Project description:Introduction:Bariatric surgery profoundly improves type 2 diabetes (T2D); however, the specific mechanisms linking distinct procedures to metabolic benefits through bile acid (BA) remodeling remain incompletely understood. This study investigates the differential effects of single-anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) compared to sleeve gastrectomy (SG) on BA profiles and their correlation with metabolic outcomes in T2D. Methods:Male Wistar rats with T2D underwent SADI-S, SG, or sham operation. Metabolic parameters, including fasting blood glucose, HbA1c, glucagon-like peptide-1 levels, triglycerides, gut microbiota composition, and comprehensive serum/faecal BA profiles, were assessed five weeks post-surgery. Statistical analyses included t-tests and Pearson correlations, with false discovery rate correction applied. Results: Both SADI-S and SG significantly ameliorated hyperglycemia, dyslipidemia, and β-cell integrity compared to sham operation, with SADI-S demonstrating superior efficacy. SADI-S induced a more pronounced elevation of portal serum BAs (34 vs. 25 species in SG), including key regulators such as chenodeoxycholic acid and lithocholic acid. Critically, multiple elevated serum BAs (e.g., chenodeoxycholic acid, lithocholic acid, glycoursodeoxycholic acid) exhibited strong negative correlations with fasting blood glucose, HbA1c, and triglycerides, while positively correlating with glucagon-like peptide-1 levels. Shifts in gut microbiota correlated with specific BA changes, supporting a 'microbiota-BA-metabolism' axis. Conclusions：SADI-S and SG induce distinct, surgery-specific BA remodeling that is significantly associated with metabolic improvements in T2D. The robust correlations between specific BA species and metabolic parameters underscore their potential as mediators and therapeutic targets. SADI-S promotes a more extensive and beneficial BA profile, aligning with its superior metabolic efficacy.

Project description:Type 1 diabetes mellitus (T1DM) results from immune mediated destruction of pancreatic beta cells. However, clinical and immunologic phenotypes of T1DM are variable. Several auto-antibodies including GADA, IA-2A, and ZnT8A, were identified in T1DM, but the prevalence of these auto-antibodies varied for a broad spectrum of T1DM. Here, we systemically profiled auto-antibodies from serum samples of 16 T1DM, 16 type 2 diabetes (T2DM) patients, and 27 healthy controls with normal glucose tolerance (NGT) using protein microarrays containing 9,480 proteins. Among 9,480 different proteins on the array, we identified novel auto-antibody candidates (EEF1A1-AAb and UBE2L3-AAb) by M-test coupled with PLS-DA. These auto-antibodies were highly present in T1DM than controls and detected in 40% of T1DM without GADA. Furthermore, these auto-antibodies might help to differentiate subtype of T1DM when combined with GADA. These novel auto-antibodies provide new diagnostic information of T1DM, as well as new insights into the pathogenesis of T1DM. Auto-antibodies from serum samples were profiled using a high-density, fluorescence-based protein microarray containing duplicate spots of 9,480 human proteins derived from the Ultimate ORF collection The cohort of patients and controls consisted of 16 T1DM, 16 T2DM patients, and 27 healthy controls with NGT. This cohort was used to screen candidate auto-antibodies using protein microarrays (ProtoArray platform version 5.0, Invitrogen Corp., Carlsbad, CA). Serum samples were drawn from T1DM patients who have 1) fasting C-peptide level <0.3 nmol/L or serum C-peptide <0.6 nmol/L after glucagon loading, 2) initiation of insulin treatment within six months after diagnosis, and 3) duration of diabetes M-bM-^IM-$12 months. Mean age of T1DM in the first cohort was 42 M-BM-1 16 years. The control serum samples were obtained from T2DM patients who were treated only with oral anti-diabetic drug at least 5 years and from NGTs who had no history of diabetes, no first-degree relatives with diabetes, a fasting plasma glucose concentration of <6.1 mmol/l, and a HbA1c value of <5.8%.

Project description:Background & Aims: Bariatric surgery is associated with improved outcomes in subjects with severe obesity. We aimed to determine the prognostic relevance of liver histology in a large cohort of obese patients undergoing bariatric surgery. Methods: In a single center cohort of 492 subjects undergoing Roux-en-Y gastric bypass bariatric surgery with routine perioperative liver biopsy at Geneva University Hospital between January 1997 to December 2004, clinical and histopathological variables were analyzed for association with overall survival. Survival of the cohort was compared to age- and sex-matched life tables from the Swiss general population and propensity score-matched subjects from the third National Health and Nutrition Examination Survey (NHANES III). A 32-gene signature was evaluated in the liver tissue of 47 non-alcoholic steatohepatitis (NASH) subjects. Results: Median body mass index was 43.6 kg/m2. Twenty-one patients (4.2%) died during a median follow-up of 10.3 years. At baseline liver histology, 12% and 16% of subjects had NASH, and fibrosis, respectively. In multivariable Cox regression, presence of NASH (hazard ratio [HR] 3.4, p=0.0087), age greater than 50 years (HR 2.7, p=0.044), hypertension (HR 3.8, p=0.021), and short-term postoperative complications (HR 2.8, p=0.048) were associated with overall survival. Compared to matched NHANES III subjects, bariatric surgery improved long-term survival (HR 0.54, p=0.035), although this benefit was not observed in the subgroup of NASH patients (HR 0.97, p=0.94). A 32-gene poor prognosis signature prediction was associated with worse overall survival within NASH subjects (n=47, HR = 7.7, p=0.03 ). Conclusions Histologically proven NASH was associated with increased long-term mortality in subjects undergoing bariatric surgery. Although survival benefit of bariatric surgery may be limited in obese patients with NASH, a 32-gene expression signature appears to predict long term mortality in these patients.

			Action	DRS
	1201-105.raw.zip	Raw
	0227-10.raw.zip	Raw
	_FUNC001.CMP	Other
	_FUNC001.DAT	Other
	_FUNC002.CMP	Other

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Hyocholic acid species as novel biomarkers for metabolic disorders

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Hyocholic acid species as novel biomarkers for metabolic disorders.

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