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Published in: Diabetology & Metabolic Syndrome 1/2018

Open Access 01-12-2018 | Research

Acute vitamin C improves cardiac function, not exercise capacity, in adults with type 2 diabetes

Authors: Rebecca L. Scalzo, Timothy A. Bauer, Kylie Harrall, Kerrie Moreau, Cemal Ozemek, Leah Herlache, Shawna McMillin, Amy G. Huebschmann, Jennifer Dorosz, Jane E. B. Reusch, Judith G. Regensteiner

Published in: Diabetology & Metabolic Syndrome | Issue 1/2018

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Abstract

Background

People with type 2 diabetes (T2D) have impaired exercise capacity, even in the absence of complications, which is predictive of their increased cardiovascular mortality. Cardiovascular dysfunction is one potential cause of this exercise defect. Acute infusion of vitamin C has been separately shown to improve diastolic and endothelial function in prior studies. We hypothesized that acute vitamin C infusion would improve exercise capacity and that these improvements would be associated with improved cardiovascular function.

Methods

Adults with T2D (n = 31, 7 female, 24 male, body mass index (BMI): 31.5 ± 0.8 kg/m2) and BMI-similar healthy adults (n = 21, 11 female, 10 male, BMI: 30.4 ± 0.7 kg/m2) completed two randomly ordered visits: IV infusion of vitamin C (7.5 g) and a volume-matched saline infusion. During each visit peak oxygen uptake (VO2peak), brachial artery flow mediated dilation (FMD), reactive hyperemia (RH; plethysmography), and cardiac echocardiography were measured. General linear mixed models were utilized to assess the differences in all study variables.

Results

Acute vitamin C infusion improved diastolic function, assessed by lateral and septal E:E’ (P < 0.01), but did not change RH (P = 0.92), or VO2peak (P = 0.33) in any participants.

Conclusion

Acute vitamin C infusion improved diastolic function but did not change FMD, forearm reactive hyperemia, or peak exercise capacity. Future studies should further clarify the role of endothelial function as well as other possible physiological causes of exercise impairment in order to provide potential therapeutic targets.
Trial registration NCT00786019. Prospectively registered May 2008
Literature
1.
go back to reference Wei M, Gibbons LW, Kampert JB, Nichaman MZ, Blair SN. Low cardiorespiratory fitness and physical inactivity as predictors of mortality in men with type 2 diabetes. Ann Intern Med. 2000;132:605–11.CrossRefPubMed Wei M, Gibbons LW, Kampert JB, Nichaman MZ, Blair SN. Low cardiorespiratory fitness and physical inactivity as predictors of mortality in men with type 2 diabetes. Ann Intern Med. 2000;132:605–11.CrossRefPubMed
2.
go back to reference 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. 1998;85:310–7.CrossRefPubMed 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. 1998;85:310–7.CrossRefPubMed
3.
go back to reference Regensteiner JG, Bauer TA, Reusch JEB. Rosiglitazone improves exercise capacity in individuals with type 2 diabetes. Diabetes Care. 2005;28:2877–83.CrossRefPubMed Regensteiner JG, Bauer TA, Reusch JEB. Rosiglitazone improves exercise capacity in individuals with type 2 diabetes. Diabetes Care. 2005;28:2877–83.CrossRefPubMed
4.
go back to reference Regensteiner JG, Popylisen S, Bauer TA, Lindenfeld J, Gill E, Smith S, et al. Oral l-arginine and vitamins E and C improve endothelial function in women with type 2 diabetes. Vasc Med. 2003;8:169–75.CrossRefPubMed Regensteiner JG, Popylisen S, Bauer TA, Lindenfeld J, Gill E, Smith S, et al. Oral l-arginine and vitamins E and C improve endothelial function in women with type 2 diabetes. Vasc Med. 2003;8:169–75.CrossRefPubMed
5.
go back to reference Wei M, Kampert JB, Barlow CE, Nichaman MZ, Gibbons LW, Ralph S, Paffenbarger J, et al. Relationship between low cardiorespiratory fitness and mortality in normal-weight, overweight, and obese men. JAMA. 1999;282:1547–53.CrossRefPubMed Wei M, Kampert JB, Barlow CE, Nichaman MZ, Gibbons LW, Ralph S, Paffenbarger J, et al. Relationship between low cardiorespiratory fitness and mortality in normal-weight, overweight, and obese men. JAMA. 1999;282:1547–53.CrossRefPubMed
6.
go back to reference 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;47:58–65.CrossRefPubMedPubMedCentral 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;47:58–65.CrossRefPubMedPubMedCentral
7.
go back to reference 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;22:1640–6.CrossRefPubMed 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;22:1640–6.CrossRefPubMed
8.
go back to reference Bjornstad P, Truong U, Dorosz JL, Cree Green M, Baumgartner A, Coe G, et al. Cardiopulmonary dysfunction and adiponectin in adolescents with type 2 diabetes. J Am Heart Assoc. 2016;5:e002804.CrossRefPubMedPubMedCentral Bjornstad P, Truong U, Dorosz JL, Cree Green M, Baumgartner A, Coe G, et al. Cardiopulmonary dysfunction and adiponectin in adolescents with type 2 diabetes. J Am Heart Assoc. 2016;5:e002804.CrossRefPubMedPubMedCentral
9.
go back to reference Nadeau KJ, Zeitler PS, Bauer TA, Brown MS, Dorosz JL, Draznin B, et al. Insulin resistance in adolescents with type 2 diabetes is associated with impaired exercise capacity. J Clin Endocrinol Metab. 2009;94:3687–95.CrossRefPubMedPubMedCentral Nadeau KJ, Zeitler PS, Bauer TA, Brown MS, Dorosz JL, Draznin B, et al. Insulin resistance in adolescents with type 2 diabetes is associated with impaired exercise capacity. J Clin Endocrinol Metab. 2009;94:3687–95.CrossRefPubMedPubMedCentral
10.
go back to reference Bauer TA, Reusch JEB, 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;30:2880–5.CrossRefPubMed Bauer TA, Reusch JEB, 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;30:2880–5.CrossRefPubMed
11.
go back to reference Padilla DJ, McDonough P, Behnke BJ, Kano Y, Hageman KS, Musch TI, et al. Effects of type II diabetes on capillary hemodynamics in skeletal muscle. Am J Physiol Heart Circ Physiol. 2006;291:H2439–44.CrossRefPubMed Padilla DJ, McDonough P, Behnke BJ, Kano Y, Hageman KS, Musch TI, et al. Effects of type II diabetes on capillary hemodynamics in skeletal muscle. Am J Physiol Heart Circ Physiol. 2006;291:H2439–44.CrossRefPubMed
12.
go back to reference Mason McClatchey P, Bauer TA, Regensteiner JG, Schauer IE, Huebschmann AG, Reusch JEB. Dissociation of local and global skeletal muscle oxygen transport metrics in type 2 diabetes. J Diabetes Complications. 2017;31(8):1311–7.CrossRefPubMed Mason McClatchey P, Bauer TA, Regensteiner JG, Schauer IE, Huebschmann AG, Reusch JEB. Dissociation of local and global skeletal muscle oxygen transport metrics in type 2 diabetes. J Diabetes Complications. 2017;31(8):1311–7.CrossRefPubMed
13.
go back to reference Giam B, Chu PY, Kuruppu S, Smith AI, Horlock D, Kiriazis H, et al. N-Acetylcysteine attenuates the development of cardiac fibrosis and remodeling in a mouse model of heart failure. Physiol Rep. 2016;4:e12757.CrossRefPubMedPubMedCentral Giam B, Chu PY, Kuruppu S, Smith AI, Horlock D, Kiriazis H, et al. N-Acetylcysteine attenuates the development of cardiac fibrosis and remodeling in a mouse model of heart failure. Physiol Rep. 2016;4:e12757.CrossRefPubMedPubMedCentral
14.
go back to reference Silver MA, Langsjoen PH, Szabo S, Patil H, Zelinger A. Effect of atorvastatin on left ventricular diastolic function and ability of coenzyme Q10 to reverse that dysfunction. Am J Cardiol. 2004;94:1306–10.CrossRefPubMed Silver MA, Langsjoen PH, Szabo S, Patil H, Zelinger A. Effect of atorvastatin on left ventricular diastolic function and ability of coenzyme Q10 to reverse that dysfunction. Am J Cardiol. 2004;94:1306–10.CrossRefPubMed
15.
go back to reference Adarsh K, Kaur H, Mohan V. Coenzyme Q10(CoQ10) in isolated diastolic heart failure in hypertrophic cardiomyopathy (HCM). BioFactors. 2008;32:145–9.CrossRefPubMed Adarsh K, Kaur H, Mohan V. Coenzyme Q10(CoQ10) in isolated diastolic heart failure in hypertrophic cardiomyopathy (HCM). BioFactors. 2008;32:145–9.CrossRefPubMed
16.
go back to reference Ozemek C, Hildreth KL, Groves DW, Moreau KL. Acute ascorbic acid infusion increases left ventricular diastolic function in postmenopausal women. Maturitas. 2016;92:154–61.CrossRefPubMedPubMedCentral Ozemek C, Hildreth KL, Groves DW, Moreau KL. Acute ascorbic acid infusion increases left ventricular diastolic function in postmenopausal women. Maturitas. 2016;92:154–61.CrossRefPubMedPubMedCentral
17.
go back to reference Limberg JK, Harrell JW, Johansson RE, Eldridge MW, Proctor LT, Sebranek JJ, et al. Microvascular function in younger adults with obesity and metabolic syndrome: role of oxidative stress. Am J Physiol Heart Circ Physiol. 2013;305:H1230–7.CrossRefPubMedPubMedCentral Limberg JK, Harrell JW, Johansson RE, Eldridge MW, Proctor LT, Sebranek JJ, et al. Microvascular function in younger adults with obesity and metabolic syndrome: role of oxidative stress. Am J Physiol Heart Circ Physiol. 2013;305:H1230–7.CrossRefPubMedPubMedCentral
18.
go back to reference Richards JC, Crecelius AR, Larson DG, Dinenno FA. Acute ascorbic acid ingestion increases skeletal muscle blood flow and oxygen consumption via local vasodilation during graded handgrip exercise in older adults. Am J Physiol Heart Circ Physiol. 2015;309:H360–8.CrossRefPubMedPubMedCentral Richards JC, Crecelius AR, Larson DG, Dinenno FA. Acute ascorbic acid ingestion increases skeletal muscle blood flow and oxygen consumption via local vasodilation during graded handgrip exercise in older adults. Am J Physiol Heart Circ Physiol. 2015;309:H360–8.CrossRefPubMedPubMedCentral
19.
go back to reference Trinity JD, Wray DW, Witman MAH, Layec G, Barrett-O’Keefe Z, Ives SJ, et al. Ascorbic acid improves brachial artery vasodilation during progressive handgrip exercise in the elderly through a nitric oxide-mediated mechanism. Am J Physiol Heart Circ Physiol. 2016;310:H765–74.CrossRefPubMedPubMedCentral Trinity JD, Wray DW, Witman MAH, Layec G, Barrett-O’Keefe Z, Ives SJ, et al. Ascorbic acid improves brachial artery vasodilation during progressive handgrip exercise in the elderly through a nitric oxide-mediated mechanism. Am J Physiol Heart Circ Physiol. 2016;310:H765–74.CrossRefPubMedPubMedCentral
20.
go back to reference Sallis JF, Haskell WL, Wood PD, Fortmann SP, Rogers T, Blair SN, et al. Physical activity assessment methodology in the five-city project. Am J Epidemiol. 1985;121:91–106.CrossRefPubMed Sallis JF, Haskell WL, Wood PD, Fortmann SP, Rogers T, Blair SN, et al. Physical activity assessment methodology in the five-city project. Am J Epidemiol. 1985;121:91–106.CrossRefPubMed
21.
go back to reference Eskurza I, Monahan KD, Robinson JA. Effect of acute and chronic ascorbic acid on flow-mediated dilatation with sedentary and physically active human ageing. J Physiol (Lond.). 2004;556:315–24.CrossRef Eskurza I, Monahan KD, Robinson JA. Effect of acute and chronic ascorbic acid on flow-mediated dilatation with sedentary and physically active human ageing. J Physiol (Lond.). 2004;556:315–24.CrossRef
22.
go back to reference Moreau KL, DePaulis AR, Gavin KM, Seals DR. Oxidative stress contributes to chronic leg vasoconstriction in estrogen-deficient postmenopausal women. J Appl Physiol. 2006;102:890–5.CrossRefPubMed Moreau KL, DePaulis AR, Gavin KM, Seals DR. Oxidative stress contributes to chronic leg vasoconstriction in estrogen-deficient postmenopausal women. J Appl Physiol. 2006;102:890–5.CrossRefPubMed
23.
go back to reference Ting HH, Timimi FK, Boles KS, Creager SJ, Ganz P, Creager MA. Vitamin C improves endothelium-dependent vasodilation in patients with non-insulin-dependent diabetes mellitus. J Clin Invest. 1996;97:22–8.CrossRefPubMedPubMedCentral Ting HH, Timimi FK, Boles KS, Creager SJ, Ganz P, Creager MA. Vitamin C improves endothelium-dependent vasodilation in patients with non-insulin-dependent diabetes mellitus. J Clin Invest. 1996;97:22–8.CrossRefPubMedPubMedCentral
24.
go back to reference Scalzo RL, Moreau KL, Ozemek C, Herlache L, McMillin S, Gilligan S, et al. Exenatide improves diastolic function and attenuates arterial stiffness but does not alter exercise capacity in individuals with type 2 diabetes. J Diabetes Complications. 2017;31:449–55.CrossRefPubMed Scalzo RL, Moreau KL, Ozemek C, Herlache L, McMillin S, Gilligan S, et al. Exenatide improves diastolic function and attenuates arterial stiffness but does not alter exercise capacity in individuals with type 2 diabetes. J Diabetes Complications. 2017;31:449–55.CrossRefPubMed
25.
go back to reference Moreau KL, Deane KD, Meditz AL, Kohrt WM. Tumor necrosis factor-α inhibition improves endothelial function and decreases arterial stiffness in estrogen-deficient postmenopausal women. Atherosclerosis. 2013;230:390–6.CrossRefPubMed Moreau KL, Deane KD, Meditz AL, Kohrt WM. Tumor necrosis factor-α inhibition improves endothelial function and decreases arterial stiffness in estrogen-deficient postmenopausal women. Atherosclerosis. 2013;230:390–6.CrossRefPubMed
26.
go back to reference Corretti MC, Anderson TJ, Benjamin EJ. 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;39:257–65.CrossRefPubMed Corretti MC, Anderson TJ, Benjamin EJ. 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;39:257–65.CrossRefPubMed
27.
go back to reference Quiñones MA, Otto CM, Stoddard M, Waggoner A, Zoghbi WA, Doppler Quantification Task Force of the Nomenclature and Standards Committee of the American Society of Echocardiography. Recommendations for quantification of Doppler echocardiography: a report from the Doppler Quantification Task Force of the Nomenclature and Standards Committee of the American Society of Echocardiography. J Am Soc Echocardiogr. 2002;15:167–84.CrossRefPubMed Quiñones MA, Otto CM, Stoddard M, Waggoner A, Zoghbi WA, Doppler Quantification Task Force of the Nomenclature and Standards Committee of the American Society of Echocardiography. Recommendations for quantification of Doppler echocardiography: a report from the Doppler Quantification Task Force of the Nomenclature and Standards Committee of the American Society of Echocardiography. J Am Soc Echocardiogr. 2002;15:167–84.CrossRefPubMed
28.
go back to reference Hiatt WR, Huang SY, Regensteiner JG, Micco AJ, Ishimoto G, Manco-Johnson M, et al. Venous occlusion plethysmography reduces arterial diameter and flow velocity. J Appl Physiol. 1989;66:2239–44.CrossRefPubMed Hiatt WR, Huang SY, Regensteiner JG, Micco AJ, Ishimoto G, Manco-Johnson M, et al. Venous occlusion plethysmography reduces arterial diameter and flow velocity. J Appl Physiol. 1989;66:2239–44.CrossRefPubMed
29.
go back to reference Frustaci A, Kajstura J, Chimenti C, Jakoniuk I, Leri A, Maseri A, et al. Myocardial cell death in human diabetes. Circ Res. 2000;87:1123–32.CrossRefPubMed Frustaci A, Kajstura J, Chimenti C, Jakoniuk I, Leri A, Maseri A, et al. Myocardial cell death in human diabetes. Circ Res. 2000;87:1123–32.CrossRefPubMed
30.
go back to reference Fearon IM, Faux SP. Oxidative stress and cardiovascular disease: novel tools give (free) radical insight. J Mol Cell Cardiol. 2009;47:372–81.CrossRefPubMed Fearon IM, Faux SP. Oxidative stress and cardiovascular disease: novel tools give (free) radical insight. J Mol Cell Cardiol. 2009;47:372–81.CrossRefPubMed
31.
go back to reference Pitocco D, Tesauro M, Alessandro R, Ghirlanda G, Cardillo C. Oxidative stress in diabetes: implications for vascular and other complications. Int J Mol Sci. 2013;14:21525.CrossRefPubMedPubMedCentral Pitocco D, Tesauro M, Alessandro R, Ghirlanda G, Cardillo C. Oxidative stress in diabetes: implications for vascular and other complications. Int J Mol Sci. 2013;14:21525.CrossRefPubMedPubMedCentral
33.
go back to reference Silberman GA, Fan THM, Liu H, Jiao Z, Xiao HD, Lovelock JD, et al. Uncoupled cardiac nitric oxide synthase mediates diastolic dysfunction. Circulation. 2010;121:519–28.CrossRefPubMedPubMedCentral Silberman GA, Fan THM, Liu H, Jiao Z, Xiao HD, Lovelock JD, et al. Uncoupled cardiac nitric oxide synthase mediates diastolic dysfunction. Circulation. 2010;121:519–28.CrossRefPubMedPubMedCentral
34.
go back to reference Layland J, Li J-M, Shah AM. Role of cyclic GMP-dependent protein kinase in the contractile response to exogenous nitric oxide in rat cardiac myocytes. J Physiol (Lond.). 2004;540:457–67.CrossRef Layland J, Li J-M, Shah AM. Role of cyclic GMP-dependent protein kinase in the contractile response to exogenous nitric oxide in rat cardiac myocytes. J Physiol (Lond.). 2004;540:457–67.CrossRef
35.
go back to reference Cree Green M, Newcomer BR, Brown MS, Baumgartner AD, Bergman B, Drew B, et al. Delayed skeletal muscle mitochondrial ADP recovery in youth with type 1 diabetes relates to muscle insulin resistance. Diabetes. 2015;64:383–92.CrossRefPubMed Cree Green M, Newcomer BR, Brown MS, Baumgartner AD, Bergman B, Drew B, et al. Delayed skeletal muscle mitochondrial ADP recovery in youth with type 1 diabetes relates to muscle insulin resistance. Diabetes. 2015;64:383–92.CrossRefPubMed
36.
go back to reference Patti ME, Butte AJ, Crunkhorn S, Cusi K, Berria R, Kashyap S, et al. Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: potential role of PGC1 and NRF1. PNAS. 2003;100:8466–71.CrossRefPubMedPubMedCentral Patti ME, Butte AJ, Crunkhorn S, Cusi K, Berria R, Kashyap S, et al. Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: potential role of PGC1 and NRF1. PNAS. 2003;100:8466–71.CrossRefPubMedPubMedCentral
37.
go back to reference Keller AC, Knaub LA, Miller MW, Birdsey N, Klemm DJ, Reusch JE. Saxagliptin restores vascular mitochondrial exercise response in diabetes. J Cardiovasc Pharmacol. 2015;65:137–47.PubMedPubMedCentral Keller AC, Knaub LA, Miller MW, Birdsey N, Klemm DJ, Reusch JE. Saxagliptin restores vascular mitochondrial exercise response in diabetes. J Cardiovasc Pharmacol. 2015;65:137–47.PubMedPubMedCentral
Metadata
Title
Acute vitamin C improves cardiac function, not exercise capacity, in adults with type 2 diabetes
Authors
Rebecca L. Scalzo
Timothy A. Bauer
Kylie Harrall
Kerrie Moreau
Cemal Ozemek
Leah Herlache
Shawna McMillin
Amy G. Huebschmann
Jennifer Dorosz
Jane E. B. Reusch
Judith G. Regensteiner
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Diabetology & Metabolic Syndrome / Issue 1/2018
Electronic ISSN: 1758-5996
DOI
https://doi.org/10.1186/s13098-018-0306-9

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