Changes in Blood microRNA Expression and Early Metabolic Responsiveness 21 Days Following Bariatric Surgery

Background: Early metabolic responses following bariatric surgery appear greater than expected given the initial weight loss and coincide with improvement in diabetes. We hypothesized that small non-coding microRNA changes might contribute to regulating mechanisms for metabolic changes and weight loss in patients with severe obesity and diabetes.Methods: Twenty-nine type 2 patients with severe obesity (mean BMI 46.2 kg/m2) and diabetes underwent Roux-en-Y gastric bypass (RYGB) surgery. Clinical measurements and fasting blood samples were taken preoperatively and at day 21 postoperatively. Normalization of fasting glucose and HbA1c following bariatric surgery (short-term diabetes remission) was defined as withdrawal of anti-diabetic medication and fasting glucose < 100 mg/dL (5.6 mmol/L) or HbA1c < 6.0%. MicroRNA expression was determined by quantitative polymerase chain reaction and tested for significant changes after surgery.Results: BMI decreased by 3.8 kg/m2 21 days postoperatively. Eighteen of 29 RYGB (62%) had short-term diabetes remission. Changes from pre- to post-surgery in 32 of 175 microRNAs were nominally significant (p < 0.05). Following multiple comparison adjustment, changes in seven microRNAs remained significant: miR-7-5p, let-7f-5p, miR-15b-5p, let-7i-5p, miR-320c, miR-205-5p, and miR-335-5p. Four pathways were over-represented by these seven microRNAs, including diabetes and insulin resistance pathways.Conclusion: Seven microRNAs showed significant changes 21 days after bariatric surgery. Functional pathways of the altered microRNAs were associated with diabetes-, pituitary-, and liver-related disease, with expression in natural killer cells, and pivotal intestinal pathology suggesting possible mechanistic roles in early diabetes responses following bariatric surgery

Health Outcomes of Gastric Bypass Patients Compared to Nonsurgical, Nonintervened Severely Obese

Favorable health outcomes at 2 years postbariatric surgery have been reported. With exception of the Swedish Obesity Subjects (SOS) study, these studies have been surgical case series, comparison of surgery types, or surgery patients compared to subjects enrolled in planned nonsurgical intervention. This study measured gastric bypass effectiveness when compared to two separate severely obese groups not participating in designed weight-loss intervention. Three groups of severely obese subjects (N = 1,156, BMI ≥ 35 kg/m2) were studied: gastric bypass subjects (n = 420), subjects seeking gastric bypass but did not have surgery (n = 415), and population-based subjects not seeking surgery (n = 321). Participants were studied at baseline and 2 years. Quantitative outcome measures as well as prevalence, incidence, and resolution rates of categorical health outcome variables were determined. All quantitative variables (BMI, blood pressure, lipids, diabetes-related variables, resting metabolic rate (RMR), sleep apnea, and health-related quality of life) improved significantly in the gastric bypass group compared with each comparative group (all P < 0.0001, except for diastolic blood pressure and the short form (SF-36) health survey mental component score at P < 0.01). Diabetes, dyslipidemia, and hypertension resolved much more frequently in the gastric bypass group than in the comparative groups (all P < 0.001). In the surgical group, beneficial changes of almost all quantitative variables correlated significantly with the decrease in BMI. We conclude that Roux-en-Y gastric bypass surgery when compared to severely obese groups not enrolled in planned weight-loss intervention was highly effective for weight loss, improved health-related quality of life, and resolution of major obesity-associated complications measured at 2 years

Longitudinal Changes in Cardiac Structure and Function in Severe Obesity: 11‐Year Follow‐Up in the Utah Obesity Study

Background Progressive cardiac remodeling and worsening myocardial function over time have been proposed as potential mediators of heart failure in obesity. Methods and Results We serially assessed cardiac structure and function in 254 subjects participating in a longitudinal study of obesity. Demographic, clinical, laboratory, and echocardiographic features were determined at baseline and 2‐, 6‐, and 11‐year follow‐up. We measured body mass index ( BMI ) exposure as the area under the curve of the BMI at each of the 4 visits. At enrollment, mean age of the subjects was 47 years, 79% were women, mean BMI was 44 kg/m 2 , 26% had diabetes mellitus, 48% had hypertension, and 53% had hyperlipidemia. Between baseline and 11 years, BMI increased by 1.1 and 0.3 kg/m 2 in men and women, respectively. There were modest increases in left ventricular ( LV ) end‐diastolic volume, LV mass, and left atrial volume, and significant decreases in early/late mitral diastolic flow velocity ratio and E wave deceleration time. However, there were no significant changes in LV ejection fraction or ratio of early mitral diastolic flow velocity/early mitral annular velocity, whereas right ventricular fractional area change increased. Significant predictors of the change in LV mass were male sex, baseline BMI , BMI area under the curve, and change in LV stroke volume, but not smoking, hypertension, or diabetes mellitus. Conclusions In long‐standing, persistent severe obesity, there was evidence of cardiac remodeling over a period of 11 years, but no clear worsening of systolic or diastolic function. Measures of remodeling were most strongly related to BMI . The observed changes might predispose to heart failure with preserved ejection fraction, but are not classic for an evolving dilated cardiomyopathy. </jats:sec

Twelve-year changes in protein profiles in patients with and without gastric bypass surgery

AbstractGastric bypass surgery results in long-term weight loss due to re-routing of the gastro-intestinal anatomy and dietary intake alterations. Studies have examined protein change during rapid weight loss (up to 1 year post-surgery), but whether protein changes are maintained long-term after weight stabilization is unknown. To identify proteins and pathways involved with the long-term beneficial effects of weight loss, abundances of 1297 blood-circulating proteins were measured at baseline, 2 and 12 years after Roux-en-Y gastric bypass surgery. Protein changes were compared between 234 surgery and 144 non-surgery subjects with severe obesity, with discovery and replication subgroups. Seventy-one protein changes were associated with 12-year BMI changes and 58 (7 unique) with surgical status. Protein changes, including ApoM, were most strongly associated with long-term changes in lipids (HDL-C and triglycerides). Inflammation, adipogenesis, cellular signaling, and complement pathways were implicated. Short-term improvements in protein levels were maintained long-term, even after some weight regain.</jats:p

A two-centre implementation of the Douglas-Kroll transformation in relativistic calculations

An implementation of the Douglas–Kroll (DK) transformation is described within a new relativistic quantum chemistry code, MAGIC, which performs calculations on systems containing heavy atoms. This method reduces the computational cost in terms of memory requirements that are associated with completeness identities in the DK implementation by factorizing the one-electron matrices into smaller ones that depend only on two atoms at a time. Examples are presented

Association of Patient Age at Gastric Bypass Surgery With Long-term All-Cause and Cause-Specific Mortality

IMPORTANCE: Bariatric surgery has been shown to be effective in reducing total and cause-specific long-term mortality. Whether the long-term mortality benefit of surgery applies to all ages at which surgery is performed is not known. OBJECTIVES: To examine if gastric bypass surgery was equally effective in reducing mortality across different age-at-surgery groups. DESIGN: Total and cause-specific mortality rates and hazard ratios were estimated from a retrospective cohort within four categories defined by age at surgery: <35, 35–44, 45–54, and 55–74 years. Mean follow-up was 7.2 years. SETTING: Gastric bypass surgical patients seen at a private surgical practice from 1984 to 2002. PARTICIPANTS: A cohort of 7925 gastric bypass surgery patients and 7925 group-matched, non-operated severely obese subjects identified through driver license records. Matching criteria included year of surgery to year of driver license application, gender, 5-year age groups and three BMI categories. INTERVENTION: Roux-en-Y gastric bypass surgery. MAIN OUTCOME: Total and cause-specific mortality compared between those with and without gastric bypass surgery using hazard ratios. RESULTS: The mean age at surgery was 39.5±10.5 years and the mean pre-surgical BMI was 45.3±7.4 kg. Compared with non-operated subjects, adjusted all-cause mortality after gastric bypass surgery was significantly lower for the 35–44, 45–54, and 55–74 year age groups (hazard ratios (HR) of 0.54 (95% confidence interval of 0.38–0.77), 0.43 (0.30–0.62), and 0.50 (0.31–0.70), respectively; all p<0.005) but was not lower for the <35 year age group (HR 1.22 (0.82–1.81)). The lack of mortality benefit in the <35 age group primarily derived from a significantly higher number of externally-caused deaths (HR 2.53 (1.27–5.07)). Gastric bypass patients had a significantly lower age-related increase in mortality than non-operated severely obese subjects (p=0.0014). CONCLUSIONS: Gastric bypass surgery was associated with improved long-term survival for all ages-at-surgery >35 years, with externally-caused deaths only elevated in younger women. Gastric bypass surgery is protective against mortality even for older patients and also reduces the age-related increase in mortality observed in severely obese non-surgical subjects

Changes in Blood microRNA Expression and Early Metabolic Responsiveness 21 Days Following Bariatric Surgery

Background: Early metabolic responses following bariatric surgery appear greater than expected given the initial weight loss and coincide with improvement in diabetes. We hypothesized that small non-coding microRNA changes might contribute to regulating mechanisms for metabolic changes and weight loss in patients with severe obesity and diabetes.Methods: Twenty-nine type 2 patients with severe obesity (mean BMI 46.2 kg/m2) and diabetes underwent Roux-en-Y gastric bypass (RYGB) surgery. Clinical measurements and fasting blood samples were taken preoperatively and at day 21 postoperatively. Normalization of fasting glucose and HbA1c following bariatric surgery (short-term diabetes remission) was defined as withdrawal of anti-diabetic medication and fasting glucose Results: BMI decreased by 3.8 kg/m2 21 days postoperatively. Eighteen of 29 RYGB (62%) had short-term diabetes remission. Changes from pre- to post-surgery in 32 of 175 microRNAs were nominally significant (p Conclusion: Seven microRNAs showed significant changes 21 days after bariatric surgery. Functional pathways of the altered microRNAs were associated with diabetes-, pituitary-, and liver-related disease, with expression in natural killer cells, and pivotal intestinal pathology suggesting possible mechanistic roles in early diabetes responses following bariatric surgery.Other InformationPublished in: Frontiers in EndocrinologyLicense: https://creativecommons.org/licenses/by/4.0/See article on publisher's website: https://dx.doi.org/10.3389/fendo.2018.00773</p