Vascular Function in Women with Previous Gestational Diabetes mellitus

Abstract

It is hypothesised that vascular dysfunction, which characterises type 2 diabetes, may predate development of hyperglycaemia. 17 women with previous gestational diabetes mellitus, and thus at risk of developing type 2 diabetes, were matched with normal controls for body mass index, menstrual phase, smoking, age, blood pressure, and lipid profiles. All had normal glucose tolerance. Tests of microvascular and macrovascular function, including endothelium-dependent and -independent vasodilatation, were performed. Laser Doppler fluximetry of maximum skin microvascular hyperaemia in response to local heating of the dorsum of the foot to 42°C for 30 min was impaired in subjects compared to controls [subjects = 1.15 (0.73–1.73) V median (range) versus controls = 1.50 (0.95–2.29) V, p = 0.008]. There were no differences in laser Doppler perfusion imaging of responses to forearm skin iontophoresis of acetylcholine [subjects = 1.59 (0.32–2.55) V median (range) versus controls = 1.79 (0.72–2.06) V; p = 0.81] and sodium nitroprusside [subjects = 1.39 (0.8–3.14) V versus controls = 1.41 (0.34–2.19) V; p = 0.68], ultrasound estimation of brachial artery flow-mediated dilatation [subjects = 1.65 (–0.5–9.07)% versus controls = 2.77 (0.63–6.6)%; p = 0.42] and glyceryl trinitrate-induced dilatation [subjects = 15.20 (6.64–20.91)% versus controls = 15.92 (3.94–22.09)%; p = 0.48]. Microvascular maximum hyperaemia was impaired in the index group, suggesting the presence of a defect in vascular function. This defect was not explained by those aspects of endothelial function measured by the other techniques.

The Role of Oxidative Stress in Female Reproduction and Pregnancy

“…NF-κB and MAPK activate expression of several pro-inflammatory genes, including pro-inflammatory cytokines, the adhesion molecules vascular cell adhesion molecule (VCAM)-1, and intercellular cell adhesion molecule (ICAM)-1, and RAGE causing cellular inflammation. This is consistent with gestational diabetes being closely associated with low-grade inflammation (Kirwan et al, 2002) and atherosclerosis (Anastasiou et al, 1998;Hannemann et al, 2002). Additionally, the activation of cytokines by AGE in human placenta may also be involved in insulin resistance associated with gestational diabetes (Colomiere et al, 2009).…”

Review of gestational diabetes mellitus effects on vascular structure and function

“…10,12,13,19 The remaining studies each used differing criteria, ranging from serum glucose values proposed by Carpenter and Coustan, 22 …”

“…Two studies 10,17 asked subjects to refrain from smoking 'on the day of the study', while Volpe et al 13 and Gunderson et al 21 included subjects who were smokers. Hannemann et al 10,a Hu et al 11,a Volpe et al 13,b Fakhrzadeh et al 16,b Akinci et al 17,b Akinci et al 18,b Gunderson et al 21,b Age ( Brewster et al 15,b Freire et al 19,b Anastasiou et al 7,b Bo et al 9,b Pleiner et al 12,b Heitritter et al 20,b Age ( Brewster et al 15,b Freire et al 19,b Anastasiou et al 7,b Bo et al 9,b Pleiner et al 12,b Heitritter et al 20 Banerjee et al 8,a Davenport et al 14,b Age ( studies 7,10,11,14,17 reported waist-to-hip ratio, with previous GDM women having a higher ratio in three studies. 2,11,17 Of those reporting, waist circumference ranged from 71.7 ± 8.8 to 87 ± 0.6 cm in the controls and 73.6 ± 5.7 to 92 ± 13.19 cm in the previous GDM cases (Table 2).…”

Transdermal iontophoresis as an in-vivo technique for studying microvascular physiology

“…Also, it has been suggested that acetylcholine induces vasodilation through stimulation of sensory nerves (Berghoff et al, 2002). Despite conflicting evidence regarding the mechanisms by which the drug causes vasodilatation, ACh is commonly delivered iontophoretically to test endothelial function in a variety of clinical conditions, including diabetes (Arora et al, 1998;Cohen et al, 2008;Hannemann et al, 2002;Morris et al, 1995) , hypertension (Cupisti et al, 2000b;Farkas et al, 2004;Kellogg et al, 1998;Monostori et al, 2010), pre-eclampsia (Blaauw et al, 2005;Eneroth-Grimfors et al, 1993;Khan et al, 2005), Raynauds phenomenon (Anderson et al, 1996;Hettema et al, 2009;Khan and Belch, 1999), renal failure (Cupisti et al, 2000a), HIV (Monsuez et al, 2000) and heart failure (Andersson et al, 2005;Balmain et al, 2007). Also, it has been applied to investigate the effects of smoking (Pellaton et al, 2002), age (Rossi et al, 2002a), gender (Algotsson et al, 1995), hyperoxia (Rousseau et al, 2010;Yamazaki, 2007) and exercise (Lenasi and Strucl, 2004;Rossi et al, 2002b).…”