Antje Damms-Machado

Multicenter evaluation of an interdisciplinary 52-week weight loss program for obesity with regard to body weight, comorbidities and quality of life—a prospective study

Objectives:To determine the effectiveness of a structured multidisciplinary non-surgical obesity therapy program on the basis of a temporary low-calorie-diet for 12 weeks, and additional intervention modules to enhance nutritional education, to increase physical activity and to modify eating behavior.Design:Prospective multicenter observational study in obese individuals undergoing a medically supervised outpatient-based 52-week treatment in 37 centers in Germany.Subjects:A total of 8296 participants with a body mass index (BMI) of >30 kg m−2 included within 8.5 years.Measurements:Main outcome measures were body weight loss, waist circumference (WC), blood pressure, quality of life and adverse events.Results:In females, initial body weight was reduced after the 1-year-intervention by 19.6 kg (95% confidence intervals 19.2–19.9 kg) and in males by 26.0 kg (25.2–26.8) according to per protocol analysis of 4850 individuals. Intention-to-treat (ITT) analysis revealed a weight reduction of 15.2 kg (14.9–15.6) in females and 19.4 kg (18.7–20.1) in males. Overall, the intervention resulted in mean reduction in WC of 11 cm; it reduced the prevalence of the metabolic syndrome by 50% and the frequency of hypertension from 47 to 29% of all participants (ITT, all P<0.001). The beneficial effects could be documented for up to 3 years and comprised significant improvement of health-related quality of life. The incidence of adverse effects was low; the only event repeatedly observed and possibly related to either the intervention or the underlying disease was biliary disorders.Conclusion:The present non-surgical intervention program is a highly effective treatment of obesity grades I–III and obesity-related diseases, and therefore, could be a valuable basis for future weight maintenance strategies required for sustained success.

Effects of Surgical and Dietary Weight Loss Therapy for Obesity on Gut Microbiota Composition and Nutrient Absorption

Evidence suggests a correlation between the gut microbiota composition and weight loss caused by caloric restriction. Laparoscopic sleeve gastrectomy (LSG), a surgical intervention for obesity, is classified as predominantly restrictive procedure. In this study we investigated functional weight loss mechanisms with regard to gut microbial changes and energy harvest induced by LSG and a very low calorie diet in ten obese subjects (n = 5 per group) demonstrating identical weight loss during a follow-up period of six months. For gut microbiome analysis next generation sequencing was performed and faeces were analyzed for targeted metabolomics. The energy-reabsorbing potential of the gut microbiota decreased following LSG, indicated by the Bacteroidetes/Firmicutes ratio, but increased during diet. Changes in butyrate-producing bacterial species were responsible for the Firmicutes changes in both groups. No alteration of faecal butyrate was observed, but the microbial capacity for butyrate fermentation decreased following LSG and increased following dietetic intervention. LSG resulted in enhanced faecal excretion of nonesterified fatty acids and bile acids. LSG, but not dietetic restriction, improved the obesity-associated gut microbiota composition towards a lean microbiome phenotype. Moreover, LSG increased malabsorption due to loss in energy-rich faecal substrates and impairment of bile acid circulation. This trial is registered with ClinicalTrials.gov NCT01344525.

Micronutrient deficiency in obese subjects undergoing low calorie diet

BackgroundThe prevalence of micronutrient deficiencies is higher in obese individuals compared to normal-weight people, probably because of inadequate eating habits but also due to increased demands among overweight persons, which are underestimated by dietary reference intakes (DRI) intended for the general population. We therefore evaluated the dietary micronutrient intake in obese individuals compared to a reference population and DRI recommendations. Furthermore, we determined the micronutrient status in obese subjects undergoing a standardized DRI-covering low-calorie formula diet to analyze if the DRI meet the micronutrient requirements of obese individuals.MethodsIn 104 subjects baseline micronutrient intake was determined by dietary record collection. A randomly assigned subgroup of subjects (n = 32) underwent a standardized DRI-covering low-calorie formula diet over a period of three months. Pre- and post-interventional intracellular micronutrient status in buccal mucosa cells (BMC) was analyzed, as well as additional micronutrient serum concentrations in 14 of the subjects.ResultsPrior to dietetic intervention, nutrition was calorie-rich and micronutrient-poor. Baseline deficiencies in serum concentrations were observed for 25-hydroxyvitamin-D, vitamin C, selenium, iron, as well as ß-carotene, vitamin C, and lycopene in BMC. After a three-month period of formula diet even more subjects had reduced micronutrient levels of vitamin C (serum, BMC), zinc, and lycopene. There was a significant negative correlation between lipophilic serum vitamin concentrations and body fat, as well as between iron and C-reactive protein.ConclusionsThe present pilot study shows that micronutrient deficiency occurring in obese individuals is not corrected by protein-rich formula diet containing vitamins and minerals according to DRI. In contrast, micronutrient levels remain low or become even lower, which might be explained by insufficient intake, increased demand and unbalanced dispersal of lipophilic compounds in the body.Trial registrationThe study was registered at ClinicalTrials.gov (NCT01344525). The study protocol comprises only a part of the approved trial protocol.

Characterization of the Gut Microbial Community of Obese Patients Following a Weight-Loss Intervention Using Whole Metagenome Shotgun Sequencing.

Background/Objectives Cross-sectional studies suggested that obesity is promoted by the gut microbiota. However, longitudinal data on taxonomic and functional changes in the gut microbiota of obese patients are scarce. The aim of this work is to study microbiota changes in the course of weight loss therapy and the following year in obese individuals with or without co-morbidities, and to asses a possible predictive value of the gut microbiota with regard to weight loss maintenance. Subjects/Methods Sixteen adult patients, who followed a 52-week weight-loss program comprising low calorie diet, exercise and behavioral therapy, were selected according to their weight-loss course. Over two years, anthropometric and metabolic parameters were assessed and microbiota from stool samples was functionally and taxonomically analyzed using DNA shotgun sequencing. Results Overall the microbiota responded to the dietetic and lifestyle intervention but tended to return to the initial situation both at the taxonomical and functional level at the end of the intervention after one year, except for an increase in Akkermansia abundance which remained stable over two years (12.7x103 counts, 95%CI: 322–25100 at month 0; 141x103 counts, 95%CI: 49-233x103 at month 24; p = 0.005). The Firmicutes/Bacteroidetes ratio was higher in obese subjects with metabolic syndrome (0.64, 95%CI: 0.34–0.95) than in the “healthy obese” (0.27, 95%CI: 0.08–0.45, p = 0.04). Participants, who succeeded in losing their weight consistently over the two years, had at baseline a microbiota enriched in Alistipes, Pseudoflavonifractor and enzymes of the oxidative phosphorylation pathway compared to patients who were less successful in weight reduction. Conclusions Successful weight reduction in the obese is accompanied with increased Akkermansia numbers in feces. Metabolic co-morbidities are associated with a higher Firmicutes/Bacteroidetes ratio. Most interestingly, microbiota differences might allow discrimination between successful and unsuccessful weight loss prior to intervention.

Analysis of the intestinal microbiota using SOLiD 16S rRNA gene sequencing and SOLiD shotgun sequencing

BackgroundMetagenomics seeks to understand microbial communities and assemblages by DNA sequencing. Technological advances in next generation sequencing technologies are fuelling a rapid growth in the number and scope of projects aiming to analyze complex microbial environments such as marine, soil or the gut. Recent improvements in longer read lengths and paired-sequencing allow better resolution in profiling microbial communities. While both 454 sequencing and Illumina sequencing have been used in numerous metagenomic studies, SOLiD sequencing is not commonly used in this area, as it is believed to be more suitable in the context of reference-guided projects.ResultsTo investigate the performance of SOLiD sequencing in a metagenomic context, we compared taxonomic profiles of SOLiD mate-pair sequencing reads with Sanger paired reads and 454 single reads. All sequences were obtained from the bacterial 16S rRNA gene, which was amplified from microbial DNA extracted from a human fecal sample. Additionally, from the same fecal sample, complete genomic microbial DNA was extracted and shotgun sequenced using SOLiD sequencing to study the composition of the intestinal microbiota and the existing microbial metabolism. We found that the microbiota composition of 16S rRNA gene sequences obtained using Sanger, 454 and SOLiD sequencing provide results comparable to the result based on shotgun sequencing. Moreover, with SOLiD sequences we obtained more resolution down to the species level. In addition, the shotgun data allowed us to determine a functional profile using the databases SEED and KEGG.ConclusionsThis study shows that SOLiD mate-pair sequencing is a viable and cost-efficient option for analyzing a complex microbiome. To the best of our knowledge, this is the first time that SOLiD sequencing has been used in a human sample.

Gut permeability is related to body weight, fatty liver disease, and insulin resistance in obese individuals undergoing weight reduction

BACKGROUND Obesity and associated metabolic disorders are related to impairments of the intestinal barrier. OBJECTIVE We examined lactulose:mannitol (Lac:Man) permeability in obese individuals with and without liver steatosis undergoing a weight-reduction program to test whether an effective weight-loss program improves gut barrier function and whether obese patients with or without liver steatosis differ in this function. DESIGN Twenty-seven adult, nondiabetic individuals [mean ± SD body mass index (BMI; in kg/m2): 43.7 ± 5.2; 78% with moderate or severe liver steatosis] were included in the follow-up intervention study (n = 13 by month 12). All patients reduced their weight to a mean ± SD BMI of 36.4 ± 5.1 within 12 mo. We assessed barrier functions by the oral Lac:Man and the fecal zonulin tests. Insulin resistance was assessed by the homeostatic model assessment index (HOMA), and liver steatosis by sonography and the fatty liver index (FLI). RESULTS The Lac:Man ratio and circulating interleukin (IL) 6 concentration decreased during intervention from 0.080 (95% CI: 0.073, 0.093) to 0.027 (95% CI: 0.024, 0.034; P < 0.001) and from 4.2 ± 1.4 to 2.8 ± 1.6 pg/mL (P < 0.01), respectively. At study start, the Lac:Man ratio was higher in patients with moderate or severe steatosis than in those without any steatosis (P < 0.001). The Lac:Man ratio tended to correlate with HOMA (ρ = 0.55, P = 0.052), which correlated with FLI (ρ = 0.75, P < 0.01). A multiple-regression analysis led to a final model explaining FLI best through BMI, waist circumference, and the Lac:Man ratio. CONCLUSIONS Intestinal permeability is increased in obese patients with steatosis compared with obese patients without. The increased permeability fell to within the previously reported normal range after weight reduction. The data suggest that a leaky gut barrier is linked with liver steatosis and could be a new target for future steatosis therapies. This trial was registered at clinicaltrials.gov as NCT01344525.

Gender Differences in the Outcome of Obesity Treatments and Weight Loss Maintenance - A Systematic Review

Obesity is one of the major health concerns of today. The aim of the study was to review existing literature comparing gender differences in Weight Loss (WL) and Weight Loss Maintenance (WLM). A systematic review of published studies (to November 2009) examining WL and WLM and provided results separated by gender was conducted. Two reviewers selected studies for inclusion, assessed quality, and extracted data. The database search identified 1072 references for screening and 229 were selected for possible inclusion. A search update in August 2011 identified an additional 186 references and 62 were selected for possible inclusion. Fifty-four studies were included. Seventeen studies included surgical WL procedures and 37 studies examined nonsurgical WL treatments. For both types of WL treatment, about half of the studies reported higher absolute WL in men whereas the other half of the studies reported no gender differences. The majority of the 12 studies on WLM reported no gender differences. Meta-analysis revealed higher relative weight loss in men compared to women. WL treatment outcome appears to be in favour of WL in men. More research attention should be paid to gender specifics regarding WL treatment and WLM.

Nutritional Deficiencies in Obese Sleeve Gastrectomy Patients

Since the early 2000s, there has been an exponential rise in the bariatric procedure sleeve gastrectomy (SG) for the treatment of morbid obesity, resulting in promising short- and midterm efficacy associated with substantial weight loss and remission of comorbidities. By resecting the greater curvature of the gastric body, a sleeved stomach is formed. The complex procedures through which the beneficial effects of SG and the impact on surgically modified food digestion, which may promote nutrient deficiencies and protein malnutrition, are poorly understood. The first studies showed that after the procedure patients are mainly at risk of developing deficiencies in vitamin D, calcium, vitamin B12, folate, iron, and zinc. Besides the increased postoperative incidence of nutritional deficiencies, commonly observed preoperative deficits in bariatric surgery candidates include diet-related complications in the postoperative period. Moreover, following SG, protein energy malnutrition can occur due to intolerance to protein-rich foods. Recent data indicate the need for lifelong multivitamin supplementation following restrictive SG. In addition, controlled trials are needed to define the type and dosage of micronutrients required for general postoperative care.

Changes in Plasma Acylcarnitine and Lysophosphatidylcholine Levels Following a High-Fructose Diet: A Targeted Metabolomics Study in Healthy Women

Background: The consumption of high amounts of fructose is associated with metabolic diseases. However, the underlying mechanisms are largely unknown. Objective: To determine the effects of high fructose intake on plasma metabolomics. Study design: We enrolled 12 healthy volunteers (six lean and six obese women, age 24–35 years) in a crossover intervention study. All participants carried out three diets: (1) low fructose (<10 g/day); (2) high fructose (100 g/day) from natural food sources (fruit); and (3) high fructose (100 g/day) from high fructose syrup (HFS). Outcome measures: The primary outcome was changes in plasma metabolites measured by targeted metabolomics. Results: High compared to low fructose diets caused a marked metabolite class separation, especially because of changes in acylcarnitine and lysophosphatidylcholine levels. Both high fructose diets resulted in a decrease in mean acylcarnitine levels in all subjects, and an increase in mean lysophosphatidylcholine and diacyl-phosphatidylcholine levels in obese individuals. Medium chain acylcarnitines were negatively correlated with serum levels of liver enzymes and with the fatty liver index. Discussion: The metabolic shifts induced by high fructose consumption suggest an inhibition of mitochondrial β-oxidation and an increase in lipid peroxidation. The effects tended to be more pronounced following the HFS than the fruit diet.