Intraduodenal Administration of Intact Pea Protein Effectively Reduces Food Intake in Both Lean and Obese Male Subjects

BACKGROUND: Human duodenal mucosa secretes increased levels of satiety signals upon exposure to intact protein. However, after oral protein ingestion, gastric digestion leaves little intact proteins to enter the duodenum. This study investigated whether bypassing the stomach, through intraduodenal administration, affects hormone release and food-intake to a larger extent than orally administered protein in both lean and obese subjects. METHODS: Ten lean (BMI:23.0±0.7 kg/m²) and ten obese (BMI:33.4±1.4 kg/m²) healthy male subjects were included. All subjects randomly received either pea protein solutions (250 mg/kg bodyweight in 0.4 ml/kg bodyweight of water) or placebo (0.4 ml/kg bodyweight of water), either orally or intraduodenally via a naso-duodenal tube. Appetite-profile, plasma GLP-1, CCK, and PYY concentrations were determined over a 2 h period. After 2 h, subjects received an ad-libitum meal and food-intake was recorded. RESULTS: CCK levels were increased at 10(p<0.02) and 20(p<0.01) minutes after intraduodenal protein administration (IPA), in obese subjects, compared to lean subjects, but also compared to oral protein administration (OPA)(p<0.04). GLP-1 levels increased after IPA in obese subjects after 90(p<0.02) to 120(p<0.01) minutes, compared to OPA. Food-intake was reduced after IPA both in lean and obese subjects (-168.9±40 kcal (p<0.01) and -298.2±44 kcal (p<0.01), respectively), compared to placebo. Also, in obese subjects, food-intake was decreased after IPA (-132.6±42 kcal; p<0.01), compared to OPA. CONCLUSIONS: Prevention of gastric proteolysis through bypassing the stomach effectively reduces food intake, and seems to affect obese subjects to a greater extent than lean subjects. Enteric coating of intact protein supplements may provide an effective dietary strategy in the prevention/treatment of obesity

Herniation Pits in Human Mummies: A CT Investigation in the Capuchin Catacombs of Palermo, Sicily

Herniation pits (HPs) of the femoral neck were first described in a radiological publication in 1982 as round to oval radiolucencies in the proximal superior quadrant of the femoral neck on anteroposterior radiographs of adults. In following early clinical publications, HPs were generally recognized as an incidental finding. In contrast, in current clinical literature they are mentioned in the context of femoroacetabular impingement (FAI) of the hip joint, which is known to cause osteoarthritis (OA). The significance of HPs in chronic skeletal disorders such as OA is still unclear, but they are discussed as a possible radiological indicator for FAI in a large part of clinical studies

A genome-wide association search for type 2 diabetes genes in African Americans

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations

A genome-wide association search for type 2 diabetes genes in African Americans

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations

Effect of ileal fat perfusion on satiety and hormone release in healthy volunteers.

Objective:The ileal brake is a feedback mechanism activated by nutrients, especially fat, with marked effects on satiety. The effects of low doses of ileal fat on satiety are largely unknown. We therefore studied the effect of ileal vs oral delivery of low doses of fat on satiety and gut peptide secretion.Design:Randomized, single-blind crossover design.Subjects:Sixteen healthy, normal-weight volunteers (6 male; mean age 26 years, mean body mass index 22.4).Intervention:Participants were intubated with a 290-cm-long nasoileal tube and consumed, on 3 consecutive days, either a liquid breakfast with 3 g fat followed by an ileal placebo infusion at t=105-150 min (treatment C) or a fat-free liquid breakfast followed by an ileal infusion of either an emulsion of 3 g (treatment I3g) or 9 g (treatment I9g) fat (safflower oil).Measurements:Satiety parameters by visual analog scales and plasma concentrations of CCK and PYY.Results:C significantly increased satiety and CCK secretion compared with the fat-free breakfast. Ileal fat perfusion of both 3 and 9 g (I3g and I9g) significantly increased satiety during and after fat perfusion, without differences in satiety between I3g and I9g. During ileal fat infusion, CCK increased dose dependently, whereas PYY concentrations increased significantly only after 9 g of fat. Secretion of CCK but not of PYY correlated to satiety levels.Conclusion:Postprandial satiety following a liquid breakfast can be effectively and significantly increased by small amounts (as little as 3 g) of fat perfused into the ileum. Ileal fat dose-dependently increased CCK but not PYY secretion. The satiating effect of ileal fat may be partly mediated by CCK.International Journal of Obesity advance online publication, 16 September 2008; doi:10.1038/ijo.2008.166

Influence of acute exercise on hyperglycemia in insulin-treated type 2 diabetes.

INTRODUCTION: The impact of exercise on blood glucose homeostasis has not been assessed in long-standing type 2 diabetes patients receiving exogenous insulin treatment. PURPOSE: To study the effects of an acute bout of exercise on the subsequent 24-h blood glucose excursions under free-living conditions in insulin-treated type 2 diabetes patients. METHODS: Eleven male type 2 diabetes patients (59 +/- 2 yr) performed an acute bout of exercise. One day before the exercise bout, a continuous glucose monitoring system (GlucoDay, A. Menarini Diagnostics) was inserted subcutaneously in the periumbilical region. The glucose sensor continuously measured glucose concentrations in the dialysate during a 48-h period. RESULTS: The prevalence of hyperglycemic glucose excursions was reduced by 39% during a 24-h period (equivalent to 3 h) after an acute bout of exercise (P < 0.05). Average glucose concentrations 24 h before and after the exercise bout did not differ (NS). Mean dialysate glucose concentrations and the prevalence of hyperglycemic periods correlated strongly with baseline blood HbA1c concentrations (Pearson's R = 0.69, P < 0.05). CONCLUSION: An acute bout of exercise effectively reduces the prevalence of hyperglycemia during a 24-h period under free-living conditions in long-standing type 2 diabetes patients on exogenous insulin therapy

Mycobacterium avium ssp. paratuberculosis als mogelijke oorzaak van de ziekte van Crohn: resultaten van een patientenstudie in Nederland.

De bacterie Mycobacterium avium ssp. paratuberculosis (Map) wordt beschouwd als een mogelijke oorzaak van de ziekte van Crohn (morbus Crohn, MC). In samenwerking met Gelre ziekenhuizen heeft het RIVM een onderzoek uitgevoerd naar het voorkomen van Map in darmbiopten van patienten met MC, patienten met Ulcerative Colitis (UC) en controlepersonen zonder darmontsteking. De aanwezigheid van Map in de darmbiopten werd onderzocht met behulp van kweekmethoden, een DNA amplificatiemethode (PCR) en een immunologische detectiemethode (immunoperoxidase kleuring, IP-kleuring). Met de PCR-methode werd Map aangetoond in 7% van de MC-patienten, 8% van de UC-patienten en 5% van de controlepersonen. Met de gecombineerde kweek- en PCR-methoden waren gemiddeld 25% van de MC-patienten, 7% van de UC patienten en 27% van de controlepersonen positief. Met behulp van de IP-kleuring werd Map aangetoond in 20% van de MC-patienten, 13% van de UC-patienten en 29% van de controlepersonen. De resultaten van de kweek- en PCR-methoden tonen geen significant verschil tussen de aanwezigheid van Map in MC-patienten vergeleken met controlepersonen. De resultaten van de IP-kleuring tonen zelfs een hoger percentage Map-positieve controlepersonen vergeleken bij MC-patienten. Onze resultaten tonen duidelijk aan dat Map zowel bij MC-patienten als bij UC-patienten en controlepersonen voorkomt. Naast de aanwezigheid van Map is ook gekeken naar de aanwezigheid van Chlamydia in de biopten. Op grond van IP en in situ hybridisatie kleuringen bleken Chlamydiae in grote aantallen aanwezig te zijn in de biopten van MC- en UC-patienten en nauwelijks aanwezig in de biopten van controle patienten.In conclusie: onze resultaten ondersteunen niet de hypothese dat Map direct betrokken is bij de ziekte van Crohn, maar sluiten ook niet uit dat Map een rol speelt bij het ontstaan van de ziekte van Crohn in een gevoelig deel van de populatie.A case control study was performed to investigate the possible role of Mycobacterium avium ssp. paratuberculosis (Map) in the aetiology of Crohn's disease (CD). Biopsy samples were collected from the ileum and colon of CD patients, Ulcerative Colitis (UC) patients and control persons. The biopsy samples were either cultured in MGIT and BACTEC medium, formaline-fixed, or immediately snap-frozen in liquid N2. The presence of Map bacteria in the cultures was determined using a nested PCR assay targeted to the conserved IS900 DNA-sequence of Map. 27% of CD patients, 6% of UC patients, and 28% of control persons were positive for MGIT-PCR. The BACTEC cultures resulted in a slightly smaller percentage of PCR positive patients, 22% for CD patients, 7% for UC patients and 25% for control persons. The presence of Map was further studied applying the IS900-PCR directly on DNA from frozen biopsy samples. 7% of CD patients, 8% of UC patients and 5% of control persons were PCR positive for Map. The presence of Map was also investigated in formalin-fixed biopsies samples using a hyperimmune antiserum to the M. avium-complex. With immunoperoxidase (IP) staining, M. avium-complex antigens were observed in biopsy samples from 20% of CD patients, 13% of UC patients and 29% of control persons. Surprisingly, these data show even a 50% higher presence of Map-antigens in control persons (29%) compared to CD patients (20%). Our data clearly show that Map is present both in IBD patients (CD and UC) and in control persons. The results of culturing and IP staining show a good correlation; with both techniques, an average of 23% of CD patients and 27% of control persons is positive for Map. Remarkably, the results of culturing and IP staining show an even higher prevalence of Map in control persons compared to CD patients. Moreover, only in a few instances patients were positive in two different tests (PCR, IP, MGIT and BACTEC), and even with both culturing assays almost no overlap in positive results is observed. This result indicates that the number of Map cells in human tissue is very low, and that the prevalence of Map in the population of IBD patients and of control persons is difficult to estimate. Unexpectedly, we obtained evidence that members of the Chlamydiales family are present in high amounts in most of the CD and UC patients, whereas they were of low incidence in control persons.In conclusion, our data do not support the hypothesis that Map is directly involved in Crohn's disease, but does not exclude that Map infection may play a role in the aetiology of Crohn's Disease for a susceptible subset of the population.LNV/VW