Continuous glucose monitoring in acute ischemic stroke patients treated with endovascular therapy: A pilot study to assess feasibility and accuracy.

INTRODUCTION: Hyperglycemia is common in acute ischemic stroke and is associated with larger infarct volume and unfavorable functional outcome, also in patients who undergo reperfusion therapy. Hyperglycemia during reperfusion may be a therapeutic target. However, previous randomized trials on the effect of glucose lowering in the acute phase of ischemic stroke failed to demonstrate effects on clinical outcome. Inaccurate glucose measurements and not focussing on patients who undergo reperfusion therapy are possible explanations. Our aim was to study the feasibility and accuracy of continuous glucose monitoring (CGM) in patients with acute ischemic stroke undergoing endovascular treatment (EVT). METHODS: All consecutive patients with ischemic stroke and large vessel occlusion (LVO) of the anterior circulation who were eligible for endovascular therapy within 24 hours of symptom onset and presenting at the emergency department of Isala Hospital Zwolle, the Netherlands, were enrolled in this study. CGM was performed using a Freestyle Libre Flash 2 device (FSL-CGM, Abbot Diabetes Care, Alameda, California, USA) which was implanted on arrival at the emergency department. Feasibility was defined as the number of patients who could be registered for 24 hours and delay in door-to-groin time because of sensor implantation. Accuracy of CGM versus capillary and venous based plasma glucose values was determined with the Parkes error grid analysis. RESULTS: Twenty-three patients were included of whom 20 completed 24 hours monitoring (87%). One patient did not give permission to use the data; one sensor broke during implantation and one meter was broken after a sensor was shot in so no measurements could be recorded. There was no significant delay in treatment due to implantation of the sensor and no adverse events. One hundred percent of CGM data are in zones A and B of the Parkes error grid analysis so data out of the sensor can be interpreted as accurate. CONCLUSION: In this study, we showed that continuous glucose monitoring in patients with acute ischemic stroke due to large vessel occlusion of the anterior circulation in patients who were treated with endovascular therapy is feasible, safe and accurate.

Effect of metformin on outcome after acute ischemic stroke in patients with type 2 diabetes mellitus.

INTRODUCTION: Diabetes mellitus is a well-known risk factor for ischemic stroke and is associated with unfavorable outcome after stroke. Metformin is recommended as first-line treatment in these patients. Pre-stroke metformin use might have neuroprotective properties resulting in reduced stroke severity. However, results of the effects of pre-stroke metformin use on functional outcome are conflicting and has not been previously described in patients with type 2 diabetes mellitus regardless of stroke severity or revascularization treatment. In this study, we aimed to assess the association between metformin use and functional outcome in patients with type 2 diabetes mellitus and acute ischemic stroke. METHODS: We used data from patients with known type 2 diabetes mellitus who were admitted with acute ischemic stroke between 2017 and 2021 in the Isala Hospital Zwolle and Medisch Spectrum Twente (MST) Enschede, the Netherlands. The association between pre-stroke metformin use and favorable functional outcome at 3 months (defined as modified Rankin Scale (mRS) < 3) was expressed as Odds Ratios (ORs) with corresponding confidence intervals (CIs). Adjustments were made for age, sex, hyperglycemia on admission and revascularization treatment by means of multiple logistic regression. RESULTS: Nine hundred thirty seven patients were included of whom 592 patients (63%) used metformin. Six hundred seventy eight (74%) patients were hyperglycemic on admission. Median mRS was 3 (IQR 2-6) and 593 patients (63%) had a favorable outcome. Pre-stroke metformin use was associated with favorable outcome (aOR of 1.94 (95%- CI 1.45-2.59)). CONCLUSION: In this study, we showed that pre-stroke metformin use was associated with favorable outcome after acute ischemic stroke in patients with diabetes mellitus type 2.

Association of hyperglycemia and computed tomographic perfusion deficits in patients who underwent endovascular treatment for acute ischemic stroke caused by a proximal intracranial occlusion: A subgroup analysis of a randomized phase 3 trial (MR CLEAN).

INTRODUCTION: Hyperglycemia is highly prevalent in patients with acute ischemic stroke and is associated with increased risk of symptomatic intracranial hemorrhage, larger infarct size and unfavorable outcome. Furthermore, glucose may modify the effect of endovascular treatment (EVT) in patients with ischemic stroke. Hyperglycemia might lead to accelerated conversion of penumbra into infarct core. However, it remains uncertain whether hyperglycemia on admission is associated with the size of penumbra or infarct core in acute ischemic stroke. In this study, we aimed to assess the association between hyperglycemia and Computed Tomographic Perfusion (CTP) derived parameters in patients who underwent EVT for acute ischemic stroke. METHODS: We used data from the MR CLEAN study (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands). Hyperglycemia was defined as admission serum glucose of >7.8 mmol/L. Dichotomized and quantiles of glucose levels were related to size of core, penumbra and core penumbra ratio. Hypoperfused area is mean transient time 45% higher than that of the contralateral hemisphere. Core is the area with cerebral blood volume of <2 mL/100 g and penumbra is the area with cerebral blood volume > 2 mL/100 g. Core-penumbra ratio is the ischemic core divided by the total volume of hypoperfused tissue (core plus penumbra) multiplied by 100. Adjustments were made for age, sex, NIHSS on admission, onset-imaging time and diabetes mellitus. RESULTS: Hundred seventy-three patients were included. Median glucose level on admission was 6.5 mmol/L (IQR 5.8-7.5 mmol/L) and thirty-five patients (20%) were hyperglycemic. Median core volume was 33.3 mL (IQR 13.6-62.4 mL), median penumbra volume was 80.2 mL (IQR 36.3-123.5 mL) and median core-penumbra ratio was 28.5% (IQR 18.6-45.8%). Patients with hyperglycemia on admission had larger core volumes and core penumbra ratio than normoglycemic patients with a regression coefficient of 15.1 (95% confidence interval (CI), 1.8 to 28.3) and 11.5 (95% confidence interval (CI), 3.4 to 19.7) respectively. CONCLUSION: Hyperglycemia on admission was associated with larger ischemic core volume and larger core-penumbra ratio in patients with acute ischemic stroke who underwent endovascular treatment.

Metabolic syndrome and pre-eclampsia.

OBJECTIVE: To evaluate the association between different pre-eclampsia (PE) phenotypes and the development of metabolic syndrome postpartum, in order to identify the subgroup of formerly pre-eclamptic women with a worse cardiovascular risk profile requiring tailored postpartum follow-up. METHODS: This was a cohort study of 1102 formerly pre-eclamptic women in whom cardiovascular and cardiometabolic evaluation was performed at least 3 months postpartum. Women were divided into four subgroups based on PE resulting in delivery before 34 weeks (early-onset (EO)) or at or after 34 weeks (late onset (LO)) of gestation and whether they delivered a small-for-gestational-age (SGA) neonate. Metabolic syndrome was diagnosed as the presence of hyperinsulinemia along with two or more of: body mass index ≥ 30 kg/m2 ; dyslipidemia; hypertension; and microalbuminuria or proteinuria. Data were compared between groups using ANOVA after Bonferroni correction. Odds ratios (OR) were calculated using logistic regression to determine the association between metabolic syndrome and the four subgroups. We constructed receiver-operating characteristics curves and computed the area under the curve (AUC) to quantify the ability of different obstetric variables to distinguish between women who developed metabolic syndrome and those who did not. RESULTS: The prevalence of metabolic syndrome was higher in women with EO-PE and SGA (25.8%) than in those with EO-PE without SGA (14.7%) (OR 2.01 (95% CI, 1.34-3.03)) and approximately five-fold higher than in women with LO-PE with SGA (5.6%) (OR 5.85 (95% CI, 2.60-13.10)). In women with LO-PE, the prevalence of metabolic syndrome did not differ significantly between women with and those without SGA. Multivariate analysis revealed that a history of SGA, a history of EO-PE and systolic blood pressure at the time of screening are the best predictors of developing metabolic syndrome postpartum. The AUC of the model combining these three variables was 74.6% (95% CI, 70.7-78.5%). The probability of the presence of metabolic syndrome was calculated as: P = 1/(1 + e-LP ), where LP is linear predictor = -8.693 + (0.312 × SGA (yes = 1)) + (0.507 × EO-PE (yes = 1)) + (0.053 × systolic blood pressure). CONCLUSIONS: The incidence of metabolic syndrome postpartum was associated more strongly with EO-PE in combination with SGA as compared with LO-PE or EO-PE without SGA. Both time of onset of PE and fetal growth affect the risk of metabolic syndrome after a pre-eclamptic pregnancy. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Impaired fasting glucose is associated with unfavorable outcome in ischemic stroke patients treated with intravenous alteplase.

OBJECTIVES: Hyperglycemia on admission and diabetes mellitus type II are associated with unfavorable outcome in stroke patients. We studied whether impaired fasting glucose (IFG) is associated with unfavorable outcome in ischemic stroke patients treated with intravenous alteplase as well and if IFG is a stronger prognostic factor than hyperglycemia on admission. METHODS: We studied 220 consecutive patients with ischemic stroke treated with intravenous alteplase. In all nondiabetic patients, fasting glucose was determined on day 2-5. IFG was defined as fasting glucose level of ≥ 5.6 mmol/L, hyperglycemia on admission as glucose levels ≥ 7.9 mmol/L. The primary effect measure was the adjusted common odds ratio (acOR) for a shift in the direction of worse outcome on the modified Rankin Scale at 3 months, estimated with ordinal logistic regression, and adjusted for common prognostic factors. RESULTS: The fasting glucose levels were available in 194 and admission glucose levels in 215 patients. Sixty-three (32.5%) had IFG, 58 (27%) hyperglycemia on admission and 32 (14.6%) pre-existent diabetes. Patients with IFG showed a shift towards worse functional outcome compared with patients with normal fasting glucose levels (acOR 2.77; 95% CI 1.54-4.97), which was stronger than hyperglycemia on admission (acOR 1.75; 95% CI 0.91-3.4). CONCLUSIONS: IFG is associated with unfavorable outcome after treatment with intravenous alteplase for acute ischemic stroke. IFG predicts unfavorable outcome better than hyperglycemia on admission.

Glucose in prediabetic and diabetic range and outcome after stroke.

OBJECTIVES: Newly diagnosed disturbed glucose metabolism is highly prevalent in patients with stroke. Limited data are available on their prognostic value on outcome after stroke. We aimed to assess the association of glucose in the prediabetic and diabetic range with unfavourable short-term outcome after stroke. MATERIALS AND METHODS: We included 839 consecutive patients with ischemic stroke and 168 patients with intracerebral haemorrhage. In all nondiabetic patients, fasting glucose levels were determined on day 2-4. Prediabetic range was defined as fasting glucose of 5.6-6.9 mmol/L, diabetic range as ≥7.0 mmol/L, pre-existent diabetes as the use of anti-diabetic medication prior to admission. Outcome measures were poor functional outcome or death defined as modified Rankin Scale (mRS) score >2 and discharge not to home. The association of prediabetic range, diabetic range and pre-existent diabetes (versus normal glucose) with unfavourable outcome was expressed as odds ratios, estimated with multiple logistic regression, with adjustment for prognostic factors. RESULTS: Compared with normal glucose, prediabetic range (aOR 1.8; 95%CI 1.1-2.8), diabetic range (aOR 2.5; 95%CI 1.3-4.9) and pre-existent diabetes (aOR 2.6; 95%CI 1.6-4.0) were associated with poor functional outcome or death. Patients in the prediabetic range (aOR 0.6; 95%CI 0.4-0.9), diabetic range (aOR 0.4; 95%CI 0.2-0.9) and pre-existent diabetes (aOR 0.6; 95%CI 0.4-0.9) were more likely not to be discharged to home. CONCLUSIONS: Patients with glucose in the prediabetic and diabetic range have an increased risk of unfavourable short-term outcome after stroke. These findings illustrate the potential impact of early detection and treatment of these patients.

Increased admission and fasting glucose are associated with unfavorable short-term outcome after intra-arterial treatment of ischemic stroke in the MR CLEAN pretrial cohort.

BACKGROUND: Limited data are available on the impact of fasting glucose on outcome after intra-arterial treatment (IAT). We studied whether hyperglycemia on admission and impaired fasting glucose (IFG) are associated with unfavorable outcome after IAT in acute ischemic stroke. METHODS: Patients were derived from the pretrial registry of the MR CLEAN-trial. Hyperglycemia on admission was defined as glucose>7.8mmol/L, IFG as fasting glucose>5.5mmol/L in the first week of admission. Primary effect measure was the adjusted common odds ratio (acOR) for a shift in the direction of worse outcome on the modified Rankin Scale at discharge, estimated with ordinal logistic regression, adjusted for common prognostic factors. RESULTS: Of the 335 patients in which glucose on admission was available, 86 (26%) were hyperglycemic, 148 of the 240 patients with available fasting glucose levels (62%) had IFG. Median admission glucose was 6.8mmol/L (IQR 6-8). Increased admission glucose (acOR 1.2, 95%CI 1.1-1.3), hyperglycemia on admission (acOR 2.6, 95%CI 1.5-4.6) and IFG (acOR 2.8, 95%CI 1.4-5.6) were associated with worse functional outcome at discharge. CONCLUSION: Increased glucose on admission and IFG in the first week after stroke onset are associated with unfavorable short-term outcome after IAT of acute ischemic stroke.

Safety and feasibiLIty of Metformin in patients with Impaired glucose Tolerance and a recent TIA or minor ischemic stroke (LIMIT) trial - a multicenter, randomized, open-label phase II trial.

BACKGROUND AND PURPOSE: We aimed to assess the safety, feasibility, and effects on glucose metabolism of treatment with metformin in patients with TIA or minor ischemic stroke and impaired glucose tolerance. METHODS: We performed a multicenter, randomized, controlled, open-label phase II trial with blinded outcome assessment. Patients with TIA or minor ischemic stroke in the previous six months and impaired glucose tolerance (2-hour post-load glucose levels of 7.8-11.0 mmol/l) were randomized to metformin, in a daily dose of 2 g, or no metformin, for three months. Primary outcome measures were safety and feasibility of metformin, and the adjusted difference in 2-hour post-load glucose levels at three months. This trial is registered as an International Standard Randomized Controlled Trial Number 54960762. RESULTS: Forty patients were enrolled; 19 patients were randomly assigned metformin. Nine patients in the metformin group had side effects, mostly gastrointestinal, leading to permanent discontinuation in four patients after 3-10 weeks. Treatment with metformin was associated with a significant reduction in 2-hour post-load glucose levels of 0·97 mmol/l (95% CI 0·11-1·83) in the on-treatment analysis, but not in the intention-to-treat analysis (0·71 mmol/l; 95% CI -0·36 to 1·78). CONCLUSIONS: Treatment with metformin in patients with TIA or minor ischemic stroke and impaired glucose tolerance is safe, but leads to minor side effects. If tolerated, it may lead to a significant reduction in post-load glucose levels. This suggests that the role of metformin as potential therapeutic agent for secondary stroke prevention should be further explored.

Nephrocalcinosis as adult presentation of Bartter syndrome type II.

Bartter syndrome consists a group of rare autosomal-recessive renal tubulopathies characterised by renal salt wasting, hypokalaemic metabolic alkalosis, hypercalciuria and hyperreninaemic hyperaldosteronism. It is classified into five types. Mutations in the KCNJ1 gene (classified as type II) usually cause the neonatal form of Bartter syndrome. We describe an adult patient with a homozygous KCNJ1 mutation resulting in a remarkably mild phenotype of neonatal type Bartter syndrome.

Vitamin D deficiency in patients with erythropoietic protoporphyria.

BACKGROUND: The main symptom of patients with erythropoietic protoporphyria (EPP) is painful photosensitivity, starting within minutes of sun exposure and leading to sun-avoidance. As 80-100% of vitamin D is synthesized under the influence of sunlight, we investigated whether the avoidance of sunlight exposure in the Dutch EPP patient population causes vitamin D deficiency. Furthermore, we studied the relation between vitamin D levels, total erythrocyte protoporphyrin and quality of life. METHODS: In a cross-sectional study of 48 Dutch EPP patients (mean age 41.4 years; range 16-77; 23 male, 25 female), we assessed serum 25-hydroxyvitamin D (25(OH)D) levels between June and November 2007, as well as total erythrocyte protoporphyrin (TEP) levels and Dermatology Life Quality Index (DLQI) scores. RESULTS: Mean serum 25(OH)D was 66 nmol/L (range 18-140, quartiles 36, 87). Twenty-two patients (46%; 15 male, 7 female) were vitamin D deficient. There was a significant difference (p = 0.029) in mean serum 25(OH)D between female (mean 75 nmol/L, range 18-140) and male patients (mean 55 nmol/L, range 18-115). The level of serum 25(OH)D showed a negative correlation with total erythrocyte protoporphyrin (TEP) (Pearson rank correlation (r(p)) = -0.337; p = 0.034). Serum 25(OH)D was inversely associated with scores of the Dermatology Life Quality Index (DLQI) (Spearman's rho correlation (r(s)) = -0.486; p = 0.001). CONCLUSIONS: The prevalence of vitamin D deficiency is high in the Dutch EPP population, especially in male patients, and correlates with the severity of EPP. Screening for and treatment of vitamin D deficiency should therefore be implemented in the care of these patients.