A Novel Polymorphism in 11β-Hydroxysteroid Dehydrogenase Type 2 Gene (HSD11B2) Is Associated with High Urinary Excretion of Tetrahydro-11-Deoxycortisol (THS) in Essential Hypertensive Patients.

The 11β-hydroxysteroid dehydrogenase (11β-HSD) isoenzymes catalyse the interconversion of cortisol and cortisone. Type 1 11β-HSD mainly converts cortisone into active cortisol. Type 2 11β-HSD inactivates cortisol in mineralocorticoid target tissues, and its activity can be inhibited by glycyrrhetinic acid (GA). Inactivation of cortisol to cortisone is impaired in a subgroup of patients with primary hypertension. To study where this defect is located, we measured cortisol and cortisone concentrations in arterial plasma, in saliva and across the forearm at baseline and after administration of GA in normotensive and hypertensive subjects. GA (500mg) or placebo was administered orally to 20 normotensive subjects in a placebo-controlled double-blind fashion. Further, we compared the effect of GA in 20 patients with primary hypertension with that in 20 normotensive subjects. Cortisol and cortisone were measured in plasma from the brachial artery and vein and in saliva. Samples were obtained at 0, 90 and 150min. Forearm blood flow (FBF) was measured simultaneously. Forearm production of corticosteroid hormones was assessed by multiplying the arteriovenous difference in corticosteroid concentration by FBF. The cortisol/cortisone ratio in arterial plasma remained at baseline levels after placebo (4.9±1.2; mean±S.D.), while after GA the ratio increased similarly in normotensive subjects (12.3±3.4) and in hypertensive patients (12.2±3.7). A similar effect of GA on the salivary cortisol/cortisone ratio was found. In both normotensive subjects and hypertensive patients no forearm production of cortisol or cortisone could be demonstrated, either at baseline or after administration of GA. Thus, both before and after GA administration, we did not find any difference in systemic and salivary 11β-HSD type 2 activity between subjects with primary hypertension and normotensive controls. Further, both at baseline and after GA administration we were not able to demonstrate net inactivation or re-activation of cortisol and cortisone by the 11β-HSD isoenzymes in the forearm in either normotensive or primary hypertensive subjects.

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M.479 Prevalence of an altered nocturnal decline of blood pressure in hypertensive patients with type 2 diabetes

Atherosclerosis ◽

10.1016/s0021-9150(04)90477-7 ◽

2004 ◽

Vol 5 (1) ◽

pp. 111

Author(s):

C CALVO

Keyword(s):

Blood Pressure ◽

Type 2 Diabetes ◽

Hypertensive Patients

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Short-Term Reproducibility of Non-Dipping Pattern in Type 2 Diabetic Hypertensive Patients

High Blood Pressure & Cardiovascular Prevention ◽

10.2165/00151642-200512030-00013 ◽

2005 ◽

Vol 12 (3) ◽

pp. 151

Author(s):

V. Fusi ◽

C. Cuspidi ◽

S. Meani ◽

L. Lonati ◽

C. Valerio ◽

...

Keyword(s):

Short Term ◽

Hypertensive Patients ◽

Type 2 Diabetic

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Determination of risk factors associated with inflammation in hypertensive patients with type-2 diabetes mellitus in a Palestinian Diabetes Study

Current Medical Research and Opinion ◽

10.1080/03007995.2021.1941826 ◽

2021 ◽

pp. 1-1

Author(s):

Mohammed S. Ellulu ◽

Ihab A. Naser ◽

Sahar M. Abuhajar ◽

Ahmed A. Najim

Keyword(s):

Diabetes Mellitus ◽

Risk Factors ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Hypertensive Patients ◽

Factors Associated

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The effect of liraglutide and sitagliptin on oxidative stress in persons with type 2 diabetes

Scientific Reports ◽

10.1038/s41598-021-90191-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Suvanjaa Sivalingam ◽

Emil List Larsen ◽

Daniel H. van Raalte ◽

Marcel H. A. Muskiet ◽

Mark M. Smits ◽

...

Keyword(s):

Oxidative Stress ◽

Type 2 Diabetes ◽

Nucleic Acid ◽

Urinary Excretion ◽

Post Hoc Analysis ◽

Significant Difference ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Post Hoc

AbstractGlucagon-like peptide 1 receptor agonists have shown cardioprotective effects which have been suggested to be mediated through inhibition of oxidative stress. We investigated the effect of treatment with a glucagon-like peptide 1 receptor agonist (liraglutide) on oxidative stress measured as urinary nucleic acid oxidation in persons with type 2 diabetes. Post-hoc analysis of two independent, randomised, placebo-controlled and double-blinded clinical trials. In a cross-over study where persons with type 2 diabetes and microalbuminuria (LIRALBU, n = 32) received liraglutide (1.8 mg/day) or placebo for 12 weeks in random order, separated by 4 weeks of wash-out. In a parallel-grouped study where obese persons with type 2 diabetes (SAFEGUARD, n = 56) received liraglutide (1.8 mg/day), sitagliptin (100 mg/day) or placebo for 12 weeks. Endpoints were changes in the urinary markers of DNA oxidation (8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG)) and RNA oxidation [8-oxo-7,8-dihydroguanosine (8-oxoGuo)]. In LIRALBU, we observed no significant differences between treatment periods in urinary excretion of 8-oxodG [0.028 (standard error (SE): 0.17] nmol/mmol creatinine, p = 0.87) or of 8-oxoGuo [0.12 (0.12) nmol/mmol creatinine, p = 0.31]. In SAFEGUARD, excretion of 8-oxodG was not changed in the liraglutide group [2.8 (− 8.51; 15.49) %, p = 0.62] but a significant decline was demonstrated in the placebo group [12.6 (− 21.3; 3.1) %, p = 0.02], resulting in a relative increase in the liraglutide group compared to placebo (0.16 nmol/mmol creatinine, SE 0.07, p = 0.02). Treatment with sitagliptin compared to placebo demonstrated no significant difference (0.07 (0.07) nmol/mmol creatinine, p = 0.34). Nor were any significant differences for urinary excretion of 8-oxoGuo liraglutide vs placebo [0.09 (SE: 0.07) nmol/mmol creatinine, p = 0.19] or sitagliptin vs placebo [0.07 (SE: 0.07) nmol/mmol creatinine, p = 0.35] observed. This post-hoc analysis could not demonstrate a beneficial effect of 12 weeks of treatment with liraglutide or sitagliptin on oxidatively generated modifications of nucleic acid in persons with type 2 diabetes.

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