Impairments in microvascular function and skeletal muscle oxygenation in women with gestational diabetes mellitus: links to cardiovascular disease risk factors

Δίπλα, Κωνσταντίνα; Triantafyllou, Αreti; Grigoriadou, Iris; Kintiraki, Evangelia; Triantafyllou, G.; Poulios, P; Vrabas, Ioannis S.; Zafeiridis, Andreas; Δούμα, Στέλλα; Goulis, Dimitrios G.

doi:10.1007/s00125-016-4129-7

Cited by 52 publications

(50 citation statements)

References 48 publications

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“…24,28 The NIRS device, placed at the forearm, noninvasively, monitored changes in muscle oxygenation, by measuring micromolar (µmol/L) relative changes from baseline for oxygenated, deoxygenated, and total hemoglobin. 29,30 NIRS also assessed the tissue saturation index (TSI), as an absolute parameter for muscle oxygenation.…”

Section: Testing Procedures and Instrumentationmentioning

confidence: 99%

“…Muscle microvascular function was assessed during reactive hyperemia, as previously described. 24 In brief, after calibration, with the participant in the seated position, baseline values were obtained, and a 5-minute arterial occlusion was performed. The cuff was rapidly inflated to suprasystolic levels (ie, 250 mm Hg), to obstruct blood flow to forearm muscles and measure the maximal capacity for oxygen extraction by skeletal muscles.…”

Section: Testing Procedures and Instrumentationmentioning

confidence: 99%

“…After a subsequent 10-minute rest, the participant's maximal voluntary contraction (MVC) was assessed, 24 using a digital dynamometer (Biopac), followed by a 3-minute submaximal handgrip exercise test (at 30% MVC). The participant had visual feedback to maintain the force output to the predetermined MVC percentage.…”

Section: Testing Procedures and Instrumentationmentioning

confidence: 99%

“…In accordance, a slow TSI during reperfusion has been previously shown in patients with coronary heart disease, overt metabolic syndrome, and gestational diabetes mellitus and associated with cardiovascular risk factors. 24,38,39 A slow reperfusion TSI was revealed as an independent predictor of mortality in patients with sepsis. …”

mentioning

confidence: 98%

“…Using the arterial occlusion/reoxygenation maneuver, the NIRS technology provides information on skeletal muscle's oxidative capacity, microvascular function, and muscle oxygenation at rest and during exercise. [22][23][24][25] Our aims were to examine in vivo skeletal muscle oxygenation and microvascular function (as assessed by muscle microvascular reactivity), at rest and during submaximal handgrip exercise, and their associations with (1) arterial stiffness and other macrovascular function indices and (2) BP responses during handgrip exercise, in newly diagnosed, never-treated patients with hypertension (HYP) and age-, sex-, and BMI-matched normotensive individuals (NORMO). We hypothesized that (1) untreated individuals with hypertension will present compromised muscle oxygenation and impaired microvascular function versus normotensives and (2) these alterations could limit oxygen delivery to exercising muscles in hypertensive patients versus normotensives and contribute to further amplifications in BP responses during exercise in the former group.…”

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confidence: 99%

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Impaired Muscle Oxygenation and Elevated Exercise Blood Pressure in Hypertensive Patients

et al. 2017

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E ssential hypertension is characterized by sustained elevations of blood pressure (BP) that can lead to target organ damage and an increased risk for cardiovascular disease. 1Potential life-threatening outcomes of hypertension, such as stroke, renal insufficiency, and cardiac hypertrophy, had been initially perceived as a result of macrovascular alterations. These macrovascular events, however, do not occur independently of microvascular derangement. [2][3][4] Studies have shown that alterations in microvascular structure (rarefaction), vasomotor tonus (enhanced vasoconstriction or blunted vasodilation), and endothelial dysfunction are principal processes in the pathogenesis of hypertension and are evident in several organs/tissue types. [5][6][7][8] In the skeletal muscle, microvascularization is important for oxygen and nutrient supply and for effective metabolite clearance. Studies in hypertension have shown structural or functional impairments in the microvasculature within skeletal muscles, 8 implying a reduced capacity for oxygen delivery and exchange. Furthermore, animal studies using experimental models of hypertension suggested that mitochondrial dysfunction (ie, decreased expression of mitochondrial components and defects in respiratory complexes) and increased oxidative stress result in impaired oxidative capacity and reduced mitochondrial ATP production.9,10 Importantly, in these animals, the mitochondrial dysfunction and the reduced oxidative capacity were present before the development of hypertension, suggesting a possible role of these processes to the pathogenesis of hypertension.11 However, information on skeletal muscle microvascular alterations and oxidative Abstract-This study examined in vivo (1) skeletal muscle oxygenation and microvascular function, at rest and during handgrip exercise, and (2) their association with macrovascular function and exercise blood pressure (BP), in newly diagnosed, never-treated patients with hypertension and normotensive individuals. Ninety-one individuals (51 hypertensives and 40 normotensives) underwent office and 24-hour ambulatory BP, arterial stiffness, and central aortic BP assessment, followed by a 5-minute arterial occlusion and a 3-minute submaximal handgrip exercise. Changes in muscle oxygenated and deoxygenated hemoglobin and tissue oxygen saturation were continuously monitored by nearinfrared spectroscopy and beat-by-beat BP by Finapres. Hypertensives had higher (P<0.001) central aortic BP and pulse wave velocity versus normotensives and exhibited (1) a blunted tissue oxygen saturation response during occlusion, with slower (P=0.006) deoxygenation rate, suggesting reduced muscle oxidative capacity, and (2) a slower reoxygenation rate and blunted hyperemic response (P<0.05), showing reduced microvascular reactivity. Muscle oxygenation responses were correlated with aortic systolic and pulse pressure and augmentation index (P<0.05; age and body mass index (BMI) adjusted). When exercising at the same submaximal intensity, hypertensives required a sig...

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Section: Testing Procedures and Instrumentationmentioning

confidence: 99%

Section: Testing Procedures and Instrumentationmentioning

confidence: 99%

Section: Testing Procedures and Instrumentationmentioning

confidence: 99%

mentioning

confidence: 98%

mentioning

confidence: 99%

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Impaired Muscle Oxygenation and Elevated Exercise Blood Pressure in Hypertensive Patients

et al. 2017

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SIRT3 deficiency is resistant to autophagy‐dependent ferroptosis by inhibiting the AMPK/mTOR pathway and promoting GPX4 levels

Han

Jiang

et al. 2020

Journal Cellular Physiology

134

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Ferroptosis, an autophagy‐dependent cell death, is characterized by lipid peroxidation and iron accumulation, closely associated with pathogenesis of gestational diabetes mellitus (GDM). Sirtuin 3 (SIRT3) has positive regulation on phosphorylation of activated protein kinase (AMPK), related to maintenance of cellular redox homeostasis. However, whether SIRT3 can confer autophagy by activating the AMPK‐mTOR pathway and consequently promote induction of ferroptosis is unknown. We used human trophoblastic cell line HTR8/SVneo and porcine trophoblastic cell line pTr2 to deterimine the mechanism of SIRT3 on autophagy and ferroptosis. The expression of SIRT3 protein was significantly elevated in trophoblastic cells exposed to high concentrations of glucose and ferroptosis‐inducing compounds. Increased SIRT3 expression contributed to classical ferroptotic events and autophagy activation, whereas SIRT3 silencing led to resistance against both ferroptosis and autophagy. In addition, autophagy inhibition impaired SIRT3‐enhanced ferroptosis. On the contrary, autophagy induction had a synergistic effect with SIRT3. Based on mechanistic investigations, SIRT3 depletion inhibited activation of the AMPK‐mTOR pathway and enhanced glutathione peroxidase 4 (GPX4) level, thereby suppressing autophagy and ferroptosis. Furthermore, depletion of AMPK blocked induction of ferroptosis in trophoblasts. We concluded that upregulated SIRT3‐enhanced autophagy activation by promoting AMPK‐mTOR pathway and decreasing GPX4 level to induce ferroptosis in trophoblastic cells. SIRT3 deficiency was resistant to high glucose‐ and erastin‐induced autophagy‐dependent ferroptosis and is, therefore, a potential therapeutic approach for treating GDM.

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Impact of gestational diabetes on pelvic floor: A prospective cohort study with three‐dimensional ultrasound during two‐time points in pregnancy

Filho

Pinheiro

Prudêncio

et al. 2020

Neurourology and Urodynamics

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Aim: To evaluate the pelvic floor (PF) biometry using three-dimensional ultrasound (US) at two-time points of gestational in pregnant women with gestational diabetes mellitus (GDM). Methods: A prospective cohort study conducted at the Perinatal Diabetes Research Center including 44 pregnant women with GDM and 66 pregnant women without GDM at 24 to 28 weeks of gestation. Three-dimensional transperineal US was performed at 24 to 28 and 34 to 38 weeks of gestation in the lithotomy position at rest. The axial plane of the minimal Levator hiatal dimensions was used to determine Levator ani muscle and Hiatal area (HA) biometry at 24 to 28 and 34 to 38 weeks of gestation. Results: Of the 110 pregnant women, 100 (90.9%) completed the follow-up at 34 to 38 weeks of gestation. The evaluation by US showed a negative biometric change between the two-time points, during pregnancy in women with GDM; in the HA (β coefficient: estimative of effect in biometric progression according to GDM diagnosis, using the non-GDM group as reference = −6.76; P = .020), anteroposterior diameter (β = −5.07; P = .019), and Levator ani thickness (β = −12.34; P = .005). Conclusions: Pregnant women with GDM had a significantly lower than expected percentage of changes in biometry of Levator ani thickness and HA from 24 to 28 to 34 to 38 weeks of gestation when compared with the group of pregnant women without GDM. GDM alters the morphology of PF structures assessed by three

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Impairments in microvascular function and skeletal muscle oxygenation in women with gestational diabetes mellitus: links to cardiovascular disease risk factors

Cited by 52 publications

References 48 publications

Impaired Muscle Oxygenation and Elevated Exercise Blood Pressure in Hypertensive Patients

Impaired Muscle Oxygenation and Elevated Exercise Blood Pressure in Hypertensive Patients

SIRT3 deficiency is resistant to autophagy‐dependent ferroptosis by inhibiting the AMPK/mTOR pathway and promoting GPX4 levels

Impact of gestational diabetes on pelvic floor: A prospective cohort study with three‐dimensional ultrasound during two‐time points in pregnancy

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