scholarly journals Pioglitazone for primary stroke prevention in Asian patients with type 2 diabetes and cardiovascular risk factors: A retrospective study

2020 ◽  
Author(s):  
Yi-Chih Hung ◽  
Lu-Ting Chiu ◽  
Hung-Yu Huang ◽  
Da-Tian Bau

Abstract Background: Studies assessing the efficacy of pioglitazone solely for primary stroke prevention in Asian patients with type 2 diabetes mellitus (DM) and present multiple cardiovascular (CV) risk factors are rare. Thus, we aimed to assess the effect of pioglitazone on primary stroke prevention in Asian patients with type 2 DM without established CV diseases but with risk factors for CV diseases. Methods: Between 2000 and 2012, we enrolled patients aged ≥18 years, who were newly diagnosed with type 2 diabetes and had at least one of the following CV risk factors: hypertension and hyperlipidemia. Patients with a history of stroke and those using insulin or glucagon-like peptide-1 agonist for more than 3 months were excluded. Patients were divided into the pioglitazone and non-pioglitazone groups based on their receipt of pioglitazone during the follow-up period. Propensity-score matching (1:1) was used to balance the distribution of the baseline characteristics and medications. Follow-up was terminated upon ischemic stroke development, withdrawal from the insurance system, or on December 31, 2013, whichever occurred first. The overall incidence of new-onset ischemic stroke in the two groups was subsequently compared. The subgroup analyses of ischemic stroke were conducted using different baseline features. Additionally, the effect of pioglitazone exposure dose on the occurrence of ischemic stroke was evaluated. Chi-square test, Student’s t-test, competing risk regression models, Kaplan–Meier method, and log-rank test were some of the statistical tests conducted.Results: A total of 13 078 patients were included in the pioglitazone and non-pioglitazone groups. Compared with patients who did not receive pioglitazone, those administered pioglitazone had a lower risk of developing ischemic stroke (adjusted hazard ratio: 0.78; 95% confidence interval: 0.62–0.95). The subgroup analyses defined by different baseline features did not reveal significant alterations in the observed effect of pioglitazone. Moreover, a significant decreasing trend in ischemic stroke risk with an increase in pioglitazone dose (p-value for trend = 0.04) was observed.Conclusion: Pioglitazone use decreased the risk of new-onset ischemic stroke in Asian patients with type 2 DM and CV risk factors.Trial registration number: CMUH104-REC2-115-CR4

2020 ◽  
Author(s):  
Yi-Chih Hung ◽  
Lu-Ting Chiu ◽  
Hung-Yu Huang ◽  
Da-Tian Bau

Abstract Background: To date, studies assessing the efficacy of pioglitazone solely for primary stroke prevention in Asian patients with type 2 diabetes mellitus (DM) and present multiple cardiovascular (CV) risk factors are rare. Thus, we aimed to assess the effect of pioglitazone on primary stroke prevention in Asian type 2 DM patients without established CV diseases but with risk factors for CV diseases. Methods: Between 2000 and 2012, we enrolled patients aged ≥18 years who were newly diagnosed with type 2 diabetes and had at least one of the following CV risk factors: hypertension, hyperlipidemia, proteinuria, and obesity. Patients with a history of stroke and those using insulin or glucagon-like peptide-1 agonist for more than 3 months were excluded. Patients were divided into the pioglitazone user group and non-pioglitazone user group based on their receipt of pioglitazone during the follow-up period. Propensity-score matching (1:1) was used to balance the distribution of the baseline characteristics and medications. Follow-up was terminated upon ischemic stroke development, withdrawal from the insurance system, or on December 31, 2013, whichever occurred first. The overall incidence of new-onset ischemic stroke in the two groups was subsequently compared. Subgroup analyses of ischemic stroke were conducted using different baseline features. Additionally, the effect of the pioglitazone exposure dose on the occurrence of ischemic stroke was evaluated. The chi-square test, Student’s t-test, Kaplan–Meier method, and log-rank test were some of the statistical tests conducted herein.Results: A total of 6,637 patients were included in the pioglitazone and non-pioglitazone group. Compared to patients who did not receive pioglitazone, those administered pioglitazone had a lower risk of developing ischemic stroke (adjusted hazard ratio: 0.72; 95% confidence interval: 0.57–0.9). Subgroup analyses defined by different baseline features did not reveal significant alterations to the observed effect of pioglitazone. Moreover, a significant trend regarding the decrease in ischemic stroke risk and the increase in pioglitazone dose (p-value for trend=0.03) was observed.Conclusion: Pioglitazone use decreased the risk of new-onset ischemic stroke in Asian patients with type 2 DM and CV risk factors.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T Youssri ◽  
M Ohlsson ◽  
V Hamrefors ◽  
O Mellander

Abstract Introduction Endothelin 1 is a potent vasoconstrictor released from mainly vascular endothelial cells and to a lesser extent adipose, muscle and renal tissues. Its involvement in cardiovascular disease is well documented, with increasing ET-1 levels correlated to cardiovascular events. Less is however, known about its role in insulin resistance and type 2 diabetes. Purpose To test if ET-1 plasma levels predict the risk of developing type 2 diabetes independently of known risk factors. Method The Malmo Preventive project is a prospective single centre population-based study which recruited 33 346 inhabitants in Malmo, Sweden between 1974–1992. A follow up study was conducted between 2002 and 2006 on willing participants of which 18 240 accepted. Cardiovascular risk factors were documented along with blood plasma samples frozen to −80°C available for further analysis among approximately 5000 subjects. Record linkage with national and regional diagnoses and drug prescription registries was performed to identify all new onset type 2 diabetes cases in this cohort during a mean follow-up period of nine years. C-terminal proendothelin-1 (proET-1), a stable precursor to ET-1, levels were analysed by a double sandwich immunoassay (ThermoFisher) among 4536 individuals with complete data and without diabetes at baseline. The subjects were divided into quartiles based on proET-1 levels and hazard ratios (HR) for new onset diabetes were calculated by Cox Proportional Hazards Model adjusting for age, gender, smoking, hypertension, body mass index (BMI) and fasting glucose. Results There was a positive relationship between increasing proET-1 quartiles and age (p<0.001), hypertension (p<0.001), BMI (p<0.001) and smoking (p<0.001). There was no significant relationship between ET-1 quartiles and fasting glucose (p=0.08) and gender (p=0.21). In models adjusted for age, gender, smoking, hypertension, fasting glucose and BMI among non-diabetic subjects each 1 standard deviation increment of proET-1 conferred a hazard ratio (95% confidence interval) for new onset diabetes during follow up period of 1.12 (1.00–1.26) (p=0.05). The hazard ratio for incident diabetes in quartile 4 (Q4) vs quartile 1 (Q1) was 1.40 (1.03–1.92) (p=0.03). Of note, the predictive value of proET-1 was markedly higher among individuals without pre-diabetes (fasting glucose <6.1) with a hazard ratio of 1.27 per standard deviation proET-1 (CI 1.09–1.49, p=0.02) and 2.18 (CI 1.41–3.36, p<0.001) when comparing proET-1 Q4 vs Q1. There was no significant relationship between the risk of new onset diabetes and proET-1 levels among pre-diabetic individuals. Conclusion Raised proET-1 levels among non-diabetic individuals independently predict risk of new onset type 2 diabetes. The predictive value is driven by the part of the population without prediabetes, suggesting that proET-1 might identify individuals at “hidden high risk”, i.e. indivduals who do not get medical attention by having prediabetes. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Knut & Alice Wallenberg Foundation Clinical Scholars and Göran Gustafsson Foundation


Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Gregory A Nichols ◽  
Shreekant Parasuraman ◽  
Sandra Joshua-Gotlib

Risk of ischemic stroke is approximately doubled in patients with diabetes. To reduce risk, managing diabetes includes optimizing glycemic, blood pressure (BP), and low-density lipoprotein cholesterol (LDL-C) control. We studied which risk factors alone or in combination were most strongly associated with stroke hospitalizations. We identified 26,924 Kaiser Permanente Northwest members with type 2 diabetes and no known prior cardiovascular disease hospitalization. Beginning in 2002, we identified the earliest point patients had glycosolated hemoglobin (HbA1c), systolic BP (SBP), and LDL-C measurements within 6 months of each other and followed them until they died, disenrolled, or 31 December 2011. Outcome was hospitalization with primary diagnosis of ischemic stroke. Using mean HbA1c, SBP, and LDL-C between baseline and end of follow-up, we identified dichotomous categories of control of HbA1c (<7%), SBP (<130 mm Hg) and LDL-C (<100 mg/dL) and estimated the relative risk of stroke hospitalization independently associated with all combinations of risk factors controlling for age, sex, diabetes duration, comorbidities, body mass index, smoking, and pharmacotherapy. Mean (SD) age of patients was 59 (12) years; 50% were men. Over mean (SD) follow-up of 6.2 (2.8) years, 606 (2.3%) patients were hospitalized for ischemic stroke. Compared with patients with all 3 risk factors in control, patients who had no risk factors controlled or only HbA1c controlled had >2-fold increased risk of ischemic stroke. Patients who controlled both SBP and LDL-C had significantly lower risk relative to control of all 3 risk factors. In this observational study, maintaining control of SBP over 6.2 years was essential to reduction of ischemic stroke risk. Simultaneous control of LDL-C further reduced risk, but HbA1c control <7% did not mitigate stroke risk beyond SBP and LDL-C control. Further research is needed to evaluate the relationship between HbA1c control and stroke risk.


2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Minrui Chen ◽  
Weiliang Luo ◽  
Jiming Li ◽  
Kaiyi Cao ◽  
Xiaohui Li ◽  
...  

Objective. To explore the associations between type 2 diabetes mellitus (DM) and stroke by evaluating the clinical risk factors, characteristics, and outcomes of acute ischemic stroke (AIS) patients with and without type 2 DM. Methods. A total of 1,156 AIS patients (including 410 with type 2 DM (AIS-DM group)) and 746 without type 2 DM (AIS-NDM group)) were included. Patients’ demographics, auxiliary examinations, clinical manifestations, and treatment outcomes were recorded and analyzed. Results. Among the included AIS patients, 35.46% had type 2 DM. The AIS-DM group had less males (59.76% versus 70.64%), less smokers (33.90% versus 41.96%), more patients with hypertension (72.93% versus 63.94%; p = 0.002 ), higher triglyceride levels (42.93% versus 25.08%; p ≤ 0.01 ), and lower total cholesterol (147.06 mg/dl versus 175.31 mg/dl) than the AIS-NDM group. The proportion of patients with large artery atherosclerosis (LAA) in the AIS-DM group was lower (77.56% versus 85.92%; p < 0.05 ) than that in the AIS-NDM group, and the proportion of patients with small arterial occlusions (SAO) in the AIS-DM group was higher (27.07% versus 13.67%; p < 0.05 ) than that in the AIS-NDM group. The mean National Institutes of Health Stroke Scale (NIHSS) score at admission in the AIS-DM group was lower than that in the AIS-NDM group (4.39 versus 5.00; p = 0.008 ), but there was no significant difference in the NIHSS score or the modified Rankin Scale score between the two groups at discharge. A total of 85 AIS patients underwent intravenous thrombolysis treatment with recombinant tissue plasminogen activator (rtPA). The door-to-needle time (DNT) did not differ significantly between the groups (49.39 ± 30.40 min versus 44.25 ± 15.24 min; p = 0.433 ). In addition, there were no significant differences in the baseline NIHSS score, 7-day NIHSS score, and mRS score at discharge between the groups. After intravenous thrombolysis with rtPA, the AIS-NDM group had better recovery (44.30% versus 29.20%; p = 0.017 ) and a higher ratio of good treatment outcome at discharge (65.60% versus 54.20%; p = 0.762 ). Conclusions. Type 2 DM is associated with AIS and its risk factors, such as dyslipidemia and hypertension. Patients in the AIS-DM group had less LAA and smaller arterial occlusions, and DM could exacerbate the short-term clinical outcomes in AIS patients.


BMJ Open ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. e035813 ◽  
Author(s):  
Dybesh Regmi ◽  
Saif Al-Shamsi ◽  
Romona D. Govender ◽  
Juma Al Kaabi

ObjectivesA high body mass index (BMI) is associated with risk of type 2 diabetes mellitus (DM). The United Arab Emirates (UAE) is experiencing a marked increase in obesity. Nonetheless, no data are available regarding the incidence of type 2 DM in the high-risk adult UAE population. Therefore, this study aimed to evaluate the incidence rate and risk of developing type 2 DM among individuals with above-normal BMI in the UAE.DesignA retrospective cohort study.SettingOutpatient clinics at a tertiary care centre in Al Ain, UAE.ParticipantsThree hundred and sixty-two overweight or obese adult UAE nationals who visited outpatient clinics between April 2008 and December 2008.Primary outcome measurePatients with type 2 DM were identified based on diagnosis established by a physician or through glycated haemoglobin (HbA1c) levels ≥6.5% during the follow-up period (until April 2018).ResultsThe overall incidence rate of type 2 DM during the median follow-up time of 8.7 years was 16.3 (95% CI 12.1 to 21.4) cases per 1000 person-years. Incidence rates in men and women were 17.7 (95% CI 11.6 to 25.9) and 15.0 (95% CI 9.8 to 22.2) cases per 1000 person-years, respectively. Multivariable Cox proportional hazard analysis determined older age and obesity in women and pre-diabetes in men to be independent risk factors for developing type 2 DM.ConclusionsThe incidence rate of type 2 DM in overweight and obese UAE nationals is high. In addition to screening, current strategies should strongly emphasise lifestyle modifications to decrease HbA1c and BMI levels in this high-risk population.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Malik ◽  
H Chen ◽  
A Cooper ◽  
M Gomes ◽  
V Hejjaji ◽  
...  

Abstract Background In patients with type 2 diabetes (T2D), optimal management of cardiovascular (CV) risk factors is critical for primary prevention of CV disease. Purpose To describe the association of country income and patient socioeconomic factors with risk factor control in patients with T2D. Methods DISCOVER is a 37-country, prospective, observational study of 15,983 patients with T2D enrolled between January 2016 and December 2018 at initiation of 2nd-line glucose-lowering therapy and followed for 3 years. In patients without known CV disease with sub-optimally controlled risk factors at baseline, we examined achievement of risk factor control (HbA1c &lt;7%, BP &lt;140/90 mmHg, appropriate statin) at the 3 year follow-up. Countries were stratified by gross national income (GNI)/capita, per World Bank report. We explored variability across countries in risk factor control achievement using hierarchical logistic regression models and examined the association of country- and patient-level economic factors with risk factor control. Results Among 9,613 patients with T2D but without CV disease (mean age 57.2 years, 47.9% women), 83.1%, 37.5%, and 66.3% did not have optimal control of glucose, BP, and statins, respectively, at baseline. Of these, 40.8%, 55.5%, and 28.6% achieved optimal control at 3 years of follow-up. There was substantial variability in achievement of risk factor control across countries (Figure) but no association of country GNI/capita on achievement of risk factor control (Table). Insurance status, which differed substantially by GNI group, was strongly associated with glycemic control, with no insurance and public insurance associated with lower odds of patients achieving HbA1c &lt;7%. Conclusions In a global cohort of patients with T2D, a substantial proportion do not achieve risk factor control even after 3 years of follow-up. The variability across countries in risk factor control is not explained by the GNI/capita of the country. Proportion of patients at goal Funding Acknowledgement Type of funding source: Private company. Main funding source(s): The DISCOVER study is funded by AstraZeneca


2018 ◽  
Vol 54 (4) ◽  
pp. 238-244 ◽  
Author(s):  
David Martinez-Gomez ◽  
Irene Esteban-Cornejo ◽  
Esther Lopez-Garcia ◽  
Esther García-Esquinas ◽  
Kabir P Sadarangani ◽  
...  

ObjectivesWe examined the dose–response relationship between physical activity (PA) and incidence of cardiovascular disease (CVD) risk factors in adults in Taiwan.MethodsThis study included 1 98 919 participants, aged 18–97 years, free of CVD, cancer and diabetes at baseline (1997–2013), who were followed until 2016. At baseline, participants were classified into five PA levels: inactive’ (0 metabolic equivalent of task (MET)-h/week), ‘lower insufficiently active’ (0.1–3.75 MET-h/week), ‘upper insufficiently active’ (3.75–7.49 MET-h/week), ‘active’ (7.5–14.99 MET-h/week) and ‘highly active’ (≥15 MET-h/week]. CVD risk factors were assessed at baseline and at follow-up by physical examination and laboratory tests. Analyses were performed with Cox regression and adjusted for the main confounders.ResultsDuring a mean follow-up of 6.0±4.5 years (range 0.5–19 years), 20 447 individuals developed obesity, 19 619 hypertension, 21 592 hypercholesterolaemia, 14 164 atherogenic dyslipidaemia, 24 275 metabolic syndrome and 8548 type 2 diabetes. Compared with inactive participants, those in the upper insufficiently active (but not active) category had a lower risk of obesity (HR 0.92; 95% CI 0.88 to 0.95), atherogenic dyslipidaemia (0.96; 0.90 to 0.99), metabolic syndrome (0.95; 0.92 to 0.99) and type 2 diabetes (0.91; 0.86 to 0.97). Only highly active individuals showed a lower incidence of CVD risk factors than their upper insufficiently active counterparts.ConclusionCompared with being inactive, doing half the recommended amount of PA is associated with a lower incidence of several common biological CVD risk factors. Given these benefits, half the recommended amount of PA is an evidence based target for inactive adults.


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