Abstract TP200: Independent Contribution of HbA1c, Systolic Blood Pressure, and LDL Cholesterol Control to Risk of Ischemic Stroke Hospitalizations in Type 2 Diabetes

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.

2020 ◽  
Vol 182 (4) ◽  
pp. 429-438
Author(s):  
Sharon Li Ting Pek ◽  
Su Chi Lim ◽  
Keven Ang ◽  
Pek Yee Kwan ◽  
Wern Ee Tang ◽  
...  

Introduction Diabetic peripheral neuropathy (DPN) is a common microvascular complication in patients with type 2 diabetes (T2D). Apart from hyperglycemia, few modifiable risk factors have been identified. Endothelin-1 is a potent vasoconstrictor peptide, implicated in the causal pathway of microangiopathy. We investigated whether baseline plasma endothelin-1 and other metabolic and vascular risk factors predicted the incidence of DPN. Design This is a 3-year observational, cohort study. Methods In patients with T2D (n = 2057), anthropometric data, fasting blood, and urine were collected for biochemistry and urine albumin/creatinine measurements. Forearm cutaneous endothelial reactivity was assessed by iontophoresis and laser Doppler flowmetry/imaging. Measurements were repeated on follow-up. Incident DPN was considered present if an abnormal finding in monofilament (<8 of 10 points) or neurothesiometer testing was ≥25 volts on either foot at 3-year follow-up, but normal at baseline. Plasma endothelin-1 was assessed by ELISA. Results At baseline, mean age of patients was 57.4 ± 10.8 years old and prevalence of DPN was 10.8%. Of the 1767 patients without DPN, 1250 patients returned for follow-up assessment ((2.9 ± 0.7) years), with a 10.7% incidence of DPN. Patients with incident DPN had significantly higher baseline endothelin-1 (1.43 (1.19–1.73) vs 1.30 (1.06–1.63)) pg/mL, P < 0.0001. Multivariable Cox proportional hazards ratio showed a 1-s.d. increase in log endothelin-1 (adjusted HR: 4.345 (1.451–13.009), P = 0.009), systolic blood pressure (per 10-unit) (adjusted HR: 1.107 (1.001–1.223), P = 0.047) and diabetes duration (adjusted HR: 1.025 (1.004–1.047), P = 0.017) predicted incident DPN, after adjustment for glycemic control, eGFR, albuminuria, peripheral arterial disease and retinopathy status. Conclusion Higher baseline endothelin-1, blood pressure and diabetes duration were significant and independent predictors for incident DPN. Validation of our findings in independent cohorts and molecular mechanistic studies will help better our understanding on the role of endothelin-1 in DPN.


2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Michelangela Barbieri ◽  
Maria Rosaria Rizzo ◽  
Ilaria Fava ◽  
Celestino Sardu ◽  
Nicola Angelico ◽  
...  

Background. We investigated the predictive value of morning blood pressure surge (MBPS) on the development of microalbuminuria in normotensive adults with a recent diagnosis of type 2 diabetes.Methods. Prospective assessments of 24-hour ambulatory blood pressure monitoring and urinary albumin excretion were performed in 377 adult patients. Multivariate-adjusted Cox regression models were used to assess hazard ratios (HRs) between baseline and changes over follow-up in MBPS and the risk of microalbuminuria. The MBPS was calculated as follows: mean systolic BP during the 2 hours after awakening minus mean systolic BP during the 1 hour that included the lowest sleep BP.Results. After a mean follow-up of 6.5 years, microalbuminuria developed in 102 patients. An increase in MBPB during follow-up was associated with an increased risk of microalbuminuria. Compared to individuals in the lowest tertile (−0.67±1.10 mmHg), the HR and 95% CI for microalbuminuria in those in the highest tertile of change (24.86±6.92 mmHg) during follow-up were 17.41 (95% CI 6.26–48.42);pfor trend <0.001. Mean SD MBPS significantly increased in those who developed microalbuminuria from a mean [SD] of 10.6[1.4]to 36.8[7.1],p<0.001.Conclusion. An increase in MBPS is associated with the risk of microalbuminuria in normotensive adult patients with type 2 diabetes.


2019 ◽  
Vol 7 (1) ◽  
pp. e000787 ◽  
Author(s):  
Rianneke de Ritter ◽  
Simone J S Sep ◽  
Carla J H van der Kallen ◽  
Miranda T Schram ◽  
Annemarie Koster ◽  
...  

ObjectiveTo investigate whether adverse differences in levels of cardiovascular risk factors in women than men, already established when comparing individuals with and without diabetes, are also present before type 2 diabetes onset.Research design and methodsIn a population-based cohort study of individuals aged 40-75 years (n=3410; 49% women, 29% type 2 diabetes (oversampled by design)), we estimated associations with cardiometabolic and lifestyle risk factors of (1) pre-diabetes and type 2 diabetes (reference category: normal glucose metabolism) and (2) among non-diabetic individuals, of continuous levels of hemoglobin A1c (HbA1c). Age-adjusted sex differences were analyzed using linear and logistic regression models with sex interaction terms.ResultsIn pre-diabetes, adverse differences in cardiometabolic risk factors were greater in women than men for systolic blood pressure (difference, 3.02 mm Hg; 95% CI:−0.26 to 6.30), high-density lipoprotein (HDL) cholesterol (difference, −0.10 mmol/L; 95% CI: −0.18 to −0.02), total-to-HDL cholesterol ratio (difference, 0.22; 95% CI: −0.01 to 0.44), triglycerides (ratio: 1.11; 95% CI: 1.01 to 1.22), and inflammation markers Z-score (ratio: 1.18; 95% CI: 0.98 to 1.41). In type 2 diabetes, these sex differences were similar in direction, and of greater magnitude. Additionally, HbA1c among non-diabetic individuals was more strongly associated with several cardiometabolic risk factors in women than men: per one per cent point increase, systolic blood pressure (difference, 3.58 mm Hg; 95% CI: −0.03 to 7.19), diastolic blood pressure (difference, 2.10 mm Hg; 95% CI: −0.02 to 4.23), HDL cholesterol (difference, −0.09 mmol/L; 95% CI: −0.19 to 0.00), and low-density lipoprotein cholesterol (difference, 0.26 mmol/L; 95% CI: 0.05 to 0.47). With regard to lifestyle risk factors, no consistent pattern was observed.ConclusionOur results are consistent with the concept that the more adverse changes in cardiometabolic risk factors in women (than men) arise as a continuous process before the onset of type 2 diabetes.


2020 ◽  
Vol 105 (9) ◽  
pp. 3025-3035
Author(s):  
Silvio E Inzucchi ◽  
Kamlesh Khunti ◽  
David H Fitchett ◽  
Christoph Wanner ◽  
Michaela Mattheus ◽  
...  

Abstract Context Control of multiple cardiovascular (CV) risk factors reduces CV events in individuals with type 2 diabetes. Objective To investigate this association in a contemporary clinical trial population, including how CV risk factor control affects the CV benefits of empagliflozin, a sodium-glucose cotransporter-2 inhibitor. Design Post hoc analysis. Setting Randomized CV outcome trial (EMPA-REG OUTCOME). Participants Type 2 diabetes patients with established CV disease. Intervention Empagliflozin or placebo. Main Outcome Measures Risk of CV outcomes—including the treatment effect of empagliflozin—by achieving 7 goals for CV risk factor control at baseline: (1) glycated hemoglobin &lt;7.5%, (2) low-density lipoprotein cholesterol &lt;100 mg/dL or statin use, (3) systolic blood pressure &lt;140 mmHg and diastolic blood pressure &lt;90 mmHg, (4) pharmacological renin-angiotensin-aldosterone system blockade, (5) normoalbuminuria, (6) aspirin use, (7) nonsmoking. Results In the placebo group, the hazard ratio (HR) for CV death was 4.00 (95% CI, 2.26–7.11) and 2.48 (95% CI, 1.52–4.06) for patients achieving only 0–3 or 4–5 risk factor goals at baseline, respectively, compared with those achieving 6–7 goals. Participants achieving 0–3 or 4–5 goals also had increased risk for the composite outcome of hospitalization for heart failure or CV death (excluding fatal stroke) (HR 2.89 [1.82–4.57] and 1.90 [1.31–2.78], respectively) and 3-point major adverse CV events (HR 2.21 [1.53–3.19] and 1.42 [1.06–1.89]). Empagliflozin significantly reduced these outcomes across all risk factor control categories (P &gt; 0.05 for treatment-by-subgroup interactions). Conclusions Cardiovascular risk in EMPA-REG OUTCOME was inversely associated with baseline CV risk factor control. Empagliflozin’s cardioprotective effect was consistent regardless of multiple baseline risk factor control.


2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Khalid Al-Rubeaan ◽  
Fawaz Al-Hussain ◽  
Amira M. Youssef ◽  
Shazia N. Subhani ◽  
Ahmad H. Al-Sharqawi ◽  
...  

The main aim of this study is to determine the prevalence and risk factors of ischemic stroke among diabetic patients registered in the Saudi National Diabetes Registry (SNDR) database. A cross-sectional sample of 62,681 diabetic patients aged ≥25 years was used to calculate ischemic stroke prevalence and its risk factors. Univariate and multivariate logistic regression analyses were used to assess the roles of different risk factors. The prevalence of ischemic stroke was 4.42% and was higher in the older age group with longer diabetes duration. Poor glycemic control and the presence of chronic diabetes complications were associated with a high risk of ischemic stroke. History of smoking and type 2 diabetes were more frequent among stroke patients. Obesity significantly decreased the risk for ischemic stroke. Regression analysis for ischemic stroke risk factors proved that age ≥45 years, male gender, hypertension, coronary artery disease (CAD), diabetes duration ≥10 years, insulin use, and hyperlipidemia were significant independent risk factors for ischemic stroke. We conclude that ischemic stroke is prevalent among diabetic individuals, particularly among those with type 2 diabetes. Good glycemic, hypertension, and hyperlipidemia control, in addition to smoking cessation, are the cornerstones to achieve a significant reduction in ischemic stroke risk.


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


2016 ◽  
Vol 9 (1) ◽  
pp. 224 ◽  
Author(s):  
Mohamed H. Al-Thani ◽  
Heba S. Nasser ◽  
Suzan Sayegh ◽  
Alexandra Haddad ◽  
Eman Sadoun

Type 2 diabetes mellitus (T2DM) is a major global health problem. The present study examines the relationship between the metabolic, anthropometric and Finnish risk score (FINDRISC) among normal and pre-diabetic adults. Subjects (n = 1319, aged above 18 years) from the Qatari population were classified into two groups based on their hemoglobin A1c (HbA1c) measurements (non-diabetic A1c<5.6% and pre-diabetic 5.6% ≤ A1c ≤ 6.4%) were examined for their anthropometric (height, weight and waist circumference), metabolic [fat, fat free mass (FFM), muscle mass (MM), total body water (TBW), bone mass, degree of obesity, basal metabolic rate (BMR), body mass index (BMI), metabolic age, visceral fat rating, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (Total-C), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), fasting / random plasma glucose (FPG / RPG), HbA1c and vitamin D (VitD)] and FINDRISC. Means and frequencies were determined in aggregate and by subgroups for all variables and correlations between categorical variables were tested to estimate the association between the anthropometric and metabolic risk factors with the FINDRISC. A percentage of 74.8% (n = 987) of the study population aged below 45 years old and their overall BMI was 28.8±5.2kg/m2 (overweight). Pre-diabetic subgroup have shown a statistically higher FINDRISC compared to their non-diabetic counterparts (11.2±4.1 vs. 9.8±4, p<0.001). The FINDRISC was significantly and directly correlated with the BMI, HbA1c and FPG. However, HbA1c was correlated directly with BMI, SBP, DBP, FPG / RPG and indirectly with the levels of HDL. This study demonstrates an apparent relationship between the HbA1c and FINDRISC score. Pursuing further research on this association may permit using HbA1c with the FINDRISC in predicting the risk of T2DM to be a better tool rather than using the current FPG/RPG, OGTT methods.


Author(s):  
Yuto Saijo ◽  
Hiroshi Okada ◽  
Masahide Hamaguchi ◽  
Momoko Habu ◽  
Kazushiro Kurogi ◽  
...  

(1) Background: As no study has evaluated the risk factors contributing to the development of type 2 diabetes according to body weight mass (BMI) categories in a large cohort and over a long period in a Japanese population, we aimed to assess them in 46,001 Japanese individuals; (2) Methods: This long-term retrospective cohort study included individuals who participated in a medical health checkup program at Panasonic Corporation from 2008 to 2018. In total, 3,208 participants developed type 2 diabetes. The BMI at 2008 were divided into 3 groups: BMI < 22 kg/m2, 22 ≤ BMI < 25 kg/m2, and BMI ≥ 25 kg/m2 to evaluate the risk factors for type 2 diabetes; (3) Results: Cox regression analyses revealed that the significant risk factors were age, BMI, systolic blood pressure, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, fasting plasma glucose, current smoking status, and alcohol consumption in populations with BMI ≥ 25.0 kg/m2. The risk factors in the population with 22 ≤ BMI < 25 kg/m2 were identical to that of BMI ≥ 25.0 kg/m2 excluding systolic blood pressure, low-density lipoprotein cholesterol, and skipping breakfast. However, in the population with BMI < 22.0 kg/m2, no association was found as to BMI, SBP, LDL cholesterol level, and triglycerides; (4) Conclusions: The risk factors for developing diabetes were quite different between the population with BMI < 22 kg/m2 and the population with 22 ≤ BMI < 25 kg/m2 or BMI ≥ 25 kg/m2 in a Japanese population.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Seyyed Saeed Moazzeni ◽  
Reyhane Hizomi Arani ◽  
Samaneh Asgari ◽  
Fereidoun Azizi ◽  
Farzad Hadaegh

Abstract Background Childbearing may increase the future risk of developing type 2 diabetes mellitus (T2DM) in mothers. However, the issue is not clear completely and not investigated in the Middle East, a region with a high burden of T2DM. In the current study, we examined the association of parity/live birth number with incident T2DM among Iranian women. Methods The study population included 2552 women aged 30–65 years recruited in 1999–2001 and were followed for incident T2DM by 3-year intervals. Multivariable Cox proportional hazard models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of the parity/live birth number for incident T2DM. Parity number was defined as the number of live childbirth (number of live birth) plus the number of stillbirth (defined as birth of an infant that died after the 20th week of pregnancy in the uterus). Results During a median follow-up of 15.4 years, 557 incident T2DM cases have occurred. After adjustment for potential T2DM risk factors and reproductive factors, each additional parity caused a 9% higher risk for incident T2DM. Moreover, compared to women with one parity, those with 3 and ≥ 4 parity had HRs of 1.73 [95% CI: 1.06–2.83] and 2.23 [1.36–3.65], respectively. After further adjustment for body mass index (BMI) and waist circumference, although the HRs were attenuated prominently, parity ≥ 4 was associated with significantly higher risk (HR: 1.72 [1.05–2.83]); even after further adjustment for triglycerides (TG)/ high-density lipoprotein cholesterol (HDL-C), the risk remained marginally significant (HR: 1.64 [1.00–2.70; P value: 0.051]). For the number of live birth, the results were also similar. Moreover, in a sensitivity analysis, when we considered BMI change during follow-up as another covariate, generally, the effect sizes did not change; the trend of HRs across categories of parity number remained marginally significant (P value: 0.064). Conclusions During a long-term follow-up, after adjustment for potential T2DM risk factors, reproductive factors, obesity indices, and TG/HDL-C (insulin resistance surrogate), we demonstrated that higher parity/live birth numbers could be associated with increased risk of T2DM development among Iranian women. Moreover, even after further adjustment for BMI change, the suggestive higher risk was still found.


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