Insulin detemir offers improved glycemic control compared with NPH insulin in people with type 1 diabetes - A randomized clinical trial

OBJECTIVE—Insulin detemir is a soluble long-acting basal insulin analog designed to overcome the limitations of conventional basal insulin formulations. Accordingly, insulin detemir has been compared with NPH insulin with respect to glycemic control (HbA1c, prebreakfast glucose levels and variability, and hypoglycemia) and timing of administration. RESEARCH DESIGN AND METHODS—People with type 1 diabetes (n = 408) were randomized in an open-label, parallel-group trial of 16-week treatment duration using either insulin detemir or NPH insulin. Insulin detemir was administered twice daily using two different regimens, either before breakfast and at bedtime (IDetmorn+bed) or at a 12-h interval (IDet12h). NPH insulin was administered before breakfast and at bedtime. Mealtime insulin was given as the rapid-acting insulin analog insulin aspart. RESULTS—With both insulin detemir groups, clinic fasting plasma glucose was lower than with NPH insulin (IDet12h vs. NPH, −1.5 mmol/l [95% CI −2.51 to −0.48], P = 0.004; IDetmorn+bed vs. NPH, −2.3 mmol/l (−3.32 to −1.29), P < 0.001), as was self-measured prebreakfast plasma glucose (P = 0.006 and P = 0.004, respectively). The risk of minor hypoglycemia was lower in both insulin detemir groups (25%, P = 0.046; 32%, P = 0.002; respectively) compared with NPH insulin in the last 12 weeks of treatment, this being mainly attributable to a 53% reduction in nocturnal hypoglycemia in the IDetmorn+bed group (P < 0.001). Although HbA1c for each insulin detemir group was not different from the NPH group, HbA1c for the pooled insulin detemir groups was significantly lower than for the NPH group (mean difference −0.18% [−0.34 to −0.02], P = 0.027). Within-person between-day variation in self-measured prebreakfast plasma glucose was lower for both detemir groups (both P < 0.001). The NPH group gained weight during the study, but there was no change in weight in either of the insulin detemir groups (IDet12h vs. NPH, −0.8 kg [−1.44 to −0.24], P = 0.006; IDetmorn+bed vs. NPH, −0.6 kg [−1.23 to −0.03], P = 0.040). CONCLUSIONS—Overall glycemic control with insulin detemir was improved compared with NPH insulin. The data provide a basis for tailoring the timing of administration of insulin detemir to the individual person’s needs

Materials for Diabetes Therapeutics

This review is focused on the materials and methods used to fabricate closed-loop systems for type 1 diabetes therapy. Herein, we give a brief overview of current methods used for patient care and discuss two types of possible treatments and the materials used for these therapies–(i) artificial pancreases, comprised of insulin producing cells embedded in a polymeric biomaterial, and (ii) totally synthetic pancreases formulated by integrating continuous glucose monitors with controlled insulin release through degradable polymers and glucose-responsive polymer systems. Both the artificial and the completely synthetic pancreas have two major design requirements: the device must be both biocompatible and be permeable to small molecules and proteins, such as insulin. Several polymers and fabrication methods of artificial pancreases are discussed: microencapsulation, conformal coatings, and planar sheets. We also review the two components of a completely synthetic pancreas. Several types of glucose sensing systems (including materials used for electrochemical, optical, and chemical sensing platforms) are discussed, in addition to various polymer-based release systems (including ethylene-vinyl acetate, polyanhydrides, and phenylboronic acid containing hydrogels).Juvenile Diabetes Research Foundation International (17-2007-1063)Leona M. and Harry B. Helmsley Charitable Trust (09PG-T1D027)United States. National Institutes of Health (F32 EB011580-01

A cluster randomised trial, cost-effectiveness analysis and psychosocial evaluation of insulin pump therapy compared with multiple injections during flexible intensive insulin therapy for type 1 diabetes: the REPOSE Trial.

BACKGROUND: Insulin is generally administered to people with type 1 diabetes mellitus (T1DM) using multiple daily injections (MDIs), but can also be delivered using infusion pumps. In the UK, pumps are recommended for patients with the greatest need and adult use is less than in comparable countries. Previous trials have been small, of short duration and have failed to control for training in insulin adjustment. OBJECTIVE: To assess the clinical effectiveness and cost-effectiveness of pump therapy compared with MDI for adults with T1DM, with both groups receiving equivalent structured training in flexible insulin therapy. DESIGN: Pragmatic, multicentre, open-label, parallel-group cluster randomised controlled trial, including economic and psychosocial evaluations. After participants were assigned a group training course, courses were randomly allocated in pairs to either pump or MDI. SETTING: Eight secondary care diabetes centres in the UK. PARTICIPANTS: Adults with T1DM for > 12 months, willing to undertake intensive insulin therapy, with no preference for pump or MDI, or a clinical indication for pumps. INTERVENTIONS: Pump or MDI structured training in flexible insulin therapy, followed up for 2 years. MDI participants used insulin analogues. Pump participants used a Medtronic Paradigm(®) Veo(TM) (Medtronic, Watford, UK) with insulin aspart (NovoRapid, Novo Nordisk, Gatwick, UK). MAIN OUTCOME MEASURES: Primary outcome - change in glycated haemoglobin (HbA1c) at 2 years in participants whose baseline HbA1c was ≥ 7.5% (58 mmol/mol). Key secondary outcome - proportion of participants with HbA1c ≤ 7.5% at 2 years. Other outcomes at 6, 12 and 24 months - moderate and severe hypoglycaemia; insulin dose; body weight; proteinuria; diabetic ketoacidosis; quality of life (QoL); fear of hypoglycaemia; treatment satisfaction; emotional well-being; qualitative interviews with participants and staff (2 weeks), and participants (6 months); and ICERs in trial and modelled estimates of cost-effectiveness. RESULTS: We randomised 46 courses comprising 317 participants: 267 attended a Dose Adjustment For Normal Eating course (132 pump; 135 MDI); 260 were included in the intention-to-treat analysis, of which 235 (119 pump; 116 MDI) had baseline HbA1c of ≥ 7.5%. HbA1c and severe hypoglycaemia improved in both groups. The drop in HbA1c% at 2 years was 0.85 on pump and 0.42 on MDI. The mean difference (MD) in HbA1c change at 2 years, at which the baseline HbA1c was ≥ 7.5%, was -0.24% [95% confidence interval (CI) -0.53% to 0.05%] in favour of the pump (p = 0.098). The per-protocol analysis showed a MD in change of -0.36% (95% CI -0.64% to -0.07%) favouring pumps (p = 0.015). Pumps were not cost-effective in the base case and all of the sensitivity analyses. The pump group had greater improvement in diabetes-specific QoL diet restrictions, daily hassle plus treatment satisfaction, statistically significant at 12 and 24 months and supported by qualitative interviews. LIMITATION: Blinding of pump therapy was not possible, although an objective primary outcome was used. CONCLUSION: Adding pump therapy to structured training in flexible insulin therapy did not significantly enhance glycaemic control or psychosocial outcomes in adults with T1DM. RESEARCH PRIORITY: To understand why few patients achieve a HbA1c of < 7.5%, particularly as glycaemic control is worse in the UK than in other European countries. TRIAL REGISTRATION: Current Controlled Trials ISRCTN61215213. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 20. See the NIHR Journals Library website for further project information

Rimonabant (acomplia®), obésité et diabiète de type 2

Le rimonabant (Acomplia®) est une molécule au mécanisme d'action original, antagoniste du récepteur CB1 du système endocannabinoïde qui joue un rôle majeur dans la régulation de l'équilibre énergétique du corps. Ce système hyperactivé peut contribuer à une dérégulation métabolique. En le bloquant, le rimonabant est le seul médicament combinant un effet direct sur le métabolisme glucidique et pouvant favoriser une perte de poids avec diminution du périmètre abdominal (patients obèses ou en surpoids avec diabète de type 2). Dans ce travail, par l'observation de plusieurs études cliniques,nous avons essayé dégager l'intérêt du Rimonabant dans le traitement de l'obésité et du diabète de type 2. Toutefois, la fréquence des effets indésirables (troubles psychiques) a conduit à recommander des précautions d'emploi renforcées, à suspendre son AMM et à arrêter toute étude clinique élaborée par le laboratoire.TOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF

Grossesse et chirurgie bariatrique (intérêt de la mesure continue du glucose pour l'évaluation du profil glycémique de femmes enceintes après un bypass gastrique)

TOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF

Etude des troubles de la glycorégulation dans la population adulte atteinte de mucoviscidose suivie au CHU de Toulouse

Au vu de l'augmentation de l'espérance de vie des patients, le diabète de la mucoviscidose (DM), est devenu la première co-morbidité de la mucoviscidose. Notre étude rétrospective sur dossiers évalue le dépistage, la prévalence et les caractéristiques associées des troubles de la glycorégulation dans la population adulte atteinte de mucoviscidose suivie au CHU de Toulouse de 2000 à 2006. Les recommandations élaborées en 2000 au CHU de Toulouse, basées sur la réalisation d'une HGPO annuelle, ont été très insuffisamment appliquées. La proportion de troubles de la glycorégulation est cependant importante dans notre population. Notre étude retrouve l'association du DM avec des facteurs de risque établis : l'insuffisance pancréatique exocrine, un âge précoce de diagnostic de la mucoviscidose et un VEMS bas, mais aussi avec des facteurs non établis, qui demandent confirmation par des études ultérieures.TOULOUSE3-BU Santé-Centrale (315552105) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Levemir (analogue de l'insuline humaine, d'action prolongée)

Après un rapide historique de la découverte du diabète et de l'insuline, un chapitre présente de manière succincte la physiopathologie des diabètes de type 1 et 2, ainsi que leurs complications. Un chapitre est consacré aux insulines, leurs structures générales et leurs modes d'action, ainsi qu'une présentation des divers traitements actuellement disponibles et des règles d'insulinothérapie pour obtenir un traitement plus efficace. Puis nous verrons comment l'insuline Levemir® s'intègre dans l'insulinothérapie et quels avantages elle apporte aux patients diabétiques. Pour ceci en plus de la pharmacodynamie et pharmacocinétique, nous étudierons chez les diabétiques de type 1 et 2 son effet par rapport aux traitements déjà existants sur le contrôle glycémique, les hypoglycémies et sur la prise de poids du patient. Enfin, un dernier chapitre est consacré aux insulines inhalées.TOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF

Diabète du sujet âgé (revue de la littérature et étude de l'impact du diabète sur l'histoire naturelle de la maladie d'Alzheimer à partir de 686 patients de la cohorte Real.fr / Caroline Sanz ; Hélène Hanaire)

La prévalence du diabète et de la maladie d'Alzheimer augmente avec l'avance en âge, en particulier dans les pays développés. Nous avons étudié l'effet du diabète sur les déclins cognitif et fonctionnel, l'institutionnalisation et la survie, dans une cohorte française de sujets atteints de maladie d'Alzheimer suivis durant 4 ans. Dans cette cohorte, nous avons découvert que les sujets diabétiques, par comparaison aux non diabétiques, étaient plus dépendants à l'inclusion, avaient un déclin cognitif moindre et un déclin fonctionnel identique au cours des 4 années de suivi ; et ne présentaient pas une évolution plus péjorative de la maladie d'Alzheimer (décès ou institutionnalisation). En conclusion, le diabète n'avait pas un effet négatif sur l'évolution de la maladie d'Alzheimer.TOULOUSE3-BU Santé-Centrale (315552105) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF