André Grimaldi

Screening for Liver Fibrosis by Using a Noninvasive Biomarker in Patients With Diabetes

BACKGROUND & AIMS Patients with diabetes are at risk for nonalcoholic fatty liver disease leading to advanced fibrosis, cirrhosis, and liver cancer. We examined the efficacy of a screening strategy with a noninvasive fibrosis biomarker (FibroTest) in patients with diabetes. METHODS We prospectively studied 1131 consecutive patients without a history of liver disease seen for diabetes. The biomarker data were obtained, and patients with presumed advanced fibrosis were reinvestigated by a hepatologist using elastography and, if necessary, ultrasonography, endoscopy, or liver biopsy. RESULTS The biomarker predicted advanced fibrosis in 63 of 1131 (5.6%) patients. A total of 45 patients was reinvestigated, and advanced fibrosis was confirmed in 32 patients, a 2.8% (32/1131) prevalence of confirmed advanced fibrosis, 5 cases of cirrhosis, and 4 cases of hepatocellular carcinoma. In the population with type 2 diabetes who were 45 years or older, the prevalence of confirmed advanced fibrosis was 4.3% (30/696), and hepatocellular carcinoma was 5.7 of 1000 (4/696). CONCLUSIONS The fibrosis biomarker might be used for the detection of advanced fibrosis in patients with type 2 diabetes.

Ankle-to-Brachial Ratio Index Underestimates the Prevalence of Peripheral Occlusive Disease in Diabetic Patients at High Risk for Arterial Disease

Ankle-to-brachial ratio index (ABI) is a simple method recommended for screening and evaluating peripheral arterial occlusive disease (PAOD) severity in diabetic patients. However, it has been suggested that subclinical media artery calcification could falsely normalize ABI (1), and prevalence of effective arterial occlusive disease when arteries are not compressible is not clear (2). Therefore, defining clinically relevant peripheral arterial occlusion on an ABI threshold of <0.9 could lead to misclassifying many diabetic patients, especially in a population at high risk for PAOD and arterial calcification (age, kidney disease, and hypertension). We evaluated the accuracy of ABI in screening and evaluating PAOD in such a population. …

The Charcot foot

The Charcot foot Neuroarthropathy, or Charcot foot, was first described by Jean-Martin Charcot in 1883 in patients with tabes dorsalis, but nowadays it is reported most frequently as a complication of diabetes. Two-thirds of people with Charcot foot have type 2 diabetes. Men and women are equally affected. The disorder affects about 0.2% of people with diabetes, but minor arthropathic changes can be noted in up to 3%. Also, radiographic examinations can show healed fractures that patients were unaware of. Charcot foot arises typically in patients with severe distal symmetrical neuropathy, who are generally in their 50s or 60s and who have had diabetes for at least a decade. Frequent

Significant Variations in Elastometry Measurements Made Within Short-term in Patients With Chronic Liver Diseases

BACKGROUND & AIMS Transient elastometry is a noninvasive procedure used to measure fibrosis when patients are diagnosed with liver disease; it might be used to monitor changes over time. We investigated whether there are short-term variations in stiffness measurements that are not attributable to changes in fibrosis by studying patients with stable liver disease. METHODS We performed a retrospective analysis of 531 paired liver stiffness measurements made by Fibroscan when the study began (LSM1) and at follow-up (LSM2), more than 1 day and less than 1 year apart, from 432 stable (for body mass index, waist circumference, and alcohol consumption), untreated, immunocompetent patients with chronic liver disease (from January 2006 through March 2009). Variations between the first and follow-up measurements were expressed as absolute (LSM2-LSM1, kPa) or relative ([LSM2-LSM1]/LSM1*100) or as changes in fibrosis stage. RESULTS There was >20% variation in 49.7%, >30% in 34.3%, and >50% in 12.2% of paired measurements; this variation was constant across the spectrum of LSM1 values. The variations produced a 1-fibrosis stage difference in 31.5% of pairs and a ≥ 2-stage difference in 9.8% of pairs. Patients with LSM1 >7 kPa had increased probability of having a different stage of fibrosis at LSM2, compared with patients with LSM1 <7 kPa. Factors associated with variation included measurements made by 2 different operators or at least 1 non-senior operator, ratios of interquartile range:median values, significant fibrosis (≥ 7 kPa) at LSM1, baseline body mass index, or a 2-fold difference in level of alanine aminotransferase between measurements. When the analyses were restricted to measurements made by the same operator, the variation was slightly reduced; fibrosis stage differed between measurements for only 34.3% of cases. CONCLUSIONS Operator-related and patient-related factors produce significant variations in liver stiffness measurements made by transient elastometry, limiting its use in monitoring patients. These variations are unrelated to disease progression. The lowest levels of variation occur in measurements made in patients with no or early-stage fibrosis or by a single experienced operator.

Intensive cardiovascular risk factors therapy and prevalence of silent myocardial ischaemia in patients with type 2 diabetes.

BACKGROUND Screening for silent myocardial ischaemia (SMI) is a controversial strategy undergoing intensive risk factor therapy. AIMS To assess the prevalence of SMI and coronary artery disease (CAD) in asymptomatic type 2 diabetic patients at high cardiovascular risk (two additional risk factors or more) and undergoing long-term intensive risk factor therapy and tight glycaemic control. METHODS SMI screening, using isotopic or echographic stress tests, was carried out in 122 asymptomatic type 2 diabetic patients at high cardiovascular risk and undergoing long-term intensive risk factor therapy. Coronary angiography was proposed if SMI was detected. Long-term follow-up data on death, myocardial infarction and revascularization were obtained by telephone call or clinical review. RESULTS The mean age was 65+/-6 years and 74% of patients were men. The mean duration of diabetes was 15+/-9 years. The mean number of additional risk factors was 2.9, 32% of patients had microalbuminuria and 12% had peripheral arterial disease. SMI was detected in 20 (16%) patients. Seven (6%) patients had significant CAD treated successfully by angioplasty (n=6) or bypass surgery (n=1). The positive predictive value of the non-invasive screening test for the diagnosis of significant CAD (stenosis>50%) was 39%. The event rate was very low (1.6%) at 2-year follow-up. CONCLUSION Long-term intensive risk factor therapy in high-risk patients with type 2 diabetes is associated with low prevalence of SMI and detected CAD. Optimal medical therapy and revascularization of significant CAD are associated with a low cardiovascular event rate at two years.

Limitations of the so-called “intensified” insulin therapy in type 1 diabetes mellitus

Intensive insulin treatment is defined by basal-prandial insulin therapy which tries to reproduce physiological insulin secretion. This requires 3 to 5 injections and self-monitoring of blood glucose 4 to 5 times a day. Patients who accept their disease and the demanding treatment regimen most often achieve HbA1(c) < 7.5%. Severe complications of diabetes can be avoided without increasing the risk of severe hypoglycemia. However, 50% of type 1 diabetic patients do not reach this objective. The reasons are: the disease itself, the diabetic patient, or the physician. Brittle diabetes with severe, repeated episodes of hypoglycemia and inversely persistent postprandial hyperglycemia prevents patients from reaching the ideal glycemic target. More often, the main obstacle is related to psychological problems: difficulties in self-regulation, denial of the disease, or phobia of hypoglycemia with avoidance behavior. Frequently, young women present eating disorders which can explain the poor diabetes control. The physician himself may be implicated in these poor glycemic results by not prescribing the right tools to obtain optimal glycemic control (staying with just two daily injections with premixed insulin) or by assigning glycemic targets inaccessible for the patient, or when an empathic relationship cannot be established between the patient and the physician. Patient empowerment is the key to the success of functional insulin treatment.

Identification of factors associated with impaired hypoglycaemia awareness in patients with type 1 and type 2 diabetes mellitus.

OBJECTIVES To assess clinical factors associated with impaired hypoglycaemia awareness (HA). METHODS Survey of 241 type 1 and type 2 diabetic patients hospitalised in a diabetes department for a diabetes education program. Demographic, diabetes and psychiatric characteristics and subjective hypoglycaemic symptoms were recorded by a self-report questionnaire. RESULTS Age and body mass index (BMI) was greater and glycated haemoglobin was lower in diabetic patients reporting impaired HA, however, these latter differences became not significant when age was included as a covariate. There were significantly more current smokers among those with impaired HA and controlling for age accentuated this difference. Current treatment by insulin was not associated with impaired HA. Backward stepwise logistic regression showed that type 2 diabetic patients were twice as likely to have impaired HA than type 1 diabetic patients (OR = 2.195, 95% CI: 1.017-4.734, P = 0.04). Moreover, higher age, current smoking and type 2 diabetes interacted significantly in increasing the likelihood of impaired HA. Among those with impaired HA more patients experienced drowsiness and nervousness and less patients reported tremor during the hypoglycaemic episodes. No other symptoms were associated with impaired HA. CONCLUSION Type 2 diabetic patients, whether on insulin or not, and especially if they are of advanced age and if they smoke, are at increased risk of impaired HA.

Effects of bed-time insulin versus pioglitazone on abdominal fat accumulation, inflammation and gene expression in adipose tissue in patients with type 2 diabetes.

AIMS/HYPOTHESIS Intra-abdominal fat (IAF) and inflammatory markers are correlated with cardio-vascular risk. We compared the impact of bed-time insulin versus pioglitazone treatment on these parameters in type 2 diabetic (T2D) patients. METHODS Twenty-eight T2D patients poorly controlled with metformin and sulfonylurea were randomized to receive add-on therapy with pioglitazone or bed-time NPH insulin. IAF and subcutaneous fat (SCF) content, systemic low-grade inflammation level and expression of inflammation related genes in SCF, were measured before and after 24 weeks of treatment. RESULTS Insulin and pioglitazone resulted in a significant decrease in HbA1c (-1.6% and -1.2%, respectively) and a significant increase in total body fat mass (1+/-2.3 and 3.3+/-2.7 kg, respectively). There was no change in IAF content after both treatments whereas significant increase in SCF content was only seen after pioglitazone treatment (p<0.05 versus insulin). hsCRP level decreased after pioglitazone and ferritin level decreased after insulin treatment. No change in mRNA expression of inflammation related genes was found after either treatment. CONCLUSION/INTERPRETATION This suggests that a 24-week treatment with pioglitazone or bed-time insulin has a similar impact on intra-abdominal fat mass and systemic low-grade inflammation.

Should diabetic patients be asked to test their blood glucose 90 to 120 minutes after the beginning of their meals

There are three distinct objectives in reducing the post-prandial blood glucose peaks: 1st to reduce the risk of foetal macrosomia in pregnancy, 2nd to reduce cardiovascular morbi-mortality, 3rd to lower the HbA1c. With 6-7 glycaemic controls per day and fractionning their meals, motivated women with gestational diabetes reach this goal. But there is no data today directly proving that post-prandial glycaemia is specifically related to the development of micro and macrovascular complications. So to reduce the cardiovascular risk, there are more arguments in favour of lowering HbA1c or prescribing statins than in prescribing a hypoglycaemic drug acting selectively on post-prandial glycaemia. Lastly, to reduce HbA1c near to the goal of 7%, the most important is to reduce the preprandial glycaemia below 1.20 g/l. The patients must be required to monitor their post-prandial glycaemia 2 hours after the beginning of the meal only when the aim is to lower the HbA1c below 7% or 6.5%, for example during pregnancy, or in case of discrepancy between glycaemia at 8 a.m. and 7 p.m. (below 1.20 g/)l and HbA1c (above 7%). In other cases, in type 2 diabetes, two glycaemias per day, fasting and vesperal, seems sufficient.

P81 L’art au service de la maladie chronique

Introduction Pour ameliorer la prise en charge de la maladie chronique, le malade doit comprendre qui il est, comment il reagit face a l’adversite, aux evenements de la vie. Exprimer ses emotions est souvent difficile voire impossible dans le langage parle. En revanche, par le biais du dessin ou de l’ecriture, il est plus facile de se livrer. Patients et methodes Dans l’unite d’education, pour les diabetiques type 1 (6 patients), nous avons mis en place avec l’aide d’un metteur en scene et des acteurs professionnels, des ateliers nommes le « theâtre du vecu ». A ce jour, 4 sessions ont ete realisees. Il s’agit pour les patients d’ecrire une page sur le theme de leur choix. Les consignes d’ecritures sont les suivantes sous forme de monologue ou de dialogue. Le texte doit commencer par l’allusion a une date ou un evenement qui a marque un moment important de votre vie. Puis, le texte doit inclure « un petit rien qui finit par envahir ». Enfin, le texte doit finir par « puis tout est devenu comme si… ». Des themes sont proposes : A – je suis dans un espace noir, il y a quelqu’un a cote de moi, j’ai envie de lui parler B – dans une chambre, un personnage annonce a un autre une nouvelle qui risque de changer completement sa vie C – un personnage est enferme dans une cage transparente. Il y a quelqu’un a cote de lui, il a envie de lui parler D – un personnage est devant un miroir, il parle a travers le miroir a quelqu’un, il a envie de lui dire quelque chose d’important E – dans une chambre magique sont accrochees 2 photos, elles sortent de leur cadre et je parle avec elles Les textes sont joues par les acteurs sous la direction des patients qui deviennent metteurs en scene. Resultats Les patients ecrivent sur des sujets qu’ils n’ont jamais evoque auparavant. Que ce soit des craintes pour l’avenir, pour leurs enfants, ou la peur de parler de leur maladie. « une photo prise en 2007, tout va bien, j’ai une famille, une maison, un travail… Oui, c’est vrai, le diabete en 2007, mais tout va bien… » (une voix off) « oui, mais l’angoisse… » « non, tout va bien… » (la voix off) « oui, mais tes enfants… ? » « c’est vrai, pourvu que… ». Ou encore « mon fils de 9 ans m’a demande si je serai la, a ses 18 ans, j’ai repondu « oui bien sur, mon cheri », mais au fond de moi, je sais bien que ce n’est pas vrai… Ou encore cette conversation a trois : SMS : bonjour, comment vas-tu, j’espere que tu ne souffres pas trop ? MOI : voila, ils imaginent que j’ai ete operee… LUI : « tu leur a dit quoi avant de partir ? » MOI « rien, ce n’est pas si grave, je serai au boulot lundi… » SMS : donne nous ton numero de fixe de ta chambre, le portable ne passe pas, MOI : si je reponds, je ne saurai pas quoi dire… un petit rien qui finit par envahir… LUI : « dis leur la verite, ce ne sera pas la revolution » MOI : « je ne peux pas, je ne l’ai jamais dit pour mon diabete… ». Conclusion Chaque texte ecrit renvoie a la personnalite du patient, a ses difficultes, a ses emotions, tres souvent a son insu. En assistant a la « representation », chacun pris par l’emotion assiste a des tranches de vie le plus souvent douloureuses. Ces ateliers permettent une veritable metacognition. Ils mettent en scene les relations du patient avec sa maladie, ses difficultes, ses emotions, ses interrogations. Au travers des textes, les soignants reconnaissent souvent le patient qui a ecrit et decouvrent mieux qui il est. Les patients quant a eux soulignent la charge emotionnelle que cette experience a engendre, cela renforce leur solidarite et leurs echanges. Ils etaient tous reserves avant de participer puis disent tous avoir eu de la chance de vivre cette experience.