The Impact of Exercise on Insulin Action in Type 2 Diabetes Mellitus Prevention and Control 2005

8/12/2019 The Impact of Exercise on Insulin Action in Type 2 Diabetes Mellitus Prevention and Control 2005

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T h e Im p ac t o f E xerc ise o n In su l in A c t io n in T yp e D iab e tes M e l li tu s :Re la t io n sh ip to P reven t io n an d Co n t ro lS h e r i R . C o l b e r g P h D F A C S MA s s o c i a te P r o f e s s o r o f E x e r c i s e S c i e n c e , E x e r c i s e S c i e n c e , S p o r t , P h y s i c a l E d u c a t io n , a n d R e c r e a t io n D e p a r t m e n t ,O l d D o m i n i o n U n i v e r s i ty , N o r f o l k , V i r g i n i a

ABSTRACTB a c k g r o u n d : The interactions betwe en ins ulin and physical activity are varied and complex. Control of blood glucose

levels relies heavily on the balance between insulin and opposing counterregulatory endocrine hormones that bind totheir respective receptors in muscle, adipose, and liver tissues. Other metabolic factors--such as fuel use and availabil-ity, exercise intensity and durati on, train ing status, and visceral fat levels --also affect physical activity done by indiv id-uals with ins ulin 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 with acute sessions of physicalactivity and more extended exercise training, focusing special attention on their relationship to both exercise andresting glycemia as it relates to type 2 DM preve ntion and control. Also discussed are strategies that indivi duals withtype 2 DM can use to engage in appropriate physical training to control DM and prevent other insulin-related healthproblems.

M e t h o d s : The content of this article was based on an electronic search of the literature using Pu bMed a nd the selectionof key search terms alone an d in combination, including exercise, aerobic training, resistance exercise, insulin , hyperglycem ia,diabetes, diabetes prevention, and humans . Articles that app eared in relevant, combine d searches of these terms were exam-ined back to the ye ar 2000. A seconda ry search of articles related to type 2 DM a nd exercise was con ducte d via referencesfoun d in these cited studies that m et the search criteria.

Results: Current research suggests that type 2 DM can be prevented and controlled with increased physical activity.With respect to the possibili ty of reversal of a prediabetes state, both aerobic and resistance training may pla y imp orta ntroles in these processes. Altho ugh ind ivid uals with DM are usu ally instruc ted to exercise to improv e 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, abnormalinsulin action in the body is associated with not only prediabetes an d DM but also with a host of other insulin-relatedhealth conditio ns, includ ing cardiovascular disease.

Conclus ion: A more thorough und ers tan din g of the association among ins ulin, exercise, glycemia, and DM will lead tobetter control of these ind epe nde nt factors in health a nd disease states. Insulin. 2006;1:85-98) Copyr igh t 2006 ExcerptaMedica, Inc.

K e y w o r d s : insuli n, exercise, type 2 diabetes mellitus, blood glucose.

I N T R O D U C T I O NThe interactions among insulin and insulin action, counter-regulatory hormone release, blood glucose regulation, andphysical activity are varied and complex. Control of bloodglucose levels relies on the balanced release of insulin andother redun dant endocrine hormones; the proper function-ing of hormone receptors found particularly in insulin-sensitive muscle, adipose tissues, and the liver; and othermetabolic factors such as fuel use a nd availability.1 3 More-over, individ uals with diabetes mellitus DM) are usuallyinstruc ted by their health care provider s to exercise, but is itsafe and effective for these ind ivid uals to do so? In addition,abnormal insulin action in the body is associated not only

c c e p t e d or pub l ica t ion Oc tobe r 18 2 005 .P r in t e d i n th e U S A R e p r o d u c t io n i n w h o l e or par t i s n o t p e r m i tt e d

with prediabe tes an d type 2 DM but also with a host of otherinsulin-related health conditions.

The purpose of the current article was to discuss howthese aforementioned variables interact with acute sessionsof physical activity and more extended exercise training,focusing special attent ion on their relationshi p to both exer-cise and resting glycemia as it relates to type 2 DM preven-tion and control. A secondary purpos e was to discuss strate-gies that indivi dual s with type 2 DM can use to engage inappropriate physical training to control DM and preventother insul in-rela ted health problems. To adequa tely ad-dress this topic with regard to prevention and control oftype 2 DM, the acute hormonal responses to exercise must

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I n s u l i n J u ly 2 6f i r st b e e x a m i n e d . I n a d d i t i o n , a r e v i e w o f t h e e f f e c ts o f e x e r -c i se t r a i n i n g - - b o t h a e r o b i c a n d r e s i s t a n c e - - o n i n s u l i n a ct i o ni n t h e b o d y i s r e l e v a n t to u n d e r s t a n d i n g t h e g l y c e m i c r e-s p o n s e s d u r i n g r e s t i n g a n d e x e r c i s e c o n d i t i o n s . T h i s a r t i c l ei n c l u d e s a d i s c u s s i o n o f i n s u l i n s e n s i t i v i t y r e l a t e d t o p h y s i -c a l a c t i v i ty le v e l s a n d l e a d s d i r e c t l y i n t o a r e v i e w o f c u r r e n ts t u d i e s i n v e s t i g a t i n g t h e p r e v e n t i o n a n d c o n t r o l o f t y p e 2 D Mw i t h p h y s i c a l a c ti v it y . M o r e o v e r , i t d i s c u s s e s s o m e o f t h eg u i d e l i n e s f o r c h o o s i n g a p p r o p r i a t e e x e r c i s e f o r th e s e i n -d i v i d u a l s . F i n a ll y , t h e r o l e o f e x e rc i s e in D M m a n a g e m e n ta n d o t h e r i n s u l i n - r e la t e d b e n e fi t s o f p h y s i c a l a c t i v i t y a ree x p l o r e d .M TE RI LS ND M E THODST h e c o n t e n t o f t h i s a r t i c l e w a s b a s e d o n a n e l e c t r o n i c s e a r c ho f th e l i t e r a t u re u s i n g P u b M e d a n d t h e s e l e ct i o n o f k e ys e a r c h t e r m s a l o n e a n d i n c o m b i n a t i o n , i n c l u d i n g exerciseaerobic t ra in ing res is tance exerc ise insu l in hyperglycemia d ia-be tes d iabe tes prevent ion a n d h u m a n s . M o r e t h a n 5 0 00 a r t i c le sw e r e i d e n t i f i e d in t h is m a n n e r . A r t i c l e s t h a t a p p e a r e d i n r e l e -v a n t , c o m b i n e d s e a r ch e s o f t h e s e te r m s w e r e e x a m i n e db a c k t o t h e y e a r 2 0 00 . A s e c o n d a r y s e a r c h o f a r t ic l e s r e l a t e dt o t y p e 2 D M a n d e x e r ci s e w a s c o n d u c t e d v i a r e f e re n c e sf o u n d i n t h e s e c i t e d s t u d i e s t h a t m e t t h e s e a r c h c r i t e r i a .A r t i c le s s e le c t e d f or t h e c u r r e n t s t u d y w e r e c o n s i d e r e d v a l i do n c e t h e s u b je c t i n c l u s i o n a n d r e s e a r c h m e t h o d s w e r er e v i e w e d b y t h e a u t h o r a n d t h e u s e o f a p p r o p r i a t e s u b j e c ti n c l u s io n c r i te r ia a n d m a t c h e d c o n t r o l g r o u p s w a s v e r i f i e d .I NSULIN ND OTHE R HO RM ON L RE S PONS E STO CU TE EXERCISEW h e n a p e r s o n e x e r c is e s , h i s o r h e r b o d y i m m e d i a t e l y r e -s p o n d s b y r e l e a s i n g a n u m b e r o f c o u n t e r r e g u l a t o r y h o r -m o n e s t h a t r a is e a n d m a i n t a i n b l o o d g l u c o s e l e v e ls .2,3 A t a n yg i v e n t i m e , a r e l a t iv e l y li m i t e d s u p p l y o f g l u c o s e i s s to r e d a sg l y c o g e n i n m u s c l e s a n d t h e l iv e r , w i t h a f a r le s s e r a m o u n tc i r c u la t i n g i n t h e b l o o d s t r e a m . H o w e v e r , a b l o o d g l u c o s el e v e l o f > 65 m g / d L ( >3 .6 m M , o r c l i n i c a l ly d e f i n e d h y p o -g l y c e m i a ) m u s t b e m a i n t a i n e d a t a ll t i m e s f o r p r o p e r b r a i na n d n e r v o u s s y s t e m f u n c t i o n i n g . B e c a us e c a r b o h y d r a t e s a r et h e p r i m a r y f u e l t h a t th e h u m a n b o d y u s e s d u r i n g e x e rc i se ,t h e l i v e r m u s t a c t q u i c k l y t o r e p l a c e t h e b l o o d g l u c o s e t h a tt h e e x e r c i s i n g m u s c l e s a r e c o n s u m i n g a t a fa s t e r ra t et h r o u g h h e p a t i c g l y c o g e n o l y s i s o r g l u c o n e o g e n e s i s . 1

T h e c o u n t e r r e g u l a t o r y h o r m o n e s r e l e a s e d d u r i n g e x e r -c i s e w i t h t h e m o s t i m m e d i a t e e f f e ct (i e, c a t e c h o l a m i n e s ,g l u c a g o n ) s i g n a l t h e l i v e r t o b e g i n r e l e a s i n g m o r e g l u c o s e . 2E p i n e p h r i n e r a i se s a p e r s o n ' s h e a r t r a t e a n d s i g n a l s e x e rc i s -i n g m u s c l e s t o b r e a k d o w n s t o r e d g l y c o g e n a n d t r i g l y c -e r i d e s , a n d i t a l s o s u p p r e s s e s t h e r e l e a s e o f i n s u l i n f r o m t h e~ - c e ll s . G l u c a g o n h a s t h e m o s t d i r e c t e f fe c t o n t h e l i v e r ' sp r o d u c t i o n o f g lu c o s e ; th e r e l e a s e o f g l u c a g o n f r o m p a n c r e -a t i c s - c e l l s is i n v e r s e l y r e l a t e d t o p o r t a l l e v e l s o f c i r c u l a t i n gi n s u l i n d u r i n g e x e rc i se . 3 O t h e r h o r m o n e s - - s u c h a s n o r e p i -n e p h r i n e , g r o w t h h o r m o n e , a n d c o r t i s o l - - e f fe c t i v e l y r e d i s -t r i b u t e b l o o d f l o w t o a c t i v e ti s s u e s , p r o v i d i n g a l t e r n a t e f u e l s

s u c h a s f r e e f a tt y a c i d s ( F F A s ) a n d l a c t a t e t o w o r k i n g m u s -c l e s a n d t h e l i v e r d u r i n g p h y s i c a l a c ti v i ty .

B o t h d e c r e m e n t s i n i n s u l i n a n d i n c r e m e n t s i n g l u c a g o np l a y i m p o r t a n t r o l e s in t h e p r e v e n t i o n o f h y p o g l y c e m i a d u r -i n g e x e r c is e ; t h e y d o s o in c o n c e r t b y s t i m u l a t i n g i n c r e m e n t si n g l u c o s e p r o d u c t i o n b y t h e l i v e r.3 W h i l e th e c o m b i n e dr e c i p r o c a l c h a n g e s i n t h e c i r c u l a t i n g l e v e l s o f t h e s e h o r -m o n e s a r e g e n e r a l l y e ff e c ti v e a t m a i n t a i n i n g b l o o d g l u c o s el e v e ls d u r i n g p r o l o n g e d p h y s i c a l a c ti v it y , e v e n e n d u r a n c ea t hl e te s w h o d o n o t h a v e D M m a y d e v e l o p h y p o g l y c e m i ad u r i n g a n e x t e n d e d s e s s i o n o f e x e r c is e d u e t o th e e x t r e m ed e m a n d s t h a t s u c h a c t i v i ti e s p u t o n r e l a t i v e l y l i m i t e d c a r b o -h y d r a t e s t or e s . I n p e o p l e w i t h D M , a n i n s u ff i c ie n t d e c re a s ei n p o r t a l v e in i n s u l i n l e v e ls c a n i m p a i r t h e p r o d u c t i o n o fa d e q u a t e b l o o d g l u c o s e a n d p o t e n t i a l l y re s u l t i n h y p o -g l y c e m i a .4 C o n v e r s e l y , in t e n s e e x e r c i s e ( e g , h e a v y w e i g h tl i f t in g o r s p r i n t i n g ) c a u s e s a n e x a g g e r a t e d r e l e a s e o f e p i -n e p h r i n e a n d n o r e p i n e p h r i n e , w h i c h a r e th e p r i m e r e g u l a -t o r s of g lu c o s e o v e r p r o d u c t i o n d u r i n g s u c h e x e r c is e a n d m a yr e s u l t in t r a n s i e n t h y p e r g l y c e m i a . 2I n t h e a b s e n c e o f t h e p h y s i o l o g i c e x e r c i s e - i n d u c e d d e -c r e a se i n i n s u l in l e v e l s (a s e x p e r i e n c e d b y m a n y i n d i v i d u a l sw i t h t y p e 2 D M t r e a t e d w i t h i n s u l i n i nj e c ti o n s ), b l o o d g l u c o s el e v e ls m a y f a ll c o n s i d e r a b l y f a s te r e v e n t h o u g h c o m p e n s a -t o r y m e c h a n i s m s w o r k t o i n c r e a se g l u c o s e p r o d u c t i o n . 4 I np e o p l e w h o d o n o t h a v e D M , t h e e f fe c ts o f c a t e c h o l a m i n e s ,c o r ti s o l, a n d g r o w t h h o r m o n e a t l e as t p a r t i a l l y c o m p e n s a t ef o r s u c h a l t e r a t i o n s i n t h e i n s u l i n - t o - g l u c a g o n r a t i o . 3,4

W i t h p h y s i c a l a c t i v i ty a s a n a d d e d v a r i a b l e , r e g u l a t i o n o fg l y c e m i a c a n b e fu r t h e r c o m p l i c a t e d . A n t e c e d e n t m o d e r a t e -i n t e n s it y e x e rc i s e h a s b e e n s h o w n t o b l u n t a u t o n o m i c , n e u -r o e n d o c r i n e , a n d m e t a b o l i c c o u n t e r r e g u l a t o r y r e s p o n s e s t os u b s e q u e n t e x e r c i se o r t o h y p o g l y c e m i a e v e n i n p e o p l e w h od o n o t h a v e D M . 5,6 R e p e a t e d e p i s o d e s o f p r o l o n g e d e x e r c is eo f b o t h l o w ( eg , s l o w w a l k i n g ) a n d m o d e r a t e ( eg , b r i s k w a l k -i n g ) i n t e n s it i e s h a v e b e e n d e m o n s t r a t e d t o b l u n t t h e c o u n -t e r r e g u l a t o r y r e l e a s e o f e p i n e p h r i n e , n o r e p i n e p h r i n e , g l u -c a g o n , g r o w t h h o r m o n e , a n d p a n c r e a t i c p o l y p e p t i d e , a s w e l la s th e p r o d u c t i o n o f e n d o g e n o u s g l u c o s e, in r e s p o n s e t on e x t - d a y h y p o g l y c e m i a . 6 T h u s , s u c h p r i o r a c t i v i t y m a y i n -c r e a se t h e r is k a p e r s o n w i t h D M h a s o f e x p e r i e n c i n g a m o r es e v e r e h y p o g l y c e m i c e v e n t .

A t r es t , t h e a v e r a g e h u m a n b o d y u s u a l l y u s e s a f u e l m i xo f N 6 0 f a t a n d 40 c a r b o h y d r a t e ( w i t h i n s i g n i f i c a n t p r o -t e in u s e ); h o w e v e r , d u r i n g e x e rc i se , c a r b o h y d r a t e s s u p p l yt h e m a j o r i t y o f t h e f u el ( a n d e v e n m o r e s o d u r i n g i n t e n sew o r k o u t s ) . 1,7 F i g u r e 1 d e m o n s t r a t e s t h e r e l a t i v e f u e l u s e i n8 e n d u r a n c e - t r a i n e d w o m e n ( a g e s 1 8 -3 1 y e a r s ) a t v a r y i n ge x e r c i s e i n te n s i t i e s . 7 T h i s r e l i a n c e o n c a r b o h y d r a t e s m a k e st h e d e p l e t i o n o f b o t h m u s c l e g l y c o g e n a n d b l o o d g l u c o s ei n e v i t a b l e i f th e a c t i v i t y i s p r o l o n g e d , p a r t i c u l a r l y i f c i r c u l a t-i n g i n s u l i n l ev e l s r e m a i n h i g h e r t h a n n o r m a l .

P l a s m a F F A s c a n a ls o b e u s e d b u t c o n t r i b u t e m o s t d u r i n gm i l d - to m o d e r a t e - i n t e n s i t y w o r k o u t s . H o w e v e r , t h e m o b i -l i z a ti o n o f t h i s a l te r n a t e f u e l m a y a l s o b e c o m p r o m i s e db y e l e v a t e d i n s u l i n l e v e ls o r i m p a i r e d i n s u l i n a c ti o n . F o r

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u s c l er ig lycer idesPlasma FFAPlasma g lucose8 5M a x im a l c a l o r i c co n t r i b u t i o n o f p l a sm a f r e e f a t ty a c i d s ( F F A s ) a n d g l u co se a n d m in im a l co n t r i b u t i o n o f m u sc le t ri -g l y c e r i d e a n d g l y c o g e n s to r es i n r e la t i o n to e x e r c i s e i n t e n s it y i n 8 e n d u r a n c e - t r a i n e d w o m e n ( a g e s 1 8 - 3 1 y e a r s ) .U s e d w i t h p e r m i s s i o n fr o m Jou rna l o f Ap p l i ed P hys io logy V o lu m e 8 8 , 2 0 0 0 ; 1 7 0 7 - 1 7 1 4 . 7

i n s t a n c e , i n 8 m e n w i t h t y p e 2 D M w i t h a m e a n ( S E ) a g e o f5 2.6 ( 3.1 ) y e a r s ( c o m p a r e d w i t h 8 c o n t r o l s w i t h o u t D M ; m e a n[ SE ] a g e , 4 5.1 [ 1.4 ] y e a r s ) , b o t h t h e r a t e o f a p p e a r a n c e o fp l a s m a F F A s a n d t h e i r e x e r c i s e - in d u c e d i n c r e a s e in t h e i r o x i -d a t i o n c i r c u l a t io n d u r i n g 6 0 m i n u t e s o f m o d e r a t e - i n t e n s i t yc y c l i n g w e r e s i g n i f i c a n t l y l o w e r ( P < 0 . 05 ). 8 H o w e v e r , d u r -i n g e x e r c is e c o n d i ti o n s , t h e i m p a i r m e n t i n t h e d e l i v e r y o fp l a s m a - d e r i v e d F F A s to w o r k i n g m u s c l e s i n th e s e m e n w i t hD M w a s c o m p e n s a t e d f o r b y a n i n c r e a s e i n th e u s e o f I Mt r i g l y c e r i d e s , th u s k e e p i n g t o t a l fa t o x i d a t i o n s i m i l a rb e t w e e n g r o u p s . S i m i l a rl y , o t h e r r e s e a r c h e rs h a v e f o u n d t h a tt h e o v e r a l l u s a g e o f f at s a n d c a r b o h y d r a t e s i s u n a l t e r e d i np a t i e n t s w i t h t y p e 2 D M , a l t h o u g h h y p e r g l y c e m i a m a y d r i v ea g r e a t e r u s e o f c i r c u l a t i n g b l o o d g l u c o s e w i t h a l e s s e rr e l ia n c e o n m u s c l e g l y c o g e n . 9 D u r i n g r e c o v e r y f r o m e x e r -c i s e, f a t u s e a g a i n p r e d o m i n a t e s i n a l l i n d i v i d u a l s . 1T R A I N I N G IN S U L IN A C T I O N A N DP HY S ICAL A CTIV ITYM o s t o b e s e in d i v i d u a l s w i t h t y p e 2 D M e x p e r i e n c e a d e -c r e a se i n t h e i r b l o o d g l u c o s e l e v e l s d u r i n g m i l d - t o m o d e r a t e -i n t e n s i t y e x e r c i s e . 1 T h e m a g n i t u d e o f t h e d e c r e a s e i n b l o o dg l u c o s e i s r e l a t e d t o t h e d u r a t i o n a n d i n t e n s i t y o f t h e e x e r -c i s e, a s w e l l a s t o p r e - e x e r c i s e g l y c e m i c c o n t r o l a n d t h e i n d i -v i d u a l ' s t r a i n i n g s t a t e . 1 13 T h i s e f f e c t is o n l y a c u t e , h o w e v e r ,a n d r e l a t e d t o t h e b o u t o f e x e r c i se . T h e a b i l i t y o f m o r ei n t e n s e o r p r o l o n g e d e x e r ci s e t o a c u t e l y e n h a n c e i n s u l i n s e n -s i t i v i t y u s u a l l y r e s u l t s i n m o r e e f f e c ti v e p o s t e x e r c i s e g l y -c e m i c c o n t r o l i n p e o p l e w i t h i n s u l i n r e s i st a n c e o r t y p e 2 D Mw h e n t h e y u n d e r t a k e s u c h a c t i v it i es .13

I n a d d i t i o n , e x e r c i s e t r a i n i n g c a n r e s u l t i n a m o r e l a s t i n ge f f e c t on t he a c t i on o f i n s u l i n . 11,14,15 Fo r i n s t a n c e , i n o be s ep e o p l e o f a ll a g e s u n d e r g o i n g j u s t i w e e k o f t ra i n i n g , in s u l i ns e n s i t iv i t y i m p r o v e d , d e m o n s t r a t i n g t h a t i t c a n b e a c u t e l ye n h a n c e d b y r e g u l a r p h y s i c a l tr a i n i n g w i t h o u t w e i g h t l o s sa n d w i t h o u t e v o k i n g a t r u e t r a i n i n g a d a p t a t i o n i n m u s c l e , 14a l t h o u g h s u c h a n e f f ec t c a n b e e v o k e d w i t h t r a i n i n g a d a p t a -t i o n s a s w e l l . M o r e p r o l o n g e d p h y s i c a l t ra i n i n g c a n e n h a n c eb o t h t h e r e s p o n s i v e n e s s o f m u s c l e s t o i n s u l i n a s w e l l a s b a s a lb l o o d g l u c o s e u p t a k e . I n h u m a n s k e l e ta l m u s c l e c e ll s t a k e nf r o m e i t h e r e n d u r a n c e - t r a i n e d ( n = 1 2 ; m e a n [ S D ] a g e , 2 3 . 0[ 1 . 4 ] y e a r s ) o r s e d e n t a r y ( n = 8 ; m e a n [ S D ] a g e , 2 3 . 4 [ 1 . 0 ]y e a r s ) m e n , t h e m y o t u b e s e x h i b i t e d a d o s e r e s p o n s e f o rg l u c o s e u p t a k e w i t h i n c r e a s in g i n s u l i n c o n c e n t r a ti o n s , w i t hm a x i m a l g l u c o s e u p t a k e 1 . 5 - f o l d o v e r b a s a l le v e l s . B a s a lg l u c o s e u p t a k e , h o w e v e r , w a s f o u n d t o b e s i g n i fi c a n t ly e le -v a t e d ( b y N7 5 ; P < 0 .0 5) w i t h e n d u r a n c e t r a i n i n g , a l t h o u g ht h e r e l a t iv e i n c re a s e i n i n s u l i n - m e d i a t e d g l u c o s e u p t a k e w a ss i m i l a r b e t w e e n s u b j e c t g r o u p s . 11 I n 8 h e a l t h y y o u n g m e n , 1 8t o 2 5 y e a r s o f a g e , 6 w e e k s o f m o d e r a t e - i n t e n s i t y c y c l i n g p e r -f o r m e d f o r 1 h o u r 5 d a y s a w e e k w a s c a p a b l e o f i n c r e a s in gn o t o n l y t h e i r i n s u l i n s e n s i t i v i t y b u t a l s o t h e i r g l u c o s e e f f e c -t i v e n e s s ( ie , t h e a b i l i t y of h y p e r g l y c e m i a t o p r o m o t e g l u c o s ed i s p o s a l a t b a s a l i n s u l i n l e v e l s ) f o r a t le a s t i w e e k a f t e r c es -s a t i o n o f t h e i r t r a i n i n g r e g i m e n . 15

xe r c i se t r a i n i n g ca n r e su lt in a m o r e l a s t in g e f fe c t o n t h ea c t i o n o f i n su l i n .

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I n s u l i n J u ly 2 0 0 6R e l a t i v e l e v e l s o f i n s u l in s e n s i t i v i t y a r e a p p a r e n t l y

a f f e ct e d b y a v a r i e t y o f v a r i a b le s , in c l u d i n g a n i n d i v i d u a l ' sa g e a n d t r a i n i n g s t a t u s . 12,16 18 I n a r e c e n t s t u d y o f a g r o u p o fo l d e r i n d i v i d u a l s (8 m e n a n d 2 w o m e n , a g e s 7 7 - 8 7 y e a r s) ,b o t h a e r o b i c p o w e r a n d i n s u l i n a c t io n i m p r o v e d i n r e s p o n s et o h i g h - i n t e n s i t y a e r o b i c e x e r c i s e t r a i n i n g , b u t t h e i r i m -p r o v e m e n t s i n i n s u l in a c ti o n w e r e a t t e n u a t e d c o m p a r e dw i t h i m p r o v e m e n t s n o r m a l l y f o u n d i n m i d d l e - a g e d s u b je c tsu n d e r g o i n g t h e s a m e t r a i n i n g p r o g r a m . 16 S i m i l a rl y , m o d e r a t e -t o h e a v y - i n t e n s i t y a e r o b i c t r a i n i n g ( ie , 6 0 - 9 5 o f m a x i m a lh e a r t r a te ) t h a t w a s d o n e 3 ti m e s a w e e k f o r 6 m o n t h s w a ss h o w n t o i m p r o v e i n s u l i n s e n s i t i v i t y i n b o t h y o u n g e r ( n = 14 ;m e a n [ SD ] a g e , 2 9.1 [ 4.6 ] y e a r s ) a n d o l d e r ( n = 8 ; m e a n [ SD ]a g e , 6 2.3 [ 4 .7 ] y e a r s ) w o m e n . 17 A l t h o u g h o n l y t h e o l d e r w o m -e n d e c r e a s e d th e i r b o d y w e i g h t ( b y 4 ) , t h e e n h a n c e m e n t i ni n s u l i n s e n s it i v i ty p e r s i s t e d o n l y i n t h e y o u n g e r w o m e n f o r7 2 t o 1 2 0 h o u r s a f t e r t h e l a s t e x e r c i s e s e s s i o n . T h i s f i n d i n gs u g g e s t s t h a t in o l d e r w o m e n , i m p r o v e m e n t s i n i n s u li n s e n -s i t i v i t y r e s u l t m o r e d i r e c t l y f r o m t h e a c u t e e f f e c t o f t h e l a s ts e s s i o n t h a n c h r o n i c t r a i n i n g a d a p t a t i o n s . 17 C o n v e r s e l y ,a n o t h e r s t u d y o n m u s c l e m i t o c h o n d r i a l f u n c ti o n , m u s c l e f a to x i d a t i v e c a p a c it y , a n d i n s u l i n s e n s i t iv i t y c o m p a r e d t r a i n e dy o u n g ( m e a n [ SD ] a g e , 2 4.2 [ 2 .6 ] y e a r s ) a n d e l d e r l y ( m e a n [ SD ]a g e , 66 .6 [3 .2 ] y e a r s ) i n d i v i d u a l s v e r s u s s e d e n t a r y i n d i v i d u -a l s i n t h e s a m e a g e g r o u p s . 18 T h i s s t u d y f o u n d t h a t a l l o f t h ea f o r e m e n t i o n e d v a r i a b l e s i m p r o v e d s i m i l a r l y i n b o t h g r o u p sw i t h 8 w e e k s o f a e ro b i c tr a i n i n g , s u g g e s t i n g t h a t t h e e l d e r l ys u b j e c ts w e r e n o t i m p a i r e d b y a g e b u t r a t h e r b y p h y s i c a l in -a c t i v it y . I n m o s t i n d i v i d u a l s , r e g a r d l e s s o f a g e , t h e a c u t e e f -f e c ts o f r e c e n t e x e r c is e a r e m o r e p r o m i n e n t ; h o w e v e r , r e g u l a rp a r t i c i p a t i o n i n p h y s i c a l a c ti v i t i e s i s r e q u i r e d f o r s u s t a i n a b l ei m p r o v e m e n t s i n g l u c o s e h o m e o s t a s i s a n d i n s u l in a c t i o n . 12

egu la r par t i c ipa t ion in phys ica l ac t iv i t ies is requ i red fo rs u s t a in a b le im p r o v e m e n t s i n g l u c o s e h o m e o s t a s i s a n d

insu l in ac t ion

T h e m e t a b o l i c e f f e ct s o f v a r y i n g e x e r c i s e in t e n s i t i e s a l s om u s t b e c o n s i d e r e d . H i g h e r i n t e n s i ty a e r o b i c tr a i n i n g c l e a r lyi m p r o v e s i n s u l i n s e n s i t i v i t y , 16 b u t s o m e s t u d i e s h a v e i n v e s -t i g a t e d w h e t h e r l e ss v i g o r o u s w o r k o u t s h a v e a s i m i la r o u t-c o m e . I n a s t u d y c o n d u c t e d b y H o u m a r d e t a l, 19 1 54 m i d d l e -a g e d ( m e a n a g e , 5 1 .4 - 5 3. 1 y e a r s a c r o s s s u b j e c t g r o u p s ) ,s e d e n t a r y , a n d o v e r w e i g h t s u b j e ct s ( 50 w o m e n , i n c l u s iv eo f e th n i c m i n o r i t ie s ) e n g a g e d i n d i f fe r e n t v o l u m e s a n di n t e n s i t i e s o f a e r o b i c t r a i n i n g f o r 6 m o n t h s . O n e g r o u p p a r -t i c i p a t e d i n l o w - v o l u m e / m o d e r a t e - i n t e n s i t y t r a i n i n g c o n -s i s ti n g o f ~ 1 2 m i l e s o f w a l k i n g w e e k l y d o n e a t 4 0 t o 5 5 o fp e a k o x y g e n c o n s u m p t i o n ; a n o t h e r g r o u p w a s a s s i g n e d tol o w - v o l u m e / h i g h - i n t e n s i t y w o r k o u t s e n t a i li n g ~1 2 m i l e s o fw e e k l y jo g g i n g ; a n d a t h i r d g r o u p j o g g e d ~ 2 0 m i l e s p e r w e e k( c a t e g o r i z e d a s a h i g h - v o l u m e / h i g h - i n t e n s i t y a e r o b i c t r a in -i n g) . A l t h o u g h a f o u r t h s e d e n t a r y c o n t r o l g r o u p e x p e r i e n c e da d e c r e a s e i n i n s u l i n s e n s i t i v i t y b y t h e e n d o f t h e t r a i n i n g

p e r i o d , a l l 3 e x er c i se g r o u p s w e r e f o u n d t o h a v e e n h a n c e di n s u l i n a c t i o n r e s u l t i n g f r o m t h e i r v a r i e d t r a i n i n g . T h e 2g r o u p s t h a t e x e r c i s e d N1 70 m i n u t e s p e r w e e k ( ie , t h e l o w -v o l u m e / m o d e r a t e - i n t e n s i t y a n d th e h i g h - v o l u m e / h i g h -i n t e n s it y g r o u p s ) e x p e r i e n c e d m o r e i m p r o v e m e n t s i n i n s u li ns e n s i t iv i t y t h a n t h e l o w - v o l u m e / h i g h - i n t e n s i t y g r o u p t h a to n l y e x e r c i s e d f o r N l 15 m i n u t e s w e e k l y ( P < 0.0 5 ) ( F i g u r e 2 ).T h e s e f i n d i n g s s u g g e s t t h a t e x e r c is e d u r a t i o n m a y b e r e l a-t i v e l y m o r e i m p o r t a n t t h a n t r a i n in g i n t e n s i t y to i m p r o v ei n s u l i n a c t io n i n o v e r w e i g h t p e o p l e .

S k e l e t a l m u s c l e i n s u l i n r e s i s t a n c e a p p e a r s t o e n t a i l d y s -r e g u l a t i o n o f b o t h g l u c o s e a n d f a t ty a c i d m e t a b o l i s m . I n a1 6 - w e e k s t u d y i n v o l v i n g m o d e r a t e - i n t e n s i t y p h y s i c a l a c ti v -i t y c o m b i n e d w i t h c a l o r ie r e d u c t i o n in 9 o b e s e m e n a n d1 6 o b e s e w o m e n ( m e a n [S D ] a g e , 39 [4 ] y e a r s ) w h o d i d n o th a v e t y p e 2 D M , i n s u l i n s e n s i t i v i t y ( m e a n [S E] ) w a s i m -p r o v e d b y 4 9 ( 10 ) b y t h e e n d o f t h e s t u d y . 2 O f i n t e re s t ,t h e s tr o n g e s t p r e d i c t o r o f t h i s i m p r o v e m e n t w a s e n h a n c e df a s t i n g r a t e s o f f a t o x i d a t i o n , w h i c h a c c o u n t e d f o r 5 2 o f t h ev a r i a n c e , s u g g e s t i n g p o s t a b s o r p t i v e f a t o x i d a t i o n i s a k e ya s p e c t o f i m p r o v e d i n s u l i n s e n s i t i v it y , a t l e a s t i n o b e s e s u b -j e ct s w h o d o n o t h a v e D M . S i m i la r ly , o t h e r s t u d i e s h a v ef o u n d t h a t e x e r c is e t r a in i n g i n c r e as e s i n t r a m y o c e l l u l a r l i p i dc o n t e n t i n o l d e r i n d i v i d u a l s ( 6 5 - 7 0 y e a r s o l d ) i n p a r a l l e lw i t h a n e n h a n c e d c a p a c i t y f o r f a t o x i d a t i o n . 12,21

T h e r e l a t io n s h i p b e t w e e n i m p a i r e d i n s u l i n a ct i o n a n dv i s c e r a l a d i p o s e c o n t e n t i s e v e n m o r e i m p o r t a n t i n p a t i e n t sw i t h t y p e 2 D M w h o g e n e r a l l y h a v e a b d o m i n a l o b e s it y .G i a n n o p o u l o u e t a12 2 r e c e n t l y e x a m i n e d t h e e f f e c ts o f d i e t -i n g , a e r o b i c ex e r c i s e, a n d a c o m b i n a t i o n o f t h e 2 i n 33 p o s t -m e n o p a u s a l a n d o b e s e o ld e r w o m e n ( m e a n a g e , 5 7 y e a r s )w i t h t y p e 2 D M w h o h a d b e e n d i a g n o s e d w i t h D M f o r a tl e a s t 1 y e a r a n d w e r e b e i n g t r e a t e d e i t h e r w i t h o r a l h y p o -g l y c e m i c a g e n t s ( n = 2 2) o r n o m e d i c a t i o n s ( n = 11 ). A f t e r1 4 w e e k s , t h e i r b o d y w e i g h t a n d t o t a l b o d y f a t d e c r e a s e d s i m i -l a r l y w h e t h e r t h e w o m e n f o l l o w e d a l o w - c a l o r ie d i e t h i g h i nm o n o u n s a t u r a t e d f a ts o r t h e y c o m b i n e d t h i s d i e t w i t h e x e r -c i se ( d e f i n e d a s m o d e r a t e w a l k i n g f o r 50 m i n u t e s 3 t im e s aw e e k ) . I n t h e g r o u p a s s i g n e d t o e x e r c is e al o n e , th e i r t o t a l b o d yf a t d e c r e a s e d b y l e s s t h a n h a l f a s m u c h a s th o s e w h o f o l l o w e dt h e s p e c i f i e d d i e t p l a n , r e g a r d l e s s o f t h e i r e x e r c i s e s t a t u s .N e v e r t h e l e s s , o n l y t h o s e s u b j e c t s w h o e x e r c i s e d , i r r e s p e c t i v eo f w e i g h t l o s s , e x p e r i e n c e d a s i g n i f i c a n t d e c r e a s e ( P < 0 .0 5 )i n v i s c e r a l f a t le v e l s ( F i g u r e 3 ). T h e s t r o n g e s t p r e d i c t o r o f i m -p r o v e d i n s u l i n a c t io n i n t h e s e w o m e n w i t h t y p e 2 D M w a se n h a n c e d f a s t i n g r a t e s o f f a t o x i d a t i o n , a n d b o t h e x e r c i s ea n d w e i g h t l o s s ( b u t n o t d i e t a l o n e ) i n c r e a s e d p o s t a b s o r p -t i v e fa t o x i d a t i o n a s w e l l . O f p a r t i c u l a r n o t e i n t h i s s t u d y w a st h a t d i e t i n g a lo n e r e d u c e d S C a n d t o t a l a b d o m i n a l f a t b u tn o t v i s c e r a l a d i p o s e c o n t e n t w i t h o u t a d d e d e x e rc i se . M o r e -o v e r, t h o s e i n d i v i d u a l s w h o e x e r c i s ed m a i n t a i n e d a l l o f t he i rm u s c l e m a s s ; i n d i v i d u a l s w h o b o t h e x e r c i s e d a n d f o l l o w e dt h e s p e c i f i e d d i e t l o s t l e s s o f t h e i r m u s c l e t h a n t h o s e i n d i v i d -u a l s w h o d i d n o t f o l l o w t h e s p e c i f i e d d ie t .

I n c o n tr a s t, a 1 6 -w e e k s t u d y i n v o l v i n g 4 1 m e n a n d 4 9 w o m -e n ( a g e s 2 1 - 8 7 y e a r s ) w h o e n g a g e d i n a e r o b i c e x e r c is e t r a i n -

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R e la t iv e c hanges ( ) (a f te r t r a in in g /b e fo re t r a in ing ) i n t he i ns u li n s ens i t iv i t y i nde x (S i ) de r i v e d f r om the IV g lu -c os e to le ranc e tes t i n t he c on t ro l an d ex e rc i s e g rou ps (N = 154 ) . L ow /M od = l ow -v o lum e/m odera te - i n tens i t yt r a i n i n g ; L o w / H i g h = lo w - v o l u m e / h i g h - in t e n s i t y t r a i n i n g ; H i g h / H i g h = h i g h - v o lu m e / h i g h - in t e n s i t y t r a i n i n g . L in ea t 0 r ep res en ts no c hange . * S ig n i f i c an t d i ff e renc e f r om c on t ro l (P < 0 .05 ) . tS ign i f i c an t d i ff e renc e f rom theL o w / H i g h g r o u p (P < 0 . 0 5 ) . U s e d w i t h p e r m i s si on f ro m Jo u r n a l o f A p p l i e d P h ys io lo g y V o l u m e 9 6 , 2 0 0 4 ; 1 0 1 -106 .19

i n g f o u n d t h a t t h e i r in s u l i n s e n s i ti v i t y d e c r e a s e d w i t h a g ea n d w a s i n v e r s e l y r e la t e d t o a b d o m i n a l f a t c o n t e n t ( r =- 0 .6 5 ) . 23 H o w e v e r , i n s u l i n s e n s i t i v i t y i m p r o v e d a f t e r t r a i n i n go n l y i n y o u n g i n d i v i d u a l s i n t h is s t u d y , n o t i n t h e m i d d l e -a g e d o r o l d e r s u b je c t s. I n a n o t h e r s t u d y o f a g r o u p o f p r e -m e n o p a u s a l w o m e n ( m e a n a g e o f 4 1. 3- 43 .9 y e a r s a c r o ssg r o u p s ) , 1 4 w e e k s o f e i t h e r d i e t - i n d u c e d w e i g h t l o s s ( n = 1 5) ,e x e r c i s e - i n d u c e d w e i g h t l o s s ( n = 1 7) , o r e x e r c i s e w i t h o u tw e i g h t l o s s ( n = 12 ) r e s u l t e d i n s i m i l a r d e c r e a s e s i n v i s c e r a lf a t i n a l l g r o u p s ( c o m p a r e d w i t h 1 0 w e i g h t - s t a b l e c o n t r o l s ) ,a l t h o u g h i n s u l in s e n s i t i v i t y i m p r o v e d o n l y i n t h e e x e r c is ew e i g h t l o s s g r o u p . 24 C l e v e n g e r e t a l , 25 h o w e v e r , d e m o n -s t r a t e d t h a t h a b i t u a l e n d u r a n c e e x e r c is e m a y n o t p r e v e n ta g e - a s s o c i a t e d d e c li n e s in i n s u l i n a c t io n , w h i c h a p p e a r t o b ei n d e p e n d e n t o f a d ip o s i t y .

A c u t e c h a n g e s i n i n s u li n a c t i o n c a n b e l a r g e l y e x p l a i n e db y c a r b o h y d r a t e u s e d u r i n g a n a c t i vi ty . W h e n c a r b o h y d r a t eu s e i s s u b s t a n t i a l - - a s i t i s d u r i n g 3 0 m i n u t e s o f c o n t i n u o u s ,m o d e r a t e e x e r c i s e - - b l o o d g lu c o s e l ev e l s d e c r e a s e d u r i n gt h e a c t i v i t y , e v e n i n i n d i v i d u a l s w i t h t y p e 2 D M . 26 W h e n ac o n s i d e r a b l e a m o u n t o f m u s c l e g l y c o g e n i s d e p l e t e d w i t hm o r e p r o l o n g e d a c ti v it y , t h e i n t a k e o f c a r b o h y d r a t e s d u r i n gt h e a c t i v i ty m a y b e u s e f u l i n p r o v i d i n g g l u c o s e t o d e l a yf a t i g u e a n d t o m o d e r a t e g l y c o g e n d e p l e t i o n , p a r t i c u l a r l y w h e ne x e r c i s i n g f o r > 1 h o u r . 10,27 T h e s e r e s p o n s e s m a y b e a l t e r e db y p r e d i a b e t e s o r D M , h o w e v e r . A r e c e n t s t u d y b y B r a u n e ta128 f o u n d t h a t t o t a l c a r b o h y d r a t e o x i d a t i o n a n d e s t i m a t e dm u s c l e g l y c o g e n u s e d u r i n g a n a c u t e s e s s i o n o f e xe r c is e w e r e

s i g n i f i c a n t l y l o w e r ( P < 0 .0 5 ) i n i n s u l i n - r e s i s t a n t w o m e nc o m p a r e d w i t h s i m i l a r l y o v e r w e i g h t b u t i n s u l i n - se n s i t iv ec o u n t e r p a r t s , e v e n th o u g h b l o o d g l u c o s e u p t a k e w a s u n a l -t e r e d b y d i f f e r e n c e s i n i n s u l i n a c t i o n .F o r _>2 h o u r s a f t e r w a r d s , p r i o r a c t i v i t y a ls o c a u s e s a n e n -h a n c e d u p t a k e o f b l o o d g l u c o s e fo r g l y c o g e n s y n t h e si s . Inm u s c l e c e l l s , a t l e a s t 2 d i s t i n c t m e c h a n i s m s e x i s t t o s t i m u l a t eg l u c o s e u p t a k e d u r i n g e x e r c is e a n d p o s t e x e r c i s e g lu c o s e u s ea n d g l y c o g e n s y n t h es i s : o n e i s i n s u li n d e p e n d e n t ( w h i c h m a yb e a l t e r e d i n i n d i v i d u a l s w i t h i n s u l i n r e s i s t a n c e o r t y p e 2 D M )a n d t h e o t h e r is in s u l i n i n d e p e n d e n t i n r e s p o n s e t o m u s c l ec o n t r a c t i o n s . 13 I m m e d i a t e l y a f t e r a c u t e e x e r c i se , g l y c o g e nd e p l e t i o n c a n s t i m u l a t e a d d i t i o n a l g l u c o s e u p t a k e , 29 w h i c hc a n o c c u r m o r e r a p i d l y f o r s e v e r a l h o u r s a f te r a n a c u t e s e s -s i o n o f e x e r ci s e w i t h m i n i m a l i n s u l in r e q u i r ed .

A n i n d i v i d u a l s tr a i n i n g s t a tu s m u s t a l s o b e c o n s i d e r e dw h e n p r e d i c t i n g g l y c e m i c r e s p o n s e s t o a n a c ti v it y . A e r o b i ct r a i n i n g i n c r e a s e s t h e p r o p o r t i o n o f fa t u t i l iz a t i o n f o r s i m i l a rl o w - o r m o d e r a t e - i n t e n s i t y a c t i v i ty d o n e a f te r t h e t r a i n i n ge f f ec t h a s o c c u r r e d ; u s i n g a g r e a t e r p r o p o r t i o n o f f a t s p a r e sm u s c l e g l y c o g e n a n d b l o o d g l u c o s e a n d a l l o w s f o r m o r ee f f e c t i v e g l y c e m i c c o n t r o l d u r i n g a c t i v i t i e s . 1 H o w e v e r , i ni n d i v i d u a l s w i t h h y p e r g l y c e m i a , b e i n g t r a i n e d m a y r e s u l t ina l e s s e r d e c r e a s e i n g l y c e m i a d u r i n g a c u t e e x e r c is e . 13

C h a n g e s i n f u el u t i l iz a t i o n w i t h t r a i n i n g m a y r e q u i r es m a l l e r c o m p e n s a t o r y a d j u s t m e n t s to c a r b o h y d r a t e o ri n s u l i n i n ta k e w h e n g r e a t e r a m o u n t s o f fa t a re a b l e to b e u t i -l i z e d d u r i n g s u c h a c t i v it ie s . H o w e v e r , t h e s e c h a n g e s a p p l y

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R e la ti ve r is k o f d e v e l o p i n g d i a b e t e s m e l l it u s a c c o r d i n g t o A ) m e a n d u r a t i o n o f m o d e r a t e t o v i g o r o u s p h y s i c a la c t i v i t y d u r i n g f o ll o w - u p < 1 , 1 - 2 . 4 , a n d _ >2 .5 h / w k ) ; a n d B ) m e a n d u r a t io n o f w a l k i n g f o r e x e r c i s e < 1 , 1 - 2 . 4 ,a n d _ > 2 .5 h / w k ) i n t h e F i n ni s h D i a b e t e s P r e v e n ti o n S t ud y . M o d e l 1 : A d j u s t e d f o r a g e , s e x , a n d e i t h e r 1 ) c h a n g ein m o d e r a t e t o v i g o r o u s l e isu r e -t im e p h ys i ca l a c t i v i t y L T P A) f r o m b a se l i n e a n d m e a n l o w- i n t e n s i t y L T P A d u r i n gf o l lo w - u p a n d i t s c h a n g e f r o m b a s e l in e ; o r 2 ) c h a n g e i n d u r a t i o n o f w a l k i n g f o r e x e r c i s e f ro m b a s e l i n e a n d o t h e rf o rm s o f L T P A . M o d e l 2 : A d j u s t e d f o r v a r i a b l e s i n m o d e l 1 a n d m e a n v a l u e s o f d i e t a r y i n ta k e o f e n e r g y , to t a la n d s a t u r a te d f a t, a n d f i b e r d u r i n g f o l lo w - u p a n d t h e i r c h a n g e s fr o m b a s e l i n e . M o d e l 3 : A d j u s t e d f o r v a r i a b l e si n m o d e l 2 a n d m e a n b o d y m a s s i n d e x d u r i n g f o l lo w - u p a n d it s c h a n g e f r om b a s e l i n e . C o p y r i g h t 2 0 0 5A m e r i c a n D i a b e t e s A s s o c i a t io n . F r o m Diabetes V o l. 5 4 , 2 0 0 5 ; 1 5 8 - 1 6 5 . 40 M o d i f i e d w i t h p e r m i s s io n fr om TheAm erican Diabetes Association.

- 9 3 -


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Insul in July 2 6t r a i n i n g h a s a l s o b e e n s h o w n t o i n c r e as e G S a c t i v it y a n dG L U T 4 p r o t e i n e x p r e s s i o n , b u t n o t i n s u l i n s i g n a l i n g , in b o t ho v e r w e i g h t c o n t r o l s a n d i n d i v i d u a l s w i t h t y p e 2 D M . 48

F i n a l ly , p h y s i c a l t r a i n i n g m a y e n h a n c e p a n c r e a t i c ] 3 -c ellf u n c t i o n ( a n d t h e r e f o r e i n s u l i n s e c r e t o r y c a p a c i t y ) i n p e o p l ew i t h t y p e 2 D M . I n h e a lt h y , y o u n g i n d i v i d u a l s , p h y s i c a l f it -n e s s t r a i n i n g i n c r e a s e s i n s u l i n s e n s i t iv i t y b u t l o w e r s t h e c a p a c -i t y t o s e c r e te i n s u l i n ( a l b e i t l e s s is n e e d e d ) . P a t i e n t s w i t ht y p e 2 D M w e r e c a t e g o r i z e d i n to l o w ( n = 8 ; m e a n a g e ,4 9 .5 y e a r s ) a n d m o d e r a t e ( n = 1 6; m e a n a g e , 5 3 .5 y e a r s )i n s u l i n s e c re t o rs b a s e d o n t h e i r C - p e p t i d e r e s p o n s e s t o a n I Vg l u c a g o n t e s t (a f te r 5 d a y s p e r w e e k o f m o d e r a t e c y c l in g f or3 m o n t h s ) . 49 T h e m o d e r a t e s e c r e t o r s s h o w e d s i g n i f i c a n ti n c r e a s e s ( P < 0 . 0 5) i n ] 3 -c el l r e s p o n s i v e n e s s t o 1 8 - a n d2 5 - m M h y p e r g l y c e m i a a n d t o a r g in i n e s ti m u l a t i o n . H o w -e v e r, n o c h a n g e w a s o b s e r v e d i n l o w s e c r e to r s a n d s e d e n -t a r y c o n t r o l s .EF F ECT IVE EXERCI SE F O R PEO PL E W I T HT YPE 2 D I ABET ES M EL L I T UST o e x e r c is e e ff e c t i v e ly a n d s a fe l y , i n d i v i d u a l s w i t h t y p e 2 D Mm u s t u n d e r s t a n d t h e p h y s i o l o g y b e h i n d t h e i r b o d i e s ' e x e r-c i s e re s p o n s e s . F i r s t, it is i m p o r t a n t t o r e c o g n i z e t h a t n o t a l lp h y s i c a l a c t iv i t ie s a re e q u a l a n d t h a t t h e i n t e n s i ty a n d d u r a -t i o n o f p h y s i c a l a c t i v i t i e s c a n g r e a t l y a f f e c t t h e r e s u l t a n tg l y c e m i c r e s p o n s e s . I n t e n s e a c t iv i t ie s s u c h a s h e a v y w e i g h tl i f t in g o r n e a r - m a x i m a l e x e r c i s e c a n c a u s e t r a n s i e n t e l e v a -t i o n s i n b l o o d g l u c o s e l e v e l s d u e t o a n e x a g g e r a t e d r e l e as e o fg l u c o s e - r a i s in g h o r m o n e s s u c h a s e p i n e p h r i n e . 2 C o n v e r s e l y ,i n t e r m i t t e n t h i g h - i n t e n s i t y e x e r ci s e u n d e r t a k e n i m m e d i a t e l ya f t er b r e a k f a s t b y 8 i n d i v i d u a l s w i t h t y p e 2 D M t r e a t e d b yd i e t o n l y r e s u l t e d i n s t e a d i n r e d u c e d b l o o d g l u c o s e c o n c e n -t r a t i o n s a n d i n s u l i n s e c r e t i o n i n a s t u d y b y L a r s e n e t a l . 5T h i s w a s l i k e l y d u e t o e l e v a t e d c i r c u l a t i n g i n s u l i n l e v e l s i nr e s p o n s e t o f o o d i n g e s t i on . A s m e n t i o n e d p r e v i o u s l y , a c t iv i -t i es t h a t a r e o f l o n g e r d u r a t i o n a n d l o w e r i n t e n s i t y g e n e r a l l yr e s u l t i n a d e c l i n e i n b l o o d g l u c o s e l e v e l s i n a l l i n d i v i d u a l sw i t h DM . 1 13

I n h e a l t h y i n d i v i d u a l s o r in t h o s e w i t h t y p e 2 D M w h o s ed i s e a s e i s b e i n g c o n t r o l l e d w i t h d i e t a n d e x e r c i s e a l o n e , t h er i s k o f d e v e l o p i n g l o w b l o o d s u g a r d u r i n g e x e r c is e i s m i n i -m a l . T h u s, s t r i n g e n t r e c o m m e n d a t i o n s a r e u s u a l l y n o t n e c-e s s a r y t o e n s u r e b l o o d g l u c o s e c o n t r o l w i t h e x e r c is e . B l o o dg l u c o s e m o n i t o r i n g s h o u l d b e p e r f o r m e d b e f o r e a n d a f te r a na c t i v i t y t o a s s e s s i t s e f fe c t o n g l y c e m i a . S u p p l e m e n t i n g w i t hc a r b o h y d r a t e s i s g e n e r a l ly n o t n e e d e d w i t h t h e s e p a ti e n t s;h o w e v e r , b l o o d g l u c o s e m o n i t o r i n g w i l l re v e a l w h i c h i n d i -v i d u a l s m a y n e e d a d d i t i o n a l c a r b o h y d r a t e s to p r e v e n th y p o g l y c e m i a d u r i n g a n d a f te r e xe r ci se . T h e s e i n d i v i d u a l sc a n b e s u p p l e m e n t e d a t a r a te o f 1 5 g / h o n a p r e l i m i n a r yb a s i s u n t i l o p t i m a l i n t a k e c a n b e d e t e r m i n e d w i t h g l u c o s em o n i t o r i n g . 13

P r o l o n g e d e x e r c i se , h o w e v e r , h a s a g r e a t e r p o t e n t i a l t oc a u s e h y p o g l y c e m i a b o t h d u r i n g a n d a f t er e x e rc i se , p a r t i c u -l a r l y i n p e o p l e t r e a t e d w i t h k e r a t i n o r a l h y p o g l y c e m i ca g e n t s o r e x o g e n o u s i n s u li n . To p r e v e n t h y p o g l y c e m i a ,

t h e se i n d i v i d u a l s w i l l li k e ly n e e d t o c o n s u m e r a p i d l ya b s o r b e d c a r b o h y d r a t e s t o c o u n t e r b a l a n c e d e c l in e s in b l o o dg l u c o s e le v e l s a n d / o r t o r e d u c e t h e ir o r a l m e d i c a t i o n s o ri n s u l i n d o s i n g b e f o r e e x e r c i s e . 1 1 3 2 7 U s e o f o r a l h y p o -g l y c e m i c a g e n ts , p a r t i c u l a r l y t h o s e w i t h a l o n g e r d u r a t i o ns u c h a s g l y b u r i d e , c a r r y a h i g h e r r i s k o f e x e r c i s e - i n d u c e dh y p o g l y c e m i a th a n w h e n t y p e 2 D M i s t r e at e d w i t h d i e t a n de x e r c i s e a l o n e . 27 E v e n n e w e r g e n e r a t i o n , s h o r t e r - a c t i n g s u l -f o n y l u r e a s s u c h a s g l i m e p i r i d e a n d g l i b e n c l a m i d e c a n i n c r e a s et h e r i s k o f h y p o g l y c e m i a . 27 I n p a t i e n t s w i t h p o s t a b s o r p t i v et y p e 2 D M , t h e h y p o g l y c e m i c a c ti o n o f g l i b e n c l a m i d e a n de x e r c is e w a s e n h a n c e d w h e n t h e tr e a t m e n t s w e r e c o m -b i n e d , r e f l e ct i ng a n i n c r e a s e d i n h i b i ti o n b y g l i b e n c l a m i d e -e n h a n c e d i n s u l in l e v e ls o f h e p a t i c g l u c o s e p r o d u c t i o n w h e ns u c h p r o d u c t i o n i s a c c e l e r a t e d b y e x e r c is e .

I n s u l i n u s e c r e a t e s i ts o w n s e t o f s p e c i a l i z e d e x e r c i sec o n c e r n s . F o r r e g u l a r , p l a n n e d e x e r c i se , s h o r t - a c t i n g p r e -e x e r ci s e in s u l i n d o s e s w i l l li k e l y n e e d t o b e l o w e r e d t o p r e -v e n t h y p o g l y c e m i a f r o m o c c u r r i n g in p e o p l e w i t h t y p e 2 D Mw h o a r e t a k i n g i n s u l i n t h e r a p y . N e w e r , s y n t h e t i c i n s u l i na n a l o g u e s , s u c h a s i n s u li n l i s p ro , al s o i n d u c e m o r e r a p i dd e c r e a s e s i n b l o o d g l u c o s e c o n c e n t r a t i o n s t h a n r e g u l a rh u m a n i n s u l i n d u e t o t h e i r f a s t e r a b s o r p t i o n . 51 C o n s e q u e n t -l y, p e o p l e w i t h t y p e 2 D M w h o e x e r c is e w i ll n e e d t o c h e c kt h e i r b l o o d s u g a r l e v e ls b e f o re , o c c a s i o n a l ly d u r i n g , a n da f t e r e x e r c i s e t o m o n i t o r i t s e f f ec t s a n d c o m p e n s a t e w i t ha p p r o p r i a t e d i e t a r y a n d / o r m e d i c a t i o n r e g i m e n c h a n g e s . 1

eop le w ith t ype 2 DM w ho exerc ise w i l l need to checkthei r b lood suga r levels before occas ional ly dur ing and

af ter exerc ise to mo ni tor i ts ef fects and comp ensate w i thappropr ia te d ie tary a nd /or med ica t ion reg imen changes .

H o w e v e r , i f o n l y l o n g e r - a c t i n g i n s u l in s , s u c h a s i n s u l i ng l a r g i n e , a r e b e i n g a b s o r b e d f r o m S C d e p o t s d u r i n g p h y s -i c al a c ti v it i es , im m e d i a t e d e c l i n e s i n g l y c e m i a d u r i n g e x e r -c i se m a y n o t b e a s l ik e l y . F o r e x a m p l e , a n i n t e n s e3 0 - m i n u t e p e r i o d o f e x e r ci s e b y i n d i v i d u a l s w i t h t y p e 1 D Mw a s n o t s h o w n t o i n cr e a s e t h e a b s o r p t i o n r a t e o f s u b c u t a -n e o u s l y i n j e c t e d , b a s a l , l o n g - a c t i n g i n s u l i n a n a l o g u e s s u c ha s i n s u l i n g l a r g i n e , 52 a n d s i m i l a r f in d i n g s w o u l d b e e x p e c t e di n th o s e w i t h t y p e 2 D M u s i n g s i m i l a r s u p p l e m e n t a l b a s a li n s u l i n s .

L a t e r - o n s et h y p o g l y c e m i a b e c o m e s a g r e a t e r c o n c e r n w h e nc a r b o h y d r a t e s t o r e s ( ie , m u s c l e a n d l i v e r g l y c o g e n ) a red e p l e t e d d u r i n g a n e x e r c i s e s e s si o n . H i g h - i n t e n s i ty e x e r c i s e s - -s u c h a s r e p e a t e d i n t e r v a l t r a i n i n g - - r e s u l t i n s u b s t a n t ia ld e p l e t i o n o f m u s c l e g l y c o g e n , w h i c h i n c r e a se s t h e r i s k f orl a t e r - o n s e t h y p o g l y c e m i a , p a r t i c u l a r l y i f c e r t a i n d i a b e t i cm e d i c a t i o n s s u c h a s s u p p l e m e n t a l i n s u l i n o r lo n g e r - l a s t in gs u l f o n y l u r e a s a r e t a k e n. 27 C o n s u m i n g m o d e r a t e a m o u n t s o fc a r b o h y d r a t e s ( 5 - 3 0 g ) d u r i n g a n d w i t h i n 3 0 m i n u t e s a f t e re x h a u s t i v e , g l y c o g e n - d e p l e t i n g e x er c is e w i ll l o w e r h y p o -g l y c e m i a r i s k a n d a l l o w f o r m o r e e f f i c i e n t r e s t o r a t i o n o f

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V o l um e 1 N u m b e r 3 S . R . C o l b e r g

m u s c l e g l y c o g e n a n d p o t e n t i a l s u p e r c o m p e n s a t i o n . 29 T o e f-f e c t iv e l y m a i n t a i n g l y c e m i c c o n t ro l a n d o p t i m i z e g l y c o g e nr e s y n t h e s i s , s o m e a d d i t i o n a l i n s u l i n ( a l b e it l e s s t h a n u s u a l )m a y s t il l b e r e q u i r e d b y i n d i v i d u a l s w i t h t y p e 2 D M w h o a r et r e a t e d w i t h i n s u l i n t o fa c i l i ta t e g l u c o s e u p t a k e i n th e i m m e -d i a t e p o s t e x e r c is e p e r i o d .

T h e A m e r i c a n D i a b e te s A s s o c ia t io n ( A D A ) r e c o m m e n d st h a t c a r b o h y d r a t e i n g e s t i o n i s n e e d e d f o r p r e - e x e r ci s e b l o o dg l u c o s e l e v e l s o f < 10 0 m g / d L ( < 5. 5 m M ) l ; h o w e v e r , t h i sr e c o m m e n d a t i o n w o u l d a p p l y o n l y to p e o p l e w i t h t y p e i o rt y p e 2 D M w h o a r e t a k in g s u p p l e m e n t a l i n s u l i n in j e c ti o n s o ru s i n g c e r t a i n s u l f o n y l u r e a s . 27,51 F o r p e o p l e w h o s e d i s e a s e i sc o n t r o l l e d w i t h d i e t o r o r a l a n t i d i a b e t i c m e d i c a t i o n s a l o n e ,e x t r a c a r b o h y d r a t e s a r e g e n e r a l l y n o t r e q u i r e d d u r i n g e x e r -c i se l a s ti n g < 1 h o ur . C l i n i c i a n s r e c o m m e n d t h a t p e o p l e w i t ht y p e 2 D M w h o a r e t r e a t e d w i t h i n s u l i n i n g e s t a t l e a s t 1 5 go f c a r b o h y d r a t e b e f o r e e x e r c i se f o r a s t a r t in g b l o o d g l u c o s el e v e l o f 12 5 m g / d L( 6.9 m M ) , a n a b n o r m a l g l y c e m i c r e s p o n s e t o e x e r c is e i sn o t u s u a l l y e x p e r i e n c e d u n t i l l e v e l s e x c e e d t w i c e t h a t , o r2 50 m g / d L (1 3.9 m M ) , a n d t h e n l i k e l y o n l y i n i n d i v i d u a l sw h o a r e i n s u l i n d e f i c i e n t ( e g, t h o s e w i t h t y p e i o r t y p e 2 D Mw h o h a v e v e r y l i tt le o r n o e n d o g e n o u s i n s u l in p r o d u c t i o n ) . 1K e t o n e b o d y p r o d u c t i o n m a y i n c r e a s e a n d r e s u l t in k e t o si s ,a l t h o u g h t h is is v e r y u n c o m m o n i n t y p e 2 D M . A m o r ea p p r o p r i a t e r e c o m m e n d a t i o n f o r e x e rc i s e rs w i t h t y p e 2 D Mi s s i m p l y t o u s e c a u t i o n w h e n u n d e r t a k i n g p h y s i c a l a c t iv i -t i e s i f t h e i r g l u c o s e l e v e l s a r e 3 00 m g / d L ( 16 .7 m M ) w i t h o u tk e t o s i s r a t h e r t h a n f o r e g o i n g t h e e x e rc i s e , m e a n i n g t h a t t h e ys h o u l d m o n i t o r b l o o d g l u c o s e l ev e l s f r e q u e n t l y a n d h y d r a t ea d e q u a t e l y t o p r e v e n t p r o b l e m s . 1,13 I f h y p e r g l y c e m i a o c c u r sa c u t e l y a f t e r a m e a l , a d e c r e a s e i n b l o o d g l u c o s e w i t h a e r o -b i c e x e r c i s e w i l l l i k e l y r e s u l t a s l o n g a s l e v e l s o f c i r c u l a t i n gi n s u l i n a r e e l e v a t e d . 26

A s f a r a s t h e f r e q u e n c y , d u r a t i o n , a n d t y p e o f a c t i v i ti e st h a t a n y o n e w i t h t y p e 2 D M s h o u l d e n g a g e i n , t h e c u r r e n tr e c o m m e n d a t i o n s f r o m t h e A D A 13 a n d o t h e r s g e n e r a l l y f o l-l o w t h e U S S u r g e o n G e n e r a l ' s r e c o m m e n d a t i o n 53 t o a c c u -m u l a t e a t l e a s t 30 m i n u t e s o f m o d e r a t e - i n t e n s i t y a e r o b i ca c t i v i ty m o s t d a y s o f t h e w e e k . T h e s e r e c o m m e n d a t i o n s a r eb a s e d o n t h e f i n d i n g t h a t i n s u l in s e n s i t i v i ty is e n h a n c e d b y as i n g l e b o u t o f a e r o b i c e x e r c i se f o r o n l y 2 4 to 7 2 h o u r s i n n o n -d i a b e t i c i n d i v i d u a l s , d e p e n d i n g o n t h e d u r a t i o n a n d i n t e n -s i t y o f t h e a c t i v i t y ; s o m e r e c e n t s t u d i e s , h o w e v e r , i n d i c a t et h a t o l d e r i n d i v i d u a l s m a y n o t e x p e r i e n c e lo n g - l i v e d g a i n si n t h e i r l e v e l o f i n s u l i n a c t i o n . 17,25 B e c a u s e t h e d u r a t i o n o f i n -c r e a s e d i n s u l i n s e n s i t i v i t y is l i k e l y m u c h l e s s t h a n 7 2 h o u r s ,i t i s r e c o m m e n d e d t h a t s u c c e s s iv e e x e r c is e s e ss i o n s b e s e p a -r a t e d b y n o m o r e t h a n t h i s a m o u n t o f t i m e , o r t h a t in d i v i d u -

a l s w i t h D M s h o u l d n o t l e t m o r e t h a n 2 d a y s l a p s e b e t w e e nb o u t s o f e x e r c is e a n d t h a t t h e y e x e r c i s e a t l e a s t 3 n o n c o n s e c -u t i v e d a y s p e r w e e k . 13 T h e i r e x e r c i s e s h o u l d c o n s i s t o f l o w -t o m o d e r a t e - i n t e n s i t y p h y s i c a l a c t iv i t y l a s t in g a m i n i m u m o f1 0 t o 1 5 m i n u t e s p e r s e s s i o n , w i t h t h e i r g o a l b e i n g 3 0 m i n -u t e s a t a t im e . T h e m o d e o f e x e rc i s e m a y v a r y d e p e n d i n g o nt h e p r e s e n c e o f c o e x i s t in g c o m p l i c a t i o n s s u c h a s p e r i p h e r a ln e u r o p a t h y o r d e g e n e r a t i v e a r t h ri t is , w h i c h m a y r e q u i r e a l -t e r n a t i v e s t h a t a r e n o n - w e i g h t - b e a r i n g ( e g , s t a t i o n a r y c y c l in g ,a r m c h a i r e x e r c i s e s, s w i m m i n g o r o t h e r a q u a t i c a c t i v i ti e s ).1,13

nd iv idua ls w i t h D M s hou ld n o t le t m ore t han 2 day s l aps ebetween b outs of exerc ise. They should exerc ise at leas t 3 non-

c ons ec u t iv e day s pe r w ee k c ons i st ing o f l ow - t o m od era te -in tens i ty phys ica l ac t iv i ty las t ing a m in imum of 1 0 to 15minutes per sess ion.

I n a d d i t i o n , r e s i s t a n c e t r a i n i n g i s r e c o m m e n d e d f o r p a -t i e n ts w i t h t y p e 2 D M b e c a u s e i t h a s t h e p o t e n t i a l t o i m p r o v em u s c u l a r s t r e n g t h a n d e n d u r a n c e , e n h a n c e f le x i bi li ty , i m -p r o v e b o d y c o m p o s i t i o n , a n d d e c r e a s e ri s k f o r c a rd i o v a s c u -l a r d i s e a s e , a ll w h i l e i n c r e a s i n g a m o u n t s o f in s u l i n - s e n s i t i v em u s c l e m a s s . 33 35 O l d e r r e c o m m e n d a t i o n s s t a t e d t h a t i ts h o u l d i d e a l ly be u n d e r t a k e n a m i n i m u m o f t w i ce w e e k l y a sp a r t o f a w e l l - r o u n d e d e x e r c i se p r o g r a m ( i n c l u d i n g a e r o b ica n d f l e x i b i l it y t r a i n i n g ) a n d i n c l u d e 8 t o 10 e x e r c i s e s i n v o l v -i n g t h e m a j o r m u s c l e g r o u p s , d o i n g a m i n i m u m o f 1 s e t o f1 0 to 1 5 r e p e t i t i o n s t o n e a r f a t i g u e . 1 A l t h o u g h e v e n t w i c e -w e e k l y t r a in i n g h a s p r o v e n b e n e f i ts f o r m e n w i t h t y p e2 D M , 34 a r e c e n t s t u d y b y D u n s t a n e t a 15 4 s h o w e d t h a t1 8 m e n w i t h t y p e 2 D M a g e d 6 0 to 8 0 y e a r s s u c c e s s f u l ly p r o -g r e s s e d o v e r 6 m o n t h s o f re s i st a n c e tr a i n i n g t o c o m p l e t i n g3 s et s o f 8 to 1 0 r e p e t i t i o n s d o n e a t 7 5 % t o 80 % o f m a x i m a lo n 8 t o 1 0 e x e r c is e s th r i c e w e e k l y . T h e s u b j e c t s a l s o e x p e r i -e n c e d m u c h g r e a t e r in c r e a s e s in m u s c l e m a s s , d e c r e a s e s inb o d y f a t , a n d i m p r o v e m e n t s i n o v e r a l l g l y c e m i c c o n tr o l.T h u s , a t r a i n i n g p r o t o c o l s u c h a s t h i s l a t t e r o n e m a y b e a b e t -te r go al . 13

O t h e r r e c o m m e n d a t i o n s f o r e x e r c is e r s w i t h t y p e 2 D Mf o c u s m o r e o n s a f e e x e r c is e p a r t i c i p a t i o n i f t h e r e i s t h e p r e s -e n c e o r t h e p o s s i b i l i t y o f d e v e l o p i n g D M - r e l a te d c o m p l i -c a t i o n s, s u c h a s c a r d i o v a s c u l a r d i s e a s e , h y p e r t e n s i o n , n e u r o p -a t h y , o r o t h e r m i c r o v a s c u l a r c o m p l i c a t io n s . A f u l l d i s c u s s i o no f t h e se c o m p l i c a t i o n s i s b e y o n d t h e s c o p e o f t h i s r e v ie w , b u tr e a d e r s a r e r e f e r re d t o t h e A m e r i c a n C o l l e g e o f S p o r t s M e d i -c i n e 's p o s i t i o n s t a n d o n e x e r c i s e a n d t y p e 2 D M 1 a n d a m o r er e c e n t r e v i e w b y S i g a l e t a11 3 f o r a d d i t i o n a l i n f o r m a t i o n . A sa g e n e r a l r e c o m m e n d a t i o n , b e f o r e b e g i n n i n g a n e x e r c i s ep 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 ou n d e r g o a m e d i c a l e v a l u a t i o n t o s c r e e n f or th e p r e s e n c e o fm a c r o v a s c u l a r a n d m i c r o v a s c u l a r c o m p l i c a t io n s p o t e n t i a l l ye x a c e r b a t e d b y e x e rc is e . T h e e x a m i n a t i o n s h o u l d s c r ee nf o r o v e r a l l g l y c e m i c c o n t r o l , p h y s i c a l l i m i t a t i o n s w i t hr e s p e c t t o j o i n t p r o b l e m s c o m m o n t o D M , p r e s c r i b e d m e d i -

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I n s u l i n J u ly 2 0 0 6

c a t io n s , a n d t h e t y p e a n d s e v e r i t y o f D M c o m p l i c a t i o n s e g ,c a r d i o v a s c u l a r h e a l t h , p e r i p h e r a l a r t e r ia l d i s e a s e , r e t i n o p a -t h y, n e p h r o p a t h y , p e r i p h e r a l a n d a u t o n o m i c n e u r o p a t h i e s ) .A g r a d e d e x e r c i se t e s t m a y b e r e c o m m e n d e d t o s cr e e n fo rc a r d i o v a s c u l a r d i s e a s e d e p e n d i n g o n t h e a g e o f t h e p e r s o na n d h i s o r h e r D M d u r a t i o n . 1

e f o r e b e g i n n i n g a n e x e r c is e p r o g r a m , i n d iv i d u a ls w i t ht 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 m e d i c a l e v a l u a ti o n

t o s c r e e n f o r t h e p r e s e n c e o f m a c r o v a s c u l a r a n d m i c r o v a s -c u l a r c o m p l i c a t io 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 e x e r c is e .

OTH ER INSULIN RE LATED BENEFITS OF EXERCISEM a n y c h r o n ic d i s e a s e s i n a d d i t i o n t o t y p e 2 D M a r e r e la t e dt o r e d u c t i o n s i n i n s u l i n s e n s i t i v it y , i n c l u d i n g h y p e r t e n s i o n ,h e a r t d i s e a s e , a n d s t r o k e . 5 54 7 P h y s i c a l t r a i n i n g a l s o a p p e a r st o e n h a n c e ~ - ce ll i n s u l in p r o d u c t i o n i n i n d i v i d u a l s w i t ht y p e 2 D M a s l o n g a s a d e q u a t e a m o u n t s o f f u n c t i o n i n g~ - c e l ls r e m a i n i n t h e p a n c r e a s . 49

E x e r c i s e c a n r e s u l t i n m o r e r e s t f u l a n d l o n g e r s l e e p . R e -c e n t s t u d i e s h a v e l i n k e d s l e e p i n g l e s s e g , o n l y 5 h o u r s an i g h t ) w i t h a n i n c r e a s e d i n c i d e n c e o f o v e r w e i g h t , o b e s i ty ,a n d i n s u l i n r e s i s t a n c e i n h e a lt h y , y o u n g a d u l t s ; s le e p d i s t u r -b a n c e s h a v e b e e n a s s o c i a t e d w i t h a n i n c r e a s e d i n c i d e n c e o ft y p e 2 D M i n t h e g e n e r a l p o p u l a t i o n . 58

P h y s i c a l a c t iv i t y m a y a c t u a l l y p l a y a r o l e i n p r e v e n t i n gD M - r e l a t e d c o m p l i c a t io n s i n c l u d i n g b o t h m i c r o v a s c u l a ra n d m a c r o v a s c u l a r ) b y a m e l i o r a t i n g a s t a t e o f l o w - l e v e li n f l a m m a t i o n a s s o c i a t e d w i t h i n s u l i n r e s i s ta n c e a n d c h r o n ich y p e r g l y c e m i a . 59,6 E v i d e n c e i s m o u n t i n g t h a t a d i p o s e t i s s u ec o n t r i b u t e s t o t h e p r o d u c t i o n o f t u m o r n e c r o s i s f a c t o r - ~

T N F - ~ ) , a c y t o k i n e n o w b e l i e v e d t o b e a d r i v i n g f o r c eb e h i n d i n s u li n r e s is t a n c e a n d d y s l i p i d e m i a , 58 r a t h e r t h a ni n t e rl e u k i n -6 . R e g u l a r e x e r c i se a p p a r e n t l y e n h a n c e s t h e s u p -

p r e s s i o n o f T N F - ~ a n d t h e r e b y o f f e rs p r o t e c ti o n a g a i n s t a n yi n s u l i n r e s i s t a n c e i t m a y c a u s e , a l o n g w i t h i t s a s s o c i a t e dh e a l t h i s s u e s .

A e r o b i c e x er c is e t r a i n in g h a s b e e n s h o w n t o i m p r o v ee n d o t h e l i a l f u n c t io n i n d i f fe r e n t v a s c u l a r b e d s i n p e o p l ew i t h t y p e 2 D M ; o n e s t u d y t h a t e x a m i n e d 1 6 i n d i v i d u a l sw i t h t y p e 2 D M u s e d f o r e a r m p l e t h y s m o g r a p h y a n d i n tr a -b r a c h i a l i n f u s i o n s o f s o d i u m n i t r o p r u s s i d e a st i m u l a t o r o fe n d o t h e l i u m - i n d e p e n d e n t v a s o d i l a t i o n ) a n d a c e t y l c h o li n e

a n e n d o t h e l i u m - d e p e n d e n t v a s o d i l a t o r ) t o d e t e r m i n e t h a t8 w e e k s o f a er o b i c ex e r c is e t ra i n i n g e n h a n c e s e n d o t h e l i u m -d e p e n d e n t v a s o d i l a t i o n i n b o t h c o n d u i t a n d r e s is t a n c e v e s -s e ls . 61 T h u s , i f e n d o t h e l i a l d y s f u n c t i o n i s a n i n t e g r a l c o m p o -n e n t o f t h e p a t h o g e n e s i s o f v a s c u l a r d i s e a s e , as i s c u r r e n t lyb e l i e v e d , a s t r o n g a r g u m e n t c a n b e m a d e f o r t h e i n c l u s i o n o fa n e x e r c is e p r o g r a m i n th e m a n a g e m e n t o f t y p e 2 D M .CONCLUSIONST h e i n t e r a c t i o n s o f in s u l i n a n d e x e r c i s e h a v e h e a l t h r a m i f i c a -t i o n s i n D M m a n a g e m e n t t h a t m u s t b e a c k n o w l e d g e d a n dm o r e f u l ly u n d e r s t o o d . C l i n i c ia n s n e e d t o c l e a rl y u n d e r -s t a n d a n d c o m m u n i c a t e r e l e v a n t f a ct o rs , s u c h a s t h e a c t io na n d a v a i l a b i l it y o f c i r cu l a t in g i n s u l i n a n d c o u n t e r r e g u l a t o r yh o r m o n e r e s p o n s e s , s o t h a t p a t i e n t s w i t h t y p e 2 D M c a ns a f e l y a n d e f f e c t i v e l y b e n e f i t f r o m p h y s i c a l a c t i v i t y w i t h o u tf e a r o f u n b a l a n c i n g t h e i r g l y c e m i c c o n t r o l . T h e m o s t r e c e n tr e s e a rc h o n i n s u l in s e n s i t i v i t y l e a v e s n o d o u b t t h a t p h y s i c a la c t i v i t y - - p o s s i b l y i n c o m b i n a t i o n w i t h o t h e r l i fe s t y lec h a n g e s t h a t i m p a c t v i s c e r a l f a t - - p l a y s a m a j o r r o l e i n t h ep r e v e n t i o n a n d c o n t r o l o f i n s u l i n r e s i s t a n c e , p r e d i a b e t e s ,a n d t y p e 2 D M . M o r e o v e r , e v e n p e o p l e w i t h t y p e 2 D M c a na n d s h o u l d p a r t i c i p a t e i n r e g u l a r p h y s i c a l a c t iv i ty , i n c l u d i n gb o t h a e r o b ic a n d r e s is t a n c e t r ai n i n g . A d d i t i o n a l s t u d i e s a r en e e d e d t o i n v e s t ig a t e t h e a n t i - i n f l a m m a t o r y e f fe c t o f p h y s i -c a l a c t i v i t y a n d o t h e r l i f e s t y l e c h a n g e s o n t h e c o n t r o l a n dp r e v e n t i o n o f D M , a s w e l l a s t h e i m p a c t o f i n f l a m m a t i o n o no t h e r i n s u l i n - r e l a t e d h e a l t h c o n c e r n s .

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A d d r e s s c o rr e s p o n d e n c e t o Sheri R. Colberg PhD FACSM Exercise Science Sport Physical Education and RecreationDepartment Old Dominion University Norfolk VA 23529. E-mail: [email protected]

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The Impact of Exercise on Insulin Action in Type 2 Diabetes Mellitus Prevention and Control 2005