Shifts in intestinal microbiota after duodenal exclusion favor glycemic control and weight loss: a randomized controlled trial.

BACKGROUND: In recent years, studies indicate gut microbiota as an important modulator in the pathophysiology of type 2 diabetes. Environmental and genetic factors interact to control the host's intestinal microbiota, triggering metabolic disorders such as obesity and insulin resistance. OBJECTIVES: The objective of this study was to identify the fecal microbiota in adult type 2 diabetes patients and to assess changes in composition after metabolic surgery. SETTING: University Hospital of the University of São Paulo. METHODS: Twenty-one patients were enrolled in a randomized controlled study divided into 2 arms. One group underwent duodenal-jejunal bypass surgery with minimal gastric resection, and fecal samples were collected before the operation and after 6 and 12 months. The other group received medical care (standard care group) and was followed for 12 months. Fecal samples were collected at baseline and after 6 and 12 months. Fecal microbiota was analyzed using high-throughput sequencing with V4 16 S rRNA primers. RESULTS: The fecal microbiota in duodenal-jejunal bypass surgery with minimal gastric resection group (Bacteroides, Akkermansia, and Dialister) exhibited increased abundance and diversity compared with that in the standard care group; however, the increase in A. muciniphila was only statistically significant in the surgical group, probably due to the study's small sample size. CONCLUSIONS: The data presented suggest that duodenal-jejunal bypass surgery with minimal gastric resection increases microbial richness and abundancy, mainly for those bacteria related to weight loss and metabolic control (Akkermansia), providing a better understanding of the role of microbiota in type 2 diabetes regulation and its changes after metabolic surgery.

Assessment of the body composition of patients with polycystic ovary syndrome using dual-energy X-ray absorptiometry.

OBJECTIVE: To compare the body composition among patients with polycystic ovary syndrome (PCOS) and patients without PCOS. METHODS: A cross-sectional study enrolled patients aged 12-39 years, with body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters) at least 18.5 but below 25, who attended the Endocrine Gynecology Clinic of Santa Casa de Sao Paulo School of Medical Sciences, Brazil, between January 1, 2014, and July 31, 2015. Anthropometric measurements, metabolic and androgenic profiles, and dual-energy X-ray absorptiometry measurements were compared between patients with PCOS and those without PCOS. RESULTS: In total, 102 eligible patients attended the study clinical during the study period; 43 were excluded owing to not meeting the inclusion criteria or declining to undergo complete study testing, and 15 withdrew from the study. Of the 44 participants, 28 had PCOS and 16 were included in the control group. Serum 17-hydroxyprogesterone concentration (P=0.046), leg-fat (P=0.031), and truncal-fat (P=0.001) were all higher among patients with PCOS. CONCLUSION: The present study demonstrated increased truncal and leg fat among women with PCOS. The study did not detect any difference in insulin parameters but larger studies could be more suitably powered to investigate this. CLINICALTRIALS.GOV: NCT02467751.

Effect of Duodenal-Jejunal Bypass Surgery on Glycemic Control in Type 2 Diabetes: A Randomized Controlled Trial.

OBJECTIVE: To determine whether upper gastrointestinal tract (UGI) bypass itself has beneficial effects on the factors involved in regulating glucose homeostasis in patients with type 2 diabetes (T2D). METHODS: A 12-month randomized controlled trial was conducted in 17 overweight/obese subjects with T2D, who received standard medical care (SC, n = 7, BMI = 31.7 ± 3.5 kg/m(2) ) or duodenal-jejunal bypass surgery with minimal gastric resection (DJBm) (n = 10; BMI = 29.7 ± 1.9 kg/m(2)). A 5-h modified oral glucose tolerance test was performed at baseline and at 1, 6, and 12 months after surgery or starting SC. RESULTS: Body weight decreased progressively after DJBm (7.9 ± 4.1%, 9.6 ± 4.2%, and 10.2 ± 4.3% at 1, 6, and 12 months, respectively) but remained stable in the SC group (P < 0.001). DJBm, but not SC, improved: (1) oral glucose tolerance (decreased 2-h glucose concentration, P = 0.039), (2) insulin sensitivity (decreased homeostasis model assessment of insulin resistance, P = 0.013), (3) early insulin response to a glucose load (increased insulinogenic index, P = 0.022), and (4) overall glycemic control (reduction in HbA1c with fewer diabetes medications). CONCLUSIONS: DJBm causes moderate weight loss and improves metabolic function in T2D. However, our study cannot separate the benefits of moderate weight loss from the potential therapeutic effect of UGI tract bypass itself on the observed metabolic improvements.

Effects of gastric bypass surgery in patients with type 2 diabetes and only mild obesity.

OBJECTIVE: Roux-en-Y gastric bypass (RYGB) ameliorates type 2 diabetes in severely obese patients through mechanisms beyond just weight loss, and it may benefit less obese diabetic patients. We determined the long-term impact of RYGB on patients with diabetes and only class I obesity. RESEARCH DESIGN AND METHODS: Sixty-six consecutively selected diabetic patients with BMI 30-35 kg/m(2) underwent RYGB in a tertiary-care hospital and were prospectively studied for up to 6 years (median 5 years [range 1-6]), with 100% follow-up. Main outcome measures were safety and the percentage of patients experiencing diabetes remission (HbA(1c) <6.5% without diabetes medication). RESULTS: Participants had severe, longstanding diabetes, with disease duration 12.5 ± 7.4 years and HbA(1c) 9.7 ± 1.5%, despite insulin and/or oral diabetes medication usage in everyone. For up to 6 years following RYGB, durable diabetes remission occurred in 88% of cases, with glycemic improvement in 11%. Mean HbA(1c) fell from 9.7 ± 1.5 to 5.9 ± 0.1% (P < 0.001), despite diabetes medication cessation in the majority. Weight loss failed to correlate with several measures of improved glucose homeostasis, consistent with weight-independent antidiabetes mechanisms of RYGB. C-peptide responses to glucose increased substantially, suggesting improved ß-cell function. There was no mortality, major surgical morbidity, or excessive weight loss. Hypertension and dyslipidemia also improved, yielding 50-84% reductions in predicted 10-year cardiovascular disease risks of fatal and nonfatal coronary heart disease and stroke. CONCLUSIONS: This is the largest, longest-term study examining RYGB for diabetic patients without severe obesity. RYGB safely and effectively ameliorated diabetes and associated comorbidities, reducing cardiovascular risk, in patients with a BMI of only 30-35 kg/m(2).

Moderate effect of duodenal-jejunal bypass surgery on glucose homeostasis in patients with type 2 diabetes.

Gastric bypass surgery causes resolution of type 2 diabetes (T2DM), which has led to the hypothesis that upper gastrointestinal (UGI) tract diversion, itself, improves glycemic control. The purpose of this study was to determine whether UGI tract bypass without gastric exclusion has therapeutic effects in patients with T2DM. We performed a prospective trial to assess glucose and ß-cell response to an oral glucose load before and at 6, 9, and 12 months after duodenal-jejunal bypass (DJB) surgery. Thirty-five overweight or obese adults (BMI: 27.0 ± 4.0 kg/m(2)) with T2DM and 35 sex-, age-, race-, and BMI-matched subjects with normal glucose tolerance (NGT) were studied. Subjects lost weight after surgery, which was greatest at 3 months (6.9 ± 4.9%) with subsequent regain to 4.2 ± 5.3% weight loss at 12 months after surgery. Glycated hemoglobin (HbA(1c)) decreased from 9.3 ± 1.6% before to 7.7 ± 2.0% at 12 months after surgery (P < 0.001), in conjunction with a 20% decrease in the use of diabetes medications (P < 0.05); 7 (20%) subjects achieved remission of diabetes (no medications and HbA(1c) <6.5%). The area under the curve after glucose ingestion was ~20% lower for glucose but doubled for insulin and C-peptide at 12 months, compared with pre-surgery values (all P < 0.01). However, the ß-cell response was still 70% lower than subjects with NGT (P < 0.001). DJB surgery improves glycemic control and increases, but does not normalize the ß-cell response to glucose ingestion. These findings suggest that altering the intestinal site of delivery of ingested nutrients has moderate therapeutic effects by improving ß-cell function and glycemic control.

New clinical score to diagnose nonalcoholic steatohepatitis in obese patients.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most frequent disease associated with abnormal liver tests that is characterized by a wide spectrum of liver damage, ranging from simple macro vesicular steatosis to steatohepatitis (NASH), cirrhosis or liver carcinoma. Liver biopsy is the most precise test to differentiate NASH from other stages of NAFLD, but it is an invasive and expensive method. This study aimed to create a clinical laboratory score capable of identify individual with NASH in severely obese patients submitted to bariatric surgery. METHODS: The medical records from 66 patients submitted to gastroplasty were reviewed. Their chemistry profile, abdominal ultrasound (US) and liver biopsy done during the surgical procedure were analyzed. Patients were classified into 2 groups according to liver biopsy: Non-NASH group - those patients without NAFLD or with grade I, II or III steatosis; and NASH group - those with steatohepatitis or fibrosis. The t-test was used to compare each variable with normal distribution between NASH and Non-NASH groups. When comparing proportions of categorical variables, we used chi-square or z-test, where appropriate. A p-value < 0.05 was considered statistically significant. RESULTS: 83% of patients with obesity grades II or III showed NAFLD, and the majority was asymptomatic. Total Cholesterol (TC)≥200 mg/dL, alanine aminotransferase (ALT) ≥30, AST/ALT ratio (AAR)≤ 1, gammaglutaril-transferase (γGT)≥30 U/L and abdominal US, compatible with steatosis, showed association with NASH group. We proposed 2 scores: Complete score (TC, ALT, AAR, γGT and US) and the simplified score, where US was not included. The combination of biochemical and imaging results improved accuracy to 84.4% the recognition of NASH (sensitivity 70%, specificity 88.6%, NPV 91.2%, PPV 63. 6%). CONCLUSION: Alterations in TC, ALT, AAR, γGT and US are related to the most risk for NASH. The combination of biochemical and imaging results improved accuracy to 84.4% the recognition of NASH. Additionally, negative final scores exclude the presence of an advanced illness. Using this score, the severity of fatty liver infiltration would be predicted without the risks associated with hepatic biopsy.