We aimed to study whether visit-to-visit variability of glycated hemoglobin A 1c (HbA 1c) is associated with incident major adverse cardiovascular events (MACE), all-cause mortality, and type 2 diabetes in people without diabetes. RESEARCH DESIGN AND METHODS We included primary care patients with no history of diabetes or cardiovascular disease and with three annual HbA 1c measurements within normal range (<6.5% [48 mmol/mol]). For each individual, we measured the HbA 1c variability as the SD of the residuals obtained from a linear regression on the three HbA 1c measurements. From the linear regression, we also obtained the estimated index HbA 1c (intercept) and the trend over time (slope). Follow-up began at the date of the third measurement. Associations between HbA 1c variability and outcome were analyzed using Cox regression, adjusted for traditional risk factors, intercept, and trend and reported as hazard ratio per SD increase in variability (HR SD). RESULTS In total, 6,756 individuals were included. During a median follow-up time of 6.3 years, 996 developed MACE, 856 died, and 1,267 developed type 2 diabetes. We found a significant association between increasing HbA 1c variability and incident MACE (HR SD 1.09 [95% CI 1.03-1.15]) and all-cause mortality (HR SD 1.13 [95% CI 1.07-1.20]), whereas there were no associations with type 2 diabetes (HR SD 1.00 [95% CI 0.95-1.05]). We calculated 5-year absolute risks of MACE and all-cause mortality and found clinically relevant differences across several age, sex, comorbidity, and HbA 1c variability-defined subgroups. CONCLUSIONS In a primary care population free of diabetes and cardiovascular disease, high HbA 1c variability was associated with increased risks of MACE and all-cause mortality. Type 2 diabetes is an important risk factor for major adverse cardiovascular events (MACE) and premature death from cardiovascular causes (1,2). Glycated hemoglobin A 1c (HbA 1c) is a readily available and highly reproducible biomarker that reflects the 3-month average plasma glucose concentration; it can be measured in the nonfasting state, and a value $6.5% (48 mmol/mol) is considered diagnostic for diabetes (3).

Aim To investigate the effect of diabetes duration on glycaemic control, measured using mean glycated haemoglobin (HbA1c) level, and mortality risk within different age, sex and clinically relevant, comorbidity‐defined subgroups in an elderly population with type 2 diabetes (T2D). Methods We studied older (≥65 years) primary care patients with T2D, who had three successive annual measurements of HbA1c taken between 2005 and 2013. The primary exposure was the mean of all three HbA1c measurements. Follow‐up began on the date of the third measurement. Individual mean HbA1c levels were categorized into clinically relevant groups (<6.5% [<48 mmol/mol]; 6.5%‐6.9% [48‐52 mmol/mol]; 7%‐7.9% [53‐63 mmol/mol]; 8%‐8.9% [64‐74 mmol/mol]; and ≥9% [≥75 mmol/mol]). We used multiple Cox regression to study the effect of glycaemic control on the hazard of all‐cause mortality, adjusted for age, sex, use of concomitant medication, and age‐ and disease‐related comorbidities. Results A total of 9734 individuals were included. During a median (interquartile range) follow‐up of 7.3 (4.6‐8.7) years, 3320 individuals died. We found that the effect of mean HbA1c on all‐cause mortality depended on the duration of diabetes (P for interaction <.001). For individuals with short diabetes duration (<5 years), the risk of death increased with poorer glycaemic control (increasing HbA1c), whereas for individuals with longstanding diabetes (≥5 years), we found a J‐shaped association, where a mean HbA1c level between 6.5% and 7.9% [48 and 63 mmol/mol] was associated with the lowest risk of death. For individuals with longstanding diabetes, both low (<6.5% [<48 mmol/mol]; hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.07‐1.37, P = .002) and high mean HbA1c levels (≥9.0% [≥75 mmol/mol]; HR 1.60, 95% CI 1.28‐1.99, P < .001) were associated with an increased risk of death. We also calculated 5‐year absolute risks of all‐cause mortality, separately for short and long diabetes duration, and found similar risk patterns across different age groups, sex and comorbidity strata. Conclusions In elderly individuals with T2D, the effect of glycaemic control (measured by HbA1c) on all‐cause mortality depended on the duration of diabetes. Of particular clinical importance, we found that strict glycaemic control was associated with an increased risk of death among individuals with long (≥ 5 years) diabetes duration. Conversely, for individuals with short diabetes duration, strict glycaemic control was associated with the lowest risk of death. These results indicate that tight glycemic control may be beneficial in people with short duration of diabetes, whereas a less stringent target may be warranted with longer diabetes exposure.

Background: In equine medicine, 12-lead electrocardiograms (ECGs) rarely are used, which may in part be a result of shortcomings in the existing guidelines for obtaining 12-lead ECGs in horses. The guidelines recommend placing the limb leads on the extremities, which is inappropriate because the ventricular mean electrical axis is then perpendicular to the limb leads, leading to large variations in ECG configuration even among healthy horses. From an electrophysiological point of view, the leads instead should be parallel to the electrical axis to minimize variability. Objective: Develop an improved method for obtaining 12-lead ECGs in horses based on electrophysiology and cardiac electrical vectors relevant to horses. Animals: Thirty-five healthy Standardbred horses. Methods: Two ECGs obtained at rest; 1 ECG with the electrodes placed according to the method developed in the present study, the Copenhagen method, and 1 ECG following existing guidelines. Results: In the Copenhagen method, we repositioned the limb electrodes to the thorax to better capture the electrical activity of the heart. Variation in the mean electrical axis decreased dramatically with the Copenhagen method (SD decreased from 24.6 to 1.6 , P < .001). Consequently, this new method provided stable ECGs with repeatable configurations. Conclusions and Clinical Importance: With this novel method, the ECG is recorded with respect to the electric axis to fully realize the potential of 12-lead ECG in horses. The Copenhagen method delivered more consistent and reliable ECG recordings compared to existing guidelines. The Copenhagen method potentially allows for expanded use of 12-lead ECGs in equine medicine.

BackgroundIn a c-VEP BCI setting, test subjects can have highly varying performances when different pseudorandom sequences are applied as stimulus, and ideally, multiple codes should be supported. On the other hand, repeating the experiment with many different pseudorandom sequences is a laborious process.AimsThis study aimed to suggest an efficient method for choosing the optimal stimulus sequence based on a fast test and simple measures to increase the performance and minimize the time consumption for research trials.MethodsA total of 21 healthy subjects were included in an online wheelchair control task and completed the same task using stimuli based on the m-code, the gold-code, and the Barker-code. Correct/incorrect identification and time consumption were obtained for each identification. Subject-specific templates were characterized and used in a forward-step first-order model to predict the chance of completion and accuracy score.ResultsNo specific pseudorandom sequence showed superior accuracy on the group basis. When isolating the individual performances with the highest accuracy, time consumption per identification was not significantly increased. The Accuracy Score aids in predicting what pseudorandom sequence will lead to the best performance using only the templates. The Accuracy Score was higher when the template resembled a delta function the most and when repeated templates were consistent. For completion prediction, only the shape of the template was a significant predictor.ConclusionsThe simple and fast method presented in this study as the Accuracy Score, allows c-VEP based BCI systems to support multiple pseudorandom sequences without increase in trial length. This allows for more personalized BCI systems with better performance to be tested without increased costs.