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Gut microbiota metabolites, amino acid metabolites and improvements in insulin sensitivity and glucose metabolism: the POUNDS Lost trial.
Heianza, Y, Sun, D, Li, X, DiDonato, JA, Bray, GA, Sacks, FM, Qi, L
Gut. 2019;(2):263-270
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Abstract
OBJECTIVE Alterations in gut microbiota have been linked to host insulin resistance, diabetes and impaired amino acid metabolism. We investigated whether changes in gut microbiota-dependent metabolite of trimethylamine N-oxide (TMAO) and its nutrient precursors (choline and L-carnitine) were associated with improvements in glucose metabolism and diabetes-related amino acids in a weight-loss diet intervention. DESIGN We included 504 overweight and obese adults who were randomly assigned to one of four energy-reduced diets varying in macronutrient intake. The 6-month changes (Δ) in TMAO, choline and L-carnitine levels after the intervention were calculated. RESULTS Greater decreases in choline and L-carnitine were significantly (p<0.05) associated with greater improvements in fasting insulin concentrations and homeostasis model assessment of insulin resistance (HOMA-IR) at 6 months. The reduction of choline was significantly related to 2-year improvements in glucose and insulin resistance. We found significant linkages between dietary fat intake and ΔTMAO for changes in fasting glucose, insulin and HOMA-IR (pinteraction <0.05); a greater increase in TMAO was related to lesser improvements in the outcomes among participants who consumed a high-fat diet. In addition, ΔL-carnitine and Δcholine were significantly related to changes in amino acids (including branched-chain and aromatic amino acids). Interestingly, the associations of ΔTMAO, Δcholine and ΔL-carnitine with diabetes-related traits were independent of the changes in amino acids. CONCLUSION Our findings underscore the importance of changes in TMAO, choline and L-carnitine in improving insulin sensitivity during a weight-loss intervention for obese patients. Dietary fat intake may modify the associations of TMAO with insulin sensitivity and glucose metabolism. TRIAL REGISTRATION NUMBER NCT00072995.
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Therapeutic effects of cerebrolysin added to risperidone in patients with schizophrenia dominated by negative symptoms.
Xiao, S, Xue, H, Li, G, Yuan, C, Li, X, Chen, C, Wu, HZ, Mitchell, P, Zhang, M
The Australian and New Zealand journal of psychiatry. 2012;(2):153-60
Abstract
OBJECTIVE Cerebrolysin is a nootropic drug with unique neurotrophic activities directly affecting cerebral neurons. This study evaluated the efficacy and safety of cerebrolysin added to risperidone in patients with schizophrenia dominated by negative symptoms. METHODS The trial was a double-blind, placebo-controlled, parallel-group design. A total of 109 patients who met the DSM-IV diagnostic criteria for schizophrenia were randomly assigned to cerebrolysin (cerebrolysin plus risperidone, n=55) or placebo (risperidone only, n=54) groups. Intravenous infusions of 30 ml cerebrolysin or placebo were given once daily from Monday to Friday for 4 weeks. Efficacy was assessed with measurements including the Positive and Negative Symptoms Scale (PANSS), Wechsler Memory Scale (WMS), modified Chinese Wechsler Adult Intelligence Scale (mWAIS). and Clinical Global Impression (CGI). RESULTS Patients in both groups demonstrated improvements in psychiatric symptoms and cognitive and memory performance as assessed by PANSS, mWAIS, and WMS over the trial. There was no difference in rates of change in the PANSS total score or negative score between the two treatment groups. Patients treated with cerebrolysin showed significantly greater improvements in cognitive and memory function from week 2. No severe treatment adverse events were observed in either group. The frequency of adverse events was comparable between the two groups at the end of the treatment. CONCLUSION Cerebrolysin added to risperidone did not augment the efficacy of risperidone in treating the psychotic symptoms of schizophrenia patients over an 8-week trial. Cerebrolysin at 30 ml per day as an adjunctive treatment was safe and may improve cognitive and memory functions of patients with schizophrenia dominated by negative symptoms.