Bernard Vialettes

Low Plasma Levels of Pancreatic Polypeptide in Obesity

Plasma levels of pancreatic polypeptide (PP) were studied in a group of 22 normal and 22 obese subjects after an overnight fast. In a second group of 10 normal and 13 obese adults, PP secretion was stimulated by a protein-rich meal. The results indicate lower fasting PP values in the obese subjects and a decreased response during the second phase of the meal-induced secretion. This could suggest a possible role of PP in obesity.

Pulmonary autoimmunity as a feature of autoimmune polyendocrine syndrome type 1 and identification of KCNRG as a bronchial autoantigen

Patients with autoimmune polyendocrine syndrome type 1 (APS-1) suffer from multiple organ-specific autoimmunity with autoantibodies against target tissue-specific autoantigens. Endocrine and nonendocrine organs such as skin, hair follicles, and liver are targeted by the immune system. Despite sporadic observations of pulmonary symptoms among APS-1 patients, an autoimmune mechanism for pulmonary involvement has not been elucidated. We report here on a subset of APS-1 patients with respiratory symptoms. Eight patients with pulmonary involvement were identified. Severe airway obstruction was found in 4 patients, leading to death in 2. Immunoscreening of a cDNA library using serum samples from a patient with APS-1 and obstructive respiratory symptoms identified a putative potassium channel regulator (KCNRG) as a pulmonary autoantigen. Reactivity to recombinant KCNRG was assessed in 110 APS-1 patients by using immunoprecipitation. Autoantibodies to KCNRG were present in 7 of the 8 patients with respiratory symptoms, but in only 1 of 102 APS-1 patients without respiratory symptoms. Expression of KCNRG messenger RNA and protein was found to be predominantly restricted to the epithelial cells of terminal bronchioles. Autoantibodies to KCNRG, a protein mainly expressed in bronchial epithelium, are strongly associated with pulmonary involvement in APS-1. These findings may facilitate the recognition, diagnosis, characterization, and understanding of the pulmonary manifestations of APS-1.

Pancreatic Regenerating Gene Overexpression in the Nonobese Diabetic Mouse During Active Diabetogenesis

The reg gene has previously been shown to be associated with regeneration of pancreatic islets. Strategies for influencing the replication and the growth of the β-cell mass may be important for prevention and/or treatment of type I diabetes. In this study, we have examined the level of reg gene expression at various degrees of diabetogenesis in the pancreas of the NOD mouse (male, female, and cyclophosphamide-treated male) using both human reg cDNA as the probe and dot blot analysis. The expression of the reg gene was found to be significantly increased in female mice compared with male mice, and in both cases, the expression level was not influenced by age. Nondiabetic female mice have a significantly higher expression of the gene than diabetic female mice, and there was a positive correlation between the age of diabetes onset and the reg mRNA level. In addition, overexpression of the reg gene was found in male mice treated by cyclophosphamide, an agent known to be a potent inducer of diabetes in male NOD mice. None of these results were found in the diabetes-resistant control OF1 mice, in which pancreatic reg gene expression did not differ between female and male mice treated or untreated with cyclophosphamide. All of these data suggest that there is a strong correlation between reg gene expression in the pancreas of the NOD mouse and the likelihood of developing diabetes.

Obesity and diabetes.

Summary and ConclusionsFat mass per se has little effect on the progression of obesity towards diabetes. Predominance of fat in the upper part of the body resulting in android obesity is at least the clinical reflection of factors which lead obesity to progress towards diabetes and atherosclerosis. Therefore this type of obesity may be termed diabetogenic and atherogenic obesity. Insulin and cortisol secretion in obesity are not correlated with body fat but with the predominance of fat in the upper part of the body. Diabetogenic obesity may evolve through 5 stages from initial obesity without diabetes to insulin-dependent diabetes in previously obese subjects. Aside from the characteristics of body fat distribution, the mechanisms which induce or interrupt this progression remain unknown.

Specific adipocytokines profiles in patients with hyperactive and/or binge/purge form of anorexia nervosa

Objective:The aim of our study was to determine whether eating behaviors and/or physical activity level may explain contradicting results in adipocytokines levels in anorexia nervosa (AN).Subjects/Methods:Fasting levels of circulating adipocytokines (adiponectin, resistin and leptin), insulin, glucose, C-reactive protein, cytokines (tumor necrosis factor-α and interleukin (IL)-1β), body composition and resting energy expenditure were measured in 24 women AN patients and 14 women controls. These parameters were compared according to AN subtypes: 15 patients with restrictive (R-AN) form versus 9 patients with binge/purge (BP-AN) form; 15 patients with hyperactive (H-AN) form versus 9 patients with nonhyperactive (NH-AN) form.Results:BP-AN patients had significantly higher serum adiponectin levels compared with R-AN patients (P<0.05), and H-AN patients had higher serum leptin and lower serum resistin levels compared with NH-AN patients (P<0.05 for both).Conclusions:Our study shows specific adipocytokines profiles depending on the subtype of AN: restrictive versus binge/purge and hyperactive versus Nonhyperactive forms. We suggest that these biological signatures could interfere with the outcome of the disease.

Scleredema adultorum of Buschke: an under recognized skin complication of diabetes

Scleredema of Buschke or scleredema diabetorum is a skin complication of diabetes with deposits of collagen and aminoglycans in the dermis. This disease characterized by thickening and hardening of the skin, is usually localized in nape, back and shoulder areas. Consequences could be a decrease in motility of the shoulders and an impairment of respiratory function. Other possible complications are sleep apnoea syndrome and monoclonal gammapathy. Type 1 or type 2 diabetes may be associated with scleredema of Buschke in more than 50% of cases. Diabetes-related risk factors are long duration of the disease, presence of microangiopathy, overweight and need of insulin. Various specific treatments proposed in the literature are poorly validated. In most severe cases, radiation therapy may be useful.

Immunogenicity of Long-Term Intraperitoneal Insulin Administration With Implantable Programmable Pumps: Metabolic consequences

OBJECTIVE To assess immunogenicity of intraperitoneal insulin infusion via implanted pumps by two methods and to evaluate the possible influence of an increased antibody level on metabolic and clinical parameters. RESEARCH DESIGN AND METHODS We studied insulin antibody levels in 17 type I diabetic patients before and until 24 months after implantation of a programmable pump delivering insulin intraperitoneally. Antibody levels were determined by radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA). They were correlated with HbA1c, insulin requirements, free insulin, and the incidence of hypoglycemia. RESULTS Insulin antibodies increased as soon as the 3rd month after implantation. This increase was sustained throughout the study period (month 0, 25.4 ± 16.2%; month 3, 41.2 ± 23.5%; month 12, 45.9 ± 26%; month 24, 48.7 ± 25%). The data was correlated with the two assay methods (RIA and ELISA). Postimplantation level was correlated with preimplantation level, which could indicate a predictive value of the latter. No correlation was observed with any metabolic parameters, particularly the number of hypoglycemic episodes. CONCLUSIONS Our results indicate that intraperitoneal insulin administration by implantable programmable pumps leads to an increase of insulin antibodies, which are probably high-affinity antibodies (recognized by both RIA and ELISA). This increase in insulin immunogenicity did not induce significant metabolic consequences, which is reassuring for the future of programmable insulin pumps.

Significant lower VVH7-like immunoreactivity serum level in diabetic patients: Evidence for independence from metabolic control and three key enzymes in hemorphin metabolism, cathepsin D, ACE and DPP-IV

Low circulating VVH7-like immunoreactivity (VVH7 i.r) level was amazingly observed in human diabetic sera. Here, we examined the impact of diabetes type, clinico-biological features and metabolic control on circulating VVH7 i.r level in this disease. ELISA test was used to measure VVH7 i.r in sera of 120 diabetic patients (type 1 diabetes in 64, type 2 diabetes in 56). Three enzymatic tests were also applied to determine serum cathepsin D (CD), dipeptidyl peptidase IV (DPP-IV) and angiotensin-converting enzyme (ACE) activities. A subgroup of 24 type 1 diabetic patients negative for microalbuminuria and hypertension were submitted to an ambulatory blood pressure monitoring to evaluate the relationship between VVH7 i.r level and blood pressure parameters. The mean serum concentration of VVH7 i.r was drastically reduced in diabetic patients (0.91+/-0.93 micromol/l versus 5.63+/-1.11 micromol/l in controls) (p<0.001). A negative correlation between VVH7 i.r level and daytime diastolic blood pressure existed in type 1 diabetic patients. There was no association of low VVH7 i.r with either type of diabetes or HbA1c level. An increase of cathepsin D activity was found in serum of diabetic patients compared to controls (0.47 U/ml versus 0.15 U/ml, respectively) whereas DPPIV activity was significantly decreased in diabetic sera (50.81 U/ml versus 282.10 U/l respectively). Diminution of VVH7 i.r in sera of diabetic patients was confirmed but still remained unexplained. Relationships between higher systolic blood pressure and decrease of VVH7 i.r reinforce the need to investigate this pathway in this disease to elucidate its role in macro- and micro-angiopathy.

The Impact of Weight Normalization on Quality of Recovery in Anorexia Nervosa

Background: There is little agreement on what constitutes remission in anorexia nervosa. Objective: This study compared the medical, psychological, and social status of 2 female populations previously treated for anorexia nervosa and differing in their achievement of normal weight. Design: One hundred forty-one patients responded to a questionnaire documenting morphometric parameters, subjective perception of outcome, concerns about body shape and diet, and quality of familial, emotional, and professional life. Two groups were defined according to body mass index (BMI): normal (n u200a=u200a 69) with BMI ≥ 18.5 kg/m2, and subnormal (n u200a=u200a 72) with BMI < 18.5 kg/m2. In addition, subgroups (21 in each category) were interviewed. An age-matched control population composed of 156 women, either students or Health Services employees, responded to a similar questionnaire. Results: Only a minority of patients assessed themselves as recovered, and there was no statistically significant difference in perception of recovery between normal BMI and subnormal BMI groups (27.5% and 15.3%, respectively). As expected, underweight patients reported significantly more frequent purging behaviors, amenorrhea, recent hospitalization, and prolonged student status. In contrast, there were no significant differences in terms of pregnancy rate, psychiatric comorbidities, social integration, sexual activity, and self-assessment of professional and familial life. In comparison to control subjects, former anorexia patients with normalized BMI more frequently reported vomiting, fear of high-calorie foods, and treatment for depression. Conclusions: These few long-term advantages observed after BMI normalization suggest that normalization of nutritional status remains an important target in anorexia nervosa. However, the persistence of psychological distress after nutritional recovery confirms that more effective treatments are needed that target long-term psychological recovery.

Aggressive multimodal therapy of sporadic malignant insulinoma can improve survival: a retrospective 35-year study of 12 patients.

AIMnSporadic malignant insulinoma (SMI) is a rare disease, and the consequent paucity of data in the literature and the development of aggressive treatments for liver metastases have led us to retrospectively analyze a series of 12 cases of SMI.nnnMETHODSnEvery patient presenting with SMI, according to the WHO 2004 histopathology criteria, between 1970 and June 2005 in Marseille was included in the study. Patients with multiple endocrine neoplasia type 1 (MEN-1) and tumours of uncertain malignant potential were excluded.nnnRESULTSnThe ratio of male/female was 4/8, and mean age at diagnosis was 52.5 years. A 48-h fasting test in 10 patients was conclusive in nine, after a mean duration of 12 h 45 min. SMI size ranged from 7-120 mm (mean 30.3mm). Six patients had liver metastases and one had isolated lymph-node invasion. Surgery was performed in 12 patients. Five persisting diseases (mean follow-up of 1.8 years) required other treatments (chemoembolization, radiofrequency thermoablation [RFTA], liver transplantation); one patient relapsed 8.5 years after surgery; six were still in complete remission (mean follow-up of 5.8 years), and one patient had died by the time of the 24-month follow-up.nnnCONCLUSIONnAggressive sequential multimodal therapy can prolong the survival of patients with SMI even in the presence of liver metastases.