Impaired Erythropoietin Response to Hypoxia in Type 2 Diabetes

Overview

Journal Acta Diabetol

Specialty Endocrinology

Date 2024 Apr 3

PMID 38570345

Authors

Frank Wojan

Sten Stray-Gundersen

Jiahui Zhao

Sophie Lalande

Affiliations

Soon will be listed here.

Abstract

Aims: Patients with type 2 diabetes have a 20% lower total blood volume than age- and weight-matched healthy adults, suggesting a reduced capacity to transport oxygen in this population. Intermittent hypoxia, consisting of alternating short bouts of breathing hypoxic and normoxic air, increases erythropoietin levels, the hormone regulating red blood cell production, in young and older adults. The objective of this study was to determine the effect of a single session of intermittent hypoxia on erythropoietin levels and hemoglobin mass, the absolute mass of hemoglobin contained in red blood cells, in patients with type 2 diabetes.

Methods: Ten patients with type 2 diabetes were exposed to an intermittent hypoxia protocol consisting of eight 4-min cycles at a targeted oxygen saturation of 80% interspersed with normoxic cycles to resaturation. Erythropoietin and hemoglobin mass responses to intermittent hypoxia in patients with type 2 diabetes were compared to previously published data from an identical intermittent hypoxia protocol performed in age-matched older adults.

Results: Intermittent hypoxia increased erythropoietin levels in older adults but did not induce any change in erythropoietin levels in patients with type 2 diabetes (3.2 ± 2.2 vs. 0.2 ± 2.7 mU/ml, p = 0.01). Hemoglobin mass indexed to body weight was 21% lower in patients with type 2 diabetes than in older adults (8.1 ± 1.7 vs. 10.2 ± 2.1 g/kg, p < 0.01).

Conclusions: These findings suggest an impaired erythropoietin response to decreased oxygen levels in patients with type 2 diabetes, which may contribute to the reduced oxygen transport capacity observed in this population.

Citing Articles

Protective Influence of SGLT-2 Inhibitors Against Heart Failure in Type 2 Diabetes Mellitus Through Longitudinal Clinical Database Analysis.

Nagy A, Toth A, Bak N, Ulambayar B, Ghanem A, Sztanek F J Clin Med. 2024; 13(23).

PMID: 39685552 PMC: 11642396. DOI: 10.3390/jcm13237093.

References

Schmidt W, Prommer N . Impact of alterations in total hemoglobin mass on VO 2max. Exerc Sport Sci Rev. 2010; 38(2):68-75. DOI: 10.1097/JES.0b013e3181d4957a. View

Baldi J, Aoina J, Whalley G, Carrick-Ranson G, Walsh H, OShaughnessy H . The effect of type 2 diabetes on diastolic function. Med Sci Sports Exerc. 2006; 38(8):1384-8. DOI: 10.1249/01.mss.0000228954.90591.95. View

Lalande S, Gusso S, Hofman P, Baldi J . Reduced leg blood flow during submaximal exercise in type 2 diabetes. Med Sci Sports Exerc. 2008; 40(4):612-7. DOI: 10.1249/MSS.0b013e318161aa99. View

Regensteiner J, Sippel J, McFarling E, Wolfel E, Hiatt W . Effects of non-insulin-dependent diabetes on oxygen consumption during treadmill exercise. Med Sci Sports Exerc. 1995; 27(6):875-81. View

Mac Ananey O, Malone J, Warmington S, OShea D, Green S, Egana M . Cardiac output is not related to the slowed O2 uptake kinetics in type 2 diabetes. Med Sci Sports Exerc. 2010; 43(6):935-42. DOI: 10.1249/MSS.0b013e3182061cdb. View

OConnor E, Green S, Kiely C, OShea 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; 118(8):1031-9. DOI: 10.1152/japplphysiol.01040.2014. View

Wilkerson D, Poole D, Jones A, Fulford J, Mawson D, Ball C . 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. 2010; 300(3):R685-92. DOI: 10.1152/ajpregu.00479.2010. View

Lalande S, Hofman P, Baldi J . Effect of reduced total blood volume on left ventricular volumes and kinetics in type 2 diabetes. Acta Physiol (Oxf). 2010; 199(1):23-30. DOI: 10.1111/j.1748-1716.2010.02081.x. View

Koponen A, Peltonen J, Paivinen M, Aho J, Hagglund H, Uusitalo A . Low total haemoglobin mass, blood volume and aerobic capacity in men with type 1 diabetes. Eur J Appl Physiol. 2012; 113(5):1181-8. DOI: 10.1007/s00421-012-2532-4. View

10.

Resnick H, Foster G, Bardsley J, Ratner R . Achievement of American Diabetes Association clinical practice recommendations among U.S. adults with diabetes, 1999-2002: the National Health and Nutrition Examination Survey. Diabetes Care. 2006; 29(3):531-7. DOI: 10.2337/diacare.29.03.06.dc05-1254. View

11.

Ross R, Blair S, Arena R, Church T, Despres J, Franklin B . Importance of Assessing Cardiorespiratory Fitness in Clinical Practice: A Case for Fitness as a Clinical Vital Sign: A Scientific Statement From the American Heart Association. Circulation. 2016; 134(24):e653-e699. DOI: 10.1161/CIR.0000000000000461. View

12.

Jelkmann W . Regulation of erythropoietin production. J Physiol. 2010; 589(Pt 6):1251-8. PMC: 3082088. DOI: 10.1113/jphysiol.2010.195057. View

13.

Craig K, Williams J, Riley S, Smith H, Owens D, Worthing D . Anemia and diabetes in the absence of nephropathy. Diabetes Care. 2005; 28(5):1118-23. DOI: 10.2337/diacare.28.5.1118. View

14.

Mojiminiyi O, Abdella N, Zaki M, El Gebely S, Mohamedi H, Aldhahi W . Prevalence and associations of low plasma erythropoietin in patients with Type 2 diabetes mellitus. Diabet Med. 2006; 23(8):839-44. DOI: 10.1111/j.1464-5491.2006.01893.x. View

15.

Bosman D, Osborne C, Marsden J, Macdougall I, Gardner W, Watkins P . Erythropoietin response to hypoxia in patients with diabetic autonomic neuropathy and non-diabetic chronic renal failure. Diabet Med. 2002; 19(1):65-9. DOI: 10.1046/j.1464-5491.2002.00634.x. View

16.

Jelkmann W . Erythropoietin. Front Horm Res. 2016; 47:115-27. DOI: 10.1159/000445174. View

17.

Schmidt W, Eckardt K, Hilgendorf A, Strauch S, Bauer C . Effects of maximal and submaximal exercise under normoxic and hypoxic conditions on serum erythropoietin level. Int J Sports Med. 1991; 12(5):457-61. DOI: 10.1055/s-2007-1024713. View

18.

Wojan F, Stray-Gundersen S, Nagel M, Lalande S . Short exposure to intermittent hypoxia increases erythropoietin levels in healthy individuals. J Appl Physiol (1985). 2021; 130(6):1955-1960. DOI: 10.1152/japplphysiol.00941.2020. View

19.

Wojan F, Stray-Gundersen S, Massoudian S, Lalande S . Brief exposure to intermittent hypoxia increases erythropoietin levels in older adults. J Appl Physiol (1985). 2023; 135(1):88-93. DOI: 10.1152/japplphysiol.00172.2023. View

20.

Lalande S, Kelsey J, Joyner M, Johnson B . Determination of blood volume by pulse CO-oximetry. Physiol Meas. 2011; 33(1):19-27. PMC: 4033710. DOI: 10.1088/0967-3334/33/1/19. View