Resistance Training and Cardiometabolic Health

Blood Pressure Clinical Trial

Official title:

Resistance Training and Cardiometabolic Health

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03325933
• Other study ID #: STUDY00006617
• Status: Terminated
• Phase: N/A
• Start date: September 21, 2017
• Est. completion date: August 31, 2020

Study information

• Verified date: April 2021
• Source: Arizona State University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will investigate the relationship between resistance training load and repetitions on cardiometabolic outcomes. The primary objective of this clinical trial is to determine whether high load or low load resistance exercise training affects arterial stiffness in overweight or obese men and women. Our secondary objectives are to investigate the effects of high and low load RT on vascular function, cardiac structure, and markers of insulin sensitivity. Finally, we are going to preliminarily explore the effects of resistance training on intestinal bacteria.

Description:

While it has been firmly established that aerobic exercise training is an effective modality for managing cardiometabolic disease risk, the influence of resistance training (RT) is not as well characterized. It is well established that RT improves muscular strength, size, cross sectional area, and bone mineral density. Alterations in muscle fiber type, glycolytic and oxidative enzyme profile, skeletal muscle proteins, and rates of protein synthesis also occur in response to RT and are obtained from skeletal muscle biopsies. Data from quasi-experimental studies suggest that moderate-to-high repetition RT with lower training loads may positively affect skeletal muscle proteins (Glucose Transporter Type 4 (GLUT4), Hexokinase 2 (HK2), and Adenylate kinase 2 (AK2) involved in insulin signaling in non-diabetic, obese men. However, data on high load, low rep RT on these variables is lacking. Thus, we will collect skeletal muscle biopsies to determine if changes in insulin signaling skeletal muscle proteins are present in response to both training with both high and low training loads. There is also a body of evidence suggesting that RT may improve VO2peak values in individuals with low baseline VO2peak values via a possible increase in capillary density, however, results are currently mixed. Low VO2peak values in overweight and obese individuals are positively associated with high risk of cardiovascular and all-cause mortality. Thus, we will measure VO2peak values to determine if (A) starting previously untrained obese individuals with RT can also improve VO2peak and (B) potential changes in VO2peak are load dependent. RT has also been reported to improve insulin sensitivity and central pressure. Additionally, aerobic exercise training may positively influence alterations in the intestinal microbiome, with no currently available evidence on the effects of RT, Although RT has been shown to be beneficial for improving arterial stiffness and insulin sensitivity, most of the available literature is based on protocols prescribing moderate-to-high repetitions and thus lower training loads. Thus, the effects of prescribing higher training loads on the aforementioned variables are not fully understood.

Increased arterial stiffness (as characterized by carotid-femoral pulse wave velocity (PWV) and augmentation index) is a clinical marker for cardiovascular disease and an independent risk factor for adverse cardiovascular events and all-cause mortality. Increased arterial stiffness has is positively associated with insulin resistance and type II diabetes. In the early stages of insulin resistance, peripheral insulin action, which occurs primarily in the skeletal muscle is impaired. This leads to a compensatory increase in insulin release in order to maintain glucose homeostasis, thus leading to hypertrophy of the pancreatic β cells. During the early stages of insulin resistance, fasting glucose levels will remain normal, with hyperglycemia manifesting in the later stages. Chronic hyperinsulinemia and hyperglycemia in turn cause increases in the renin-angiotensin aldosterone system as well expression of the angiotensin type I receptor in vascular tissue, thus stimulating VSMC proliferation, which leads to an increase in arterial stiffness. Chronic hyperglycemia and/or type II diabetes can lead to an increase in the production of advanced glycation end products (AGEs), which are proteins or lipids that become glycated due to exposure to glucose. Excessive production of AGEs can lead to an increase in collagen cross linking in the vascular walls, which thus leads to an increase in arterial stiffness.

Thus, it appears that increases in arterial stiffness occur due to perturbations in pulsatile shear and flow, which leads to abnormal turnover of scaffolding proteins, specifically excessive collagen production, and the proliferation of VSMCs, which results in a stiffer vasculature. This is exacerbated by the insulin resistant and/or hyperglycemic state due to an increase in local activity of the RAAS and expression of angiotensin I receptor activation in the vascular wall and an increase in age production, which leads to an increase in VSMCs and collagen cross-linking, respectively, thus further contributing to the development of a stiffer vasculature. These structural changes can have deleterious downstream consequences that include ischemic heart disease, myocardial infarction, and heart failure.

Current studies on the effects of RT on arterial stiffness have reported mixed results. It has been suggested that training with higher loads may cause greater increases in stiffness than training with lower loads due to greater acute elevations in blood pressure that occur with high load RT. Case control studies have reported that resistance trained young and middle aged non obese men demonstrated higher levels of arterial stiffness when compared to their aged-matched counterparts. Alternative cross-sectional studies reported that muscular strength was inversely related with arterial stiffness. Follow-up randomized control trials (RCT) investigated changes in arterial stiffness after several months of RT in non-obese, resistance training naïve adults. Improvements in central pressure, in the absence of changes in PWV, have been reported in non-diabetic obese adults after 12 weeks of RT but the study lacked an effective control group. Additionally, improvements in insulin sensitivity in non-diabetic obese males after 12 weeks of RT but was not a randomized controlled trial (RCT). Improvements in endothelial function has also been reported after six months of progressive RT that included both moderate and high training loads. This is significant because endothelial dysfunction is a downstream consequence of increased arterial stiffness, and thus an improvement in endothelial function, as measured by relative flow mediated dilation (%FMD), in response to RT is a reflects an improvement in vascular function, which is unlikely to occur in conjunction with an increase in vascular stiffness. To our knowledge, there are no current published RCTs on the effects of high load RT that have measured both arterial stiffness and endothelial function. This study will follow up on previous studies by comparing the effects of two distinct RT protocols (high load vs low load) on arterial stiffness as, measured by PWV and augmentation index, and endothelial function, as measured by %FMD, to a nonexercising control group.

A body of literature exists to suggest that morphological changes of the left ventricle take place in response to resistance training. Case control studies have reported that elite resistance trained athletes demonstrate evidence of left ventricular wall thickening. The increase in left ventricular wall thickness is referred to as concentric hypertrophy, which occurs in response to a chronic increase in afterload. This occurs in the presence of increased arterial stiffness, uncontrolled hypertension, and aortic stenosis, all of which can lead to heart failure (HF). RT induced concentric hypertrophy appears to be a physiological training adaptation, similar to the eccentric hypertrophy that takes place in response to aerobic training, and thus does not appear to be deleterious. Furthermore, current RCTs on the effects of RT on morphological changes of the LV suggest that this adaptation does not always occur or may occur in response to specific training volumes, frequencies, intensities, and/or over a longer training duration. Since the main outcome of this study is arterial stiffness, which is a precursor for concentric hypertrophy of the LV, we will also measure left ventricular wall thickness to see if A) morphological changes in the LV take place and B) if LV morphological changes are influenced by training load.

Thus, it appears that moderate training loads are shown to improve insulin sensitivity in obese individuals. This is significant because insulin resistance is a precursor to increases in arterial stiffness. However, the effects of training with higher loads on insulin sensitivity is a current gap in the literature. It has been previously proposed that high load RT may reduce arterial compliance and/or lead to concentric hypertrophy of the left ventricular walls. However, current evidence suggests that both moderate and high training loads improve endothelial function, without negatively affecting the left ventricular wall. Since endothelial dysfunction is a negative downstream consequence of an increase in arterial stiffness, it is unlikely that it would improve in conjunction with an increase in stiffness. Thus, this study will be the first to measure all of these variables to determine if and how they are influenced by training load.

The intestinal human microbiome is a recent target of interest due to its role in metabolic disease risk. Current evidence reports a link between cardiometabolic diseases and changes in the intestinal microbiota. The effects of exercise training on changes in the intestinal microbiome is also currently under investigation. Evidence in rat models currently suggest that voluntary and controlled aerobic exercise training is associated with favorable changes in the gut microbiome. However, human studies on the effects of exercise on the intestinal microbiome are currently lacking. .

The purpose of this study is to investigate the effects and potential differences between high load and low load RT on arterial stiffness. Based on the above described gaps in the literature the current study will serve as a follow up RCT to previous studies and will further explore the link between RT, arterial stiffness, and insulin sensitivity. From an exploratory stand-point we will examine changes if any in the gut microbiome following resistance training versus control. The proposed study will serve as a follow up RCT to investigate the differences between high load and low load RT on markers of arterial stiffness and insulin sensitivity. This study will also serve as the first RCT to investigate the long-term effects of RT in the intestinal microbiome. Studies investigating the effects of high load/low repetition RT on cardiometabolic biomarkers are currently lacking, with the current body of literature focusing on the effects of moderate and low loads and high repetitions, with limited data on the effects of high load RT.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 62
• Est. completion date: August 31, 2020
• Est. primary completion date: August 31, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Male and female

• 18-55 years of age

• BMI 25-40

• No recent history of starting a structured exercise program or diet in the last 3 months

Exclusion Criteria:

• Current smoker and/or recreational drug user

• Answers "yes" to one or more questions on the Physical Activity Readiness Questionnaire

• Diagnosed diabetes, heart disease

• History of anabolic steroid use in the past six months

• Taking medications for treatment of diabetes, heart disease, and hypertension.

• Orthopedic or musculoskeletal contraindications to resistance training

• Unwilling to follow any aspect of the study protocol including blood sampling and weight training

Related Conditions & MeSH terms

• Blood Pressure
• Endothelial Dysfunction
• Hypersensitivity
• Insulin Resistance
• Insulin Sensitivity

Intervention

Other:
• High Load/Low Rep Resistance Training
Participants will be prescribed High Load/Low Rep resistance training.
• Low Load/High Rep Resistance Training
Participants will be prescribed Low Load/High Rep resistance training.

Locations

Country	Name	City	State
United States	Arizona State University	Phoenix	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Arizona State University

Country where clinical trial is conducted

United States, 

References & Publications (43)

Abdul-Ghani MA, DeFronzo RA. Pathophysiology of prediabetes. Curr Diab Rep. 2009 Jun;9(3):193-9. Review. — View Citation

Angadi SS, Mookadam F, Lee CD, Tucker WJ, Haykowsky MJ, Gaesser GA. High-intensity interval training vs. moderate-intensity continuous exercise training in heart failure with preserved ejection fraction: a pilot study. J Appl Physiol (1985). 2015 Sep 15;119(6):753-8. doi: 10.1152/japplphysiol.00518.2014. Epub 2014 Sep 4. — View Citation

Ashor AW, Lara J, Siervo M, Celis-Morales C, Mathers JC. Effects of exercise modalities on arterial stiffness and wave reflection: a systematic review and meta-analysis of randomized controlled trials. PLoS One. 2014 Oct 15;9(10):e110034. doi: 10.1371/journal.pone.0110034. eCollection 2014. Review. — View Citation

Bertovic DA, Waddell TK, Gatzka CD, Cameron JD, Dart AM, Kingwell BA. Muscular strength training is associated with low arterial compliance and high pulse pressure. Hypertension. 1999 Jun;33(6):1385-91. — View Citation

Clarke SF, Murphy EF, O'Sullivan O, Lucey AJ, Humphreys M, Hogan A, Hayes P, O'Reilly M, Jeffery IB, Wood-Martin R, Kerins DM, Quigley E, Ross RP, O'Toole PW, Molloy MG, Falvey E, Shanahan F, Cotter PD. Exercise and associated dietary extremes impact on gut microbial diversity. Gut. 2014 Dec;63(12):1913-20. doi: 10.1136/gutjnl-2013-306541. Epub 2014 Jun 9. — View Citation

Cohen ND, Dunstan DW, Robinson C, Vulikh E, Zimmet PZ, Shaw JE. Improved endothelial function following a 14-month resistance exercise training program in adults with type 2 diabetes. Diabetes Res Clin Pract. 2008 Mar;79(3):405-11. Epub 2007 Nov 19. — View Citation

Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, Deanfield J, Drexler H, Gerhard-Herman M, Herrington D, Vallance P, Vita J, Vogel R; International Brachial Artery Reactivity Task Force. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol. 2002 Jan 16;39(2):257-65. Erratum in: J Am Coll Cardiol 2002 Mar 20;39(6):1082. — View Citation

Cortez-Cooper MY, Anton MM, Devan AE, Neidre DB, Cook JN, Tanaka H. The effects of strength training on central arterial compliance in middle-aged and older adults. Eur J Cardiovasc Prev Rehabil. 2008 Apr;15(2):149-55. doi: 10.1097/HJR.0b013e3282f02fe2. — View Citation

Croymans DM, Krell SL, Oh CS, Katiraie M, Lam CY, Harris RA, Roberts CK. Effects of resistance training on central blood pressure in obese young men. J Hum Hypertens. 2014 Mar;28(3):157-64. doi: 10.1038/jhh.2013.81. Epub 2013 Sep 5. — View Citation

Croymans DM, Paparisto E, Lee MM, Brandt N, Le BK, Lohan D, Lee CC, Roberts CK. Resistance training improves indices of muscle insulin sensitivity and ß-cell function in overweight/obese, sedentary young men. J Appl Physiol (1985). 2013 Nov 1;115(9):1245-53. doi: 10.1152/japplphysiol.00485.2013. Epub 2013 Aug 22. — View Citation

Davis CC, Ellis TJ, Amesur AK, Hewett TE, Di Stasi S. IMPROVEMENTS IN KNEE EXTENSION STRENGTH ARE ASSOCIATED WITH IMPROVEMENTS IN SELF-REPORTED HIP FUNCTION FOLLOWING ARTHROSCOPY FOR FEMOROACETABULAR IMPINGEMENT SYNDROME. Int J Sports Phys Ther. 2016 Dec;11(7):1065-1075. — View Citation

Dickinson JM, Volpi E, Rasmussen BB. Exercise and nutrition to target protein synthesis impairments in aging skeletal muscle. Exerc Sport Sci Rev. 2013 Oct;41(4):216-23. doi: 10.1097/JES.0b013e3182a4e699. Review. — View Citation

Fahs CA, Heffernan KS, Ranadive S, Jae SY, Fernhall B. Muscular strength is inversely associated with aortic stiffness in young men. Med Sci Sports Exerc. 2010 Sep;42(9):1619-24. doi: 10.1249/MSS.0b013e3181d8d834. — View Citation

Fleck SJ, Kraemer WJ. Resistance Training: Physiological Responses and Adaptations (Part 2 of 4). Phys Sportsmed. 1988 Apr;16(4):108-24. doi: 10.1080/00913847.1988.11709485. — View Citation

Gaesser GA, Tucker WJ, Jarrett CL, Angadi SS. Fitness versus Fatness: Which Influences Health and Mortality Risk the Most? Curr Sports Med Rep. 2015 Jul-Aug;14(4):327-32. doi: 10.1249/JSR.0000000000000170. — View Citation

Hellsten Y, Nyberg M. Cardiovascular Adaptations to Exercise Training. Compr Physiol. 2015 Dec 15;6(1):1-32. doi: 10.1002/cphy.c140080. Review. — View Citation

Julia M, Dupeyron A, Laffont I, Parisaux JM, Lemoine F, Bousquet PJ, Hérisson C. Reproducibility of isokinetic peak torque assessments of the hip flexor and extensor muscles. Ann Phys Rehabil Med. 2010 Jun;53(5):293-305. doi: 10.1016/j.rehab.2010.05.002. Epub 2010 Jun 22. English, French. — View Citation

Kawano H, Tanimoto M, Yamamoto K, Sanada K, Gando Y, Tabata I, Higuchi M, Miyachi M. Resistance training in men is associated with increased arterial stiffness and blood pressure but does not adversely affect endothelial function as measured by arterial reactivity to the cold pressor test. Exp Physiol. 2008 Feb;93(2):296-302. Epub 2007 Oct 2. — View Citation

Micklesfield LK, Goedecke JH, Punyanitya M, Wilson KE, Kelly TL. Dual-energy X-ray performs as well as clinical computed tomography for the measurement of visceral fat. Obesity (Silver Spring). 2012 May;20(5):1109-14. doi: 10.1038/oby.2011.367. Epub 2012 Jan 12. — View Citation

Mihl C, Dassen WR, Kuipers H. Cardiac remodelling: concentric versus eccentric hypertrophy in strength and endurance athletes. Neth Heart J. 2008 Apr;16(4):129-33. — View Citation

Mitchell GF, Hwang SJ, Vasan RS, Larson MG, Pencina MJ, Hamburg NM, Vita JA, Levy D, Benjamin EJ. Arterial stiffness and cardiovascular events: the Framingham Heart Study. Circulation. 2010 Feb 2;121(4):505-11. doi: 10.1161/CIRCULATIONAHA.109.886655. Epub 2010 Jan 18. — View Citation

Miyachi M, Donato AJ, Yamamoto K, Takahashi K, Gates PE, Moreau KL, Tanaka H. Greater age-related reductions in central arterial compliance in resistance-trained men. Hypertension. 2003 Jan;41(1):130-5. — View Citation

Miyachi M, Kawano H, Sugawara J, Takahashi K, Hayashi K, Yamazaki K, Tabata I, Tanaka H. Unfavorable effects of resistance training on central arterial compliance: a randomized intervention study. Circulation. 2004 Nov 2;110(18):2858-63. Epub 2004 Oct 18. — View Citation

Miyachi M. Effects of resistance training on arterial stiffness: a meta-analysis. Br J Sports Med. 2013 Apr;47(6):393-6. doi: 10.1136/bjsports-2012-090488. Epub 2012 Jan 20. Review. — View Citation

Nagueh SF, Smiseth OA, Appleton CP, Byrd BF 3rd, Dokainish H, Edvardsen T, Flachskampf FA, Gillebert TC, Klein AL, Lancellotti P, Marino P, Oh JK, Alexandru Popescu B, Waggoner AD; Houston, Texas; Oslo, Norway; Phoenix, Arizona; Nashville, Tennessee; Hamilton, Ontario, Canada; Uppsala, Sweden; Ghent and Liège, Belgium; Cleveland, Ohio; Novara, Italy; Rochester, Minnesota; Bucharest, Romania; and St. Louis, Missouri. Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2016 Dec;17(12):1321-1360. Epub 2016 Jul 15. Review. — View Citation

O'Sullivan O, Cronin O, Clarke SF, Murphy EF, Molloy MG, Shanahan F, Cotter PD. Exercise and the microbiota. Gut Microbes. 2015;6(2):131-6. doi: 10.1080/19490976.2015.1011875. Epub 2015 Mar 24. — View Citation

Ohnishi H, Saitoh S, Takagi S, Ohata J, Isobe T, Kikuchi Y, Takeuchi H, Shimamoto K. Pulse wave velocity as an indicator of atherosclerosis in impaired fasting glucose: the Tanno and Sobetsu study. Diabetes Care. 2003 Feb;26(2):437-40. — View Citation

Okamoto T, Masuhara M, Ikuta K. Effect of low-intensity resistance training on arterial function. Eur J Appl Physiol. 2011 May;111(5):743-8. doi: 10.1007/s00421-010-1702-5. Epub 2010 Oct 24. — View Citation

Okamoto T, Masuhara M, Ikuta K. Effects of muscle contraction timing during resistance training on vascular function. J Hum Hypertens. 2009 Jul;23(7):470-8. doi: 10.1038/jhh.2008.152. Epub 2008 Dec 18. — View Citation

Okamoto T, Masuhara M, Ikuta K. Upper but not lower limb resistance training increases arterial stiffness in humans. Eur J Appl Physiol. 2009 Sep;107(2):127-34. doi: 10.1007/s00421-009-1110-x. Epub 2009 Jun 17. — View Citation

Rakobowchuk M, McGowan CL, de Groot PC, Bruinsma D, Hartman JW, Phillips SM, MacDonald MJ. Effect of whole body resistance training on arterial compliance in young men. Exp Physiol. 2005 Jul;90(4):645-51. Epub 2005 Apr 22. — View Citation

Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988 Dec;37(12):1595-607. Review. — View Citation

Safar ME, Czernichow S, Blacher J. Obesity, arterial stiffness, and cardiovascular risk. J Am Soc Nephrol. 2006 Apr;17(4 Suppl 2):S109-11. Review. — View Citation

Schram MT, Henry RM, van Dijk RA, Kostense PJ, Dekker JM, Nijpels G, Heine RJ, Bouter LM, Westerhof N, Stehouwer CD. Increased central artery stiffness in impaired glucose metabolism and type 2 diabetes: the Hoorn Study. Hypertension. 2004 Feb;43(2):176-81. Epub 2003 Dec 29. — View Citation

Spence AL, Carter HH, Naylor LH, Green DJ. A prospective randomized longitudinal study involving 6 months of endurance or resistance exercise. Conduit artery adaptation in humans. J Physiol. 2013 Mar 1;591(5):1265-75. doi: 10.1113/jphysiol.2012.247387. Epub 2012 Dec 17. — View Citation

Spence AL, Naylor LH, Carter HH, Buck CL, Dembo L, Murray CP, Watson P, Oxborough D, George KP, Green DJ. A prospective randomised longitudinal MRI study of left ventricular adaptation to endurance and resistance exercise training in humans. J Physiol. 2011 Nov 15;589(Pt 22):5443-52. doi: 10.1113/jphysiol.2011.217125. Epub 2011 Oct 3. — View Citation

Strasser B, Arvandi M, Pasha EP, Haley AP, Stanforth P, Tanaka H. Abdominal obesity is associated with arterial stiffness in middle-aged adults. Nutr Metab Cardiovasc Dis. 2015 May;25(5):495-502. doi: 10.1016/j.numecd.2015.01.002. Epub 2015 Jan 28. — View Citation

Tinken TM, Thijssen DH, Black MA, Cable NT, Green DJ. Time course of change in vasodilator function and capacity in response to exercise training in humans. J Physiol. 2008 Oct 15;586(20):5003-12. doi: 10.1113/jphysiol.2008.158014. Epub 2008 Aug 28. — View Citation

Vlachopoulos C, Aznaouridis K, Stefanadis C. Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis. J Am Coll Cardiol. 2010 Mar 30;55(13):1318-27. doi: 10.1016/j.jacc.2009.10.061. Review. — View Citation

Wildman RP, Mackey RH, Bostom A, Thompson T, Sutton-Tyrrell K. Measures of obesity are associated with vascular stiffness in young and older adults. Hypertension. 2003 Oct;42(4):468-73. Epub 2003 Sep 2. — View Citation

Yang Q, Cogswell ME, Flanders WD, Hong Y, Zhang Z, Loustalot F, Gillespie C, Merritt R, Hu FB. Trends in cardiovascular health metrics and associations with all-cause and CVD mortality among US adults. JAMA. 2012 Mar 28;307(12):1273-83. doi: 10.1001/jama.2012.339. Epub 2012 Mar 16. — View Citation

Yoshizawa M, Maeda S, Miyaki A, Misono M, Saito Y, Tanabe K, Kuno S, Ajisaka R. Effect of 12 weeks of moderate-intensity resistance training on arterial stiffness: a randomised controlled trial in women aged 32-59 years. Br J Sports Med. 2009 Aug;43(8):615-8. doi: 10.1136/bjsm.2008.052126. Epub 2008 Oct 16. — View Citation

Zieman SJ, Melenovsky V, Kass DA. Mechanisms, pathophysiology, and therapy of arterial stiffness. Arterioscler Thromb Vasc Biol. 2005 May;25(5):932-43. Epub 2005 Feb 24. Review. — View Citation

* Note: There are 43 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Maximal Oxygen Consumption	Measured via VO2peak testing using an integrated metabolic system.	Change from Baseline VO2peak at 12 weeks
Primary	Arterial Stiffness	Measured via pulse wave velocity	Change from Baseline Pulse Wave Velocity at 12 weeks
Secondary	Insulin Sensitivity	Measured via oral glucose tolerance testing (OGTT)	Change from Baseline Matsuda Index at 12 weeks
Secondary	Endothelial Function	Measured via flow mediated dilation (FMD)	Change from Baseline %FMD at 12 weeks
Secondary	Cardiac echocardiography	Measured using ultrasound	Changes in systolic and diastolic parameters from baseline to 12 weeks
Secondary	Isokinetic Strength	Measured via dynamometry	Change from Baseline isokinetic strength at 12 weeks
Secondary	Isometric Strength	Measured via dynamometry	Change from Baseline Isometric strength at 12 weeks
Secondary	Hexokinase	Measured via skeletal muscle biopsies	Change from Baseline in insulin signalling proteins at 12 weeks
Secondary	Insulin signaling proteins	Measured via skeletal muscle biopsies	Change from Baseline in insulin signaling proteins at 12 weeks
Secondary	Muscle Volume	Measured via ultrasonography	Change from Baseline Muscle Volume at 12 weeks
Secondary	Body Composition	Measured via Dual X-Ray Absorptiometry (DXA)	Change from Baseline body composition at 12 weeks
Secondary	Central Systolic Pressure	Measured via Pulse Wave Analysis	Change from Baseline Central Systolic Pressure at 12 weeks
Secondary	Central Diastolic Pressure	Measured via Pulse Wave Analysis	Change from Baseline Central Systolic Pressure at 12 weeks