Type 1 diabetes patients increase CXCR4+ and CXCR7+ haematopoietic and endothelial progenitor cells with exercise, but the response is attenuated

Background: Exercise mobilizes angiogenic cells, which stimulate vascular repair. However, limited research suggests exercise-induced increase of endothelial progenitor cell (EPCs) is completely lacking in type 1 diabetes (T1D). Clarification, along with investigating how T1D influences exercise-induced increases of other angiogenic cells (hematopoietic progenitor cells; HPCs) and cell surface expression of chemokine receptor 4 (CXCR4) and 7 (CXCR7), is needed. Methods: Thirty T1D patients and 30 matched non-diabetes controls completed 45 minutes of incline walking. Circulating HPCs (CD34+ , CD34+ CD45dim) and EPCs (CD34+ VEGFR2+ , CD34+CD45dimVEGFR2+ ), and subsequent expression of CXCR4 and CXCR7, were enumerated by flow cytometry at rest and post-exercise. Results: Counts of HPCs, EPCs and expression of CXCR4 and CXCR7 were significantly lower at rest in the T1D group. In both groups, exercise increased circulating angiogenic cells. However, increases was largely attenuated in the T1D group, up to 55% lower, with CD34+ (331±437 Δcells/mL vs 734±876 Δcells/mL p=0.048), CD34+VEGFR2+ (171±342 Δcells/mL vs 303±267 Δcells/mL, p=0.006) and CD34+ VEGFR2+CXCR4+ (126±242 Δcells/mL vs 218±217 Δcells/mL, p=0.040) significantly lower. Conclusion: Exercise-induced increases of angiogenic cells is possible in T1D patients, albeit attenuated compared to controls. Decreased mobilization likely results in reduced migration to, and repair of, vascular damage, potentially limiting the cardiovascular benefits of exercise. Trial registration: ISRCTN6373920

Pharmacokinetic Profile of Incremental Oral Doses of Dietary Nitrate in Young and Older Adults: A Crossover Randomized Clinical Trial

BACKGROUND: Dietary nitrate consumption can increase concentrations of nitrate and nitrite in blood, saliva, and urine. Whether the change in concentrations is influenced by age is currently unknown. OBJECTIVES: We aimed to measure changes in nitrate and nitrite concentrations in plasma, urine, and saliva and exhaled NO concentrations after single incremental doses of dietary nitrate in young and older healthy adults. METHODS: Twelve young (18–35 y old) and 12 older (60–75 y old) healthy, nonsmoking participants consumed single doses of 100 g, 200 g, 300 g whole beetroot (BR) and 1000 mg potassium nitrate (positive control) ≥7 d apart in a crossover, randomized clinical trial. Plasma nitrate and nitrite concentrations and exhaled NO concentrations were measured over a 5-h period. Salivary nitrate and nitrite concentrations were measured over a 12-h period and urinary nitrate over a 24-h period. Time, intervention, age, and interaction effects were measured with repeated-measures ANOVAs. RESULTS: Dose-dependent increases were seen in plasma, salivary, and urinary nitrate after BR ingestion (all P ≤ 0.002) but there were no differences between age groups at baseline (all P ≥ 0.56) or postintervention (all P ≥ 0.12). Plasma nitrite concentrations were higher in young than older participants at baseline (P = 0.04) and after consumption of 200 g (P = 0.04; +25.7 nmol/L; 95% CI: 0.97, 50.3 nmol/L) and 300 g BR (P = 0.02; +50.3 nmol/L; 95% CI: 8.57, 92.1 nmol/L). Baseline fractional exhaled NO (FeNO) concentrations were higher in the younger group [P = 0.03; +8.60 parts per billion (ppb); 95% CI: 0.80, 16.3 ppb], and rose significantly over the 5-h period, peaking 5 h after KNO(3) consumption (39.4 ± 4.5 ppb; P < 0.001); however, changes in FeNO were not influenced by age (P = 0.276). CONCLUSIONS: BR is a source of bioavailable dietary nitrate in both young and older adults and can effectively raise nitrite and nitrate concentrations. Lower plasma nitrite and FeNO concentrations were found in older subjects, confirming the impact of ageing on NO bioavailability across different systems. This trial was registered at www.isrctn.com as ISRCTN86706442

Whole beetroot consumption reduces systolic blood pressure and modulates diversity and composition of the gut microbiota in older participants

Background: Age-associated decline in physiological function has been identified as the main factor increasing disease risk, including cardiovascular (CVD) and gastrointestinal tract (GIT) diseases. Nutritional interventions encompassing dietary inorganic nitrates, such as nitrate rich beetroot may reduce the risk for CVD and GIT. Objective: Assess the impact of whole beetroot on blood pressure (BP), microbiota profile and functional measures (physical and bowel). Design: Thirty-six healthy participants were recruited (mean age 67 ± 6 years; body mass index (BMI) 25 ± 2 kg/m) and assigned randomly to a beetroot (n = 19) or control group (n = 17). Beetroot group consumed 150 g of whole beetroot and a medium-sized banana and the control group consumed a medium-sized banana every second day for 8 weeks. Resting BP, microbiota profiling, physical activity, urinary nitrate, short-chain fatty acids (SCFA) and Bristol Stool Score (BSS) were measured at 0, 4 and 8 weeks. Plasma nitrate was measured at weeks 0 and 8. Results: The beetroot group had a resting systolic BP reduction of 8.0 mmHg (p = 0.03), lower relative abundance of the phyla Bacteroidetes (p = 0.04), and a higher relative abundance of genus Alistipes (p = 0.03), increased Shannon diversity index (p = 0.03), fibre intake of 7 g/day (p < 0.01), nitrate intake 145 mg/day (p < 0.01), urinary nitrate of 460 μmol/L (p = 0.02) and SCFA concentrations (p < 0.05). However, 8 weeks of beetroot consumption did not have any impact upon functional measures, urine or plasma nitrate and BSS. Conclusion: In a randomised controlled trial, consuming whole beetroot for 8 weeks resulted in modification of risk factors for CVD and GIT disorders in older participants. Physical measures were unaffected and further assessment of more sensitive measures of functional performance are required to ascertain if whole beetroot may offer additional physiological benefits in older populations. Although the data here is promising, further mechanistic studies and larger clinical trials are required to confirm the findings