Methotrexate Hepatotoxicity in Psoriatics: Report of 104 Patients from Nova Scotia, with Analysis of Risks from Obesity, Diabetes and Alcohol Consumption During Long Term Follow-Up

BACKGROUND AND DESIGN: Methotrexate (MTX) hepatotoxicity in psoriatic patients is well recognized, but there are discrepancies in the reported incidence and associated risk factors. This retrospective study describes 104 Nova Scotian patients with psoriasis seen between 1979 and 1990. Patients received MTX over one to 11 years (mean 3.38), with baseline and annual follow-up liver biopsies. Clinical data were obtained by chart review. Statistical analysis evaluated the risks associated with obesity, diabetes, alcohol consumption and duration of therapy, with the histological grade of liver biopsies.RESULTS: Of the 104 patients, 35 were obese, 10 were diabetic and 37 occasionally consumed alcohol. At the end of the study, 21 patients had developed severe hepatic fibrosis (grade IIIB), and three developed liver cirrhosis (grade IV). Significant risk of severe hepatotoxicity is related to diabetes (P=0.02) but not to obesity (P=0.12) or alcohol consumption (P=0.12). All patients with cirrhosis took MTX for two years in standard doses of 20 to 25 mg/week.CONCLUSIONS: In this first Canadian study evaluating MTX hepatotoxicity in psoriatics, the incidence of severe hepatotoxicity is high: 23.1% (24 of 104 patients). This study shows that diabetic patients are particularly at increased risk of MTX hepatotoxicity. Occasional alcohol consumption is not associated with increased risk. Three patients who developed cirrhosis over two years of standard MTX therapy may represent a subset of psoriatics with increased hepatic susceptibility to MTX. Another three patients whose severe hepatic fibrosis had regressed upon discontinuation of MTX, but who developed accelerated recurrence of the severe hepatic fibrosis upon resumption of MTX therapy, also suggest the possibility of unusual sensitivity to the drug. These cases emphasize the need for continuing surveillance, with regular liver biopsies, of psoriatic patients on MTX.

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Abstract P050: Association Between Glycemic Control and Short-term Mortality Varies Across the Spectrum of Coronary Artery Disease

Circulation ◽

10.1161/circ.135.suppl_1.p050 ◽

2017 ◽

Vol 135 (suppl_1) ◽

Author(s):

Sridharan Raghavan ◽

Wenhui G Liu ◽

P. Michael Ho ◽

Mary E Plomondon ◽

Anna E Baron ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Glycemic Control ◽

Diabetes Management ◽

Significant Risk ◽

Short Term ◽

Increased Risk ◽

Short Term Mortality ◽

Artery Disease

Background: Diabetes is a significant risk factor for cardiovascular disease, but optimal glycemic control strategies remain unclear. In particular, trials of intensive glycemic control have highlighted a tension between increased mortality risk and macrovascular benefits. In this study we aimed to assess whether the burden of coronary artery disease (CAD) modifies the association between glycemic control and short-term mortality. Methods: We studied veterans with diabetes who underwent elective cardiac catheterization between 2005 and 2013 in a retrospective analysis of data from the VA Clinical Assessment, Reporting, and Tracking (CART) Program. Primary exposures were time-varying HbA1c over two years of follow-up after index catheterization, categorized as <6%, 6-6.49%, 6.5-6.99%, 7-7.99%, 8-8.99%, and >=9%, and burden of CAD, categorized as no CAD, non-obstructive CAD, or obstructive CAD. Primary outcome was two-year all-cause mortality. A total of 17394 participants had, on average, five HbA1c measurements over two years of follow-up. We used multivariable Cox proportional hazards regression to estimate the association between HbA1c and mortality, adjusting for demographic and clinical covariates and CAD burden, and including a term for interaction between HbA1c and CAD burden. Results: In adjusted models with 6.5 ≤ HbA1c ≤ 6.99% as the reference category, HbA1c < 6% was associated with increased risk of mortality (HR 1.55 [1.25, 1.92]), whereas HbA1c categories above 7% were not. We observed significant interaction between glycemic control and CAD burden (interaction p=0.0005); the increased risk of short-term mortality at HbA1c < 6% was limited to individuals with non-obstructive and obstructive CAD (Figure 1). Conclusions: HbA1c below 6% was associated with increased risk of short-term mortality, but only in individuals with CAD. CAD burden may thus inform individualized diabetes management strategies, specifically treatment de-escalation in individuals with any angiographically-defined CAD.

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Abstract WP218: Increased Systolic Blood Pressure Variability Among Diabetic Patients is Associated With Higher Risk of Incident Stroke: A Secondary Analysis of ACCORDION

Stroke ◽

10.1161/str.51.suppl_1.wp218 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Adam H de Havenon ◽

Ka-Ho Wong ◽

Eva Mistry ◽

Mohammad Anadani ◽

Shadi Yaghi ◽

...

Keyword(s):

Blood Pressure ◽

Blood Pressure Variability ◽

Proportional Hazards ◽

Secondary Analysis ◽

Cox Proportional Hazards ◽

Diabetic Patients ◽

Adjusted Risk ◽

Cox Proportional Hazards Models ◽

Increased Risk

Background: Increased blood pressure variability (BPV) has been associated with stroke risk, but never specifically in patients with diabetes. Methods: This is a secondary analysis of the Action to Control Cardiovascular Risk in Diabetes Follow-On Study (ACCORDION), the long term follow-up extension of ACCORD. Visit-to-visit BPV was analyzed using all BP readings during the first 36 months. The primary outcome was incident ischemic or hemorrhagic stroke after 36 months. Differences in mean BPV was tested with Student’s t-test. We fit Cox proportional hazards models to estimate the adjusted risk of stroke across lowest vs. highest quintile of BPV and report hazard ratios along with 95% confidence intervals (CI). Results: Our analysis included 9,241 patients, with a mean (SD) age of 62.7 (6.6) years and 61.7% were male. Mean (SD) follow-up was 5.7 (2.4) years and number of BP readings per patient was 12.0 (4.3). Systolic, but not diastolic, BPV was higher in patients who developed stroke (Table 1). The highest quintile of SBP SD was associated with increased risk of incident stroke, independent of mean blood pressure or other potential confounders. (Table 2, Figure 1). There was no interaction between SBP SD and treatment arm assignment, although the interaction for glucose approached significance (Table 2). Conclusion: Higher systolic BPV was associated with incident stroke in a large cohort of diabetic patients. Future trials of stroke prevention may benefit from interventions targeting BPV reduction.

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Relationship between alcohol consumption and cancer in rural Chinese adults: 1 5- year follow-up cohort study

10.21203/rs.3.rs-48959/v1 ◽

2020 ◽

Author(s):

Yue Zhang ◽

Jingyi Li ◽

Nannan Cheng ◽

Jie Yang ◽

Lijing Ye ◽

...

Keyword(s):

Cohort Study ◽

Alcohol Consumption ◽

Cancer Incidence ◽

Rural China ◽

Density Lipoprotein ◽

Estimating Equation ◽

Chinese Adults ◽

Increased Risk ◽

Risk Of Cancer

Abstract Background：We aimed to evaluate the association between alcohol consumption and risk of cancer incidence among rural Chinese adults. Methods: We utilized data from a community-based cohort study in rural China enrolled in 2003 and followed up prospectively up to 2018. Generalized estimating equation models were used to obtain odds ratios (OR) and 95% confidence intervals (CI) to analyze the relationship between alcohol consumption and cancer incidence. Results: After an average of 15 years of follow-up, a total of 9870 adult participants were included in this study. The results of the regression analysis for males showed that former drinkers had a significantly increased risk of cancer compared to never drinkers ([OR]2.46,95%[CI](1.43-4.23)). The cancer risk for current drinkers with heavy alcohol consumption(>400g/week) significantly increased ([OR]1.66,95% [CI] (1.18-2.34))compared to never drinkers. Among current drinkers, for every 100g of alcohol consumed per week, the risk of cancer increased by 15%. Among current drinkers, those aged 53.5 years or older , had a significant increase in the risk of cancer ([OR]1.26,95% [CI](1.12-1.42), for those with triglycerides ≥150 mg/dL, the risk of cancer was even higher ([OR]1.50,95%[CI](1.20-1.88), P for interaction 0.018), and for those with high density lipoprotein cholesterol (HDLC)<40 mg/dL, the risk of cancer increased the greatest ([OR]2.03,95%[CI](1.36-3.04), P for interaction 0.005). Conclusions: Among middle-aged and elderly males in rural China, the risk of cancer significantly increased among former and heavy current drinkers compared with never drinkers. Age, triglycerides, and HDLC may increase the risk of cancer along with alcohol consumption.

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Antibodies against Malondialdehyde in Haemodialysis Patients and Its Association with Clinical Outcomes: Differences between Subclasses and Isotypes

Journal of Clinical Medicine ◽

10.3390/jcm9030753 ◽

2020 ◽

Vol 9 (3) ◽

pp. 753

Author(s):

Shailesh Kumar Samal ◽

Abdul Rashid Qureshi ◽

Mizanur Rahman ◽

Peter Stenvinkel ◽

Johan Frostegård

Keyword(s):

Significant Risk ◽

Premature Death ◽

C Reactive Protein ◽

Reactive Protein ◽

Multivariate Risk ◽

Increased Risk ◽

All Cause Mortality ◽

Low Levels ◽

Antibody Levels

Patients on haemodialysis (HD-patients) have an increased risk of premature death. Low levels of IgM antibodies against malondialdehyde (anti-MDA) are associated with increased risk of cardiovascular disease (CVD) with underlying potential mechanisms described. Here, we studied subclasses and isotypes of anti-MDA in 210 HD-patients with mortality as outcome (56% men, median age 66, Interquartile range (IQR) 51–74 years, vintage time 29 (15–58) months, mean follow up period of 41 (20–60)months). Patients were also divided into inflamed c-reactive protein (CRP >5.6 mg/mL) and non-inflamed. Antibody levels were measured by ELISA. In multivariate risk analysis, patients in low tertile of IgM anti-MDA sub-distribution hazard ratio (sHR 0.54); 95% confidence interval (CI: 0.34–0.89) inversely and significantly associated with all-cause mortality after five years, after adjusting for confounders. Low tertile of IgG (sHR 0.48, 95%CI: 0.25–0.90, p = 0.02) and IgG1 (sHR 0.50, CI: 0.24–1.04, p = 0.06) was associated low mortality among non-inflamed patients. In contrast, anti-MDA IgG2 among inflamed patients was significantly associated with increased mortality, IgG2(sHR 2.33, CI: 1.16–4.68, p = 0.01). IgM anti-MDA was a novel biomarker among HD-patients with low levels being associated with mortality, while low levels of IgG and IgG1 but not IgA anti-MDA were associated with mortality only among non-inflamed patients. IgG2 anti-MDA was a significant risk marker among inflamed patients, which could be related to infection.

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Awaking Blood Pressure Surge and Progression to Microalbuminuria in Type 2 Normotensive Diabetic Patients

Journal of Diabetes Research ◽

10.1155/2016/5876792 ◽

2016 ◽

Vol 2016 ◽

pp. 1-6 ◽

Cited By ~ 5

Author(s):

Michelangela Barbieri ◽

Maria Rosaria Rizzo ◽

Ilaria Fava ◽

Celestino Sardu ◽

Nicola Angelico ◽

...

Keyword(s):

Blood Pressure ◽

Type 2 Diabetes ◽

Cox Regression ◽

Blood Pressure Monitoring ◽

Adult Patients ◽

Diabetic Patients ◽

Increased Risk ◽

Pressure Surge

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.

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Evaluation of Chronic Transfusion (Tx) Practices in Children with Sickle Cell Disease (SCD): A Survey of STOP II Investigators.

Blood ◽

10.1182/blood.v104.11.3732.3732 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3732-3732 ◽

Cited By ~ 2

Author(s):

Ofelia Alvarez ◽

Scott Miller ◽

Brian Berman ◽

Clark Brown ◽

James Casella ◽

...

Keyword(s):

Iron Overload ◽

Stroke Prevention ◽

Packed Red Blood Cells ◽

Increased Risk ◽

Hb S ◽

Liver Biopsies ◽

Machine Programming ◽

Key Barrier ◽

Total Exchange

The follow-up Stroke Prevention Trial (STOP II) attempts to optimize tx therapy for primary stroke prevention in children with SCD who are at increased risk due to an abnormal Doppler ultrasound. A survey of participating investigators (PIs) was performed in order to assess tx practices; 12 PIs out of 26 responded. To begin chronic tx, 42 % of the PIs preferred erythrocytapheresis (ECP), partial or total exchange to bring hemoglobin (Hb) S <30%, 33% used frequent txs over a month, and the rest used either method. For continuation of chronic tx, 5 PIs used only simple tx for their pts, 2 used partial exchange (phlebotomy and simple tx), and 5 used either simple tx or exchange to transfuse their patients (pts). The most common reason to choose a method was intravenous (IV) accessibility. 4 PIs mentioned that they start with simple tx but later might use exchange if unable to keep Hb S <30% or to avoid iron overload. For simple tx, most PIs ordered 10–15 ml/kg leucoreduced, Rh and Kell compatible, S negative packed red blood cells (PRBC). Pts returned for the next tx, depending on prior pre-tx Hb S (goal < 30%), or every 4 weeks unless Hb S was >30%. Most PIs had a post-tx target hematocrit (Hct) 35–36%, but a third of them did not have one. Pre-tx Hct and/or Hb S (but not post-tx values) were used to predict the timing of the next tx by 83% of the group. When performing ECP, the PIs participated in the decision of how much to exchange pts only 33% of the time; generally ECP was planned by a blood bank physician and/or by machine programming. Chelation began either after 12–30 months of tx (median 18 months), or after serum ferritin 1000–2500 ng/ml (median 2000). 67% of the PIs obtained liver biopsies in all or some of the STOP II pts. Indications for liver biopsies were cited as routine for transfused pts (5 PIs) or depending on ferritin values (6 PIs). Deferoxamine 25–50 mg/kg was infused subcutaneously over 8–10 hours 5–7 nights a week in all pts. Eight PIs reported the use of central venous lines (ports) in some pts to facilitate IV access. Barriers cited to effective chronic tx were: pt compliance with chelation (7 reported it as most important), IV access, pt compliance with tx schedule, hypersplenism, and alloimmunization. We conclude that hematologists :(1) Administer leucoreduced Rh and Kell compatible, S negative PRBC to keep pre-tx Hb S levels <30%, (2) use pre-tx Hb S and Hct to predict next tx, usually every 3–4 weeks, (3) monitor and treat iron overload, and (4) report that poor compliance with chelation is a key barrier to an effective tx program. Although liver biopsy to monitor iron stores and partial/total exchange to limit iron overload are accepted interventions, medical practice still varies.

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The Challenge of Lipid Management in Patients with Diabetes or Other Endocrine Disorders

European Endocrinology ◽

10.17925/ee.2011.07.02.92 ◽

2010 ◽

Vol 7 (2) ◽

pp. 92

Author(s):

Alberico L Catapano ◽

Liliana Grigore ◽

Angela Pirillo ◽

◽

...

Keyword(s):

Statin Therapy ◽

Meta Analysis ◽

Diabetic Patients ◽

Endocrine Disorders ◽

Lipid Management ◽

Increased Risk ◽

Patients With Diabetes ◽

Associated Risk Factors

Diabetes increases the risk of developing cardiovascular disease (CVD), and several guidelines suggest that subjects with diabetes are at high risk of developing CVD. The increased risk can be attributed, at least in part, to associated risk factors, including hypertension and dyslipidaemia. The role of statins in primary and secondary prevention of CVD is well established, and the positive effect has been clearly demonstrated also in patients with type 2 diabetes. A number of studies have evaluated the effect of statin therapy on incident CVD and shown that statin therapy produces a great reduction in cardiovascular risk, but a recent meta-analysis revealed a slight increase in the risk of developing diabetes. Such risk is, however, low, especially when compared with the reduction in cardiovascular events and should not interfere with the choice of treating diabetic patients with a cholesterol-lowering therapy.

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Increased Risk of Valvular Heart Disease in Systemic Sclerosis: An Underrecognized Cardiac Complication

The Journal of Rheumatology ◽

10.3899/jrheum.201005 ◽

2021 ◽

pp. jrheum.201005

Author(s):

Reto D. Kurmann ◽

Edward A. El-Am ◽

Yasser A. Radwan ◽

Avneek S. Sandhu ◽

Cynthia S. Crowson ◽

...

Keyword(s):

Heart Disease ◽

Systemic Sclerosis ◽

Valvular Heart Disease ◽

Cardiac Involvement ◽

Significant Risk ◽

Fold Increase ◽

Significant Risk Factor ◽

Increased Risk ◽

Incident Cases

Objective Cardiac involvement is a poor prognostic marker in systemic sclerosis (SSc). While diastolic dysfunction, myocardial fibrosis, and arrhythmias are traditionally considered features of primary cardiac involvement in SSc, the incidence of valvular heart disease (VHD) is not well reported. Our objective was to examine the prevalence of VHD at time of SSc diagnosis and incidence of VHD during follow up compared to non-SSc subjects. Methods Medical records of patients with suspicion of SSc were reviewed to identify incident cases. SSc subjects were matched 1:2 by age- and sex to non-SSc subjects. Results The study included 78 incident SSc cases and 156 non-SSc comparators [56 years (± 15.7), 91% female]. A nearly 4-fold increase in the prevalence of moderate/severe VHD prior to SSc diagnosis compared to non-SSc subjects (6% vs. 0%; P=0.004) was identified. During follow up, 18 SSc and 12 non-SSc patients developed moderate/severe VHD. The cumulative incidence of VHD at 10 years after SSc incidence/index was 17.9% (95% CI: 10.7-29.9%) in patients with SSc compared with 2.3% (95% CI: 0.7-6.3%) in non-SSc subjects (HR: 4.23; 95% CI: 2.03-8.83). Coronary heart disease was the only significant risk factor for VHD. Conclusion SSc patients have a 4-fold increase in the prevalence of moderate/severe VHD at diagnosis compared to non-SSc patients. They also have a 4-fold increased risk of developing moderate/severe VHD after diagnosis of SSc. Aortic stenosis and mitral regurgitation have a much higher prevalence in SSc patients, besides secondary tricuspid regurgitation. Underlying mechanisms for this association require further elucidation.

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Post-Anticoagulation Cessation D-Dimer Testing and VTE Recurrence in Real-World Australian Audit

Blood ◽

10.1182/blood-2018-99-118661 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1227-1227

Author(s):

Julie Wang ◽

Rowena Brook ◽

Alison Slocombe ◽

Lisa Hong ◽

Prahlad Ho

Keyword(s):

Risk Factor ◽

Significant Risk ◽

Significant Risk Factor ◽

Risk Of Recurrence ◽

Increased Risk ◽

Recurrent Vte ◽

Residual Thrombus ◽

Repeat Imaging ◽

D Dimer

Abstract Aim Elevated D-dimer post-anticoagulation cessation is a recognised risk factor for recurrent venous thromboembolic events (VTE). In particular, raised D-dimer post cessation has been associated with increased risk of recurrence in unprovoked major VTE. Currently in Australia, D-dimer has not been widely used in practice to stratify the risk of VTE recurrence. This study aims to retrospectively analyse the effect of routine D-dimer testing and it's association with VTE recurrence. Methods A retrospective evaluation was performed on 1024 patients with a diagnosis of VTE at a tertiary hospital in Australia between January 2013 and December 2016. Data collected included demographics, results and timing of D-dimer testing and serial imaging results. Results 1024 patients were reviewed with a total median follow up of 12 months (range 0-59 months). D-dimer was tested in 189 patients (18.5%) within 90 days after cessation of anticoagulation. Of these patients, median age was 58 (18-92) and 55.3% (n=105) were female. 33.3% (n=63) had isolated distal deep vein thrombosis (IDDVT), 66.3% (n=126) had above knee DVT (AKDVT)/pulmonary embolus (PE), 54.5% (n=103) of VTE were provoked. Abnormal post cessation D-dimer (>500) was found in 72 patients (37.9%). Of these, 25 patients were restarted on anticoagulation; one had recurrent VTE whilst on low dose apixaban 2.5mg BD and one had recurrence after cessation of anticoagulation at a later date. Patients with elevated D-dimer post cessation had a higher rate of recurrence with the highest risk in patients with D-dimer >1000 (RR 7.38, p=<0.01) outlined in Table 1. Of the 164 patients with post cessation D-dimer testing who remained off anticoagulation there were a total of 24 (12.6%) episodes of recurrent VTE. Elevated D-dimer post anticoagulation cessation was a significant risk factor for recurrence in both provoked VTE (RR 4.21, p=0.01) and unprovoked VTE cohorts (RR 4.55, p=0.008) outlined in Table 2. When provoked VTE were sub-categorised, raised D-dimer demonstrated the most statistical significance in VTE provoked by travel (RR 13.5 p=0.06). Of the patients with post anticoagulation cessation D-dimer testing 170 patients (89.9%) had repeat imaging to assess for residual thrombus. In the subgroup of patients with no residual thrombus, elevated D-dimer was a significant risk factor for VTE recurrence (RR 6.4, p=<0.01). Patients with normal D-dimer and no residual thrombus had the lowest rate of recurrence 5.4% (n=4) see Table 3. When stratified by type of VTE, elevated D-dimer post anticoagulation cessation was significantly related to risk for recurrence in the overall IDDVT sub-cohort (RR 4.09, p=0.007). This was not significant for the AKDVT/PE sub cohort (RR 3.24, p=0.079). However, for patients with unprovoked AKDVT or PE, having D-dimer tested post anticoagulation, regardless of result, was associated with lower rates of VTE recurrence RR 0.30 (p=0.02) compared to those who had no D-dimer testing as part of follow-up. Conclusion Post treatment D-dimer testing may have a clinical role in stratifying the risk of VTE recurrence along with repeat imaging to detect residual thrombus. Elevated D-dimer post anticoagulation cessation is associated with increased risk of VTE recurrence for both provoked and unprovoked VTE with highest risk in patients with D-dimer >1000. Patients with no residual thrombus and a negative D-dimer post anticoagulation cessation had the lowest rate of recurrence. In the subgroup of patients with provoked VTE and IDDVT a positive D-dimer post cessation was associated with 4.21 and 4.09 relative risk of recurrence respectively, suggesting that the role of D-dimer testing can be extended to these subpopulations. Interestingly, in patients with unprovoked AKDVT or PE, having post-cessation D-dimer testing performed, regardless of result, was associated with a significantly lower rate of VTE recurrence compared to patients without D-dimer testing, which may be related to specialist review and recommencement of anticoagulation in high-risk patients. Disclosures No relevant conflicts of interest to declare.

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Long-term glycemic variability and risk of stroke in patients with diabetes: a meta-analysis

Diabetology & Metabolic Syndrome ◽

10.1186/s13098-021-00770-0 ◽

2022 ◽

Vol 14 (1) ◽

Author(s):

Xiaoli Ren ◽

Zhiyun Wang ◽

Congfang Guo

Keyword(s):

Standard Deviation ◽

Coefficient Of Variation ◽

Meta Analysis ◽

Glycemic Variability ◽

Diabetic Patients ◽

Increased Risk ◽

Follow Up Studies ◽

Patients With Diabetes

Abstract Objectives Long-term glycemic variability has been related to increased risk of vascular complication in patients with diabetes. However, the association between parameters of long-term glycemic variability and risk of stroke remains not fully determined. We performed a meta-analysis to systematically evaluate the above association. Methods Medline, Embase, and Web of Science databases were searched for longitudinal follow-up studies comparing the incidence of stroke in diabetic patients with higher or lower long-term glycemic variability. A random-effect model incorporating the potential heterogeneity among the included studies were used to pool the results. Results Seven follow-up studies with 725,784 diabetic patients were included, and 98% of them were with type 2 diabetes mellitus (T2DM). The mean follow-up duration was 7.7 years. Pooled results showed that compared to those with lowest category of glycemic variability, diabetic patients with the highest patients had significantly increased risk of stroke, as evidenced by glycemic variability analyzed by fasting plasma glucose coefficient of variation (FPG-CV: risk ratio [RR] = 1.24, 95% confidence interval [CI] 1.11 to 1.39, P < 0.001; I2 = 53%), standard deviation of FPG (FPG-SD: RR = 1.16, 95% CI 1.02 to 1.31, P = 0.02; I2 = 74%), HbA1c coefficient of variation (HbA1c-CV: RR = 1.88, 95% CI 1.61 to 2.19 P < 0.001; I2 = 0%), and standard deviation of HbA1c (HbA1c-SD: RR = 1.73, 95% CI 1.49 to 2.00, P < 0.001; I2 = 0%). Conclusions Long-term glycemic variability is associated with higher risk of stroke in T2DM patients.

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