Introduction Débuter/gérer une insulinothérapie est souvent considéré comme une étape délicate en médecine générale. Patients et méthodes Cette étude observationnelle belge a été réalisée en ...2011-2013 auprès de 150 médecins généralistes représentatifs, invités à débuter/optimiser une insulinothérapie si nécessaire chez 523 patients DT2. L’évaluation a été faite avant et après un suivi de 6 ± 1 mois. Résultats Les caractéristiques des patients à l’inclusion étaient: âge moyen: 65.5 années ; HbA1c: 8,8 % ; taux élevé de complications, sans relation avec le taux actuel d’HbA1c mais bien avec la durée du diabète. Chez 85 % des patients, le traitement comportait des antidiabétiques oraux: metformine (> 80 %), sulfamide/glinide (± 40 %) et/ou DPP-4 inhibiteur (14 %). Certains étaient traités par un analogue du GLP-1 (7 %) ou déjà par insuline (46 %): 50 % insuline basale dont 12 % glargine, 14 % rapide ou ultrarapide et 44 % prémixée. L’instauration d’une insulinothérapie (glargine chez > 50 %) a été décidée pour contrôle glycémique jugé insuffisant (96,3 %) et l’optimisation de l’insulinothérapie (principalement NPH → glargine, ajout d’un analogue ultrarapide) pour contrôle estimé insuffisant (57,9 %), hypoglycémies (17,2 %) ou les deux (17,2 %). À 6 mois, l’HbA1c a diminué de 8,79 % à 7,52 % (– 1,27 % ; IC 95 %: – 1,43, – 1,11 ; p < 0,001 ; 27.6 % avec HbA1c < 7 % vs 5,9 % à l’inclusion, p < 0,001) et la glycémie à jeun de 1,89 à 1,34 g/L (– 0,54 g/L ; IC 95 %: – 0,62, – 0,47 ; p < 0,001), avec peu d’hypoglycémies (non sévères) en 6 mois. Les médecins interrogés ont globalement rapporté une impression positive: familiarité avec l’insuline (94 %), facilité d’ajuster l’insulinothérapie (80 %), sans crainte des hypoglycémies (85 %). Conclusion L’instauration et l’optimisation de l’insulinothérapie dans le DT2 entraînent une amélioration importante du contrôle glycémique, avec peu d’épisodes hypoglycémiques et une impression globalement positive de la part des médecins. Ces résultats doivent inciter les médecins généralistes à débuter plus tôt l’insulinothérapie et à l’optimiser si nécessaire. Déclaration d’intérêt Les auteurs déclarent avoir un intérêt avec un organisme privé, industriel ou commercial en relation avec le sujet présenté. Enquête réalisée grâce au soutien de Sanofi.
BACKGROUND Cigarette smoking is associated with lower fecundity rates, adverse reproductive outcomes and a higher risk of IVF failures. Over the last few decades, prevalence of smoking among women of ...reproductive age has increased. This review focuses on current knowledge of the potential effects of smoke toxicants on all reproductive stages and the consequences of smoke exposure on reproductive functions. METHODS We conducted a systematic review of the scientific literature on the impact of cigarette smoking and smoke constituents on the different stages of reproductive function, including epidemiological, clinical and experimental studies. We attempted to create hypotheses and find explanations for the deleterious effects of cigarette smoke observed in experimental studies. RESULTS Cigarette smoke contains several thousand components (e.g. nicotine, polycyclic aromatic hydrocarbons and cadmium) with diverse effects. Each stage of reproductive function, folliculogenesis, steroidogenesis, embryo transport, endometrial receptivity, endometrial angiogenesis, uterine blood flow and uterine myometrium is a target for cigarette smoke components. The effects of cigarette smoke are dose-dependent and are influenced by the presence of other toxic substances and hormonal status. Individual sensitivity, dose, time and type of exposure also play a role in the impact of smoke constituents on human fertility. CONCLUSIONS All stages of reproductive functions are targets of cigarette smoke toxicants. Further studies are necessary to better understand the deleterious effects of cigarette smoke compounds on the reproductive system in order to improve health care, help to reduce cigarette smoking and provide a better knowledge of the molecular mechanisms involved in reproductive toxicology.
There is a need to develop surrogates for treatment efficacy in the neoadjuvant setting to speed-up drug development and stratify patients according to outcome. Preclinical studies showed that ...chemotherapy induces an antitumor immune response. In order to develop new surrogates for drug efficacy, we assessed the prognostic value of tumor-infiltrating lymphocytes (TIL) on residual disease after neoadjuvant chemotherapy (NACT) in patients with triple-negative breast cancer (TNBC).
Three hundred four TNBC patients with residual disease after NACT were retrospectively identified in three different hospitals. Hematoxylin and eosin-stained slides from surgical postchemotherapy specimens were evaluated for intratumoral (It-TIL) and stromal (Str-TIL) TIL. Cases were classified as High-TIL if It-TIL and/or Str-TIL >60%.
TIL were assessable for 278 cases. Continuous It-TIL and Str-TIL variables were strong prognostic factors in the multivariate model, both for metastasis-free hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.77–0.96, P = 0.01 and HR 0.85, 95% CI 0.75–0.98, P = 0.02 for Str-TIL and It-TIL, respectively and overall survival (HR 0.86, 95% CI 0.77–0.97, P = 0.01 and HR 0.86, 95% CI 0.75–0.99, P = 0.03 for Str-TIL and It-TIL, respectively). The 5-year overall survival rate was 91% (95% CI 68% to 97%) for High-TIL patients (n = 27) and 55% (95% CI 48% to 61%) for Low-TIL patients (HR 0.19, 95% CI 0.06–0.61, log-rank P = 0.0017). The major prognostic impact of TIL was seen for patients with large tumor burden following NACT (residual tumor >2 cm and/or node metastasis). In all but one High-TIL case, It-TIL and Str-TIL values were lower on the prechemotherapy sample.
The presence of TIL in residual disease after NACT is associated with better prognosis in TNBC patients. This parameter may represent a new surrogate of drug efficacy to test investigational agents in the neoadjuvant setting and a new prognostic marker to select patients at high risk of relapse.
Training volume is paramount in the magnitude of physiological adaptations following resistance training. However, patients with severe COPD are limited by dyspnea during traditional two-limb ...low-load/high-repetition resistance training (LLHR-RT), resulting in suboptimal training volumes. During a single exercise session, single-limb LLHR-RT decreases the ventilatory load and enables higher localized training volumes compared with two-limb LLHR-RT.
Does single-limb LLHR-RT lead to more profound effects compared with two-limb LLHR-RT on exercise capacity (6-min walk distance 6MWD), health status, muscle function, and limb adaptations in patients with severe COPD?
Thirty-three patients (mean age 66 ± 7 years; FEV
39 ± 10% predicted) were randomized to 8 weeks of single- or two-limb LLHR-RT. Exercise capacity (6MWD), health status, and muscle function were compared between groups. Quadriceps muscle biopsy specimens were collected to examine physiological responses.
Single-limb LLHR-RT did not further enhance 6MWD compared with two-limb LLHR-RT (difference, 14 -12 to 39 m. However, 73% in the single-limb group exceeded the known minimal clinically important difference of 30 m compared with 25% in the two-limb group (P = .02). Health status and muscle function improved to a similar extent in both groups. During training, single-limb LLHR-RT resulted in a clinically relevant reduction in dyspnea during training compared with two-limb LLHR-RT (-1.75; P = .01), but training volume was not significantly increased (23%; P = .179). Quadriceps muscle citrate synthase activity (19%; P = .03), hydroxyacyl-coenzyme A dehydrogenase protein levels (32%; P < .01), and capillary-to-fiber ratio (41%; P < .01) were increased compared with baseline after pooling muscle biopsy data from all participants.
Single-limb LLHR-RT did not further increase mean 6MWD compared with two-limb LLHR-RT, but it reduced exertional dyspnea and enabled more people to reach clinically relevant improvements in 6MWD. Independent of execution strategy, LLHR-RT improved exercise capacity, health status, muscle endurance, and enabled several physiological muscle adaptations, reducing the negative consequences of limb muscle dysfunction in COPD.
ClinicalTrials.gov; No.: NCT02283580; URL: www.clinicaltrials.gov.
Introduction L’insuline dégludec (IDég), une nouvelle insuline basale formant des multi-hexamères solubles après injection sous-cutanée, possède un effet hypoglycémiant ultra-long et stable. Ces ...propriétés pourraient diminuer l’hypoglycémie nocturne par rapport à ce qui est observé avec d’autres analogues de l’insuline et devraient permettre à davantage de patients d’atteindre les valeurs cibles de glycémie à jeun (GAJ) sans risque d’hypoglycémie. Patients et méthodes Cette analyse poolée a étudié la proportion de patients diabétiques de type 2 (DT2) atteignant la GAJ cible (< 5 mmol/L 90 mg/dL) sans hypoglycémie nocturne confirmée dans quatre essais randomisés en ouvert et en « treat-to-target » (titration forcée), où les patients (n = 2 380) recevaient soit l’IDég soit l’insuline glargine (IGlar) administrées ×1/j en association avec des antidiabétiques oraux, pendant 26 ou 52 semaines. L’hypoglycémie confirmée était définie par une glycémie plasmatique < 3,1 mmol/L (56 mg/dL) ou des épisodes sévères nécessitant une assistance, et l’hypoglycémie nocturne confirmée par des épisodes ayant lieu entre 00 h 01 et 05 h 59. Le critère a été analysé par un modèle de régression logistique incluant le traitement, le sexe, l’essai, le traitement antidiabétique à la sélection et la région comme facteurs fixes, et l’âge et la GAJ à l’inclusion comme covariables. Résultats La proportion de patients atteignant la GAJ cible était plus importante avec IDég comparée à IGlar (respectivement 40,9 % et 29,4 %). De plus, les patients traités par IDég présentaient moins fréquemment des épisodes d’hypoglycémie nocturne confirmée vs IGlar (respectivement 13,3 % et 16,6 %). La probabilité d’atteindre la GAJ cible sans hypoglycémie nocturne confirmée était supérieure de 82 % avec IDég comparée à IGlar : odds ratio estimé IDég/IGlar = 1,82 IC95 % 1,49 ; 2,22. Conclusion Les patients DT2 sont plus enclins à atteindre la GAJ cible sans hypoglycémie nocturne confirmée avec IDég qu’avec IGlar. Ces résultats pourraient avoir des implications importantes dans l’atteinte du contrôle glycémique en pratique clinique.
Pulmonary surfactant is a crucial and dynamic lung structure whose primary functions are to reduce alveolar surface tension and facilitate breathing. Though disruptions in surfactant homeostasis are ...typically thought of in the context of respiratory distress and premature infants, many lung diseases have been noted to have significant surfactant abnormalities. Nevertheless, preclinical and clinical studies of pulmonary disease too often overlook the potential contribution of surfactant alterations - whether in quantity, quality or composition - to disease pathogenesis and symptoms. In inflammatory lung diseases, whether these changes are cause or consequence remains a subject of debate. This review will outline 1) the importance of pulmonary surfactant in the maintenance of respiratory health, 2) the diseases associated with primary surfactant dysregulation, 3) the surfactant abnormalities observed in inflammatory pulmonary diseases and, finally, 4) the available research on the interplay between surfactant homeostasis and smoking-associated lung disease. From these published studies, we posit that changes in surfactant integrity and composition contribute more considerably to chronic inflammatory pulmonary diseases and that more work is required to determine the mechanisms underlying these alterations and their potential treatability.
Skin aging is a multifactorial process influenced by internal and external factors. The contribution of different environmental factors has been well established individually in the last few years. ...On the one hand, man is rarely exposed to a single factor, and on the other hand, there is very little knowledge about how these extrinsic factors may interact with each other or even how the skin may react to chronic exposure. This study aimed to evaluate the effect on skin aging of a chronic co-exposure of tissue-engineered skin substitutes to cigarette smoke extract (CSE) and solar simulator light (SSL). Skin substitutes were reconstructed according to the self-assembly method and then exposed to CSE followed by irradiation with SSL simultaneously transmitting UVA1, visible light and infrared. When skin substitutes were chronically exposed to CSE and SSL, a significant decrease in procollagen I synthesis and the inhibition of Smad2 phosphorylation of the TGF-β signaling pathway were observed. A 6.7-fold increase in MMP-1 activity was also observed when CSE was combined with SSL, resulting in a decrease in collagen III and collagen IV protein expression. The secretory profile resulting from the toxic synergy was investigated and several alterations were observed, notably an increase in the quantities of pro-inflammatory cytokines. The results also revealed the activation of the ERK1/2 (3.4-fold) and JNK (3.3-fold) pathways. Taken together, the results showed that a synergy between the two environmental factors could provoke premature skin aging.
Achieving optimal blood glucose control in Type 1 diabetes is a delicate balance between ensuring tight glycaemic control and achieving this without the expense of hypoglycaemia and weight gain, two ...major factors impacting quality of life. This is a real challenge for people with Type 1 diabetes and underpins many of the struggles they face in self‐managing on a day‐to‐day basis. The main goals of insulin delivery are to try to simulate the physiology of β‐cell insulin secretion as closely as possible and to overcome the challenges of peripheral insulin administration by achieving rapidity of onset with mealtime insulins and stability of the glucose‐lowering effects of long‐acting insulins. Since the early days of human insulin use, there have been many developments in insulin formulations that aim to achieve these goals as much as possible, thus contributing to better glycaemic control whilst minimizing hypoglycaemia. In the present review we discuss the currently available insulin analogues and the challenges of achieving glucose control using current analogues in those on multiple daily injections, and appraise the evidence base for newer‐generation insulin analogues, such as insulin degludec, glargine U300, faster‐acting insulin aspart and BioChaperone lispro. We also highlight new insulins in development and unmet needs in people with Type 1 diabetes.
What's new?
In people with Type 1 diabetes the aim is to optimize insulin delivery in order to balance successfully the risk of hypoglycaemia whilst maintaining tight glycaemic control.
Many new insulin analogues are available for people with Type 1 diabetes, including more rapidly acting mealtime insulins and longer‐acting and more concentrated basal insulins.
In this review, we discuss the challenges of insulin delivery using first‐generation insulin analogues and the potential benefits and disadvantages of newer agents, and assess the risk of hypoglycaemia and safety of all insulin analogues.
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