Impaired microvascular insulin-dependent dilation in women with a history of gestational diabetes.

Women with a history of gestational diabetes mellitus (GDM) have significantly greater lifetime risk of developing cardiovascular disease and type 2 diabetes compared to women who had an uncomplicated pregnancy (HC). Microvascular endothelial dysfunction, mediated via reduced nitric oxide (NO)-dependent dilation secondary to increases in oxidative stress, persists after pregnancy complicated by GDM. We examined whether this microvascular dysfunction reduces insulin-mediated vascular responses in women with a history of GDM. We assessed in vivo microvascular endothelium-dependent vasodilator function by measurement of cutaneous vascular conductance responses to graded infusion of acetylcholine (10-10 - 10-1M) and insulin (10-8 - 10-4M) in control sites and sites treated with 15mM L-NAME [NG-nitro-l-arginine methyl ester; NO-synthase (NOS) inhibitor] or 5mM L-ascorbate. We also measured protein expression of total endothelial NOS (eNOS), insulin-mediated eNOS phosphorylation, and endothelial nitrotyrosine in isolated endothelial cells from GDM and HC. Women with a history of GDM had reduced acetylcholine- (P<0.001) and insulin- (P<0.001) mediated dilation and the NO-dependent responses to both acetylcholine (P=0.006) and insulin (P=0.006) were reduced in GDM compared to HC. Insulin stimulation increased phosphorylated eNOS content in HC (P=0.009) but had no effect in GDM (P=0.306). Ascorbate treatment increased acetylcholine- (P<0.001) and insulin- (P<0.001) mediated dilation in GDM, and endothelial cell nitrotyrosine expression was higher in GDM compared to HC (P=0.014). Women with a history of GDM have attenuated microvascular vasodilation responses to insulin, and this attenuation is mediated, in part, by reduced NO-dependent mechanisms. Our findings implicate increased endothelial oxidative stress in this microvascular insulin resistance.

Resistance exercise breaks during prolonged sitting augment the blood flow response to a subsequent oral glucose load in sedentary adults.

Sitting-induced impairments in postprandial blood flow are an important link between sedentary behaviour and cardiometabolic disease risk. The objective of this work was to examine the effects of resistance exercise breaks (REB) performed every 30 min during an otherwise sedentary 3-h period on the vasodilatory response to a subsequent oral glucose load in sedentary adults. Twenty-four sedentary adults (27 ± 7 years, 16 females) completed two conditions. Fasting blood glucose, insulin, popliteal artery blood flow (PABF) and gastrocnemius perfusion were measured immediately before standardized breakfast consumption. After breakfast, the 3-h REB or uninterrupted (SIT) intervention period commenced. Participants sat at a workstation, and popliteal artery shear rate (PASR) was measured 60 and 120 min into this period. In the REB condition, participants performed a 3-min REB (3 × [20 s squats, 20 s high knees, 20 s calf raises]) every 30 min. Following the intervention period, baseline measurements were repeated. Participants then consumed a 75 g glucose beverage, and PABF and perfusion were measured every 30-60 min for the following 120 min. Relative to SIT, REB increased PASR at 60 min (+31.4 ± 9.2/s, P = 0.037) and 120 min (+37.4 ± 10.2/s, P = 0.019) into the intervention period. Insulin and glucose increased (P < 0.001) in response to glucose consumption, with no differences between conditions (P ≥ 0.299). In response to the glucose load, perfusion (1.57 vs. 1.11 mL/100 mL/min, P = 0.023) and PABF (+45.3 ± 11.8 mL/min, P = 0.001) were greater after REB versus SIT. Performing 3-min REB every 30 min during an otherwise sedentary 3-h period augmented leg blood flow responses to an oral glucose load. HIGHLIGHTS: What is the central question of this study? Can 3-min resistance exercise breaks (REB) performed during an otherwise sedentary 3-h period augment the vasodilatory response to a subsequent oral glucose load in sedentary adults? What is the main finding and its importance? Performing 3-min REB, which included squats, high knees, and calf raises, every 30 min augmented lower limb blood flow responses to a subsequent oral glucose load compared to 3 h of uninterrupted sitting in sedentary adults. Sitting-induced impairment in postprandial vasodilatory function has been identified as a link between sedentary behaviour and cardiometabolic disease. Thus, the current study presents a potentially effective strategy to offset this risk.