Cardiorespiratory fitness in individuals with type 2 diabetes mellitus: a systematic review and meta-analysis

Macedo, Aline Chagastelles Pinto de; Schaan, Camila Wohlgemuth; Bock, Patricia Martins; Pinto, Mariana Brutto de; Botton, Cintia Ehlers; Umpierre, Daniel; Schaan, Beatriz D.

doi:10.20945/2359-4292-2023-0040

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Archives of Endocrinology and Metabolism

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Original Article • Arch. Endocrinol. Metab. 67 (5) • 2023 • https://doi.org/10.20945/2359-4292-2023-0040 copy

Cardiorespiratory fitness in individuals with type 2 diabetes mellitus: a systematic review and meta-analysis

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Objective:

To conduct a systematic review and meta-analysis assessing the cardiorespiratory fitness (CRF) among individuals with and without type 2 diabetes

Materials and methods:

The current review was registered in PROSPERO under the number CRD42018082718. MEDLINE, EMBASE, and Cochrane Library databases were searched from inception through February 2022. Eligibility criteria consisted of observational or interventional studies that evaluated CRF through cardiopulmonary exercise testing or six-minute walk test in individuals with type 2 diabetes compared with individuals without type 2 diabetes. For data extraction, we used baseline CRF assessments of randomized clinical trials or follow-up CRF assessments in observational studies. We performed a meta-analysis using maximal oxygen consumption (VO₂max), and distance walked in the 6MWT as primary outcomes. They were extracted and expressed as mean differences (MDs) and 95% CIs between treatment and comparator groups. The meta-analysis was conducted using Review Manager (RevMan) software.

Results:

Out of 8,347 studies retrieved, 77 were included. Compared with individuals without type 2 diabetes, individuals with diabetes achieved a lower VO₂max (−5.84 mL.kg⁻¹.min⁻¹, 95% CI −6.93, −4.76 mL.kg⁻¹.min⁻¹, p = <0.0001; I² = 91%, p for heterogeneity < 0.0001), and a smaller distance walked in 6MWT (−93.30 meters, 95% CI −141.2, −45.4 meters, p > 0.0001; I²: 94%, p for heterogeneity < 0.0001).

Conclusion:

Type 2 diabetes was associated with lower cardiorespiratory fitness, as observed by lower VO₂max on maximal tests, and smaller distance walked in 6MWT, however the quality of studies was low.

Keywords
Exercise tolerance; review; meta-analysis; diabetes mellitus

Study	Sample size (n)		Sex	Diabetes duration (years)	Matched groups	Medication	Ergometer	Protocol	VO₂ peak/max
Study	DM	C	Sex	Diabetes duration (years)	Matched groups	Medication	Ergometer	Protocol	VO₂ peak/max
Andrade-Mayorga and cols. (2020) (⁷⁹79 Andrade-Mayorga O, Mancilla R, Díaz E, Alvarez C. Heart Rate During an Exercise Test and Acute High-intensity Interval Training in Type 2 Diabetes. Int J Sports Med. 2020 Jun;41(6):365-72. doi: 10.1055/a-1015-0591. https://doi.org/10.1055/a-1015-0591... )	13	32	M/W	NR	NR	NR	Cycle ergometer	Modified Astrand	VO₂ peak
Baldi and cols. (2003) (²⁴24 Baldi JC, Aoina JL, Oxenham HC, Bagg W, Doughty RN. Reduced exercise arteriovenous O2 difference in Type 2 diabetes. J Appl Physiol (1985). 2003 Mar;94(3):1033-8. doi: 10.1152/japplphysiol.00879.2002. https://doi.org/10.1152/japplphysiol.008... )	11	12	M/W	5.4 ± 3.1	Age, BMI, and habitual physical activity	Antidiabetics and antihypertensives	Cycle ergometer	Initial workloads 25 or 50 Wt, increments 15-25 W	VO₂ max
Baldi and cols. (2006) (⁸⁰80 Baldi JC, Aoina JL, Whalley GA, Carrick-Ranson G, Walsh HA, O'Shaughnessy H, et al. The effect of type 2 diabetes on diastolic function. Med Sci Sports Exerc. 2006 Aug;38(8):1384-8. doi: 10.1249/01.mss.0000228954.90591.95. https://doi.org/10.1249/01.mss.000022895... )	13	15	M/W	5.4 ± 3.1	Age and BMI	Antidiabetics and antihypertensives	Cycle ergometer	Initial workloads 25 or 50 Wt, increments 15-25 W	VO₂ max
Bauer and cols. (2007) (⁶⁰60 Bauer TA, Reusch JE, Levi M, Regensteiner JG. Skeletal muscle deoxygenation after the onset of moderate exercise suggests slowed microvascular blood flow kinetics in type 2 diabetes. Diabetes Care. 2007 Nov;30(11):2880-5. doi: 10.2337/dc07-0843. https://doi.org/10.2337/dc07-0843... )	11	11	M/W	NR	No	NR	Cycle ergometer	Incremental 10-20 Wt/min	VO₂ peak
Baynard and cols. (2005) (⁵⁰50 Baynard T, Franklin RM, Goulopoulou S, Carhart R Jr, Kanaley JA. Effect of a single vs multiple bouts of exercise on glucose control in women with type 2 diabetes. Metabolism. 2005 Aug;54(8):989-94. doi: 10.1016/j.metabol.2005.02.015. https://doi.org/10.1016/j.metabol.2005.0... )	9	6	W	NR	Age	Antidiabetics	Treadmill	Starting at 2.5 mph, increased 2%mph 3.5mph reached	VO₂ peak
Bergman and cols. (2015) (³¹31 Bergman BC, Brozinick JT, Strauss A, Bacon S, Kerege A, Bui HH, et al. Serum sphingolipids: relationships to insulin sensitivity and changes with exercise in humans. Am J Physiol Endocrinol Metab. 2015 Aug 15;309(4):E398-408. doi: 10.1152/ajpendo.00134.2015. https://doi.org/10.1152/ajpendo.00134.20... )	15	14	M/W	NR	No	Antidiabetics	Cycle ergometer	Workload adjusted to maintain determined intensity	VO₂ max
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Durrer and cols. (2017) (⁸²82 Durrer C, Francois M, Neudorf H, Little JP. Acute high-intensity interval exercise reduces human monocyte Toll-like receptor 2 expression in type 2 diabetes. Am J Physiol Regul Integr Comp Physiol. 2017 Apr 1;312(4):R529-R538. doi: 10.1152/ajpregu.00348.2016. https://doi.org/10.1152/ajpregu.00348.20... )	10	9	M/W	NR	Age	Antidiabetics	Cycle ergometer	Ramp protocol (15 Wt/min at 50 rpm)	VO₂ peak
Fluckey and cols. (1994) (⁸³83 Fluckey JD, Hickey MS, Brambrink JK, Hart KK, Alexander K, Craig BW. Effects of resistance exercise on glucose tolerance in normal and glucose-intolerant subjects. J Appl Physiol (1985). 1994 Sep;77(3):1087-92. doi: 10.1152/jappl.1994.77.3.1087. https://doi.org/10.1152/jappl.1994.77.3.... )	10	3	M/W	2.8 ± NR	Age	NR	Treadmill	Modified Naughton-Balke	VO₂ max
Fujii and cols. (2017) (⁸⁴84 Fujii N, Meade RD, Akbari P, Louie JC, Alexander LM, Boulay P, et al. No effect of ascorbate on cutaneous vasodilation and sweating in older men and those with type 2 diabetes exercising in the heat. Physiol Rep. 2017 Apr;5(7):e13238. doi: 10.14814/phy2.13238. https://doi.org/10.14814/phy2.13238... )	12	12	M	7.5 ± 4.4	No	Antidiabetics, insulin, statins, and antihypertensives	Cycle ergometer	NR	VO₂ peak
Green and cols. (2003) (²⁷27 Green DJ, Walsh JH, Maiorana A, Best MJ, Taylor RR, O'Driscoll JG. Exercise-induced improvement in endothelial dysfunction is not mediated by changes in CV risk factors: pooled analysis of diverse patient populations. Am J Physiol Heart Circ Physiol. 2003 Dec;285(6):H2679-87. doi: 10.1152/ajpheart.00519.2003. https://doi.org/10.1152/ajpheart.00519.2... )	15	16	NR	NR	No	Antidiabetics, insulin, statins, and antihypertensives	Cycle ergometer	Initial workload 20 and 60 Wt, increased 20-25 Wt increments each 3 min	VO₂ peak
Groen and cols. (2019) (⁸⁵85 Groen MB, Knudsen TA, Finsen SH, Pedersen BK, Hellsten Y, Mortensen SP. Reduced skeletal-muscle perfusion and impaired ATP release during hypoxia and exercise in individuals with type 2 diabetes. Diabetologia. 2019 Mar;62(3):485-93. doi: 10.1007/s00125-018-4790-0. https://doi.org/10.1007/s00125-018-4790-... )	9	8	M/W	8 ± 3	No	Antidiabetics	Cycle ergometer	Initial workload 50-100 Wt, increases 25 Wt each 1min	VO₂ peak
Gulsin and cols. (2020) (⁸⁶86 Gulsin GS, Swarbrick DJ, Athithan L, Brady EM, Henson J, Baldry E, et al. Effects of Low-Energy Diet or Exercise on Cardiovascular Function in Working-Age Adults With Type 2 Diabetes: A Prospective, Randomized, Open-Label, Blinded End Point Trial. Diabetes Care. 2020 Jun;43(6):1300-10. doi: 10.2337/dc20-0129. https://doi.org/10.2337/dc20-0129... )	87	36	M/W	4.7 ± 3.8	No	Antidiabetics, insulin, and antihypertensives	Cycle ergometer	Incremental	VO₂ peak
Hansen and cols. (2014) (²⁸28 Hansen D, Dendale P. Modifiable predictors of chronotropic incompetence in male patients with type 2 diabetes. J Cardiopulm Rehabil Prev. 2014 May-Jun;34(3):202-7. doi: 10.1097/HCR.0000000000000039. https://doi.org/10.1097/HCR.000000000000... )	33	18	M	5.2 ± 4.4	No	Antidiabetics, insulin, statins, and antihypertensives	Cycle ergometer	Initial workload 45 Wt, increments 45 Wt each 3-min.	VO₂ peak
Hernández-Alvarez and cols. (2010) (9)	12	7	M/W	2.5 ± 1.9	Age and BMI	Antidiabetics and insulin	Treadmill	Stepwise	VO₂ max
Holton and cols. (2003) (³⁶36 Holton DR, Colberg SR, Nunnold T, Parson HK, Vinik AI. The effect of an aerobic exercise training program on quality of life in type 2 diabetes. Diabetes Educ. 2003 Sep-Oct;29(5):837-46. doi: 10.1177/014572170302900513. https://doi.org/10.1177/0145721703029005... )	9	10	M/W	NR	Age, gender, and BMI	NR	Cycle ergometer	Initial workload 0 Wt or 20 Wt, 20 Wt increment every 3 min., cadence 50 rpm.	VO₂ peak
Huebschmann and cols. (2009) (³⁷37 Huebschmann AG, Reis EN, Emsermann C, Dickinson LM, Reusch JE, Bauer TA, et al. Women with type 2 diabetes perceive harder effort during exercise than nondiabetic women. Appl Physiol Nutr Metab. 2009 Oct;34(5):851-7. doi: 10.1139/H09-074. https://doi.org/10.1139/H09-074... )	13	26	W	3.9 ± 3.9	No	Antidiabetics	Cycle ergometer	Initial workload 0 Wt, increments 10 Wt/min., cadence at 60 rpm	VO₂ peak
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Jae and cols. (2016) (²³23 Jae SY, Franklin BA, Choo J, Yoon ES, Choi YH, Park WH. Fitness, Body Habitus, and the Risk of Incident Type 2 Diabetes Mellitus in Korean Men. Am J Cardiol. 2016 Feb 15;117(4):585-9. doi: 10.1016/j.amjcard.2015.11.046. https://doi.org/10.1016/j.amjcard.2015.1... )	170	3600	M	NR	No	NR	Treadmill	Bruce	VO₂ peak
Karavelioglu and cols. (2013) (⁸⁷87 Karavelioglu Y, Karapinar H, Gul İ, Kucukdurmaz Z, Yilmaz A, Akpek M, et al. Blood pressure response to exercise is exaggerated in normotensive diabetic patients. Blood Press. 2013 Feb;22(1):21-6. doi: 10.3109/08037051.2012.701045. https://doi.org/10.3109/08037051.2012.70... )	67	68	M/W	5.2 ± 4.1	Age and gender	Antidiabetics and insulin	Treadmill	Bruce	VO₂ peak
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Kennedy and cols. (1999) (²²22 Kennedy JW, Hirshman MF, Gervino EV, Ocel JV, Forse RA, Hoenig SJ, et al. Acute exercise induces GLUT4 translocation in skeletal muscle of normal human subjects and subjects with type 2 diabetes. Diabetes. 1999 May;48(5):1192-7. doi: 10.2337/diabetes.48.5.1192. https://doi.org/10.2337/diabetes.48.5.11... )	5	5	M/W	NR	No	Antidiabetics	Cycle ergometer	Incremental (2-min. stages)	VO₂ max
Lalande and cols. (2008) (³⁹39 Lalande S, Gusso S, Hofman PL, Baldi JC. Reduced leg blood flow during submaximal exercise in type 2 diabetes. Med Sci Sports Exerc. 2008 Apr;40(4):612-7. doi: 10.1249/MSS.0b013e318161aa99. https://doi.org/10.1249/MSS.0b013e318161... )	8	11	M	5.0 ± 8.4	Weight and habitual activity level	Antidiabetics	Cycle ergometer	Initial workload 40 Wt, increases 15 Wt/min.	VO₂ max
Larsen and cols. (2009) (⁵¹51 Larsen S, Ara I, Rabøl R, Andersen JL, Boushel R, Dela F, et al. Are substrate use during exercise and mitochondrial respiratory capacity decreased in arm and leg muscle in type 2 diabetes? Diabetologia. 2009 Jul;52(7):1400-8. doi: 10.1007/s00125-009-1353-4. https://doi.org/10.1007/s00125-009-1353-... )	8	15	M	4.0 ± 2.8	Age and BMI	Antidiabetics	Cycle ergometer	NR	VO₂ max
Mac Ananey and cols. (2011) (⁴⁰40 Mac Ananey O, Malone J, Warmington S, O'Shea D, Green S, Egaña M. Cardiac output is not related to the slowed O2 uptake kinetics in type 2 diabetes. Med Sci Sports Exerc. 2011 Jun;43(6):935-42. doi: 10.1249/MSS.0b013e3182061cdb. https://doi.org/10.1249/MSS.0b013e318206... )	9	20	W	1-5years	No	Antidiabetics, insulin, statins, and antihypertensives	Cycle ergometer	Initial workload 40 Wt, increases 20 Wt each 3 min., cadence 60 rpm	VO₂ peak
Madsen and cols. (2015) (⁴¹41 Madsen SM, Thorup AC, Overgaard K, Jeppesen PB. High Intensity Interval Training Improves Glycaemic Control and Pancreatic β Cell Function of Type 2 Diabetes Patients. PLoS One. 2015 Aug 10;10(8):e0133286. doi: 10.1371/journal.pone.0133286. https://doi.org/10.1371/journal.pone.013... )	10	13	M/W	NR	Age, height, and weight	Antidiabetics, statins, and antihypertensives	Cycle ergometer	Initial workload 80-100 Wt, increases 15 W/min., cadence 60 rpm.	VO₂ max
Martin and cols. (1995) (¹⁰10 Martin IK, Katz A, Wahren J. Splanchnic and muscle metabolism during exercise in NIDDM patients. Am J Physiol. 1995 Sep;269(3 Pt 1):E583-90. doi: 10.1152/ajpendo.1995.269.3.E583. https://doi.org/10.1152/ajpendo.1995.269... )	8	7	M	4.7 ± 3.6	Age and weight	Antidiabetics	Cycle ergometer	NR	VO₂ max
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Meneilly and cols. (1996) (⁸⁸88 Meneilly GS, Elliott T, Tessier D, Hards L, Tildesley H. NIDDM in the elderly. Diabetes Care. 1996 Dec;19(12):1320-5. doi: 10.2337/diacare.19.12.1320. https://doi.org/10.2337/diacare.19.12.13... )	33	25	M/W	3.0 ± 5.7	Age and weight	Antidiabetics and antihypertensives	Cycle ergometer	Workload increases 16.6 Wt each 30s.	VO₂ max
Meneilly and cols. (1999) (⁸⁹89 Meneilly GS, Elliott T. Metabolic alterations in middle-aged and elderly obese patients with type 2 diabetes. Diabetes Care. 1999 Jan;22(1):112-8. doi: 10.2337/diacare.22.1.112. https://doi.org/10.2337/diacare.22.1.112... )	34	19	M/W	3.0 ± 4.3	Age and weight	Antidiabetics and antihypertensives	Cycle ergometer	Workload increases 16.6 Wt each 30s.	VO₂ max
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Oberbach and cols. (2006) (⁶⁷67 Oberbach A, Bossenz Y, Lehmann S, Niebauer J, Adams V, Paschke R, et al. Altered fiber distribution and fiber-specific glycolytic and oxidative enzyme activity in skeletal muscle of patients with type 2 diabetes. Diabetes Care. 2006 Apr;29(4):895-900. doi: 10.2337/diacare.29.04.06.dc05-1854. https://doi.org/10.2337/diacare.29.04.06... )	10	15	M/W	NR	Age and BMI	NR	Cycle ergometer	Graded	VO₂ max
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O'Connor and cols. (2015) (⁵³53 O'Connor E, Green S, Kiely C, O'Shea D, Egana M. Differential effects of age and type 2 diabetes on dynamic vs. peak response of pulmonary oxygen uptake during exercise. J Appl Physiol (1985). 2015 Apr 15;118(8):1031-9. doi: 10.1152/japplphysiol.01040.2014. https://doi.org/10.1152/japplphysiol.010... )	33	21	M	3.9 ± 2.5	Age	Antidiabetics	Cycle ergometer	Incremental	VO₂ peak
Pinna and cols. (2021) (⁹⁰90 Pinna V, Doneddu A, Roberto S, Magnani S, Ghiani G, Mulliri G, et al. Combined mental task and metaboreflex impair cerebral oxygenation in patients with type 2 diabetes mellitus. Am J Physiol Regul Integr Comp Physiol. 2021 Apr 1;320(4):R488-99. doi: 10.1152/ajpregu.00288.2020. https://doi.org/10.1152/ajpregu.00288.20... )	13	13	M/W	At least 1 year	Age and sex	Antidiabetics	Cycle ergometer	Incremental	VO₂ max
Regensteiner and cols. (1995) (⁵⁵55 Regensteiner JG, Sippel J, McFarling ET, Wolfel EE, Hiatt WR. Effects of non-insulin-dependent diabetes on oxygen consumption during treadmill exercise. Med Sci Sports Exerc. 1995 Jun;27(6):875-81.)	10	10	M/W	6.7 ± 6.8	Age, gender, weight, and physical activity	Antidiabetics	Treadmill	Modified Naughton	VO₂ max
Regensteiner and cols. (1998) (⁵⁶56 Regensteiner JG, Bauer TA, Reusch JE, Brandenburg SL, Sippel JM, Vogelsong AM, et al. Abnormal oxygen uptake kinetic responses in women with type II diabetes mellitus. J Appl Physiol (1985). 1998 Jul;85(1):310-7. doi: 10.1152/jappl.1998.85.1.310. https://doi.org/10.1152/jappl.1998.85.1.... )	10	20	W	3.0 ± 2.0	Age, gender, weight, and physical activity	Antidiabetics	Cycle ergometer	Workload increases 10 Wt/min.	VO₂ max
Regensteiner and cols. (2009) (⁵⁷57 Regensteiner JG, Bauer TA, Reusch JE, Quaife RA, Chen MY, Smith SC, et al. Cardiac dysfunction during exercise in uncomplicated type 2 diabetes. Med Sci Sports Exerc. 2009 May;41(5):977-84. doi: 10.1249/MSS.0b013e3181942051. https://doi.org/10.1249/MSS.0b013e318194... )	10	10	W	3.6 ± 0	No	Antidiabetics	Cycle ergometer	Workload increases 10 Wt/min.	VO₂ peak
Regensteiner and cols. (2015) (⁴³43 Regensteiner JG, Bauer TA, Huebschmann AG, Herlache L, Weinberger HD, Wolfel EE, et al. Sex differences in the effects of type 2 diabetes on exercise performance. Med Sci Sports Exerc. 2015 Jan;47(1):58-65. doi: 10.1249/MSS.0000000000000371. https://doi.org/10.1249/MSS.000000000000... )	29	34	M/W	3.1 ± 2.8	No	Antidiabetics and statins	Cycle ergometer	Workload increases 10-25 Wt/min.	VO₂ peak
Ribeiro and cols. (2008) (¹¹11 Ribeiro IC, Iborra RT, Neves MQ, Lottenberg SA, Charf AM, Nunes VS, et al. HDL atheroprotection by aerobic exercise training in type 2 diabetes mellitus. Med Sci Sports Exerc. 2008 May;40(5):779-86. doi: 10.1249/MSS.0b013e3181632d2d. https://doi.org/10.1249/MSS.0b013e318163... )	21	11	M/W	8.6 ± 8.2	No	Antidiabetics, statins, and antihypertensives	Cycle ergometer	Workload increases 10-15 Wt/min.	VO₂ max
Scalzo and cols. (2018) (⁴⁴44 Scalzo RL, Bauer TA, Harrall K, Moreau K, Ozemek C, Herlache L, et al. Acute vitamin C improves cardiac function, not exercise capacity, in adults with type 2 diabetes. Diabetol Metab Syndr. 2018 Feb 14;10:7. doi: 10.1186/s13098-018-0306-9. https://doi.org/10.1186/s13098-018-0306-... )	31	21	M/W	NR	BMI	Antidiabetics	Cycle ergometer	Workload increases 10-20 Wt/min.	VO₂ peak
Scalzo and cols. (2022) (⁴⁹49 Scalzo RL, Schauer IE, Rafferty D, Knaub LA, Kvaratskhelia N, Johnson TK, et al. Single-leg exercise training augments in vivo skeletal muscle oxidative flux and vascular content and function in adults with type 2 diabetes. J Physiol. 2022 Feb;600(4):963-78. doi: 10.1113/JP280603. https://doi.org/10.1113/JP280603... )	19	22	M/W	NR	No	Antidiabetics	Cycle ergometer	Incremental	VO₂ peak
Scheede-Bergdahl and cols. (2009) (⁹¹91 Scheede-Bergdahl C, Benee Olsen D, Reving D, Boushel R, Dela F. Cardiovascular disease markers in type 2 diabetes: the effects of a moderate home-based exercise training programme. Diab Vasc Dis Res. 2009 Oct;6(4):291-6. doi: 10.1177/1479164109341689. https://doi.org/10.1177/1479164109341689... )	12	9	M	5.1 ± 3.8	Age, weight, and body fat	Antidiabetics, statins, and antihypertensives	Cycle ergometer	NR	VO₂ peak
Scheede-Bergdahl and cols. (2014) (⁴⁵45 Scheede-Bergdahl C, Bergdahl A, Schjerling P, Qvortrup K, Koskinen SO, Dela F. Exercise-induced regulation of matrix metalloproteinases in the skeletal muscle of subjects with type 2 diabetes. Diab Vasc Dis Res. 2014 Sep;11(5):324-34. doi: 10.1177/1479164114535943. https://doi.org/10.1177/1479164114535943... )	12	9	M	5.1 ± 3.8	No	Antidiabetics, statins and antihypertensives	Cycle ergometer	NR	VO₂ peak
Schneider and cols. (1984) (⁴⁶46 Schneider SH, Amorosa LF, Khachadurian AK, Ruderman NB. Studies on the mechanism of improved glucose control during regular exercise in type 2 (non-insulin-dependent) diabetes. Diabetologia. 1984 May;26(5):355-60. doi: 10.1007/BF00266036. https://doi.org/10.1007/BF00266036... )	20	11	M	NR	Age, gender, and weight	None	Cycle ergometer	Workload increments of 25 Wt, each 3 min.	VO₂ max
Schneider and cols. (1988) (³⁰30 Schneider SH, Kim HC, Khachadurian AK, Ruderman NB. Impaired fibrinolytic response to exercise in type II diabetes: effects of exercise and physical training. Metabolism. 1988 Oct;37(10):924-9. doi: 10.1016/0026-0495(88)90148-5. https://doi.org/10.1016/0026-0495(88)901... )	16	9	M/W	NR	Age, gender, and weight	None	Cycle ergometer	NR	VO₂ max
Schreuder and cols. (2014) (⁶⁸68 Schreuder TH, Maessen MF, Tack CJ, Thijssen DH, Hopman MT. Life-long physical activity restores metabolic and cardiovascular function in type 2 diabetes. Eur J Appl Physiol. 2014 Mar;114(3):619-27. doi: 10.1007/s00421-013-2794-5. https://doi.org/10.1007/s00421-013-2794-... )	27	9	M	NR	Age, gender, and weight	Antidiabetics, insulin, statins, and antihypertensives	Cycle ergometer	Initial workload 10 Wt, increases 10 Wt/min., cadence 60-80 rpm	VO₂ max
Segerstrom and cols. (2011) (⁶⁹69 Segerström ÅB, Elgzyri T, Eriksson KF, Groop L, Thorsson O, Wollmer P. Exercise capacity in relation to body fat distribution and muscle fibre distribution in elderly male subjects with impaired glucose tolerance, type 2 diabetes and matched controls. Diabetes Res Clin Pract. 2011 Oct;94(1):57-63. doi: 10.1016/j.diabres.2011.05.022. https://doi.org/10.1016/j.diabres.2011.0... )	39	53	M	NR	Age	Antidiabetics and insulin	Cycle ergometer	Initial workload 30 Wt, increases 15 Wt/min., cadence 60 rpm	VO₂ peak
Simões and cols. (2010) (¹³13 Simões HG, Moreira SR, Moffatt RJ, Campbell CS. Methods to identify the anaerobic threshold for type-2 diabetic and non-diabetic subjects. Arq Bras Cardiol. 2010 Jan;94(1):71-8. doi: 10.1590/s0066-782x2010000100012. https://doi.org/10.1590/s0066-782x201000... )	10	10	NR	NR	No	Antidiabetics	Cycle ergometer	Initial workload 15 Wt, increases 15 Wt each 3 min.	VO₂ max
Simões and cols. (2013) (⁴⁷47 Simões HG, Asano RY, Sales MM, Browne RA, Arsa G, Motta-Santos D, et al. Type 2 diabetes elicits lower nitric oxide, bradykinin concentration and kallikrein activity together with higher DesArg(9)-BK and reduced post-exercise hypotension compared to non-diabetic condition. PLoS One. 2013 Nov 12;8(11):e80348. doi: 10.1371/journal.pone.0080348. https://doi.org/10.1371/journal.pone.008... )	10	10	M/W	6.0 ±1.1	Age, weight, and BMI	Antidiabetics and antihypertensives	Cycle ergometer	Initial workload 15 Wt, increases 15 Wt each 3 min.	VO₂ peak
Suk and cols. (2015) (⁹²92 Suk MH, Moon YJ, Park SW, Park CY, Shin YA. Maximal Fat Oxidation Rate during Exercise in Korean Women with Type 2 Diabetes Mellitus. Diabetes Metab J. 2015 Aug;39(4):328-34. doi: 10.4093/dmj.2015.39.4.328. https://doi.org/10.4093/dmj.2015.39.4.32... )	12	12	W	7.8 ± 2.1	BMI	None	Cycle ergometer	Initial workload 20% of Wmax, increments 30-60% Wmax each 3 min.	VO₂ max
Tadic and cols. (2021) (⁶⁵65 Tadic M, Suzic-Lazic J, Vukomanovic V, Cuspidi C, Ilic S, Celic V. Functional capacity and left ventricular diastolic function in patients with type 2 diabetes. Acta Diabetol. 2021 Jan;58(1):107-13. doi: 10.1007/s00592-020-01600-x. https://doi.org/10.1007/s00592-020-01600... )	30	55	M/W	NR	No	Antidiabetics and insulin	Treadmill	Modified Bruce	VO₂ peak
Tobin and cols. (2008) (⁹³93 Tobin LW, Kiens B, Galbo H. The effect of exercise on postprandial lipidemia in type 2 diabetic patients. Eur J Appl Physiol. 2008 Feb;102(3):361-70. doi: 10.1007/s00421-007-0587-4. https://doi.org/10.1007/s00421-007-0587-... )	8	7	M	4.9 ± 3.3	Age, gender, and BMI	Antidiabetics	Cycle ergometer	Graded	VO₂ max
Van Tienen and cols. (2012) (⁶¹61 van Tienen FH, Praet SF, de Feyter HM, van den Broek NM, Lindsey PJ, Schoonderwoerd KG, et al. Physical activity is the key determinant of skeletal muscle mitochondrial function in type 2 diabetes. J Clin Endocrinol Metab. 2012 Sep;97(9):3261-9. doi: 10.1210/jc.2011-3454. https://doi.org/10.1210/jc.2011-3454... )	8	12	M	12.5 ± 7.7	Age, weight, and BMI	NR	Cycle ergometer	Incremental	VO₂ peak
Vind and cols. (2011) (⁹⁴94 Vind BF, Pehmøller C, Treebak JT, Birk JB, Hey-Mogensen M, Beck-Nielsen H, et al. Impaired insulin-induced site-specific phosphorylation of TBC1 domain family, member 4 (TBC1D4) in skeletal muscle of type 2 diabetes patients is restored by endurance exercise-training. Diabetologia. 2011 Jan;54(1):157-67. doi: 10.1007/s00125-010-1924-4. https://doi.org/10.1007/s00125-010-1924-... )	13	13	M	3.7 ± 2.8	Age and BMI	Antidiabetics and antihypertensives	Cycle ergometer	Initial workload 60-70% HRmax, increases 30 Wt each 3 min., cadence of 60 rpm	VO₂ peak
Vukomanovic and cols. (2020) (⁹⁵95 Vukomanovic V, Suzic-Lazic J, Celic V, Cuspidi C, Grassi G, Galderisi M, et al. Is there association between left atrial function and functional capacity in patients with uncomplicated type 2 diabetes? Int J Cardiovasc Imaging. 2020 Jan;36(1):15-22. doi: 10.1007/s10554-019-01680-z. https://doi.org/10.1007/s10554-019-01680... )	64	72	M/W	NR	No	NR	Treadmill	Modified Bruce	VO₂ peak
Vukomanovic and cols. (2019) (⁹⁶96 Vukomanovic V, Suzic-Lazic J, Celic V, Cuspidi C, Petrovic T, Grassi G, et al. The relationship between functional capacity and left ventricular strain in patients with uncomplicated type 2 diabetes. J Hypertens. 2019 Sep;37(9):1871-6. doi: 10.1097/HJH.0000000000002125. https://doi.org/10.1097/HJH.000000000000... )	70	80	M/W	3 (1-5)	No	Antidiabetics and insulin	Treadmill	Modified Bruce	VO₂ peak
Vukomanovic and cols. (2019) (⁹⁷97 Vukomanovic V, Suzic-Lazic J, Celic V, Cuspidi C, Petrovic T, Ilic S, et al. Association between functional capacity and heart rate variability in patients with uncomplicated type 2 diabetes. Blood Press. 2019 Jun;28(3):184-90. doi: 10.1080/08037051.2019.1586431. https://doi.org/10.1080/08037051.2019.15... )	53	62	M/W	NR	No	Antidiabetics	Treadmill	Modified Bruce	VO₂ peak
Wilkerson and cols. (2011) (⁴⁸48 Wilkerson DP, Poole DC, Jones AM, Fulford J, Mawson DM, Ball CI, et al. Older type 2 diabetic males do not exhibit abnormal pulmonary oxygen uptake and muscle oxygen utilization dynamics during submaximal cycling exercise. Am J Physiol Regul Integr Comp Physiol. 2011 Mar;300(3):R685-92. doi: 10.1152/ajpregu.00479.2010. https://doi.org/10.1152/ajpregu.00479.20... )	12	12	M	<5 years	Age and weight	Antidiabetics and antihypertensives	Cycle ergometer	Ramp (15 Wt/min.)	VO₂ max
Wilmot and cols. (2014) (¹⁴14 Wilmot EG, Leggate M, Khan JN, Yates T, Gorely T, Bodicoat DH, et al. Type 2 diabetes mellitus and obesity in young adults: the extreme phenotype with early cardiovascular dysfunction. Diabet Med. 2014 Jul;31(7):794-8. doi: 10.1111/dme.12431. https://doi.org/10.1111/dme.12431... )	20	20	M/W	4.7 ± 4.0	Age	Antidiabetics and antihypertensives	Cycle ergometer	NR	VO₂ max
Wilson and cols. (2017) (⁵⁸58 Wilson GA, Wilkins GT, Cotter JD, Lamberts RR, Lal S, Baldi JC. Impaired ventricular filling limits cardiac reserve during submaximal exercise in people with type 2 diabetes. Cardiovasc Diabetol. 2017 Dec 19;16(1):160. doi: 10.1186/s12933-017-0644-1. https://doi.org/10.1186/s12933-017-0644-... )	17	16	M/W	8.3 ± 9.5	Age, gender, BMI, physical activity	Antidiabetics and insulin	Cycle ergometer	Initial workload 25-50 Wt, increases 25-50 Wt each 1min	VO₂ peak
Yu and cols. (2016) (⁷⁰70 Yu TY, Jee JH, Bae JC, Hong WJ, Jin SM, Kim JH, et al. Delayed heart rate recovery after exercise as a risk factor of incident type 2 diabetes mellitus after adjusting for glycometabolic parameters in men. Int J Cardiol. 2016 Oct 15;221:17-22. doi: 10.1016/j.ijcard.2016.06.149. https://doi.org/10.1016/j.ijcard.2016.06... )	180	1594	NR	NR	Age and gender	NR	Treadmill	Bruce	VO₂ peak
Zbinden-Foncea and cols. (2013) (⁶³63 Zbinden-Foncea H, van Loon LJ, Raymackers JM, Francaux M, Deldicque L. Contribution of nonesterified fatty acids to mitogen-activated protein kinase activation in human skeletal muscle during endurance exercise. Int J Sport Nutr Exerc Metab. 2013 Jun;23(3):201-9. doi: 10.1123/ijsnem.23.3.201. https://doi.org/10.1123/ijsnem.23.3.201... )	10	5	NR	NR	No	Antidiabetics	Cycle ergometer	Incremental	VO₂ max
Zierath and cols. (1996) (⁷²72 Zierath JR, He L, Gumà A, Odegoard Wahlström E, Klip A, Wallberg-Henriksson H. Insulin action on glucose transport and plasma membrane GLUT4 content in skeletal muscle from patients with NIDDM. Diabetologia. 1996 Oct;39(10):1180-9. doi: 10.1007/BF02658504. https://doi.org/10.1007/BF02658504... )	7	7	M	5 ± 5.2	Age and BMI	Antidiabetics	Cycle ergometer	Initial workload 50 Wt, increases 50 Wt each 5 min.	VO₂ max

Study	Sample Size		Sex	Diabetes duration (years)	Medications	Protocol	Estim.VO₂ (mL/kg/min)
Study	DM	C	Sex	Diabetes duration (years)	Medications	Protocol	DM	C
Awotidebe and cols. (2014) (⁹⁸98 Awotidebe TO, Adedoyin RA, Yusuf AO, Mbada CE, Opiyo R, Maseko FC. Comparative functional exercise capacity of patients with type 2-diabetes and healthy controls: a case control study. Pan Afr Med J. 2014 Nov 7;19:257. doi: 10.11604/pamj.2014.19.257.4798. https://doi.org/10.11604/pamj.2014.19.25... )	35	35	M/W	NR	NR	ATS	10.2 ± 1.5	10.9 ± 1.3
Awotidebe and cols. (2016) (⁹⁹99 Awotidebe TO, Ativie RN, Oke KI, Akindele MO, Adedoyin RA, Olaogun MO, et al. Relationships among exercise capacity, dynamic balance and gait characteristics of Nigerian patients with type-2 diabetes: an indication for fall prevention. J Exerc Rehabil. 2016 Dec 31;12(6):581-8. doi: 10.12965/jer.1632706.353. https://doi.org/10.12965/jer.1632706.353... )	125	125	M/W	<5 years	Antidiabetics	ATS	7.6 ± 0.6	9.6 ± 0.6
Heberle and cols. (2021) (⁶⁴64 Heberle I, Tonelli DC, Benedetti TB, Delevatti RS. Similar functional capacity and handgrip strength of trained elderly women with and without type 2 diabetes mellitus: A cross-sectional study. Complement Ther Clin Pract. 2021 May;43:101318. doi: 10.1016/j.ctcp.2021.101318. https://doi.org/10.1016/j.ctcp.2021.1013... )	13	13	W	11.92 ± 10.77	Antidiabetics and statins	NR	NR	NR
IJzerman and cols. (2012) (⁵⁹59 IJzerman TH, Schaper NC, Melai T, Meijer K, Willems PJ, Savelberg HH. Lower extremity muscle strength is reduced in people with type 2 diabetes, with and without polyneuropathy, and is associated with impaired mobility and reduced quality of life. Diabetes Res Clin Pract. 2012 Mar;95(3):345-51. doi: 10.1016/j.diabres.2011.10.026. https://doi.org/10.1016/j.diabres.2011.1... )	137	19	M/W	NR	NR	NR	NR	NR
Ozdirenc and cols. (2003) (⁶²62 Ozdirenç M, Biberoğlu S, Ozcan A. Evaluation of physical fitness in patients with Type 2 diabetes mellitus. Diabetes Res Clin Pract. 2003 Jun;60(3):171-6. doi: 10.1016/s0168-8227(03)00064-0. https://doi.org/10.1016/s0168-8227(03)00... )	30	30	M/W	7.1 ± 6.2	Antidiabetics and insulin	NR	14.6 ± 2.9	17.0 ± 1.8

PubMed
#1(“Diabetes Mellitus, Type 2”[title] OR “Diabetes Mellitus”[title] OR “Diabetes Mellitus, Noninsulin-Dependent”[title] OR “Diabetes Mellitus, Ketosis-Resistant”[title] OR “Diabetes Mellitus, Ketosis Resistant”[title] OR “Ketosis-Resistant Diabetes Mellitus”[title] OR “Diabetes Mellitus, Non Insulin Dependent”[title] OR “Diabetes Mellitus, Non-Insulin-Dependent”[title] OR “Non-Insulin-Dependent Diabetes Mellitus”[title] OR “Diabetes Mellitus, Stable”[title] OR “Stable Diabetes Mellitus”[title] OR “Diabetes Mellitus, Type II”[title] OR “NIDDM”[title] OR “Diabetes Mellitus, Noninsulin Dependent”[title] OR “Diabetes Mellitus, Maturity-Onset”[title] OR “Diabetes Mellitus, Maturity Onset”[title] OR “Maturity-Onset Diabetes Mellitus”[title] OR “Maturity Onset Diabetes Mellitus”[title] OR “MODY”[title] OR “Diabetes Mellitus, Slow-Onset”[title] OR “Diabetes Mellitus, Slow Onset”[title] OR “Slow-Onset Diabetes Mellitus”[title] OR “Type 2 Diabetes Mellitus”[title] OR “Noninsulin-Dependent Diabetes Mellitus”[title] OR “Noninsulin Dependent Diabetes Mellitus”[title] OR “Maturity-Onset Diabetes”[title] OR “Diabetes, Maturity-Onset”[title] OR “Maturity Onset Diabetes”[title] OR “Type 2 Diabetes”[title] OR “Diabetes, Type 2”[title] OR “Diabetes Mellitus, Adult-Onset”[title] OR “Adult-Onset Diabetes Mellitus”[title] OR “Diabetes Mellitus, Adult Onset”[title] OR “DM2”[title] OR “diabetics”[tiab])
#2(“Exercise Therapy”[Mesh] OR “Resistance Training”[Mesh] OR “Muscle Stretching Exercises”[Mesh] OR “Exercise Movement Techniques”[Mesh] OR “Exercise”[Mesh] OR “Cardiorespiratory Fitness”[Mesh] OR “evaluation cardiopulmonary” OR “Ergospirometry” OR “Functional capacity” OR “Tests of exercise endurance” OR “six-minute walk” OR “Exercise testing” OR “stress testing” OR “Oxygen Consumption” OR “Cardiopulmonary exercise testing” OR “Exercises” OR “Physical Exercise” OR “Physical Exercise” OR “Physical Exercises” OR “Isometric Exercises” OR “Isometric Exercise” OR “Warm Up Exercise” OR “Aerobic Exercises” OR “Aerobic Exercise” OR “Exercise Therapies” OR “Pilates Training” OR “Strength Training” OR “Strengthening Programs” OR “Weight Lifting Exercise Program” OR “Weight Bearing Strengthening Program” OR “Weight Bearing Exercise Program” OR “Effort test” OR “Fitness, Cardiorespiratory” OR “peak oxygen uptake” OR “maximal oxygen consumption” OR “peak oxygen consumption”)
#1 AND #2
Embase
#1 ‘non insulin dependent diabetes mellitus’/exp
#2‘exercise’/exp OR ‘exercise tests’/exp OR ‘cardiorespiratory fistness’/exp OR cardiopulmonary exercise test’/exp OR ‘ergoespirometry’/exp OR ‘six-minute walk test’/exp OR ‘maximal oxygen uptake’/exp OR functional status assessment’/exp or ‘treadmill exercise test’/exp
#3‘non diabetic patient’/exp OR ‘control group’/exp OR ‘normal human’/exp
#1 AND #2 AND #3
Cochrane
“exercise”
AND
“diabetes mellitus, type 2”

Study	Year	Selection	Comparability	Outcome	Total score
Andrade-Mayorga and cols. (⁷⁹79 Andrade-Mayorga O, Mancilla R, Díaz E, Alvarez C. Heart Rate During an Exercise Test and Acute High-intensity Interval Training in Type 2 Diabetes. Int J Sports Med. 2020 Jun;41(6):365-72. doi: 10.1055/a-1015-0591. https://doi.org/10.1055/a-1015-0591... )	2020	1	0	2	3
Awotidebe and cols. (⁹⁸98 Awotidebe TO, Adedoyin RA, Yusuf AO, Mbada CE, Opiyo R, Maseko FC. Comparative functional exercise capacity of patients with type 2-diabetes and healthy controls: a case control study. Pan Afr Med J. 2014 Nov 7;19:257. doi: 10.11604/pamj.2014.19.257.4798. https://doi.org/10.11604/pamj.2014.19.25... )	2014	1	1	1	3
Awotidebe and cols. (⁹⁹99 Awotidebe TO, Ativie RN, Oke KI, Akindele MO, Adedoyin RA, Olaogun MO, et al. Relationships among exercise capacity, dynamic balance and gait characteristics of Nigerian patients with type-2 diabetes: an indication for fall prevention. J Exerc Rehabil. 2016 Dec 31;12(6):581-8. doi: 10.12965/jer.1632706.353. https://doi.org/10.12965/jer.1632706.353... )	2016	2	0	1	3
Baldi and cols. (²⁴24 Baldi JC, Aoina JL, Oxenham HC, Bagg W, Doughty RN. Reduced exercise arteriovenous O2 difference in Type 2 diabetes. J Appl Physiol (1985). 2003 Mar;94(3):1033-8. doi: 10.1152/japplphysiol.00879.2002. https://doi.org/10.1152/japplphysiol.008... )	2003	0	0	1	1
Baldi and cols. (⁸⁰80 Baldi JC, Aoina JL, Whalley GA, Carrick-Ranson G, Walsh HA, O'Shaughnessy H, et al. The effect of type 2 diabetes on diastolic function. Med Sci Sports Exerc. 2006 Aug;38(8):1384-8. doi: 10.1249/01.mss.0000228954.90591.95. https://doi.org/10.1249/01.mss.000022895... )	2006	1	0	0	1
Bauer and cols. (⁶⁰60 Bauer TA, Reusch JE, Levi M, Regensteiner JG. Skeletal muscle deoxygenation after the onset of moderate exercise suggests slowed microvascular blood flow kinetics in type 2 diabetes. Diabetes Care. 2007 Nov;30(11):2880-5. doi: 10.2337/dc07-0843. https://doi.org/10.2337/dc07-0843... )	2007	1	0	1	2
Baynard and cols. (⁵⁰50 Baynard T, Franklin RM, Goulopoulou S, Carhart R Jr, Kanaley JA. Effect of a single vs multiple bouts of exercise on glucose control in women with type 2 diabetes. Metabolism. 2005 Aug;54(8):989-94. doi: 10.1016/j.metabol.2005.02.015. https://doi.org/10.1016/j.metabol.2005.0... )	2005	1	0	1	2
Bergman and cols. (³¹31 Bergman BC, Brozinick JT, Strauss A, Bacon S, Kerege A, Bui HH, et al. Serum sphingolipids: relationships to insulin sensitivity and changes with exercise in humans. Am J Physiol Endocrinol Metab. 2015 Aug 15;309(4):E398-408. doi: 10.1152/ajpendo.00134.2015. https://doi.org/10.1152/ajpendo.00134.20... )	2015	0	0	1	1
Boon and cols. (³²32 Boon H, Blaak EE, Saris WH, Keizer HA, Wagenmakers AJ, van Loon LJ. Substrate source utilisation in long-term diagnosed type 2 diabetes patients at rest, and during exercise and subsequent recovery. Diabetologia. 2007 Jan;50(1):103-12. doi: 10.1007/s00125-006-0482-2. https://doi.org/10.1007/s00125-006-0482-... )	2007	1	0	1	2
Borghouts and cols. (¹²12 Borghouts LB, Wagenmakers AJ, Goyens PL, Keizer HA. Substrate utilization in non-obese Type II diabetic patients at rest and during exercise. Clin Sci (Lond). 2002 Dec;103(6):559-66. doi: 10.1042/cs1030559. https://doi.org/10.1042/cs1030559... )	2002	0	0	1	1
Brandenburg and cols. (³³33 Brandenburg SL, Reusch JE, Bauer TA, Jeffers BW, Hiatt WR, Regensteiner JG. Effects of exercise training on oxygen uptake kinetic responses in women with type 2 diabetes. Diabetes Care. 1999 Oct;22(10):1640-6. doi: 10.2337/diacare.22.10.1640. https://doi.org/10.2337/diacare.22.10.16... )	1999	2	2	0	4
Chance and cols. (⁸¹81 Chance WW, Rhee C, Yilmaz C, Dane DM, Pruneda ML, Raskin P, et al. Diminished alveolar microvascular reserves in type 2 diabetes reflect systemic microangiopathy. Diabetes Care. 2008 Aug;31(8):1596-601. doi: 10.2337/dc07-2323. https://doi.org/10.2337/dc07-2323... )	2008	0	1	0	1
Colberg and cols. (³⁵35 Colberg SR, Parson HK, Nunnold T, Holton DR, Swain DP, Vinik AI. Change in cutaneous perfusion following 10 weeks of aerobic training in Type 2 diabetes. J Diabetes Complications. 2005 Sep-Oct;19(5):276-83. doi: 10.1016/j.jdiacomp.2005.02.006. https://doi.org/10.1016/j.jdiacomp.2005.... )	2005	0	0	1	1
Colberg and cols. (³⁴34 Colberg SR, Parson HK, Nunnold T, Herriott MT, Vinik AI. Effect of an 8-week resistance training program on cutaneous perfusion in type 2 diabetes. Microvasc Res. 2006 Mar;71(2):121-7. doi: 10.1016/j.mvr.2005.11.005. https://doi.org/10.1016/j.mvr.2005.11.00... )	2006	0	0	1	1
Cusi and cols. (²⁵25 Cusi KJ, Pratipanawatr T, Koval J, Printz R, Ardehali H, Granner DK, et al. Exercise increases hexokinase II mRNA, but not activity in obesity and type 2 diabetes. Metabolism. 2001 May;50(5):602-6. doi: 10.1053/meta.2001.22568. https://doi.org/10.1053/meta.2001.22568... )	2001	0	0	0	0
Dela and cols. (²¹21 Dela F, Mikines KJ, Larsen JJ, Galbo H. Glucose clearance in aged trained skeletal muscle during maximal insulin with superimposed exercise. J Appl Physiol (1985). 1999 Dec;87(6):2059-67. doi: 10.1152/jappl.1999.87.6.2059. https://doi.org/10.1152/jappl.1999.87.6.... )	1999	0	0	0	0
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	N. of studies	VO₂
	N. of studies	MD	95% CI	p	I²
Overall results	72	−5.84	(−6.93; −4.76)	<0.001	91.0%
Men	22	−4.84	(−6.60; −3.08)	<0.001	82.6%
Women	7	−7.45	(−11.52; −3.39)	<0.001	93.9%

Covariates	N of obs.	Coefficient	95%IC	p	Adjusted R²
BMI	68	−0.4988	−0.94; −0.05	0.03	10.75%
Age	72	0.0005	−0.13; 0.13	0.99	−2.10%
HbA1c	62	−0.7480	−1.58; 0.08	0.08	4.48%
Duration of diabetes	40	0.1221	−0.49; 0.73	0.69	−4.21%

Sociedade Brasileira de Endocrinologia e Metabologia Rua Botucatu, 572 - Conjuntos 81/83, 04023-061 São Paulo SP Brasil, Tel: (55 11) 5575-0311 - São Paulo - SP - Brazil
E-mail: aem.editorial.office@endocrino.org.br

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[1] Correspondence to: Patricia Martins Bock, Laboratório de Atividade Física, Diabetes e Doença Cardiovascular (LADD), Centro de Pesquisa Clínica, Hospital de Clínicas de Porto Alegre Rua Ramiro Barcelos, 2.350 90035-003 – Porto Alegre, RS, Brasil. patriciabock74@gmail.com