Evaluation de la mise en place d'un suivi médical et éducatif de la mesure continue du glucose dans la prise en charge du diabète de type 1 instable

BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Microgels sensibles au glucose pour la delivrance d'insuline

Le traitement du diabète de type 1 en boucle fermée représente un enjeu majeur tant sur le plan sociétal que thérapeutique. L une des solutions consiste en une formulation thérapeutique basée sur des microvéhicules capables de délivrer la bonne dose d insuline selon une cinétique adaptée aux variations de la glycémie. Les microgels sont des particules de polymère réticulé formant des édifices submicrométriques tridimensionnels gonflés par un solvant, dont le taux de gonflement dépend des conditions environnementales. Leur porosité permet à la fois l encapsulation d espèces et leur libération à une vitesse dépendant de leur diffusion à travers le réseau. Nous avons synthétisé des microgels à base de poly(N-alkylacrylamide) fonctionnalisés par des récepteurs du glucose dérivés de l acide phénylboronique. Ces microgels, à la base thermosensibles, présentent la propriété de changer de volume en fonction de la concentration en glucose et se présentent comme d excellents candidats pour la délivrance auto-régulée d insuline dans le cadre du traitement du diabète. Ils permettent la délivrance répétée de doses d insuline modulée par la glycémie. La quantité d insuline encapsulée a pu être améliorée en structurant les microgels en architecture cœur-écorce ou capsule.En outre, nous avons utilisé ces microgels pour développer des capteurs au glucose, sélectifs vis-à-vis des autres saccharides et quelques études de cytotoxicité ont été amorcées et ont permis d établir avec satisfaction que certains de nos objets n étaient pas toxiques.Les résultats obtenus ont donc permis d affirmer que la technologie des microgels sensibles au glucose peut répondre de manière conceptuelle aux attentes des patients diabétiques pour permettre la délivrance d insuline en boucle fermée.Bioresponsive hydrogels can change many of their physical properties in response to the recognition of a target in the solution. In particular, changes in hydrogel swelling lead in turn to controllable changes in shape, volume, pore size, mechanical and optical properties. We focus our research on the development of glucose-responsive microgels which hold promising interest in the field of both sensing and drug delivery. These cross-linked polymer particles, made of highly swollen networks, can swell proportionally to the concentration of glucose in the surrounding medium. Since they are porous, they can entrap a drug and release it a rate dependent on their swelling degree, which is of particular interest in the case of insulin as a drug. Such systems could be used as self-regulated insulin delivery systems for diabetes treatment. With that aim, we have designed microgels able to sense glucose concentrations in the patho-physiological range, under physiological conditions. Insulin was successfully loaded into the nanogels and was shown to be released at a rate dependent on glucose concentration. Furthermore, microgels with a controlled internal structure were synthesized, such as core-shell microgels and capsules. These latter developments led to improvements in terms of insulin encapsulation efficiency and glucose-triggered delivery. Besides, other nanogel formulations were investigated, in order to improve both their biocompatibility as well as the selectivity of their response to glucose compared to other saccharides.BORDEAUX1-Bib.electronique (335229901) / SudocSudocFranceF

Perioperative management of adult diabetic patients. Specific situations

Working party approved by the French Society of Anaesthesia and Intensive Care Medicine (SFAR) and the French Society for the study of Diabetes (SFD)International audienceAmbulatory surgery can be carried out in diabetic patients. By using a strict organisational and technical approach, the risk of glycaemic imbalance is minimised, allowing the patients to return to their previous way of life more quickly. Taking into account the context of ambulatory surgery, with a same day discharge, the aims are to minimise the changes to antidiabetic treatment, to maintain adequate blood sugar control and to resume oral feeding as quickly as possible. The preoperative evaluation is the same as for a hospitalised patient and recent glycaemic control (HbA1c) is necessary. Perioperative management and the administration of treatment depend on the number of meals missed. The patient can return home after taking up usual feeding and treatment again. Hospitalisation is necessary if significant glycaemic imbalance occurs. In pregnancy, it is necessary to distinguish between known pre-existing diabetes (T1D or T2D) and gestational diabetes, defined as glucose intolerance discovered during pregnancy. During labour, blood sugar levels should be maintained between 0.8 and 1.4 g/L (4.4–8.25 mmol/L). Control of blood sugar levels is obtained by using a continuous administration of insulin using an electronic syringe (IVES) together with a glucose infusion. Post-partum, management depends on the type of diabetes: in T1D and T2D patients a basal-bolus scheme is restarted with decreased doses while in gestational diabetes insulin therapy is stopped after delivery. Antidiabetic treatment is again necessary if blood sugar levels remain > 1.26 g/L (7 mmol/L)

The role of the diabetologist

National audienceIt is necessary to refer a patient to a diabetologist perioperatively in several circumstances. Preoperatively, the patient is referred if diabetes is discovered or if glycaemic disequilibrium is detected (HbA 1c 8%). During the hospital stay, a diabetologist should be consulted if diabetes is discovered, if there is glycaemic disequilibrium despite treatment or if dif ficulties in resuming previous treatments arise. Postoperatively, and away from the hospital, all diabetic patients with HbA 1c > 8% should have a consultation with a iabetologist.Il convient d'adresser un patient à un diabétologue en périopératoire dans plusieurs circonstances. En préopératoire, le patient lui est adressé si un diabète est dépisté ou si on constate un déséquilibre glycémique (HbA 1c 8 %). Pendant l'hospitalisation, il faut faire appel à un diabétologue si un diabète est découvert, s'il existe un déséquilibre glycémique malgré la prise en charge ou s'il survient des difficultés à la reprise du traitement antérieur. En postopératoire et à distance de l'hospitalisation, tous les diabétiques qui ont une HbA 1c > 8 % doivent bénéficier d'une consultation avec un diabétologu

Perioperative management of adult diabetic patients. Review of hyperglycaemia: definitions and pathophysiology

Working party approved by the French Society of Anaesthesia and Intensive Care Medicine (SFAR) and the French Society for the study of Diabetes (SFD)International audienceDiabetes mellitus is defined by chronic elevation of blood glucose linked to insulin resistance and/or insulinopaenia. Its diagnosis is based on a fasting blood-glucose level of ≥ 1.26 g/L or, in some countries, a blood glycated haemoglobin (HbA1c) level of > 6.5%. Of the several forms of diabetes, type-2 diabetes (T2D) is the most common and is found in patients with other risk factors. In contrast, type-1 diabetes (T1D) is linked to the autoimmune destruction of β-pancreatic cells, leading to insulinopaenia. Insulin deficiency results in diabetic ketoacidosis within a few hours. ‘Pancreatic’ diabetes develops from certain pancreatic diseases and may culminate in insulinopaenia. Treatments for T2D include non-insulin based therapies and insulin when other therapies are no longer able to control glycaemic levels. For T1D, treatment depends on long (slow)-acting insulin and ultra-rapid analogues of insulin administered according to a ‘basal-bolus’ scheme or by continuous subcutaneous delivery of insulin using a pump. For patients presenting with previously undiagnosed dysglycaemia, investigations should determine whether the condition corresponds to pre-existing dysglycaemia or to stress hyperglycaemia. The latter is defined as transient hyperglycaemia in a previously non-diabetic patient that presents with an acute illness or undergoes an invasive procedure. Its severity depends on the type of surgery, the aggressiveness of the procedure and its duration. Stress hyperglycaemia may lead to peripheral insulin resistance and is an independent prognostic factor for morbidity and mortality

Perioperative management of adult diabetic patients. Postoperative period

Working party approved by the French Society of Anaesthesia and Intensive Care Medicine (SFAR) and the French Society for the study of Diabetes (SFD)International audienceFollow on from continuous intravenous administration of insulin with an electronic syringe (IVES) is an important element in the postoperative management of a diabetic patient. The basal-bolus scheme is the most suitable taking into account the nutritional supply and variable needs for insulin, reproducing the physiology of a normal pancreas: (i) slow (long-acting) insulin (= basal) which should immediately take over from IVES insulin simulating basal secretion; (ii) ultra-rapid insulin to simulate prandial secretion (= bolus for the meal); and (iii) correction of possible hyperglycaemia with an additional ultra-rapid insulin bolus dose. A number of schemes are proposed to help calculate the dosages for the change from IV insulin to subcutaneous insulin and for the basal-bolus scheme. Postoperative resumption of an insulin pump requires the patient to be autonomous. If this is not the case, then it is mandatory to establish a basal-bolus scheme immediately after stopping IV insulin. Monitoring of blood sugar levels should be continued postoperatively. Hypoglycaemia and severe hyperglycaemia should be investigated. Faced with hypoglycaemia 16.5 mmol/L (3 g/L) in a T1D or T2D patient treated with insulin, investigations for ketosis should be undertaken systematically. In T2D patients, unequivocal hyperglycaemia should also call to mind the possibility of diabetic hyperosmolarity (hyperosmolar coma). Finally, the modalities of recommencing previous treatments are described according to the type of hyperglycaemia, renal function and diabetic control preoperatively and during hospitalisation

Perioperative management of adult diabetic patients. Preoperative period

Working party approved by the French Society of Anaesthesia and Intensive Care Medicine (SFAR) and the French Society for the study of Diabetes (SFD)International audienceIn diabetic patients undergoing surgery, we recommend assessing glycaemic control preoperatively by assessing glycated haemoglobin (HbA1c) levels and recent capillary blood sugar (glucose) levels, and to adjust any treatments accordingly before surgery, paying particular attention to specific complications of diabetes. Gastroparesis creates a risk of stasis and aspiration of gastric content at induction of anaesthesia requiring the use of a rapid sequence induction technique. Cardiac involvement can be divided into several types. Coronary disease is characterised by silent myocardial ischaemia, present in 30–50% of T2D patients. Diabetic cardiomyopathy is a real cause of heart failure. Finally, cardiac autonomic neuropathy (CAN), although rarely symptomatic, should be investigated because it causes an increased risk of cardiovascular events and a risk of sudden death. Several signs are suggestive of CAN, and confirmation calls for close perioperative surveillance. Chronic diabetic kidney disease (diabetic nephropathy) aggravates the risk of perioperative acute renal failure, and we recommend measurement of the glomerular filtration rate preoperatively. The final step of the consultation concerns the management of antidiabetic therapy. Preoperative glucose infusion is not necessary if the patient is not receiving insulin. Non-insulin drugs are not administered on the morning of the intervention except for metformin, which is not administered from the evening before. The insulins are injected at the usual dose the evening before. The insulin pump is maintained until the patient arrives in the surgical unit. It should be remembered that insulin deficiency in a T1D patient leads to ketoacidosis within a few hours

Perioperative management of adult diabetic patients. The role of the diabetologist

Working party approved by the French Society of Anaesthesia and Intensive Care Medicine (SFAR) and the French Society for the study of Diabetes (SFD)International audienceA patient should be referred to a diabetologist perioperatively in several circumstances: preoperative recognition of a previously unknown diabetes or detection of glycaemic imbalance (HbA1c 8%); during hospitalisation, recognition of a previously unknown diabetes, persisting glycaemic imbalance despite treatment or difficulty resuming previously used chronic treatment; postoperatively and after discharge from hospital, for all diabetic patients in whom HbA1c is > 8%

Preoperative period

National audienceIn diabetic patients undergoing surgery, it is necessary to evaluate how well glycaemic levels are controlled preoperatively. This evaluation assesses glycated haemoglobin (HbA1c) levels and recent capillary blood sugar levels. Treatment adaptation may be necessary before surgery The specific complications of diabetes should be investigated. Gastroparesis creates (3 risk of stasis and aspiration at the time of anaesthetic induction, which requires the use of a rapid sequence induction technique. Cardiac involvement can be divided into several types. Coronary artery disease is characteristic due to the high prevalence of silent myocardial ischemia, present in 30-50% of T2D patients. Diabetic cardiomyopathy is a significant cause of heart failure. Finally, cardiac autonomic neuropathy (CAN), although rarely symptomatic, should be investigated because it causes an increase in cardiovascular events and a risk of sudden death. Several signs are suggestive of CAN. When present, it calls for closer perioperative surveillance. Chronic diabetic renal disease aggravates the risk of acute perioperative renal failure. It is important to measure the glomerular filtration rate preoperatively. The final step of the consultation concerns the management of glucose lowering therapy Preoperative glucose infusion is not necessary if the patient is not receiving insulin. Non-insulin based drugs are not administered on the morning of the procedure except for met formin which is not administered from the evening before. The insulins are injected at the usual dose the evening before. The patient's personal insulin pump is maintained until arrival of the patient in the surgical unit. It should be remembered that insulin deficiency in a T1D patient leads to ketoacidosis within a few hours.En préopératoire, il est nécessaire d’évaluer l’équilibre glycémique du diabétique. Cette évaluation repose sur l’hémoglobine glyquée (HbA1c) et les glycémies capillaires récentes. Une adaptation des traitements peut être nécessaire avant la chirurgie. Les complications spécifiques du diabète doivent être recherchées. La gastroparésie crée un risque de stase et d’inhalation à l’induction anesthésique imposant une induction type « estomac plein ». L’atteinte cardiaque se divise en plusieurs entités. La maladie coronaire se distingue par l’ischémie myocardique silencieuse, présente chez 30 à 50 % des diabétiques de type 2. La cardiomyopathie diabétique est une cause authentifiée d’insuffisance cardiaque. Enfin, la neuropathie autonome cardiaque, rarement symptomatique doit être recherchée car à l’origine d’une augmentation des évènements cardiovasculaires et du risque de mort subite. Plusieurs signes permettent de la suspecter. Sa confirmation impose une surveillance périopératoire rapprochée. La maladie rénale chronique diabétique aggrave le risque d’insuffisance rénale aiguë périopératoire. L’évaluation du débit de filtration glomérulaire est indispensable en pré opératoire. La dernière étape de la consultation s’intéresse à la gestion des traitements hypoglycémiants. La perfusion glucosée en préopératoire n’est pas nécessaire si le patient ne reçoit pas d’insuline. Les médicaments non insuliniques ne sont pas administrés le matin de l’intervention sauf la metformine qui n’est pas administrée dès la veille au soir. Les insulines sont injectées la veille au soir aux posologies habituelles. La pompe à insuline est maintenue jusqu’à l’arrivée au bloc opératoire. On rappelle qu’une carence en insuline chez un diabétique de type 1 conduit à une acidocétose en quelques heures

Postoperative period

Transition from continuous intravenous insulin infusion administered intraoperatively is an important element in the postoperative management of a diabetic patient. The basal-bolus scheme is the most suitable strategy taking into account the nutritional supply and variable needs for insulin. It reproduces the physiology of a normal pancreas: (i) long-acting insulin (= basal) which should immediately take over from intravenous insulin simulating basal secretion; (ii) ultra-rapid insulin to simulate prandial secretion (= bolus for the meal); and (iii) correction of possible hyperglycaemia (= corrective bolus). A number of schemes are proposed to help calculate the dosages for transition from IV insulin to subcutaneous insulin and for the basal-bolus scheme. Postoperative resumption of a personal insulin pump requires the patient to be autonomous. If not, it is mandatory to establish a basal-bolus scheme immediately after stopping IV insulin. Monitoring of blood sugar levels should be continued postoperatively. Hypoglycaemia and severe hyperglycaemia should be investigated. Faced with hypoglycaemia 16.5 mmol/L (3 g/L) in a T1D or T2D patient treated with insulin, investigations for ketosis should be undertaken systematically. In T2D patients, unequivocal hyperglycaemia should also call to mind the possibility of diabetic hyperosmolarity (hyperosmolar coma). Finally, the modalities of recommencing previous treatments are described according to the type of hyperglycaemia, renal function and the quality of the diabetic control before and during hospitalisation.ILe relais de l’insuline IVSE administrée en peropératoire constitue un élément essentiel de la prise en charge du patient diabétique en postopératoire. Le schéma basal-bolus est le plus adapté compte tenu des apports nutritionnels et des besoins variables en insuline. Il reproduit la physiologie d’un pancréas normal : (i) une insuline lente (= basal) qui doit relayer sans délai l’insuline IVSE simulant la sécrétion basale ; (ii) des insulines ultrarapides pour simuler la sécrétion prandiale (= bolus pour le repas) ; et (iii) pour permettre la correction d’une éventuelle hyperglycémie (= bolus correcteur). Des schémas sont proposés pour aider au calcul de posologies pour le passage de l’insuline intraveineuse à l’insuline sous-cutanée et pour le schéma basal-bolus. La reprise en postopératoire d’une pompe à insuline impose que le patient soit autonome. Sinon, il est obligatoire de mettre en place un schéma basal-bolus sans délai à l’arrêt de l’insuline intraveineuse. La surveillance glycémique doit être poursuivie en postopératoire. Les hypoglycémies et les hyperglycémies graves doivent être recherchées. Devant une hypoglycémie 16,5 mmol/L (3 g/L) chez le DT1 et chez le DT2 traité par insuline, la recherche d’une cétose doit être systématique. Chez les DT2, une hyperglycémie franche doit également faire évoquer une hyperosmolarité diabétique (coma hyperosmolaire). Enfin, les modalités de reprise des traitements antérieurs sont détaillées selon le type d’hyperglycémie, la fonction rénale et l’équilibre du diabète en préopératoire et durant l’hospitalisation