Type 2 Diabetes Mellitus and Hypertension

Lastra, Guido; Syed, Sofia; Kurukulasuriya, L. Romayne; Manrique, Camila; Sowers, James R.

doi:10.1016/j.ecl.2013.09.005

Cited by 261 publications

(209 citation statements)

References 123 publications

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“…These may contribute to hypertension [7] or to increased arterial stiffness related to vascular calcification or accumulation of collagen [8,9] that could partly explain the increased risk of vascular complications associated with T2DM [4].…”

Section: Introductionmentioning

confidence: 99%

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Effects of empagliflozin on blood pressure and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes

Chilton

Tikkanen

Cannon

et al. 2015

Diabetes Obesity Metabolism

417

283

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Aims:To determine the effects of empagliflozin on blood pressure (BP) and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes mellitus (T2DM). Methods:We conducted a post hoc analysis of data from a phase III trial in patients with T2DM and hypertension receiving 12 weeks' empagliflozin and four phase III trials in patients with T2DM receiving 24 weeks' empagliflozin (cohort 1, n = 823; cohort 2, n = 2477). BP was measured using 24-h BP monitoring (cohort 1) or seated office measurements (cohort 2).Results: Empagliflozin reduced systolic BP (SBP) and diastolic BP in both cohorts (p < 0.001 vs placebo), without increasing heart rate. Empagliflozin reduced pulse pressure (PP; adjusted mean difference vs placebo cohort 1: −2.3 mmHg; cohort 2: −2.3 mmHg), mean arterial pressure (MAP; cohort 1, −2.3 mmHg; cohort 2, −2.1 mmHg) and double product (cohort 1, −385 mmHg × bpm; cohort 2, −369 mmHg × bpm) all p < 0.001 vs placebo. There was a trend towards a reduction in the ambulatory arterial stiffness index (AASI) with empagliflozin in cohort 1 (p = 0.059 vs placebo). AASI was not measured in cohort 2. Subgroup analyses showed that there were greater reductions in PP with increasing baseline SBP in cohort 1 (p = 0.092). In cohort 2, greater reductions in MAP were achieved in patients with higher baseline SBP (p = 0.027) and greater reductions in PP were observed in older patients (p = 0.011). Conclusions IntroductionCardiovascular (CV) disease is the major cause of morbidity and mortality in patients with type 2 diabetes (T2DM) [1]. The risk of CV disease in adults with diabetes is double that in adults without diabetes, and diabetes is estimated to account for 10-12% of all vascular deaths [2]. Patients with T2DM often have numerous CV risk factors and a multifactorial approach to addressing CV risk, including controlling glycaemia, blood pressure (BP) and body weight, is recommended in these patients [1,3].The metabolic abnormalities that are characteristic of diabetes, such as hyperglycaemia, excess free fatty acids and insulin resistance, can lead to suppression of nitric oxide production and activation of the renin-angiotensin system, leading to oxidative stress, endothelial dysfunction and activation of the receptor for advanced glycation end products (RAGE) [4][5][6]. These may contribute to hypertension [7] or to increased arterial stiffness related to vascular calcification or accumulation ofCorrespondence to: Odd Erik Johansen, Boehringer Ingelheim Norway KS, Asker, Norway. E-mail: odd_erik.johansen@boehringer-ingelheim.com This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.collagen [8,9] that could partly explain the increased risk of vascular complications associated with T2DM [4].Arterial stiffness is a strong predictor of CV events, heart failure and death [10][11][12]...

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Section: Introductionmentioning

confidence: 99%

“…These may contribute to hypertension [7] or to increased arterial stiffness related to vascular calcification or accumulation of…”

Section: Introductionmentioning

confidence: 99%

Effects of empagliflozin on blood pressure and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes

Chilton

Tikkanen

Cannon

et al. 2015

Diabetes Obesity Metabolism

417

283

View full text Add to dashboard Cite

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Section: Discussionmentioning

confidence: 99%

“…Hypertension is approximately twice as frequent in diabetes mellitus (DM) compared with non-DM patients 6) and RHTN is highly associated with DM, 7) but the etiology of hypertension and cardiovascular complications in DM patients is not fully understood. 8) It was reported that add-on treatment of an MR antagonist alleviated persistent albuminuria in DM patients with conventional antihypertensive treatment, 9) which suggests that aberrant MR activation could be also an underlying mechanism of hypertension in DM patients.…”

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confidence: 99%

High Glucose Stimulates Mineralocorticoid Receptor Transcriptional Activity Through the Protein Kinase C β Signaling

et al. 2017

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SummaryActivation of mineralocorticoid receptor (MR) is shown in resistant hypertension including diabetes mellitus. Although protein kinase C (PKC) signaling is involved in the pathogenesis of diabetic complications, an association between PKC and MR is not known. Activation of PKCα and PKCβ by TPA (12-OTetradecanoylphorbol 13-acetate) increased MR proteins and its transcriptional activities in HEK293-MR cells. In contrast, a high glucose condition resulted in PKCβ but not PKCα activation, which is associated with elevation of MR protein levels and MR transcriptional activities. Reduction of endogenous PKCβ by siRNA decreased those levels. Interestingly, high glucose did not affect MR mRNA levels, but rather decreased ubiquitination of MR proteins. In db/db mice kidneys, levels of phosphorylated PKCβ2, MR and Sgk-1 proteins were elevated, and the administration of PKC inhibitor reversed these changes compared to db/+ mice. These data suggest that high glucose stimulates PKCβ signaling, which leads to MR stabilization and its transcriptional activities.( 3) which have elucidated that add-on therapy of MR antagonist is beneficial for the improvement of prognosis in heart failure patients, we became aware in recent decades that aberrant MR activation could be crucially involved in cardiovascular morbidity and mortality. Indeed it is prevalently known that primary aldosteronism, in which aldosterone excess causes hypertension through MR activation, increases the risk of cardiovascular events such as myocardial infarction and arrhythmia by three-to five-fold over essential hypertension.4) Additionally, add-on treatment of an MR antagonist has also been demonstrated to be effective in resistant hypertension (RHTN), 5) suggesting that activation of MR would play a key role on the progression of RHTN. These clinical findings has been driving many researchers to focus on the molecular mechanism of aberrant MR activation in RHTN and its related organ damages, but a detailed mechanism remains largely unknown.Hypertension is approximately twice as frequent in diabetes mellitus (DM) compared with non-DM patients 6) and RHTN is highly associated with DM, 7) but the etiology of hypertension and cardiovascular complications in DM patients is not fully understood.8) It was reported that add-on treatment of an MR antagonist alleviated persistent albuminuria in DM patients with conventional antihypertensive treatment, 9) which suggests that aberrant MR activation could be also an underlying mechanism of hypertension in DM patients. We have recently proposed such MR antagonist-responsive hypertension as "MR-associated hypertension" 10) and investigated the molecular actions of MR, among which we identified several novel coregulators of MR. 11,12) DM is a major cause of macro-and microvascular complications. The molecular mechanisms for those vascular complications have been explained by several moFrom the

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“…The cause of hypertension in Turner syndrome is multi-factorial [14]. Factors involved in the pathogenesis of hypertension and diabetes include inappropriate activation of the renin-angiotensin-aldosterone (RAA) system, oxidative stress, inflammation, impaired insulin-mediated vasodilatation, increased stimulation of sympathetic nervous system (SNS) and abnormal sodium excretion by the kidney [15]. The contribution of both RAA axis and SNS in the pathogenesis of hypertension remains uncertain.…”

Section: Introductionmentioning

confidence: 99%

Korzystny wpływ estradiolu na ciśnienie tętnicze, nie na stężenia glukozy i lipidów kobiet z zespołem Turnera

Irzyniec

Jeż

2016

Arterial Hypertension

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Introduction. Turner syndrome (TS) is the form of gonadal malfunction. Arterial hypertension, elevated LDL and glucose and decreased HDL levels are characteristic of TS-women. Hormone therapy is a treatment for short stature and sex hormone deficits. Hormonal replacement therapy (HRT) reduces the risk of cardiovascular diseases. A large percentage of TS-women do not comply with doctors' orders regarding HRT. The analysis of 17b estradiol(E 2 ) levels and the assessment of blood pressure, lipid and carbohydrate metabolisms in TS-women it is possible to state whether HRT decreases the risk of cardiovascular diseases? Material and methods. The group of 95 TS-women, who declared HRT, were investigated. The information about HRT was collected during the anamnesis. E 2 , total cholesterol (TC), high (HDL) and low (LDL) density lipoproteins, triglycerides (TG) and glucose were assessed. Patients were divided into subgroups with E 2 ≥ 110 pmol/L (n = 34) (HE) and < 110 pmol/L (n = 61) (LE) respectively. Results. Arterial hypertension was diagnosed in 26.3%. The groups did not differ in systolic 119 ± 20 versus 118 ± 14 and diastolic 82 ± 13 versus 80 ± 10 mm Hg blood pressure. Despite the higher concentrations of E 2 in HE, no differences were found in weights, lipids and glucose concentrations. Negative correlations between E 2 and body mass (r = -0.25, p = 0.04) and diastolic blood pressure (r = -0.28, p = 0.02) as well as positive between E 2 and glucose (r = 0.24, p < 0.05) were observed only in HE. No correlations between E 2 and lipids were found. Conclusions. 1. Only 1/3 TS-women, who declare HRT, have a satisfactory level of E 2 . 2. In TS-women HRT does not affect glucose and lipid metabolisms. 3. Negative correlation between E 2 and diastolic blood pressure in TS-women suggest beneficial effect of estrogens in hypertension.

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Type 2 Diabetes Mellitus and Hypertension

Cited by 261 publications

References 123 publications

Effects of empagliflozin on blood pressure and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes

Effects of empagliflozin on blood pressure and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes

High Glucose Stimulates Mineralocorticoid Receptor Transcriptional Activity Through the Protein Kinase C β Signaling

Korzystny wpływ estradiolu na ciśnienie tętnicze, nie na stężenia glukozy i lipidów kobiet z zespołem Turnera

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