Elevation in blood flow and shear rate prevents hyperglycemia-induced endothelial dysfunction in healthy subjects and those with type 2 diabetes

Hyperglycemia, commonly present after a meal, causes transient impairment in endothelial function. We examined whether increases in blood flow (BF) protect against the hyperglycemia- mediated decrease in endothelial function in healthy subjects and patients with type 2 diabetes mellitus (T2DM). Ten healthy subjects and 10 age- and sex-matched T2DM patients underwent simultaneous bilateral assessment of brachial artery endothelial function by means of flow- mediated dilation (FMD), using high-resolution echo-Doppler. FMD was examined before and 60, 120 and 150 minutes after a 75-gr oral glucose challenge. We unilaterally manipulated BF by heating one arm between minute 30 and 60. Oral glucose administration caused a statistically significant, transient increase in blood glucose in both groups (P<0.001). Forearm skin temperature, brachial artery BF and shear rate significantly increased in the heated arm (P<0.001), and to a greater extent compared to the non-heated arm in both groups (interaction- effect, P<0.001). The glucose load caused a transient decrease in FMD% (P<0.05), whilst heating significantly prevented the decline (interaction-effect: P<0.01). Also when correcting for changes in diameter and shear rate, we found that the hyperglycemia-induced decrease in FMD can be prevented by local heating (P<0.05). These effects on FMD were observed in both groups. Our data indicate that non-metabolically driven elevation in BF and shear rate can similarly prevent the hyperglycemia-induced decline in conduit artery endothelial function in healthy volunteers and in patients with type 2 diabetes. Additional research is warranted to confirm that other interventions increasing BF and shear rate equally protect the endothelium when challenged by hyperglycemia

A comparison of dicarbonyl stress and advanced glycation endproducts in lifelong endurance athletes vs. sedentary controls

Objectives: Dicarbonyl stress and high concentrations of advanced glycation endproducts (AGEs) relate to an elevated risk for cardiovascular diseases (CVD). Exercise training lowers the risk for future CVD. We tested the hypothesis that lifelong endurance athletes have lower dicarbonyl stress and AGEs compared to sedentary controls and that these differences relate to a better cardiovascular health profile. Design: Cross-sectional study. Methods: We included 18 lifelong endurance athletes (ATH, 61±7years) and 18 sedentary controls (SED, 58±7years) and measured circulating glyoxal (GO), methylglyoxal (MGO) and 3-deoxyglucosone (3DG) as markers of dicarbonyl stress. Furthermore, we measured serum levels of protein-bound AGEs NE(open)-(carboxymethyl)lysine (CML), NE(open)-(carboxyethyl)lysine (CEL), methylglyoxal-derived hydroimidazolone-1 (MG-H1), and pentosidine. Additionally, we measured cardiorespiratory fitness (VO2peak) and cardiovascular health markers. Results: ATH had lower concentrations of MGO (196 [180-246] vs. 242 [207-292] nmol/mmol lysine, p=0.043) and 3DG (927 [868-972] vs. 1061 [982-1114] nmol/mmol lysine, p<0.01), but no GO compared to SED. ATH demonstrated higher concentrations CML and CEL compared to SED. Pentosidine did not differ across groups and MG-H1 was significantly lower in ATH compared to SED. Concentrations of MGO en 3DG were inversely correlated with cardiovascular health markers, whereas CML and CEL were positively correlated with VO2peak and cardiovascular health markers. Conclusion: Lifelong exercise training relates to lower dicarbonyl stress (MGO and 3DG) and the AGE MG-H1. The underlying mechanism and (clinical) relevance of higher CML and CEL concentrations among lifelong athletes warrants future research, since it conflicts with the idea that higher AGE concentrations relate to poor cardiovascular health outcomes. © 2017 Sports Medicine Australia

Eight-week exercise training in humans with obesity: Marked improvements in insulin sensitivity and modest changes in gut microbiome.

OBJECTIVE: Obesity is associated with impaired gut microbiota diversity, which has been linked to the development of type 2 diabetes. This study aims to examine the effects of an 8-week aerobic exercise intervention on insulin sensitivity, visceral adiposity, and gut microbiota diversity and composition in participants with obesity. METHODS: Fourteen participants (mean [SD], age 51 [11] years; BMI 34.9 [4.9] kg/m2 ) performed an 8-week exercise intervention (2 to 4 times/week on 65% to 85% of heart rate reserve). Insulin sensitivity (hyperinsulemic euglycemic clamp), cardiorespiratory fitness (maximal oxygen uptake), visceral adiposity (dual-energy X-ray absorptiometry scan) and gut microbiota composition (16S rRNA gene sequencing) were measured before and after the intervention. RESULTS: Insulin sensitivity showed a significant increase (pre: 3.8 [1.9] mg/min/kg; post: 4.5 [1.7] mg/min/kg; p = 0.007) after training, whereas visceral adiposity decreased (pre: 959 [361] cm3 ; post: 897 [364] cm3 ; p = 0.02). No change in gut microbiota α- or β-diversity was found. At the genus level, the abundance of Ruminococcus gauvreauii (p = 0.02); Lachnospiraceae FCS020 group (p = 0.04), and Anaerostipes (p = 0.04) significantly increased after exercise training. Significant positive correlations were present for M-value (R. gauvreauii) and VO2 max (R. gauvreauii and Anaerostipes). CONCLUSIONS: Eight-week exercise training in humans with obesity leads to marked improvements in insulin sensitivity and body composition and is accompanied by modest changes in 3 gut microbiome genera, all belonging to the Firmicutes phylum

Cytokine responses to repeated, prolonged walking in lean versus overweight/obese individuals.

OBJECTIVES: Obesity is characterized by a pro-inflammatory state, which plays a role in the pathogenesis of metabolic and cardiovascular disease. An exercise bout causes a transient increase in pro-inflammatory cytokines, whilst training has anti-inflammatory effects. No previous study examined whether the exercise-induced increase in pro-inflammatory cytokines is altered with repeated prolonged exercise bouts and whether this response differs between lean and overweight/obese individuals. DESIGN: Lean (n=25, BMI 22.9±1.5kg/m2) and age-/sex-matched overweight/obese (n=25; BMI 27.9±2.4kg/m2) individuals performed walking exercise for 30, 40 or 50km per day on four consecutive days (distances similar between groups). METHODS: Circulating cytokines (IL-6, IL-10, TNF-α, IL-1β and IL-8) were examined at baseline and <30min after the finish of each exercise day. RESULTS: At baseline, no differences in circulating cytokines were present between groups. In response to prolonged exercise, all cytokines increased on day 1 (IL-1β: P=0.02; other cytokines: P<0.001). IL-6 remained significantly elevated during the 4 exercise days, when compared to baseline. IL-10, TNF-α, IL-1β and IL-8 returned to baseline values from exercise day 2 (IL-10, IL-1β, IL-8) or exercise day 3 (TNF-α) onward. No significant differences were found between groups for all cytokines, except IL-8 (Time*Group Interaction P=0.02). CONCLUSIONS: These data suggest the presence of early adaptive mechanisms in response to repeated prolonged walking, demonstrated by attenuated exercise-induced elevations in cytokines on consecutive days that occur similar in lean and overweight/obese individuals