Association of HbA1c levels with vascular complications and death in patients with type 2 diabetes: evidence of glycaemic thresholds

Aims/hypothesis

There is conflicting evidence regarding appropriate glycaemic targets for patients with type 2 diabetes. Here, we investigate the relationship between HbA_1c and the risks of vascular complications and death in such patients.

Methods

Eleven thousand one hundred and forty patients were randomised to intensive or standard glucose control in the Action in Diabetes and Vascular disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. Glycaemic exposure was assessed as the mean of HbA_1c measurements during follow-up and prior to the first event. Adjusted risks for each HbA_1c decile were estimated using Cox models. Possible differences in the association between HbA_1c and risks at different levels of HbA_1c were explored using linear spline models.

Results

There was a non-linear relationship between mean HbA_1c during follow-up and the risks of macrovascular events, microvascular events and death. Within the range of HbA_1c studied (5.5?C10.5%), there was evidence of ??thresholds??, such that below HbA_1c levels of 7.0% for macrovascular events and death, and 6.5% for microvascular events, there was no significant change in risks (all p?>?0.8). Above these thresholds, the risks increased significantly: every 1% higher HbA_1c level was associated with a 38% higher risk of a macrovascular event, a 40% higher risk of a microvascular event and a 38% higher risk of death (all p?Conclusions/interpretation In patients with type 2 diabetes, HbA_1c levels were associated with lower risks of macrovascular events and death down to a threshold of 7.0% and microvascular events down to a threshold of 6.5%. There was no evidence of lower risks below these levels but neither was there clear evidence of harm.

Trial Registration:

ClinicalTrial.gov NCT00145925

Funding:

Servier and the National Health and Medical Research Council of Australia (project grant ID 211086 and programme grant IDs 358395 and 571281)     

Diagnosis of myocardial infarction following hospitalisation for exacerbation of COPD

Cardiovascular disease is common in chronic obstructive pulmonary disease (COPD) and raised troponin is common in exacerbations. However, the prevalence of myocardial infarction following hospitalisation for exacerbation of COPD is unknown. Patients aged ≥ 40 yrs hospitalised with acute exacerbation of COPD (n = 242) with ≥ 10 pack-yrs of cigarette smoking were included in a prospective case series conducted in four hospitals. Patients whose primary presenting complaint was chest pain or who had an alternative diagnosis were excluded. Chest pain histories, serial ECGs and troponin levels were obtained. The mean ± SD age was 69 ± 9 yrs; 108 (45%) patients were male and almost half were current smokers. 124 (51%; 95% CI 48-58%) patients had chest pain, which was exertional in 62 (26%). 24 (10%) had raised troponin, among whom, 20 (8.3%; 95% CI 5.1-12.5%) had chest pain and/or serial ECG changes, fulfilling the 2007 Universal Definition of Myocardial Infarction. Neither chest pain (p = 0.77) nor serial ECG changes (p = 0.39) were associated with raised troponin. Raised troponin, chest pain and serial ECG changes are common in patients admitted to hospital with exacerbation of COPD. Overall, one in 12 patients met the criteria for myocardial infarction. Whether these patients would benefit from further cardiac investigation is unknown.     

Quantitative ultrasonography of facial muscles

Introduction: There is no standardized method for examination of facial muscles with ultrasound. The purpose of this study was to identify those facial muscles accessible for reliable identification and to provide reference data. Methods: In healthy subjects all facial muscles were screened for visibility, separation from adjacent muscles, and reliability of landmarks. Bilateral scans of reliable muscles were performed in 40 adult volunteers. Results: Six facial muscles were clearly demarcated with ultrasound. These were: frontalis, orbicularis oculi, orbicularis oris, depressor anguli oris, depressor labii inferioris, and mentalis muscles. Cross-sectional area and muscle thickness showed gender differences and were independently related to age for some muscles. A significant left–right side difference was only seen for the orbicularis oculi muscle in women. Conclusions: These data demonstrate the usefulness of ultrasonography to assess facial muscles and provide reference values that can be applied in the clinical setting. Muscle Nerve 47: 878–883, 2013     

Cardiac output monitoring to guide fluid replacement in head and neck microvascular free flap surgery-what is current practice in the UK?

Appropriate fluid balance is an important factor in the survival of free flaps, and recently there has been a shift towards more conservative fluid regimens. Several surgical specialties have made extensive use of the relatively non-invasive method of measuring cardiac output (CO) to optimise fluid balance during and after surgery, which has resulted in a shorter hospital stay, but little has been published in head and neck surgery. To ascertain its use in the head and neck we sent a postal questionnaire to the anaesthetic departments of 40 major head and neck units identified from the 2010 database of the British Association of Oral and Maxillofacial Surgeons (BAOMS). Questions were asked about the number of free flaps done in the unit each year, the monitoring of central venous and arterial blood pressure (and inotrope protocols), optimal target variables, and whether CO was monitored (with type of device). Thirty-two units responded (80%). While 26 units (81%) routinely monitored central venous pressure (CVP), CO was monitored in only 3 units (9%). There was a wide range of responses in relation to optimal variables and use of inotropes. As with other specialties, it is likely that CO monitoring will become widely used in head and neck reconstructive surgery. Not only does it enhance fluid optimisation, but it may also reduce hospital stay and morbidity. Appropriate clinical studies are urgently needed to evaluate its use in our specialty.     

Single‐Center Experience With HeartMate II Left Ventricular Assist Device Explantation

In patients with continuous flow left ventricular assist devices (CF‐LVADs) myocardial recovery is uncommon. Given the heterogeneity of the population implanted and low incidence of recovery, the discovery of native left ventricular (LV) recovery and criteria for explantation of CF‐LVAD system is not clearly determined. We sought to analyze the characteristics of the patients who underwent CF‐LVAD explantation at our institution. Prospectively collected data on patients supported with CF‐LVADs were reviewed retrospectively. Patients who underwent CF‐LVAD explants were identified and their characteristics were analyzed with a focus on patient presentation and determinants of explantability. From November 2006 to June 2014, 223 patients (181 male, 42 female) underwent implantation of HeartMate II LVAD. Seven female (16.7%) and one male (0.6%) patients were explanted (P < 0.001). Mean age was 43 ± 9 years and etiology for cardiomyopathy was ischemic in three (37.5%) patients, nonischemic in four (50%) patients, and mixed in the one (12.5%) male patient of the cohort. Five (62.5%) patients presented acutely with significant hemolysis, and were found to have LV improvement as well as reduced, absent, or reversed diastolic flow velocities on echocardiography. Overall, mean lactate dehydrogenase level before explantation was 1709 ± 1168 U/L compared to the mean baseline level of 601 ± 316 U/L (P = 0.048). Mean LV ejection fraction (LVEF) improved from 17 ± 7% preimplant to 56 ± 11% pre‐explantation (P < 0.001). Median number of days on CF‐LVAD support was 870 (interquartile range, 209–975) while mean duration of follow‐up after the CF‐LVAD explantation was 276 ± 240 days. Mean LVEF dropped from 46 ± 19% postexplantation to 34 ± 10% during the most recent follow‐up (P = 0.015). At our institution, patients who underwent LVAD explants were predominantly women with nonischemic cardiomyopathy. Clinical evidence of hemolysis and echocardiographic evidence of reduced or absent diastolic flow velocities were common findings in these patients. Over time, patient's native LV function declined in the absence of LVAD (after LVAD explantation). Significant challenges remain in predicting LV recovery and identifying those individuals who have recovered myocardial function significant enough to be explanted.     

Thinking outside the glenohumeral box: Hierarchical shape variation of the periarticular anatomy of the scapula using statistical shape modeling

Variation in the shape of the glenoid and periarticular anatomy of the scapula has been associated with shoulder pathology. The goal of this study was to identify the modes of shape variation of periarticular scapular anatomy in relation to the glenoid in nonpathologic shoulders. Computed tomography scans of 31 cadaveric scapulae, verified to be free of pathology, were three-dimensionally reconstructed. Statistical shape modeling and principal component analysis identified the modes of shape variation across the population. Corresponding linear and angular measurements quantified the morphometric variance identified by the modes. Linear measures were normalized to the radius of the inferior glenoid to account for differences in the scaling of the bones. Five modes captured 89.7% of total shape variation of the glenoid and periarticular anatomy. Apart from size differences (mode 1: 33.0%), acromial anatomy accounted for the largest variation (mode 2: 32.0%). Further modes described variation in glenoid inclination (mode 3: 11.8%), coracoid orientation and size (mode 4: 9.0%), and variation in coracoacromial (CA) morphology (mode 5: 3.1%). The average scapula had a mean acromial tilt of 49 ± 7°, scapular spine angle of 61 ± 6°, the glenoid inclination of 84 ± 4°, coracoid deviation angle of 26 ± 4°, coracoid length of 3.7 ± 0.3 glenoid radii, and a CA base length of 5.6 ± 0.5 radii. In this study, the identified shape modes explain almost all of the variance in scapular anatomy. The acromion exhibited the highest variance of all periarticular anatomic structures of the scapula in relation to the glenoid, which may play a role in many shoulder pathologies.