Exercise in type 2 diabetes:The mechanisms of resistance and endurance training☆

Sulin Cheng *,Urho M.Kujala

a School of Kinesiology,Shanghai University of Sport,Shanghai 200438,China

b Department of Health Sciences,University of Jyv?skyl?,Jyv?skyl?,P.O.Box 35(LL),FI-40014,Finland

Exercise in type 2 diabetes:The mechanisms of resistance and endurance training☆

Sulin Chenga,b,*,Urho M.Kujalab

aSchool of Kinesiology,Shanghai University of Sport,Shanghai 200438,China

bDepartment of Health Sciences,University of Jyv?skyl?,Jyv?skyl?,P.O.Box 35(LL),FI-40014,Finland

This highlight article focuses on the effects of different types of exercise on the prevention and treatment of type 2 diabetes and on future challenges in developing effective preventive strategies.

1.Current prevalence of diabetes in China

Cardiovascular diseases have become the leading cause of death in China.1Diabetes is amajor risk factor for cardiovasculardiseases and the rapid change in lifestyle is the main reason for theincreased risk for cardiovascular diseases inChina.1—3The China NationalDiabetesand Metabolic Disorders Study,3consisting of a nationally representative sample of 46,239 adults,found that age-standardized prevalence of diabetes was 10.6%among men and 8.8%among women,and for prediabetes the figures were 16.1%and 14.9%formen and women,respectively.This corresponds to 92.4 million adults with diabetes and 148.2 million adults with prediabetes.Clearly diabetes has become a huge public health challenge in China and developing effective preventive strategies for diabetes is therefore essential.3

2.Endurance(aerobic)and strength(resistance)exercise training in the prevention and treatmentoftype 2 diabetes

The first randomized controlled trial including an exercise only arm in the prevention of diabetes was conducted inChina from 1986 to 1992,and the results suggested that increased aerobic exercise has an independent role in the prevention of type 2 diabetes after 6 years of intervention.4Since the pioneering study by Eriksson et al.5it has been known that,in addition to aerobic training,strength training is also beneficial for type 2 diabetes patients.A randomized controlled study by Sigal et al.6showed that both aerobic training and resistance training alone improve glycemic controlin patients with type 2 diabetes,and the improvement after 22 weeks of exercise training seems to be greater with combined,rather than they are applied in isolation.A recent study conducted by van Dijk et al.7concluded that a single session of resistance-or endurance-type exercise reduces the prevalence of hyperglycaemia and improves glycaemic control during the subsequent 24 h period in individuals with impaired glucose tolerance,and in insulin-treated and noninsulin-treated type 2 diabetic patients.Despite these shortterm and relatively long-term randomized controlled trials,it is still not well known whether increased volume or combination of training modalities is more important than exercise type.Furthermore,the mechanistic differences between the two training modalities in improving glycemic control are unclear.8

Skeletal muscles typically represent more than one-third of body mass and play an important role in whole-body energy metabolism.During exercise,work is mainly done by skeletal muscles and this work is mediated by various signaling pathways.At the cellular level,exercise increases insulin-dependent glucose transport and hexokinase II activity.9Furthermore,muscular contraction induces an increase in translocation of glucose transporter type 4 through AMP-activated protein kinase signaling pathways during endurance exercise training in the acute phase.10,11After exercising,increased adenosine triphosphate synthesis and,later,increased mitochondrial biogenesis via activation of peroxisome-proliferator activated receptor-γcoactivator 1α,increases muscle insulin sensitivity in the post-exercise period.12Another proposed mechanism is increased membrane permeability accompanied by elevated insulinstimulated microvascular perfusion in the post-exercise state which could favor glucose uptake.12

The cellularmechanisms ofacute resistance-type exercise are lessclear.An increase in muscle massovertime hasbeen thought to account for the benefits of resistance exercise on glycaemic control and the associated expansion of glucose disposal capacity.13The study by van Dijk etal.7showed thata single bout ofresistance exercise reduced the prevalence ofhyperglycaemia by about36%during the 24-h post-exercise period.The authors ascribed these acute improvements in glycaemic control following resistance exercise to directimprovements in insulindependentand insulin-independentglucose uptake,similarto the effects generally observed after endurance exercise.However,it remains to be established whether resistance exercise can also modulate glycaemic control throughout subsequent day/s,and whetherthe acute glucoregulatory effects ofresistance exercise remain atlowerintensities.7Morestudiesareneeded to determine whether strength or endurance type training should be recommended to improve glycaemic control.

The effects of training on skeletal muscle and glucose metabolism may be also modulated by variants in genes.A recent study conducted by Barres et al.14showed that acute aerobic exercise alters global and gene-specific promoter methylation in skeletal muscle suggesting that DNA hypomethylation is an early event in contraction-induced gene activation.Further,they found thatexercise-induced effects on DNA methylation are dependent on exercise intensity.These findings provide further evidence that the epigenetic marks across the genome are subjectto more dynamic variations than previously appreciated.14

3.Future challenges

Both in-depth mechanistic studies and long-term trials are needed to clarify the overall long term effects of different types of training on disease progression,occurrence of related cardio-vascular diseases,complications and mortality. One of the novel mechanisms needing further study is microRNAs and their regulation in the context of insulin resistance.15Furthermore,adipose tissue has an important role as an energy store and dysregulation of its function also predicts cardio-metabolic diseases.Recently,the importance and interaction of muscle and adipose tissues for disease risk has received much attention.16The large-scale potential of exercise training probably lies in its ability to induce many health benefits at the same time leading to better fitness and function in later years.17Our understanding of genetics,the effects of exercise and their interactions is accumulating rapidly.In addition to clarifying these relationships using different modern approaches there is a continuous need to carry out large-scale long-term randomized controlled trials to explore the effects of exercise.Differences in the determinants and potential to respond to exercise training by age need more study.Overall,a life-long physically active lifestyle seems to bestow the highest health benefits. Consequently,long-term adherence to exercise advice rather than specific modes of exercise might ultimately determine efficacy to improve glycaemia and the associated morbidity and mortality.

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6.Sigal RJ,Kenny GP,Boule NG,Wells GA,Prud’homme D,Fortier M, etal.Effects of aerobic training,resistance training,or both on glycemic control in type 2 diabetes:a randomized trial.Ann Int Med 2007;147:357—69.

7.van Dijk JW,Manders RJ,Tummers K,Bonomi AG,Stehouwer CD, Hartgens F,etal.Both resistance-and endurance-type exercise reduce the prevalence of hyperglycaemia in individuals with impaired glucose tolerance and in insulin-treated and non-insulin-treated type 2 diabetic patients.Diabetologia 2012;55:1273—82.

8.Roden M.Exercise in type 2 diabetes:to resistorto endure?Diabetologia 2012;55:1235—9.

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11.O’Neill HM,Maarbjerg SJ,Crane JD,Jeppesen J,Jorgensen SB, Schertzer JD,et al.AMP-activated protein kinase(AMPK)β1β2 muscle nullmice revealan essentialrole for AMPK in maintaining mitochondrial content and glucose uptake during exercise.Proc Natl Acad Sci USA 2011;108:16092—7.

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13.Eves ND,Plotnikoff RC.Resistance training and type 2 diabetes: considerations for implementation at the population level.Diabetes Care 2006;29:1933—41.

14.Barres R,Yan J,Egan B,Treebak JT,Rasmussen M,Fritz T,et al.Acute exercise remodels promoter methylation in human skeletal muscle.Cell Metab 2012;15:405—11.

15.Gallagher IJ,Scheele C,Keller P,Nielsen AR,Remenyi J,Fischer CP, etal.Integration of microRNA changes in vivo identifies novelmolecular features of muscle insulin resistance in type 2 diabetes.Genome Med 2010;2:9.

16.Leskinen T,Rinnankoski-Tuikka R,Rintala M,Seppanen-Laakso T, Pollanen E,Alen M,et al.Differences in muscle and adipose tissue gene expression and cardio-metabolic risk factors in the members of physical activity discordant twin pairs.PLoS One 2010;5:E12609.

17.Kujala UM.Evidence on the effects ofexercise therapy in the treatmentof chronic disease.Br J Sports Med 2009;43:550—5.

Received 12 April 2012;accepted 15 April2012

☆This study was supported by the 2012 National Science and Technology Infrastructure Program(Grant No.2012BAK21B00).

*Corresponding author.Shanghai University of Sport,Schoolof Kinesiology, Shanghai200438,China.

E-mail address:sulin.cheng@jyu.fi(S.Cheng)

Peer review under responsibility of Shanghai University of Sport

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