Recent Advances in the Management of Diabetes Mellitus

peer reviewedThe recent epidemic of type 2 diabetes and the recognition that achieving specific glycemic goals can reduce morbidity have made the effective treatment of hyperglycemia a priority. The new therapeutic agents and the development of algorithms for the adjustment of therapy might contribute to an improved management of the disease. Moreover, type 2 diabetes is frequently associated with other co-morbidities (obesity, hypertension, dyslipidaemia, prothrombotic state). The appropriate management of patients with type 2 diabetes requires a global approach targeting each risk factor in order to reduce cardiovascular morbidity and mortality. This challenge represents a major public health issue. In type 1 diabetes patients, intensive therapy such as in the Diabetes Control and Complications Trial (DCCT) has been shown to obtain long-term beneficial effects on the reduction of the risk of progressive retinopathy, neuropathy and nephropathy and of the risk of cardiovascular disease. This benefit reinforces the original DCCT message that intensive therapy should be implemented as early as possible in people with type 1 diabetes. The recent development of new insulin analogues and the technical improvements of portable insulin pumps might contribute to obtain such a better metabolic control.RÉSUMÉ : L’augmentation d’incidence, quasi épidémique, du diabète de type 2 et la démonstration que l’obtention de bons taux glycémiques permettait de réduire la morbidité ont fait du traitement de l’hyperglycémie une priorité. Le développement de nouvelles classes thérapeutiques et la mise au point d’algorithmes de traitement contribuent à améliorer cette prise en charge. De plus, le diabète de type 2 est souvent associé à d’autres comorbidités (obésité, hypertension artérielle, dyslipidémies, état pro-thrombotique). La prise en charge du patient diabétique de type 2 requiert une approche globale visant à corriger chaque facteur de risque, ce qui permet de réduire substantiellement la mortalité cardio-vasculaire. Cette stratégie doit être considérée comme un objectif majeur de santé publique. Chez le sujet diabétique de type 1, un traitement intensif, comme celui imposé dans l’étude DCCT, permet d’obtenir une réduction prolongée du risque de survenue et de progression de la rétinopathie, de la neuropathie, de la néphropathie ainsi que du risque de maladie cardio-vasculaire. Ce bénéfice persistant renforce le message initial de l’étude DCCT qui avait démontré que le traitement intensif du diabète de type 1 devait être instauré dès le début de la maladie. Le développement récent des analogues de l’insuline et les améliorations techniques des pompes à insuline portables pourraient contribuer à atteindre un meilleur contrôle métabolique

Outcomes of Patients with Asymptomatic Aortic Stenosis Followed Up in Heart Valve Clinics

Importance: The natural history and the management of patients with asymptomatic aortic stenosis (AS) have not been fully examined in the current era. Objective: To determine the clinical outcomes of patients with asymptomatic AS using data from the Heart Valve Clinic International Database. Design, Setting, and Participants: This registry was assembled by merging data from prospectively gathered institutional databases from 10 heart valve clinics in Europe, Canada, and the United States. Asymptomatic patients with an aortic valve area of 1.5 cm2 or less and preserved left ventricular ejection fraction (LVEF) greater than 50% at entry were considered for the present analysis. Data were collected from January 2001 to December 2014, and data were analyzed from January 2017 to July 2018. Main Outcomes and Measures: Natural history, need for aortic valve replacement (AVR), and survival of asymptomatic patients with moderate or severe AS at entry followed up in a heart valve clinic. Indications for AVR were based on current guideline recommendations. Results: Of the 1375 patients included in this analysis, 834 (60.7%) were male, and the mean (SD) age was 71 (13) years. A total of 861 patients (62.6%) had severe AS (aortic valve area less than 1.0 cm2). The mean (SD) overall survival during medical management (mean [SD] follow up, 27 [24] months) was 93% (1%), 86% (2%), and 75% (4%) at 2, 4, and 8 years, respectively. A total of 104 patients (7.6%) died under observation, including 57 patients (54.8%) from cardiovascular causes. The crude rate of sudden death was 0.65% over the duration of the study. A total of 542 patients (39.4%) underwent AVR, including 388 patients (71.6%) with severe AS at study entry and 154 (28.4%) with moderate AS at entry who progressed to severe AS. Those with severe AS at entry who underwent AVR did so at a mean (SD) of 14.4 (16.6) months and a median of 8.7 months. The mean (SD) 2-year and 4-year AVR-free survival rates for asymptomatic patients with severe AS at baseline were 54% (2%) and 32% (3%), respectively. In those undergoing AVR, the 30-day postprocedural mortality was 0.9%. In patients with severe AS at entry, peak aortic jet velocity (greater than 5 m/s) and LVEF (less than 60%) were associated with all-cause and cardiovascular mortality without AVR; these factors were also associated with postprocedural mortality in those patients with severe AS at baseline who underwent AVR (surgical AVR in 310 patients; transcatheter AVR in 78 patients). Conclusions and Relevance: In patients with asymptomatic AS followed up in heart valve centers, the risk of sudden death is low, and rates of overall survival are similar to those reported from previous series. Patients with severe AS at baseline and peak aortic jet velocity of 5.0 m/s or greater or LVEF less than 60% have increased risks of all-cause and cardiovascular mortality even after AVR. The potential benefit of early intervention should be considered in these high-risk patients

Role of vitamin D supplementation in the management of musculoskeletal diseases: update from an European Society of Clinical and Economical Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) working group.

Vitamin D is a key component for optimal growth and for calcium-phosphate homeostasis. Skin photosynthesis is the main source of vitamin D. Limited sun exposure and insufficient dietary vitamin D supply justify vitamin D supplementation in certain age groups. In older adults, recommended doses for vitamin D supplementation vary between 200 and 2000 IU/day, to achieve a goal of circulating 25-hydroxyvitamin D (calcifediol) of at least 50 nmol/L. The target level depends on the population being supplemented, the assessed system, and the outcome. Several recent large randomized trials with oral vitamin D regimens varying between 2000 and 100,000 IU/month and mostly conducted in vitamin D-replete and healthy individuals have failed to detect any efficacy of these approaches for the prevention of fracture and falls. Considering the well-recognized major musculoskeletal disorders associated with severe vitamin D deficiency and taking into account a possible biphasic effects of vitamin D on fracture and fall risks, an European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) working group convened, carefully reviewed, and analyzed the meta-analyses of randomized controlled trials on the effects of vitamin D on fracture risk, falls or osteoarthritis, and came to the conclusion that 1000 IU daily should be recommended in patients at increased risk of vitamin D deficiency. The group also addressed the identification of patients possibly benefitting from a vitamin D loading dose to achieve early 25-hydroxyvitamin D therapeutic level or from calcifediol administration