Roux-en-Y Gastric Bypass Versus Medical Treatment for Type 2 Diabetes Mellitus in Obese Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The aim of the study is to compare Roux-en-Y gastric bypass (RYGB) surgery versus medical treatment for type 2 diabetes mellitus (T2DM) in obese patients.Bariatric surgery can achieve remission of T2DM in obese patients. RYGB surgery has been performed as one of the most common surgical treatment options for obese patients with T2DM, but the efficacy of RYGB surgery comparing with medical treatment alone has not been conclusively determined.A systematic literature search identified randomized controlled trials (RCTs) evaluating RYGB surgery versus medical treatment for T2DM in obese patients was conducted in PubMed, Embase, Cochrane Database, and Cochrane Clinical Trials Registry. This systematic review and meta-analysis were performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. The primary outcome was T2DM remission. Additional analyses comprised hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), body mass index (BMI), waist circumference, serum lipid level, blood pressure, medication use, and adverse events. Random-effects meta-analyses were calculated and presented as weighted odds ratio (OR) or mean difference (MD) with 95% confidence intervals (CI).Six RCTs concerning 410 total obese T2DM patients were included. Follow-up ranged from 12 to 60 months. RYGB surgery was associated with a higher T2DM remission rate (OR: 76.37, 95% CI: 20.70-281.73, P < 0.001) and serum level of high-density lipoprotein cholesterol (MD: 0.24 mmol/L, 95% CI 0.18-0.30 mmol/L, P < 0.001) than medical treatment alone. HbA1c (MD: -1.25%, 95% CI: -1.88% to -0.63%, P < 0.001), BMI (MD: -6.54 kg/m, 95% CI: -9.28 to -3.80 kg/m, P < 0.001), waist circumference (MD: -15.60 cm, 95% CI: -18.21 to -13.00 cm, P < 0.001), triglyceride (MD: -0.87 mmol/L, 95% CI: -1.17 to -0.57 mmol/L, P < 0.001), low-density lipoprotein cholesterol (MD: -0.32 mmol/L, 95% CI: -0.62 to -0.02 mmol/L, P = 0.04), systolic blood pressure (MD: -2.83 mm Hg, 95% CI: -4.88 to -0.78 mm Hg, P < 0.01) were lower after RYGB surgery. However, FPG (MD: -1.58 mmol/L, 95% CI: -3.58 to 0.41 mmol/L, P = 0.12), total cholesterol (MD: -0.40 mmol/L, 95% CI: -0.92 to 0.12 mmol/L, P = 0.13), and diastolic blood pressure (MD: 0.28 mm Hg, 95% CI: -1.89 to 2.45 mm Hg, P = 0.80) were not significantly different between the 2 treatment groups. The medicine use and quality of life were solely improved in the surgical group. Nutritional deficiencies and anemia were noted more frequently in the RYGB group.RYGB surgery is superior to medical treatment for short- to medium-term remission of T2DM, improvement of metabolic condition, and cardiovascular risk factors. Further RCTs should address the safety and long-term benefits of RYGB surgery on obese patients with T2DM.

Circadian clock gene expression regulates cancer cell growth through glutaminase.

Glutamine is an essential amino acid for malignant tumor cells. Glutaminase that metabolizes glutamine reaches a maximum expression in tumors immediately before the maximum proliferation rate. Tumor cells grow at different rates during the day. We postulated that the activity of glutaminase in tumor cells is subject to the regulation of circadian clock gene. We measured glutaminase by western blot analysis and circadian clock gene expression by real-time polymerase chain reaction in the liver and tumor cells at six equispaced time points of the day in individual mice of a 12/12 h light/dark schedule. The results showed that the tumor-bearing mice, under normal diurnal conditions, are circadianly entrained, as reflected by the normal host locomotor activity rhythms and rhythmic liver clock gene expression. The tumors within these mice are also circadianly organized, as reflected by circadian clock gene (Bmal1) expression. What is most remarkable is that kidney-type glutaminase also showed circadian rhythms in the same pattern with tumor circadian clock gene expression in liver cancer xenograft model, indicating that conditionally inhibiting glutaminase activity may provide a new target for cancer therapy.

Association of MTHFR 677T variant allele with risk of intracerebral haemorrhage: a meta-analysis.

BACKGROUND: Previous studies concerning the association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and risk of intracerebral haemorrhage (ICH) reported conflicting results. A meta-analysis of published studies was performed to allow a more reliable estimate of this association. METHODS: Relevant studies concerning the association between MTHFR C677T polymorphism and risk of ICH were included into this meta-analysis. Odds ratios (OR) and 95% confidence intervals (CI) were determined for this gene-disease association using fixed or random effect models. RESULTS: Finally, 16 studies with a total of 1828 cases and 4067 controls were included. Meta-analyses of a total of 16 studies showed that there was an obvious association of MTHFR 677T allele with risk of ICH under all four comparison models (OR(T vs. C)=1.38, 95% CI 1.17-1.62, P<0.001; OR(TT vs. CC)=1.90 95% CI 1.42-2.55, P<0.001; OR(TT vs. TC/CC)=1.38 95% CI 1.20-1.59, P<0.001; OR(TT/TC vs. CC)=1.41 95% CI 1.12-1.78, P=0.003). Besides, both subgroup analyses and sensitivity analysis further identified the association above. CONCLUSION: The MTHFR 677T allele is associated with risk of ICH, and individuals with TT genotype have an obviously higher risk of ICH than those with the CC genotype.

Intestinal permeability in rats with CCl4-induced portal hypertension.

AIM: To investigate the intestinal barrier changes in rats with CCl4-induced portal hypertension. METHODS: The permeability of intestinal barrier detected by Lanthanum as a tracer was evaluated in rats. Bacterial translocation and plasma endotoxin were also determined. RESULTS: The incidence of bacterial translocation was 85% in rats with CCl4-induced portal hypertension, which was significantly higher than that in control rats (20%, P<0.01). Plasma endotoxin level was significantly higher in experimental group than in control group. Permeability of the epithelial mucosa and pathological alteration were increased in the ileum and the microvilli became shorter and thinner in rats with portal hypertension. CONCLUSION: Bacterial translocation occurs in rats with CCl4-induced portal hypertension and increased permeability between epithelial cells contributes to the translocation.

Role of perioperative parenteral nutrition in severely malnourished patients with Crohn's disease.

AIM: To evaluate the effect of perioperative parenteral nutrition on serum immunoglobulin, weight change, and post-operative outcome in severely malnourished patients with Crohn's disease. METHODS: Thirty-two severely malnourished patients with Crohn's disease who had undergone surgery in our hospital were reviewed. Sixteen patients who received perioperative parenteral nutrition were enrolled in the study group, and the other 16 patients who did not receive parenteral nutrition were enrolled in the control group. Serum immunoglobulin, body mass index (BMI), liver function, weight change, and postoperative complications were evaluated. RESULTS: Serum IgM levels elevated 1 wk before surgery in both groups, and decreased to normal value (from 139+/-41 to 105+/-29 mg/dL, P = 0.04) 4 wk after operation in the study group, while no significant changes was noted in the control group (from 133+/-16 to 129+/-13 mg/dL, P = 0.34). There were no significant changes in concentrations of IgG and IgA. The BMI of the study group increased from 13.9+/-0.6 to 15.3+/-0.7 kg/m(2) (P = 0.02) with no significant change in the control group (14.1+/-0.7 and 14.5+/-0.5, respectively, P = 0.81). The percentage of resuming work was higher in the study group than in the control group. CONCLUSION: Perioperative parenteral nutrition possibly ameliorates the humoral immunity, reverses malnutrition, and facilitates rehabilitation.

Effects of postoperative enteral immune-enhancing diet on plasma endotoxin level, plasma endotoxin inactivation capacity and clinical outcome.

This study examined the postoperative plasma endotoxin level, plasma endotoxin inactivation capacity and clinical outcome after administration of an enteral diet supplemented with glutamine, arginine and omega-3-fatty acid in patients undergoing gastrointestinal operations on an prospective, randomized and double-blind design. 40 patients undergoing gastrointestinal operations were randomized into two groups, with each having 20 patients. One group received standard enteral nutrition and the other was fed the formulation supplemented with glutamine, arginine and omega-3-fatty acid. The two groups were isonitrogenous. The infusion was started from day 1 after surgery and continued for 7 days. Blood samples were collected on the morning of day 1 before operation and on the morning of 1, 4 and 7 day(s) after operation and analyzed for plasma endotoxin level and endotoxin inactivation capacity (EIC). Our study found no differences between the two groups on plasma endotoxin level. After surgery a rapid reduction in plasma endotoxin inactivation capacity was observed in both groups, a significant recovery of the plasma endotoxin inactivation capacity was observed on morning of day 4 after surgery in the study group (0.12 +/- 0.02 EU/mL and 0.078 +/- 0.022 EU/mL respectively, P < 0.01). Shortened hospital stay was observed in the experimental group (11.7 +/- 2.0 days in the control group and 10.6 +/- 1.2 days in the experimental group respectively, P = 0.03). It is concluded that perioperative parenteral nutrition supplemented with glutamine, arginine and omega-3-fatty acid ameliorated postoperative immunodepression but without direct effect on endotoxemia.

Effects of perioperative parenteral glutamine-dipeptide supplementation on plasma endotoxin level, plasma endotoxin inactivation capacity and clinical outcome.

BACKGROUND & AIMS: We evaluated perioperative plasma endotoxin, plasma soluble CD14 molecule (sCD14), plasma endotoxin inactivation capacity (EIC) changes and clinical outcome after glutamine was provided in parenteral feedings to patients on whom gastrointestinal operations were performed using a prospective, randomized, double-blind study design. METHODS: Forty patients undergoing gastrointestinal operations were randomized into two groups, each had 20 patients. One group received standard parenteral nutrition and the other received the same formulation but supplemented with the dipeptide alanyl-glutamine, the two groups were isonitrogenous. The infusion was started from 1 day before operation to the 3rd day after operation for 5 days. Blood samples were collected on the morning of 1 day before operation, 3h after operation, and on the morning of 1, 4 and 7 days after operation and analyzed for plasma endotoxin level, plasma sCD14 level and EIC. RESULTS: There were no differences between the two groups on plasma endotoxin level. After surgery a rapid reduction in plasma EIC was observed in both groups, a significant restoration of the plasma EIC was observed on the morning of 1 and 4 days after surgery in the study group (0.12+/-0.02 and 0.078+/-0.022 EU/mL, respectively, P < 0.01). A significant rise in plasma sCD14 level was found in the study group on the morning of 1 and 4 days after surgery (14.32+/-1.69 and 10.34+/-1.14 microg/mL, respectively, P < 0.01). Shortened hospital stay was observed in the study group (11.7+/-2.0 days in the control group and 10.6+/-1.2 days on the study group respectively, P = 0.03). CONCLUSION: Perioperative parenteral nutrition supplemented with dipeptide alanyl-glutamine ameliorated postoperative immunodepression without direct effect on endotoxemia.

Methodological studies on plasma endotoxin level and endotoxin inactivation capacity.

To establish stable methods for detecting plasma endotoxin level and endotoxin inactivation capacity in a normal population and general surgical patients and evaluate their perioperative changes. 50 healthy people and 50 patients receiving gastrointestinal operation were enrolled, their plasma endotoxin levels and plasma endotoxin inactivation capacity were assayed. Our results showed that plasma endotoxin levels were 0.044 +/- 0.009 EU/ml in the normal population and 0.044 +/- 0.023 EU/ml in the preoperative patients. Endotoxin level peaked 3 h after the operation (0.223 +/- 0.041 EU/ml), and then decreased rapidly on the first day after the operation (0.134 +/- 0.164 EU/ml). Endotoxin inactivation capacity also had the same time course as endotoxin level. Systemic inflammatory response syndrome and infection induced another elevation in the time course. It is concluded that establishing the endotoxin standard curve by using pyrogenic free water is better than by using plasma. Plasma endotoxin inactivation capacity can be used as an indirect indicator of postoperative immune depression. Plasma endotoxin level and endotoxin inactivation capacity peaked shortly after operation, indicating surgical stress is closely related with the changes.

[The role of nutritional status on serum immunoglobulins, body weight and postoperative infectious-related complications in patients with Crohn's disease receiving perioperative parenteral nutrition].

OBJECTIVE: To evaluate the role of nutritional status on serum immunoglobulins, body weight and postoperative infectious-related complications in patients with Crohn's disease receiving perioperative parenteral nutrition (PN). METHODS: 32 patients with Crohn's disease receiving perioperative parenteral nutrition in our department between 1984 and 1994 were enrolled in this survey. 16 patients with loss of body weight in the range of 15%-30% were assigned to the malnutrition group, the other 16 patients with normal weight or loss of body weight less than 15% to the control group. Serum IgM, IgG and IgA levels were measured before and after PN by enzyme-linked immunosorbent assays. Liver function, body weight changes and postoperative complications were also analyzed. RESULTS: IgM levels were elevated before PN in both groups [control group: (133 +/- 16) mg/dl, malnutrition group: (139 +/- 41) mg/dl; normal value: (110 +/- 35) mg/dl; P = 0.04], decreased to normal value [(105 +/- 29) mg/dl, P = 0.02] in the malnutrition group while having no obvious changes in the control group [(129 +/- 13) mg/dl, P = 0.34]. No significant changes in concentrations of IgG and IgA were found (P in the range of 0.20-0.57). The average weight gain was 1.862 kg in malnutrition group [before PN: (45.8 +/- 8.9) kg, after PN: (48.0 +/- 8.8) kg; P = 0.005] and no significant changes in the control group [before PN: (55.6 +/- 6.1) kg, after PN: (56.3 +/- 6.0) kg; P = 0.46]. There was an increase in infectious complications in the control group (control group: 4 cases, 25%, malnourished group: 2 cases, 12.5%; P = 0.13). CONCLUSIONS: Perioperative parenteral nutrition ameliorated the humoral immunity, increased the body weight in patients with obvious malnutrition, whereas it had little value for those without or with mild malnutrition.

[Assay of carnitine in plasma and urine of healthy adults].

OBJECTIVE: To determine the levels of carnitine in plasma and daily excretion of carnitine in urine of healthy adults so as to provide the reference standard for studying the changes of carnitine in patients. METHODS: Carnitine in plasma and urine was assayed with high performance liquid chromatography (HPLC). The levels of total carnitine (TC), free carnitine (FC) and acetyl-carnitine (AC) in fasting plasma and the daily excretion of TC, FC and AC in urine were assayed in 40 healthy adults (20 men and 20 women) with standard diet. RESULTS: Good linearity (r 2 > or = 0.999) was observed in assaying TC, FC and AC. The relative standard deviation (RSD) was lower than 9.1% and bias lower than 5.6%. It was showed that the plasmatic levels of TC, FC and AC in healthy men [(53.1 +/- 8.5), (41.2 +/- 6.1), (6.2 +/- 0.6) mumol/L] were significantly higher than those in healthy women [(45.4 +/- 5.6), (35.2 +/- 4.9), (5.7 +/- 0.7) mumol/L] (P = 0.002, 0.002, 0.035). The daily urinary excretion of TC, FC and AC in healthy men [(386.1 +/- 22.9), (180.5 +/- 31.8), (33.8 +/- 3.3) mumol] were also significantly higher than those in healthy women [(240.1 +/- 35.6), (112.7 +/- 22.6), (29.3 +/- 4.3) mumol] (P < 0.0005, < 0.0005, < 0.0005) when the adults were given standard diet. Both the plasmatic levels and the daily urinary excretion of TC, FC and AC were of significantly positive correlation with lean body mass (LBM) (r = 0.501-0.856). The (TC-FC)/FC ratios in plasma were 0.29 +/- 0.05 for male and 0.29 +/- 0.04 for female. CONCLUSION: Good precision and accuracy were observed in assaying carnitine with HPLC. After standard diet, both the level of carnitine in fasting plasma and the daily urinary carnitine excretion of healthy adults were positively correlated with LBM.