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I n s u l i n

The Impact of Exercise on Insulin Acti on in Type 2 Diabetes Mellitus:


Relationship to Prevention and Control
Sheri R. Colberg, P h D , FACSM
A s s ociate P rofes s or o f E xercis e S cience, E xercis e S cience, S po rt, P hys ical E ducation, and R ecreation Department,
O l d Dominion Univers ity, Norfolk, Virginia
ABSTRACT
B a c k g r o u n d : The interactions bet ween i nsul i n and physical activity are varied and complex. Control of blood glucose
levels relies heavily on the balance bet ween i nsul i n and opposi ng counterregulatory endocrine hormones that bi nd to
their respective receptors in muscle, adipose, and liver tissues. Other metabolic factors--such as fuel use and availabil-
ity, exercise intensity and duration, training status, and visceral fat levels--also affect physical activity done by i ndi vi d-
uals wi t h i nsul i n resistance and type 2 diabetes mellitus (DM).
O b j e c t i v e s : The purpose of this article was to discuss how certain variables interact wi t h acute sessions of physical
act i vi t y and more ext ended exercise t rai ni ng, focusi ng special at t ent i on on their rel at i onshi p to bot h exercise and
resting glycemia as it relates to type 2 DM prevent i on and control. Also discussed are strategies that i ndi vi dual s wi t h
type 2 DM can use to engage i n appropri at e physical t rai ni ng to control DM and prevent other i nsul i n-rel at ed health
problems.
Methods: The content of this article was based on an electronic search of the literature usi ng PubMed and the selection
of key search terms alone and in combination, i ncl udi ng exercise, aerobic training, resistance exercise, insulin, hyperglycemia,
diabetes, diabetes prevention, and humans. Articles that appeared in relevant, combi ned searches of these terms were exam-
ined back to the year 2000. A secondary search of articles related to type 2 DM and exercise was conducted via references
found in these cited studies that met the search criteria.
Results: Current research suggests that type 2 DM can be prevent ed and controlled with increased physical activity.
With respect to the possibility of reversal of a prediabetes state, both aerobic and resistance training may play i mport ant
roles in these processes. Al t hough i ndi vi dual s with DM are usual l y instructed to exercise to improve control of their dis-
ease, their special metabolic situation can lead them into hypoglycemic or hyperglycemic conditions. When recom-
mended guidelines are followed, however, physical activities can be done safely and effectively. In addition, abnormal
i nsul i n action in the body is associated with not only prediabetes and DM but also wi t h a host of other insulin-related
health conditions, i ncl udi ng cardiovascular disease.
Conclusion: A more thorough underst andi ng of the association among insulin, exercise, glycemia, and DM will lead to
better control of these i ndependent factors in health and disease states. (Insulin. 2006;1:85-98) Copyright 2006 Excerpta
Medica, Inc.
Key words: insulin, exercise, type 2 diabetes mellitus, blood glucose.
INTRODUCTION
The interactions among i nsul i n and i nsul i n action, counter-
regulatory hormone release, blood glucose regulation, and
physical activity are varied and complex. Control of blood
glucose levels relies on the balanced release of i nsul i n and
other r edundant endocrine hormones; the proper function-
i ng of hor mone receptors found part i cul arl y i n i nsul i n-
sensitive muscle, adipose tissues, and the liver; and other
metabolic factors such as fuel use and availability. 1 3 More-
over, i ndi vi dual s with diabetes mellitus (DM) are usual l y
instructed by their health care providers to exercise, but is it
safe and effective for these i ndi vi dual s to do so? In addition,
abnormal i nsul i n action in the body is associated not only
Accepted for publication October 18, 2 0 0 5 .
P r i n t e d i n th e U S A . R e p r o d u c t i o n i n w h o l e or part is n o t p e r m i t t e d .
with prediabetes and type 2 DM but also with a host of other
insulin-related health conditions.
The purpose of the current article was to discuss how
these aforementioned variables interact wi t h acute sessions
of physical activity and more extended exercise training,
focusing special attention on their relationship to both exer-
cise and resting glycemia as it relates to type 2 DM preven-
tion and control. A secondary purpose was to discuss strate-
gies that i ndi vi dual s with type 2 DM can use to engage in
appropriate physical training to control DM and prevent
other insulin-related health problems. To adequately ad-
dress this topic with regard to prevent i on and control of
type 2 DM, the acute hormonal responses to exercise must
1557-o843/o6/$19.oo
C o p y r i g h t 2006 Excerpta Medi ca, I n c .
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I nsul i n July 2 0 0 6
fi rst be exami ned. I n addi t i on, a r evi ew of t he effects of exer -
ci se t r a i n i n g - - b o t h aer obi c a nd r e s i s t a nc e - - on i nsul i n act i on
i n t he b o d y is r el evant t o u n d e r s t a n d i n g t he gl ycemi c re-
s pons es dur i ng r est i ng a nd exerci se condi t i ons. Thi s ar t i cl e
i ncl udes a di s cus s i on of i nsul i n s ens i t i vi t y r el at ed to phys i -
cal act i vi t y l evel s a nd l eads di r ect l y i nt o a r evi ew of cur r ent
st udi es i nvest i gat i ng t he pr event i on and cont rol of t ype 2 DM
wi t h phys i c a l act i vi t y. Mor eover , i t di s cus s es s ome of t he
gui de l i ne s for c hoos i ng a p p r o p r i a t e exer ci se for t hese i n-
di vi dual s . Fi nal l y, t he r ol e of exerci se i n DM ma n a g e me n t
a nd ot her i ns ul i n- r el at ed benef i t s of phys i cal act i vi t y ar e
expl or ed.
MATERIALS AND METHODS
The cont ent of t hi s ar t i cl e wa s ba s e d on an el ect roni c sear ch
of t he l i t er at ur e us i ng Pu b Me d a nd t he sel ect i on of key
sear ch t er ms al one a nd i n combi nat i on, i ncl udi ng exercise,
aerobic training, resistance exercise, insulin, hyperglycemia, dia-
betes, diabetes prevention, a nd humans. Mor e t han 5000 ar t i cl es
wer e i dent i f i ed i n t hi s manner . Ar t i cl es t hat a p p e a r e d i n rel e-
vant , c o mb i n e d s ear ches of t hes e t e r ms we r e e x a mi n e d
back t o t he ye a r 2000. A s e c onda r y sear ch of ar t i cl es r el at ed
to t ype 2 DM a nd exerci se wa s c onduc t e d vi a r ef er ences
f ound i n t hese ci t ed s t udi es t hat met t he sear ch cri t eri a.
Ar t i cl es sel ect ed for t he cur r ent s t udy wer e cons i der ed va l i d
once t he subj ect i ncl us i on a n d r esear ch me t h o d s wer e
r e vi e we d by t he aut hor a nd t he use of a ppr opr i a t e subj ect
i ncl usi on cr i t er i a a nd ma t c he d cont r ol gr oups wa s ver i f i ed.
INSULIN AND OTHER HORMONAL RESPONSES
TO ACUTE EXERCISE
Whe n a pe r s on exerci ses, hi s or her b o d y i mme di a t e l y re-
s p o n d s by r el easi ng a n u mb e r of count er r egul at or y hor -
mone s t hat r ai se a nd ma i nt a i n bl ood gl ucose l evel s. 2,3 At a ny
gi ven t i me, a r el at i vel y l i mi t ed s u p p l y of gl ucose is s t or ed as
gl ycogen i n mus cl es a nd t he liver, wi t h a far l esser a mount
ci r cul at i ng i n t he bl oods t r eam. However , a bl ood gl ucose
l evel of >65 mg / d L (>3.6 mM, or cl i ni cal l y def i ned hypo-
gl ycemi a) mus t be ma i nt a i ne d at al l t i mes for pr ope r br ai n
a nd ne r vous s ys t em f unct i oni ng. Because c a r bohydr a t e s ar e
t he p r i ma r y fuel t hat t he h u ma n b o d y uses dur i ng exerci se,
t he l i ver mus t act qui ckl y to r epl ace t he bl ood gl ucose t hat
t he exer ci s i ng mus cl es ar e c ons umi ng at a f ast er r at e
t hr ough hepat i c gl ycogenol ys i s or gl uconeogenesi s. 1
The count er r egul at or y hor mone s r el eas ed dur i ng exer -
ci se wi t h t he mos t i mme di a t e effect (ie, cat echol ami nes,
gl ucagon) si gnal t he l i ver to begi n r el easi ng mor e gl ucose. 2
Epi nephr i ne r ai ses a pe r s on' s hear t r at e a nd si gnal s exerci s-
i ng mus cl es to br eak d o wn s t or ed gl ycogen a nd t r i gl yc-
er i des, a nd i t al so s uppr es s es t he r el ease of i nsul i n f r om t he
~-cells. Gl ucagon has t he mos t di r ect effect on t he l i ve r ' s
pr oduc t i on of gl ucose; t he r el ease of gl ucagon f r om pancr e-
at i c s - cel l s is i nver s el y r el at ed to por t al l evel s of ci r cul at i ng
i nsul i n dur i ng exercise. 3 Ot her h o r mo n e s - - s u c h as nor epi -
nephr i ne, gr owt h hor mone, a nd cor t i s ol - - ef f ect i vel y r edi s-
t r i but e bl ood f l ow to act i ve t i ssues, pr ovi di ng al t er nat e fuel s
such as free f at t y aci ds (FFAs) a nd l act at e to wor ki ng mus -
cles a nd t he l i ver dur i ng phys i cal act i vi t y.
Both decr ement s i n i nsul i n a nd i ncr ement s i n gl ucagon
pl a y i mpor t a nt r ol es in t he pr e ve nt i on of hypogl yc e mi a dur -
i ng exercise; t hey do so i n concer t by s t i mul at i ng i ncr ement s
i n gl ucose pr oduc t i on by t he liver. 3 Whi l e t he c ombi ne d
r eci pr ocal changes in t he ci r cul at i ng l evel s of t hese hor -
mones ar e gener al l y effect i ve at ma i nt a i ni ng bl ood gl ucose
l evel s dur i ng pr ol onge d phys i cal act i vi t y, even e ndur a nc e
at hl et es who do not have DM ma y de ve l op hypogl yc e mi a
dur i ng an e xt e nde d sessi on of exerci se due to t he ext r eme
d e ma n d s t hat such act i vi t i es p u t on r el at i vel y l i mi t ed car bo-
hydr a t e st ores. I n pe opl e wi t h DM, an i nsuf f i ci ent decr ease
i n por t al vei n i nsul i n l evel s can i mpa i r t he pr oduc t i on of
a de qua t e bl ood gl ucose a nd pot ent i al l y r esul t i n hypo-
gl ycemi a. 4 Conver sel y, i nt ense exerci se (eg, he a vy we i ght
l i f t i ng or spr i nt i ng) causes an e xa gge r a t e d r el ease of epi -
ne phr i ne a nd nor epi nephr i ne, whi c h ar e t he pr i me r egul a-
t or s of gl ucose ove r pr oduc t i on dur i ng such exerci se a nd ma y
r esul t i n t r ans i ent hype r gl yc e mi a . 2
In t he absence of t he phys i ol ogi c exer ci s e- i nduced de-
cr ease i n i nsul i n l evel s (as exper i enced by ma n y i ndi vi dua l s
wi t h t ype 2 DM t r eat ed wi t h i nsul i n injections), bl ood gl ucose
l evel s ma y fal l cons i der abl y f ast er even t hough compens a-
t or y me c ha ni s ms wo r k to i ncr ease gl ucose pr oduct i on. 4 In
pe opl e who do not have DM, t he effects of cat echol ami nes,
cort i sol , a nd gr owt h hor mone at l east pa r t i a l l y c ompe ns a t e
for such al t er at i ons i n t he i ns ul i n- t o- gl ucagon rat i o. 3,4
Wi t h phys i cal act i vi t y as an a d d e d var i abl e, r egul at i on of
gl ycemi a can be f ur t her compl i cat ed. Ant e c e de nt mode r a t e -
i nt ensi t y exerci se has been s hown to bl unt aut onomi c, neu-
r oendocr i ne, a nd met abol i c count er r egul at or y r es pons es to
s ubs equent exerci se or to hypogl yc e mi a even i n pe opl e who
do not have DM. 5,6 Repeat ed epi s odes of pr ol onge d exerci se
of bot h l ow (eg, sl ow wal ki ng) a nd mode r a t e (eg, br i sk wa l k-
i ng) i nt ensi t i es have been de mons t r a t e d to bl unt t he coun-
t er r egul at or y r el ease of epi nephr i ne, nor epi nephr i ne, gl u-
cagon, gr owt h hor mone, a nd pancr eat i c pol ype pt i de , as wel l
as t he pr oduc t i on of e ndoge nous gl ucose, i n r es pons e to
ne xt - da y hypogl yc e mi a . 6 Thus, such pr i or act i vi t y ma y i n-
cr ease t he r i sk a pe r s on wi t h DM has of exper i enci ng a mor e
sever e hypogl yc e mi c event .
At rest , t he aver age h u ma n b o d y us ua l l y uses a fuel mi x
of N60% fat a nd 40% c a r bohydr a t e ( wi t h i nsi gni f i cant pr o-
t ei n use); however , dur i ng exerci se, c a r bohydr a t e s s u p p l y
t he maj or i t y of t he fuel ( and even mor e so dur i ng i nt ense
wor kout s ) . 1,7 Fi gur e 1 de mons t r a t e s t he r el at i ve f uel use i n
8 e ndur a nc e - t r a i ne d wo me n (ages 18-31 year s) at va r yi ng
exerci se i nt ensi t i es. 7 Thi s r el i ance on c a r bohydr a t e s makes
t he de pl e t i on of bot h mus cl e gl ycogen a nd bl ood gl ucose
i nevi t abl e if t he act i vi t y is pr ol onge d, pa r t i c ul a r l y if ci r cul at -
i ng i nsul i n l evel s r emai n hi gher t han nor mal .
Pl as ma FFAs can al so be us e d but cont r i but e mos t dur i ng
mi l d- t o mode r a t e - i nt e ns i t y wor kout s . However , t he mobi -
l i zat i on of t hi s al t er nat e fuel ma y al so be c ompr omi s e d
by el evat ed i nsul i n l evel s or i mpa i r e d i nsul i n act i on. For
- 86-
Vol ume 1, Nu mb e r 3 S.R. Co l b e r g
c
E
._Q
s_.
U
s_.
O
Figure 1 .
4 0 0 1
O F i i
25 45 65
% of Ma x i ma l O x y g e n Upt ake
Muscle glycogen
M u s c le
triglycerides
Plasma FFA
Plasma glucose
85
Ma x i ma l c al or i c cont r i but i on of pl asma free f at t y ac i ds (FFAs) a n d gl ucose a n d mi ni mal c ont r i but i on of muscle tri-
g l y c e r i d e a n d g l y c o g e n stores in r el at i on t o exer ci se i nt ensi t y in 8 endur anc e- t r ai ned women (ages 1 8 - 3 1 year s) .
Used wi t h per mi ssi on from Journal of Appl i ed Physiology, Vol ume 8 8 , 2 0 0 0 ; 1 7 0 7 - 1 7 1 4 . 7
i nst ance, i n 8 me n wi t h t ype 2 DM wi t h a me a n (SE) age of
52.6 (3.1) year s ( compar ed wi t h 8 cont r ol s wi t hout DM; mean
[SE] age, 45.1 [1.4] year s) , bot h t he r at e of a ppe a r a nc e of
pl a s ma FFAs a nd t hei r exer ci s e- i nduced i ncr ease in t hei r oxi -
dat i on ci r cul at i on dur i ng 60 mi nut e s of mode r a t e - i nt e ns i t y
cycl i ng wer e si gni f i cant l y l ower (P < 0.05). 8 However , dur -
i ng exerci se condi t i ons, t he i mpa i r me nt i n t he de l i ve r y of
p l a s ma - d e r i v e d FFAs to wor ki ng mus cl es i n t hese me n wi t h
DM wa s c ompe ns a t e d for by an i ncr ease i n t he use of I M
t r i gl yc e r i de s , t hus k e e p i n g t ot al f at o x i d a t i o n s i mi l a r
be t we e n gr oups . Si mi l arl y, ot her r esear cher s have f ound t hat
t he over al l us age of fat s a nd c a r bohydr a t e s is unal t er ed i n
pat i ent s wi t h t ype 2 DM, a l t hough hype r gl yc e mi a ma y dr i ve
a gr eat er use of ci r cul at i ng bl ood gl ucose wi t h a l esser
r el i ance on mus cl e gl ycogen. 9 Dur i ng r ecover y f r om exer -
cise, fat use agai n pr e domi na t e s i n al l i ndi vi dual s . 1
TRAINING, INSULIN ACTION, AND
PHYSICAL ACTIVITY
Mos t obese i ndi vi dua l s wi t h t ype 2 DM exper i ence a de-
cr ease i n t hei r bl ood gl ucose l evel s dur i ng mi l d- to moder at e-
i nt ens i t y exercise. 1 The ma gni t ude of t he decr eas e i n bl ood
gl ucose is r el at ed to t he dur a t i on a nd i nt ens i t y of t he exer -
cise, as wel l as to pr e- exer ci se gl ycemi c cont r ol a nd t he i ndi -
v i d u a l ' s t r ai ni ng st at e. 1 13 Thi s effect is onl y acut e, however ,
a nd r el at ed to t he bout of exerci se. The abi l i t y of mor e
i nt ense or pr ol onge d exerci se to acut el y enhance i nsul i n sen-
si t i vi t y us ua l l y r esul t s i n mor e effect i ve post exer ci se gl y-
cemi c cont r ol i n pe opl e wi t h i nsul i n r esi st ance or t ype 2 DM
whe n t hey unde r t a ke such act i vi t i es. 13
In addi t i on, exerci se t r ai ni ng can r esul t i n a mor e l ast i ng
effect on t he act i on of i nsul i n. 11,14,15 For i nst ance, i n obese
pe opl e of al l ages unde r goi ng j ust i we e k of t r ai ni ng, i nsul i n
s ens i t i vi t y i mpr ove d, de mons t r a t i ng t hat it can be acut el y
enhanced by r egul ar phys i c a l t r ai ni ng wi t hout we i ght l oss
a nd wi t hout evoki ng a t r ue t r ai ni ng a da pt a t i on i n muscl e, 14
al t hough such an effect can be e voke d wi t h t r ai ni ng a da pt a -
t i ons as wel l . Mor e p r o l o n g e d phys i cal t r ai ni ng can enhance
bot h t he r es pons i venes s of mus cl es to i nsul i n as wel l as bas al
bl ood gl ucose upt ake. In h u ma n skel et al mus cl e cel l s t aken
f r om ei t her e ndur a nc e - t r a i ne d (n = 12; me a n [SD] age, 23.0
[1.4] year s) or s e de nt a r y (n = 8; me a n [SD] age, 23.4 [1.0]
year s) men, t he myot ube s exhi bi t ed a dos e r es pons e for
gl ucose upt a ke wi t h i ncr easi ng i ns ul i n concent r at i ons, wi t h
ma xi ma l gl ucose upt a ke 1. 5-fold over bas al l evel s. Basal
gl ucose upt ake, however , wa s f ound t o be si gni f i cant l y el e-
va t e d (by N75%; P < 0.05) wi t h e ndur a nc e t r ai ni ng, al t hough
t he r el at i ve i ncr ease i n i ns ul i n- me di a t e d gl ucose upt a ke wa s
si mi l ar be t we e n subj ect gr oups . 11 I n 8 heal t hy y o u n g men, 18
to 25 ye a r s of age, 6 we e ks of mode r a t e - i nt e ns i t y cycl i ng per -
f or med for 1 hour 5 da ys a we e k wa s capabl e of i ncr easi ng
not onl y t hei r i ns ul i n sensi t i vi t y but al so t hei r gl ucose effec-
t i veness (ie, t he abi l i t y of hype r gl yc e mi a to pr omot e gl ucose
di s pos a l at bas al i nsul i n l evel s) for at l east i we e k aft er ces-
sat i on of t hei r t r ai ni ng r egi men. 15
E
xerci se t r a i n i n g can result in a more l ast i ng effect on the
act i on of i nsul i n.
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I n s u l i n July 2 0 0 6
Rel at i ve l evel s of i ns ul i n s e ns i t i vi t y ar e a p p a r e n t l y
af f ect ed by a var i et y of var i abl es, i ncl udi ng an i ndi vi dua l ' s
age a nd t r ai ni ng st at us. 12,16 18 I n a r ecent s t udy of a gr oup of
ol der i ndi vi dua l s (8 me n a nd 2 wome n, ages 77-87 year s) ,
bot h aer obi c p o we r a nd i ns ul i n act i on i mp r o v e d i n r es pons e
to hi gh- i nt ens i t y aer obi c exerci se t r ai ni ng, but t hei r i m-
pr ove me nt s in i nsul i n act i on wer e a t t e nua t e d c o mp a r e d
wi t h i mpr ove me nt s nor ma l l y f ound i n mi d d l e - a g e d subj ect s
under goi ng t he s ame t r ai ni ng pr ogr am. 16 Similarly, moder at e-
to heavy- i nt ens i t y aer obi c t r ai ni ng (ie, 60%-95% of ma xi ma l
hear t rat e) t hat wa s done 3 t i mes a we e k for 6 mont hs wa s
s hown to i mpr ove i nsul i n sensi t i vi t y i n bot h younge r (n = 14;
me a n [SD] age, 29.1 [4.6] year s) a nd ol der (n = 8; me a n [SD]
age, 62.3 [4.7] year s) women. 17 Al t hough onl y t he ol der wom-
en decr eas ed t hei r b o d y we i ght ( by 4%), t he e nha nc e me nt i n
i nsul i n s ens i t i vi t y per s i s t ed onl y i n t he y o u n g e r wo me n for
72 t o 120 hour s aft er t he l ast exerci se sessi on. Thi s f i ndi ng
s ugges t s t hat i n ol der wome n, i mpr ove me nt s i n i nsul i n sen-
si t i vi t y r esul t mor e di r ect l y f r om t he acut e effect of t he l ast
sessi on t han chr oni c t r ai ni ng a da pt a t i ons . 17 Conver sel y,
anot her s t udy on mus cl e mi t ochondr i al f unct i on, mus cl e fat
oxi dat i ve capaci t y, a nd i ns ul i n s ens i t i vi t y c o mp a r e d t r ai ned
young ( mean [SD] age, 24.2 [2.6] year s) a nd el der l y ( mean [SD]
age, 66.6 [3.2] year s) i ndi vi dua l s ver s us s e de nt a r y i ndi vi du-
al s i n t he s ame age gr oups. 18 Thi s s t udy f ound t hat al l of t he
af or ement i oned var i abl es i mp r o v e d s i mi l ar l y i n bot h gr oups
wi t h 8 we e ks of aer obi c t r ai ni ng, s ugges t i ng t hat t he el der l y
subj ect s wer e not i mpa i r e d by age but r at her by phys i c a l i n-
act i vi t y. I n mos t i ndi vi dual s , r egar dl es s of age, t he acut e ef-
fects of r ecent exerci se ar e mor e pr omi nent ; however , r egul ar
par t i ci pat i on i n phys i c a l act i vi t i es is r equi r ed for s us t ai nabl e
i mpr ove me nt s i n gl ucose homeos t as i s a nd i nsul i n act i on. 12
R
e g u l a r p a r t i c i p a t i o n in physical activities is required f o r
sustainable improvements in g l u c o s e homeostasis a n d
insulin action.
The met abol i c effects of va r yi ng exerci se i nt ensi t i es al so
mus t be consi der ed. Hi ghe r i nt ens i t y aer obi c t r ai ni ng cl ear l y
i mpr ove s i nsul i n sensi t i vi t y, 16 but s ome s t udi es have i nves-
t i gat ed whe t he r l ess vi gor ous wor kout s have a si mi l ar out -
come. In a s t udy c onduc t e d by Ho u ma r d et al, 19 154 mi ddl e -
a ge d ( mean age, 51.4-53.1 year s acr oss subj ect gr oups) ,
sedent ar y, a nd ove r we i ght subj ect s (50% wome n, i ncl usi ve
of et hni c mi nor i t i es) e nga ge d i n di f f er ent vol ume s a nd
i nt ensi t i es of aer obi c t r ai ni ng for 6 mont hs. One gr oup par -
t i ci pat ed i n l o w- v o l u me / mo d e r a t e - i n t e n s i t y t r ai ni ng con-
si st i ng of ~12 mi l es of wa l ki ng we e kl y done at 40% to 55% of
pe a k oxygen cons umpt i on; anot her gr oup wa s as s i gned to
l o w- v o l u me / h i g h - i n t e n s i t y wor kout s ent ai l i ng ~12 mi l es of
we e kl y j oggi ng; a nd a t hi r d gr oup j ogged ~20 mi l es pe r we e k
( cat egor i zed as a hi gh- vol ume / hi gh- i nt e ns i t y aer obi c t r ai n-
ing). Al t hough a f our t h s e de nt a r y cont r ol gr oup exper i enced
a decr eas e i n i nsul i n s ens i t i vi t y by t he end of t he t r ai ni ng
per i od, al l 3 exerci se gr oups wer e f ound to have enhanced
i nsul i n act i on r es ul t i ng f r om t hei r va r i e d t r ai ni ng. The 2
gr oups t hat exer ci sed N170 mi nut es pe r we e k (ie, t he l ow-
v o l u me / mo d e r a t e - i n t e n s i t y a n d t he h i g h - v o l u me / h i g h -
i nt ensi t y gr oups ) exper i enced mor e i mpr ove me nt s i n i nsul i n
s ens i t i vi t y t han t he l ow- vol ume / hi gh- i nt e ns i t y gr oup t hat
onl y exer ci sed for Nl15 mi nut es we e kl y (P < 0.05) ( Fi gur e 2).
These f i ndi ngs s ugges t t hat exerci se dur a t i on ma y be r el a-
t i vel y mor e i mpor t a nt t han t r ai ni ng i nt ens i t y to i mpr ove
i nsul i n act i on i n ove r we i ght peopl e.
Skel et al mus cl e i nsul i n r esi st ance a ppe a r s to ent ai l dys -
r egul at i on of bot h gl ucose a nd f at t y aci d met abol i s m. In a
16-week s t udy i nvol vi ng moder at e- i nt ens i t y phys i cal act i v-
i t y c ombi ne d wi t h cal or i e r educt i on i n 9 obese me n a nd
16 obese wo me n ( mean [SD] age, 39 [4] year s) who d i d not
have t ype 2 DM, i nsul i n s ens i t i vi t y ( mean [SE]) wa s i m-
p r o v e d by 49% (10%) by t he e nd of t he st udy. 2 Of i nt er est ,
t he s t r onges t pr edi ct or of t hi s i mp r o v e me n t wa s e nha nc e d
f ast i ng r at es of fat oxi dat i on, whi c h account ed for 52% of t he
var i ance, s ugges t i ng pos t a bs or pt i ve fat oxi dat i on is a key
aspect of i mp r o v e d i nsul i n sensi t i vi t y, at l east i n obese s ub-
j ect s who do not have DM. Si mi l arl y, ot her s t udi es have
f ound t hat exerci se t r ai ni ng i ncr eases i nt r amyocel l ul ar l i pi d
cont ent i n ol der i ndi vi dua l s (65-70 ye a r s ol d) i n par al l el
wi t h an e nha nc e d capaci t y for fat oxi dat i on. 12,21
The r el at i ons hi p be t we e n i mpa i r e d i nsul i n act i on a nd
vi scer al a di pos e cont ent is even mor e i mpor t a nt i n pat i ent s
wi t h t ype 2 DM who gener al l y have a bdomi na l obesi t y.
Gi a nnopoul ou et a122 r ecent l y e xa mi ne d t he effects of di et -
i ng, aer obi c exerci se, a nd a combi nat i on of t he 2 i n 33 pos t -
me nopa us a l a nd obese ol der wo me n ( mean age, 57 year s)
wi t h t ype 2 DM who ha d been di a gnos e d wi t h DM for at
l east 1 year a nd wer e bei ng t r eat ed ei t her wi t h or al hypo-
gl ycemi c agent s (n = 22) or no medi cat i ons (n = 11). Af t er
14 weeks, t hei r body wei ght and t ot al body fat decr eased si mi -
l ar l y whe t he r t he wo me n f ol l owed a l ow- cal or i e di et hi gh i n
monouns a t ur a t e d fat s or t hey c ombi ne d t hi s di et wi t h exer -
cise ( def i ned as mode r a t e wa l ki ng for 50 mi nut es 3 t i mes a
week). In t he gr oup assi gned to exercise al one, t hei r t ot al body
fat decr eased by l ess t han hal f as much as t hose who f ol l owed
t he speci f i ed di et pl an, r egar dl es s of t hei r exerci se st at us.
Never t hel ess, onl y t hose subj ect s who exer ci sed, i r r espect i ve
of we i ght l oss, exper i enced a si gni f i cant decr eas e (P < 0.05)
in vi scer al fat l evel s ( Fi gur e 3). The st r ongest pr e di c t or of i m-
p r o v e d i ns ul i n act i on i n t hes e wo me n wi t h t ype 2 DM wa s
enhanced f ast i ng r at es of fat oxi dat i on, a nd bot h exerci se
a nd we i ght l oss ( but not di et al one) i ncr eas ed pos t a bs or p-
t i ve fat oxi dat i on as wel l . Of par t i cul ar not e i n t hi s s t udy wa s
t hat di et i ng al one r e duc e d SC a nd t ot al a bdomi na l fat but
not vi scer al a di pos e cont ent wi t hout a d d e d exerci se. Mor e-
over, t hose i ndi vi dua l s who exer ci sed ma i nt a i ne d al l of t hei r
mus cl e mass; i ndi vi dua l s who bot h exer ci sed a nd f ol l owed
t he speci f i ed di et l ost l ess of t hei r mus cl e t han t hose i ndi vi d-
ual s who d i d not f ol l ow t he speci f i ed di et .
In cont rast , a 16-week s t udy i nvol vi ng 41 men and 49 wom-
en (ages 21-87 year s) who e nga ge d in aer obi c exerci se t r ai n-
- 88-
Volume 1, Number 3 S.R. Col ber g
Figure 2 .
1 2 0 -
1 0 0 -
8 0 -
~n- 6 O -
E
. m
4 0 -
0
. 4:
2 0 -
* t
I
* t
I T - - l - - - - l
- 2 0 -
Control Low/Mod Low/High High/High
Study Gr oup
Relative changes (%) (after t r a i n i n g / b e f o r e t rai ni ng) in the insulin sensi t i vi t y i ndex (Si) der i ved from the IV glu-
cose tolerance test in the control and exerci se gr oups (N = 154). L o w / Mo d = l ow-vol ume/ moderat e-i nt ensi t y
t r ai ni ng; L o w/ Hi g h = l ow- vol ume/ hi gh- i nt ensi t y t r ai ni ng; H i g h / H i g h = hi gh- vol ume/ hi gh- i nt ensi t y t r ai ni ng. Line
at 0 represents no change. * Si gni f i c ant di f f erence from control (P < 0 . 0 5 ) . t Si gni f i c ant difference from the
L o w/ Hi g h gr oup (P < 0. 05) . Used wi t h permission from Journal of Appl i ed Physiology, Volume 9 6 , 2 0 0 4 ; 1 0 1 -
106.19
i ng f ound t hat t hei r i nsul i n s ens i t i vi t y decr eas ed wi t h age
a nd wa s i nver s el y r el at ed to a bdomi na l fat cont ent (r =
-0.65). 23 However , i nsul i n sensi t i vi t y i mpr ove d aft er t r ai ni ng
onl y i n young i ndi vi dua l s i n t hi s st udy, not in t he mi ddl e -
a ge d or ol de r subj ect s. I n a not he r s t u d y of a gr oup of pr e-
me n o p a u s a l wo me n ( mean age of 41. 3-43. 9 ye a r s acr oss
gr oups) , 14 we e ks of ei t her di e t - i nduc e d we i ght l oss (n = 15),
exer ci s e- i nduced we i ght l oss (n = 17), or exerci se wi t hout
we i ght l oss (n = 12) r es ul t ed i n si mi l ar decr eas es i n vi scer al
fat i n al l gr oups ( compar ed wi t h 10 wei ght - s t abl e cont rol s),
a l t hough i nsul i n s ens i t i vi t y i mp r o v e d onl y i n t he exerci se
we i ght l oss gr oup. 24 Cl evenger et al, 25 however , de mon-
s t r at ed t hat ha bi t ua l e ndur a nc e exerci se ma y not pr e ve nt
age- as s oci at ed decl i nes i n i ns ul i n act i on, whi c h a p p e a r to be
i n d e p e n d e n t of adi posi t y.
Acut e changes i n i nsul i n act i on can be l ar gel y expl ai ned
by c a r bohydr a t e use dur i ng an act i vi t y. Whe n c a r bohydr a t e
use is s u b s t a n t i a l - - a s i t is dur i ng 30 mi nut es of cont i nuous,
mode r a t e e xe r c i s e - - bl ood gl ucose l evel s decr ease dur i ng
t he act i vi t y, even i n i ndi vi dua l s wi t h t ype 2 DM. 26 Whe n a
cons i der abl e a mount of mus cl e gl ycogen is de pl e t e d wi t h
mor e pr ol onge d act i vi t y, t he i nt ake of c a r bohydr a t e s dur i ng
t he act i vi t y ma y be usef ul i n pr ovi di ng gl ucose to de l a y
fat i gue a nd to moder at e gl ycogen depl et i on, par t i cul ar l y when
exer ci si ng for >1 hour. 10,27 These r es pons es ma y be al t er ed
by pr e di a be t e s or DM, however . A r ecent s t udy by Br aun et
a128 f ound t hat t ot al c a r bohydr a t e oxi dat i on a nd es t i mat ed
muscl e gl ycogen use dur i ng an acut e sessi on of exerci se wer e
si gni f i cant l y l ower (P < 0.05) i n i ns ul i n- r es i s t ant wo me n
c ompa r e d wi t h s i mi l ar l y ove r we i ght but i ns ul i n- s ens i t i ve
count er par t s , even t hough bl ood gl ucose upt a ke wa s unal -
t er ed by di f f er ences i n i nsul i n act i on.
For _>2 hour s af t er war ds , pr i or act i vi t y al so causes an en-
ha nc e d upt a ke of bl ood gl ucose for gl ycogen synt hesi s. In
mus cl e cells, at l east 2 di s t i nct me c ha ni s ms exi st to s t i mul at e
gl ucose upt a ke dur i ng exerci se a nd post exer ci se gl ucose use
a nd gl ycogen synt hesi s: one is i nsul i n de pe nde nt ( whi ch ma y
be al t er ed i n i ndi vi dual s wi t h i nsul i n resi st ance or t ype 2 DM)
a nd t he ot her is i nsul i n i nde pe nde nt i n r es pons e to mus cl e
cont r act i ons. 13 I mme di a t e l y af t er acut e exerci se, gl ycogen
de pl e t i on can s t i mul at e a ddi t i ona l gl ucose upt ake, 29 whi ch
can occur mor e r a pi dl y for s ever al hour s aft er an acut e ses-
si on of exerci se wi t h mi ni ma l i nsul i n r equi r ed.
An i ndi vi dua l ' s t r ai ni ng st at us mus t al so be cons i der ed
whe n pr e di c t i ng gl ycemi c r es pons es to an act i vi t y. Aer obi c
t r ai ni ng i ncr eases t he pr opor t i on of fat ut i l i zat i on for si mi l ar
l ow- or moder at e- i nt ens i t y act i vi t y done aft er t he t r ai ni ng
effect has occur r ed; us i ng a gr eat er pr opor t i on of fat s par es
mus cl e gl ycogen a nd bl ood gl ucose a nd al l ows for mor e
effect i ve gl ycemi c cont r ol dur i ng act i vi t i es. 1 However , i n
i ndi vi dua l s wi t h hype r gl yc e mi a , bei ng t r ai ned ma y r esul t i n
a l esser decr eas e i n gl ycemi a dur i ng acut e exerci se. 13
Changes i n fuel ut i l i zat i on wi t h t r ai ni ng ma y r equi r e
s ma l l e r c o mp e n s a t o r y a d j u s t me n t s t o c a r b o h y d r a t e or
i nsul i n i nt ake whe n gr eat er a mount s of fat ar e abl e t o be ut i -
l i zed dur i ng such act i vi t i es. However , t hese changes a ppl y
- 89-
I n s u l i n July 2 0 0 6
Pretreatment
[ ] Posttreatment
G"
E
Di et + Di et
Exerci se
I
Exerci se
15,000 1
__11
Di et + Di et
Exerci se
I
Exerci se
G"
m E
0
"-0 .--
._Q I.~
0 0
<
Di et + Di et
Exerci se
I
Exerci se
F i g u r e 3 . Changes in vi sceral adi pose tissue (VAT),
SC adi pose tissue (SAT), and total abdomi nal
a d i p o s e tissue in a st udy of 33 post-
menopausal women wi t h t ype 2 di abet es
mellitus before and af t er 14 weeks of di et
a n d / o r exercise intervention. * P < 0 . 0 5 versus
pretreatment. Reprinted wi t h permission from
Gi annopoul ou I, Ploutz-Snyder LL, Car har t R,
et al . Exercise is required f or viscerel f at loss
in postmenopausal women wi t h type 2 diabetes.
J Clin Endocrinol Metab. 2 0 0 5 ; 9 0 : 1 5 1 1 - 1 5 1 8 . 22
Copy r i ght 2 0 0 5 , The Endocrine Society.
onl y t o l ow- or moder at e- i nt ensi t y physi cal wor k. Dur i ng
acute, har d- i nt ensi t y (ie, done at 15% above vent i l at or y
t hreshol d levels) exercise, t he ut i l i zat i on of car bohydr at es
(i ncl udi ng bl ood glucose) is act ual l y furt her i ncreased by
aerobic t rai ni ng, even in mi ddl e- aged men (mean [SE] age,
52.3 [1.6] years). 3
Finally, t he gl ycemi c effects of resistance ver sus aerobic
exercise mus t be consi dered. I n nonobese, young wo me n
(18-35 year s of age), 6 mont hs of either aerobic or resistance
t rai ni ng i mpr oved muscul ar gl ucose di sposal , albeit by dif-
ferent mechani sms. 31 An increase in their amount of fat-free
mass (FFM) f r om resistance t rai ni ng cont r i but ed to gl ucose
upt ake f r om a mass effect (ie, upt ake dr i ven by el evat ed
bl ood gl ucose levels) wi t hout al t eri ng t he intrinsic capaci t y
of muscl e t o r es pond t o insulin; conversely, aerobic t rai ni ng
enhanced gl ucose di sposal i ndependent l y of changes in FFM
or maxi mal aerobic capacity. This fi ndi ng suggest s t hat such
changes resul t ed f r om enhanced i nsul i n sensitivity.
Al t hough resistance exercise can acut el y raise bl ood gl u-
cose levels due to its hi gh i nt ensi t y and exagger at ed count er -
r egul at or y hor monal response, 2 resistance t rai ni ng in gen-
eral appear s to be beneficial to gl ycemi c cont rol and i nsul i n
sensitivity, part i cul arl y in i ndi vi dual s wi t h t ype 2 DM. 10,13
Such t rai ni ng done by i ndi vi dual s wi t h t ype 2 DM or ot hers
wi t hout DM increases t he levels of gl ucose t r anspor t er 4
(GLUT4) in t rai ned muscl e, al ong wi t h i nsul i n receptors,
prot ei n kinase B, gl ycogen synt hase (GS), and GS total activ-
ity after acut e training. 32
R
esistance t r ai ni ng in general appears to be beneficial to
glycemic control and insulin sensitivity, par t i cul ar l y in
i ndi vi dual s wi t h type 2 DM.
Researchers have al so obs er ved an i mpr ove me nt in
i nsul i n sensitivity in mi ddl e- aged, nonobese i ndi vi dual s
wi t h t ype 2 DM whos e disease is cont rol l ed wi t h either di et
al one or oral hypogl ycemi c agent s and who are i nvol ved in
exercise training. For 9 pr evi ousl y sedent ar y subjects who
had a mean (SD) age of 46.8 (8.9) years (compared wi t h 8 con-
trols wi t h a mean [SD] age of 51.9 [8.2] years), 4 t o 6 weeks
of moderat e-i nt ensi t y, hi gh- vol ume resistance t rai ni ng done
5 days per week resul t ed in si gni fi cant l y great er (P < 0.05)
insulin action (measured wi t h a hyperi nsul i nemi c-eugl ycemi c
clamp), despi t e no change in t he t rai ned subj ect s' maxi mal
aerobic capacity. 33
In a recent st udy by lbaftez et al, 34 t wi ce-weekl y progres-
sive resistance training done for 16 weeks by 10 older men
(mean [SD] age, 66.6 [3.1] years) wi t h newl y di agnosed
t ype 2 DM resulted in a 46.3% increase in insulin sensitivity
(P < 0.01), al ong wi t h a 7.1% reduct i on in fasting glycemia
(P < 0.05) and a significant loss (P < 0.001) of visceral fat
despite their 15.5% average hi gher calorie intake (Figure 4).
When 4 mont hs of resistance exercise were added to an exist-
ing aerobic training pr ogr am for overweight, similarly aged
- 90-
Volume 1, Number 3 S.R. Col berg
1 2 0 0 - 5.5
co
E
i .J_
-5
c
7:
0
" - 0
.._Q
<~
1 1 0 0 -
1 0 0 0 -
9 0 0 -
8 0 0 -
7 0 0 -
6 0 0 -
5 0 0 -
4 0 0 -
3 0 0 -
0
-0
I
Pretraining 6 W e e k s
* t
i t /
o ' 1
I
Pretraining 1 6 W e e k s
5.0
4.5
4.0
3.5 ~ I C
3.0 3 co
~ , ' ~
2.5 ~ <
2.0 3 o._
1.5
1.0
0.5
Figure 4. Total abdomi nal fat and insulin sensitivity, given as mean values, at pretrai ni ng and after a 16-week strength-
trai ni ng peri od for each subject in a study of 1 0 ol der men (mean [SD] age, 66. 6 [3.1] years) wi t h type 2 dia-
betes mellitus. * P < 0. 001 and t p < 0.01 versus the correspondi ng pretrai ni ng value. Copyr i ght 2 0 0 5
Ameri can Diabetes Association. From Diabetes Care, Vol. 28, 2 0 0 5 ; 6 6 2 - 6 6 7 . 34 Reprinted wi t h permission from
The American Diabetes Association.
men (n = 7) in another study, 35 insulin responses to an oral glu-
cose tolerance test decreased by a mean of 25% (P < 0.01), com-
pared with no change in men who engaged in aerobic activities
only (n = 8). This latter finding suggests that resistance train-
ing may exert an even more substantial effect on insulin action.
PREVENTION AND CONTROL OF
DIABETES MELLITUS WITH PHYSICAL ACTIVITY
Over the past decade, researchers have assessed the exercise
habits of certain popul at i ons and have concluded that regu-
lar physical activity is associated wi t h a lower risk for the
devel opment of type 2 DM. 36,37 However, earlier research
consisted of prospective, observational studies of large num-
bers of people, usi ng activity questionnaires or brief physi-
cal exami nat i ons to assess their current health status,
lifestyle habits, and risk factors; such studies relied heavily
on often unreliable, self-reported exercise habits. Self-
reported "active" individuals, nevertheless, were still gener-
ally leaner with lower levels of abdomi nal fat, better glucose
levels and i nsul i n action, and a lower risk of developing DM
t han their sedentary counterparts. 36 Likewise, Manson et a137
exami ned the potential role of physical activity in the pri-
mary prevent i on of type 2 DM by observing a cohort of
87,253 middle-aged US women (aged 34-59 years) for 8 years.
They found that women who engaged in vigorous exercise
at least once a week had a lower risk of devel opi ng DM (age-
adjusted relative risk, 0.67; P < 0.001) compared with women
who did not exercise, irrespective of being obese.
More recently, l andmark clinical trials have directly ex-
ami ned the impact of regular physical activity on the pre-
vent i on of type 2 DM. 38,39 The Diabetes Prevention Program
(DPP) st udi ed 3234 overweight US adults wi t h impaired
glucose tolerance at high risk for DM, almost half of whom
belonged to high-risk mi nori t y groups, such as African
Americans or Hispanics. 38 Participants in the lifestyle arm of
the st udy were asked to follow a low-fat diet and increase
their exercise to include 150 mi nut es per week of a moderate-
intensity activity (such as brisk walking, spread out over at
least 3 days and done for a mi ni mum of 10 mi nut es at a
time). After 3 years, people who changed their lifestyle had
reduced their average risk of devel opi ng DM by 58%.
Moreover, this reduced risk was evi dent regardless of their
ethnicity, age, or sex, and was even greater among i ndi vi du-
als who were _>60 years of age. A similarly designed Finnish
lifestyle st udy of high-risk i ndi vi dual s also resulted in a 58%
reduction in the risk of devel opi ng DM. 39
Al t hough the initial DPP results di d not directly test the
cont ri but i on of physical activity wi t hout si mul t aneous
-91-
I n s u l i n J u l y 2 0 0 6
changes in di et a nd b o d y wei ght , t he act i ve pa r t i c i pa nt s l ost
a mean of onl y 7% of t hei r b o d y wei ght . 38 I ndi vi dua l s i n t he
Fi nni sh l i f est yl e s t udy s i mi l ar l y l ost b o d y wei ght , l owe r e d
t hei r fat i nt ake, at e l ess s a t ur a t e d fat a nd mor e fiber, a nd
a d d e d 30 mi nut es of dai l y wa l ki ng a nd occasi onal r esi st ance
t r ai ni ng. 39 A pos t hoc anal ys i s c ompl e t e d by Laaks onen et
al 4 r ecent l y conf i r med t hat Fi nni sh subj ect s who i ncr eas ed
t hei r l ei sur e- t i me phys i c a l act i vi t y to i ncl ude mode r a t e to
vi gor ous or st r enuous, s t r uct ur ed phys i cal act i vi t i es wer e
63% t o 65% l ess l i kel y t o de ve l op DM. Low- i nt ens i t y t r ai n-
i ng, l ei sur e- t i me phys i cal act i vi t y, a nd wa l ki ng conf er r ed
a ddi t i ona l benef i t s ( Fi gur e 5). For exampl e, i ndi vi dua l s en-
gagi ng i n _>2.5 hour s pe r we e k of wa l ki ng dur i ng t he f ol l ow-
up p e r i o d (n = 157) wer e 63% to 69% l ess l i kel y to de ve l op
DM t han t hose who wa l k e d <1 hour pe r we e k (n = 192). Thi s
f i ndi ng s ugges t s t hat t he t ot al i ncr ease in phys i cal a c t i v i t y - -
r at her t han t he i nt ens i t y of t he e xe r c i s e - - wa s t he var i abl e
mos t s t r ongl y as s oci at ed wi t h a l ower r i sk of de ve l opi ng t he
di sease. 4
Ot her r esear ch has s hown t hat t ype 2 DM ma y be pr e-
vent abl e a nd pr e di a be t e s ma y be r ever si bl e. 41~3 Anot he r
l i f est yl e i nt er vent i on s t udy i nvol vi ng sedent ar y, i nsul i n-
r esi st ant , mi ddl e - a ge d adul t s (12 wome n, 6 men; me a n [SD]
age, 51.9 [5.8] year s) c onduc t e d by Duncan et a141 de mon-
s t r at ed t hat 30 mi nut es of mode r a t e wa l k i n g ~ : t o n e 3 to
7 da ys pe r we e k for 6 mo n t h s - - r e v e r s e d t he pr edi abet i c
st at e of i ndi vi dua l s (as de t e r mi ne d wi t h a f r equent l y s am-
p l e d IV gl ucose t ol er ance test) wi t hout a change i n t hei r
di et s or a ny l oss of b o d y wei ght . I n t hi s st udy, however ,
i nsul i n s ens i t i vi t y wa s r et es t ed onl y 24 to 48 hour s aft er t he
l ast sessi on of exerci se, pos s i bl y conf oundi ng t he r esul t s
wi t h i t s acut e effects. Nonet hel es s , enhanced gl ucose upt a ke
wa s evi dent i n i ndi vi dua l s wh o exer ci sed wi t hout any a ddi -
t i onal i nsul i n r el ease or l oss of a bdomi na l fat.
Pr ogr es s i on t o wa r d a di agnos i s of t he met abol i c syn-
dr ome i n mi ddl e - a ge d me n a nd wo me n over a 5- year p e r i o d
al so has been pr e di c t e d by t hei r phys i c a l act i vi t y ener gy
expendi t ur e, i nde pe nde nt of aer obi c fi t ness, obesi t y, a nd
ot her conf oundi ng fact ors. 42 Dai l y wa l ki ng by i t sel f r educes
vi s c e r a l a d i p o s i t y a n d i mp r o v e s i ns ul i n sensi t i vi t y, as
de mons t r a t e d i n a s t udy c onduc t e d by Mi ya t a ke et al. 43 I n
31 obese Japanese mal es r angi ng i n age f r om 32 to 50 year s,
l evel s of i nt r a - a bdomi na l vi scer al a di pos e t i ssue wer e mos t
cl osel y cor r el at ed wi t h subj ect s' i nsul i n r esi st ance ( t est ed
wi t h t he homeos t as i s mode l as s es s ment i ndex t hat uses fast -
i ng i nsul i n a nd bl ood gl ucose l evel s). Fur t her mor e, da i l y
wal ki ng, r at her t han i mpr ove me nt s i n exerci se capaci t y, wa s
di r ect l y r el at ed to r educt i ons i n vi scer al a di pos i t y i n t hese
subj ect s. 43
Physi cal act i vi t y can i mpr ove gl ycemi c cont r ol i n t hose
a l r e a dy di a gnos e d wi t h t ype 2 DM, a nd i t a ppe a r s t hat
mos t of t he a dva nt a ge s of phys i c a l act i vi t y for pe opl e wi t h
t ype 2 DM ar e r eal i zed t hr ough i mpr ove me nt s i n i nsul i n
act i on. 33,34,44 Acut e i mpr ove me nt s i n i nsul i n s ens i t i vi t y i n
wo me n wi t h t ype 2 DM have been f ound whe t he r t hey
e nga ge d i n l ow- or hi gh- i nt ens i t y wa l ki ng as l ong as t he
t ot al exerci se ener gy e xpe ndi t ur e wa s equi val ent . 44 Mor e-
over, i n pe opl e wi t h t ype 2 DM, i nsul i n sensi t i vi t y wi t h-
out t he acut e benef i t of r ecent exerci se has been s hown to i m-
pr ove by 48% aft er 4 t o 6 we e ks of onl y moder at e- i nt ens i t y
( done at 40%-50% of ma xi ma l oxygen upt ake) r esi st ance
t r ai ni ng, wi t h mi ni ma l change i n b o d y fat or mus cl e a nd no
change i n ma xi ma l aer obi c capaci t y. 33
Si mi l arl y, for 10 me n ( mean [SD] age, 66.6 [3.1] year s)
who wer e ne wl y di a gnos e d wi t h t ype 2 DM, par t i ci pat i on i n
a t wi ce- weekl y pr ogr es s i ve r esi st ance t r ai ni ng p r o g r a m for
16 we e ks r es ul t ed i n bot h si gni f i cant mus cl e mas s gai n a nd
s ubs t ant i al l oss of b o d y fat ( par t i cul ar l y f r om t he abdomen) ;
t hese out comes occur r ed des pi t e a 15.5% i ncr ease i n t he
a mount of cal or i es cons umed, al ong wi t h a si zabl e i ncr ease
i n t hei r i nsul i n sensi t i vi t y. 34
In ol der wo me n wi t h t ype 2 DM ( mean age of 59. 4-
63.4 ye a r s acr oss gr oups) , t he combi nat i on of aer obi c a nd
r esi st ance t r ai ni ng ma y r esul t i n even gr eat er i mpr ove me nt s
i n t hei r i nsul i n act i on a nd gl ucose use, as wel l as a l ar ger
decr ease in t hei r a bdomi na l fat c ompa r e d wi t h aer obi c t r ai n-
i ng a l o n e - - a l l whi l e i ncr easi ng t he dens i t y of t hei r mus -
cles. 45 Thus, bot h aer obi c a nd anaer obi c f or ms of t r ai ni ng
a ppe a r to i mpr ove s ens i t i vi t y to i nsul i n and, as a r esul t ,
assi st i n l ower i ng a ny el evat i ons i n bl ood gl ucose l evel s a nd
ma i nt a i ni ng cl oser to nor ma l gl ycemi c l evel s.
Regul ar phys i cal act i vi t y is r equi si t e, however . Whi l e t he
effects of a si ngl e wo r k o u t ma y l ast f r om i hour (aft er shor t ,
mi l d exerci se) to up to 1 or 2 da ys (for pr ol onge d, i nt ense
act i vi t i es), t he effects of r egul ar t r ai ni ng begi n to r ever se
wi t hi n 2 to 3 days , even t hough mus cl e mas s ma y have
i ncr eas ed af t er t r ai ni ng. 46 For i nst ance, i n 7 mal e a nd 2 fe-
mal e moder at el y t r ai ned subj ect s ( mean [SD] age, 51 [3] years),
5 da ys of mode r a t e t r ai ni ng done 45 mi nut es dai l y r es ul t ed
i n a 43% l oss i n i nsul i n s ens i t i vi t y me a s ur e d by an or al gl u-
cose t ol er ance t est af t er i da y of i nact i vi t y a nd a 66% l oss i n
i nsul i n s ens i t i vi t y aft er 3 days . 46
W
r h i l e t h e e f f e c t s o f a s i n g l e w o r k o u t m a y l a s t f r o m
1 h o u r ( a f t e r s h o r t , m i l d e x e r c i s e ) t o u p t o 1 o r 2 d a y s
( f o r p r o l o n g e d , i n t e n s e a c t i v i t i e s ) , t h e e f f e c t s o f r e g u l a r t r a i n -
i n g b e g i n t o r e v e r s e w i t h i n 2 t o 3 d a y s .
Exerci se i t sel f enhances i ns ul i n- s t i mul at ed gl ucose di s-
posal . Chr i st - Rober t s et a147 c ompa r e d 2 gr oups of s ubj e c t s - -
i gr oup of 17 i ndi vi dua l s who wer e over wei ght , i nsul i n resi s-
tant, and di d not have DM, and anot her gr oup of 9 over wei ght ,
i ns ul i n- r e s i s t a nt i n d i v i d u a l s wh o al so h a d t y p e 2 DM- -
dur i ng 30 mi nut es of mode r a t e exerci se unde r t a ke n wi t h
a hype r i ns ul i ne mi c - e ugl yc e mi c i nsul i n cl amp. They f ound
t hat t he i nsul i n i nf usi on s yner gi s t i cal l y i ncr eas ed i nsul i n-
s t i mul a t e d gl ucose di s pos a l a nd st or age, as wel l as pos t exer -
cise gl ucose upt ake, i n bot h gr oups. However , i ncr eas ed
i nsul i n r ecept or s i gnal i ng occur r ed onl y i n t he gr oup wh o
di d not have DM. Ei ght we e ks of mode r a t e aer obi c exerci se
- 92-
Vol ume 1, Nu mb e r 3 S.R. Co l b e r g
A
>.
P=0. 16
i F
Model 1 Model 2
P < 0.001
Mo d e r a t e t o Vi g o r o u s
LTPA Dur i ng Fol l ow- up ( h / wk )
P < 0.001
<1 hour
[ ] 1-2.4 hours
[ ] _>2.5 hours
P = 0.27
Model 3
P = 0.001
F i g u r e 5 .
>.
I r
Model 1 Model 2
Wa l k i n g f or Exercise
Dur i ng Fol l ow- up ( h / wk )
Model 3
Relative r i sk of d e v e l o p i n g d i a b e t e s mel l i t us a c c o r d i n g t o (A) mean d u r a t i o n of moder at e t o v i g o r o u s physi cal
a c t i v i t y d u r i n g f ol l ow- up ( <1, 1 - 2 . 4 , a n d _>2.5 h / w k ) ; a n d (B) mean d u r a t i o n of w a l k i n g f or exer ci se ( <1, 1 - 2 . 4 ,
a n d _>2.5 h / w k ) in t he Fi nni sh Di abet es Prevent i on Study. Mo d e l 1: Adj ust ed f or a g e , sex, a n d ei t her (1) c h a n g e
in moder at e t o v i g o r o u s leisure-time phy s i c al a c t i v i t y (LTPA) from basel i ne a n d mean l ow- i nt ensi t y LTPA d u r i n g
f ol l ow- up a n d its c h a n g e from basel i ne; o r (2) c h a n g e in d u r a t i o n of w a l k i n g f or exer ci se from basel i ne a n d ot her
forms of LTPA. Mo d e l 2: Adj us t ed f or v a r i a b l e s in model 1 a n d mean val ues of d i e t a r y i nt ake of ener gy, t ot al
a n d sat ur at ed fat, a n d f i b e r d u r i n g f ol l ow- up a n d t hei r c hanges from basel i ne. Mo d e l 3: Adj us t ed f or v a r i a b l e s
in model 2 a n d mean b o d y mass i n d e x d u r i n g f ol l ow- up a n d its c h a n g e from basel i ne. C o p y r i g h t 2 0 0 5
Ame r i c a n Di abet es As s oc i at i on. Fr om Diabetes, Vol . 5 4 , 2 0 0 5 ; 1 5 8 - 1 6 5 . 40 Mo d i f i e d wi t h per mi ssi on from The
American Diabetes Association.
- 9 3 -
Insulin July 2 0 0 6
t r ai ni ng has al so been s hown t o i ncr ease GS act i vi t y a nd
GLUT4 pr ot ei n expr essi on, but not i nsul i n si gnal i ng, in bot h
ove r we i ght cont r ol s a nd i ndi vi dua l s wi t h t ype 2 DM. 48
Fi nal l y, phys i cal t r ai ni ng ma y enhance pancr eat i c ]3-cell
f unct i on ( and t her ef or e i nsul i n secr et or y capaci t y) i n pe opl e
wi t h t ype 2 DM. In heal t hy, young i ndi vi dual s , phys i c a l fit-
ness t r ai ni ng i ncreases i nsul i n sensi t i vi t y but l ower s t he capac-
i t y to secret e i nsul i n ( al bei t l ess is needed) . Pat i ent s wi t h
t ype 2 DM wer e cat egor i zed i nt o " l ow" (n = 8; me a n age,
49.5 year s) a nd " mode r a t e " (n = 16; me a n age, 53.5 year s)
i nsul i n secr et or s ba s e d on t hei r C- pe pt i de r es pons es to an IV
gl ucagon t est (aft er 5 da ys pe r we e k of mode r a t e cycl i ng for
3 mont hs) . 49 The " mode r a t e " secr et or s s howe d si gni f i cant
i ncr eases (P < 0.05) i n ]3-cell r es pons i venes s to 18- a nd
25- mM hype r gl yc e mi a a nd t o ar gi ni ne st i mul at i on. How-
ever, no change wa s obs e r ve d i n " l ow" secr et or s a nd s eden-
t ar y cont rol s.
EFFECTIVE EXERCISE FOR PEOPLE WI TH
TYPE 2 DIABETES MELLITUS
To exerci se effect i vel y a nd safely, i ndi vi dua l s wi t h t ype 2 DM
mus t unde r s t a nd t he phys i ol ogy be hi nd t hei r bodi e s ' exer -
ci se r esponses. Fi rst , i t is i mpor t a nt to r ecogni ze t hat not al l
phys i c a l act i vi t i es ar e equal a nd t hat t he i nt ens i t y a nd dur a -
t i on of phys i cal act i vi t i es can gr eat l y affect t he r es ul t ant
gl ycemi c r esponses. I nt ense act i vi t i es such as he a vy wei ght
l i f t i ng or ne a r - ma xi ma l exerci se can cause t r ans i ent el eva-
t i ons i n bl ood gl ucose l evel s due to an e xa gge r a t e d r el ease of
gl ucos e- r ai s i ng hor mone s such as epi nephr i ne. 2 Conver sel y,
i nt er mi t t ent hi gh- i nt ens i t y exerci se unde r t a ke n i mme di a t e l y
af t er br eakf as t by 8 i ndi vi dua l s wi t h t ype 2 DM t r eat ed by
di et onl y r es ul t ed i ns t ead i n r e duc e d bl ood gl ucose concen-
t r at i ons a nd i nsul i n secr et i on i n a s t udy by Lar sen et al. 5
Thi s wa s l i kel y due to el evat ed ci r cul at i ng i nsul i n l evel s i n
r es pons e to f ood i ngest i on. As me nt i one d pr evi ousl y, act i vi -
t i es t hat ar e of l onger dur a t i on a nd l ower i nt ens i t y gener al l y
r esul t i n a decl i ne i n bl ood gl ucose l evel s i n al l i ndi vi dua l s
wi t h DM. 1 13
I n heal t hy i ndi vi dua l s or i n t hose wi t h t ype 2 DM whos e
di s eas e is bei ng cont r ol l ed wi t h di et a nd exerci se al one, t he
r i sk of de ve l opi ng l ow bl ood s ugar dur i ng exerci se is mi ni -
mal . Thus, s t r i ngent r e c omme nda t i ons ar e us ua l l y not nec-
es s ar y to ensur e bl ood gl ucose cont r ol wi t h exerci se. Bl ood
gl ucose moni t or i ng s houl d be pe r f or me d bef or e a nd aft er an
act i vi t y to assess i t s effect on gl ycemi a. Suppl e me nt i ng wi t h
c a r bohydr a t e s is gener al l y not n e e d e d wi t h t hese pat i ent s;
however , bl ood gl ucose moni t or i ng wi l l r eveal whi c h i ndi -
v i d u a l s ma y ne e d a ddi t i ona l c a r bohydr a t e s t o pr e ve nt
hypogl yc e mi a dur i ng a nd aft er exerci se. These i ndi vi dua l s
can be s u p p l e me n t e d at a r at e of 15 g / h on a pr e l i mi na r y
basi s unt i l opt i ma l i nt ake can be de t e r mi ne d wi t h gl ucose
moni t or i ng. 13
Pr ol onged exerci se, however , has a gr eat er pot ent i al to
cause hypogl yc e mi a bot h dur i ng a nd af t er exerci se, par t i cu-
l ar l y i n pe opl e t r eat ed wi t h ker at i n or al hypogl yc e mi c
agent s or exogenous i nsul i n. To pr e ve nt hypogl yc e mi a ,
t hese i n d i v i d u a l s wi l l l i kel y ne e d t o c ons ume r a p i d l y
a bs or be d c a r bohydr a t e s to count er bal ance decl i nes i n bl ood
gl ucose l evel s a n d / o r to r educe t hei r or al medi cat i ons or
i ns ul i n dos i ng bef or e e x e r c i s e . 1,13,27 Use of or al h y p o -
gl ycemi c agent s, pa r t i c ul a r l y t hose wi t h a l onger dur a t i on
such as gl ybur i de, car r y a hi gher r i sk of exer ci s e- i nduced
hypogl yc e mi a t han whe n t ype 2 DM is t r eat ed wi t h di et a nd
exerci se al one. 27 Even ne we r gener at i on, shor t er - act i ng sul -
f onyl ur eas such as gl i mepi r i de a nd gl i bencl ami de can i ncrease
t he r i sk of hypogl yc e mi a . 27 I n pat i ent s wi t h pos t a bs or pt i ve
t ype 2 DM, t he hypogl yc e mi c act i on of gl i bencl ami de a nd
exerci se wa s e nha nc e d whe n t he t r eat ment s wer e com-
bi ned, r ef l ect i ng an i ncr eas ed i nhi bi t i on by gl i bencl ami de-
enhanced i nsul i n l evel s of hepat i c gl ucose pr oduc t i on whe n
such pr oduc t i on is accel er at ed by exerci se.
I nsul i n use cr eat es i t s own set of s peci al i zed exerci se
concerns. For regul ar, p l a n n e d exerci se, s hor t - act i ng pr e-
exerci se i nsul i n dos es wi l l l i kel y ne e d t o be l owe r e d to pr e-
vent hypogl yc e mi a f r om occur r i ng i n pe opl e wi t h t ype 2 DM
who ar e t aki ng i nsul i n t her apy. Newer , synt het i c i nsul i n
anal ogues , such as i nsul i n l i spr o, al so i nduce mor e r a pi d
decr eas es i n bl ood gl ucose concent r at i ons t han r egul ar
h u ma n i nsul i n due to t hei r f ast er abs or pt i on. 51 Cons equent -
ly, pe opl e wi t h t ype 2 DM who exerci se wi l l need to check
t hei r bl ood s ugar l evel s bef or e, occasi onal l y dur i ng, a nd
aft er exerci se t o moni t or i t s effects a nd c ompe ns a t e wi t h
a ppr opr i a t e di et ar y a n d / o r me di c a t i on r egi men changes. 1
p
eople with type 2 DM who exercise wi l l need to check
their blood sugar levels before, occasionally during, and
after exercise to monitor its effects and compensate with
appropriate dietary a n d / o r medication regimen changes.
However , if onl y l onger - act i ng i nsul i ns, such as i nsul i n
gl ar gi ne, ar e bei ng a bs or be d f r om SC de pot s dur i ng phys -
i cal act i vi t i es, i mme di a t e decl i nes i n gl ycemi a dur i ng exer -
ci se ma y n o t be as l i kel y. For e x a mp l e , an i n t e n s e
30- mi nut e p e r i o d of exerci se by i ndi vi dua l s wi t h t ype 1 DM
wa s not s hown to i ncr ease t he abs or pt i on r at e of s ubcut a-
neous l y i nj ect ed, basal , l ong- act i ng i nsul i n anal ogues such
as i ns ul i n gl ar gi ne, 52 a nd s i mi l ar f i ndi ngs wo u l d be expect ed
i n t hose wi t h t ype 2 DM us i ng s i mi l ar s uppl e me nt a l bas al
i nsul i ns.
Lat er-onset hypogl ycemi a becomes a great er concern when
c a r bohydr a t e st or es (ie, mus cl e a nd l i ver gl ycogen) ar e
depl et ed dur i ng an exercise session. Hi gh- i nt ensi t y exer ci s es - -
such as r e pe a t e d i nt er val t r a i ni ng- - r e s ul t i n s ubs t ant i al
depl et i on of mus cl e gl ycogen, whi ch i ncr eases t he r i sk for
l at er - onset hypogl yc e mi a , pa r t i c ul a r l y if cer t ai n di abet i c
medi cat i ons such as s uppl e me nt a l i nsul i n or l onger - l as t i ng
s ul f onyl ur eas ar e t aken. 27 Cons umi ng mode r a t e a mount s of
c a r bohydr a t e s (5-30 g) dur i ng a nd wi t hi n 30 mi nut e s aft er
exhaust i ve, gl yc oge n- de pl e t i ng exerci se wi l l l ower hypo-
gl ycemi a r i sk a nd al l ow for mor e effi ci ent r es t or at i on of
- 94-
Volume 1, Number 3 S.R. Col ber g
mus cl e gl ycogen a nd pot ent i al s uper compens at i on. 29 To ef-
f ect i vel y ma i nt a i n gl ycemi c cont r ol a nd opt i mi z e gl ycogen
r esynt hesi s, s ome a ddi t i ona l i nsul i n (al bei t l ess t han usual )
ma y st i l l be r equi r ed by i ndi vi dua l s wi t h t ype 2 DM who ar e
t r eat ed wi t h i nsul i n to faci l i t at e gl ucose upt a ke i n t he i mme -
di at e post exer ci se per i od.
The Ame r i c a n Di abet es As s oci at i on ( ADA) r e c omme nds
t hat c a r bohydr a t e i nges t i on is n e e d e d for pr e- exer ci se bl ood
gl ucose l evel s of <100 mg / d L (<5.5 mM)l ; however , t hi s
r e c omme nda t i on wo u l d a p p l y onl y to pe opl e wi t h t ype i or
t ype 2 DM who ar e t aki ng s uppl e me nt a l i nsul i n i nj ect i ons or
us i ng cer t ai n sul f onyl ur eas. 27,51 For pe opl e whos e di s eas e is
cont r ol l ed wi t h di et or or al ant i di abet i c medi cat i ons al one,
ext r a c a r bohydr a t e s are gener al l y not r equi r ed dur i ng exer -
ci se l ast i ng <1 hour. Cl i ni ci ans r e c omme nd t hat pe opl e wi t h
t ype 2 DM who ar e t r eat ed wi t h i nsul i n i ngest at l east 15 g
of c a r bohydr a t e bef or e exerci se for a st ar t i ng bl ood gl ucose
l evel of <100 mg / d L; t he exact quant i t y d e p e n d s on ot her
var i abl es such as whe n t he i nj ect ed i nsul i n pe a ks a nd t he
dur a t i on of t he activity. 13 I n al l cases, i nt ense, s hor t pe r i ods
of exerci se wo u l d r equi r e a l esser c a r bohydr a t e i nt ake, if any,
due to a gr eat er r el ease of count er r egul at or y hor mones . 2
Anot he r ADA r e c omme nda t i on addr es s es exerci se dur -
i ng hype r gl yc e mi c condi t i ons. Al t hough hype r gl yc e mi a is
of t en def i ned as any bl ood gl ucose val ue >125 mg / d L
(6.9 mM) , an a bnor ma l gl ycemi c r es pons e to exerci se is
not us ual l y exper i enced unt i l l evel s exceed t wi ce t hat , or
250 mg / d L (13.9 mM) , a nd t hen l i kel y onl y i n i ndi vi dua l s
who ar e i nsul i n def i ci ent (eg, t hose wi t h t ype i or t ype 2 DM
who have ve r y l i t t l e or no e ndoge nous i nsul i n pr oduct i on) . 1
Ket one b o d y pr oduc t i on ma y i ncr ease a nd r esul t i n ket osi s,
a l t hough t hi s is ve r y u n c o mmo n i n t ype 2 DM. A mor e
a ppr opr i a t e r e c omme nda t i on for exer ci ser s wi t h t ype 2 DM
is s i mpl y to "use caut i on" whe n unde r t a ki ng phys i cal act i vi -
t i es if t hei r gl ucose l evel s ar e 300 mg / d L (16.7 mM) wi t hout
ket osi s r at her t han f or egoi ng t he exerci se, me a ni ng t hat t hey
s houl d moni t or bl ood gl ucose l evel s f r equent l y a nd h y d r a t e
a de qua t e l y t o pr e ve nt pr obl ems . 1,13 If hype r gl yc e mi a occur s
acut el y aft er a meal , a decr ease i n bl ood gl ucose wi t h aer o-
bi c exerci se wi l l l i kel y r esul t as l ong as l evel s of ci r cul at i ng
i nsul i n ar e el evat ed. 26
As far as t he frequency, dur at i on, a nd t ype of act i vi t i es
t hat a nyone wi t h t ype 2 DM s houl d engage in, t he cur r ent
r e c omme nda t i ons f r om t he ADA 13 a nd ot her s gener al l y fol -
l ow t he US Sur geon Gener al ' s r e c omme nda t i on 53 to accu-
mul at e at l east 30 mi nut e s of mode r a t e - i nt e ns i t y aer obi c
act i vi t y mos t da ys of t he week. These r e c omme nda t i ons ar e
ba s e d on t he f i ndi ng t hat i nsul i n s ens i t i vi t y is e nha nc e d by a
si ngl e bout of aer obi c exerci se for onl y 24 t o 72 hour s i n non-
di abet i c i ndi vi dual s , d e p e n d i n g on t he dur a t i on a nd i nt en-
si t y of t he act i vi t y; s ome r ecent st udi es, however , i ndi cat e
t hat ol de r i ndi vi dua l s ma y not exper i ence l ong- l i ved gai ns
i n t hei r l evel of i nsul i n act i on. 17,25 Because t he dur a t i on of i n-
cr eas ed i nsul i n s ens i t i vi t y is l i kel y much l ess t han 72 hour s,
i t is r e c o mme n d e d t hat successi ve exerci se sessi ons be s epa-
r a t e d by no mor e t han t hi s a mo u n t of t i me, or t hat i ndi vi du-
al s wi t h DM s houl d not l et mor e t han 2 da ys l aps e be t we e n
bout s of exerci se a nd t hat t hey exerci se at l east 3 noncons ec-
ut i ve da ys pe r week. 13 Thei r exerci se s houl d consi st of l ow-
to moder at e- i nt ens i t y phys i c a l act i vi t y l ast i ng a mi n i mu m of
10 to 15 mi nut e s pe r sessi on, wi t h t hei r goal bei ng 30 mi n-
ut es at a t i me. The mode of exerci se ma y va r y d e p e n d i n g on
t he pr es ence of coexi st i ng compl i cat i ons such as pe r i phe r a l
ne ur opa t hy or degener at i ve ar t hr i t i s, whi ch ma y r equi r e al -
t er nat i ves t hat are non- we i ght - be a r i ng (eg, st at i onar y cycl i ng,
ar mchai r exerci ses, s wi mmi ng or ot her aquat i c act i vi t i es). 1,13
I
ndividuals wi t h DM should not let more than 2 days lapse
between bouts of exercise. They should exercise at least 3 non-
consecutive days per week, consisting of low- to moderate-
intensity physical act i vi t y lasting a minimum of 10 to 15
minutes per session.
In addi t i on, r esi st ance t r ai ni ng is r e c o mme n d e d for pa -
t i ent s wi t h t ype 2 DM becaus e i t has t he pot ent i al to i mpr ove
mus c ul a r s t r engt h a nd endur ance, enhance fl exi bi l i t y, i m-
pr ove b o d y compos i t i on, a nd decr ease r i sk for car di ovas cu-
l ar di sease, al l whi l e i ncr easi ng a mount s of i ns ul i n- s ens i t i ve
mus cl e mass. 33 35 Ol der r e c omme nda t i ons s t at ed t hat i t
s houl d i deal l y be unde r t a ke n a mi n i mu m of t wi ce we e kl y as
pa r t of a we l l - r ounde d exerci se p r o g r a m ( i ncl udi ng aer obi c
a nd f l exi bi l i t y t r ai ni ng) a nd i ncl ude 8 t o 10 exerci ses i nvol v-
i ng t he maj or mus cl e gr oups , doi ng a mi n i mu m of 1 set of
10 to 15 r epet i t i ons to near fat i gue. 1 Al t hough even t wi ce-
we e kl y t r ai ni ng has pr ove n benef i t s for me n wi t h t ype
2 DM, 34 a r ecent s t u d y by Duns t a n et a154 s h o we d t hat
18 me n wi t h t ype 2 DM a ge d 60 to 80 year s successf ul l y pr o-
gr es s ed over 6 mont hs of r esi st ance t r ai ni ng to compl et i ng
3 set s of 8 to 10 r epet i t i ons done at 75% to 80% of ma xi ma l
on 8 to 10 exer ci ses t hr i ce weekl y. The subj ect s al so exper i -
enced much gr eat er i ncr eases in mus cl e mass, decr eases i n
b o d y fat, a nd i mpr ove me nt s i n over al l gl ycemi c cont rol .
Thus, a t r ai ni ng pr ot ocol such as t hi s l at t er one ma y be a bet -
t er goal . 13
Ot her r e c omme nda t i ons for exer ci ser s wi t h t ype 2 DM
focus mor e on safe exerci se par t i ci pat i on if t her e is t he pr es -
ence or t he pos s i bi l i t y of de ve l opi ng DM- r el at ed compl i -
cat i ons, such as car di ovascul ar di sease, hyper t ens i on, neur op-
athy, or ot her mi cr ovascul ar compl i cat i ons. A ful l di scussi on
of t hese compl i cat i ons is b e y o n d t he scope of t hi s revi ew, but
r eader s ar e r ef er r ed t o t he Ame r i c a n Col l ege of Spor t s Me di -
ci ne' s pos i t i on s t and on exerci se a nd t ype 2 DM 1 a nd a mor e
r ecent r evi ew by Si gal et a113 for a ddi t i ona l i nf or mat i on. As
a gener al r ecommendat i on, bef or e begi nni ng an exerci se
p r o g r a m, i n d i v i d u a l s wi t h t ype 2 DM ar e a d v i s e d t o
unde r go a medi cal eval uat i on to scr een for t he pr es ence of
macr ovas cul ar a nd mi cr ovas cul ar compl i cat i ons pot ent i al l y
exacer bat ed by exercise. The exami nat i on s houl d scr een
for over al l gl yc e mi c cont r ol , phys i c a l l i mi t a t i ons wi t h
r espect to j oi nt pr obl e ms c o mmo n to DM, pr es cr i bed me di -
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I n s u l i n J u l y 2 0 0 6
cat i ons, a nd t he t ype a nd s ever i t y of DM compl i cat i ons (eg,
car di ovas cul ar heal t h, pe r i phe r a l ar t er i al di sease, r et i nopa-
thy, nephr opat hy, pe r i phe r a l a nd aut onomi c neur opat hi es ) .
A g r a d e d exerci se t est ma y be r e c o mme n d e d t o scr een for
car di ovas cul ar di s eas e d e p e n d i n g on t he age of t he pe r s on
a nd hi s or her DM dur at i on. 1
B
e f o r e b e g i n n i n g a n e x e r c i s e p r o g r a m , i n d i v i d u a l s w i t h
t y p e 2 D M a r e a d v i s e d t o u n d e r g o a me d i c a l e v a l u a t i o n
t o scr een f o r t he p r e s e n c e o f ma c r o v a s c u l a r a n d mi c r o v a s -
c u l a r c o mp l i c a t i o n s p o t e n t i a l l y e x a c e r b a t e d b y ex er c i s e.
OTHER INSULIN-RELATED BENEFITS OF EXERCISE
Ma ny chr oni c di s eas es i n a ddi t i on to t ype 2 DM ar e r el at ed
to r educt i ons i n i nsul i n sensi t i vi t y, i ncl udi ng hyper t ens i on,
hear t di sease, a nd st roke. 5547 Physi cal t r ai ni ng al so a ppe a r s
to enhance ~-cell i nsul i n pr oduc t i on i n i ndi vi dua l s wi t h
t ype 2 DM as l ong as a de qua t e a mount s of f unct i oni ng
~-cells r emai n i n t he pancr eas. 49
Exerci se can r esul t i n mor e r est f ul a nd l onger sl eep. Re-
cent s t udi es have l i nked s l eepi ng l ess (eg, onl y 5 hour s a
ni ght ) wi t h an i ncr eas ed i nci dence of over wei ght , obesi t y,
a nd i nsul i n r esi st ance i n heal t hy, y o u n g adul t s; sl eep di s t ur -
bances have been as s oci at ed wi t h an i ncr eas ed i nci dence of
t ype 2 DM i n t he gener al popul at i on. 58
Physi cal act i vi t y ma y act ual l y p l a y a r ol e in pr e ve nt i ng
DM- r el at ed compl i cat i ons ( i ncl udi ng bot h mi cr ovas cul ar
a nd macr ovas cul ar ) by amel i or at i ng a st at e of l ow- l evel
i nf l a mma t i on as s oci at ed wi t h i nsul i n r esi st ance a nd chr oni c
hyper gl ycemi a. 59,6 Evi dence is mount i ng t hat a di pos e t i ssue
cont r i but es to t he pr oduc t i on of t umor necr osi s f act or - ~
( TNF- ~) , a c yt oki ne n o w be l i e ve d t o be a d r i v i n g f or ce
b e h i n d i ns ul i n r es i s t ance a n d d y s l i p i d e mi a , 58 r at her t ha n
i nt er l euki n- 6. Regul ar exerci se a ppa r e nt l y enhances t he s up-
pr es s i on of TNF- ~ a nd t her eby offers pr ot ect i on agai ns t any
i nsul i n r esi st ance i t ma y cause, al ong wi t h i t s as s oci at ed
heal t h i ssues.
Aer obi c exerci se t r ai ni ng has been s hown to i mpr ove
endot hel i al f unct i on i n di f f er ent vas cul ar be ds i n pe opl e
wi t h t ype 2 DM; one s t udy t hat e xa mi ne d 16 i ndi vi dua l s
wi t h t ype 2 DM us e d f or ear m p l e t h y s mo g r a p h y a nd i nt r a-
br achi al i nf usi ons of s o d i u m ni t r opr us s i de (a s t i mul at or of
e ndot he l i um- i nde pe nde nt vas odi l at i on) a nd acet yl chol i ne
(an e n d o t h e l i u m- d e p e n d e n t vas odi l at or ) to de t e r mi ne t hat
8 we e ks of aer obi c exerci se t r ai ni ng enhances e ndot he l i um-
d e p e n d e n t va s odi l a t i on i n bot h condui t a nd r esi st ance ves-
sels. 61 Thus, if endot hel i al dys f unct i on is an i nt egr al c ompo-
nent of t he pa t hoge ne s i s of vas cul ar di sease, as is cur r ent l y
bel i eved, a s t r ong a r gume nt can be ma d e for t he i ncl us i on of
an exerci se p r o g r a m i n t he ma n a g e me n t of t ype 2 DM.
CONCLUSIONS
The i nt er act i ons of i nsul i n a nd exerci se have heal t h r ami f i ca-
t i ons in DM ma n a g e me n t t hat mus t be a c knowl e dge d a nd
mor e f ul l y under s t ood. Cl i ni ci ans ne e d to cl ear l y unde r -
s t and a nd c ommuni c a t e r el evant fact ors, such as t he act i on
a nd avai l abi l i t y of ci r cul at i ng i ns ul i n a nd count er r egul at or y
hor mone r esponses, so t hat pat i ent s wi t h t ype 2 DM can
saf el y a nd ef f ect i vel y benef i t f r om phys i c a l act i vi t y wi t hout
fear of unbal anci ng t hei r gl ycemi c cont rol . The mos t r ecent
r esear ch on i nsul i n s ens i t i vi t y l eaves no doubt t hat phys i cal
a c t i v i t y - - p o s s i b l y i n c o mb i n a t i o n wi t h ot he r l i f es t yl e
changes t hat i mpact vi scer al f a t - - p l a y s a maj or r ol e in t he
pr e ve nt i on a nd cont r ol of i nsul i n r esi st ance, pr edi abet es ,
a nd t ype 2 DM. Mor eover , even pe opl e wi t h t ype 2 DM can
a nd s houl d par t i ci pat e in r egul ar phys i cal act i vi t y, i ncl udi ng
bot h aer obi c a nd r esi st ance t r ai ni ng. Addi t i ona l s t udi es ar e
n e e d e d to i nvest i gat e t he a nt i - i nf l a mma t or y effect of phys i -
cal act i vi t y a nd ot her l i f est yl e changes on t he cont r ol a nd
pr e ve nt i on of DM, as wel l as t he i mpact of i nf l a mma t i on on
ot her i ns ul i n- r el at ed heal t h concerns.
REFERENCES
1. Brooks GA. Importance of the ' cr ossover ' concept in exer-
cise metabolism. Cl i n Exp Pharmacol Physiol. 1 9 9 7 ; 2 4 : 8 8 9 -
8 9 5 .
2. Kr ei sman SH, Halter JB, Vranic M, Marliss EB. Combi ned infu-
sion of epi nephr i ne and norepinephrine during moderate exer-
cise reproduces the glucoregulatory response of intense exercise.
Diabetes. 2 0 0 3 ; 5 2 : 1 3 4 7 - 1 3 5 4 .
3. Hi r s c h IB, Ma r k e r J C, Smith 13, e t a l . Insulin and glucagon in pre-
vention of hypoglycemia during exercise in humans. Am J PhysioL
1991 ; 2 6 0 : E6 9 5 - E7 0 4 .
4. Wasserman DH, Lacy DB, Colburn CA, et al. Efficiency of com-
pensation f or absence of fall in i nsul i n dur i ng exercise. Am J
Physiol. 1991 ; 261 : E5 8 7 - E5 9 7 .
5. Galassetti P, Ma n n S, Tate D, et al. Effect of morning exercise on
counterregulatory responses to subsequent, afternoon exercise.
J Appl Physiol. 2 0 0 1 ; 9 1 : 9 1 - 9 9 .
6. Galasselti P, Mann S, Tate D, et al. Effects of antecedent prolonged
exercise on subsequent counterregulatory responses to hypogly-
cemia. Am J Physiol Endocrinol Metab. 2001 ; 2 8 0 : E 9 0 8 - E 9 1 7 .
7. Romi j n JA, Coyl e EF, Sidossis LS, et al. Substrate metabolism dur-
ing different exercise intensities in endurance-trained women.
J Appl PhysioL 2 0 0 0 ; 8 8 : 1 7 0 7 - 1 7 1 4 .
8. Blaak EE, van AggeI-Leijssen DP, Wagenmakers AJ, et al. Impaired
oxi dat i on of plasma-derived fatty acids in type 2 di abet i c
subjects dur i ng moderate-intensity exercise. Diabetes. 2 0 0 0 ; 4 9 :
2 1 0 2 - 2 1 0 7 .
9. Col ber g SR, Hagber g JM, Mc Co l e SD, et al. Utilization of glyco-
gen but not plasma glucose is reduced in individuals wi t h
NI DDM dur i ng mild-intensity exercise. J Appl Physiol. 1996; 81 :
2 0 2 7 - 2 0 3 3 .
10. Al br i ght A, Franz M, Hornsby G, et al. American Col l ege of
Sports Medi c i ne position stand. Exercise and type 2 diabetes.
Med Sci Sports Exerc. 2 0 0 0 ; 3 2 : 1 3 4 5 - 1 3 6 0 .
- 96-
V o l u me 1, N u m b e r 3 S.R. C o l b e r g
11. Berggren JR, Tanner C J, Koves TR, et al. Glucose uptake in mus-
cle cell cultures f r o m endurance-trained me n . Med Sci Sports
Exerc. 2 0 0 5 ; 3 7 : 5 7 9 - 5 8 4 .
12. Boul e NG, Weisnagel S J, Lakka TA, et al, for lhe HERITAGE Family
Study. Effects of exercise training on glucose homeostasis: The
HERITAGE Family Study. Diabetes Care. 2 0 0 5 ; 2 8 : 1 0 8 - 1 1 4 .
13. Sigal R J, Kenny GP, Wasserman DH, Castaneda-Sceppa C.
Physical act i vi t y/ exer ci se and type 2 diabetes. Diabetes Care.
2 0 0 4 ; 2 7 : 2 5 1 8 - 2 5 3 9 .
14. Denton JC, Schuhz R, Jamurtas AZ, A n g e l o p o u l o s TJ.
Improvements in glucose tolerance in obese mal es wi t h abnor-
mal glucose tolerance following 10 days of aer obi c exercise.
Prev Med. 2 0 0 4 ; 3 8 : 8 8 5 - 8 8 8 .
15. Ni shi da , Hi gaki , Tokuyama K, et al. Ef f ect of mi l d exercise
training on glucose effectiveness in healthy men. Diabetes Care.
2 0 0 1 ; 2 4 : 1 0 0 8 - 1 0 1 3 .
16. Evans EM, Racette SB, Peterson LR, et al. Aer obi c power and
insulin action improve in response to endurance exercise train-
i ng in healthy 7 7 - 8 7 y r olds. J Appl PhysioL 2 0 0 5 ; 9 8 : 4 0 - 4 5 .
17. Goul et ED, Mel ancon M O , Aubertin-Leheudre M, Dionne U.
Aer obi c training improves insulin sensitivity 7 2 - 1 2 0 h after the
last exercise session in younger but not in ol der women. Eur J
Appl PhysioL 2 0 0 5 ; 9 5 : 1 4 6 - 1 5 2 .
18. Rimbert V, Boirie , Bedu M, et al. Muscle fat oxi dat i ve capac-
i t y is not impaired by a g e but b y physical inactivity: Association
wi t h insulin sensitivity. FASEBJ. 2 0 0 4 ; 1 8 : 7 3 7 - 7 3 9 .
19. Houmard JA, Tanner C J, Slentz CA, et al. Ef f ect of the volume
and intensity of exercise training on i nsul i n sensitivity. J Appl
Physiol. 2 0 0 4 ; 9 6 : 1 0 1 - 1 0 6 .
2 0 . Goodpast er BH, Katsiaras A, Kelley DE. Enhanced fat oxi dat i on
through physical activity is associated wi t h improvements in
insulin sensitivity in obesity. Diabetes. 2 0 0 3 ; 5 2 : 2 1 9 1 - 2 1 9 7 .
2 1 . Pr uchni c R, Katsiaras A, He J, et al. Exercise training increases
intramyocellular l i pi d and oxi dat i ve capaci t y in ol der adults. Am
J Physiol Endocrinol Metab. 2 0 0 4 ; 2 8 7 : E 8 5 7 - E 8 6 2 .
2 2 . Gi annopoul ou I, Ploutz-Snyder LL, Car har t R, et al. Exercise is
required f or visceral fat l oss in postmenopausal women wi t h
type 2 diabetes. J Cfin Endocrinol Metab. 2 0 0 5 ; 9 0 : 1 5 1 1 - 1 5 1 8 .
2 3 . Short KR, Vittone JL, Bi gel ow ML, et al. Impact of aer obi c exer-
cise training on age-related changes in i nsul i n sensitivity and
muscle oxi dat i ve capacity. Diabetes. 2 0 0 3 ; 5 2 : 1 8 8 8 - 1 8 9 6 .
2 4 . Ross R, Janssen I, Dawson J, et al. Exercise-induced reduction in
obesily and insulin resistance in women: A randomized conlrolled
trial. Obes Res. 2 0 0 4 ; 1 2 : 7 8 9 - 7 9 8 .
2 5 . Clevenger CM, Parker Jones P, Tanaka H, et al. Decline in insulin
action wi t h a g e in endurance-trained humans. J Appl Physiol.
2 0 0 2 ; 9 3 : 2 1 0 5 - 2 1 1 1 .
2 6 . Poirier P, Ma wh i n n e y S, Gr ondi n L, et al. Prior meal enhances
the plasma glucose lowering effect of exercise in lype 2 diabetes.
Med Sci Sports Exerc. 2001 ; 3 3 : 1 2 5 9 - 1 2 6 4 .
2 7 . Larsen J J, Dela F, Ma d s b a d S, et al. Interaction of sulfonylureas
and exercise on glucose homeostasis in type 2 di abet i c patients.
Diabetes Care. 1 9 9 9 ; 2 2 : 1 6 4 7 - 1 6 5 4 .
2 8 . Braun B, Sharoff C, Chipkin SR, Beaudoin F. Effects of insulin
resistance on substrate utilization during exercise in ov er wei ght
women. J Appl Physiol. 2 0 0 4 ; 9 7 : 9 9 1 - 9 9 7 .
2 9 . Halse R, Bonavaud SM, Armstong JL, et al. Control of gl ycogen
synthesis by glucose, gl ycogen, and i nsul i n in cultured human
muscle cells. Diabetes. 2 0 0 1 ; 5 0 : 7 2 0 - 7 2 6 .
30. Manet t a J, Brun JF, Perez-Martin A, et al. Fuel oxi dat i on dur i ng
exercise in middle-aged men: Rol e of training and glucose dis-
posal. Med Sci Sports Exerc. 2 0 0 2 ; 3 4 : 4 2 3 - 4 2 9 .
31. Poehl man ET, Dvorak RV, De Ni n o WF, et al. Effects of resistance
lraining and endurance lraining on insulin sensitivity in nonobese,
young women: A controlled r andomi zed trial. J Cfin Endocrinol
Metabol. 2 0 0 0 ; 8 5 : 2 4 6 3 - 2 4 6 8 .
32. Hohen MK, Zacho M, Gaster M, et al. Strength lraining increases
insulin-mediated glucose uptake, GLUT4 content, and insulin sig-
naling in skeletal muscle in patients with lype 2 diabetes. Diabetes.
2 0 0 4 ; 5 3 : 2 9 4 - 3 0 5 .
33. I s hi i T, Yamakita T, Sato T, et al. Resistance training improves
insulin sensitivity in NI DDM subjects wi t hout altering maximal
oxygen uptake. Diabetes Care. 1 9 9 8 ; 2 1 : 1 3 5 3 - 1 3 5 5 .
34. Iba~ez J, Izquierdo M, Arguelles I, et al. Twice-weekly progres-
sive resistance training decreases abdomi nal fat and improves
insulin sensitivity in ol der men wi t h type 2 diabetes. Diabetes
Care. 2 0 0 5 ; 2 8 : 6 6 2 - 6 6 7 .
35. Ferrara CM, Mc Cr o n e SH, Brendle D, et al. Met abol i c effects of
the addi t i on of resistive to aer obi c exercise in ol der me n . Int J
Sport Nutr Exerc Metab. 2 0 0 4 ; 1 4 : 7 3 - 8 0 .
36. Hu FB, Sigal R J, Rich-Edwards JW, et al . Wa l k i n g com-
par ed wi t h vi gor ous physical act i vi t y and risk o f type 2 di a-
betes in women: A prospective study. JAMA. 1 9 9 9 ; 2 8 2 : 1 4 3 3 -
1 4 3 9 .
37. Manson JE, Rimm EB, Stampfer MJ, et al. Physical activity and
incidence of non-insulin-dependent diabetes mellitus in women.
Lancet. 1991 ; 3 3 8 : 7 7 4 - 7 7 8 .
38. Knowl er WC , Barrett-Connor E, Fowler SE, et al , f or the
Diabetes Prevention Program Research Gr oup. Reduction in the
incidence of type 2 diabetes wi t h lifestyle intervention or met-
formin. N Engl J Med. 2 0 0 2 ; 3 4 6 : 3 9 3 - 4 0 3 .
39. Tuomilehto J, Lindstrom J, Eriksson JG, et al , f or the Finnish
Diabetes Prevention Study Gr oup. Prevention of type 2 diabetes
mellitus by changes in lifestyle among subjects wi t h impaired
glucose tolerance. N EnglJ Med. 2001 ; 3 4 4 : 1 3 4 3 - 1 3 5 0 .
4 0 . Laaksonen DE, Lindstrom J, Lak k a TA, et al, f or the Finnish
Diabetes Prevention Study. Physical activity in the prevention of
type 2 diabetes: The Finnish diabetes prevention study. Diabetes.
2 0 0 5 ; 5 4 : 1 5 8 - 1 6 5 .
4 1 . Duncan GE, Perri MG , Theriaque DW, et al. Exercise training,
wi t hout we i g h t loss, increases insulin sensitivity and postheparin
plasma lipase activity in previously sedentary adults. Diabetes
Care. 2 0 0 3 ; 2 6 : 5 5 7 - 5 6 2 .
4 2 . Ekel und U, Brage S, Franks PW, et al. Physical activity ener gy
expenditure predicts progression t owar d the metabolic syn-
drome independently of aer obi c fitness in middle-aged healthy
Caucasians: The Medi c al Research Council Ely Study. Diabetes
Care. 2 0 0 5 ; 2 8 : 1 1 9 5 - 1 2 0 0 .
4 3 . Mi y at ak e N, Ni shi kawa H, Morishita A, et al. Dai l y wal ki ng
reduces visceral adi pose tissue areas and improves insulin resis-
tance in Japanese obese subjects. Diabetes Res Clin Pract.
2 0 0 2 ; 5 8 : 1 0 1 - 1 0 7 .
- 9 7 -
I n s u l i n Jul y 2 0 0 6
44. Braun B, Zimmermann MB, Kretchmer N. Effects of exercise
intensily on insulin sensitivily in women wilh non-insulin-dependent
diabetes mellitus. J Appl PhysioL 1995; 78: 300-306.
45. Cuff D J, Menei l l y GS, Martin A, et al. Effective exercise modal-
i ty to reduce insulin resistance in women with type 2 diabetes.
Diabetes Care. 2003; 26: 2977- 2982.
46. Ki ng DS, Baldus PJ, Sharp RL, et al. Time course for exercise-
induced alterations in insulin action and glucose tolerance in
middle-aged people. J Appl Physiol. 1995; 78: 17-22.
47. Christ-Roberts C, Pratipanawatr T, Pratipanawatr W, et al.
Increased i nsul i n receptor signaling and glycogen synthase
activity contribute to the synergistic effect of exercise on insulin
action. J Appl Physiol. 2003; 95: 2519- 2529.
48. Christ-Roberts C, Pratipanawatr T, Pratipanawatr W, et al.
Exercise training increases glycogen synlhase activily and GLUT4
expression but not insulin signaling in overweight nondiabetic
and lype 2 diabetic subjects. Metabolism. 2004; 53: 1233-1242.
49. Dela F, von Linstow ME, Mikines K.I, Galbo H. Physical training
may enhance beta-cell function in type 2 diabetes. Am J Physiol
Endocrinol Metab. 2004;287:E 1024-E 1031.
50. Larsen J J, Dela F, Madsbad S, Galbo H. The effect of intense
exercise on postprandial glucose homeostasis in type II diabetic
patients. Diabetologia. 1999; 42: 1282- 1292.
51. Yamakita T, Ishii T, Yamagami K, et al. Glycemic response dur-
ing exercise after administration of insulin lispro compared with
that after administration of regular human insulin. Diabetes Res
Clin Pract. 2002; 57: 17- 22.
52. Peter R, Luzio DS, Dunseath G, et al. Effects of exercise on the
absorption of insulin glargine in patients with type 1 diabetes.
Diabetes Care. 2005; 28: 560- 565.
53. US Dept of Health and Human Services. The Surgeon General's
call to action to prevent and decrease overweight and obesity.
Rockville, Md: US Dept of Health and Human Services, Public
Health Service, Office of the Surgeon General; 2001.
54. Dunstan DW, Daly RM, Owen N, et al. High-intensity resistance
training improves glycemic control in older patients with type 2
diabetes. Diabetes Care. 2002; 25: 1729- 1736.
55. Bravata DM, Wells CK, Kernan WN, et al. Association between
impaired insulin sensitivity and slroke. Neuroepidemiology. 2005;
25: 69- 74.
56. Dagres N, Sailer B, Haude M, et al. Insulin sensitivily and coronary
vasoreactivity: Insulin sensitivity relates to adenosine-stimulated coro-
nary flow response in human subjects. Clin Endocrinol (Oxf). 2004;
61: 724- 731.
57. Sung KC, Ryu SH. Insulin resistance, body mass index, waist cir-
cumference are independent risk factor for high blood pressure.
Cfin Exp Hypertens. 2004; 26: 547- 556.
58. Meisinger C, Heier M, Loewel H, for the MONI CA/ KORA
Augsburg Cohort Study. Sleep disturbance as a predictor of
type 2 diabetes mellitus in men and women from the general
population. Diabetologia. 2005; 48: 235- 241.
59. Savage DB, Petersen KF, Shulman GI. Mechanisms of insulin
resistance in humans and possi bl e l i nks with inflammation.
Hypertension. 2005; 45: 828- 833.
60. Petersen AM, Pedersen BK. The anti-inflammatory effect of exer-
cise. J Appl PhysioL 2005; 98: 1154- 1162.
61. Maiorana A, O'Driscoll G, Cheetham C, et al. The effect of
combined aerobic and resistance exercise training on vascular
function in type 2 diabetes. J Am Coil Cardiol. 2001 ; 38: 860-
866.
A d d r e s s c o r r e s p o n d e n c e t o : Sheri R. Colberg, PhD, FACSM, Exercise Science, Sport, Physical Education, and Recreation
Department, Old Dominion University, Norfolk, VA 23529. E-mail: scolberg@odu.edu
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