SGLT2 inhibitors and the cardiorenal continuum: a paradigm shift in the treatment of patients with T2D

Type 2 diabetes mellitus (T2D) represents a sig- nificant public health problem, with a dramat- ically increasing prevalence. T2D is considered a progressive disease that develops macro- and microvascular complications such as cardiovas- cular disease (CVD), heart failure (HF), and chronic kidney disease (CKD), which are closely interconnected and constitute the main causes of morbidity and mortality in these patients. Over time, finding new pharmacological approaches to protect against these cardiorenal events (the ‘‘cardiorenal continuum’’) has become the fundamental objective of research aimed at these patients

Shrinking the lymphatic filariasis map of Ethiopia: reassessing the population at risk through nationwide mapping

BACKGROUND Mapping of lymphatic filariasis (LF) is essential for the delineation of endemic implementation units and determining the population at risk that will be targeted for mass drug administration (MDA). Prior to the current study, only 116 of the 832 woredas (districts) in Ethiopia had been mapped for LF. The aim of this study was to perform a nationwide mapping exercise to determine the number of people that should be targeted for MDA in 2016 when national coverage was anticipated. METHODOLOGY/PRINCIPAL FINDING A two-stage cluster purposive sampling was used to conduct a community-based cross-sectional survey for an integrated mapping of LF and podoconiosis, in seven regional states and two city administrations. Two communities in each woreda were purposely selected using the World Health Organization (WHO) mapping strategy for LF based on sampling 100 individuals per community and two purposely selected communities per woreda. Overall, 130 166 people were examined in 1315 communities in 658 woredas. In total, 140 people were found to be positive for circulating LF antigen by immunochromatographic card test (ICT) in 89 communities. Based on WHO guidelines, 75 of the 658 woredas surveyed in the nine regions were found to be endemic for LF with a 2016 projected population of 9 267 410 residing in areas of active disease transmission. Combining these results with other data it is estimated that 11 580 010 people in 112 woredas will be exposed to infection in 2016. CONCLUSIONS We have conducted nationwide mapping of LF in Ethiopia and demonstrated that the number of people living in LF endemic areas is 60% lower than current estimates. We also showed that integrated mapping of multiple NTDs is feasible and cost effective and if properly planned, can be quickly achieved at national scale

Effectiveness and Efficiency of Persuasive Space Graphics (PSG) in Motivating UK Primary School Children’s Hand Hygiene

Good hand hygiene is necessary to control and prevent infections, but many children do not adequately wash their hands. While there are classroom communications targeted at children, the toilet space, the location of many hand hygiene activities, is neglected. This paper describes an initial evaluation of “123” persuasive space graphics (images and messages integrated within an architectural environment that encourage specific actions). The effectiveness (whether hand hygiene improves) and efficiency (the ease with which a setting can adopt and implement an intervention) is evaluated in three UK schools and one museum. Five evaluations (participant demographic, handwashing frequency, handwashing quality, design persuasiveness, stakeholder views) were conducted. In the school settings, persuasive space graphics increased the quality and frequency of handwashing. In the museum setting, frequency of handwashing slightly increased. In all settings children found the graphics persuasive, and stakeholders also believed them to be effective. Stakeholders considered persuasive space graphics a low-cost and time-efficient way to communicate. It can be concluded that persuasive space graphics are effective in increasing hand hygiene, particularly in school settings where children have a longer exposure to the graphics. Persuasive space graphics are also an efficient low-cost means of communicating hand hygiene

Nuevas estrategias terapéuticas en diabetes mellitus tipo 1

El principal determinante del riesgo de complicaciones derivadas de la diabetes mellitus tipo 1 se debe a los altos niveles de glucosa en sangre mantenidos durante largo tiempo. Para conseguir un beneficio terapéutico en pacientes con diabetes mellitus es necesario desarrollar tratamientos que permitan de manera segura, efectiva y estable mantener la normoglucemia. Lamentablemente, el tratamiento de la diabetes mellitus tipo 1 mediante el aporte exógeno de insulina no es capaz de conseguir niveles estables de glucosa en sangre, de manera que con frecuencia se producen casos de severa hipoglucemia o hiperglucemia. Hasta la fecha la única solución para reestablecer de manera permanente la normoglucemia se consigue mediante el trasplante de páncreas o de islotes pancreáticos. Sin embargo, a medida que se incrementa el número de centros especializados en el trasplante de islotes, mayor es la necesidad de islotes para su trasplante. Así pues, el estudio de nuevas fuentes de células productoras de insulina así como de nuevos tratamientos que permitan preservar o incluso aumentar la masa de células beta en los pacientes con diabetes mellitus representa un objetivo de primera necesidad en este campo. En este sentido, en la última década ha habido un avance significativo en el campo de la biología de las células madre. Sin embargo, la identificación de células apropiadas para la generación de nuevas células beta, además del desarrollo de técnicas para la caracterización de estas células, así como de ensayos y modelos animales apropiados para probar su capacidad de diferenciación tanto in vitro como in vivo son de vital importancia para la puesta en marcha de nuevas estrategias terapéuticas basadas en la aplicación de las células madre para el tratamiento de la diabetes mellitus tipo 1

High body adiposity drives glucose intolerance and increases cardiovascular risk in normoglycemic subjects

Objective: We aimed to assess the utility of the 2 - hour oral glucose tolerance test (OGTT) value to discriminate between different cardiometabolic profiles and examine the role of body composition to predict the associated increased risk for glucose impairment, beta cell dysfunction and cardiovascular disease. Methods: Subjects with normal fasting glucose (NFG) completed a 2 - h OGTT and were categorized to the carbohydrate metabolism alterations (CMA) or contro l group based upon a 2 - h glucose threshold of 7.8 mmol l - 1 . Body composition, visceral adipose tissue, OGTT - based parameters and cardiovascular risk factors (CVRF) such as hypertension, dyslipidemia, obstructive sleep apnea, non - alcoholic fatty liver disea se and smoking status, were measured. Results: Subjects with CMA exhibited a significantly higher 1 - h postload glucose, greater decline in beta cell function and CVRF profile. After multivariate adjustment, excess of total body and visceral fat was associ ated with an increased risk of CMA, - cell dysfunction, CVRF and a lower whole - body insulin sensitivity. Conclusions: These data support the ethiopathogenic role of body and visceral fat in the development of glucose derangements and CVRF early on in the metabolic dysregulation process. Thus, body composition analysis and OGTT assessment performed in individuals with NFG enables a better identification of patients at risk of developing type 2 diabetes and cardiovascular disease

A severe case of lipoatrophy due to human insulin and insulin analogs in a patient with diabetes: is an immunological mechanism involved?

The precipitin technique has been used in insulin resistance and immunity studies since the 1940s [7]. In the case described, the technique proved, once again, to be a valid method for choosing the most appropriate insulin. However, whether or not an immunological mechanism was involved in the lipoatrophic process remains uncertain, and further studies with adequate immunological assessment are necessary

Treatment of type 2 diabetes by patient profile in the clinical practice of endocrinology in Spain: Delphi study results from the think twice program

Introduction: The aim of this Delphi study is to unveil the management of patients with type 2 diabetes (T2D) and different levels of complexity in the clinical practice in Spain. Methods: Based on the common management practices of T2D profiles reported by Spanish endocrinologists, a Delphi questionnaire of 55 statements was developed and responded to by a national panel (n = 101). Results: A consensus was reached for 30 of the 55 statements. Regarding overweight patients inadequately controlled with metformin, treatment with a sodium-glucose transport protein 2 inhibitor (SGLT2-I) is preferred over treatment with a dipeptidyl peptidase-4 inhibitor (DPP4-I). If the patient is already being treated with a DPP4-I, an SGLT2-I is added on to the treatment regimen rather than replacing the DPP4-I. Conversely, if the treatment regimen includes a sulfonylurea, it is usually replaced by other antihyperglycemic agents. Current treatment trends in uncontrolled obese patients include the addition of an SGLT2-I or a glucagon-like peptide-1 receptor agonist (GLP1-RA) to background therapy. When the glycated hemoglobin target is not reached, triple therapy with metformin ? GLP1-RA ? SGLT2-I is initiated. Although SGLT2-Is are the treatment of choice in patients with T2D and heart failure or uncontrolled hypertension, no consensus was reached regarding the preferential use of SGLT2- Is or GLP1-RAs in patients with established cardiovascular disease. Conclusion: Consensus has been reached for a variety of statements regarding the management of several T2D profiles. Achieving a more homogeneous management of complex patients with T2D may require further evidence and a better understanding of the key drivers for treatment choice

Resting energy expenditure is not altered in children and adolescents with obesity. Effect of age and gender and association with serum Leptin levels

In children and adolescents, obesity does not seem to depend on a reduction of resting energy expenditure (REE). Moreover, in this young population, the interactions between either age and obesity or between age and gender, or the role of leptin on REE are not clearly understood. To compare the levels of REE in children and adolescents we studied 181 Caucasian individuals (62% girls) classified on the basis of age-and sex-specific body mass index (BMI) percentile as healthy weight (n = 50), with overweight (n = 34), or with obesity (n = 97) and in different age groups: 8–10 (n = 38), 11–13 (n = 50), and 14–17 years (n = 93). REE was measured by indirect calorimetry and body composition by air displacement plethysmography. Statistically significant differences in REE/fat-free mass (FFM) regarding obesity or gender were not observed. Absolute REE increases with age (p < 0.001), but REE/FFM decreases (p < 0.001) and there is an interaction between gender and age (p < 0.001) on absolute REE showing that the age-related increase is more marked in boys than in girls, in line with a higher FFM. Interestingly, the effect of obesity on absolute REE is not observed in the 8–10 year-old group, in which serum leptin concentrations correlate with the REE/FFM (r = 0.48; p = 0.011). In conclusion, REE/FFM is not affected by obesity or gender, while the effect of age on absolute REE is gender-dependent and leptin may influence the REE/FFM in 8–10 year-olds

Pancreas agenesis mutations disrupt a lead enhancer controlling a developmental enhancer cluster.

Sequence variants in cis-acting enhancers are important for polygenic disease, but their role in Mendelian disease is poorly understood. Redundancy between enhancers that regulate the same gene is thought to mitigate the pathogenic impact of enhancer mutations. Recent findings, however, have shown that loss-of-function mutations in a single enhancer near PTF1A cause pancreas agenesis and neonatal diabetes. Using mouse and human genetic models, we show that this enhancer activates an entire PTF1A enhancer cluster in early pancreatic multipotent progenitors. This leading role, therefore, precludes functional redundancy. We further demonstrate that transient expression of PTF1A in multipotent progenitors sets in motion an epigenetic cascade that is required for duct and endocrine differentiation. These findings shed insights into the genome regulatory mechanisms that drive pancreas differentiation. Furthermore, they reveal an enhancer that acts as a regulatory master key and is thus vulnerable to pathogenic loss-of-function mutations