Abstract

INTRODUCTION Intestinal metabolism and microbiota profiles are impaired in obesity and insulin resistance. Moreover, dysbiotic gut microbiota has been suggested to promote systemic low-grade inflammation and insulin resistance through the release of endotoxins particularly lipopolysaccharides. We have previously shown that exercise training improves intestinal metabolism in healthy men. To understand whether changes in intestinal metabolism interact with gut microbiota and its release of inflammatory markers, we studied the effects of sprint interval (SIT) and moderate-intensity continuous training (MICT) on intestinal metabolism and microbiota in subjects with insulin resistance. METHODS Twenty-six, sedentary subjects (prediabetic, n = 9; type 2 diabetes, n = 17; age, 49 [SD, 4] yr; body mass index, 30.5 [SD, 3]) were randomized into SIT or MICT. Intestinal insulin-stimulated glucose uptake (GU) and fatty acid uptake (FAU) from circulation were measured using positron emission tomography. Gut microbiota composition was analyzed by 16S rRNA gene sequencing and serum inflammatory markers with multiplex assays and enzyme-linked immunoassay kit. RESULTS V˙O2peak improved only after SIT (P = 0.01). Both training modes reduced systematic and intestinal inflammatory markers (tumor necrosis factor-α, lipopolysaccharide binding protein) (time P < 0.05). Training modified microbiota profile by increasing Bacteroidetes phylum (time P = 0.03) and decreasing Firmicutes/Bacteroidetes ratio (time P = 0.04). Moreover, there was a decrease in Clostridium genus (time P = 0.04) and Blautia (time P = 0.051). Only MICT decreased jejunal FAU (P = 0.02). Training had no significant effect on intestinal GU. Colonic GU associated positively with Bacteroidetes and inversely with Firmicutes phylum, ratio Firmicutes/Bacteroidetes and Blautia genus. CONCLUSIONS Intestinal substrate uptake associates with gut microbiota composition and whole-body insulin sensitivity. Exercise training improves gut microbiota profiles and reduces endotoxemia.

Abstract

Targeting gut microbiota with synbiotics (probiotic supplements containing prebiotic components) is emerging as a promising intervention in the comprehensive nutritional approach to reducing obesity. Weight loss resulting from low-carbohydrate high-protein diets can be significant but has also been linked to potentially negative health effects due to increased bacterial fermentation of undigested protein within the colon and subsequent changes in gut microbiota composition. Correcting obesity-induced disruption of gut microbiota with synbiotics can be more effective than supplementation with probiotics alone because prebiotic components of synbiotics support the growth and survival of positive bacteria therein. The purpose of this placebo-controlled intervention clinical trial was to evaluate the effects of a synbiotic supplement on the composition, richness and diversity of gut microbiota and associations of microbial species with body composition parameters and biomarkers of obesity in human subjects participating in a weight loss program. The probiotic component of the synbiotic used in the study contained Lactobacillus acidophilus, Bifidobacterium lactis, Bifidobacterium longum, and Bifidobacterium bifidum and the prebiotic component was a galactooligosaccharide mixture. The results showed no statistically significant differences in body composition (body mass, BMI, body fat mass, body fat percentage, body lean mass, and bone mineral content) between the placebo and synbiotic groups at the end of the clinical trial (3-month intervention, 20 human subjects participating in weight loss intervention based on a low-carbohydrate, high-protein, reduced energy diet). Synbiotic supplementation increased the abundance of gut bacteria associated with positive health effects, especially Bifidobacterium and Lactobacillus, and it also appeared to increase the gut microbiota richness. A decreasing trend in the gut microbiota diversity in the placebo and synbiotic groups was observed at the end of trial, which may imply the effect of the high-protein low-carbohydrate diet used in the weight loss program. Regression analysis performed to correlate abundance of species following supplementation with body composition parameters and biomarkers of obesity found an association between a decrease over time in blood glucose and an increase in Lactobacillus abundance, particularly in the synbiotic group. However, the decrease over time in body mass, BMI, waist circumstance, and body fat mass was associated with a decrease in Bifidobacterium abundance. The results obtained support the conclusion that synbiotic supplement used in this clinical trial modulates human gut microbiota by increasing abundance of potentially beneficial microbial species.

Abstract

BACKGROUND Although few studies have reported improved clinical outcomes with the administration of vitamin B1 and C in critically ill patients with septic shock or severe pneumonia, its clinical impact on patients with sepsis-related acute respiratory distress syndrome (ARDS) remains unclear. The purpose of this study was to evaluate the association with vitamin B and C supplementation and clinical outcomes in patients with ARDS. METHODS Patients with ARDS requiring invasive mechanical ventilation, admitted to the medical intensive care unit (ICU) were included in this study. Clinical outcomes were compared between patients administered with vitamin B1 (200 mg/day) and C (2 g/day) June 2018-May 2019 (the supplementation group) and those who did not receive vitamin B1 and C administration June 2017-May 2018 (the control group). RESULTS Seventy-nine patients were included. Thirty-three patients received vitamin B1 and C whereas 46 patients did not. Steroid administration was more frequent in patients receiving vitamin B1 and C supplementation than in those without it. There were no significant differences in the mortality between the patients who received vitamin B1 and C and those who did not. There were not significant differences in ventilator and ICU-free days between each of the 21 matched patients. CONCLUSION Vitamin B1 and C supplementation was not associated with reduced mortality rates, and ventilator and ICU-free days in patients with sepsis-related ARDS requiring invasive mechanical ventilation.

Abstract

Sarcopenia is a geriatric syndrome and it impairs physical function. Patients with type 2 diabetes mellitus (T2DM) are at a higher risk of sarcopenia. The purpose of this study is to explore characteristics of general information and metabolic factors of sarcopenia in patients with T2DM in the northeast of China, and provide information for the prevention and treatment of sarcopenia in clinical practice.Patients with T2DM aged ≥65 were recruited in Changchun from March 2017 to February 2018. Questionnaires of general information, physical examination, laboratory and imaging examination were conducted. The patients were assigned into sarcopenia group and non-sarcopenia group according to the diagnostic criteria proposed by Asian working group for sarcopenia (AWGS), and the differences between 2 groups were analyzed.A total of 132 participants were included in this study, of which, 38 (28.8%) were diagnosed with sarcopenia. 94 (71.2%) were with no sarcopenia. Logistic regression analysis showed that age (OR: 1.182, 95%CI: 1.038-1.346), trunk fat mass (TFM) (OR: 1.499, 95%CI: 1.146-1.960) and free thyroxine (FT4) (OR: 1.342, 95%CI: 1.102-1.635) were independent risk factors for sarcopenia. BMI (body mass index) (OR: 0.365, 95%CI: 0.236-0.661), exercise (OR: 0.016, 95%CI: 0.001-0.169), female (OR: 0.000, 95%CI: 0.00-0.012), metformin (OR: 0.159, 95%CI: 0.026-0.967) and TSM (trunk skeletal muscle mass) (OR: 0.395, 95%CI: 0.236-0.661) were protective factors for sarcopenia.Sarcopenia in patients with T2DM is associated with increased age, increased TFM and increased FT4 level. Regular exercise, female, metformin administrations, high BMI and increased TSM are associated with lower risk of sarcopenia.

Abstract

Importance: Treatment of pediatric obesity is challenging. Preclinical studies in mice indicated that weight and metabolism can be altered by gut microbiome manipulation. Objective: To assess efficacy of fecal microbiome transfer (FMT) to treat adolescent obesity and improve metabolism. Design, Setting, and Participants: This randomized, double-masked, placebo-controlled trial (October 2017-March 2019) with a 26-week follow-up was conducted among adolescents aged 14 to 18 years with a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 30 or more in Auckland, New Zealand. A total of 87 individuals took part-565 individuals responded to advertisements, 328 were ineligible, and 150 declined participation. Clinical data were analyzed from September 2019 to May 2020. Interventions: Single course of oral encapsulated fecal microbiome from 4 healthy lean donors of the same sex or saline placebo. Main Outcomes and Measures: Primary outcome was BMI standard deviation score at 6 weeks using intention-to-treat analysis. Secondary outcomes included body composition, cardiometabolic parameters, well-being, and gut microbiome composition. Results: Eighty-seven participants (59% female adolescents, mean [SD] age 17.2 [1.4] years) were randomized 1:1, in groups stratified by sex, to FMT (42 participants) or placebo (45 participants). There was no effect of FMT on BMI standard deviation score at 6 weeks (adjusted mean difference [aMD] -0.026; 95% CI -0.074, 0.022). Reductions in android-to-gynoid-fat ratio in the FMT vs placebo group were observed at 6, 12, and 26 weeks, with aMDs of -0.021 (95% CI, -0.041 to -0.001), -0.023 (95% CI, -0.043 to -0.003), and -0.029 (95% CI, -0.049 to -0.008), respectively. There were no observed effects on insulin sensitivity, liver function, lipid profile, inflammatory markers, blood pressure, total body fat percentage, gut health, and health-related quality of life. Gut microbiome profiling revealed a shift in community composition among the FMT group, maintained up to 12 weeks. In post-hoc exploratory analyses among participants with metabolic syndrome at baseline, FMT led to greater resolution of this condition (18 to 4) compared with placebo (13 to 10) by 26 weeks (adjusted odds ratio, 0.06; 95% CI, 0.01-0.45; P = .007). There were no serious adverse events recorded throughout the trial. Conclusions and Relevance: In this randomized clinical trial of adolescents with obesite, there was no effect of FMT on weight loss in adolescents with obesity, although a reduction in abdominal adiposity was observed. Post-hoc analyses indicated a resolution of undiagnosed metabolic syndrome with FMT among those with this condition. Further trials are needed to confirm these results and identify organisms and mechanisms responsible for mediating the observed benefits. Trial Registration: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12615001351505.

Abstract

BACKGROUND Referral to weight loss programmes is the only effective treatment for non-alcoholic fatty liver disease (NAFLD). Clinicians should advise weight loss and screen for liver fibrosis using the Enhanced Liver Fibrosis (ELF) score. AIM: To examine if the ELF score changes with weight loss. DESIGN AND SETTING Randomised controlled trial (ISRCTN85485463) in UK primary care during 2007-2008. METHOD Adults with a BMI of 27-35 kg/m2 and ≥1 risk factor for obesity-related disease were randomised to attend a community weight loss programme (n = 45) or receive usual weight loss advice from a practice nurse (n = 28). Weight and the ELF score were measured at baseline and 1 year. Analysis of covariance examined mean changes in the ELF score between groups and its relationship with weight loss. RESULTS Mean (SD) BMI was 31.10 kg/m2 (2.55) with evidence of moderate levels of liver fibrosis at baseline (mean ELF score: 8.93 [0.99]). There was no evidence that the community weight loss programme reduced the ELF score compared with usual care (difference +0.13 points, 95% CI: -0.25 to 0.52) despite greater weight loss (difference: -2.66 kg, 95% CI: -5.02 to -0.30). Mean weight loss in the whole cohort was 7.8% (5.9). There was no evidence of an association between weight change and change in ELF; the coefficient for a 5% weight loss was -0.15 (95% CI: -0.30 to 0.0002). CONCLUSION We found no evidence that the ELF score changed meaningfully following moderate weight loss. Clinicians should not use the ELF score to measure improvements in NAFLD fibrosis following weight loss programmes.

Abstract

Obesity is a global epidemic, contributing significantly to chronic non-communicable diseases, such as type 2 diabetes mellitus, cardiovascular diseases and metabolic syndrome. Metabolic flexibility, the ability of organisms to switch between metabolic substrates, is found to be impaired in obesity, possibly contributing to the development of chronic illnesses. Several studies have shown the improvement of metabolic flexibility after weight loss. In this study, we have mapped the cellular metabolism of the adipose tissue from a weight loss study to stratify the cellular metabolic processes and metabolic flexibility during weight loss. We have found that for a majority of the individuals, cellular metabolism was downregulated during weight loss, with gene expression of all major cellular metabolic processes (such as glycolysis, fatty acid β-oxidation etc.) being lowered during weight loss and weight maintenance. Parallel to this, the gene expression of immune system related processes involving interferons and interleukins increased. Previously, studies have indicated both negative and positive effects of post-weight loss inflammation in the adipose tissue with regards to weight loss or obesity and its co-morbidities; however, mechanistic links need to be constructed in order to determine the effects further. Our study contributes towards this goal by mapping the changes in gene expression across the weight loss study and indicates possible cross-talk between cellular metabolism and inflammation.

Abstract

The aim of this study was to evaluate the relationship between educational attainment and cardiorespiratory fitness (CRF) as a predictor of metabolic syndrome in a Korean population.In this single-center, retrospective cross-sectional study, 988 healthy adults (601 men and 387 women) who underwent regular health check-up in Seoul St. Mary's Hospital were analyzed. Educational attainment was categorized into 3 groups according to their final grade of educational course: middle or high school (≤12 years of education), college or university (12-16 years of education), and postgraduate (≥16 years of education). CRF was assessed by cardiopulmonary exercise testing, biceps strength, hand grip strength, bioelectrical impedance analysis, and echocardiography. Metabolic syndrome was diagnosed according to the 3rd report of the National Cholesterol Education Program.Among the subjects, 357 (36.1%) had metabolic syndrome. The postgraduate group had significantly higher peak oxygen consumption (VO2), biceps strength, hand grip strength, and peak expiratory flow than other groups (all P < .001). This group showed better left ventricular diastolic function, in terms of deceleration time of mitral inflow, maximal tricuspid valve regurgitation velocity, and left atrial volume index than other groups. Peak VO2 (%) was significantly correlated with all the parameters of metabolic syndrome, including insulin resistance (r = -0.106, P = .002), waist circumference (r = -0.387, P < .001), triglyceride (r = -0.109, P = .001), high density lipoprotein-cholesterol (r = 0.219, P < .001), systolic blood pressure (r = -0.143, P < .001), and diastolic blood pressure (r = -0.177, P < .001). And Peak VO2 (%) was found to be a predictor of metabolic syndrome (adjusted β = .988, P < .001). However, the level of education was not able to predict metabolic syndrome (postgraduate group; β = .955, P = .801).Although the postgraduate group had better CRF than other groups, the educational attainment could not exclusively predict metabolic syndrome in this study. Further research is needed to reveal the socioeconomic mechanism of developing metabolic syndrome.

Abstract

It is well known, based on the previous research, that a ketogenic diet leads to an improvement in the lipid profile and decreases cardiovascular risk factors such as hypertension. However, recent studies have also reported increased levels of total cholesterol and low-density lipoprotein cholesterol (LDL-C) as a result of this diet. It has been postulated that this elevation in LDL-C would not likely increase cardiovascular complications due to the large LDL-C particle size. In this case report, we present a case of a rapid increase, followed by a rapid correction of LDL-C, in a patient following a ketogenic diet. A 56-year-old Hispanic female with a past medical history of hypertension and fibromyalgia presented to the outpatient clinic for evaluation of fatigue. She reported that she had been following a strict ketogenic diet along with daily regular exercise for approximately 30-40 days prior to this visit. Her diet consisted of low-carbohydrate vegetables, seafood, avocados, eggs, and coconut oil. The patient's physical exam was unremarkable. At the time of the visit, her BMI was calculated at 28 kg/m2, with a weight loss of approximately six to seven pounds since starting the ketogenic diet. Her fasting lipid profile showed a total cholesterol of 283 mg/dl, LDL-C of 199 mg/dl, high-density lipoprotein cholesterol (HDL-C) of 59 mg/dl, and triglycerides levels of 124 mg/dl. She was instructed to stop the ketogenic diet and to incorporate a balanced diet, which includes a higher amount of carbohydrates and lower fat. She was also started on high-intensity atorvastatin. However, she reported experiencing myalgias soon after initiating atorvastatin; therefore, the medication was switched to rosuvastatin 10 mg at bedtime. During her follow-up appointment, she reported not having consistently taken rosuvastatin due to the concern of worsening myalgias. Her lipid profile, after four weeks of ketogenic diet discontinuation and inconsistent use of statins, showed significant improvement resulting in a total cholesterol level of 190 mg/dl and LDL-C of 106 mg/dl. Statin therapy was discontinued, and the patient maintained optimal LDL-C levels on subsequent testing. This patient showed a rapid increase in LDL-C and total cholesterol after only 30-40 days of the ketogenic diet. Her drastic elevation in LDL-C could also be explained due to the rapid weight loss, as cholesterol in the adipose tissue is known to mobilize as the fat cells shrink. Interestingly, her BMI four weeks after the discontinuation of the ketogenic diet did not change despite a marked improvement in her LDL-C. Therefore, we believe the acute onset and resolution of hyperlipidemia was secondary to the ketogenic diet itself. This study helps to better understand expectations when recommending a ketogenic diet to patients and its consequences. There is currently no statistically significant study that proves this elevation of LDL-C would not increase cardiovascular risks. Furthermore, the necessity for statin therapy in a ketogenic diet-induced hyperlipidemia remains unknown.

Abstract

CONTEXT Altered tissue-specific glucocorticoid metabolism has been described in uncomplicated obesity and type 2 diabetes. We hypothesized that weight loss induced by diet and exercise, which has previously been shown to reverse abnormal cortisol metabolism in uncomplicated obesity, also normalizes cortisol metabolism in patients with type 2 diabetes. OBJECTIVE Test the effects of a diet intervention with added exercise on glucocorticoid metabolism. DESIGN Two groups followed a Paleolithic diet (PD) for 12 weeks with added 180 min of structured aerobic and resistance exercise per week in one randomized group (PDEX). SETTING Umeå University Hospital. PARTICIPANTS Men and women with type 2 diabetes treated with lifestyle modification ± metformin were included. Twenty-eight participants (PD, n = 15; PDEX, n = 13) completed measurements of glucocorticoid metabolism. MAIN OUTCOME MEASURES Changes in glucocorticoid metabolite levels in 24-h urine samples, expression of HSD11B1 mRNA in s.c. adipose tissue and conversion of orally administered cortisone to cortisol measured in plasma. Body composition and insulin sensitivity were measured using a hyperinsulinemic-euglycemic clamp, and liver fat was measured by magnetic resonance spectroscopy. RESULTS Both groups lost weight and improved insulin sensitivity. Conversion of orally taken cortisone to plasma cortisol and the ratio of 5α-THF + 5β-THF/THE in urine increased in both groups. CONCLUSIONS These interventions caused weight loss and improved insulin sensitivity with concomitant increases in the conversion of cortisone to cortisol, which is an estimate of hepatic HSD11B1 activity. This suggests that dysregulation of liver glucocorticoid metabolism in these patients is a consequence rather than a cause of metabolic dysfunction.