Lisa M. Neff

Diet-induced weight loss reduces colorectal inflammation: implications for colorectal carcinogenesis.

BACKGROUND Epidemiologic data have shown that obesity independently increases colorectal cancer (CRC) risk, but the mechanisms are poorly understood. Obesity is an inflammatory state, and chronic colonic inflammation induces CRC. OBJECTIVE We conducted this proof-of-principle study to seek evidence of obesity-associated colorectal inflammation and to evaluate effects of diet-induced weight loss. DESIGN We measured inflammatory cytokines, gene arrays, and macrophage infiltration in rectosigmoid mucosal biopsies of 10 obese premenopausal women [mean ± SD body mass index (in kg/m(2)): 35 ± 3.5] before and after weight loss induced by a very-low-calorie diet. RESULTS Subjects lost a mean (±SD) of 10.1 ± 1% of their initial weight. Weight loss significantly reduced fasting blood glucose, total cholesterol, triglycerides, LDL, tumor necrosis factor-α (TNF-α), and interleukin (IL)-8 concentrations (P < 0.05). After weight loss, rectosigmoid biopsies showed a 25-57% reduction in TNF-α, IL-1β, IL-8, and monocyte chemotactic protein 1 concentrations (P < 0.05). T cell and macrophage counts decreased by 28% and 42%, respectively (P < 0.05). Gene arrays showed dramatic down-regulation of proinflammatory cytokine and chemokine pathways, prostaglandin metabolism, and the transcription factors STAT3 (signal transducer and activator of transcription 3) and nuclear transcription factor κB. Weight loss reduced expression of FOS and JUN genes and down-regulated oxidative stress pathways and the transcription factors ATF (activating transcription factor) and CREB (cyclic AMP response element-binding). CONCLUSIONS Our data show that diet-induced weight loss in obese individuals reduces colorectal inflammation and greatly modulates inflammatory and cancer-related gene pathways. These data imply that obesity is accompanied by inflammation in the colorectal mucosa and that diet-induced weight loss reduces this inflammatory state and may thereby lower CRC risk.

Temozolomide in the treatment of an invasive prolactinoma resistant to dopamine agonists

Prolactinomas are common tumors of the anterior pituitary gland. While conventional therapies, including dopamine agonists, transsphenoidal surgery and radiotherapy, are usually effective in controlling tumor growth, some patients develop treatment-resistant tumors. In this report, we describe a patient with an invasive prolactinoma resistant to conventional therapy that responded to the administration of the alkylating agent, temozolomide.

Algal Docosahexaenoic Acid Affects Plasma Lipoprotein Particle Size Distribution in Overweight and Obese Adults

Fish oils containing both EPA and DHA have been shown to have beneficial cardiovascular effects, but less is known about the independent effects of DHA. This study was designed to examine the effects of DHA on plasma lipid and lipoprotein concentrations and other biomarkers of cardiovascular risk in the absence of weight loss. In this randomized, controlled, double-blind trial, 36 overweight or obese adults were treated with 2 g/d of algal DHA or placebo for 4.5 mo. Markers of cardiovascular risk were assessed before and after treatment. In the DHA-supplemented group, the decrease in mean VLDL particle size (P ≤ 0.001) and increases in mean LDL (P ≤ 0.001) and HDL (P ≤ 0.001) particle sizes were significantly greater than changes in the placebo group. DHA supplementation also increased the concentrations of large LDL (P ≤ 0.001) and large HDL particles (P = 0.001) and decreased the concentrations of small LDL (P = 0.009) and medium HDL particles (P = 0.001). As calculated using NMR-derived data, DHA supplementation reduced VLDL TG (P = 0.009) and total TG concentrations (P = 0.006). Plasma IL-10 increased with DHA supplementation to a greater extent than placebo (P = 0.021), but no other significant changes were observed in glucose metabolism, insulin sensitivity, blood pressure, or markers of inflammation with DHA. In summary, DHA supplementation resulted in potentially beneficial changes in some markers of cardiometabolic risk, whereas other markers were unchanged.

Bariatric surgery: a key role for registered dietitians.

Obesity is a complex disorder that impacts all organ systems. Individuals with obesity are at increased risk for a variety of comorbid conditions, including diabetes, hypertension, dyslipidemia, heart disease, sleep apnea, some types of cancer, nonalcoholic fatty liver disease, and osteoarthritis, among others. Those at highest risk are individuals with class III obesity (body mass index !40), a group that now includes almost 5% of all adults and more than 10% of all African-American adults in the United States (1). Nonsurgical approaches to the treatment of obesity, including lifestyle modification and pharmacotherapy, typically result in average weight losses of 5% to 10% of initial body weight. Importantly, losses of this magnitude can substantially improve existing comorbidities and prevent new weight-related conditions, including diabetes (2,3). However, studies suggest that most individuals with obesity hope to lose considerably more weight, often as much as 20% to 40% of initial body weight, and they may view lesser degrees of weight loss as a disappointment or even a failure (4,5). In addition, the physiologic adaptations to weight loss, including reductions in energy expenditure and changes in hungerand satiety-promoting hormones, make it more difficult for individuals to maintain a reduced body weight over time (6). As a result, successful weight management is an elusive goal for many patients with obesity who utilize nonsurgical therapies. The four articles presented in this issue of the Journal highlight the growing importance of surgical therapies in the care of patients with obesity and the role of registered dietitians (RDs) (7-10). Current bariatric surgical techniques include the two most common procedures, Roux-en-Y gastric bypass (RYGB) and laparoscopic adjustable gastric banding (LAGB), and several less common procedures, including laparoscopic sleeve gastrectomy (LSG) and biliopancreatic diversion with duodenal switch (BPD-DS). Potential mechanisms of action are shown in the Figure and include restriction of gastric capacity, modulation of gastrointestinal hormones that influence hunger and satiety, and induction of malabsorption (11-13). Beckman and colleagues provide a comprehensive literature review of one of these mechanisms, changes in gastrointestinal (GI) hormones that occur after the RYGB procedure (9). As stated in their review, “An understanding of how GI hormones change after RYGB may help dietitians to optimize nutrition care to this patient population” (9). Knowledge of gut hormones is also important to RDs because pharmaceutical companies have focused on the manipulation of these hormones as peripheral targets for appetite regulation (14). At this time, bariatric surgery is the most effective intervention for severe obesity, producing substantial weight loss (typically on the order of 30% to 70% of excess body weight) that is largely maintained over time (15). The benefits of bariatric surgery also include high rates of remission of many obesity-associated comorbidities, including diabetes, hypertension, and dyslipidemia, as well as an improvement in quality of life and a reduction in mortality rates (15,16). As a result of this success, the number of bariatric procedures done annually has increased dramatically in recent years, as noted in the accompanying review by Kulick and colleagues (7). In light of the increasing prevalence of severe obesity, this trend is likely to continue. RDs are accustomed to working in a team environment to provide care for patients with various disorders, including obesity. In fact, team practice for the treatment of obesity has become an established model of care. Hospital nutrition teams were initially established in the 1970s, shortly after the introduction of new technology for the invasive administration of specialized parenteral and enteral nutritional products. Typically comprised of an attending physician, RD, registered nurse, and pharmacist, these teams were established to provide safe delivery of optimal nutritional support while minimizing complications. The team-oriented, multidisciplinary approach to patient care was subsequently applied to the care of patients with diabetes, as exemplified in two landmark diabetes studies: the Diabetes Control and Complications Trial (17) and the Diabetes Prevention Program (2). Interdisciplinary teams are also an important component of the chronic care model (18). It is with this perspective that the team approach to obesity care has evolved (19). In 1991, the National Institutes of Health consensus report on Gastrointestinal Surgery for Severe Obesity recommended multidisciplinary teams with medical, surgical, psychiatric, and nutritional expertise (20). In the articles by Kulick and colleagues (7) and SnyderR. F. Kushner is a professor of medicine, Division of General Medicine, and L. M. Neff is an assistant professor of medicine, Division of Endocrinology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL. Address correspondence to: Robert F. Kushner, MD, 750 N Lake Shore Dr, Rubloff 9-976, Chicago, IL 60611. E-mail: rkushner@northwestern.edu Manuscript accepted: December 15, 2009. Copyright

Emerging role of GLP-1 receptor agonists in the treatment of obesity

The prevalence of obesity has increased dramatically in recent decades, both in the US and worldwide. Pharmacotherapy can augment the weight-reducing effects of lifestyle modification and can facilitate long-term weight maintenance. However, there is a paucity of pharmacologic agents approved for the treatment of obesity, and the use of existing weight loss medications is frequently limited by contraindications, drug interactions, adverse effects, limited coverage by third-party payers, and cost. In recent years, there has been an increased understanding and appreciation of the role of gastrointestinal hormones in the control of body weight. One such hormone, GLP-1, also plays an important role in glucose homeostasis. GLP-1 receptor agonists, such as exenatide and liraglutide, have been developed and are already approved for the treatment of type 2 diabetes. There has also been interest in the use of GLP-1 receptor agonists for the treatment of obesity in nondiabetic patients. This review explores the potential utility and limitations of exenatide and liraglutide as therapeutic agents for obesity.

Relationship between obesity and anti-Müllerian hormone in reproductive-aged African American women

To determine whether there is an association between obesity and anti‐Müllerian hormone (AMH) among reproductive‐aged African American women (AAW).

MRI characterization of brown adipose tissue under thermal challenges in normal weight, overweight, and obese young men

To implement quantitative Dixon magnetic resonance imaging (MRI) methods for brown adipose tissue (BAT) characterization at inactive and cold‐activated states in normal weight, overweight, and obese subjects. The hypotheses are that MRI characteristics of BAT would differentiate between nonobese and obese subjects, and activation of BAT in response to thermal challenges that are detected by MRI would be correlated with BAT activity measured by positron emission tomography / computed tomography (PET/CT).

Core body temperature is lower in postmenopausal women than premenopausal women: potential implications for energy metabolism and midlife weight gain

ObjectiveWeight gain during the menopausal transition is common. Although studies have suggested that weight gain is more likely related to aging than menopause, there is a reduction in resting energy expenditure with surgical or natural menopause that is independent of age and changes in body composition. The underlying mechanisms could include a reduction in core body temperature. MethodsData were obtained from two related studies. Sample size was 23 men and 25 women (12 premenopausal, 13 postmenopausal). In the Clinical Research Unit, core temperature was measured every minute for 24 h using an ingested temperature sensor. ResultsThe mean 24-h core body temperature was 0.25±0.06°C lower in postmenopausal than premenopausal women (P=0.001). The mean 24 h core temperature was 0.34±0.05°C lower in men than in premenopausal women (P<0.001). ConclusionPostmenopausal women, like men, had lower core body temperatures than premenopausal women. This may have implications for midlife weight gain.

Surgery for Severe Obesity

Bariatric surgery has been demonstrated to be an effective treatment for patients with severe obesity, producing improvements in many comorbid conditions, including type 2 diabetes, hypertension, obstructive sleep apnea, and dyslipidemia. The loss of body weight and resolution of comorbidities have been more recently found to be the result of functional and metabolic changes produced by the surgical procedures. Nonetheless, bariatric surgery is still considered to be a tool that is supported by health behaviors characteristic of all weight loss programs—that is, adoption of healthy eating patterns, engagement in robust physical activity, and implementation of constructive coping strategies. In addition, patients who undergo bariatric surgery face challenges that are particular to this population, including adjustment to rapid and significant reduction in body weight, forced alterations in eating behavior, and risk of alcohol misuse. This state-of-the-art review focuses on the research and resultant recommendations regarding lifestyle management for patients who have undergone bariatric surgery.

Baseline Characteristics of the Vitamin D and Type 2 Diabetes (D2d) Study: A Contemporary Prediabetes Cohort That Will Inform Diabetes Prevention Efforts

OBJECTIVE To describe baseline characteristics of the Vitamin D and Type 2 Diabetes (D2d) study, the first large U.S. diabetes prevention clinical trial to apply current American Diabetes Association (ADA) criteria for prediabetes. RESEARCH DESIGN AND METHODS This is a multicenter (n = 22 sites), randomized, double-blind, placebo-controlled, primary prevention clinical trial testing effects of oral daily 4,000 IU cholecalciferol (D3) compared with placebo on incident diabetes in U.S. adults at risk for diabetes. Eligible participants were at risk for diabetes, defined as not meeting criteria for diabetes but meeting at least two 2010 ADA glycemic criteria for prediabetes: fasting plasma glucose (FPG) 100–125 mg/dL, 2-h postload glucose (2hPG) after a 75-g oral glucose load 140–199 mg/dL, and/or a hemoglobin A1c (HbA1c) 5.7–6.4% (39–46 mmol/mol). RESULTS A total of 2,423 participants (45% of whom were women and 33% nonwhite) were randomized to cholecalciferol or placebo. Mean (SD) age was 60 (9.9) years and BMI 32.1 (4.5) kg/m2. Thirty-five percent met all three prediabetes criteria, 49% met the FPG/HbA1c criteria only, 9.5% met the 2hPG/FPG criteria only, and 6.3% met the 2hPG/HbA1c criteria only. Black participants had the highest mean HbA1c and lowest FPG concentration compared with white, Asian, and other races (P < 0.01); 2hPG concentration did not differ among racial groups. When compared with previous prediabetes cohorts, the D2d cohort had lower mean 2hPG concentration but similar HbA1c and FPG concentrations. CONCLUSIONS D2d will establish whether vitamin D supplementation lowers risk of diabetes and will inform about the natural history of prediabetes per contemporary ADA criteria.