Effect of Two Types of Bariatric Surgery (Gastrojejunal Bypass and Sleeve Gastroplasty) on Gene Expression of Bone Remodeling Markers in Goto-Kakizaki Rats

Background

The aim of this study was to evaluate gene expression of bone remodeling markers in type 2 diabetic Goto-Kakizaki (GK) nonobese rats after gastrojejunal bypass and sleeve gastroplasty and their relationship with hormonal parameters.

Methods

We designed an experimental study in three groups of GK rats (nonoperated gastrojejunal bypass and sleeve gastroplasty). Gene expression of markers of bone remodeling and levels of insulin, leptin, and glucagon-like peptide-1 (GLP-1) were determined.

Results

GK rats had decreased levels of osteocalcin expression compared with Wistar rats. Gene expression of markers of bone remodeling in GK rats was similar in the three groups studied, although there was a trend to decreased receptor activator for nuclear factor κ B ligand (RANKL) in gastroplasty rats. Significant differences in the osteocalcin/RANKL ratio were observed between controls and gastrojejunal bypass rats compared with gastroplasty rats. The behavior of gastrointestinal hormones was antagonistic (GLP-1 gastrojejunal bypass 1.54?±?0.24 ng/ml vs. GLP-1 gastroplasty 0.673?±?0.09, p?=?0.0001; leptin gastrojejunal bypass 1,178?±?0.474 pg/ml vs. leptin gastroplasty 7,391?±?4,054 pg/ml, p?=?0.002). There was a reduction in leptin in the bypass group associated with an increase in gastrectomized rats. In gastrectomized rats, there was a trend toward an inverse relationship between leptin and RANKL (r?=??0.771, p?=?0.072). This relationship was more marked in the totality of operated rats, n?=?12 (r?=??0.608, p?=?0.036).

Conclusion

Our results show a more favorable profile of sleeve gastroplasty on bone remodeling. There was a trend to an increase in the expression of the osteocalcin gene, which is probably mediated by increased expression of leptin that inhibits the expression of RANKL.     

Sclerostin Regulation,Microarchitecture, and Advanced Glycation End-Products in the Bone of Elderly Women With Type 2 Diabetes

Increased circulating sclerostin and accumulation of advanced glycation end-products (AGEs) are two potential mechanisms underlying low bone turnover and increased fracture risk in type 2 diabetes (T2D). Whether the expression of the sclerostin-encoding SOST gene is altered in T2D, and whether it is associated with AGEs accumulation or regulation of other bone formation-related genes is unknown. We hypothesized that AGEs accumulate and SOST gene expression is upregulated in bones from subjects with T2D, leading to downregulation of bone forming genes (RUNX2 and osteocalcin) and impaired bone microarchitecture and strength. We obtained bone tissue from femoral heads of 19 T2D postmenopausal women (mean glycated hemoglobin [HbA1c] 6.5%) and 73 age- and BMI-comparable nondiabetic women undergoing hip replacement surgery. Despite similar bone mineral density (BMD) and biomechanical properties, we found a significantly higher SOST (p = .006) and a parallel lower RUNX2 (p = .025) expression in T2D compared with non-diabetic subjects. Osteocalcin gene expression did not differ between T2D and non-diabetic subjects, as well as circulating osteocalcin and sclerostin levels. We found a 1.5-fold increase in total bone AGEs content in T2D compared with non-diabetic women (364.8 ± 78.2 versus 209.9 ± 34.4 μg quinine/g collagen, respectively; p < .001). AGEs bone content correlated with worse bone microarchitecture, including lower volumetric BMD (r = −0.633; p = .02), BV/TV (r = −0.59; p = .033) and increased trabecular separation/spacing (r = 0.624; p = .023). In conclusion, our data show that even in patients with good glycemic control, T2D affects the expression of genes controlling bone formation (SOST and RUNX2). We also found that accumulation of AGEs is associated with impaired bone microarchitecture. We provide novel insights that may help understand the mechanisms underlying bone fragility in T2D. © 2020 American Society for Bone and Mineral Research (ASBMR).     

Effects of gastric bypass surgery on expression of glucose transporters and fibrotic biomarkers in kidney of diabetic fatty rats

BackgroundDiabetic nephropathy is the leading cause of chronic kidney disease. Observational studies suggest Roux-en-Y gastric bypass (RYGB) reduces progression of diabetic nephropathy.ObjectivesTo unravel the mechanisms by which RYGB is beneficial and protective for diabetic nephropathy.SettingAcademic laboratories.MethodsForty-eight Zucker diabetic fatty rats were randomized to RYGB, sham surgery (SHAM), or pair-fed (PF) groups. An oral glucose tolerance test was performed at 25 days post intervention and kidneys were harvested at 30 days. Primary outcome measures included expression of key genes and proteins in the glucose transport, oxidative stress, inflammation, and fibrosis pathways.ResultsThirty days post intervention, RYGB rats weighed 349 ± 8 g, which was lower than SHAM (436 ± 14 g, P < .001), but not PF (374 ± 18 g) rats. RYGB rats had lower fasting glucose than PF animals and improved homeostatic model assessment of insulin resistance compared with PF and SHAM groups. These enhanced metabolic outcomes were accompanied by reduced sodium-glucose co-transporter 1 (Sglt1) gene expression (−23% versus PF, P = .01) in the kidney of RYGB rats. Expression of Sglt2, Glut1, or Glut2 mRNA, or oxidative stress and inflammation markers did not differ significantly. However, RYGB surgery induced a 19% lower expression of transforming growth factor (Tgfβ) mRNA (P = .004) compared with SHAM treated animals. Notably, adenosine monophosphate-activated protein kinase phosphorylation was increased (P = .04) in kidneys of the RYGB surgery animals.ConclusionsImprovement of hyperglycemia after RYGB may reduce the glucose load on the kidney leading to a downregulation of specific glucose transporters. RYGB surgery may also attenuate kidney fibrosis through the adenosine monophosphate-activated protein kinase/TGFβ pathway.     

Effects of duodenal-jejunal exclusion on beta cell function and hormonal regulation in Goto-Kakizaki rats

BackgroundThe aim of our work was to investigate the hormones that control glycemic status and in vitro β-cell function in diabetes mellitus after a duodenal-jejunal exclusion in Goto-Kakizaki rats (Taconic, Denmark).MethodsTwenty-three rats (age, 12–14 wk) were randomized as follows: group 1 (n = 14), no intervention (control); or group 2 (n = 9), duodenal-jejunal exclusion.ResultsIn group 2, levels of glucagon and leptin were lower than in group 1 at 1 week and at 8 weeks. Glucagon-like peptide 1 levels had a significant increase at 8 weeks from basal value in group 2 and this value was higher than in group 1. The insulin secretion at 60 minutes in group 2 was higher than in group 1 (group 1, 12.9 ± 12.0 μg/L vs group 2, 41.9 ± 36.3 μg/L; P < .05). Messenger RNA (mRNA) expression of insulin at 2 months was higher in the rat pancreas of the experimental group than in the control group (group 1, .99 ± .48 mRNA amount vs group 2, 1.66 ± .33 mRNA amount; P < .05).ConclusionsGastrojejunal bypass in this model improves glucose ratios, with a significant increase of glucagon-like peptide 1 and decrease of homeostasis model assessment, glucagon, and leptin levels after surgery. This type of surgery improves mRNA insulin expression in pancreatic islets and insulin secretion as well.     

Surgical adhesive increases burst pressure and seals leaks in stapled gastrojejunostomy

BackgroundLeakage from a gastrointestinal anastomosis in bariatric surgery is a catastrophic complication and is the second-most preventable cause of death after Roux-en-Y gastric bypass. Several adjuncts for staple line reinforcement have been investigated to reduce the incidence of this complication. The purpose of our study was to determine whether a commercially available tissue sealant (BioGlue) could reinforce a stapled gastrojejunal anastomosis and whether it could seal an artificially created anastomotic leak.MethodsCircular-stapled gastrojejunostomies were performed on freshly explanted porcine stomach and intestine. Experiment 1 consisted of 10 control nonreinforced gastrojejunostomies and 10 gastrojejunostomies reinforced with BioGlue. The staple lines were submerged in saline and exposed to increased pressure using constant-rate infusion of air. The burst pressures were recorded at the point of visible leakage from the anastomosis. In experiment 2, a small defect was created in 10 gastrojejunostomies. The burst pressures were recorded before and after application of BioGlue to the anastomosis. The data were analyzed using the 2-tailed paired t test.ResultsIn experiment 1, the burst pressure was significantly increased in the reinforced gastrojejunostomies, from 27.4 ± 8.4 mm Hg to 59.1 ± 19.2 mm Hg (P <.001). In experiment 2, the defective gastrojejunostomies had an average burst pressure of 1.2 ± 0.8 mm Hg. After application of BioGlue, the burst pressure increased to 42.8 ± 15.9 mm Hg (P <.001).ConclusionThese ex vivo findings suggest that the surgical adhesive BioGlue can reinforce both intact and defective stapled gastrojejunal anastomoses. Additional in vivo study is warranted to determine whether BioGlue can prevent or help seal gastrojejunal leaks.     

The Deleterious Effect of Bariatric Surgery on Cortical and Trabecular Bone Density in the Femurs of Non-obese, Type 2 Diabetic Goto-Kakizaki Rats

Background

The effects of type 2 diabetes on bone mass and microstructure are not clear. The aim of this study was to evaluate bone microstructural properties and volumetric bone mineral density (vBMD) in type 2 diabetic Goto-Kakizaki non-obese rats after gastrojejunal bypass and their relationship with hormonal parameters.

Methods

We designed an experimental study in Goto-Kakizaki rats with and without gastrojejunal bypass, performing densitometric and microstructural studies of the distal femur using X-ray computed microtomography (micro-CT). Levels of insulin, glucagon, leptin, and glucagon-like peptide-1 (GLP-1) were also determined.

Results

We observed reduced cortical (1,488.92?±?98.2 vs. 1,727.92?±?133.45?mg/cm³, p?=?0.028) and trabecular (180.8?±?9 vs. 261.23?±?45.54?mg/cm³, p?=?0.036) vBMD in operated rats. Bone volume fraction (BV/TV) and trabecular connectivity were reduced in operated rats, while there was a reduction in cortical thickness and an increase in rod-like trabeculae at the expense of plate-like trabeculae. Leptin was reduced (1,042?±?549 vs. 2,447?±?1,035?pg/ml, p?=?0.05) and GLP-1 increased (1.62?±?0.32 vs. 0.96?±?0.1?ng/ml, p?=?0.008) but only leptin showed a significant association with vBMD

Conclusions

In type 2 diabetic Goto-Kakizaki rats, gastrojejunal bypass produces a reduction in cortical and trabecular bone mineral density and a deterioration in bone quality that could be explained, in part, by the reduction in leptin levels.     

Unraveling,contributing factors to the severity of postprandial hypoglycemia after gastric bypass surgery

BackgroundDespite the increasing prevalence of postbariatric hypoglycemia (PBH), a late metabolic complication of bariatric surgery, our understanding of its diverse manifestations remains incomplete.ObjectivesTo contrast parameters of glucose-insulin homeostasis in 2 distinct phenotypes of PBH (mild versus moderate hypoglycemia) based on nadir plasma glucose.SettingUniversity Hospital (Bern, Switzerland).MethodsTwenty-five subjects with PBH following gastric bypass surgery (age, 41 ± 12 years; body mass index, 28.1 ± 6.1kg/m²) received 75g of glucose with frequent blood sampling for glucose, insulin, C-peptide, and glucagon-like peptide 1 (GLP)-1. Based on nadir plasma glucose (</≥50mg/dL), subjects were grouped into level 1 (L1) and level 2 (L2) PBH groups. Beta-cell function (BCF), GLP-1 exposure (λ), beta-cell sensitivity to GLP-1 (π), potentiation of insulin secretion by GLP-1 (PI), first-pass hepatic insulin extraction (HE), insulin sensitivity (SI), and rate of glucose appearance (Ra) were calculated using an oral model of GLP-1 action coupled with the oral minimal model.ResultsNadir glucose was 43.3 ± 6.0mg/dL (mean ± standard deviation) and 60.1 ± 9.1mg/dL in L2- and L1-PBH, respectively. Insulin exposure was significantly higher in L2 versus L1 (P = .004). Mathematical modeling revealed higher BCF in L2 versus L1 (34.3 versus 18.8 10^-91min^-1; P = .003). Despite an increased GLP-1 exposure in L2 compared to L1 PBH (50.7 versus 31.9pmol1L^-11min110²; P = .021), no significant difference in PI was observed (P = .204). No significant differences were observed for HE, Ra, and SI.ConclusionsOur results suggest that higher insulin exposure in PBH patients with lower postprandial nadir glucose values mainly relate to a higher responsiveness to glucose, rather than GLP-1.     

Laparoscopic Roux-en-Y gastric bypass versus laparoscopic sleeve gastrectomy: a case-control study and 3 years of follow-up

BackgroundLaparoscopic sleeve gastrectomy (LSG) has become a popular surgical procedure among bariatric surgeons. Few studies have compared the efficacy of the procedure to laparoscopic Roux-en-Y gastric bypass (LRYGB). We performed a case-control study to assess the surgical results, weight progression, and remission of co-morbid conditions.MethodsFrom January 2006 to September 2009, we selected 811 patients undergoing LSG as a primary procedure. These patients were matched by age, body mass index, and gender to 786 patients undergoing LRYGB. The complication rate, mortality, and percentage of excess weight loss after 1, 2, and 3 years were analyzed.ResultsThe mean age for the LRYGB and LSG groups was 37.0 ± 10.3 and 36.4 ± 11.7 years, respectively (P = .120). Most of the patients were women (LRYGB 76.6% versus LSG 76.2%; P = .855). The preoperative body mass index before surgery was similar in both groups (LRYGB 38.0 ± 3.2 versus LSG 37.9 ± 4.6 kg/m²; P = .617). The mean operative time was longer for LRYGB (106.2 ± 33.2 versus 76.6 ± 28.0 min; P <.001), and the hospital stay was longer for LRYGB (3.4 ± 4.4 versus 2.8 ± .8 for LSG; P <.001). The early complication rate was 7.1% for LRYGB and 2.9% for LSG (P <.001), and the suture leak rate was .7% for LRYGB and .5% for LSG (P = NS). The percentage of excess weight loss for LRYGB versus LSG at 1, 2, and 3 years was 97.2% ± 24.3% versus 86.4% ± 26.4% (P <.001), 94.6% ± 30.2% versus 84.1% ± 28.3% (P <.001), and 93.1% ± 25.0% versus 86.8% ± 27.1% (P = .082), respectively. The total cholesterol level at 1 year for LRYGB versus LSG was 169.0 ± 32.9 versus 193.6 ± 38.7 mg/dL, respectively (P <.001), and the rate of diabetes remission was similar in both groups (LRYGB 86.6% versus LSG 90.9%).ConclusionLSG has become an acceptable primary bariatric procedure for obesity, with results comparable to LRYGB in this population.     

Relevance of beta-cell function for improved glycemic control after gastric bypass surgery

BackgroundResidual beta-cell function and gastrointestinal hormones have been suggested as relevant determinants of improved glycemic control ensuing Roux-en-Y gastric bypass (RYGB). The objective of this study was to compare the glycemic control up to 24 months after RYGB in C-peptide negative morbidly obese (MO) type 1 diabetes mellitus (T1 DM) women (n = 7) and C-peptide positive (>.6 ng/mL) MO women with type 2 diabetes mellitus (T2 DM, n = 7) on basal-bolus insulin therapy. The glucagon-like peptide 1 (GLP-1) and glucagon response to a mixed meal challenge were also compared between groups.MethodsPercent excess weight loss (%EWL), HbA_1c, and daily insulin dose (DID) after RYGB were compared between groups. The GLP-1 and glucagon response (area under the curve 0–120 minutes) after a mixed meal at last follow-up visit were also compared.ResultsAt 24-months, marked %EWL was observed in women with T1 DM and women with T2 DM (mean±standard error, 82.6%±11.3% and 87.4%±30.5%, respectively; P = .722]. In women with T1 DM, HbA_1c (4 months, P<.05) and DID improved transiently (P<.05, up to 8 months) but were comparable to baseline thereafter (HbA_1c: baseline, 8.3±1.2 and 24 months, 8.2±.9, P = 1.00; DID: baseline, .61±.17 and 24 months .62±.12 IU/kg/d, P = 1.00]. In contrast, in MO women with T2 DM, HbA_1c decreased significantly throughout follow–up, with 2 patients presenting diabetes remission and all but one an HbA_1c<7% at 24 months. The GLP-1 response was comparable between groups (P = .612), and was not accompanied by suppression of the glucagon response to meal intake.ConclusionsIn the absence of residual beta-cell, RYGB results in no significant benefit on glycemic control, despite a marked response of GLP-1 to meal intake.     

Up-regulated cystic fibrosis transmembrane conductance regulator after anal stenosis in rats

BackgroundThe pathophysiology of fecal incontinence from fecal impaction and rectal distension is poorly understood. We hypothesize that fecal impaction elicits up-regulation of cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated mucosal chloride channel.MethodsThe anus was ligated to produce 75% stenosis in rats. Controls received ligation without inducing stenosis. 24 to 48 hours after ligation the colon was removed. Mucosal short-circuit current was measured by Ussing chamber. Western blot analysis was used to detect CFTR expression in the colonic mucosa. Ligated rats failed to defecate, whereas control rats stooled normally.ResultsLigated colons were markedly stool filled and dilated. Water content of feces was significantly increased to 66.5% ± 1.1% (P < .01, n = 12) 24 hours after ligation, vs controls (49.5 ± 5.2%, n = 12). Baseline short-circuit current was significantly increased in the distal (78.8 ± 7.4 μA/cm², n = 8, P < .01) and mid colon (24.5 ± 2.5 μA/cm², n = 8, P < .05) 24 hours after ligation, compared to control rats (12.5 ± 3.2 μA/cm2, n = 8). CFTR expression was significantly increased 24 hours after ligation in the mid and distal colon.ConclusionWe observe that fecal impaction from anal ligation induces early compensatory up-regulation of CFTR, altering function from net absorption to net secretion in the mid and distal colon.     

Necdin–E2F4 interaction provides insulin-sensitizing effect after weight loss induced by gastric bypass surgery

BackgroundThe insulin-like growth factor-1 (IGF-1) signaling pathway promotes adipocyte differentiation and, therefore, insulin sensitivity by suppression of necdin expression, which represses peroxisome proliferator-activated receptor-gamma promoter activity by interaction with E2F4 in mouse adipocytes. The aim of the present study was to test the hypothesis that this pathway represents one of the mechanisms by which Roux-en-Y gastric bypass surgery (RYGB) induces resolution of insulin resistance.MethodsClinical samples were collected and the key biomarkers measured to test the hypothesis that the IGF-1 pathway represents 1 of the mechanisms by which RYGB induces resolution of insulin resistance in obese individuals.ResultsFree IGF-1 levels were significantly greater in the post-RYGB patients than in the pre-RYGB obese patients (2.55 ± 1.54 versus 1.32 ± .65 μg/L, P = .03) and similar to that in normal weight controls (2.54 ± 1.27 μg/L). Necdin and E2F4 gene expression in the adipose tissue was significantly downregulated after RYGB compared with obese and were similar to the levels observed in the controls. In mature human adipocytes cultured in vitro, treatment with des-IGF-1 induced downregulation of necdin and E2F4 gene expression in a dose-dependent manner (P = .01).ConclusionAfter RYGB, the insulin/IGF-1 signaling pathway is activated and could account for the observed decrease in the expression of necdin, which represses peroxisome proliferator-activated receptor-gamma promoter activity by interaction with E2F4. This could represent one of the mechanisms that induce resolution of insulin resistance after RYGB.     

Patterns of surgical weight loss and resolution of metabolic abnormalities in superobese bariatric adolescents

PurposeThe aim of the study was to compare the baseline and the 18-month follow-up for weight and metabolic characteristics of superobese (SO) (body mass index [BMI] ≥50 kg/m²) and morbidly obese (MO) (BMI <50 kg/m²) adolescents who participated in a prospective longitudinal study of gastric banding delivered in an adolescent multidisciplinary treatment program.MethodsClinical information was extracted from an institutional review board–approved database of bariatric adolescents. Fasting cytokine and acute phase protein serum levels were analyzed by enzyme-linked immunosorbent assay. Liver histopathologies were assessed using the Kleiner's classification score.ResultsOther than BMI, MO (n = 11) and SO (n = 7) patients have similar degree of insulin resistance, dyslipidemia, and nonalcoholic fatty liver disease. Serum C-reactive protein (10.2 ± 5.6 SO vs 4 ± 3.9 μg/mL MO [P < .02]) and leptin (71 ± 31 SO vs 45 ± 28 MO ng/mL [P = .04]) were more elevated in SO patients. Although weight loss is similar (30 ± 19 kg MO vs 28 ± 12 kg SO, P = .8 at 18 months; mean percent change in BMI, 22.8% ± 11.6% vs 20.5% ± 10.3% SO, P = .2), SO patients has less resolution of insulin resistance and dyslipidemia but experienced significantly improved health-related quality of life.ConclusionsThe SO adolescents demonstrate equivalent short-term weight loss and improved quality of life but delayed metabolic response to a gastric banding–based weight loss treatment program compared with MO patients, illustrating the importance of early referral for timely intervention of MO patients.     

The jejunum is the key factor in insulin resistance

BackgroundBiliopancreatic diversion (BPD) is more effective than Roux-en-Y gastric bypass (RYGB) on both insulin resistance and diabetes.ObjectivesBecause the major difference between the 2 procedures resides in the length of jejunal bypass, we investigated the role of the jejunum in insulin resistance.SettingUniversity hospital in Italy.MethodsInsulin sensitivity (IS) and secretion were measured before and 4 weeks after RYGB or BPD in 16 patients. A translational study was also conducted in 6 pigs, by isolating a jejunal loop with its vascular and nerve supply (Thiry-Vella loop [TVL]). TVL was doubly stomatized and bowel continuity restored by a side-to-side jejuno-jejunostomy. At baseline and 4 weeks postoperatively a glucose bolus was injected either in the stomach or in the TVL. Whole-body IS and jejunal heat shock proteins (HSPs) were measured. Primary porcine hepatocyte cultures were incubated with plasma or individual HSPs.ResultsWhole-body IS increased from 353.5 ± 26.7 to 442.0 ± 37.4 (P < .05) after RYGB and from 312.4 ± 14.9 to 441.2 ± 15.9 mL/m⁻²/min⁻¹ (P < .001) after BPD. Hepatic IS was unchanged after RYGB, while it increased from .3 ± .01 to .4 ± .1 (μM/pM) – 1 (P < .01) after BPD. Total insulin secretion rate remained unchanged after RYGB but decreased (from 58.3 ± 23.6 to 33.1 ± 7.8 nmol/m⁻², P < .05) after BPD. Jejunectomy in pigs enhanced IS (.3 ± .01 versus .2 ± .01 mM/pM, P < .001), while injection of glucose into TVL reduced it (.1 ± .01 versus .3 ± .01 mM/pM, P < .0001). The jejunum secreted HSPs, Hsp70, and GRP78, which impaired insulin signaling in hepatocyte cultures.ConclusionsThis study shows that jejunal bypass in both humans and pigs improves IS. Injection of glucose into the TVL in pigs determines insulin resistance. In response to glucose, the jejunum secretes HSPs that impair insulin signaling.     

Improvement in health-related quality of life in first year after laparoscopic adjustable gastric banding

BackgroundWe analyzed the health-related quality of life (HRQOL) and its determinants in the first year after laparoscopic adjustable gastric banding (LAGB). The setting was 10 Italian public and private bariatric surgery centers.MethodsData collected in an ongoing, prospective, 3-year multicenter Italian study on the changes in HRQOL after LAGB were used. HRQOL was investigated using the Medical Outcomes Study Short-Form 36 questionnaire. Hunger, satiety, and the self-perceived effects of LAGB were recorded.ResultsA total of 334 patients were enrolled. The follow-up rate was 92.2%. The percentage of excess weight loss was 39.6% ± 25.8%, with very few side effects or complications. Hunger in the morning (0–10 scale) was 4.5 ± 2.7 before surgery and 3.8 ± 2.4 after 1 year (P <.001). Satiety after a meal (0–10 scale) was 7.1 ± 2.7 before surgery and 8.2 ± 1.9 at 1 year (P <.001). The self-perceived effect of LAGB on caloric intake (0–10 scale) was 8.4 ± 1.9 after 1 year. The scores for the 8 Medical Outcomes Study Short-Form 36 subscales were significantly improved after surgery. The physical component summary score was 52.6 ± 11.9 at baseline and 79.1 ± 15.6 after 1 year (P <.001). The corresponding mental component summary scores were 52.2 ± 12.3 and 76.5 ± 17.2 (P <.001). Greater physical component summary improvement was independently associated with a low initial physical component summary (P <.001), high satiety (P = .002), a high percentage of excess weight loss (P = .013), and a high self-perceived effect of the LAGB (P = .026). Greater mental component summary improvement was associated with a low initial mental component summary (P <.001), high satiety (P <.001), a low frequency of heartburn (P = .004), and a high percentage of excess weight loss (P = .012).ConclusionsSignificant improvements in HRQOL were observed in the first year after LAGB. A poor baseline HRQOL, a high efficacy of the banding in eating control, and better weight loss might influence HRQOL changes.     

Clinical and radiographic predictors of difficult primary shoulder arthroplasty

BackgroundAnecdotally there is a spectrum of complexity in performing shoulder arthroplasty, however, there is limited information to predict easy versus difficult cases. The purpose of this study was to identify clinical and radiographic factors that are associated with difficult primary shoulder arthroplasty.MethodsAll consecutive primary shoulder arthroplasties performed by one-of-five high-volume shoulder and elbow fellowship-trained surgeons from 4/2018-8/2018 were included. Mean (range) surgeon years in practice was 19.4 (6-29). Surgeons completed a preoperative questionnaire estimating the level of complexity in performing the operation from very easy, easy, average, difficult, and very difficult. The same questionnaire was completed immediately postoperatively regarding level of complexity. Difficult group was defined if the surgeon rated as difficult or very difficult on the postoperative questionnaire. If the procedure was difficult, the postoperative questionnaire assessed what aspect of the procedure made it difficult. Demographics, clinical and radiographic factors, and procedure time were collected.ResultsDuring the study period, 224 primary shoulder arthroplasties were performed (53% reverse, 44% anatomic, 3% hemiarthroplasty with concentric glenoid reaming). Difficult group consisted of 95 shoulder arthroplasties (42.4%). Difficult group procedure time was a mean 21.8 minutes longer (120.7 ± 3.1 min vs. 98.9 ± 2.4 min; P <.001). Glenoid reaming and implantation (48.4%) were the most common reason for difficult cases, followed by glenoid exposure (33.7%). The surgeon correctly predicted level of complexity in 77% of cases (i.e., predicted difficult preoperatively and assigned difficulty postoperatively). There were 39 cases that were incorrectly predicted easy preoperatively and assigned as difficult postoperatively. Of all the cases predicted to be easy, those cases that were rated as difficult postoperatively were associated with younger age (67.1 ± 1.4 vs. 71.2 ± 0.7; P =.006), males (61.5% vs. 34.3%; P = .003), higher BMI (31.7 ± 0.9 vs. 29.6 ± 0.5; P = .045), history of instability (30.8% vs. 10.5%; P = .003), decreased passive external rotation (17.5 ± 3.1 vs. 25.1 ± 1.4, P = .031), larger inferior humeral head osteophyte (14.1mm vs. 7.8mm, P = .001) and B2 or B3 glenoids (39.3% vs. 17.2%; P =.026).Discussion and conclusionFor experienced high-volume shoulder and elbow surgeons performing primary shoulder arthroplasty, cases that were unexpectedly difficult were associated with younger age, males, stiffness, history of instability, large inferior humeral head osteophyte, and posterior glenoid bone loss. Difficulty with glenoid reaming and glenoid component implantation were the most frequent reason for difficult cases. This information may allow surgeons to anticipate difficult cases, appropriately schedule their operative day, and identify potentially difficult cases that warrant referral to high-volume shoulder arthroplasty surgeon.Level of evidenceLevel III; Prospective Case-Control Study     

Effects of surgically induced weight loss by Roux-en-Y gastric bypass on osteocalcin

BackgroundOsteocalcin (OC), a protein synthesized by osteoblasts, is a marker of bone turnover with undercarboxylated OC (ucOC) being involved in glucose homeostasis. Although laparoscopic Roux-en-Y gastric bypass (LRYGB)-induced weight loss likely alters bone turnover, data on markers of bone turnover remain less clear. The aim of this study was to examine the effect of surgically induced weight loss on OC and ucOC.MethodsA total of 32 individuals with a body mass index 50.2±10.2 kg/m² underwent LRYGB. Osteocalcin, ucOC, other blood analytes (e.g., vitamin D, leptin, total and high-molecular-weight adiponectin), and homeostasis model assessment for insulin resistance were measured before and after weight loss. The effect of an acute nutrient load on OC parameters after a mixed meal tolerance test also was assessed.ResultsSix months after surgery, there was an increase in OC (17.8±7.4 [mean±SD] [baseline] versus 31.5±9.8 ng/mL [follow-up]; P<.001) and ucOC (7.3±6.2 versus 18.5±8.9 ng/mL; P<.001). Although adiponectin increased, only the magnitude of change in OC and leptin was correlated (r =?.43; P = .017). After weight loss, an acute nutrient load reduced OC (31.5±9.8 [0-hour] versus 29.6±8.2 [2-hour] ng/mL; P = .024), whereas ucOC was higher (18.8±9.3 [0-hour] versus 21.1±8.6 [2-hour] ng/mL; P< .001).ConclusionSurgically induced weight loss was associated with increases in OC and ucOC. Underlying mechanisms are unclear, but change in OC may be related to change in leptin. After a nutrient load, the increase in ucOC suggests a potential role as a short-term compensatory regulator of glucose homeostasis.     

CCNG2 and CDK4 is associated with insulin resistance in adipose tissue

BackgroundThe involvement of cyclin G2 (CCNG2) and cyclin-dependent kinase-4 (CDK4), cell cycle regulatory proteins, in adipose tissue metabolism and insulin resistance is still unknown. The objective of this study was to analyze CCNG2 and CDK4 levels in visceral (VAT) and subcutaneous adipose tissue (SAT) from nonobese and morbidly obese patients and their relationship with insulin resistance.MethodsWe studied the mRNA and protein levels of CCNG2 and CDK4 in VAT and SAT from 12 nonobese and 23 morbidly obese patients (11 with low [MO-L-IR] and 12 with high insulin resistance [MO-H-IR]).ResultsThe nonobese patients had a significantly greater CCNG2 expression in VAT (P = .004) and SAT (P<.001) than the MO-L-IR and MO-H-IR patients. The MO-H-IR patients had a significantly lower CDK4 expression in VAT than the MO-L-IR (P = .026), but similar to the nonobese patients. CDK4 and CCNG2 expression correlated significantly in VAT (r = 0.511, P<.001) and SAT (r = .535, P = .001). In different multiple regression analysis models, CCNG2 and CDK4 expression in VAT was mainly predicted by glucose (P = .047 and P = .008, respectively), and CCNG2 expression in SAT was mainly predicted by body mass index (P = .041). No significant associations were found with CDK4 expression in SAT. Moreover, VAT CCNG2 expression was the main determinant of the improvement in the homeostasis model assessment of insulin resistance index at 3 months after bariatric surgery (B = -271.7, P = .026).ConclusionOur data show for the first time that the human CCNG2 and CDK4 expression of VAT are inversely associated with glucose and insulin resistance.