Endoscopic Duodenal–Jejunal Bypass Liner Rapidly Improves Type 2 Diabetes

Background

Bariatric procedures excluding the proximal small intestine improve glycemic control in type 2 diabetes within days. To gain insight into the mediators involved, we investigated factors regulating glucose homeostasis in patients with type 2 diabetes treated with the novel endoscopic duodenal–jejunal bypass liner (DJBL).

Methods

Seventeen obese patients (BMI 30–50 kg/m²) with type 2 diabetes received the DJBL for 24 weeks. Body weight and type 2 diabetes parameters, including HbA_1c and plasma levels of glucose, insulin, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon, were analyzed after a standard meal before, during, and 1 week after DJBL treatment.

Results

At 24 weeks after implantation, patients had lost 12.7?±?1.3 kg (p?<?0.01), while HbA_1c had improved from 8.4?±?0.2 to 7.0?±?0.2 % (p?<?0.01). Both fasting glucose levels and the postprandial glucose response were decreased at 1 week after implantation and remained decreased at 24 weeks (baseline vs. week 1 vs. week 24: 11.6?±?0.5 vs. 9.0?±?0.5 vs. 8.6?±?0.5 mmol/L and 1,999?±?85 vs. 1,536?±?51 vs. 1,538?±?72 mmol/L/min, both p?<?0.01). In parallel, the glucagon response decreased (23,762?±?4,732 vs. 15,989?±?3,193 vs. 13,1207?±?1,946 pg/mL/min, p?<?0.05) and the GLP-1 response increased (4,440?±?249 vs. 6,407?±?480 vs. 6,008?±?429 pmol/L/min, p?<?0.01). The GIP response was decreased at week 24 (baseline—115,272?±?10,971 vs. week 24—88,499?±?10,971 pg/mL/min, p?<?0.05). Insulin levels did not change significantly. Glycemic control was still improved 1 week after explantation.

Conclusions

The data indicate DJBL to be a promising treatment for obesity and type 2 diabetes, causing rapid improvement of glycemic control paralleled by changes in gut hormones.     

Systematic Review and Meta-analysis of Enhanced Recovery After Pancreatic Surgery with Particular Emphasis on Pancreaticoduodenectomies

Background

In the past decade, Enhanced Recovery after Surgery (ERAS) protocols have been implemented in several fields of surgery. With these protocols, a faster recovery and shorter hospital stay can be accomplished without an increase in morbidity or mortality. The purpose of this study was to review systematically the evidence for implementation of an ERAS protocol in pancreatic resections, with particular emphasis on pancreaticoduodenectomies (PDs).

Methods

A systematic search was performed in Medline, Embase, Pubmed, CINAHL, and the Cochrane library for papers describing an ERAS program in adult patients undergoing elective pancreatic surgery published between January 1966 and December 2012. The primary outcome measure was postoperative length of stay. Secondary outcome measures were time to recovery of normal function, overall postoperative complication rates, readmissions, and mortality. Subsequently, a meta-analysis of outcome measures focusing on PD was conducted. This systematic review and meta-analysis was performed according to the PRISMA statement.

Results

The literature search produced 248 potentially relevant papers. Of these, eight papers met the predefined inclusion criteria: five case-control studies, two retrospective studies, and one prospective study, describing a total of 1,558 patients. Only three of the studies reported data on discharge criteria and assessed time to recovery and return to normal function. Implementation of an ERAS protocol led in four of five comparative studies to a significant decrease in length of stay (reduction of 2–6 days in different studies). Meta-analysis of four studies focusing on PDs showed that there was a significant difference in complication rates in favor of the ERAS group (absolute risk difference 8.2 %, 95 % confidence interval (CI) 2.0–14.4, p = 0.008). Introduction of an ERAS protocol did not result in an increase in mortality or readmissions. Delayed gastric emptying and incidence of pancreatic fistula did not differ significantly between groups. All studies reporting on hospital costs showed a decrease after implementation of ERAS.

Conclusions

This systematic review suggests that using an ERAS protocol in pancreatic resections may help to shorten hospital length of stay without compromising morbidity and mortality. This seemed to apply to distal pancreatectomy, total pancreatectomy, and PD. Meta-analysis was performed for those studies focusing on PD and showed that there were no differences in readmission or mortality. Morbidity rates were significantly lower for patients managed according ERAS principles.     

Impaired skeletal muscle mitochondrial function in morbidly obese patients is normalized one year after bariatric surgery

BackgroundObesity and type 2 diabetes are associated with impaired skeletal muscle mitochondrial metabolism. As an intrinsic characteristic of an individual, skeletal muscle mitochondrial dysfunction could be a risk factor for weight gain and obesity-associated co-morbidities, such as type 2 diabetes. On the other hand, impaired skeletal muscle metabolism could be a consequence of obesity. We hypothesize that marked weight loss after bariatric surgery recovers skeletal muscle mitochondrial function.MethodsSkeletal muscle mitochondrial function as assessed by high-resolution respirometry was measured in 8 morbidly obese patients (body mass index [BMI], 41.3±4.7 kg/m²; body fat, 48.3%±5.2%) before and 1 year after bariatric surgery (mean weight loss: 35.0±8.6 kg). The results were compared with a lean (BMI 22.8±1.1 kg/m²; body fat, 15.6%±4.7%) and obese (BMI 33.5±4.2 kg/m²; body fat, 34.1%±6.3%) control group.ResultsBefore surgery, adenosine diphosphate (ADP)-stimulated (state 3) respiration on glutamate/succinate was decreased compared with lean patients (9.5±2.4 versus 15.6±4.4 O₂ flux/mtDNA; P<.05). One year after surgery, mitochondrial function was comparable to that of lean controls (after weight loss, 12.3±5.5; lean, 15.6±4.4 O₂ flux/mtDNA). In addition, we observed an increased state 3 respiration on a lipid substrate after weight loss (10.0±3.2 versus 14.0±6.6 O₂ flux/mtDNA; P< .05).ConclusionWe conclude that impaired skeletal muscle mitochondrial function is a consequence of obesity that recovers after marked weight loss.     

A bivalent outer membrane vesicle-based intranasal vaccine to prevent infection of periodontopathic bacteria

Periodontal disease has become a serious public health problem, not only causing tooth loss, but also inducing chronic disorders of extra-oral organs. The present study assessed an intranasal vaccine strategy to prevent periodontal disease using outer membrane vesicles (OMVs) of two major periodontopathic bacteria, Porphyromonas gingivalis (Pg) and Aggregatibacter actinomycetemcomitans (Aa). We compared the morphology, composition, and immune activity between OMVs of Pg strain ATCC 33277 and Aa strain Y4. Aa OMVs had a smoother surface and stronger lipid A activity compared to Pg OMVs. The in vitro immune activity elicited by Aa OMVs in macrophage-like cells was remarkably stronger than that of Pg OMVs. Intranasal immunization of mice with Aa OMVs alone resulted in robust, humoral immune responses in blood and saliva. Despites the intrinsically low mucosal immunogenicity of Pg OMVs alone, using Aa OMVs as a mucosal adjuvant strongly enhanced Pg-specific immune responses, resulting in both serum IgG and salivary IgA, both of which aggregated Pg and Aa cells. Furthermore, Aa OMVs were found to be a more potent mucosal adjuvant than Poly(I:C) in the context of enhancing the production of Pg-specific IgG (especially IgG2a) and IgA. In addition, in a randomized, blinded study, mice oral challenged with Pg and Aa after intranasal immunization with Pg OMVs and Aa OMVs had significantly decreased numbers of both microorganisms compared to mock-immunized mice. Furthermore, in an intracerebral injection mouse model, there were no serious adverse effects on the brain even after administrating a dose of OMVs as same as that used for intranasal administration. Taken together, the bivalent OMV intranasal vaccine may be effective in preventing colonization of periodontopathic bacteria in the oral cavity and related systemic disorders associated with periodontal diseases.     

Retrospective comparative study of the effectiveness of bariatric surgery on 3-year outcomes in the real-world clinical setting

BackgroundBariatric surgery has shown an improvement in obesity and obesity-related disease in many clinical trials and single center studies. However, real-world data, including data from non-centers of excellence, is sparse.ObjectivesTo provide clinical outcomes of patients who underwent bariatric surgery in real-world clinical setting.SettingAcademic Institution.MethodsAdults with obesity undergoing Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and a control group (CG) between 2007 and 2019 were identified. The CG represented patients with a previous visit to a bariatric surgeon without a subsequent surgery. Cohorts were matched on age, gender, ethnicity, baseline body mass index (BMI), and presence of diabetes and hypertension. Groups were compared in terms of co-morbidities, weight loss, and chronic conditions for three years.ResultsA total of 61 313 patients were identified. From these, 14 916 RYGB and 20 867 SG patients were matched to the CG (n = 16 562). The median BMI loss three years after surgery was 28.7% (interquartile range [IQR] 20.8%–36.2%) and 20.5% (IQR 13.5%–28.6%) for RYGB and SG groups, respectively. The CG had a median BMI loss of 6.7% with IQR of 20.4% decrease to 1.78% gain. At three years postoperatively, HbA1C decreased by 13% for RYGB and 5.9% for the SG group. The probabilities of remission from diabetes, hypertension, and low high-density lipoprotein cholesterol were significantly higher among patients who had surgery compared to the CG. For both RYGB and SG, the estimated probabilities of remission were similar.ConclusionThis study shows that bariatric surgery performed in the real-world clinical setting is an effective therapy for various expressions of the metabolic syndrome with results that are comparable to randomized control trials.     

Increased expression of fatty acid binding protein 4 in preeclamptic Placenta and its relevance to preeclampsia

The aim of this investigation was to determine the expression of fatty acid binding protein 4 (FABP4) in the placenta from women with preeclampsia and normal pregnancy, and to delineate the regulatory effects on thophoblast cell by FABP4. We determined the expression of FABP4 by real-time polymerase chain reaction (PCR) for messenger ribonucleic acid (mRNA) or enzyme-linked immunesorbent assay (ELISA) and Western blotting for protein. Small interference of ribonucleic acid (siRNA) and specific FABP4 inhibitor were used to inhibit FABP4. The proliferation, migration and invasion of trophoblastic cells (Swan-71 and Jar) were evaluated with cell counting kit-8, wound-healing test and transwell analysis respectively. We found the expression of FABP4 was significantly higher in the placenta of preeclamptic women than that of women with normal pregnancy (t = 4.244, P < 0.001 for mRNA; t = 4.536, P < 0.001 for protein). FABP4 siRNA significantly reduced the proliferation of trophoblasts (P < 0.001). The specific inhibition of FABP4 inhibited the proliferation of trophoblasts in a dose-dependent manner (P < 0.001) and the inhibitory effect increased as the concentration of inhibitor increased. FABP4 siRNA and specific inhibitor significantly decreased the migration (P < 0.001) and invasion (P < 0.001) of trophoblasts. We concluded the increase in placental FABP4 expression in preeclampsia may affect the function of trophoblast, and this increase may have a role in the pathogenesis of preeclampsia.     

The role of the intestinal microbiota in the development of atopic disorders

The prevalence of atopic diseases, including eczema, allergic rhinoconjunctivitis and asthma, has increased worldwide, predominantly in westernized countries. Recent epidemiological studies and experimental research suggest that microbial stimulation of the immune system influences the development of tolerance to innocuous allergens. The gastrointestinal microbiota composition may be of particular interest, as it provides an early and major source of immune stimulation and seems to be a prerequisite for the development of oral tolerance. In this review the observational studies of the association between the gut microbiota and atopic diseases are discussed. Although most studies indicated an association between the gut microbiota composition and atopic sensitization or symptoms, no specific harmful or protective microbes can be identified yet. Some important methodological issues that have to be considered are the microbiological methods used (traditional culture vs molecular techniques), the timing of examining the gut microbiota, the definition of atopic outcomes, confounding and reverse causation. In conclusion, the microbiota hypothesis in atopic diseases is promising and deserves further attention. To gain more insight into the role of the gut microbiota in the etiology of atopy, large-scale prospective birth cohort studies using molecular methods to study the gut microbiota are needed.