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Overweight and obesity are epidemic around the world. They represent a spectrum of a chronic disease causing physical, metabolic, and psychological derangements that deteriorate health. Adipose tissue may become diseased, a condition called adiposopathy. Adiposopathy includes changes in fat mass (adiposity) along with changes in adipose tissue architecture and function, and the preferential distribution of adipose tissue into some compartments like intra-abdominal (visceral) fat. All of this constitutes the pathophysiology of adipose tissue, and its contribution to this chronic disease. The standard of medical care in 2021 is to aggressively treat adiposopathy, overweight, and obesity. Bariatric surgery should be offered to patients whose disease is truly refractory to medical management with lifestyle changes, medical nutrition therapy, increased physical activity, pharmacotherapy, and non-invasive procedures. Bariatric surgery is not a cure for adiposopathy, overweight, or obesity. Rather, it is effective treatment, and can put them into remission. Bariatric surgery does not change the need to monitor and treat patients for life. Clinicians should be familiar with the risks and benefits of the bariatric procedures available, and the potential complications that may develop from them.

Abbreviations: PSMF = protein-sparing modified fast; VLCMP = very-low-calorie meal plans

Scarce data exist on pharmacotherapy for obesity in Hispanic individuals. This post hoc analysis of pooled data from 4 phase 3a trials compared the efficacy and safety of liraglutide 3.0 mg versus placebo, as adjunct to a reduced-calorie diet and physical activity, in Hispanic versus non-Hispanic subgroups.We conducted the double-blind randomized, placebo-controlled trials in adults with a minimum body mass index (BMI) of 27 kg/mBoth subgroups achieved clinically significant mean weight loss at end-of-treatment with liraglutide 3.0 mg versus placebo: Hispanics 7.0% versus 1.5%, treatment difference -5.1% (95% CI, -6.2 to -4.0); non-Hispanics 7.5% versus 2.3%, -5.2% (95% CI, -5.5 to -4.8). More individuals in both subgroups lost ≥5%,10%, and15% of their baseline weight with liraglutide 3.0 mg than with placebo. Efficacy endpoints generally did not vary with ethnicity (P.05). Adverse events were comparable between ethnic subgroups, with more gastrointestinal disorders reported with liraglutide 3.0 mg than placebo.Efficacy and safety were largely similar between Hispanic and non-Hispanic subgroups. Results support that liraglutide 3.0 mg, used with a reduced-calorie diet and physical activity, can facilitate weight loss in Hispanic individuals.A1c = glycated hemoglobin BMI = body mass index CI = confidence interval FPG = fasting plasma glucose GLP-1 = glucagon-like peptide-1 hsCRP = high-sensitivity C-reactive protein SCALE = Satiety and Clinical Adiposity - Liraglutide Evidence in individuals with and without diabetes T2DM = type 2 diabetes mellitus.

Obesity has become endemic. However, the gonadal and reproductive changes in women with overweight or obesity, who do not have polycystic ovarian syndrome (PCOS), diabetes mellitus, or dysmetabolic syndrome, have not been studied well. This chapter summarizes available information on gonadal dysfunction in women with overweight or obesity. The role of adiposopathy in these problems is addressed.

Epidemiological data have shown a strong relationship between elevated plasma cholesterol levels and cardiovascular disease. Over the past 70 years the field of clinical lipidology has emerged. The specialties of endocrinology and cardiology, which long held the ownership of lipidology, have now given way to new generations of physicians who approach lipid management from wide-ranging perspectives. The birth of bariatric endocrinology brings a different perspective to lipidology. With the knowledge that adipose tissue is central to the regulation of metabolism, interventions to address dyslipidemia as a function of adipose tissue dysfunction, or adiposopathy, will take on increasing relevance. The traditional approach of treating vascular disease, once present, has been supplanted by a systematic approach in medicine to identify and treat vascular risk factors. We now add adiposopathy as the genesis of many of these risk factors. And thus, aggressive weight management stands to prevent and treat atherogenic dyslipidemia. This chapter will review the role of adipose tissue in lipid metabolism and the changes that come about with adiposopathy. Building on the knowledge that we have, it is imperative to identify patients at risk and treat their lipids to goal. It is now equally important to address the underlying adiposopathy.

Although obesity has become endemic, the reproductive problems in men with obesity who do not have diabetes mellitus (DM) or dysmetabolic syndrome, have not been studied well. This chapter summarizes the information available to date, in order to provide the clinician with suggestions on how to approach the management of these patients. This chapter introduces the concepts of bariatric hypogonadism, hypogonadal overweight or obesity, and bariatric erectile dysfunction (ED). The role of adiposopathy in these problems is addressed, the complexity of the evaluation is summarized, and the available management options are presented.

The central nervous system regulates energy balance and energy stores. Several nuclei in the hypothalamus provide the core of this function, with input from other regions of the brain. The hypothalamus serves as an integrator of circulating and neuronal signals that reach the brain with current information on the energy state of the body. The major orexigenic signal from the periphery is ghrelin, which is made in the stomach during the fasting state. Neuropeptide Y neurons in the arcuate nucleus of the hypothalamus provide the major signaling for hunger and feeding. Orexin from the lateral hypothalamic area contributes to the generation of hunger. There are multiple peripheral anorexigenic signals, among which is leptin, one of the major hormones produced in adipose tissue. Pro-opiomelanocortin neurons in the arcuate nucleus of the hypothalamus provide the major signaling for fullness and cessation of feeding. The integration of these signals in the hypothalamus is modulated by heavy input from other areas of the brain.

Adipose tissue sits at the crossroads of metabolism. It actively participates in the day-to-day regulation of energy balance, and it is the largest reservoir of energy for long-term needs. The human body is designed to sense its current energy status. Fuel sensors are located in the abdominal cavity along the digestive tract but also in adipose tissue. Afferent signals from these sensors reach the central nervous system in the form of neural and hormonal inputs. The brain directs action to maintain a steady intake of nutrients and energy.

CKD = chronic kidney disease DM = diabetes mellitus eGFR = estimated glomerular filtration rate FDA = Food & Drug Administration.

Preview Severe metabolic complications of diabetes mellitus are a common cause of morbidity and death in both type I and type II disease. The distinctions between diabetic ketoacidosis and hyperosmolar nonketotic state are clearly defined, and accurate recognition is important for proper treatment. This article focuses on the practical aspects of evaluation and management of these serious diabetic complications in adults.

J. Michael Gonzalez-Campoy, MD, PhD, FACE1; Sachiko T. St. Jeor, PhD, RD2; Kristin Castorino, DO3; Ayesha Ebrahim, MD, FACE4; Dan Hurley, MD, FACE5; Lois Jovanovic, MD, MACE6; Jeffrey I. Mechanick, MD, FACP, FACN, FACE, ECNU7; Steven M. Petak, MD, JD, MACE, FCLM8; Yi-Hao Yu, MD, PhD, FACE9; Kristina A. Harris10; Penny Kris-Etherton, PhD, RD11; Robert Kushner, MD12; Maureen Molini-Blandford, MPH, RD13; Quang T. Nguyen, DO14; Raymond Plodkowski, MD15; David B. Sarwer, PhD16; Karmella T. Thomas, RD17

When caloric intake exceeds caloric expenditure, the positive caloric balance and storage of energy in adipose tissue often causes adipocyte hypertrophy and visceral adipose tissue accumulation. These pathogenic anatomic abnormalities may incite metabolic and immune responses that promote Type 2 diabetes mellitus, hypertension and dyslipidemia. These are the most common metabolic diseases managed by clinicians and are all major cardiovascular disease risk factors. 'Disease' is traditionally characterized as anatomic and physiologic abnormalities of an organ or organ system that contributes to adverse health consequences. Using this definition, pathogenic adipose tissue is no less a disease than diseases of other body organs. This review describes the consequences of pathogenic fat cell hypertrophy and visceral adiposity, emphasizing the mechanistic contributions of genetic and environmental predispositions, adipogenesis, fat storage, free fatty acid metabolism, adipocyte factors and inflammation. Appreciating the full pathogenic potential of adipose tissue requires an integrated perspective, recognizing the importance of 'cross-talk' and interactions between adipose tissue and other body systems. Thus, the adverse metabolic consequences that accompany fat cell hypertrophy and visceral adiposity are best viewed as a pathologic partnership between the pathogenic potential adipose tissue and the inherited or acquired limitations and/or impairments of other body organs. A better understanding of the physiological and pathological interplay of pathogenic adipose tissue with other organs and organ systems may assist in developing better strategies in treating metabolic disease and reducing cardiovascular disease risk.

We compared the vascular effects of rosiglitazone versus glyburide and evaluated asymmetric dimethylarginine (ADMA) and oxidative stress as potential mechanisms associated with changes in vascular health in patients with type 2 diabetes mellitus (T2DM). Patients were randomized to 6 months of either rosiglitazone (n = 20) or glyburide (n = 16) in addition to metformin. The following variables were measured pre- and post-treatment: glucose, insulin, homeostasis model assessment (HOMA), hemoglobin A1c (HbA1c), C-peptide, blood pressure, lipids, C-reactive protein (CRP), ADMA, 8-isoprostane, oxidized LDL cholesterol, brachial artery flow-mediated dilation (FMD), endothelium-independent dilation (EID), and brachial and carotid artery stiffness. Rosiglitazone and glyburide treatment resulted in significant and equivalent decreases in glucose (p < 0.0001) and HbA1c (p < 0.0001), with a trend toward decreased HOMA (p = 0.09). Rosiglitazone significantly decreased C-peptide (p < 0.01) with a strong trend toward decreased fasting insulin (p = 0.05). Rosiglitazone reduced CRP compared with glyburide (p = 0.001), but no differences were observed between groups for ADMA or the markers of oxidative stress. Rosiglitazone significantly improved FMD (p < 0.05) with trends toward improvements in carotid artery distension (p = 0.099) and distensibility (p = 0.078). In conclusion, compared with glyburide, rosiglitazone improves endothelial function and CRP in patients with T2DM. These improvements are not associated with reductions in ADMA or markers of oxidative stress.

Excessive adipose tissue is potentially pathogenic due to its mass effects and through adverse metabolic/immune responses, which may lead to cardiovascular disease risk factors (eg, type 2 diabetes mellitus, hypertension, dyslipidemia, and possibly atherosclerosis itself). Positive caloric balance in genetically/environmentally susceptible patients may result in adipocyte hypertrophy, visceral adipose tissue accumulation, and ectopic fat deposition, all causally associated with metabolic disease, and all anatomic manifestations of "adiposopathy" (a term used to describe adipose tissue pathology). Weight loss through improved nutrition, increased physical activity, and weight loss agents (ie, orlistat and sibutramine) improves adiposopathy and improves many metabolic diseases whose prevalence are directly associated with an increase in body fat and sedentary lifestyle. Cannabinoid receptor antagonists improve adiposopathy through weight reduction and favorable metabolic effects upon multiple body organs (including adipocytes). Peroxisome proliferator-activated receptor-gamma agonists may improve adiposopathy through recruitment of functional fat cells and apoptosis of dysfunctional fat cells.

Data suggest that carvedilol possesses antioxidant properties that might provide vascular protection. We sought to compare the effects of carvedilol and metoprolol tartrate on endothelial function and oxidative stress in a head-to-head trial.Thirty-four patients with type 2 diabetes mellitus (T2DM) and hypertension were randomized to receive either carvedilol (n = 16) or metoprolol (n = 18) in addition to their current antihypertensive medications for 5 months. The following variables were measured pre- and posttreatment: blood pressure, fasting glucose and insulin, insulin resistance by homeostasis-model assessment, hemoglobin A1c, lipids, C-reactive protein (CRP), 8-isoprostane, asymmetric dimethylarginine, oxidized LDL cholesterol, ultrasound assessment of brachial-artery flow-mediated dilation (FMD), nitroglycerin-induced endothelium-independent dilation (EID), brachial and carotid artery distension, distensibility and compliance, and carotid artery intima-media thickness (cIMT).Both carvedilol and metoprolol treatment resulted in significant and similar decreases in systolic (P.05) and diastolic (P.0001) blood pressure. Compared with metoprolol, carvedilol significantly improved FMD (P.001). No differences between groups were noted for any of the glycemic or lipid variables except for HDL cholesterol, which significantly decreased (P.05) in the metoprolol group compared with the carvedilol group. No differences were observed between groups for CRP, the markers of oxidative stress, EID, arterial stiffness, or cIMT.Compared with metoprolol, carvedilol significantly improves endothelial function in patients with T2DM. Changes in glycemic control and oxidative stress do not seem to explain the observed improvements in FMD, which suggests that other mechanisms may be involved.

Obesity, is a chronic, biological, preventable, and treatable disease. The accumulation of fat mass causes physical changes (adiposity), metabolic and hormonal changes due to adipose tissue dysfunction (adiposopathy), and psychological changes. Bariatric endocrinology was conceived from the need to address the neuro-endocrinological derangements that are associated with adiposopathy, and from the need to broaden the scope of the management of its complications. In addition to the well-established metabolic complications of overweight and obesity, adiposopathy leads to hyperinsulinemia, hyperleptinemia, hypoadiponectinemia, dysregulation of gut peptides including GLP-1 and ghrelin, the development of an inflammatory milieu, and the strong risk of vascular disease. Therapy for adiposopathy hinges on effectively lowering the ratio of orexigenic to anorexigenic signals reaching the the hypothalamus and other relevant brain regions, favoring a lower caloric intake. Adiposopathy, overweight and obesity should be treated indefinitely with the specific aims to reduce fat mass for the adiposity complications, and to normalize adipose tissue function for the adiposopathic complications. This paper defines the principles of medical practice in bariatric endocrinology—the treatment of overweight and obesity as means to treat adiposopathy and its accompanying metabolic and hormonal derangements.

Preview Severe metabolic complications of diabetes mellitus are a common cause of morbidity and death in both type I and type II disease. The distinctions between diabetic ketoacidosis and hyperosmolar nonketotic state are clearly defined, and accurate recognition is important for proper treatment. This article focuses on the practical aspects of evaluation and management of these serious diabetic complications in adults.

Collaborations between physicians, particularly those in academic medicine, and industries that develop pharmaceutical products, medical devices, and diagnostic tests have led to substantial advances in patient care. At the same time, there is a strong awareness that these relationships, however beneficial they may be, should conform to established principles of ethical professional practice. Through a writing committee drawn from diverse disciplines across several institutions, the Association of Clinical Researchers and Educators (ACRE) has written a code of conduct to provide guidance to physicians in observing these principles. Our recommendations are not intended to be prescriptive or inflexible, but rather to be of assistance to physicians in making their own personal decisions on whether, or how, to be involved in research, education, or other collaborations with industry.

The authors hypothesized that carvedilol controlled-release plus lisinopril combination therapy (C+L) would increase endothelial function and decrease oxidative stress to a greater extent than hydrochlorothiazide plus lisinopril combination therapy (H+L) in obese patients with hypertension. Twenty-five abdominally obese patients (aged 54.4±7.3 years; 14 women) with hypertension/prehypertension were enrolled in a 7-month (two 3-month treatment periods separated by a 1-month washout), randomized, double-blind, controlled, crossover clinical trial comparing C+L vs H+L. Endothelial function, measured by digital reactive hyperemic index (RHI), circulating oxidized low-density lipoprotein (oxLDL), 8-isoprostane, and asymmetric dimethylarginine (ADMA) were obtained at baseline, post-period 1, post-washout, and post-period 2. Analyses were adjusted for baseline measurements by analysis of covariance, with robust variance estimation for confidence intervals and P values. C+L treatment compared to H+L treatment significantly improved RHI (0.74, 95% confidence interval, 0.31–1.19, P =.001). This difference persisted after adjustment for the change in systolic blood pressure. No significant treatment differences were observed for oxLDL, 8-isoprostane, or ADMA. These data provide evidence that independent of blood pressure–lowering, C+L therapy improves endothelial function to a greater extent than H+L therapy. Levels of oxidative stress were not significantly different between treatments, suggesting that other mechanisms may be responsible for the improvement in endothelial function.

American Association of Clinical Endocrinologists, The Obesity Society, and American Society for Metabolic & Bariatric Surgery Medical Guidelines for Clinical Practice are systematically developed statements to assist health-care professionals in medical decision making for specific clinical conditions. Most of the content herein is based on literature reviews. In areas of uncertainty, professional judgment was applied. These guidelines are a working document that reflects the state of the field at the time of publication. Because rapid changes in this area are expected, periodic revisions are inevitable. We encourage medical professionals to use this information in conjunction with their best clinical judgment. The presented recommendations may not be appropriate in all situations. Any decision by practitioners to apply these guidelines must be made in light of local resources and individual patient circumstances. The American Society for Parenteral & Enteral Nutrition fully endorses sections of these guidelines that address the metabolic and nutritional management of the bariatric surgical patient.

American Association of Clinical Endocrinologists, The Obesity Society, and American Society for Metabolic & Bariatric Surgery Medical Guidelines for Clinical Practice are systematically developed statements to assist healthcare professionals in medical decision making for specific clinical conditions. Most of the content herein is based on literature reviews. In areas of uncertainty, professional judgment was applied. These guidelines are a working document that reflects the state of the field at the time of publication. Because rapid changes in this area are expected, periodic revisions are inevitable. We encourage medical professionals to use this information in conjunction with their best clinical judgment. The presented recommendations may not be appropriate in all situations. Any decision by practitioners to apply these guidelines must be made in light of local resources and individual patient circumstances. The American Society for Parenteral & Enteral Nutrition fully endorses sections of these guidelines that address the metabolic and nutritional management of the bariatric surgical patient.

American Association of Clinical Endocrinologists, The Obesity Society, and American Society for Metabolic & Bariatric Surgery Medical Guidelines for Clinical Practice are systematically developed ...

The number of publications about obesity has increased geometrically over the past couple of decades. The knowledge that adipose tissue is an endocrine organ gave birth to the field of bariatric endocrinology. The concept that adipose tissue may become diseased, and thus contribute to the genesis of metabolic disorders, including hyperglycemia, dyslipidemia, hypertension, male hypogonadism, and cardiovascular disease, constitutes adiposopathy. The goals of treatment for people with overweight and obesity are to decrease the burden of fat mass (adiposity), and to treat adiposopathy (i.e. to return adipose tissue function to normal). As a society, we must overcome the social, political and economic obstacles that prevent patients with overweight or obesity from gaining access to needed medical care.

Thyroid nodules are common and are frequently benign. Current data suggest that the prevalence of palpable thyroid nodules is 3% to 7% in North America; the prevalence is as high as 50% based on ultrasonography (US) or autopsy data. The introduction of sensitive thyrotropin (thyroid-stimulating hormone or TSH) assays, the widespread application of fine-needle aspiration (FNA) biopsy, and the availability of high-resolution US have substantially improved the management of thyroid nodules. This document was prepared as a collaborative effort between the American Association of Clinical Endocrinologists (AACE) and the Associazione Medici Endocrinologi (AME). Most Task Force members are members of AACE. We have used the AACE protocol for clinical practice guidelines, with rating of available evidence, linking the guidelines to the strength of recommendations. Key observations include the following. Although most patients with thyroid nodules are asymptomatic, occasionally patients complain of dysphagia, dysphonia, pressure, pain, or symptoms of hyperthyroidism or hypothyroidism. Absence of symptoms does not rule out a malignant lesion; thus, it is important to review risk factors for malignant disease. Thyroid US should not be performed as a screening test. All patients with a palpable thyroid nodule, however, should undergo US examination. US-guided FNA (US-FNA) is recommended for nodules > or = 10 mm; US-FNA is suggested for nodules < 10 mm only if clinical information or US features are suspicious. Thyroid FNA is reliable and safe, and smears should be interpreted by an experienced pathologist. Patients with benign thyroid nodules should undergo follow-up, and malignant or suspicious nodules should be treated surgically. A radioisotope scan of the thyroid is useful if the TSH level is low or suppressed. Measurement of serum TSH is the best initial laboratory test of thyroid function and should be followed by measurement of free thyroxine if the TSH value is low and of thyroid peroxidase antibody if the TSH value is high. Percutaneous ethanol injection is useful in the treatment of cystic thyroid lesions; large,symptomatic goiters may be treated surgically or with radioiodine. Routine measurement of serum calcitonin is not recommended. Suggestions for thyroid nodule management during pregnancy are presented. We believe that these guidelines will be useful to clinical endocrinologists, endocrine surgeons, pediatricians, and internists whose practices include management of patients with thyroid disorders. These guidelines are thorough and practical, and they offer reasoned and balanced recommendations based on the best available evidence.

Background Glucagon like peptide-1 (GLP-1) receptor agonist treatment may improve endothelial function via direct and indirect mechanisms. We compared the acute and chronic effects of the GLP-1 receptor agonist exenatide vs. metformin on endothelial function in patients with obesity and pre-diabetes. Methods We performed a randomized, open-label, clinical trial in 50 non-diabetic individuals (mean age 58.5 ± 10.0; 38 females) with abdominal obesity and either impaired fasting glucose, elevated HbA1c, or impaired glucose tolerance (IGT) who were randomized to receive 3-months of exenatide or metformin. Microvascular endothelial function, assessed by digital reactive hyperemia (reactive hyperemic index: RHI), C-reactive protein (CRP), circulating oxidized LDL (oxLDL), and vascular cell adhesion molecule-1 (VCAM-1) were measured at baseline and 3-months. Seven subjects with IGT participated in a sub-study comparing the effects of pre-administration of exenatide and metformin on postprandial endothelial function. Results There were no differences for the change in RHI (Δ exenatide: 0.01 ± 0.68 vs. Δ metformin: -0.17 ± 0.72, P = 0.348), CRP, oxLDL, or VCAM-1 between exenatide and metformin treatment. Triglycerides were reduced more with exenatide compared to metformin (Δ exenatide: -25.5 ± 45.7 mg/dL vs. Δ metformin: -2.9 ± 22.8 mg/dL, P = 0.032). In the sub-study, there was no difference in postprandial RHI between exenatide and metformin. Conclusions Three months of exenatide therapy had similar effects on microvascular endothelial function, markers of inflammation, oxidative stress, and vascular activation, as metformin, in patients with obesity and pre-diabetes. Clinical trials registration This study is registered on http://www.clinicaltrials.gov/: NCT00546728