biostudies-literatureBock JMHHS | NIH | National Cancer InstituteAmerican Diabetes AssociationNCI NIH HHS1407-1414https://www.ebi.ac.uk/biostudies/studies/S-EPMC9762960biostudies-literatureUnknown133(6)Patients with type 2 diabetes mellitus (T2DM) have reduced exercise capacity, indexed by lower maximal oxygen consumption (V̇o_2max) and achievement of the gas exchange threshold (GET) at a lower % V̇o_2max. The ubiquitous signaling molecule nitric oxide (NO) plays a multifaceted role during exercise and, as patients with T2DM have poor endogenous NO production, we investigated if inorganic nitrate/nitrite supplementation (an exogenous source of NO) improves exercise capacity in patients with T2DM. Thirty-six patients with T2DM (10F, 59 ± 9 yr, 32.0 ± 5.1 kg/m², HbA1c = 7.4 ± 1.4%) consumed beetroot juice containing either inorganic nitrate/nitrite (4.03 mmol/0.29 mmol) or a placebo (0.8 mmol/0.00 mmol) for 8 wk. A maximal exercise test was completed before and after both interventions. V̇o_2max was determined by averaging 15-s data, whereas the GET was identified using the V-slope method and breath-by-breath data. Inorganic nitrate/nitrite increased both absolute (1.96 ± 0.67 to 2.07 ± 0.75 L/min) and relative (20.7 ± 7.0 to 21.9 ± 7.4 mL/kg/min, <i>P</i> < 0.05 for both) V̇o_2max, whereas no changes were observed following placebo (1.94 ± 0.40 to 1.90 ± 0.39 L/min, <i>P</i> = 0.33; 20.0 ± 4.2 to 19.7 ± 4.6 mL/kg/min, <i>P</i> = 0.39). Maximal workload was also increased following inorganic nitrate/nitrite supplementation (134 ± 47 to 140 ± 51 W, <i>P</i> < 0.05) but not placebo (138 ± 32 to 138 ± 32 W, <i>P</i> = 0.98). V̇o₂ at the GET (1.11 ± 0.27 to 1.27 ± 0.38L/min) and the %V̇o_2max in which GET occurred (56 ± 8 to 61 ± 7%, <i>P</i> < 0.05 for both) increased following inorganic nitrate/nitrite supplementation but not placebo (1.10 ± 0.23 to 1.08 ± 0.21 L/min, <i>P</i> = 0.60; 57 ± 9 to 57 ± 8%, <i>P</i> = 0.90) although the workload at GET did not achieve statistical significance (group-by-time <i>P</i> = 0.06). Combined inorganic nitrate/nitrite consumption improves exercise capacity, maximal workload, and promotes a rightward shift in the GET in patients with T2DM. This manuscript reports data from a registered Clinical Trial at ClinicalTrials.gov ID: NCT02804932.<b>NEW & NOTEWORTHY</b> We report that increasing nitric oxide bioavailability via 8 wk of inorganic nitrate/nitrite supplementation improves maximal aerobic exercise capacity in patients with type 2 diabetes mellitus. Similarly, we observed a rightward shift in the gas exchange threshold. Taken together, these data indicate inorganic nitrate/nitrite may serve as a means to improve fitness in patients with type 2 diabetes mellitus.Journal of applied physiology (Bethesda, Md. : 1985)Eight weeks of inorganic nitrate/nitrite supplementation improves aerobic exercise capacity and the gas exchange threshold in patients with type 2 diabetes.PMC97629601-16-1CTS-015P30 CA086862P30CA086862Feider AJUeda KLira VABock JMHanada SHanson BESeaberg NTCasey DPMiller KAfalseEight weeks of inorganic nitrate/nitrite supplementation improves aerobic exercise capacity and the gas exchange threshold in patients with type 2 diabetes.Patients with type 2 diabetes mellitus (T2DM) have reduced exercise capacity, indexed by lower maximal oxygen consumption (V̇o_2max) and achievement of the gas exchange threshold (GET) at a lower % V̇o_2max. The ubiquitous signaling molecule nitric oxide (NO) plays a multifaceted role during exercise and, as patients with T2DM have poor endogenous NO production, we investigated if inorganic nitrate/nitrite supplementation (an exogenous source of NO) improves exercise capacity in patients with T2DM. Thirty-six patients with T2DM (10F, 59 ± 9 yr, 32.0 ± 5.1 kg/m², HbA1c = 7.4 ± 1.4%) consumed beetroot juice containing either inorganic nitrate/nitrite (4.03 mmol/0.29 mmol) or a placebo (0.8 mmol/0.00 mmol) for 8 wk. A maximal exercise test was completed before and after both interventions. V̇o_2max was determined by averaging 15-s data, whereas the GET was identified using the V-slope method and breath-by-breath data. Inorganic nitrate/nitrite increased both absolute (1.96 ± 0.67 to 2.07 ± 0.75 L/min) and relative (20.7 ± 7.0 to 21.9 ± 7.4 mL/kg/min, <i>P</i> < 0.05 for both) V̇o_2max, whereas no changes were observed following placebo (1.94 ± 0.40 to 1.90 ± 0.39 L/min, <i>P</i> = 0.33; 20.0 ± 4.2 to 19.7 ± 4.6 mL/kg/min, <i>P</i> = 0.39). Maximal workload was also increased following inorganic nitrate/nitrite supplementation (134 ± 47 to 140 ± 51 W, <i>P</i> < 0.05) but not placebo (138 ± 32 to 138 ± 32 W, <i>P</i> = 0.98). V̇o₂ at the GET (1.11 ± 0.27 to 1.27 ± 0.38L/min) and the %V̇o_2max in which GET occurred (56 ± 8 to 61 ± 7%, <i>P</i> < 0.05 for both) increased following inorganic nitrate/nitrite supplementation but not placebo (1.10 ± 0.23 to 1.08 ± 0.21 L/min, <i>P</i> = 0.60; 57 ± 9 to 57 ± 8%, <i>P</i> = 0.90) although the workload at GET did not achieve statistical significance (group-by-time <i>P</i> = 0.06). Combined inorganic nitrate/nitrite consumption improves exercise capacity, maximal workload, and promotes a rightward shift in the GET in patients with T2DM. This manuscript reports data from a registered Clinical Trial at ClinicalTrials.gov ID: NCT02804932.<b>NEW & NOTEWORTHY</b> We report that increasing nitric oxide bioavailability via 8 wk of inorganic nitrate/nitrite supplementation improves maximal aerobic exercise capacity in patients with type 2 diabetes mellitus. Similarly, we observed a rightward shift in the gas exchange threshold. Taken together, these data indicate inorganic nitrate/nitrite may serve as a means to improve fitness in patients with type 2 diabetes mellitus.2022-01-01T00:00:00Z2022 Dec2025-05-29T21:47:11.199Z2025-05-29T21:47:11.199ZS-EPMC97629603632647310.1152/japplphysiol.00478.2022