Zusammenfassung
HINTERGRUND: Eine Dysfunktion des Gefäß-Endothels, die vaskulären Erkrankungen und Typ 2 Diabetes vorausgehen kann, zeigt sich bei Patientinnen nach Gestationsdiabetes. Es ist allerdings nicht geklärt ob Adipositas, asymetrisches Dimethylarginin (ADMA), ein endogener Stickstoffmonoxid (NO) Synthese Inhibitor oder Insulin-Resistenz die beobachteten Gefäß-Veränderungen bei diesen Patientinnen zusätzlich verstärken. Ziel dieser Studie war es daher, Faktoren zu finden, die die Gefäß-Dysfunktion zusätzlich zum Gestationsdiabetes beeinträchtigen. METHODEN: 7 übergewichtige und 5 normalgewichtigen Patientinnen nach Gestationsdiabetes wurden in diese Studie eingeschlossen. Die Gefäß-Funktion wurde durch Änderungen des Unterarm-Blutflusses auf den Endothel-abhängigen Vasodilatator Acetylcholin (ACh), den Endothel-unabhängigen Vasodilatator Nitroglycerin (GTN), den Vasokonstriktor Norepinephrin (NE) und den NO-Synthase Inhibitor N(G)-monomethyl-L-arginine (L-NMMA) gemessen. ADMA wurde aus venösen Blutproben bestimmt und die Insulin-Resistenz wurde mittels eines modifizierten intravenösen Glukose-Toleranz Tests abgeschätzt. 20 gesunde, männliche Probanden dienten als historische Kontroll-Gruppe. RESULTATE: Verglichen mit Normalgewichtigen war die Reaktion des Unterarm-Blutflusses auf ACh bei übergewichtigen Frauen gestört (p < 0.05); ebenso war die Antwort auf den Vasokonstriktor NE tendenziell bei dieser Gruppe verringert. Weiters gab es signifikante Korrelationen zwischen der vaskulären Antwort auf ACh beziehungsweise L-NMMA und Body Mass Index, Serum ADMA Konzentrationen und stimulierten Glukose Werten (alle p < 0.05). Normalgewichtigen Patientinnen hatten mit der gesunden Kontrollgruppe vergleichbares Ansprechen auf ACh und ADMA Konzentrationen. SCHLUSSFOLGERUNG: Faktoren wie Übergewicht, erhöhte ADMA Werte und Insulin-Resistenz dürften starken Einfluss auf die Endotheliale Dysfunktion bei Patientinnen nach Gestationsdiabetes haben.
Summary
BACKGROUND: Dysfunction of the vascular endothelium, preceding vascular morbidity and type 2 diabetes, is present in women with previous gestational diabetes (GDM). However, it is unknown whether excess weight, insulin resistance, and asymmetric dimethylarginine (ADMA) – an endogenous nitric oxide (NO) synthase inhibitor – also contribute to the vascular changes observed in these patients. The aim of this study was therefore to identify factors other than GDM that impair vascular function. METHODS: Seven overweight and five non-overweight women with previous GDM were included in this study. Vascular function was assessed from forearm blood-flow responses to the endothelium-dependent vasodilator acetylcholine (ACh), the endothelium-independent vasodilator glyceryltrinitrate, the vasoconstrictor norepinephrine and the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA). ADMA was measured in venous blood, and insulin resistance was estimated from a modified intravenous glucose tolerance test. Twenty healthy male volunteers served as a historical control group. RESULTS: Vasodilation of forearm resistance vessels in response to ACh was impaired in overweight women when compared with non-overweight women (P < 0.05); similarly, vasoconstrictor reactivity tended to be smaller in the overweight group. In addition, there was a significant relationship between vascular responsiveness to ACh and L-NMMA, body-mass index, serum ADMA concentrations and stimulated glucose levels (all P < 0.05). ACh responses and ADMA levels in non-overweight women were similar to those of healthy controls. CONCLUSION: Factors such as obesity, increased ADMA levels and insulin resistance appear to be strong contributors to endothelial dysfunction observed in women with GDM.
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Pleiner, J., Mittermayer, F., Langenberger, H. et al. Impaired vascular nitric oxide bioactivity in women with previous gestational diabetes. Wien Klin Wochenschr 119, 483–489 (2007). https://doi.org/10.1007/s00508-007-0838-8
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DOI: https://doi.org/10.1007/s00508-007-0838-8