Cluster analysis of an insulin-dependent diabetic cohort towards the definition of clinical subtypes

Clinical and biochemical data on 111 consecutive insulin-dependent diabetic children enrolled in a longitudinal prospective study were analyzed to determine if more than one clinical expression of Type I diabetes exists. Use of multivariate statistical methods, including Correspondence Analysis, kappa-means clustering and RECPAM (RECursive Partition and AMalgamation), show that there are two well differentiated clinical expressions of IDDM each characterized by a cluster. One is characterized by later age, less severe onset, longer symptom duration, less beta-cell disappearance after 12 months, more females; the other by earlier age, more sudden and severe onset, DR 3/4, earlier disappearance of beta-cell function and more males. RECPAM analysis provides further insight into the structure of the two clusters. An other RECPAM tree identifies low, medium and high risk groups of disappearance of beta-cell function at 12 months after diagnosis.     

Islet cell surface and lymphocyte antibodies often precede the spontaneous diabetes in the BB rat

Summary The diabetic syndrome of the BB rat shows many homologies with that of human insulin-dependent diabetes and evidence that the onset of the disease is associated with the presence of autoantibodies, including islet cell surface antibodies. In this study, sera were sampled serially from weaning to 157 days of age from 26 BB rats in two low-incidence litters, and 22 rats of three high-incidence litters. Clinical and metabolic variables were monitored concurrently with blood lymphocyte counts. Islet morphology was correlated at sacrifice. In the high-incidence litters, eight rats developed insulin-dependent diabetes, five impaired glucose tolerance, and the remaining nine all showed insulitis. In the low-incidence litters, only one animal showed impaired glucose tolerance and another insulitis. In the high-incidence litters 16 rats (73%) had islet cell surface antibodies compared with 4 out of 26 (15%) low-incidence controls (p<0.002). Antibodies reactive with Wistar rat spleen lymphocytes were present in all high-incidence rats compared with 19% (5 out of 26) among the control litters (p<0.002). Time courses of islet cell surface and lymphocyte antibody appearance and their peak values varied, but already at weaning the levels of both antibodies were increased among the high-incidence litter rats (p< 0.001). Islet cell surface and/or lymphocyte antibodies were therefore present in the majority of animals at an age where neither morphological nor metabolic evidence of the diabetic syndrome were yet detected. All rats that showed any form of the syndrome were lymphopenic. These findings suggest that BB rats have an abnormal immune response which predisposes to later development of insulin-dependent diabetes, often preceded by the presence of islet cell surface and/or lymphocyte antibodies.     

Minimally Invasive Endogastric Removal of Migrated Gastric Band After Endoscopic Failure: How I Do It

Intragastric band migration is a rare and late complication of laparoscopic -adjustable gastric banding and should be recognized by all digestive surgeons. Endoscopic removal is most commonly performed, but surgery is an alternative in cases of endoscopic failure. Many different procedures have been reported. We show here (see Video) a fully laparoscopic endogastric procedure through two 5-mm antral gastrotomies. This technique can also be used to remove benign endogastric tumors. The procedure is safe and provides a large endogastric operative area, with no particular morbidity. Endogastric removal through a fully laparoscopic approach should be considered as the first alternative to endoscopic approach.     

Arginine-induced glucagon secretion in the spontaneously diabetic BB Wistar rat

The spontaneously diabetic BB Wistar rat shows many characteristics analogous to human insulin-dependent diabetes (IDDM). These include inappropriately normal immunoreactive glucagon in the presence of hyperglycemia, absolute hyperglucagonemia with severe ketosis, and hyperresponsiveness to exogenous arginine in vivo. We used an in situ pancreas preparation to further study portal vein glucagon responses to intravenous arginine. In normal rats, magnitude of response was correlated with prestimulation levels. Basal levels were significantly increased in hyperglycemic diabetics compared to controls, but responses to arginine were attenuated in both absolute and relative terms. Comparisons of responses with poor and good prior diabetes control showed no significant differences. Thus, a further anomaly of glucagon secretion has been identified in these rats.     

A unique subset of self-specific intraintestinal T cells maintains gut integrity

Lymphocytes residing in the intestinal epithelium are exclusively T cells and account for one of the largest collection of T cells in the organism. However, their function remains obscure. We and others have shown that the development of intestinal intraepithelial T cells is compromised in mutant mice prone to chronic intestinal inflammation. These results led us to directly assess their role in regulating the development of colitis secondary to transfer of primary splenic TCRalphabeta(+)CD4(+)CD45RB(hi) T cells into severe combined immunodeficiency (SCID) mice. Here we demonstrate that prior reconstitution of SCID recipients with intraintestinal TCRalphabeta(+)CD4(-)CD8alpha(+)beta(-) T cells prevents disease, and does so in an interleukin (IL)-10-dependent fashion. In contrast, reconstitution with either TCRgammadelta(+) or TCRalphabeta(+)CD4(-) CD8alpha(+)beta(+) intestinal T cells did not prevent colitis. TCRalphabeta(+)CD4(-)8alpha(+)beta(-) T cells are unique to the intestinal epithelium of both rodents and humans. Previous repertoire analyses of TCRalphabeta(+)CD4(-)CD8alpha(+)beta(-) T cells revealed a high proportion of cells expressing high affinity, self-specific TCR within this subset. We demonstrate that monoclonal, self specific TCRalphabeta(+)CD4(-)CD8alpha(+)beta(-) cells derived from TCR transgenic mice also prevent the onset of colitis. Thus, intestinal TCRalphabeta(+)CD4(-)CD8alpha(+)beta(-) T cells, selected based on their self-reactivity, maintain gut integrity in a IL-10-dependent fashion.     

Protein-free diets do not protect high-incidence diabetes-prone BioBreeding rats from diabetes

Dietary factors have been reported to affect the development of spontaneous diabetes in various colonies of inbred and outbred diabetes-prone (DP) BioBreeding (BB) rats. Several studies have attributed a protective effect to a diet omitting crude protein mixtures in favor of purified casein, hydrolyzed casein, or free amino acids. We have used inbred BB rats, all of which become diabetic in specific pathogen-free (SPF) conditions when fed ordinary rat chow, to test the capacity of 2 different protein-free diets to modulate BB rat diabetes in 2 distinct pathogen-free environments. BB rats known to all develop diabetes by 100 days of age were fed from birth with 1 of 3 diets. By 120 days of age, 100% of the animals on a standard diabetogenic chow diet, 83% of animals on an amino acid-based protein-free diet, and 100% of animals on a hydrolyzed casein-based diet had developed diabetes (P >.05). A slight delay in the age of onset was observed among rats fed the amino acid-based diet, but this delay coincided with a reduction in weight gain among these animals compared with the rats on a standard diet. Histology showed insulitis in all rats at either diabetes onset or 120 days of age. We conclude that our unique strain of specific pathogen-free BB rats are not protected from diabetes when fed an amino acid-based diet and suggest that their insensitivity to dietary manipulation may be due to an as yet unknown factor present in the diabetes-resistant (DR), but not the DP BB rat genetic background.     

Specific phenotype associated with diabetes mellitus secondary to chronic hepatitis C infection

Aim A link between chronic hepatitis C virus (HCV) infection, Type 2 diabetes mellitus and insulin resistance has been suggested by several studies. However, HCV infection appears to be associated with insulin resistance but not with the metabolic syndrome. The aim of this study was to determine whether chronic HCV infection had an impact on the clinical characteristics of Type 2 diabetes. Methods We studied retrospectively a group of patients with diabetes mellitus associated with HCV infection (HCV‐DM) and compared them with patients with conventional Type 2 diabetes (DM). Results The HCV‐DM patients had a lower body mass index (P = 0.001) and systolic blood pressure (P = 0.04) compared with patients with DM diabetes. Ten patients (27.0%) in the HCV‐DM group and 35 (47.3%) in the DM group had microalbuminuria (P = 0.04). DM patients had significantly higher serum creatinine levels than HCV‐DM patients [87 (72–108) vs. 77 (64–86) µmol/l, P = 0.02; median (interquartile range)] but creatinine clearance (Cockroft Gault calculation) was similar. One HCV‐DM patient (2.7%) and 44 DM patients (59.4%) were treated with hypolipidaemic therapy (P = 0.0001). Even although nearly two‐thirds of the overall DM group were prescribed cholesterol‐lowering drugs, DM patients had significantly higher total cholesterol, high‐density lipoprotein cholesterol and triglyceride levels than HCV‐DM patients. Conclusion Our study provides further evidence that HCV‐DM patients have specific clinical characteristics in comparison with classical DM patients. These data suggest an association between HCV virus infection and the development of insulin resistance or diabetes mellitus without the typical features of the metabolic syndrome.