of the transforming growthfactor-beta system in the patho-genesis ofdiabetic nephropathy. %en0ail. !+!2H69+:6+.

0/van Di;k , 7erl $. Pathogenesis of dia-beticnephropathy. %e& Endocr Metab Disord.!60H!29:!6.

3(asslacher , it* =, 'ahl P, "ichael .Similar risks of nephropathy in patients withtype I or type II diabetes mellitus.Nephrol Dial Transplant. +//6H0/ : 32.

61 Einseman DA, 7ranstetter D


29/35

81 (aheim EE, (olme I, (;ermann I, Eeren P.Fonfasting serum glucose and the risk of fatalstroke in diabetic and nondiabetic sub;ectsH +-year follow-up of the )slo Study. *tro)e.+//0!3H996 :999.

82 ibo ", "olina , "ontaner M, et al. Acutehyperglycemia state is associated with lowertPA-induced recanali*ation rates in strokepatients. *tro)e.!023H +90:+9/.

83Parsons "', 7arber PA, Desmond P",

et al.Acute hyperglycemia adversely af-fects stroke

outcomeH a magnetic reso-nance imaging andspectroscopy study.Ann Ne!rol. !!0!H! :!.

84 "egherbi S=, "ilan , "inier D, et al.Association between diabetes and strokesubtype on survival and functional out-come 2months after strokeH data from the =uropean7I)"=D Stroke Pro;ect. *tro)e. !226H3: 3/6.

0Sprafka M", Girnig 7A, Shahar =, "c


30/35


/0


31/35

+!2 )sterby , Parving ((, Fyberg


32/35


+2 ask-"adsen , ?ing


33/35

en*ymuria in type ! diabetic patients. %en0ail.!9!/H+// :!0.

+30 7rearley S, Shearman P, Simms "(.Pe-ripheral pulse palpationH an unreliablephysical sign.Ann % Coll *!rg Engl.+//!96H+3/ :+9+.

+33 "cDermott "",


34/35

Diabetes-Related Microvascular and MacrovascularDiseases in the Physical Therapy SettingW Todd CadePHYS THER. 2008; 88:1322-1335.

Originally published online September 18,2008 doi: 10.2522/ptj.20080008

ReferencesThis article cites 170 articles, 60 of which you canaccessfor free at:http://ptjournal.apta.org/content/88/11/1322#BIBL

Cited by This article has been cited by 12 HighWire-hostedarticles:

http://ptjournal.apta.org/content/88/11/1322#otherarticles

Subscription http://ptjournal.apta.org/subscriptions/InformationPermissions andReprints http://ptjournal.apta.org/site/misc/terms.xhtml

Information for Authors http://ptjournal.apta.org/site/misc/ifora.xhtml
http://ptjournal.apta.org/content/88/11/1322#BIBLhttp://ptjournal.apta.org/content/88/11/1322#BIBLhttp://ptjournal.apta.org/content/88/11/1322#BIBLhttp://ptjournal.apta.org/content/88/11/1322#otherarticleshttp://ptjournal.apta.org/content/88/11/1322#otherarticleshttp://ptjournal.apta.org/content/88/11/1322#otherarticleshttp://ptjournal.apta.org/subscriptions/http://ptjournal.apta.org/subscriptions/http://ptjournal.apta.org/subscriptions/http://ptjournal.apta.org/site/misc/terms.xhtmlhttp://ptjournal.apta.org/site/misc/terms.xhtmlhttp://ptjournal.apta.org/site/misc/terms.xhtmlhttp://ptjournal.apta.org/site/misc/ifora.xhtmlhttp://ptjournal.apta.org/site/misc/ifora.xhtmlhttp://ptjournal.apta.org/site/misc/ifora.xhtmlhttp://ptjournal.apta.org/content/88/11/1322#BIBLhttp://ptjournal.apta.org/content/88/11/1322#otherarticleshttp://ptjournal.apta.org/content/88/11/1322#otherarticleshttp://ptjournal.apta.org/content/88/11/1322#otherarticleshttp://ptjournal.apta.org/subscriptions/http://ptjournal.apta.org/site/misc/terms.xhtmlhttp://ptjournal.apta.org/site/misc/ifora.xhtml


35/35

Downloaded from http://ptjournal.apta.org/ by

guest on February 6, 2014
http://ptjournal.apta.org/http://ptjournal.apta.org/http://ptjournal.apta.org/

diabetes-related microvascular and macrovascular

Documents