Restricted accessResearch articleFirst published online 2023-4
Effects of Exercise Training on Inflammatory and Cardiometabolic Risk Biomarkers in Patients With Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
The interaction between type 2 diabetes mellitus (T2DM) and cardiometabolic morbidity and mortality stems from the progressive nature of inflammation underpinning both diseases. Exercise training is considered an effective treatment strategy for T2DM and cardiometabolic diseases.
Objective
The current systematic review and meta-analysis investigated the effects of exercise training on inflammatory and cardiometabolic risk biomarkers in patients with T2DM.
Data sources
Electronic databases (PubMed/Medline, Embase, Cochrane Library, CINAHL, Google Scholar, Scopus, and Web of Science) were searched for randomized controlled trials (RCTs) from inception to January 2022. We used random effects models to estimate weighted mean differences with 95% confidence intervals.
Study selection
Twenty-five RCTs were included (N = 1257 participants; mean age = 52 years). Included studies had moderate to good overall methodological quality (TESTEX = 9 (range 7–13).
Results
Meta-analysis indicated that exercise training significantly increased adiponectin and decreased fasting insulin, homeostatic model assessment for insulin resistance, tumor necrosis factor-α, interleukin-6, and C-reactive protein (ps ≤ 0.05). Subgroup analysis by type of training indicated that aerobic exercise had the most consistent beneficial effects as compared to other types of exercise training; however, there was high heterogeneity among studies.
Conclusion
Different types of exercise training increase adiponectin levels and decrease pro-inflammatory cytokines such as TNF-α, IL-6, and CRP, as well as fasting insulin and insulin resistance markers in patients with T2DM. However, these effects were not beneficial for more commonly measured cardiometabolic risk factors (i.e., lipid profiles). Additional relevant clinical trials are required to confirm these results.
Trial registration
This systematic review and meta-analysis was prospectively registered in the PROSPERO database (CRD42022307396).
AhmadiP.TorabiM.Aran ArdabiliA.AghazadehJ. (2012). Serum adiponectin and insulin sensitivity affect by aerobic exercise program in patients with type 2 diabetes mellitus. International Journal of Biosciences (IJB), 2(9), 94–101. http://www.innspub.net
2.
AnnibaliniG.LucertiniF.AgostiniD.ValloraniL.GioacchiniA.BarbieriE.GuesciniM.CasadeiL.PassaliaA.SalM. D.PiccoliG.AndreaniM.FedericiA.StocchiV. (2017). Concurrent aerobic and resistance training has anti-inflammatory effects and increases both plasma and leukocyte levels of IGF-1 in late middle-aged type 2 diabetic patients. Oxidative Medicine and Cellular Longevity, 2017, 3937842. https://doi.org/10.1155/2017/3937842
3.
BadawiA.KlipA.HaddadP.ColeD. E.BailoB. G.El-SohemyA.KarmaliM. (2010). Type 2 diabetes mellitus and inflammation: Prospects for biomarkers of risk and nutritional intervention. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 3, 173. https://doi.org/10.2147/DMSOTT.S9089
4.
BaigzadehM.Hossienpour DelavarS.SafikhaniH. (2020). The effect of training (aerobic and concurrent) and cinnamon supplementation on the plasma levels of visfatin and adiponectin in overweight diabetic men. Journal of Clinical Research in Paramedical Sciences, 9(2), e90906. https://doi.org/10.5812/jcrps.90906
5.
BalducciS.ZanusoS.NicolucciA.FernandoF.CavalloS.CardelliP.FalluccaS.AlessiE.LetiziaC.JimenezA.FalluccaF.PuglieseG. (2010). Anti-inflammatory effect of exercise training in subjects with type 2 diabetes and the metabolic syndrome is dependent on exercise modalities and independent of weight loss. Nutrition, Metabolism and Cardiovascular Diseases, 20(8), 608–617. https://doi.org/10.1016/j.numecd.2009.04.015
6.
BecicT.StudenikC.HoffmannG. (2018). Exercise increases adiponectin and reduces leptin levels in prediabetic and diabetic individuals: Systematic review and meta-analysis of randomized controlled trials. Medical Sciences, 6(4), 97. https://doi.org/10.3390/medsci6040097
7.
BoudouP.SobngwiE.Mauvais-JarvisF.VexiauP.GautierJ. (2003). Absence of exercise-induced variations in adiponectin levels despite decreased abdominal adiposity and improved insulin sensitivity in type 2 diabetic men. European Journal of Endocrinology, 149(5), 421–424. https://doi.org/10.1530/eje.0.1490421
8.
BrooksN.LayneJ.GordonP.RoubenoffR.NelsonM.Castaneda-SceppaC. (2007). Strengthtraining improves muscle quality and insulinsensitivity in hispanic older adults with type 2 diabetes. International Journal of Medical Sciences, 4(1), 19–27. https://doi.org/10.7150/ijms.4.19
9.
BusnatuS. S.SerbanoiuL. I.LacraruA. E.AndreiC. L.JercalauC. E.StoianM.StoianA. (2022). Effects of exercise in improving cardiometabolic risk factors in overweight children: A systematic review and meta-analysis. Healthcare (Basel), 10(1), 82. https://doi.org/10.3390/healthcare10010082
10.
CamposR. M.de MelloM. T.TockL.SilvaP. L.MasquioD. C.de PianoA.SanchesP. L.CarnierJ.CorgosinhoF. C.FoschiniD.TufikS.DâmasoA. R. (2014). Aerobic plus resistance training improves bone metabolism and inflammation in adolescents who are obese. The Journal of Strength & Conditioning Research, 28(3), 758–766. https://doi.org/10.1519/JSC.0b013e3182a996df
11.
CarranzaF. H.Corbatón-AnchueloA.ParejaF. B.ArrobaC. M.-A.Vega-QuirogaS.Benito-LeónJ.Serrano-RíosM. (2022). Incidence of type 2 diabetes in the elderly in Central Spain: Association with socioeconomic status, educational level, and other risk factors. Primary Care Diabetes, 16(2), 279–286. https://doi.org/10.1016/j.pcd.2021.12.016
12.
ChenX.SunX.WangC.HeH. (2020). Effects of exercise on inflammatory cytokines in patients with type 2 diabetes: A meta-analysis of randomized controlled trials. Oxidative Medicine and Cellular Longevity, 2020, 6660557. https://doi.org/10.1155/2020/6660557
13.
CohenJ. (2013). Statistical power analysis for the behavioral sciences. Routledge.
14.
CorpeleijnE.FeskensE. J.JansenE. H.MensinkM.SarisW. H.BlaakE. E. (2007). Lifestyle intervention and adipokine levels in subjects at high risk for type 2 diabetes: The study on lifestyle intervention and impaired glucose tolerance maastricht (SLIM). Diabetes Care, 30(12), 3125–3127. https://doi.org/10.2337/dc07-0457
15.
CuschieriS. (2019). Type 2 diabetes–An unresolved disease across centuries contributing to a public health emergency. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 13(1), 450–453. https://doi.org/10.1016/j.dsx.2018.11.010
16.
DarabiS.HasanvandA.NourollahiA. (2016). Assessment of the effects of anti-inflammatory of garlic; Nettle leaves and olives extracts in STZ-induced diabetic rat. Complementary Medicine Journal of Faculty of Nursing & Midwifery, 6(1), 1451–1460.
17.
Doğan DedeN.İpekçiS. H.KebapcılarL.ArslanM.KurbanS.YıldızM.GönenM. S. (2014). Influence of exercise on leptin, adiponectin and quality of life in type 2 diabetics. Turk Jem, 19(1), 7–13. https://doi.org/10.4274/tjem.2564
18.
EggerM.SmithG. D.SchneiderM.MinderC. (1997). Bias in meta-analysis detected by a simple, graphical test. British Medical Journal, 315(7109), 629–634. https://doi.org/10.1136/bmj.315.7109.629
19.
FriedmanJ. M.HalaasJ. L. (1998). Leptin and the regulation of body weight in mammals. Nature, 395(6704), 763–770. https://doi.org/10.2302/kjm.60.1
20.
GokulakrishnanK.RanjaniH.WeberM. B.PandeyG. K.AnjanaR. M.BalasubramanyamM.PrabhakaranD.TandonN.NarayanK. M.MohanV. (2017). Effect of lifestyle improvement program on the biomarkers of adiposity, inflammation and gut hormones in overweight/obese Asian Indians with prediabetes. Acta Diabetologica, 54(9), 843–852. https://doi.org/10.1007/s00592-017-1015-9
21.
GuptaA.FavaiosS.PerniolaA.MagnusonA.BerggrenL. (2011). A meta‐analysis of the efficacy of wound catheters for post‐operative pain management. Acta Anaesthesiologica Scandinavica, 55(7), 785–796. https://doi.org/10.1111/j.1399-6576.2011.02463.x
22.
HayashinoY.JacksonJ. L.HirataT.FukumoriN.NakamuraF.FukuharaS.TsujiiS.IshiiH. (2014). Effects of exercise on C-reactive protein, inflammatory cytokine and adipokine in patients with type 2 diabetes: A meta-analysis of randomized controlled trials. Metabolism: Clinical and Experimental, 63(3), 431–440. https://doi.org/10.1016/j.metabol.2013.08.018
23.
HejaziK.FerrariF. (2022) Effects of physical exercise on cardiometabolic biomarkers and inflammatory markers in children: a systematic review and meta-analysis of randomized controlled trials. Biological Research for Nursing, 24(4), 519–529. https://doi.org/10.1177/10998004221099573
24.
HigginsJ. P.ThompsonS. G.DeeksJ. J.AltmanD. G. (2003). Measuring inconsistency in meta-analyses. British Medical Journal, 327(7414), 557–560. https://doi.org/10.1136/bmj.327.7414.557
25.
IbáñezJ.IzquierdoM.Martínez‐LabariC.OrtegaF.GrijalbaA.ForgaL.IdoateF.García-UncitiM.Fernández-RealJ. M.GorostiagaE. M. (2010). Resistance training improves cardiovascular risk factors in obese women despite a significative decrease in serum adiponectin levels. Obesity, 18(3), 535–541. https://doi.org/10.1038/oby.2009.277
26.
JelleymanC.YatesT.O’DonovanG.GrayL. J.KingJ. A.KhuntiK.DaviesM. J. (2015). The effects of high‐intensity interval training on glucose regulation and insulin resistance: A meta‐analysis. Obesity Reviews, 16(11), 942–961. https://doi.org/10.1111/obr.12317
27.
JonesL. W.EvesN. D.PeddleC. J.CourneyaK. S.HaykowskyM.KumarV.WintonT. W.ReimanT. (2009). Effects of presurgical exercise training on systemic inflammatory markers among patients with malignant lung lesions. Applied Physiology, Nutrition, and Metabolism, 34(2), 197–202. https://doi.org/10.1139/H08-104
28.
JorgeM. L.de OliveiraV. N.ResendeN. M.ParaisoL. F.CalixtoA.DinizA. L. D.ResendeE. S.RopelleE. R.CarvalheiraJ. B.EspindolaF. S.JorgeP. T.GelonezeB. (2011). The effects of aerobic, resistance, and combined exercise on metabolic control, inflammatory markers, adipocytokines, and muscle insulin signaling in patients with type 2 diabetes mellitus. Metabolism: Clinical and Experimental, 60(9), 1244–1252. https://doi.org/10.1016/j.metabol.2011.01.006
29.
KadoglouN. P.IliadisF.AngelopoulouN.PerreaD.AmpatzidisG.LiapisC. D.AlevizosM. (2007). The anti-inflammatory effects of exercise training in patients with type 2 diabetes mellitus. European Journal of Preventive Cardiology, 14(6), 837–843. https://doi.org/10.1097/HJR.0b013e3282efaf50
30.
KadoglouN. P.IliadisF.LiapisC. D.PerreaD.AngelopoulouN.AlevizosM. (2007). Beneficial effects of combined treatment with rosiglitazone and exercise on cardiovascular risk factors in patients with type 2 diabetes. Diabetes Care, 30(9), 2242–2244. https://doi.org/10.2337/dc07-0341
31.
KellyA. S.SteinbergerJ.OlsonT. P.DengelD. R. (2007). In the absence of weight loss, exercise training does not improve adipokines or oxidative stress in overweight children. Metabolism: Clinical and Experimental, 56(7), 1005–1009. https://doi.org/10.1016/j.metabol.2007.03.009
32.
KimY. S.NamJ. S.YeoD. W.KimK. R.SuhS. H.AhnC. W. (2015). The effects of aerobic exercise training on serum osteocalcin, adipocytokines and insulin resistance on obese young males. Clinical Endocrinology, 82(5), 686–694. https://doi.org/10.1111/cen.12601
33.
KohutM.McCannD.RussellD.KonopkaD.CunnickJ.FrankeW.FrankeW. D.CastilloM. C.ReighardA. E.VanderahE. (2006). Aerobic exercise, but not flexibility/resistance exercise, reduces serum IL-18, CRP, and IL-6 independent of beta-blockers, BMI, and psychosocial factors in older adults. Brain, Behavior, and Immunity, 20(3), 201–209. https://doi.org/10.1016/j.bbi.2005.12.002
34.
KuY.HanK.AhnH.KwonH.KooB.KimH.MinK. (2010). Resistance exercise did not alter intramuscular adipose tissue but reduced retinol-binding protein-4 concentration in individuals with type 2 diabetes mellitus. The Journal of International Medical Research, 38(3), 782–791. https://doi.org/10.1177/147323001003800305
35.
KumarA. S.MaiyaA. G.ShastryB.VaishaliK.RavishankarN.HazariA.GundmiS.JadhavR. (2019). Exercise and insulin resistance in type 2 diabetes mellitus: A systematic review and meta-analysis. Annals of Physical and Rehabilitation Medicine, 62(2), 98–103. https://doi.org/10.1016/j.rehab.2018.11.001
36.
López-JaramilloP.Gómez-ArbeláezD.López-LópezJ.López-LópezC.Martínez-OrtegaJ.Gómez-RodríguezA.Triana-CubillosS. (2014). The role of leptin/adiponectin ratio in metabolic syndrome and diabetes. Hormone Molecular Biology and Clinical Investigation, 18(1), 37–45. https://doi.org/10.1515/hmbci-2013-0053
37.
MatsuzawaY.FunahashiT.KiharaS.ShimomuraI. (2004). Adiponectin and metabolic syndrome. Arteriosclerosis, Thrombosis, and Vascular Biology, 24(1), 29–33. https://doi.org/10.2174/13816128113199990360
38.
MendhamA. E.DuffieldR.MarinoF.CouttsA. J. (2014). A 12-week sports-based exercise programme for inactive indigenous Australian men improved clinical risk factors associated with type 2 diabetes mellitus. Journal of Science and Medicine in Sport, 18(4), 438–443. https://doi.org/10.1016/j.jsams.2014.06.013
39.
MoghadasiM.MohebbiH.Rahmani-NiaF.Hassan-NiaS.NorooziH. (2011). Effects of short-term lifestyle activity modification on adiponectin mRNA expression and plasma concentrations. European journal of sport science, 13(4), 378–385. https://doi.org/10.1080/17461391.2011.635701
40.
MoghadasiM.MohebbiH.Rahmani-NiaF.Hassan-NiaS.NorooziH.PiroozniaN. (2012). High-intensity endurance training improves adiponectin mRNA and plasma concentrations. European Journal of Applied Physiology, 112(4), 1207–1214. https://doi.org/10.1007/s00421-011-2073-2
41.
MujumdarP. P.Duerksen-HughesP. J.FirekA. F.HessingerD. A. (2011). Long-term, progressive, aerobic training increases adiponectin in middle-aged, overweight, untrained males and females. Scandinavian Journal of Clinical and Laboratory Investigation, 71(2), 101–107. https://doi.org/10.3109/00365513.2011.554995
42.
OkadaS.HiugeA.MakinoH.NagumoA.TakakiH.KonishiH.GotoY.YoshimasaY.MiyamotoY. (2010). Effect of exercise intervention on endothelial function and incidence of cardiovascular disease in patients with type 2 diabetes. Journal of Atherosclerosis and Thrombosis, 17(8), 828–833. https://doi.org/10.5551/jat.3798
43.
OuchiN.ParkerJ. L.LugusJ. J.WalshK. (2011). Adipokines in inflammation and metabolic disease. Nature Reviews Immunology, 11(2), 85–97. https://doi.org/10.1038/nri2921
44.
PageM. J.McKenzieJ. E.BossuytP. M.BoutronI.HoffmannT. C.MulrowC. D.ShamseerL.TetzlaffJ. M.AklE. A.BrennanS. E.ChouR.GlanvilleJ.GrimshawJ. M.HróbjartssonA.LaluM. M.LiT.LoderE. W.Mayo-WilsonE.McDonaldS.McGuinnessL. A.MoherD. (2021). The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. Systematic Reviews, 10(1), 89. https://doi.org/10.1186/s13643-021-01626-4
45.
PanB.GeL.XunY.-Q.ChenY.-J.GaoC.-Y.HanX.ZuoL.-Q.ShanH.-Q.YangK.-H.DingG.-W.TianJ.-H. (2018). Exercise training modalities in patients with type 2 diabetes mellitus: A systematic review and network meta-analysis. International Journal of Behavioral Nutrition and Physical Activity, 15(1), 1–14. https://doi.org/10.1186/s12966-018-0703-3
46.
ParsianH.EizadiM.KhorshidiD.KhanaliF. (2012). The effect of long-term aerobic exercise on serum adiponectin and insulin sensitivity in type 2 diabetic patients. Journal of Jahrom University of Medical Sciences, 11(1), 41–48. https://doi.org/10.29252/jmj.11.1.6
47.
PedersenB. K. (2017). Anti‐inflammatory effects of exercise: Role in diabetes and cardiovascular disease. European Journal of Clinical Investigation, 47(8), 600–611. https://doi.org/10.1111/eci.12781
48.
Rokling-AndersenM. H.ReselandJ. E.VeierødM. B.AnderssenS. A.JacobsD. R.JrUrdalP.JanssonJ.-O.DrevonC. A. (2007). Effects of long-term exercise and diet intervention on plasma adipokine concentrations. The American Journal of Clinical Nutrition, 86(5), 1293–1301. https://doi.org/10.1093/ajcn/86.5.1293
49.
Salehi-AbargoueiA.IzadiV.AzadbakhtL. (2015). The effect of low calorie diet on adiponectin concentration: A systematic review and meta-analysis. Hormone and Metabolic Research, 47(08), 549–555. https://doi.org/10.1055/s-0035-1549878
50.
ShoelsonS. E.LeeJ.GoldfineA. B. (2006). Inflammation and insulin resistance. The Journal of Clinical Investigation, 116(7), 1793–1801. https://doi.org/10.1172/JCI29069
51.
SixtS.BeerS.BlüherM.KorffN.PeschelT.SonnabendM.TeupserD.ThieryJ.AdamsV.SchulerG.NiebauerJ. (2010). Long-but not short-term multifactorial intervention with focus on exercise training improves coronary endothelial dysfunction in diabetes mellitus type 2 and coronary artery disease. European Heart Journal, 31(1), 112–119. https://doi.org/10.1093/eurheartj/ehp398
52.
SmartN. A.WaldronM.IsmailH.GiallauriaF.VigoritoC.CornelissenV.DiebergG. (2015). Validation of a new tool for the assessment of study quality and reporting in exercise training studies: TESTEX. International Journal of Evidence-Based Healthcare, 13(1), 9–18. https://doi.org/10.1097/XEB.0000000000000020
53.
SokolovskaJ.OstrovskaK.PahirkoL.VarblaneG.KrilatihaK.CirulnieksA.FolkmaneI.PiragsV.ValeinisJ.KlavinaA.SelavoL. (2020). Impact of interval walking training managed through smart mobile devices on albuminuria and leptin/adiponectin ratio in patients with type 2 diabetes. Physiological Reports, 8(13), e14506. https://doi.org/10.14814/phy2.14506
54.
VafaeimaneshJ.ParhamM.NorouziS.HamednasimiP.BagherzadehM. (2018). Insulin resistance and coronary artery disease in non-diabetic patients: Is there any correlation?Caspian journal of internal medicine, 9(2), 121. https://doi.org/10.22088/cjim.9.2.121
55.
WuY.-T.HwangC.-L.ChenC.-N.ChuangL.-M. (2011). Home-based exercise for middle-aged Chinese at diabetic risk: A randomized controlled trial. Preventive Medicine, 52(5), 337–343. https://doi.org/10.1016/j.ypmed.2011.02.018
56.
YangD.YangY.LiY.HanR. (2020). Physical exercise as therapy for type 2 diabetes mellitus: From mechanism to orientation. Annals of Nutrition & Metabolism, 74(4), 313–321. https://doi.org/10.1159/000500110
57.
YuN.RuanY.GaoX.SunJ. (2017). Systematic review and meta-analysis of randomized, controlled trials on the effect of exercise on serum leptin and adiponectin in overweight and obese individuals. Hormone and Metabolic Research, 49(03), 164–173. https://doi.org/10.1055/s-0042-121605
58.
ZhangH.TongT. K.QiuW.ZhangX.ZhouS.LiuY.HeY. (2017). Comparable effects of high-intensity interval training and prolonged continuous exercise training on abdominal visceral fat reduction in obese young women. Journal of Diabetes Research, 2017, 5071740. https://doi.org/10.1155/2017/5071740
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
