Persistent Deficits in Bone Quality in Treated Acromegaly: Evidence From Assessments of Microstructure.

Purpose: Fractures are increased in patients with acromegaly, both before and after successful acromegaly treatment. Abnormalities of bone microstructure, which may underlie this fragility, are present in active acromegaly but to what extent these improve with acromegaly treatment or persist despite biochemical remission remains unclear. To examine these questions, we studied the effects of acromegaly treatment and remission on bone quality. Methods: Sixty-five women and men with acromegaly were studied. Subgroups underwent assessments of areal bone mineral density by dual x-ray absorptiometry, trabecular bone score (TBS), and volumetric bone mineral density, microarchitecture, stiffness and failure load of the distal radius and tibia by high-resolution peripheral quantitative tomography in a longitudinal study before and after acromegaly treatment and in a cross-sectional study in which patients were compared to sex-, age-, and body mass index-matched healthy controls. Results: In the longitudinal study, significant increases in total, cortical, and trabecular densities at the radius and tibia and increased stiffness and failure load of the tibia occurred with acromegaly treatment. In the cross-sectional study, patients in biochemical remission after surgery had larger bones, lower trabecular and cortical volumetric density, and disrupted trabecular microarchitecture compared to controls. TBS did not change with acromegaly treatment but correlated with some microstructural parameters. Conclusion: We show, for the first time, that volumetric bone mineral density and microarchitecture of the peripheral skeleton improve with acromegaly treatment but remain abnormal in patients in remission after surgery compared to controls. These abnormalities, known to be associated with fractures in other populations, may play a role in the pathogenesis of persistent fragility in treated acromegaly.

Medical and Surgical Treatment of Obesity.

During the past decade, several effective antiobesity medications and devices have been developed. In addition, new information regarding the mechanism of action, benefits, and long-term efficacy of bariatric surgery continues to emerge. More than 90% of patients who qualify for therapy for obesity remain untreated. This article aims to provide an overview of the indications and efficacy of currently available medical and surgical therapies for obesity, along with a look toward promising therapies on the horizon.

Understanding the pathophysiologic pathways that underlie obesity and options for treatment.

INTRODUCTION: Obesity is a chronic, multifactorial condition with devastating health consequences. It was thought that obesity could be controlled with discipline and lifestyle changes, but we now know that the underlying pathophysiology is a dysregulation of the body's energy balance system, controlled by a complex interplay of neural, hormonal, and metabolic pathways. Recognizing obesity as a chronic disease places a greater responsibility on all health care professionals to screen and identify patients at risk and develop long-term tailored treatment plans. AREAS COVERED: This narrative review describes the central and peripheral pathways regulating obesity, the factors contributing to its development and how to effectively manage this disease. EXPERT OPINION: Obesity is a disease with pathophysiologic mechanisms and should be treated accordingly to reduce the significant risk of morbidity and mortality. Lifestyle interventions remain the cornerstones of treatment; however, these measures alone are rarely enough for long-term maintenance of weight loss. Additional interventions, such as pharmacotherapy or bariatric surgery, are indicated for many patients and should be recommended. Treatment considerations should include assessment of comorbidities or risk factors, as many anti-obesity agents and bariatric surgeries also have beneficial effects on other weight-associated comorbidities.Plain language summary: This plain language summary highlights information from a recent scientific article about obesity. Obesity is a disease that leads to excess accumulation of body fat that may negatively affect health. People can check if they have obesity by measuring their body mass index (BMI for short). The BMI is a screening tool to see if you are at risk of obesity. Obesity is defined as a BMI of 30 kg/m2 or higher with lower cut-offs in Asian populations. Obesity is a chronic health condition that leads to a shorter life span. People with obesity have a higher chance of having other health conditions, such as type 2 diabetes, fatty liver disease, heart disease, kidney problems, osteoarthritis, and some types of cancer. It can be hard for people with obesity to lose weight for various reasons. The aim of this article is to help doctors who treat people with obesity understand more about the causes for obesity, as well as the available treatment options, which include lifestyle changes, medicines, and for some people, weight loss surgery.[Figure: see text][Figure: see text][Figure: see text][Figure: see text].

Weight-loss response to naltrexone/bupropion is modulated by the Taq1A genetic variant near DRD2 (rs1800497): A pilot study.

Naltrexone/bupropion (NB) is a US Food and Drug Administration-approved antiobesity medication. Clinical trials have shown variable weight loss, with responders and non-responders. NB is believed to act on central dopaminergic pathways to suppress appetite. The Taq1A polymorphism near DRD2 (rs1800497) is associated with the density of striatal dopamine D2 receptors, with individuals carrying the A allele (AA or AG; termed A1+) having 30%-40% fewer dopamine binding sites than those who do not carry the A allele (GG; termed A1-). We performed a pilot study to assess the association of the rs1800497 ANKK1 c.2137G > A (p.Glu713Lys) variant with weight loss with NB treatment in 33 subjects. Mean (SD) weight loss was 5.9% (3.2%) for the A1+ genotype group (n = 15) and 4.2% (4.2%) for the A1- genotype group (n = 18). The mean weight loss for the A1+ genotype group was significantly greater than the predefined clinically significant 4% weight-loss target (one-sample t-test, P = .035), whereas the mean weight loss for the A1- genotype group was not (P = .85). Individuals with the A1+ genotype appear to respond better to NB than A1- individuals.

Joint international consensus statement for ending stigma of obesity.

People with obesity commonly face a pervasive, resilient form of social stigma. They are often subject to discrimination in the workplace as well as in educational and healthcare settings. Research indicates that weight stigma can cause physical and psychological harm, and that affected individuals are less likely to receive adequate care. For these reasons, weight stigma damages health, undermines human and social rights, and is unacceptable in modern societies. To inform healthcare professionals, policymakers, and the public about this issue, a multidisciplinary group of international experts, including representatives of scientific organizations, reviewed available evidence on the causes and harms of weight stigma and, using a modified Delphi process, developed a joint consensus statement with recommendations to eliminate weight bias. Academic institutions, professional organizations, media, public-health authorities, and governments should encourage education about weight stigma to facilitate a new public narrative about obesity, coherent with modern scientific knowledge.

IGF-1 levels across the spectrum of normal to elevated in acromegaly: relationship to insulin sensitivity, markers of cardiovascular risk and body composition.

PURPOSE: Activity of acromegaly is gauged by levels of GH and IGF-1 and epidemiological studies demonstrate that their normalization reduces acromegaly's excess mortality rate. However, few data are available linking IGF-1 levels to features of the disease that may relate to cardiovascular (CV) risk. Therefore, we tested the hypothesis that serum IGF-1 levels relative to the upper normal limit relate to insulin sensitivity, serum CV risk markers and body composition in acromegaly. METHODS: In this prospective, cross-sectional study conducted at a pituitary tumor referral center we studied 138 adult acromegaly patients, newly diagnosed and previously treated surgically, with fasting and post-oral glucose levels of endocrine and CV risk markers and body composition assessed by DXA. RESULTS: Active acromegaly is associated with lower insulin sensitivity, body fat and CRP levels than acromegaly in remission. %ULN IGF-1 strongly predicts insulin sensitivity, better than GH and this persists after adjustment for body fat and lean tissue mass. %ULN IGF-1 also relates inversely to CRP levels and fat mass, positively to lean tissue and skeletal muscle estimated (SM(E)) by DXA, but not to blood pressure, lipids, BMI or waist circumference. Gender interacts with the IGF-1-lean tissue mass relationship. CONCLUSIONS: Active acromegaly presents a unique combination of features associated with CV risk, reduced insulin sensitivity yet lower body fat and lower levels of some serum CV risk markers, a pattern that is reversed in remission. %ULN IGF-1 levels strongly predict these features. Given the known increased CV risk of active acromegaly, these findings suggest that of these factors insulin resistance is most strongly related to disease activity and potentially to the increased CV risk of active acromegaly.

The effect of bariatric surgery on renal function.

BACKGROUND: Obesity is associated with albuminuria and impaired renal function. We previously reported on 38 nondiabetics with improved albuminuria after Roux-en-Y gastric bypass (RYGB). METHODS: Our objectives were to evaluate changes in renal function, urinary albumin-to-creatinine ratio (UACR), and glomerular filtration rate (GFR) in a larger cohort of patients with normal or mildly impaired renal function, undergoing RYGB or sleeve gastrectomy at 1 year postop. This was a retrospective study. Inclusions: patients with preoperative and 1 year postoperative serum and urine albumin and creatinine and weight (kg). EXCLUSIONS: preop chronic kidney disease (CKD)≥Stage 3 or macroalbuminuria (UACR≥300 mg/g). PRIMARY OUTCOMES: changes in UACR and estimated GFR (eGFR) at 1 year. The setting was in a public hospital in New York City, 2004-2011. RESULTS: 158 patients met inclusion criteria; 91.8% female; mean age 40.8 years; 84.2% white Hispanic, 14.6 % black. Hypertension was present in 43.0%, diabetes mellitus in 28.5%. UACR was 21.5±3.2 mg/g, decreasing to 10.2±1.2 mg/g at 1 year (P<.0001). Microalbuminuria was present in 22/158 patients (14%) preop, resolving in 82% at 1 year; pre- versus 1 year postop eGFR, 97.5±2.2 versus 87.1±2.0 mL/min (P<.0001). Hyperfiltration was present in 8.2% preop, decreasing to 4.4% 1 year postop. CONCLUSION: In this mainly female minority population, UACR decreased within the normal range, while eGFR decreased from normal to the range for Stage 2 CKD at 1 year postop. Microalbuminuria resolved in most affected and hyperfiltration resolved in nearly half of those affected. This study is limited by its retrospective nature. Prospective studies should be performed.

Features at diagnosis of 324 patients with acromegaly did not change from 1981 to 2006: acromegaly remains under-recognized and under-diagnosed.

BACKGROUND: Traditionally, acromegaly evaded diagnosis until in its clinically obvious later stages when treatment is more difficult. Over the last 25 years diagnostic tests have improved, but whether clinical disease detection also improved was unknown, so we tested if disease severity at diagnosis had changed from 1981 to 2006. METHODS: Data on 324 consecutive acromegaly patients presenting from 1981 to 2006 at two New York City hospitals were collected by retrospective review (n = 324) and by interview (n = 200). The main complaint, acromegaly associated comorbidities, signs, symptoms, healthcare providers visited, preoperative GH and IGF-I levels and pituitary tumour size at diagnosis were compared in patients presenting in the earlier vs. later halves of the time period. RESULTS: Times from symptom onset to diagnosis were 5.9 year (early) vs. 5.2 year (late; P = NS). At diagnosis, 96% of early and late groups had facial feature changes and/or hand/foot enlargement. Comorbidities included hypertension 37% (early) vs. 36% (late), carpal tunnel syndrome (24%vs. 24%), sleep apnoea (13%vs. 29%; P < 0.01), osteoarthritis (25%vs. 23%) and diabetes mellitus (18%vs. 15%); each patient had 1.2 (early) vs. 1.3 (late; P = 0.53) comorbidities. Groups were similar in signs, symptoms, tumour size, GH and IGF-I. CONCLUSIONS: Clinical, biochemical and tumour size characteristics at diagnosis of acromegaly patients were unchanged from 1981 to 2006. Most patients still have marked manifestations of acromegaly at diagnosis, suggesting that acromegaly remains clinically under-recognized. Healthcare professionals should more commonly consider acromegaly, which can lead to earlier diagnosis and better treatment outcome.