Serge Halimi

Comment motiver le patient à changer

Serge Halimi Pôle DigiDUNE – Clinique d’endocrinologie-diabète-nutrition, CHU, Grenoble. L’ éducation thérapeutique (ETP) est à la mode. Tant mieux ! Sa reconnaissance est admise, les contours de l’indispensable formation des équipes en train d’être précisés, son financement devrait suivre. Mais au-delà de son efficacité démontrée dans quelques études, nous qui avons en charge des patients diabétiques ou des patients obèses, nous n’ignorons pas combien son succès repose sur la capacité au changement, même modeste des patients. Si difficile à obtenir. Combien d’entre-eux reconnaissent en effet « Je sais, mais je ne fais pas ! ». Pourquoi estil si difficile (pour eux seuls ?) de changer un tant soit peu. Nos patients sont-ils si peu motivés ? Pourquoi avons-nous tant de mal à les convaincre de bouger, de mieux manger et de suivre plus régulièrement leur traitement ? L’ouvrage d’Alain Golay, Grégoire Lagger et André Giordan est là pour tenter d’y répondre et leur contribution est importante. Ce livre doit figurer dans votre bibliothèque, à condition de le lire évidemment. En effet, il y est question d’un sujet clé : Comment motiver le patient à changer ? Il est le fruit des recherches de ce groupe genevois depuis deux décennies. Selon les auteurs cette éducation dite thérapeutique doit passer par cinq dimensions : d’abord l’indispensable apprentissage de connaissances (dimension cognitive), puis la prise en compte de la dimension émotionnelle (ou intentionnelle) pouvant aider à l’acceptation progressive de l’état de maladie, ensuite celle qui peut aider à saisir la façon de raisonner de chaque patient à tenter d’entrer dans son mode de « penser » (dimension infracognitive), et encore celle qui vise à aider le patient à se tourner vers ce qui constitue son comportement habituel afin de l’analyser, le décrypter (dimension métacognitive) et enfin la dimension qui est de l’ordre du ressenti, des sensations. Celles qui accompagnent, par exemple, ses comportements vis-à-vis de l’alimentation, de l’activité physique (dimension perceptive). C’est sur ces bases revisitées, formalisées, que les auteurs proposent ensuite une autre façon de bâtir les entretiens motivationnels, passer du dire au faire, faire bouger les lignes des croyances de santé, processus, démarche de déconstruction-reconstruction. L’ouvrage dans sa troisième partie propose des situations cliniques sous forme d’ateliers de pratique basés sur ces cinq dimensions. Disons-le tout de suite cet ouvrage est à lire tôt (mais pas trop) dans sa formation à l’ETP afin d’en saisir la complexité, l’exigence, la rigueur et aussi son côté le plus passionnant. À lire aussi, ensuite une fois immergé dans sa pratique, tant y sont abordées des questions essentielles, parfois un peu ardues, toujours essentielles, qui approchent de plus près les véritables enjeux de l’ETP et de la motivation. Une fois explicitées ce que sont pour les auteurs les cinq dimensions de l’ETP, des questions, parmi bien d’autres sont discutées : comment apprendre avec et contre ses conceptions, les conflits cognitifs, la notion d’obstacle à l’apprentissage. Les résistances au changement qui constituent en effet un facteur majeur et sont trop souvent négligées font l’objet d’un chapitre passionnant. Bref, tout cet ouvrage mérite d’être lu et d’être travaillé, seul et en équipe. Les exemples fournis dans les ateliers constituent une excellente base de réflexion et de mise en pratique extrapolable à bien des situations rencontrées dans nos pratiques d’ETP, de groupe comme individuelle. À lire et relire certainement.

Standardization of procedure for efficient ex vivo gene transfer into porcine pancreatic islets with cationic liposomes.

BACKGROUNDnNew strategies to improve the outcome of encapsulated porcine islet transplantation may involve the transfer of gene sequences affecting islet viability. While adenoviral vectors appear as the most efficient gene transfer system so far established for islets, non-viral-based vectors are most likely to fulfill microbiological safety criteria and be retained in the clinical setting. Our aim was to standardize the procedures of gene transfer into adult porcine islets using cationic liposome DOTAP.nnnMETHODSnPorcine islets obtained by collagenase digestion and density gradient purification were lipofected with plasmids coding for luciferase or beta-galactosidase under the control of simian virus 40 or cytomegalovirus promoter. The following parameters were explored: exposure time to vector (1-48 hr), DNA amount (1-15 microg/500 islets), and DOTAP to DNA ratio (2-16). Reporter gene expression was determined 48-72 hr after lipofection.nnnRESULTSnEfficiency and reproducibility of transfection were maximal with the following procedure: 3-hr exposure time followed by islet washing, 12 microg of DNA per 500 islets (150 microm equivalent), and DOTAP to DNA ratio of 12 microl/microg. Freshly isolated islets in large aliquots (n=4000 in 50-ml tubes) were efficiently transduced with this procedure, and distribution of gene expression was homogenous when islets were subsequently plated in 500-islet aliquots. Luciferase gene expression was detected for a minimum of 7 days after lipofection. Gene expression was also evident up to 4 weeks after islet transplantation beneath the kidney capsule of athymic mice. Transfection of islets using the beta-galactosidase vector yielded 25% positive islets. Islet viability was not adversely affected.nnnCONCLUSIONSnThis islet lipofection procedure may help achieve the local release of a bioactive peptide in the graft environment and have therapeutic applications in islet transplantation.

The Severity of Nocturnal Hypoxia but Not Abdominal Adiposity Is Associated with Insulin Resistance in Non-Obese Men with Sleep Apnea

Background Beyond obesity, sleep apnea syndrome is frequently associated with excess abdominal adiposity that could contribute to the deteriorated cardiometabolic risk profile of apneic patients. Methods The present study addressed the respective contribution of the severity of sleep apnea syndrome and excess abdominal adiposity to the cardiometabolic risk profile of 38 non obese men with polysomnography-diagnosed sleep apnea syndrome (apnea-hypopnea index >15 events/hour). These otherwise healthy men performed a 75g-oral glucose tolerance test (OGTT) with plasma lipid/inflammatory and redox profiles. Twenty-one apneic men with high-waist circumference (>94 cm) were compared to 17 apneic men with low-waist circumference. Results Apneic men with high-waist circumference had higher AUC glucose and AUC insulin than apneic men with low-waist circumference. Accordingly, apneic men with high-waist circumference had higher hepatic insulin resistance as reflected by higher HOMA-resistance index, and lower global insulin sensitivity as reflected by lower insulin sensitivity index of Matsuda (derived from OGTT). The sleep structure and the apnea-hypopnea index were not different between the two groups. However, apneic men with high-waist circumference presented with lower mean nocturnal oxyhemoglobin (SpO2). In the 38 men, waist circumference and mean nocturnal SpO2 were inversely correlated (ru200a=u200a−0.43, pu200a=u200a0.011) and were both associated with plasma glucose/insulin homeostasis indices: the higher the waist circumference, the lower the mean nocturnal SpO2, the lower the insulin-sensitivity. Finally, in multivariable regression model, mean nocturnal SpO2 and not waist circumference was associated with insulin-resistance. Conclusion Thus, excess abdominal adiposity in non obese apneic men was associated with a deteriorated insulin-sensitivity that could be driven by a more severe nocturnal hypoxemia.

Assessment of insulin resistance in fructose-fed rats with 125I-6-deoxy-6-iodo-D-glucose, a new tracer of glucose transport

PurposeInsulin resistance, characterised by an insulin-stimulated glucose transport defect, is an important feature of the pre-diabetic state that has been observed in numerous pathological disorders. The purpose of this study was to assess variations in glucose transport in rats using 125I-6-deoxy-6-iodo-D-glucose (6DIG), a new tracer of glucose transport proposed as an imaging tool to assess insulin resistance in vivo.MethodsTwo protocols were performed, a hyperinsulinaemic–euglycaemic clamp and a normoinsulinaemic–normoglycaemic protocol, in awake control and insulin-resistant fructose-fed rats. The tracer was injected at steady state, and activity in 11 tissues and the blood was assessed ex vivo at several time points. A multicompartmental mathematical model was developed to obtain fractional transfer coefficients of 6DIG from the blood to the organs.ResultsInsulin sensitivity of fructose-fed rats, estimated by the glucose infusion rate, was reduced by 40% compared with control rats. At steady state, 6DIG uptake was significantly stimulated by insulin in insulin-sensitive tissues of control rats (basal versus insulin: diaphragm, pu2009<u20090.01; muscle, pu2009<u20090.05; heart, pu2009<u20090.001), whereas insulin did not stimulate 6DIG uptake in insulin-resistant fructose-fed rats. Moreover, in these tissues, the fractional transfer coefficients of entrance were significantly increased with insulin in control rats (basal vs insulin: diaphragm, pu2009<u20090.001; muscle, pu2009<u20090.001; heart, pu2009<u20090.01) whereas no significant changes were observed in fructose-fed rats.ConclusionThis study sets the stage for the future use of 6DIG as a non-invasive means for the evaluation of insulin resistance by nuclear imaging.

Role of ACE Inhibitors in Patients with Diabetes Mellitus

The adjective ‘epidemic’ is now attributed to the rapidly growing number of patients with diabetes mellitus, mainly type 2, and the specific complications linked to this disorder. Provided they are recognised early enough, these different complications can be treated; in some patients the evolutive course of these complications can be slowed or even stopped. Furthermore, some recent observations suggest that specific tissular lesions may be prevented or even reversed.Although glycaemic control is essential, other therapeutic measures that must also be taken include those to control blood pressure and to lower lipid levels. Of the agents available to control the complications of diabetes mellitus, cardiovascular drugs, and particularly ACE inhibitors, have a pre-eminent place. Experimental and epidemiological data suggest that activation of the renin-angiotensin-aldosterone system plays an important role in increasing in the micro- and macrovascular complications in patients with diabetes mellitus. Not only are ACE inhibitors potent antihypertensive agents but there is a growing body of data indicating that also they have a specific ‘organ-protective’ effect. For the same degree of blood pressure control, compared with other antihypertensive agents, ACE inhibitors demonstrate function and tissue protection of considered organs. ACE inhibitors have been reported to improve kidney, heart, and to a lesser extent, eye and peripheral nerve function of patients with diabetes mellitus. These favourable effects are the result of inhibition of both haemodynamic and tissular effects of angiotensin II. Finally, there are a growing number of arguments favouring the use of ACE inhibitors very early in patients with diabetes mellitus.

Impact of diabetes mellitus on clinical presentation and prognosis of pancreatic cancer

INTRODUCTIONnThe aim of this study was to investigate possible effects of diabetes mellitus on clinical manifestations and prognosis of pancreatic cancer (PC).nnnPATIENTS AND METHODSnWe retrospectively reviewed the clinical files of 122 patients with PC, and divided them into two groups: those with diabetes (56 patients) and those without diabetes (66 patients). The two groups were then compared for demographic profiles, clinical manifestations of PC, features of the tumor and fatal outcomes.nnnRESULTSnMean age, sex distribution, body mass index at cancer diagnosis, prevalence of hypertension, dyslipidemia, weight loss, abdominal pain, lumbar pain, signs of dyspepsia, and size, and histological features of the tumor were similar between the two groups. The cancer was located in the head of the pancreas in 50% of those with diabetes, and 80% of those without diabetes (P=0.04). The median survival time was similar.nnnCONCLUSIONSnClinical features, tumor size and prognosis of PC are similar in people with and without diabetes. Having diabetes does not seem to contribute to earlier diagnosis of PC.

In vivo assessment of cardiac insulin resistance by nuclear probes using an iodinated tracer of glucose transport

PurposeInsulin resistance, implying depressed cellular sensitivity to insulin, is a risk factor for type 2 diabetes and cardiovascular disease. This study is the first step towards the development of a technique of insulin resistance measurement in humans with a new tracer of glucose transport, [123I]6-deoxy-6-iodo-D-glucose (6DIG).MethodsWe investigated 6DIG kinetics in anaesthetised control rats and in three models of insulin-resistant rats: fructose fed, Zucker and ZDF. The study of myocardial 6DIG activity was performed under two conditions: first, 6DIG was injected under the baseline condition and then it was injected after a bolus injection of insulin. After each injection, radioactivity was measured over 45xa0min by external detection via NaI probes, in the heart and blood. A tri-compartment model was developed to obtain fractional transfer coefficients of 6DIG from the blood to the heart.ResultsThese coefficients were significantly increased with insulin in control rats and did not change significantly in insulin-resistant rats. The ratio of the coefficient obtained under insulin to that obtained under basal conditions gave an index of cardiac insulin resistance for each animal. The mean values of these ratios were significantly lower in insulin-resistant than in control rats: 1.16u2009±u20090.06 vs 2.28u2009±u20090.18 (pu2009<u20090.001) for the fructose-fed group, 0.92u2009±u20090.05 vs 1.62u2009±u20090.25 (pu2009<u20090.01) for the Zucker group and 1.34u2009±u20090.06 vs 2.01u2009±u20090.26 (pu2009<u20090.05) for the ZDF group.ConclusionThese results show that 6DIG could be a useful tracer to image cardiac insulin resistance.

Increased matrix metalloproteinase-9 predicts poor wound healing in diabetic foot ulcers: Response to Liu et al.

In a recent study by Liu et al. (1), the complex mechanisms of diabetic foot ulcers were further elucidated. In a series of 62 ulcers, the authors report that they found—for the first time—a positive correlation between a high matrix metalloproteinase-9 (MMP-9)–to–tissue inhibitor of metalloproteinase-1 (TIMP-1) ratio and poor wound healing.nnHowever, these are not the first data enhancing the putative role of MMP-9 in the pathogenesis of chronic wounds. Ladwig et al. (2) also described a positive correlation between a high MMP-9–to–TIMP-1 ratio and poor wound healing …

High Fructose‐Fed Rats: A Model of Glomerulosclerosis Involving The Renin‐Angiotensin System and Renal Gelatinases

The use of fructose oral diets as an easy source of sugar substitute could represent at first sight an interesting carbohydrate (CH) intake, especially for diabetic patients, with weak hyperglycemic effect and allegedly reduced secondary insulin secretion. In the long run, metabolic side effects proceed from an inoperant metabolic control by fructose-6-phosphate kinase, induction of glycogen-synthase, and glycerol-3phosphate/VLDL pathways, and may favor the development of progressive insulin resistance, hyperuricemia, and hypertriglyceridemia, which links fructose-rich diets with the clinical dilemma of insulin resistance, systemic hypertension, and vascular renal lesions suspected in human metabolic syndrome X even without established NIDDM.

Une théorie du soin. Souci et amour face à la maladie

Serge Halimi Pôle DigiDUNE – Clinique d’endocrinologiediabète-nutrition, CHU, Grenoble. U ne théorie du soin. Une théorie ? Sans nul doute puisqu’il s’agit bien d’une réflexion très personnelle et profonde que nous propose Gérard Reach dans cet ouvrage. Une réflexion longuement travaillée sur la relation entre cet autre qu’est le sujet devenu malade et le soignant. Relation qui a évolué avec le temps, passant d’un paternalisme, directif plus ou moins autoritaire, quoique bienveillant, à une relation qui serait ou vise à être aujourd’hui « d’égal à égal ». Utopie, aussi, lorsqu’il s’agit de la rencontre de sujets égaux certes mais ici engagés dans une relation de nature nécessairement asymétrique. Tant d’obstacles s’y opposent. Comment faire en sorte qu’un patient qui vit à et de l’intérieur de la maladie, puisse recevoir conseils et recommandations de cet autre, certes expert, mais d’un décideur qui siège en dehors de la maladie ? Comment, pour nous, ne pas risquer de considérer le malade uniquement à travers sa maladie, son diagnostic, ses résultats en oubliant lindividu ? Celui qu’il était autrefois, avant d’être malade et qui vit toujours en lui, qui prend plus ou moins le pas selon les moments sur l’homme malade. « Le malade et son double », un concept cher à Gérard Reach et qu’il développe magistralement ici. Le médecin, quant à lui, est bien sûr sollicité en qualité d’expert. Est-il possible de lui accorder sa confiance ? Une question en premier lieu de l’ordre de la compétence de celui qui est à même de proposer un traitement, dans l’acception « technique » du terme. Mais confiance aussi parce qu’il sait être aidant, contribuant à faire progresser le malade dans une démarche qui vise à le défaire de l’ambivalence et de l’angoisse qui l’accompagnent et constituent un obstacle, une entrave à l’autonomie, à se prendre bien en charge, à sa qualité de vie, à la persistance durable dans le soin de soi. La dualité du patient. Vivre sa vie, celle d’avant la maladie, puisqu’il reste cet individu-là et vivre sa maladie depuis le moment de l’annonce. Cette ambivalence fait introduire à l’auteur le concept de soin de soi et d’amour de soi. Ceci vaut pour les deux acteurs de cette rencontre, de ce partenariat singulier, où tout est à construire, sur