Louis J. Aronne

Putative contributors to the secular increase in obesity: exploring the roads less traveled

Objective:To investigate plausible contributors to the obesity epidemic beyond the two most commonly suggested factors, reduced physical activity and food marketing practices.Design:A narrative review of data and published materials that provide evidence of the role of additional putative factors in contributing to the increasing prevalence of obesity.Data:Information was drawn from ecological and epidemiological studies of humans, animal studies and studies addressing physiological mechanisms, when available.Results:For at least 10 putative additional explanations for the increased prevalence of obesity over the recent decades, we found supportive (although not conclusive) evidence that in many cases is as compelling as the evidence for more commonly discussed putative explanations.Conclusion:Undue attention has been devoted to reduced physical activity and food marketing practices as postulated causes for increases in the prevalence of obesity, leading to neglect of other plausible mechanisms and well-intentioned, but potentially ill-founded proposals for reducing obesity rates.

Ten Putative Contributors to the Obesity Epidemic

The obesity epidemic is a global issue and shows no signs of abating, while the cause of this epidemic remains unclear. Marketing practices of energy-dense foods and institutionally-driven declines in physical activity are the alleged perpetrators for the epidemic, despite a lack of solid evidence to demonstrate their causal role. While both may contribute to obesity, we call attention to their unquestioned dominance in program funding and public efforts to reduce obesity, and propose several alternative putative contributors that would benefit from equal consideration and attention. Evidence for microorganisms, epigenetics, increasing maternal age, greater fecundity among people with higher adiposity, assortative mating, sleep debt, endocrine disruptors, pharmaceutical iatrogenesis, reduction in variability of ambient temperatures, and intrauterine and intergenerational effects as contributing factors to the obesity epidemic are reviewed herein. While the evidence is strong for some contributors such as pharmaceutical-induced weight gain, it is still emerging for other reviewed factors. Considering the role of such putative etiological factors of obesity may lead to comprehensive, cause specific, and effective strategies for prevention and treatment of this global epidemic.

Pharmacological Management of Obesity: An Endocrine Society Clinical Practice Guideline

OBJECTIVE To formulate clinical practice guidelines for the pharmacological management of obesity. PARTICIPANTS An Endocrine Society-appointed Task Force of experts, a methodologist, and a medical writer. This guideline was co-sponsored by the European Society of Endocrinology and The Obesity Society. EVIDENCE This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe the strength of recommendations and the quality of evidence. CONSENSUS PROCESS One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society, the European Society of Endocrinology, and The Obesity Society reviewed and commented on preliminary drafts of these guidelines. Two systematic reviews were conducted to summarize some of the supporting evidence. CONCLUSIONS Weight loss is a pathway to health improvement for patients with obesity-associated risk factors and comorbidities. Medications approved for chronic weight management can be useful adjuncts to lifestyle change for patients who have been unsuccessful with diet and exercise alone. Many medications commonly prescribed for diabetes, depression, and other chronic diseases have weight effects, either to promote weight gain or produce weight loss. Knowledgeable prescribing of medications, choosing whenever possible those with favorable weight profiles, can aid in the prevention and management of obesity and thus improve health.

A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity-related risk factors (COR-II).

To examine the effects of naltrexone/bupropion (NB) combination therapy on weight and weight‐related risk factors in overweight and obese participants.

Obesity-related hypertension: Pathogenesis, cardiovascular risk, and treatment-a position paper of the the obesity society and the American society of hypertension

In light of the worldwide epidemic of obesity, and in recognition of hypertension as a major factor in the cardiovascular morbidity and mortality associated with obesity, The Obesity Society and The American Society of Hypertension agreed to jointly sponsor a position paper on obesity‐related hypertension to be published jointly in the journals of each society. The purpose is to inform the members of both societies, as well as practicing clinicians, with a timely review of the association between obesity and high blood pressure, the risk that this association entails, and the options for rational, evidenced‐based treatment. The position paper is divided into six sections plus a summary as follows: pathophysiology, epidemiology and cardiovascular risk, the metabolic syndrome, lifestyle management in prevention and treatment, pharmacologic treatment of hypertension in the obese, and the medical and surgical treatment of obesity in obese hypertensive patients. Obesity (2012)

The emerging science of body weight regulation and its impact on obesity treatment

Obesity is a complex disorder characterized by the accumulation of excess adipose tissue. While obesity has long been considered a behavioral disorder, discovery of the hormone leptin in 1994 catalyzed the field of obesity research by demonstrating the existence of an afferent humoral signal from adipose tissue to the central nervous system. Current evidence suggests that once adipose tissue accumulates, a system of overlapping neuroendocrine systems prevents it from diminishing. This counter-regulatory mechanism, which has probably evolved as protection against starvation and fetal or neonatal wastage, causes changes in appetite and metabolism that make volitional weight loss difficult to achieve. Obesity is defined in terms of BMI, calculated as weight (kg)/[height (m)] 2 . Although a continuous variable, BMI has been categorized based on epidemiologic data to denote the relative risk of developing comorbid conditions. A BMI less than 25 is considered to be normal, 25‐29.9 is overweight, and greater than or equal to 30, obese. Data from the 1999 National Health Nutritional and Exercise survey demonstrated that 34% of adults in the United States were overweight, and 30.8% obese, resulting in a total of 64.8% above normal weight. The prevalence of overweight and obesity in children was 13%, a doubling since 1980, while adolescents have experienced a tripling in prevalence since then. Being overweight or obese substantially increases the risk of morbidity from a number of conditions, including type 2 diabetes mellitus (DM), hypertension, dyslipidemia, coronary heart disease, congestive heart failure, stroke, gallbladder disease, hepatic steatosis, osteoarthritis, sleep apnea, and endometrial, breast, prostate, and colon cancers. An increase in all-cause mortality is also associated with higher body weights. Adipose tissue is an active endocrine organ that produces free fatty acids and hormones, such as IL-6, TNF-α , plasminogen activation inhibitor‐1, angiotensinogen, and others, directly related to the insulin resistance, hyperlipidemia, inflammation, thrombosis, and hypertension that characterize obesity. Visceral fat appears to be the greatest contributor to these effects, probably because of its location in the portal circulation draining to the liver. Regulation of energy homeostasis The discovery of leptin and other genes responsible for obesity in rodents has had a considerable impact on our understanding of body weight regulation. Leptin (derived from Greek leptos, meaning thin) is a hormone that is produced by fat cells and circulates at levels proportional to body fat content. Leptin crosses the blood

Sustained Weight Loss Following 12-Month Pramlintide Treatment as an Adjunct to Lifestyle Intervention in Obesity

OBJECTIVE—To assess long-term weight loss efficacy and safety of pramlintide used at different dosing regimens and in conjunction with lifestyle intervention (LSI). RESEARCH DESIGN AND METHODS—In a 4-month, double-blind, placebo-controlled, dose-ranging study, 411 obese subjects were randomized to receive pramlintide (six arms: 120, 240, and 360 μg b.i.d. and t.i.d.) or placebo in conjunction with a structured LSI program geared toward weight loss. Of the 4-month evaluable subjects (n = 270), 77% opted to continue preexisting treatment during an 8-month single-blind extension (LSI geared toward weight maintenance). RESULTS—At month 4, mean weight loss from baseline in the pramlintide arms ranged from 3.8 ± 0.7 to 6.1 ± 0.8 kg (2.8 ± 0.8 kg with placebo). By month 12, initial 4-month weight loss was regained in the placebo group but was maintained in all but the 120-μg b.i.d. group. Placebo-corrected weight loss with 120 μg t.i.d. and 360 μg b.i.d. averaged 3.2 ± 1.2 kg (3.1 ± 1.1% body wt) and 3.3 ± 1.1 kg (3.1 ± 1.0% body wt), respectively, at month 4 (both P < 0.01; 4-month evaluable n = 270) and 6.1 ± 2.1 kg (5.6 ± 2.1% body wt) and 7.2 ± 2.3 kg (6.8 ± 2.3% body wt), respectively, at month 12 (both P < 0.01; 12-month evaluable n = 146). At month 12, 40 and 43% of subjects treated with 120 μg t.i.d. and 360 μg b.i.d., respectively, achieved ≥10% weight loss (vs. 12% for placebo). Nausea, the most common adverse event with pramlintide in the 4-month study (9–29% pramlintide vs. 2% placebo), was generally mild to moderate and occurred in <10% of subjects during the extension. CONCLUSIONS—When used over 12 months as an adjunct to LSI, pramlintide treatment, with low-dose three-times-daily or higher-dose two-times-daily regimens, helped obese subjects achieve greater initial weight loss and enhanced long-term maintenance of weight loss.

New Drug Targets for the Treatment of Obesity

There is a huge void in the current pharmacological treatment options for obesity. This gap is surprising given the high prevalence and associated costs of obesity. Many factors have prevented active drug development, including the poor safety and efficacy of earlier antiobesity drugs. However, there are now several compelling targets on the horizon. The new generation of antiobesity drugs offers hope for the management of obesity, but no single agent is likely to be a panacea. Rather, obesity will need to be managed like many other chronic diseases, with combination therapies and long‐term treatment in order to achieve sustained success. New targets have arisen as more research has been performed to understand the complex circuitry that controls energy homeostasis. The goal of this review is to discuss the latest pharmacological agents and strategies that are under development and that may eventually be used for the treatment of obesity.

Psychiatric illness in patients presenting for obesity treatment

The prevalence of DSM-III-R Axis I psychiatric disorders was investigated in a sample of 54 obese patients at the time of presentation for weight reduction treatment. Patients were interviewed using the Structured Clinical Interview for DSM-III-R Axis I diagnosis (SCID-I) designed to probe for the major Axis I syndromes. High rates of affective disorders, particularly those with depressive symptomatology, were found. Twenty-six percent of patients were in the midst of a current Axis I affective disorder at the time of examination. Forty-eight percent had a history of affective disorder, and 57% had at least one lifetime Axis I diagnosis. Only one patient met criteria for an Axis I eating disorder. Patients with psychiatric diagnoses could not be discriminated from those without on the basis of Body Mass Index. However, the former had significantly more impairment as measured by the Beck Depression Inventory and the Global Assessment of Functioning. These findings may have implications for the assessment and treatment of obese patients in clinical and research settings.

Obesity-related hypertension: pathogenesis, cardiovascular risk, and treatment: a position paper of The Obesity Society and the American Society of Hypertension.

In light of the worldwide epidemic of obesity, and in recognition of hypertension as a major factor in the cardiovascular morbidity and mortality associated with obesity, The Obesity Society and the American Society of Hypertension agreed to jointly sponsor a position paper on obesity‐related hypertension to be published jointly in the journals of each society. The purpose is to inform the members of both societies, as well as practicing clinicians, with a timely review of the association between obesity and high blood pressure, the risk that this association entails, and the options for rational, evidenced‐based treatment. The position paper is divided into six sections plus a summary as follows: pathophysiology, epidemiology and cardiovascular risk, the metabolic syndrome, lifestyle management in prevention and treatment, pharmacologic treatment of hypertension in the obese, and the medical and surgical treatment of obesity in obese hypertensive patients.