Scott Ritter

GLP-1 Plays a Limited Role in Improved Glycemia Shortly After Roux-en-Y Gastric Bypass: A Comparison With Intensive Lifestyle Modification

Rapid glycemic improvements following Roux-en-Y gastric bypass (RYGB) are frequently attributed to the enhanced GLP-1 response, but causality remains unclear. To determine the role of GLP-1 in improved glucose tolerance after surgery, we compared glucose and hormonal responses to a liquid meal test in 20 obese participants with type 2 diabetes mellitus who underwent RYGB or nonsurgical intensive lifestyle modification (ILM) (n = 10 per group) before and after equivalent short-term weight reduction. The GLP-1 receptor antagonist exendin(9–39)-amide (Ex-9) was administered, in random order and in double-blinded fashion, with saline during two separate visits after equivalent weight loss. Despite the markedly exaggerated GLP-1 response after RYGB, changes in postprandial glucose and insulin responses did not significantly differ between groups, and glucagon secretion was paradoxically augmented after RYGB. Hepatic insulin sensitivity also increased significantly after RYGB. With Ex-9, glucose tolerance deteriorated similarly from the saline condition in both groups, but postprandial insulin release was markedly attenuated after RYGB compared with ILM. GLP-1 exerts important insulinotropic effects after RYGB and ILM, but the enhanced incretin response plays a limited role in improved glycemia shortly after surgery. Instead, enhanced hepatic metabolism, independent of GLP-1 receptor activation, may be more important for early postsurgical glycemic improvements.

Changes in neural responsivity to highly palatable foods following roux‐en‐Y gastric bypass, sleeve gastrectomy, or weight stability: An fMRI study

This prospective, observational fMRI study examined changes over time in blood oxygen level dependent (BOLD) response to high‐ and low‐calorie foods (HCF and LCF) in bariatric surgery candidates and weight‐stable controls.

Comparison of Bariatric Surgical Procedures for Diabetes Remission: Efficacy and Mechanisms

In Brief Bariatric surgery induces a mean weight loss of 15–30% of initial body weight (depending on the procedure), as well as a 45–95% rate of diabetes remission. Procedures that induce greater weight loss are associated with higher rates of diabetes remission. Improvements in glucose homeostasis after bariatric surgery are likely mediated by a combination of caloric restriction (followed by weight loss) and the effects of altered gut anatomy on the secretion of glucoregulatory gut hormones.

Attitudes Toward Vascularized Composite Allotransplantation of the Hands and Face in an Urban Population

Background: Almost 100 hand and face transplants have been performed worldwide. Their success has generated enthusiasm within the medical community, however, little is known about public attitudes toward vascularized composite allotransplantation (VCA) of the hands and face as compared to solid organ transplantation. The objective of this survey study was to assess these attitudes and the acceptability and potential barriers to the further growth of these procedures. Methods: Cooper University Hospital Emergency Department (Camden, New Jersey) patients, accompanying family members and friends ≥18 years of age were surveyed about knowledge of and attitudes toward organ, hand, and face transplants as well as preferences as a potential VCA donor or recipient. The socioeconomic aspects of VCA also were assessed. Results: A total of 1,027 individuals participated. Approximately 70% (69.7%) of respondents indicated that they would want to be organ donors, although only 37.1% reported donor registrations on their drivers license. Respondents demonstrated greatest willingness to donate solid organs upon death: kidneys (77.5%), liver (77.1%), and heart (76.4%). Willingness to donate was less for hands (54.6%) and face (44.0%). Similarly, respondents were more willing to receive a kidney (85.2%) than a hand (60.0%) or face (49.4%). Conclusions: Respondents were more willing to be donors or recipients of solid organs than of hands or face. However, substantial percentages of individuals indicated a willingness to donate or receive hands or a face. As VCA continues to evolve, knowledge of public attitudes toward VCA will be critical for organ procurement organizations, health system engagement, and funding for relevant research.

Lifestyle Modifications and Surgical Options in the Treatment of Patients with Obesity and Type 2 Diabetes Mellitus

Abstract This article reviews recent developments in the behavioral and surgical treatment of obesity and type 2 diabetes mellitus (T2DM). Randomized controlled trials of comprehensive lifestyle–modification programs, which include dietary interventions, physical activity, and behavioral therapy, have shown weight losses of 7% to 10% of initial body weight within 4 to 6 months after treatment. These programs also reduce the likelihood of developing T2DM by 58% for individuals with impaired glucose tolerance. Long–term maintenance of these improvements requires continued implementation of the program diet, physical activity, and self–regulatory behaviors. This can be successfully facilitated by continued patient–provider contact, which is frequently delivered by phone, mail, email, or online. However, these benefits may have less impact on those with extreme obesity or more significant health problems. For these individuals, bariatric surgery may be a more appropriate treatment. Bariatric surgical procedures induce mean weight losses of 15% to 30% of initial body weight (depending on the procedure) within 2 years after surgery, as well as a 45% to 95% rate of diabetes remission. Familiarity with these developments can help physicians and patients to determine which combinations of behavioral, medical, and surgical interventions are appropriate for the treatment of obesity and T2DM.

A community overlap strategy reveals central genes and networks in heart failure

Heart failure is a leading cause of mortality, yet our understanding of the genetic interactions underlying this disease remains incomplete. Here, we harvested 1352 healthy and failing human hearts directly from transplant center operating rooms, and obtained genome-wide genotyping and gene expression measurements for a subset of 313. We built failing and non-failing cardiac regulatory gene networks, revealing important regulators and cardiac expression quantitative trait loci (eQTLs). PPP1R3A emerged as a novel regulator whose network connectivity changed significantly between health and disease. Time-course RNA sequencing after PPP1R3A knock-down validated network-based predictions of metabolic pathway expression, increased cardiomyocyte size, and perturbed respiratory metabolism. Mice lacking PPP1R3A were protected against pressure-overload heart failure. We present a global gene interaction map of the human heart failure transition, identify new cardiac eQTLs, and demonstrate the discovery potential of disease-specific networks through the description of PPP1R3A as a novel central protective regulator in heart failure.Heart failure is one of the leading causes of mortality worldwide, but its underlying molecular mechanisms are poorly understood. To obtain a systems view of the molecular networks that underlie heart failure, we harvested 1352 samples from 313 healthy and failing hearts directly from transplant operating rooms and obtained left-ventricular whole-genome gene expression and genotype measurements. From these data, we built directed regulatory gene networks and gene communities using an approach that combines network and community inference in one framework. Differences in co-expression and global and local centrality parameters pinpointed changes in the molecular interaction network associated with heart failure, as well as its network-wise genetic determinants. Connectivity of one gene, PPP1R3A, previously unassociated with heart failure, changed significantly between healthy and diseased states. Perturbation of in vitro and in vivo systems via time series transcriptome sequencing and murine cardiovascular phenotyping revealed that ablation of PPP1R3A alters disease progression.

Lessons Learned from a Randomized Controlled Trial of Bariatric Surgery versus Intensive Lifestyle Modification for Individuals with Type 2 Diabetes

Objective: Relatively few Randomized Controlled Trials (RCTs) have compared bariatric surgery to lifestyle modification for weight loss and improvements in type 2 diabetes. The Surgery or Lifestyle Intervention for Diabetes (SOLID) RCT was designed to address this insufficiency by comparing (1) Roux-en-Y Gastric Bypass surgery (RYGB), (2) Adjustable Gastric Banding surgery (AGB), and (3) A non-surgical Intensive Lifestyle Modification (ILM) for weight loss on changes in weight and diabetes status. Methods: SOLID was a RCT for the first 24 months, but due to low enrollment, was modified to a prospective observational study for the last 12 months. Results: In total, 1,290 individuals inquired about the study and completed initial screening. Of these, 209 were eligible, however only 18 were enrolled in the trial (3 RYGB, 3 AGB, 12 ILM). Multiple barriers to patient enrollment were identified, including issues related to the eligibility criteria, reluctance to accept random assignment to the three interventions, and lack of insurance coverage or availability of funds to pay for the bariatric procedures. Conclusion: These issues warrant thoughtful attention from investigators who are planning future RCTs in this area.

Emerging Tools for Computer-Aided Diagnosis and Prognostication

Although vast amounts of data are collected at clinical presentation, ranging from macroscale Magnetic Resonance Imaging (MRI) scans, to micro-scale pathology slides, to nanoscale proteins and genes, there are challenges associated with analyzing, combining, and correlating these data to make diagnostic, prognostic, and theranostic predictions [2–4]. Computerized image analysis and data integration methods have the potential to improve our understanding of the relationship between these heterogeneous multi-format, multi-scale data to better predict disease outcomes and treatment responses.