Treating diabetes with islet transplantation: lessons from the past decade in Lille.

Type 1 diabetes (T1D) is due to the loss of both beta-cell insulin secretion and glucose sensing, leading to glucose variability and a lack of predictability, a daily issue for patients. Guidelines for the treatment of T1D have become stricter as results from the Diabetes Control and Complications Trial (DCCT) demonstrated the close relationship between microangiopathy and HbA1c levels. In this regard, glucometers, ambulatory continuous glucose monitoring, and subcutaneous and intraperitoneal pumps have been major developments in the management of glucose imbalance. Besides this technological approach, islet transplantation (IT) has emerged as an acceptable safe procedure with results that continue to improve. Research in the last decade of the 20th century focused on the feasibility of islet isolation and transplantation and, since 2000, the success and reproducibility of the Edmonton protocol have been proven, and the mid-term (5-year) benefit-risk ratio evaluated. Currently, a 5-year 50% rate of insulin independence can be expected, with stabilization of microangiopathy and macroangiopathy, but the possible side-effects of immunosuppressants, limited availability of islets and still limited duration of insulin independence restrict the procedure to cases of brittle diabetes in patients who are not overweight or have no associated insulin resistance. However, various prognostic factors have been identified that may extend islet graft survival and reduce the number of islet injections required; these include graft quality, autoimmunity, immunosuppressant regimen and non-specific inflammatory reactions. Finally, alternative injection sites and unlimited sources of islets are likely to make IT a routine procedure in the future.

Risk of biliary complications in bariatric surgery.

Gallstones are commonly observed after rapid weight loss, particularly after bariatric surgery. Preventive measures of gallstone formation and potential related complications are still debated. This study aimed to propose a standardized strategy according to the results of the literature. Thus, preventive measures should be determined according to patient status (evaluated clinically and by routine ultrasound) and the type of bariatric surgery. Cholecystectomy should be performed in patients with symptomatic gallstones irrespective of the planned operation, or for asymptomatic gallstones during a gastric by-pass. In other settings, ursodesoxycholic acid should be given postoperatively for 6 months.

Feminizing adreno-cortical carcinomas in male adults. A dire prognosis. Three cases in a series of 801 adrenalectomies and review of the literature.

UNLABELLED: We describe the clinical presentation, biochemical features, diagnostic criteria, clinical course and differential diagnosis in three cases of feminizing adreno-cortical carcinoma (FACC) with a review of the literature. PATIENTS: From 1970 throughout December 2003 among a series of 801 adrenalectomies, three had been performed for FACC. RESULTS: Age at presentation was 74, 63 and 23 years. Estradiol hypersecretion was observed in 3/3 patients, 17 OH progesterone was elevated in 2/3 patients and both of them had a diminution of testosterone, delta 4 androstenedione was elevated in 1/3 patients. Imaging studies suggested malignancy in 3/3 patients by the presence of necrosis, heterogeneity, calcifications, size of the tumor and compression of adjacent organs. All patients were stage III at presentation and had a Weiss score >or=6. Size and weight of the tumors were 30, 20, 15cm and 3750, 480 and 275g respectively. All 3 patients received mitotane and cortisone post-operatively and at follow up (7, 3 and 2 years) all 3 died of the disease. CONCLUSIONS: Feminizing adreno-cortical carcinomas in adults are exceedingly rare (1-2% of adreno-cortical carcinomas). Tumors are huge and even after surgery for cure their prognosis is worse than for other varieties of adreno-cortical carcinomas either secreting or non secreting. Early diagnosis and treatment may improve overall prognosis.

Advantages to using capillary blood beta-hydroxybutyrate determination for the detection and treatment of diabetic ketosis.

Ketone body determination is indicated in all diabetic patients when the risk of ketotic decompensation exists. New methods of screening for ketosis, in particular capillary blood ketone body determination, provide analytical, technical and clinical advantages compared to the conventional ketonuria. It is proposed that a diabetic patient with hyperglycaemia (capillary blood glucose > 2.50 g.l(-1)) and capillary blood ketone bodies exceeding 0.5 mmol.l(-1) requires therapeutic management. For values greater than 3 mmol.l(-1) or in case of more serious clinical symptoms, hospitalisation is indicated, considering the high probability of ketoacidotic decompensation. The advantages of capillary blood ketone body determination including easy use, and rapid and objective results may improve management of the diabetic patient, especially in emergency situations. However, prescription by a physician of capillary blood ketone body determination should be offered to targeted populations that have a high risk of ketoacidotic decompensation, after providing education to patients that is above all aimed at preventing this metabolic complication. In this context of determining ketone bodies in capillary blood, the term "capillary blood ketone bodies" is therefore preferable to the term "capillary blood beta-hydroxybutyrate determination". Indeed, it appears more appropriate, simple, descriptive and significant both for health-care staff and for patients.

Blood glucose changes and adjustments of diet and insulin doses in type 1 diabetic patients during scuba diving (for a change in French regulations).

OBJECTIVE: In France, diabetic subjects were not allowed to dive. The principal risk is hypoglycemia during immersion. However scuba diving is allowed in many countries. To follow blood glucose changes, food intake and insulin adjustments in type 1 diabetic patients when diving, and to propose specific guidelines for such patients willing to practice recreational scuba diving. METHODS: Fifteen well-controlled (mean HbA1c: 7.2%) type 1 diabetic patients without complications were volunteer to dive under strict medical monitoring. They dove 8 times in 4 days in autumn at a depth of 20 meters, in 12 degrees C to 16 degrees C water. A strict protocol based on blood glucose was implemented to prevent hypoglycaemia. RESULTS: No case of hypoglycemia was observed and no faintness was reported underwater. Mean blood glucose before diving was 200 mg/dl (11 mmol/l). There was a mean fall in blood glucose of 40 mg/dl (2.2 mmol/l) during dives, a mean decrease in daily insulin doses by 19.3% on the last day. Daily energy intake was 3,225 Kcal in average. A continuous glucose monitoring (CGMS) was performed in one patient and showed a rather stable glycemia during immersion but a decrease within the 8 hours after. CONCLUSION: When respecting a strict protocol to prevent hypoglycaemia, the risk of hypoglycaemia appears quite low. We recommend an ideal glycemic goal of 200-250 mg/dl (11-13.75 mmol/l) before immersion, a higher reduction of insulin doses (-30%) and taking carbohydrates on board in any case. The present data have recently led the French diving federation (FESSM) to allow type 1 diabetic patients to dive with some restrictive qualification requirements: dives within the "safety curve" (no decompression curve), in above 14 degrees C water, depth limited to the median space range (6 to 20 meters), plus mandatory guidance by a diving instructor.

[Education for chronic cardiologic diseases in a transversal multidisciplinary unit: the experience of a general hospital center]. / Education des maladies chroniques en cardiologie au sein d'une unité transversale d'éducation multidisciplinaire: expérience d'un centre hospitalier général.

Treatments for congestive heart failure, hypertension and cardiovascular risk have significantly changed and have become more complex. The have also become more and more effective thanks to the results of great clinical studies that have enabled European and North-American societies to issues recommendations. The observance of the pharmacological and non-pharmacological treatments requires the education of patients and their family following guidelines that have been clearly defined by the European Society of Cardiology. This education, in which the technic of communication is very important, is common to a lot of chronic diseases and requires adequate material and human resources in order to have an optimal quality of treatment. In a society in which spending is on rise, getting such resources is not easy. However, putting in common resources of several departments can be a good solution. The experience of the Hospital Center of Douai (France) lead to the creation of a Transversal Education Unit at the end of the year 2003. This unit centralizes the efforts of several departments of care like pneumology, pediatrics, diabetology, nutrition and cardiology and allows patients suffering from co-morbidities to have access to various programs of this unit.

Efficacy and tolerance of calcium alginate versus vaseline gauze dressings in the treatment of diabetic foot lesions.

BACKGROUND: The study aimed at comparing the efficacy and tolerance of an alginate wound dressing with a vaseline gauze dressing in the treatment of diabetic foot lesions. METHODS: This open-label randomized multicenter controlled study was designed to assess the effect of an up to 6-week treatment with either calcium alginate or vaseline gauze dressings. Lesions were either acute or chronic, under cleansing, and with a surface area of 1-50 cm(2); osteomyelitis and severe hypovascularization were non-inclusion criteria. Dressings were changed every day then, once granulation had occurred, every 2 to 3 days. Primary outcome was the proportion of patients with granulation tissue over 75% of the wound area and having a 40% decrease in wound surface area; secondary outcomes were pain on dressing changes, the number of dressing changes, and adverse events. RESULTS: Seventy-seven patients were enrolled. Due to the premature cessation of treatment in 13 patients, it was decided to reduce the period of the efficacy analysis to 4 weeks (without revising the criteria of efficacy). The success rate was of 42.8% in the calcium alginate group and of 28.5% in the vaseline gauze group (not significant difference). A subsequent analysis of granulation tissue surfaces covering the wounds at week 4 (all surfaces taken together) showed a superiority of calcium alginate (p=0.04). Pain on dressing change was lower in the calcium alginate group (p=0.047) and the total number of dressing changes tended also to be lower (p=0.07). Adverse events, which occurred 4 times in the calcium alginate group and 6 times in the other, were judged independent of the treatments. CONCLUSIONS: As compared with vaseline gauze, calcium alginate appears to be more appropriate for topical treatment of diabetic foot lesions in terms of both healing and tolerance.

In vivo glucosylated LpA-I subfraction. Evidence for structural and functional alterations.

This study compared the structural and functional properties of glucosylated and non-glucosylated LpA-I particle subfractions (GLpA-I and NGLpA-I, respectively) isolated from patients with poorly controlled type 1 (insulin-dependent) diabetes. Compared with NGLpA-I, GLpA-I showed an enrichment in triglycerides (P < .05) and a depletion in phospholipid (P < .05) content. Moreover, the triglycerides-to-cholesteryl esters ratio was increased (P < .05), suggesting an increased cholesteryl ester transfer protein activity and a possible transport defect that accelerates atherogenesis. The surface-to-core constituents ratio, an indirect estimate of particles size, is lower in GLpA-I (P < .01) than in NGLpA-I, correlating well with a larger median size (P < .05) as seen by electron microscopy. The apolipoprotein (apo) A-I conformation was evaluated through determination of the immunological accessibility of three different domains defining specific epitopes for anti-apo A-I monoclonal antibodies. We observed a marked decreased accessibility for two of these regions, which interestingly have already been implicated in the interaction with cells. Cell culture data suggest that nonenzymatic glycosylation occurring on apo A-I can modify lipoprotein function, since it results in a decreased binding of GLpA-I to HeLa cells and impaired cholesterol efflux from Fu5AH rat hepatoma cells.

[Hyperthyroidism associated with pulmonary hypertension]. / Hyperthyroïdie associée à une hypertension artérielle pulmonaire.

The association of pulmonary hypertension and polyendocrinopathies or connective tissue diseases has been reported by several authors. The causes of this form of pulmonary hypertension are not clear but an autoimmune process has often been proposed. The authors report a case of non-autoimmune hyperthyroidism and reversible pulmonary hypertension after total thyroidectomy and normalisation of thyroid function. This case supports the hypothesis of a non-autoimmune aetiology of some causes of pulmonary hypertension in diseases of the thyroid.

Apo B-containing lipoprotein particles in poorly controlled insulin-dependent diabetes.

The goal of this study was to compare the structural and biological characteristics of apolipoprotein (apo) B-100-containing particle subfractions isolated from poorly controlled diabetic patients with insulin-dependent diabetes (IDDM), and healthy controls matched for sex, age and body mass index (BMI). Different apo B-containing particles were isolated by sequential immunochromatography and were free of apo A-I, apo A-II, apo A-IV and apo(a). Particles lipoprotein (Lp) B/C-III contained apo B and apo C-III. They were free of apo E. Particles Lp B/E contained apo B and apo E. They were free of apo C-III. Particles Lp B were devoided of apo C-III and apo E. All these particles could contain other known apolipoproteins not cited here, as for example apo C-II and/or apo C-I. The plasma levels of cholesterol, triglycerides, phospholipids, apo A-I, B-100, C-III, E, total Lp B/C-III, total Lp B/E were not different between patients and controls. The physico-chemical properties of Lp B/C-III and Lp B/E were similar in both groups. Only Lp B from patients exhibited some changes, an increase in the size and a decrease in the cholesterol and cholesteryl ester levels. The conformational properties of the lipoproteins were studied through their immunoreactivity against four different anti-apo B-100 monoclonal antibodies (MAb) for which sequential epitopes have been located on the protein, and one MAb for which the epitope is conformationally expressed. Again, minor changes were observed between patients and controls, and only a slight decrease in the immunoreactivity of the epitope encompassing amino-acid residues 405 to 539 of Lp B and of the conformationally expressed epitope of Lp B/C-III were found in patients. Nevertheless, whatever these conformational and/or physico-chemical modifications may be, they were not sufficient to induce functional alterations in the binding of the particles from the patients to the LDL-receptor of HeLa cells. This study shows that IDDM is not associated with any significant abnormalities in the apo-containing lipoprotein particles. The excessive occurrence of coronary heart disease (CHD) and other atherosclerotic vascular disease in patients with IDDM must have other causes.

Non-enzymatic glycosylation of apolipoprotein A-I and its functional consequences.

High-density lipoproteins (HDL) are believed to protect against atherosclerosis by promoting the process of reverse cholesterol transport. This process involves different steps including efflux of cellular cholesterol, cholesterol esterification and lipid transport and exchange. Apolipoprotein (apo) A-I, the major HDL apolipoprotein, and the HDL-associated enzyme lecithin-cholesterol acyltransferase (LCAT), which uses apo A-I as a cofactor, play a crucial role in reverse cholesterol transport. HDL may be classified into species according to their apolipoprotein content. Recent data concerning HDL particles indicate that lipoproteins containing apo A-I but not apo A-II (LpA-I) are more effective carriers of free cholesterol and are associated with a protective effect against coronary heart disease. In vitro studies have shown that glycosylated HDL are functionally abnormal and may be considered atherogenic. Our study considers the different impacts of non-enzymatic glycosylation of apo A-I or protein-HDL on the reverse cholesterol transport process.