Glucokinase activity in diabetes: too much of a good thing?

Type 2 diabetes (T2D) is a global health problem characterised by chronic hyperglycaemia due to inadequate insulin secretion. Because glucose must be metabolised to stimulate insulin release it was initially argued that drugs that stimulate glucokinase (the first enzyme in glucose metabolism) would enhance insulin secretion in diabetes. However, in the long term, glucokinase activators have been largely disappointing. Recent studies show it is hyperactivation of glucose metabolism, not glucose itself, that underlies the progressive decline in beta-cell function in diabetes. This perspective discusses if glucokinase activators exacerbate this decline (by promoting glucose metabolism) and, counterintuitively, if glucokinase inhibitors might be a better therapeutic strategy for preserving beta-cell function in T2D.     

Too much of a good thing? A critique of overemphasis on the use of ambulatory blood pressure monitoring in clinical practice

Ambulatory blood pressure monitoring (ABPM) can be considered a major achievement in clinical medicine. However, its superiority over traditional clinical measurement has often been overemphasized in the literature. In both cross-sectional and longitudinal studies, ABPM has been compared with clinical blood pressure calculated from only a few readings taken over a short period of time. For reasons of costs and practicality, ABPM should not be considered as a routine test in the assessment of the hypertensive patient. Most patients with borderline hypertension or isolated clinical hypertension can be profitably assessed with multiple clinical readings and self-blood pressure monitoring. Patients with large short-term or long-term blood pressure oscillations appear as optimal candidates to ABPM. The many methodological problems associated with the use of this technique suggest that ABPM is performed only by experienced doctors.     

How does the heart (not) die? The role of autophagy in cardiomyocyte homeostasis and cell death

Autophagy plays a critical and seemingly dual-purposed role in cardiomyocytes, being implicated as a mechanism of both cellular survival, for example, during ischemia/reperfusion injury and a mechanism of cell death at stages in which progressive myocyte alterations are beyond repair. This review aims to highlight the current literature as it relates to autophagy in cardiomyocytes. It provides background into the mechanisms of cell death, discusses the details that are known about the ubiquitin proteasome system and autophagy, delves into the pathways that are known to initiate and inhibit autophagy, and comments on the role of autophagy in cardiomyocyte homeostasis and cell death.     

Reducing cardiovascular disease risk in patients with type 2 diabetes and concomitant macrovascular disease: can insulin be too much of a good thing?

Despite improvement of microvascular outcomes as a consequence of optimal glucose control in patients with type 2 diabetes, prevention of macrovascular complications is still a major challenge. Of interest, large-scale intervention studies (Action to Control Cardiovascular Risk in Diabetes, Action in Diabetes and Vascular Disease-Preterax and Diamicron Modified Release Controlled Evaluation and Veterans Affairs Diabetes Trial) comparing standard therapy versus more intensive glucose-lowering therapy failed to report beneficial impacts on macrovascular outcomes. Consequently, it is currently under debate whether the high doses of exogenous insulin that were administered in these trials to achieve strict target glucose levels could be responsible for these unexpected outcomes. Additionally, a potential role for plasma insulin levels in predicting macrovascular outcomes has emerged in patients with or without type 2 diabetes. These observations, combined with evidence from in vitro and animal experiments, suggest that insulin might have intrinsic atherogenic effects. In this review, we summarize clinical trials, population-based studies as well as data emerging from basic science experiments that point towards the hypothesis that the administration of high insulin doses might not be beneficial in patients with type 2 diabetes and established macrovascular disease.     

The role of cardiac magnetic resonance in identifying appropriate candidates for cardiac resynchronization therapy — a systematic review of the literature

Heart Failure Reviews - Despite the strict indications for cardiac resynchronization therapy (CRT) implantation, a significant proportion of patients will fail to adequately respond to the...     

How much is not enough? A community randomized trial of a Water and Health Education programme for Trachoma and Ocular C. trachomatis infection in Niger

Objective  To determine the impact after 2 years of a water and health education (W/HE) programme on ocular Chlamydia trachomatis infection and trachoma.
Methods  We randomized 12 trachoma-endemic communities in Maradi, Niger 1:1 to W/HE intervention and control arms and collected data on 10 of the 12 villages. In the intervention villages, at least one clean water well was constructed, and a 3 month, modest health education programme was provided immediately prior to the 2 year survey. We censused all households, and 557 children ages 1–5 years were randomly selected as sentinel children and examined at baseline and at one and 2 years from baseline. Trachoma was clinically assessed and a swab taken and analyzed for C. trachomatis . Tetracycline eye ointment was provided to all children in either arm during the surveys who had signs of trachoma.
Results  Infection with C. trachomatis declined slightly, and not significantly, in the children in the control villages over the 2 years, from 15% to 11%. The decline in infection was more pronounced, and significant, in the children in the intervention villages, from 26% to 15%. However, the change in infection rates in the intervention villages was not significantly different from the change in infection rates in the control villages ( P  = 0.39, and 0.11 for change from baseline to 1 year and 2 year, respectively). There was also no difference in the change in overall trachoma rates between the two arms.
Conclusion  These data suggest that the provision of water plus a modest health education programme did not result in a significant difference in trachoma or ocular C. trachomatis infection in endemic communities in Niger. A more substantial health education intervention is likely necessary to produce change.     

The ECG in sarcoidosis – a marker of cardiac involvement? Current evidence and clinical implications

Sarcoidosis is a multisystem granulomatous disease of unknown etiology characterized by noncaseating granulomas. Cardiac involvement is often limiting patients’ prognosis. Cardiac sarcoidosis can manifest with variant cardiac arrhythmias, of which atrioventricular (AV)-block-related bradycardia and ventricular tachycardias are the most common. Although cardiac sarcoidosis remains a histopathological diagnosis, the significance of imaging modalities, especially cardiac magnetic resonance imaging is increasing rapidly but mainly remains reserved for patients with a high suspicion due to a previous arrhythmia or unknown cardiomyopathy. Thus, there is a need for screening in daily clinical practice so that possible characteristic electrocardiographic (ECG) findings may guide the way to detect the disease.We therefore evaluated the ECG as a potential tool for screening of cardiac sarcoidosis and present different electrophysiological manifestations of cardiac sarcoidosis based on a literature review.The ECG is a valuable tool for screening of cardiac involvement in patients with sarcoidosis. Several parameters have been shown to be associated with cardiac involvement in sarcoidosis such as higher-degree AV-block, QRS complex fragmentation and widening, as well as certain T wave abnormalities that may indicate cardiac involvement, of which the latter two are most promising and specific. However, prospective studies examining a large number of trials are desirable.     

Anomalous origin and course of left coronary artery—Cause of cardiac arrest in a young female athlete

Coronary artery anomalies represent a rare condition in the general population. Our case report describes a young female patient who survived sudden cardiac death caused by the left coronary artery arising atypically from the right coronary sinus.