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The interactions bet ween I nsul I and physical activity are varied and complex. I ndi vi dual s wi t h type 2 DM can use physical t rai ni ng to control DM.
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Оригинальное название
The Impact of Exercise on Insulin Action in Type 2 Diabetes Mellitus Prevention and Control 2005
The interactions bet ween I nsul I and physical activity are varied and complex. I ndi vi dual s wi t h type 2 DM can use physical t rai ni ng to control DM.
The interactions bet ween I nsul I and physical activity are varied and complex. I ndi vi dual s wi t h type 2 DM can use physical t rai ni ng to control DM.
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 . -85 - 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. - 87- 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 - - 95- 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. 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