scholarly journals Empagliflozin as a new management strategy on outcomes in patients with type 2 diabetes mellitus

2016 ◽  
Vol 19 (6) ◽  
pp. 494-510 ◽  
Author(s):  
Vladimir V. Salukhov ◽  
Tatiana Y. Demidova
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Mechanism Of Action ◽  
Glucose Lowering ◽  
Long Duration ◽  
Increased Risk ◽  
Urinary Glucose ◽  
Cv Disease

Patients with type 2 diabetes mellitus have an increased risk of cardiovascular (CV) complications. Although hyperglycaemia contributes to the pathogenesis of atherosclerosis and heart failure in these patients, glucose-lowering strategies did not have a significant effect on reducing CV risk, particularly in patients with a long duration of type 2 diabetes mellitus and prevalent CV disease (CVD). Sodium-glucose linked transporter-2 (SGLT2) inhibitors are a new class of anti-hyperglycaemic medications that increase glycaemic control via insulin-dependent mechanism of action associated with increased urinary glucose excretion.In this review, we present an analysis of the Empa-Reg Outcomes investigation, focussed on assessing the CV safety of empagliflozin, an inhibitor of SGLT2. We discuss the impressive results of trials that provide evidence on the cardiac and renal properties of empagliflozin. We present and analyse the current hypothesis on the mechanism of action of glucose-lowering medication, which has such a severe and complex impact on outcomes in patients with type 2 diabetes at high CV risk.

Abstract 16107: Combined HbA1c and Systolic Blood Pressure Reduction With Dapagliflozin in Patients With Both Inadequately Controlled Type 2 Diabetes Mellitus and Hypertension

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Michael A Weber ◽  
James List ◽  
Traci A Mansfield ◽  
Shamik J Parikh ◽  
Agata Ptaszynska
Keyword(s):  
Diabetes Mellitus ◽  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Systolic Blood Pressure ◽  
Enzyme Inhibitor ◽  
Blood Pressure Reduction ◽  
Glucose Lowering ◽  
Urinary Glucose

Background: Hypertension is a common comorbidity in patients with type 2 diabetes mellitus (T2DM). Initial treatment is usually with an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB), with other antihypertensive therapies (AHTs) added if needed. Dapagliflozin (DAPA) increases urinary glucose excretion accompanied by diuresis and weight loss, which contributes to blood pressure (BP) reduction. Here we evaluate the proportions of patients achieving combined HbA1c and systolic blood pressure (SBP) reduction with DAPA in two studies of patients with both inadequately controlled T2DM and hypertension. Methods: Patients with both inadequately controlled T2DM (HbA1c 7.0-10.5%) and hypertension (seated SBP / diastolic BP: 140-164 / 85-104 mmHg) despite receiving glucose-lowering drugs and an ACEi or ARB (Study 1) plus a 2nd AHT agent (Study 2) were randomized to receive double-blind DAPA 10 mg or placebo for 12 weeks. Primary results have been presented previously; here we present proportions of patients achieving combined changes from baseline (Δ) in HbA1c and SBP. Results: In Study 2, additional AHT drugs were thiazide/thiazide-like diuretics (~44%), calcium channel blockers (~27%), and beta blockers (~27%). Across both studies, 520 and 522 patients had available paired ΔHbA1c and ΔSBP values in the DAPA and placebo groups, respectively. More patients achieved combined ΔHbA1c and ΔSBP reduction with DAPA (n=325; 62.5%) vs placebo (n=190; 36.4%) (Figure - dotted boxes). Considering more stringent thresholds, more patients achieved combined reductions in ΔHbA1c of ≥0.5% and ΔSBP of ≥5 mmHg with DAPA (n=194; 37.3%) vs placebo (n=86; 16.5%) (Figure - solid boxes). Conclusions: In T2DM patients with hypertension on glucose-lowering therapies and an ACEi or ARB ± 1 additional AHT, adding dapagliflozin achieved clinically significant combined HbA1c and SBP reductions over 12 weeks in greater numbers of patients than placebo.

scholarly journals Anti-diabetic agents for prevention of type 2 diabetes mellitus in people with pre-diabetes: a systematic review and network meta-analysis protocol

BMJ Open ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. e029073 ◽  
Author(s):  
Xianzhe Wang ◽  
Jiabin Liu ◽  
Lijin Huang ◽  
Hai Zeng ◽  
Guoxin He ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Systematic Review ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diabetes Prevention ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Glucose Lowering ◽  
Increased Risk

IntroductionType 2 diabetes mellitus (T2DM) is a substantial health problem worldwide. Pre-diabetic state is associated with increased risk for the development of diabetes. There are various pharmacological therapies with glucose-lowering activity for diabetes prevention. Of those, most are being compared with placebo instead of active agents. The relative effects and safety of different glucose-lowering drugs still remain uncertain. To address this gap, we will conduct a systematic review and network meta-analysis (NMA) to evaluate comparative efficacy and safety of glucose-lowering agents for T2DM prevention in patients with pre-diabetes.Methods and analysisPubMed, the Cochrane library and Embase will be searched from inception to December 2019 for relevant randomised controlled trials (RCTs) that examined anti-diabetic drugs for diabetes prevention in patients with pre-diabetes. Two reviewers working independently will screen titles, abstracts and full papers. Data extraction will also be completed by two independent authors. The primary outcome will be the incidence of T2DM in patients with pre-diabetes at baseline. Secondary outcomes will include the achievement of normoglycaemia, all-cause mortality, cardiovascular mortality and hypoglycaemic event. Pairwise meta-analysis and NMA will be conducted for each outcome using a frequentist random-effects model. Additionally, subgroup analyses will also be performed. The comparison-adjusted funnel plot will be used to assess publication bias. The overall quality of evidence will be rated with the Grading of Recommendations Assessment, Development and Evaluation framework. Data analysis will be conducted using Stata V.14.0.Ethics and disseminationEthics approval is not required. We plan to submit the results of this study to a peer-review journal.PROSPERO registration numberCRD42019119157.

Abstract 14866: Plasma B-type Natriuretic Peptide Levels Are Associated With Future Cardiovascular Events in Patients With Type 2 Diabetes Mellitus Without Known Cardiovascular Disease

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Shota Ikeda ◽  
Keisuke Shinohara ◽  
Nobuyuki Enzan ◽  
Shouji Matsushima ◽  
Takeshi Tohyama ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Natriuretic Peptide ◽  
Vascular Events ◽  
Coronary Syndrome ◽  
Increased Risk ◽  
Cv Disease

Introduction: B-type natriuretic peptide (BNP) is known to predict future cardiovascular (CV) events in patients with known CV disease. However, these associations have not been investigated in patients with type 2 diabetes mellitus (T2DM) without known CV disease. We investigated whether BNP levels are associated with CV events among T2DM patients without known CV disease using the dataset of EMPATHY study. Methods and Results: The EMPATHY was a randomized controlled trial of intensive statin therapy in T2DM patients without known CV disease. CV events were defined as composite of cardiac (acute coronary syndrome and coronary revascularization [excluding heart failure]), cerebral, and vascular events. A total of 4704 patients without CV events or death during the first 12 months were included and 114 CV events occurred during a median follow-up of 37.8 months. The patients were divided based on quartile of baseline BNP levels (Q1: <7.4, Q2: 7.4-14.8, Q3: 14.8-28.7, Q4: ≥28.7 [pg/mL]). Compared to the lowest quartile of BNP, only the highest quartile was associated with increased risk for CV events after adjustment (HR 2.96, 95% CI 1.29-6.79, p=0.010). Using this highest quartile cutoff, we categorized BNP <28.7 pg/mL as low BNP and BNP ≥28.7 pg/mL as high BNP. Compared to patients with low BNP, the adjusted HRs for CV events were 2.12 (95% CI 1.35-3.34, p=0.001) in patients with high BNP at baseline and 2.64 (95% CI 1.67-4.17, p<0.001) in those with high BNP at 12 months. In analysis using serial measurement, patients who had repeatedly high BNP or had low BNP at baseline and high BNP at 12 months were in significantly higher risk for CV events compared to those who had repeatedly low BNP (HR 3.28, 95% CI 1.90-5.66, p<0.001 or HR 2.65, 95% CI 1.44-4.87, p=0.002, respectively), whereas those who had high BNP at baseline and low BNP at 12 months were not (HR 1.99, 95% CI 0.90-4.39, p=0.089). Conclusion: Increased BNP levels were associated with higher risk of CV events (excluding heart failure) in T2DM patients without known CV disease. HR for CV events was greater in patients with repeatedly high BNP than in those with high BNP at only one of the two measurements, suggesting that serial BNP measurement may be more useful for predicting future CV events in T2DM patients.

The GSTM1 and GSTT1 Null Genotypes Increase the Risk for Type 2 Diabetes Mellitus and the Subsequent Development of Diabetic Complications: A Meta-analysis

2018 ◽  
Vol 15 (1) ◽  
pp. 31-43 ◽  
Author(s):  
Sayantan Nath ◽  
Sambuddha Das ◽  
Aditi Bhowmik ◽  
Sankar Kumar Ghosh ◽  
Yashmin Choudhury
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Meta Analysis ◽  
Subsequent Development ◽  
Asian Population ◽  
Gstm1 Null Genotype ◽  
Increased Risk

Background:Studies pertaining to association of GSTM1 and GSTT1 null genotypes with risk of T2DM and its complications were often inconclusive, thus spurring the present study.Methods:Meta-analysis of 25 studies for evaluating the role of GSTM1/GSTT1 null polymorphisms in determining the risk for T2DM and 17 studies for evaluating the role of GSTM1/GSTT1 null polymorphisms in development of T2DM related complications were conducted.Results:Our study revealed an association between GSTM1 and GSTT1 null polymorphism with T2DM (GSTM1; OR=1.37;95% CI =1.10-1.70 and GSTT1; OR=1.29;95% CI =1.04-1.61) with an amplified risk of 2.02 fold for combined GSTM1-GSTT1 null genotypes. Furthermore, the GSTT1 null (OR=1.56;95%CI=1.38-1.77) and combined GSTM1-GSTT1 null genotypes (OR=1.91;95%CI=1.25- 2.94) increased the risk for development of T2DM related complications, but not the GSTM1 null genotype. Stratified analyses based on ethnicity revealed GSTM1 and GSTT1 null genotypes increase the risk for T2DM in both Caucasians and Asians, with Asians showing much higher risk of T2DM complications than Caucasians for the same. </P><P> Discussion: GSTM1, GSTT1 and combined GSTM1-GSTT1 null polymorphism may be associated with increased risk for T2DM; while GSTT1 and combined GSTM1-GSTT1 null polymorphism may increase the risk of subsequent development of T2DM complications with Asian population carrying an amplified risk for the polymorphism.Conclusion:Thus GSTM1 and GSTT1 null genotypes increases the risk for Type 2 diabetes mellitus alone, in combination or with regards to ethnicity.

Epidemiology of Hypertension and Diabetes Mellitus in Latin America

2020 ◽  
Vol 16 ◽  
Author(s):  
Patricio Lopez-Jaramillo ◽  
Jose Lopez-Lopez ◽  
Daniel Cohen ◽  
Natalia Alarcon-Ariza ◽  
Margarita Mogollon-Zehr
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Latin America ◽  
Cardiovascular Diseases ◽  
Latin American ◽  
Premature Mortality ◽  
Increased Risk ◽  
And Control

: Hypertension and type 2 diabetes mellitus are two important risk factors that contribute to cardiovascular diseases worldwide. In Latin America hypertension prevalence varies from 30 to 50%. Moreover, the proportion of awareness, treatment and control of hypertension is very low. The prevalence of type 2 diabetes mellitus varies from 8 to 13% and near to 40% are unaware of their condition. In addition, the prevalence of prediabetes varies from 6 to 14% and this condition has been also associated with increased risk of cardiovascular diseases. The principal factors linked to a higher risk of hypertension in Latin America are increased adiposity, low muscle strength, unhealthy diet, low physical activity and low education. Besides being chronic conditions, leading causes of cardiovascular mortality, both hypertension and type 2 diabetes mellitus represent a substantial cost for the weak health systems of Latin American countries. Therefore, is necessary to implement and reinforce public health programs to improve awareness, treatment and control of hypertension and type 2 diabetes mellitus, in order to reach the mandate of the Unit Nations of decrease the premature mortality for CVD.

scholarly journals Risk of Depression among Early Onset Type 2 Diabetes Mellitus Patients

2021 ◽  
pp. 1-11
Author(s):  
Baizid Khoorshid Riaz ◽  
Shahjada Selim ◽  
Megan Neo ◽  
Md Nazmul Karim ◽  
M. Mostafa Zaman
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Early Onset ◽  
Tertiary Care ◽  
Positive Family History ◽  
Depression Symptoms ◽  
Mixed Effect ◽  
Increased Risk

<b><i>Methodology:</i></b> Biochemically confirmed type 2 diabetes mellitus (T2DM) patients (<i>n</i> = 1,114) were recruited from the outpatient department of 2 tertiary care hospitals in Dhaka, Bangladesh. Face-to-face interview was conducted using a semi-structured questionnaire containing sociodemographic parameters and relevant information about depression and diabetes. Biochemical test results and treatment-related information were taken from patients’ records. The Hospital Anxiety and Depression Scale (HADS) was used to screen all patients for psychiatric manifestation. Those diagnosed by HADS were subsequently reassessed using structured clinical interview for DSM-5 Disorders – Clinician Version. T2DM diagnosed at age &#x3c;40 years were considered as early onset T2DM. Association between age of onset category and depression was assessed using multivariable mixed-effect logistic regression adjusting for random variation of the area of residence and plausible confounders. <b><i>Results:</i></b> Around a third of the participants (32.5%) were diagnosed with T2DM before the age of 40 years. Early onset T2DM patients were found to have 57% increase in the risk of developing depression (OR 1.57; 95% CI 1.13–2.28; <i>p</i> = 0.011) in comparison to those with usual onset T2DM (≥40 years). Among other factors a positive family history for diabetes (OR 1.33; 95% CI 1.03–1.78; <i>p</i> = 0.038), poor glycemic control (OR 1.31; 95% CI 1.03–1.68; <i>p</i> = 0.028), presence of 1, or more diabetic complications (OR 1.37; 95% CI 1.03–1.78; <i>p</i> = 0.011) also showed increased risk of depression. <b><i>Conclusion:</i></b> Early onset T2DM patients are at greater risk of developing depression. The finding is likely to help in setting preventive strategies aiming to reduce the presence of concomitant depression symptoms among diabetes.

scholarly journals Associations of markers of arterial stiffness and remodeling with new-onset type 2 diabetes mellitus

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
F Ahmadizar ◽  
K Wang ◽  
F Mattace Raso ◽  
MA Ikram ◽  
M Kavousi
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Arterial Stiffness ◽  
Wall Stress ◽  
Lipid Lowering ◽  
Circumferential Wall Stress ◽  
Increased Risk

Abstract Funding Acknowledgements Type of funding sources: None. Background. Arterial stiffness/remodeling results in impaired blood flow and, eventually, decreased glucose disposal in peripheral tissues and increased blood glucose. Besides, increased arterial stiffness/remodeling may lead to hypertension, as a potential reciprocal risk factor for type 2 diabetes mellitus (T2D). We, therefore, hypothesized that increased arterial stiffness/remodeling is associated with an increased risk of T2D. Purpose. To study the associations between arterial stiffness/remodeling and incident T2D. Methods. We used the prospective population-based Rotterdam Study. Common carotid arterial properties were ultrasonically determined in plaque-free areas. Aortic stiffness was estimated by carotid-femoral pulse wave velocity (cf_PWV), carotid stiffness was estimated by the carotid distensibility coefficient (carDC). Arterial remodeling was estimated by carotid artery lumen diameter (carDi), carotid intima-media thickness (cIMT), mean circumferential wall stress (CWSmean), and pulsatile circumferential wall stress (CWSpuls). Cox proportional hazard regression analysis was used to estimate the associations between arterial stiffness/remodeling and the risk of incident T2D, adjusted for age, sex, cohort, mean arterial pressure (MAP), antihypertensive medications, heart rate, non- high-density lipoprotein (HDL)-cholesterol, lipid-lowering medications, and smoking. We included interaction terms in the fully adjusted models to study whether any significant associations were modified by sex, age, blood glucose, or MAP. Spearman correlation analyses were applied to examine the correlations between measurements of arterial stiffness/remodeling and glycemic traits. Results. We included 3,055 individuals free of T2D at baseline (mean (SD) age, 67.2 (7.9) years). During a median follow-up of 14.0 years, 395 (12.9%) T2D occurred. After adjustments, higher cf_PWV (hazard ratio (HR),1.18; 95%CI:1.04-1.35), carDi (1.17; 1.04-1.32), cIMT (1.15; 1.01-1.32), and CWSpuls (1.28; 1.12-1.47) were associated with increased risk of incident T2D. After further adjustment for the baseline glucose, the associations attenuated but remained statistically significant. Sex, age, blood glucose, or MAP did not modify the associations between measurements of arterial stiffness/remodeling, and incident T2D. Among the population with prediabetes at baseline (n = 513) compared to the general population, larger cIMT was associated with a greater increase in the risk of T2D. Most measurements of arterial stiffness/remodeling significantly but weakly correlated with baseline glycemic traits, particularly with blood glucose.  Conclusions. Our study suggests that greater arterial stiffness/remodeling is independently associated with an increased risk of T2D development. Blood glucose and hypertension do not seem to play significant roles in these associations. Further studies should disentangle the underlying mechanism that links arterial stiffness/remodeling and T2D.

scholarly journals TheType 2 Deiodinase Thr92Ala PolymorphismIs Associated with Worse Glycemic Control in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Xiaowen Zhang ◽  
Jie Sun ◽  
Wenqing Han ◽  
Yaqiu Jiang ◽  
Shiqiao Peng ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Systematic Review ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glycemic Control ◽  
Meta Analysis ◽  
Increased Risk ◽  
Design And Methods ◽  
Hba1c Levels

Objective. Type 2 deiodinase (Dio2) is an enzyme responsible for the conversion of T4 to T3. The Thr92Ala polymorphism has been shown related to an increased risk for developing type 2 diabetes mellitus (T2DM). The aim of this study is to assess the association between this polymorphism and glycemic control in T2DM patients as marked by the HbA1C levels.Design and Methods.The terms “rs225014,” “thr92ala,” “T92A,” or “dio2 a/g” were used to search for eligible studies in the PubMed, Embase, and Cochrane databases and Google Scholar. A systematic review and meta-analysis of studies including both polymorphism testing and glycated hemoglobin (HbA1C) assays were performed.Results. Four studies were selected, totaling 2190 subjects. The pooled mean difference of the studies was 0.48% (95% CI, 0.18–0.77%), indicating that type 2 diabetics homozygous for the Dio2 Thr92Ala polymorphism had higher HbA1C levels.Conclusions. Homozygosity for the Dio2 Thr92Ala polymorphism is associated with higher HbA1C levels in T2DM patients. To confirm this conclusion, more studies of larger populations are needed.

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