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Resume L’hypoglycemie est une complication particulierement redoutee des patients diabetiques traites par insuline. Elle s’accompagne parfois d’une absence des signes avant-coureurs qui aggrave encore la peur de l’hypoglycemie. Cependant, il arrive souvent que des patients qui presentent cette condition manifestent au contraire une indifference vis-a-vis de l’hypoglycemie. Le but de cet article est d’en discuter les mecanismes et de montrer que cette indifference semble liee a une perte du ressenti au niveau cerebral du caractere deplaisant de l’hypoglycemie. Nous suggerons ici qu’une telle indifference pourrait representer d’une maniere generale une cause d’absence de souci de soi qui conduit a la non-observance.

Resume La non-observance vis-a-vis des traitements a long terme est un phenomene frequent, ayant des consequences graves en terme de morbi-mortalite et de couts, et elle represente donc un obstacle majeur a l’efficacites des soins. Le but de cet article introductif est de preciser certains concepts (observance, persistance), de decrire brievement les methodes utilisees pour quantifier l’observance, enfin, d’introduire une distinction entre observance active, intentionnelle, et passive, non-intentionnelle, car a l’evidence les approches pour ameliorer l’observance seront differentes. Elle constitue donc un sujet de reflexion fascinant pour tous les acteurs du systeme de sante : medecins, pharmaciens, infirmieres d’education, industrie pharmaceutique, pouvoirs publics, en particulier les assureurs (en France, l’Assurance-maladie). Ainsi, la problematique de l’observance apparait centrale en medecine, puisqu’elle impose une reflexion sur la nature meme du soin medical.

Resume L’observance pose trois defis : un defi ethique, puisque vouloir l’ameliorer risque d’etre en contradiction avec le principe d’autonomie, qui impose de respecter les souhaits des patients ; un defi instrumental, puisqu’il faut faire en sorte que les instruments du traitement d’une part, et ceux developpes pour ameliorer l’observance d’autre part, soient accessibles a tous, et puisqu’il faut prendre en compte le manque de temps qui represente une barriere evidente a l’amelioration de l’observance ; un defi paradigmatique enfin, puisque l’ampleur du phenomene de non-observance apparait telle qu’un changement de paradigme semble necessaire, sous la forme de l’avenement d’une medecine de la personne dans laquelle la relation therapeutique repose largement sur le concept de decision medicale partagee.

Resume L’observance et la non-observance des patients atteints de maladies chroniques vis-a-vis des prescriptions medicales posent une question philosophique : comment sont-elles possibles ? Elles sont analysees ici du point de vue de la philosophie de l’esprit, arrivant a la conclusion logique que la non-observance represente l’option par defaut et que l’observance necessite de mettre en jeu un principe de prevoyance qui enjoint de donner la priorite a l’avenir.

Resume A la fin du siecle dernier, au moment ou la diabetologie entrait dans son ere moderne, trois inventions conceptuelles simultanees ont transforme l’exercice de la medecine, et singulierement celle des maladies chroniques : l’evidence-based medicine, l’education therapeutique du patient, et l’application a la medecine du principe d’autonomie. Le but de cet article paraissant dans un numero celebrant le dixieme anniversaire de Medecine des maladies Metaboliques est de decrire, quarante ans plus tard, l’utilisation actuelle de ces inventions.

Resume Cet article propose de definir l’education therapeutique du patient (ETP) a partir de son objectif. Il aboutit a une definition multiple, selon que l’on se situe sur un plan technique, ethique, psychologique, ou societal. Il insiste sur la notion de partage, entre la personne qui a une maladie chronique et le soignant.

Resume Le but de cet article est d’expliquer pourquoi la non-observance des traitements est si frequente a l’adolescence. Nous proposons ici que la non-observance represente en fait la definition meme de l’adolescence, dans la mesure ou elle est le reflet de deux caracteristiques de cette periode de la vie : l’impatience et la desobeissance. Nous montrons en particulier, dans le cadre d’une hypothese evolutionnaire, comment la maturation cerebrale, qui a lieu au moment de la transition entre l’adolescence et l’âge adulte, explique l’apparition progressive de la patience et de sa consequence, l’observance en tant que soin de soi. Avant que cette maturation soit complete, il peut etre normal d’etre non-observant.

Resume Cet article decrit les progres realises dans le design des aiguilles utilisees pour l’injection d’insuline, qui sont devenues plus courtes, plus fines, plus minces, mieux biseautees, et donc de moins en moins douloureuses, meme pour des differences devenant maintenant minimes. Il montre l’impact de ces modifications dans le design des aiguilles sur les representations que les patients et les medecins se font de l’injection d’insuline, et qui ont un effet sur la prescription et l’acceptation de l’insulinotherapie. Il plaide, enfin, pour une amelioration de la communication entre les medecins et leurs patients sur ce moment essentiel du traitement du diabete.

La question de l’ethique de l’education therapeutique n’est pas aussi simple qu’il y parait de prime abord. Certes, l’education therapeutique est ethiquement necessaire, car c’est elle qui permet la fondation d’une veritable medecine de la personne qui respecte l’autonomie des personnes qui ont une maladie chronique. Cependant, elle n’echappe pas au risque de manipuler, pour leur bien, les patients, et ce risque est reel. Il est donc necessaire de montrer la difference qui existe entre persuasion, qui est legitime, et manipulation, qui serait inadmissible.

Resume Parmi les nouvelles attentes des patients, le desir de participer au projet therapeutique en tant que personne consideree dans toute sa complexite appelle une reflexion sur la coordination qui doit etre mise en place entre les differents professionnels impliques dans leur traitement afin de garantir la pleine participation des patients. Nous proposons ici que l’education therapeutique du patient represente un element structurant qui permet une telle synthese, des lors que sa raison d’etre est comprise d’une maniere generale qui pourrait representer la definition profonde de ce que l’on appelle « education therapeutique du patient » : donner un sens, c’est-a-dire a la fois une signification et une direction, a un projet therapeutique dans lequel differents professionnels interagissent avec la personne atteinte d’une maladie chronique. Ce « sens » pourrait egalement representer la definition reelle de ce que l’on appelle « parcours de soin » dans lequel l’education therapeutique du patient a donc un role planificateur.

Resume Objectifs Cette etude avait pour objectifs : (1) de mesurer l’observance des hommes et des femmes ayant une hypertension arterielle (HTA) non controlee, et (2) d’identifier, dans chaque sexe, les facteurs associes a la non-observance aux anti-HTA. Patients et methodes Les medecins generalistes (MG) devaient inclure les deux premiers patients des 2 sexes ayant une HTA non controlee sous traitement. L’observance etait estimee par le MG et avec l’auto-questionnaire (AQ) du Comite francais de lutte contre l’HTA. Les facteurs associes a la non-observance selon l’AQ ont ete selectionnes par analyse de regression logistique en pas a pas type stepwise , analyse realisee independamment chez les hommes et chez les femmes. Resultats Au total, 1630 hommes et 1612 femmes ont ete inclus dans l’analyse. L’observance au traitement etait significativement meilleure chez les femmes ou quand elle etait estimee par les MG. Le manque de motivation etait le premier facteur associe a une mauvaise observance dans les deux sexes. Considerer l’HTA comme une simple anomalie et non comme une maladie pouvant conduire a des troubles cardiaques ou cerebraux etait le deuxieme parametre commun aux deux sexes. Les autres facteurs communs etaient : rencontrer des difficultes financieres a faire face a ses besoins dans le mois et l’absence d’un depistage regulier du cancer du colon. Conclusion L’observance au traitement est meilleure chez les femmes hypertendues non controlees. La mauvaise observance est principalement associee a des facteurs non cliniques. Le manque de motivation est l’element le plus important.

Resume Comment expliquer les differences de pratiques de l’insulinotherapie par pompe externe, non seulement entre l’Europe et les Etats-Unis, et entre les pays europeens, mais egalement d’un centre a l’autre et d’un medecin a l’autre ? Existe-t-il des barrieres, chez les soignants et chez les patients, a l’utilisation d’une pompe a insuline ?

Resume Il arrive souvent que nous hesitions a prendre une decision medicale et ceci peut conduire a l’inertie clinique. Nous suggerons que cette hesitation est secondaire a l’incertitude rencontree lors des deux questions principales de l’activite medicale : – quel est le diagnostic ? – quelle est la conduite a tenir ? Nous montrons que l’application du theoreme de Bayes et de la theorie de l’action rationnelle reposant sur un calcul des utilites esperees sont battues en breche par l’imperfection de notre rationalite et la difficulte de predire les consequences des decisions a l’echelle d’un patient individuel.

Resume Le respect du principe d’autonomie prend une place importante dans l’ethique medicale contemporaine. Cet article examine de maniere critique : – pourquoi l’autonomie du patient n’est pas toujours possible ; – lorsqu’elle ne l’est pas, comment, dans le cadre du principe d’autonomie, quelqu’un (un medecin), peut decider ce qui est bon (un traitement) pour quelqu’un d’autre (un patient) sans tomber dans le paternalisme ou la manipulation ; – la place de la confiance dans le cadre d’un libre renoncement du patient a l’exercice de son autonomie.

Resume Les recommandations recentes concernant le diabete de type 2 proposent une prise en charge individualisee . Le but de cet article est de montrer qu’il s’agit de remettre en œuvre un principe fondamental de la medecine basee sur les preuves ( evidence-based medicine ) qui avait sans doute ete progressivement ignore au cours des dernieres decennies qui ont assiste a la place de plus en plus importante de cette nouvelle maniere de pratiquer la medecine : une decision medicale doit tenir compte non seulement des meilleures donnees de la science, mais egalement des caracteristiques et des preferences des patients.

Il est rare que l’activite physique ait des effets secondaires deleteres chez les patients diabetiques : la survenue d’un infarctus du myocarde ou d’une lesion des pieds survient chez des patients non prepares et non surveilles. Au contraire, la pratique reguliere d’une activite physique est associee a une diminution du risque de retinopathie, de nephropathie, de neuropathie et de macroangiopathie et doit donc etre encouragee. Une partie de l’education therapeutique du patient doit etre consacree a cet encouragement et aux precautions qui la rendront a la fois utile et sans danger.

On admet qu’un patient sur deux ne suit pas les recommandations medicales qui lui sont donnees. Cette non-observance concerne tous les aspects du soin, et ils sont souvent lies. Le but de cet article est de presenter une analyse phenomenologique de la non-observance dans les maladies chroniques, d’une part, en s’appuyant sur les donnees empiriques de la litterature et, d’autre part, en se referant a deux champs disciplinaires: la philosophie de l’esprit et la neuroeconomie. Nous proposons que la non-observance soit associee a deux traits de caractere: d’une part, l’impatience qui fait que certains individus donnent la priorite au present; d’autre part, la faiblesse de la volonte qui les empeche de decider sans reserve de donner la priorite au futur. Nous suggerons que ces deux traits de caractere sont psychologiquement lies.

Que signifie le fait qu'un patient entreprend et, surtout, poursuit indefiniment un traitement ? Il peut s'agir de la prise d'un medicament, mais aussi d'une activite comme l'autosurveillance glycemique, le suivi d'un regime, la pratique d'une activite physique. Partant du modele bien connu, decrit par Prochaska, dans lequel le patient passe par plusieurs stades qui le conduisent d'un etat ou il ne realise meme pas qu'il y a un probleme a resoudre a un changement durable de comportement, cet article propose une analyse theorique des concepts de volonte, d'intention, de decision, d'habitude et de resolution. Il montre la possibilite d'esquisser par des ponts interdisciplinaires les bases d'une veritable physiologie de l'esprit.

The aim of this study was (1) to measure adherence in males and females with uncontrolled hypertension, and (2) to identify factors associated with non-adherence to antihypertensive medication.Each general practitioner (GP) should include the first two male and the first two female patients with uncontrolled treated hypertension. Adherence to antihypertensive treatment was estimated by the GP and using the French League Against High blood pressure (FLAH) self-administered questionnaire. A stepwise logistic regression analysis was used to identify factors associated with non-adherence on the FLAH scale, independently in males and in females.A total of 1630 males and 1612 females were included in the analysis. Adherence to treatment was significantly better in females or when estimated by the GP. Lack of motivation was the first factor associated with poor adherence in both sexes. Considering hypertension as a simple anomaly and not a disease that can lead to cardiac or cerebral disorders was the second common parameter in both sexes. Other common factors were: having monthly periods of financial difficulties in facing his/her needs and absence of regular screening for colon cancer.Adherence to treatment is better in uncontrolled hypertensive females. Poor adherence is mainly associated with non-clinical factors. The lack of motivation is the most important element.

The goal of this study was to determine whether porcine islets encapsulated in hollow fibers made of AN69 copolymer can correct hyperglycemia in diabetic mice and provide normal tolerance to a glucose challenge. In vitro perifusion of hollow fibers demonstrated the rapid kinetics of insulin release in response to glucose. Two fibers containing islets were transplanted into the peritoneal cavity of each of 17 streptozotocin induced diabetic mice. In 11 mice, diabetes was reversed within 3 days with plasma glucose levels decreasing from 19.7 +/- 0.9 (mean +/- SEM) before implantation to 10.9 +/- 0.8 mmol/L. Intraperitoneal glucose tolerance tests were performed in transplanted (n = 7), nondiabetic (n = 15), and diabetic mice (n = 6). A normal glucose pattern was observed in the transplanted diabetic mice. This was achieved in the presence of plasma insulin levels lower than those observed in control nondiabetic mice, suggesting the presence of a state of hypersensitivity to insulin, which was demonstrated in this model by exogenous insulin tolerance tests. In conclusion, encapsulation of islets suspended in ultraculture medium in biocompatible membranes of AN69 can provide xenograft survival, and complete normalization of glucose tolerance can be achieved.

Background According to EULAR recommendations, long term management of gout encompasses pharmacological and non pharmacological treatments. Patient education and adherence to medication and lifestyle advices are key factors of management [1]. Objectives An observational and cross-sectional study was conducted by general practitioners (GP). The main objective was to determine factors associated with adherence to treatment of gout. Secondary objectives were to analyse adherence to lifestyle recommendations and achievement of therapeutic goal for uricaemia, and also to describe the perception of the disease and treatments. Methods Adult patients with gout, taking a urate lowering therapy for more than 3 months, were included by 630 GP. Data were collected during a unique visit. Adherence to treatment was assessed through a 5-item self-questionnaire [2,3]. Factors associated with adherence were analysed using a multivariate logistic regression. Adherence to lifestyle recommendations were assessed via questions on alcohol, beer and soda intake. Patients also completed the Brief Illness Perception Questionnaire (B-IPQ) [4] and the Beliefs about Medicines Questionnaire (BMQ) [5]. Results 1441 patients with gout (85% male, age: 64.4 ± 11.4 years) were retained in the analysis. Main symptoms were pain and swelling (85%), podagra (60%) and erythema (49%). Mean serum uric acid level was 63.4 ± 16.4 mg/L (42% were below the therapeutic goal of 60 mg/L); 85% of patients were overweighted (including 38% obese); 70% had hypertension; 62% had dyslipidemia; 24% had type 2 diabetes; they took 4.9 ± 3.5 tablets daily in average. Overall, 80% of patients were assessed as adherent to medicines and 32% to lifestyle recommendations. Main factors associated with a good adherence to medicines were: being more than 70 years (OR=1.9; CI95%: [1.2–2.9]), having an uricaemia below the therapeutic goal (OR=1.8; CI95%: [1.3–2.5]), regularly checking uricaemia (OR=1.5; CI95%: [1.0–2.1]), and taking few tablets daily (OR/unit=0.9; CI95%: [0.9–1.0]). Besides, good adherence to medicines was associated with a better perception of the disease and treatments (lower impact on quality of life, better control of gout) and a better relationship with health care professionals. Conclusions The ADAGIO study indicates that a good adherence to the pharmacological treatment of gout is associated with regular uricaemia controls and achievement of the recommended therapeutic goal, i.e. maintaining serum uric acid below 60 mg/L [1]. The data suggests that patients under multiple medications would benefit from special attention to help improving gout management. References Zhang W et al. Ann Rheum Dis, 2006. 65(10): p. 1312–24. Girerd X et al. Arch Mal Coeur Vaiss, 2001. 94(8): p. 839–42. Reach G et al. Diabetes Metab, 2011. 37(6): p. 497–504. Broadbent E et al. Journal of psychosomatic research, 2006. 60(6): p. 631–7. Horne R et al. Psychology & Health, 1999. 14(1): p. 1–24. Disclosure of Interest R.-M. FLIPO Grant/research support from: Menarini, L. Martinez Grant/research support from: Menarini, P. Maigret Employee of: Menarini, G. Reach Grant/research support from: Menarini

Resume Pourquoi le phenomene d'insulinoresistance psychologique – la resistance a l'idee de la ≪ mise a l'insuline ≫ – affecte-t-il a la fois les patients et les medecins? Le but de cet article est de montrer qu'il met en jeu des mecanismes mentaux communs aux deux protagonistes du soin: ceux qui interviennent dans toute decision humaine. Cette reflexion consacree specifiquement a l'insulinoresistance psychologique s'applique d'une maniere plus generale aux deux phenomenes de non-observance des patients et d'inertie clinique des medecins, dont elle represente un cas paradigmatique.

This paper describes the current approaches towards the development of continuous glucose monitoring system, in which glucose is measured either in blood or in the subcutaneous tissue. These systems may be used as a glycemic holter, or to display continuously the changes in glucose level, to trigger an alarm in case of hypoglycemia, or of risk of hypoglycemia, or finally to pave the way to the development of an artificial beta cell.

This text describes, in an epistemological perspective, the development of the concept of cellular therapy applied to the treatment of type 1 diabetes. Emphasis is put on three recent papers describing the success of islet allograft in diabetic patients, the development of neo-islets from stem cells isolated from the pancreas of adult mice, and the effect of hepatic cell transfection with an adenovirus bearing the gene coding for PDX-1, a transcription factor involved in the maturation of islets of Langerhans. This text tries to delineate some factors which may be involved in the chances for these techniques to reach the real world of human therapeutics.

This paper presents an analysis of an aspect of non-observance in the treatment of type 1 diabetes mellitus, the absence of adaptation of insulin dosage in spite of hyperglycemia. The adaptation of insulin dosage by the patient is described as an intentional action, performed as a habit. The problem is analysed through the causal theory of action and the concept of akrasia. These considerations may be useful to understand other aspects of therapeutic non-observance.

This paper describes the rationale and different approaches for developing islets of Langerhans xenotransplantation. Implementing this therapeutic strategy in the treatment of human diabetes mellitus requires careful consideration of its potential risks and benefits, taking into account the current status of the treatment of this disease.

As the risk of recipient contamination is a limiting factor for xenotransplantation, the use of specific pathogen-free (SPF) pigs is mandatory. This study investigated the long-term culture of SPF pig islets and evaluated their insulin production when encapsulated in AN69 hollow fibres. Insulin secretion was studied after 3 weeks (n = 10), 2 months (n = 8) and 3 months (n = 3) by 45-min incubation in the presence of 2.8, 5.5, 11 and 16.5mM glucose. Although a decrease in the amount of secreted insulin occurred (1385 +/- 421 and 4323 +/- 1068 microns U/ml at 3 weeks for 2.8 and 16.5 mM glucose respectively; 702 +/- 261 and 2397 +/- 1047 microU/ml at 2 months; 59 +/- 23 and 154 +/- 34 microU/ml at 3 months), glucose-dependent insulin secretion was observed in all cases, i.e. stimulation indices of 8.1 +/- 3.1 (p0.05 vs the presence of 5.5 mM glucose) at 3 weeks, 3.3 +/- 1.1 at 2 months and 3.0 +/- 0.7 at 3 months. The insulin secretion of encapsulated SPF pig islets, cultured for 1 or 3 weeks, was evaluated under perifusion conditions using a stimulus of 10mM glucose plus 5.5 mM theophylline. Glucose stimulation resulted in a significant two-fold increase in insulin secretion (p0.05), which was maintained over culture time. These results indicate that SPF-isolated islets remained functional when cultured for several weeks either as free or encapsulated islets, although the magnitude of insulin secretion decreased dramatically after three months of culture.

Le probleme du patient diabetique en situation de grande precarite ou sans domicile fixe (SDF) est pour la plupart des medecins urgentistes un probleme peu evalue. Aux urgences, face a l'afflux de consultants et aux problemes poses par les patients SDF, la specificite du patient SDF diabetique risque de passer inapercue. Afin de preciser les problemes poses et discuter de solutions, nous avons realise deux enquetes, l'une au niveau du SAU (Service d'accueil et des urgences) de l'hopital Avicenne (AP-HP, Bobigny), l'autre par mailing aupres de divers services francais d'accueil et d'urgences.

The hormone leptin secreted by adipocytes plays a major role in body weight homeostasis. Its main target is the hypothalamus, but it also affects several peripheral tissues directly. The direct effect of leptin on insulin secretion by pancreatic beta cells has been investigated in several studies, though with controversial results. Interpretation of these data must take into account the animal model and the leptin concentrations used. Experiments carried out on islets from ob/ob mice harbouring a mutation in the leptin gene are not representative of the leptin effect in normal animals because ob/ob islets are very sensitive to the hormone and show altered regulation of insulin secretion. In normal rodent islets, physiological concentrations of leptin seem to inhibit insulin secretion only when the islets are maximally stimulated with high concentrations of glucose associated with secretion potentiators. Several isoforms of the leptin receptor are expressed in pancreatic beta cells. Indirect experimental evidence suggests that leptin signalling in islets requires the long isoform of the receptor. The molecular mechanisms underlying the effect of leptin on insulin secretion are unknown. Our hypothesis is that physiological concentrations of leptin in normal rodents do not affect the direct pathway (coupling a rise in glucose concentration to insulin secretion) but modulate a potentiation of glucose-induced insulin secretion involving cyclic AMP or phospholipase C/protein kinase C activation.

Though the pig appears to be the islet donor of choice for grafts in diabetic patients, there may be a risk of transmission of infectious agents. In this context, we adopted a strategy of islet isolation from pigs raised and killed in specific pathogen-free (SPF) conditions as a minimum with regard to the concept of quality assurance. Accordingly, the present study investigated the function of SPF pig islets to determine whether they react qualitatively and quantitatively to nutriments, hormones and neuromediators with which they would be confronted in man and could therefore provide effective regulation during physiologic or physiopathologic situations. beta cells from 18 Large-White SPF pigs were functionally intact after 7 days in culture. Insulin stimulation indexes (SI) of 3.1 +/- 0.2, 2.2 +/- 0.1, and 4.4 +/- 0.3 were found respectively for 30 mmol/l K+, 100 mumol/l tolbutamide and 10 mmol/l theophylline. Basal insulin secretion (72.2 +/- 7.6 muU/min) had already increased significantly (p0.001) with 5.5 mmol/l glucose (184.2 +/- 25.5 muU/min, SI: 2.5 +/- 0.6), indicating that the threshold stimulatory concentration was comparable to that of human islets. Insulin secretion increased in a glucose dose-dependent manner (p0.001): SI: 3.1 +/- 0.3 and 3.6 +/- 0.2 with 11.0 mmol/l and 22.0 mmol/l glucose, which showed a satisfactory magnitude with reference to human islets. Even the subtle phenomenon of "glucose memory" was apparent in these pig islets. Arginine stimulated (p0.001) insulin secretion dose-dependently (SI: 2.2 +/- 0.3 with 5 mmol/l and 2.9 +/- 0.2 with 10 mmol/l). The ketone body beta-hydroxybutyrate (10 mmol/l) also induced insulin secretion (SI: 4.3 +/- 0.3). Insulin release was stimulated by 4 mumol/l gastric inhibitory peptide, revealing sensitivity to the hormonal enteroinsular axis, and by 2 mumol/l glucagon. Parasympathetic cholinergic influence was studied using 500 mumol/l carbamylcholine, which increased insulin secretion. The influence of orthosympathetic control and of stress situations was also studied. As in human islet response, epinephrine and the alpha 2-agonist clonidine (50 mumol/l) inhibited insulin secretion. Finally pre-culture of islets may be beneficial for graft outcome, provided that no deterioration in islet function occurs. A prolonged 21-day culture of SPF pig islets showed no decrease in insulin response to glucose, arginine and potassium, even with an unaltered threshold stimulatory glucose concentration. Thus, Large-White SPF pigs and the application of our isolation procedure provided islets with functional characteristics reproducibly compatible with potential utilisation for effective regulation of glycaemia under physiologic and physiopathologic situations in humans.

Insulin dependent diabetes mellitus is a common disease affecting 1.5 million patients in Europe. It is currently treated by multiple injections of insulin associated with blood glucose self monitoring. The goal of the treatment is to obtain near normal glucose concentration, in order to prevent the later complications (retinopathy, nephropathy, neuropathy, macroangiopathy) of the disease--which may be severe--while avoiding severe hypoglycaemia. Although diabetes therapy has improved enormously in the last few decades, intensive research is currently aimed at replacing not only the missing hormone but also the cells which normally produce insulin in the pancreas. Transplantation of insulin secreting cells as a treatment of diabetes mellitus therefore has a special significance among other applications of cell therapy, since it deals with a disease which already has an efficient therapy. The aim of this article is the discussion of the objectives and the hopes in this field.

Management of very high insulin requirements in rare extreme insulin resistance syndromes is difficult and poorly documented. We report a case of a type B insulin-resistant patient requiring approximately 10,000 units of insulin per day, i.e. beyond the possibilities of current insulin formulations and delivery devices. Only the Panomat C10 portable pump model (Disetronic) and U500 Humulin (Lilly) allowed the required rate of 400 units per hour to be attained only when the reservoir was changed twice daily and the site and catheter were changed once daily. Three months after discharge, the patient was in good general and local condition, but with only fair diabetes control (glycated haemoglobin 9.5%).