The Case for Medical Management of Obesity: A Call for Increased Physician Involvement

The United States is in the midst of an escalating epidemic of obesity. Over one-third of the adult population in the United States is currently obese and the prevalence of obesity is growing rapidly. By any criteria, obesity represents a chronic disease which is associated with a wide range of comorbidities, including coronary heart disease (CHD), Type 2 diabetes, hypertension and dyslipidemias. The comorbidities of obesity are common, occurring in over 70% of individuals with a BMI of ≥ 27. In addition to obesity itself, excessive accumulation of visceral abdominal fat and significant adult weight gain also represent health risks. Physicians have an important role to play in the treatment of obesity. Unfortunately, the medical community has not been involved actively enough to help stem the major epidemic of obesity occurring in the United States. This article puts forth a proposed model for the treatment of obesity in clinical practice, including obtaining the “vital signs” of obesity, recommending lifestyle measures, and instituting pharmacologic therapy when appropriate. By utilizing a chronic disease treatment model, physicians can join other health care professionals to effectively treat the chronic disease of obesity. Relatively modest weight loss, on the order of 510% of initial body weight can result in significant health improvements for many patients and represent an achievable goal for most obese patients.     

Gene-diet interactions in childhood obesity

Childhood overweight and obesity have reached epidemic proportions worldwide, and the increase in weight-associated co-morbidities including premature type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease will soon become major healthcare and economic problems. A number of studies now indicate that the childhood obesity epidemic which has emerged during the past 30 years is a complex multi-factorial disease resulting from interaction of susceptibility genes with an obesogenic environment. This review will focus on gene-diet interactions suspected of having a prominent role in promoting childhood obesity. In particular, the specific genes that will be presented (FTO, MC4R, and NPC1) have recently been associated with childhood obesity through a genome-wide association study (GWAS) and were shown to interact with nutritional components to increase weight gain. Although a fourth gene (APOA2) has not yet been associated with childhood obesity, this review will also present information on what now represents the best characterized gene-diet interaction in promoting weight gain.     

Does access to fast food lead to super-sized pregnant women and whopper babies?

Rise in the availability of fast-food restaurants has been blamed, at least partly, for the increasing obesity in the U.S. The existing studies of obesity have focused primarily on children, adolescents, and adults, and this paper extends the literature by raising a little-studied question and using nationally representative data to answer it. It examines the relationship between the supply of fast-food restaurants and weight gain of pregnant women and their newborns. I study prenatal weight gain because excessive weight gain has been linked to postpartum overweight/obesity and I study both tails of the birthweight distribution because the origin of obesity may be traced to the prenatal period and both tail outcomes have been associated with obesity later in life. I merge the 1998 and 2004 Natality Detail Files with the Area Resource File, and County Business Patterns, which provide data on the number of fast-food restaurants in the metropolitan area where the mother resides. The empirical model includes an extensive list of MSA characteristics and MSA fixed effects to control for factors that may be correlated with both health outcomes and restaurants’ location decision. Results reveal that the fast-food and weight gain relationship is robust to the inclusion of these controls but these controls greatly mitigate the fast food–infant health relationship. Greater access to fast-food restaurants is positively related to mothers’ probability of excessive weight gain but it does not share a statistically significant relationship with birthweight. These relationships hold in all the socioeconomic and demographic subgroups studied.     

The Obesity Epidemic and Its Impact on Urologic Care

Although heart disease and cancer are the number one and two causes of death in the United States, respectively, obesity is gaining speed as a contributing cause to both of those conditions, along with diabetes, arthritis, dyslipidemia, coronary heart disease, gallbladder disease, and certain malignancies. Nearly one-third of the adults in the United States is overweight with a body mass index (BMI) greater than 25 kg/m², and another third of the adult population is obese, with a BMI greater than 30 kg/m². This article reviews the root causes of obesity, the societal implications, and the implications of obesity on various urologic diseases.Key words: Obesity, Morbid obesity, Body mass index, Exercise, Weight loss, Diet, EpidemicMore than 20% of adults in the United States are clinically obese, defined by a body mass index (BMI) of 30 kg/m² or higher, and an additional 30% are overweight, with a BMI between 25 and 30 kg/m².¹ An environment that promotes excessive food intake and discourages physical activity lies at the root of the current obesity epidemic. Although humans have excellent physiologic mechanisms to defend against body weight loss, they have only weak physiologic mechanisms to defend against body weight gain when food is abundant. So much has been discussed about the obesity epidemic that it’s easy to think the issue is being blown out of proportion. After all, people putting on a few pounds may not seem to warrant the proclamation of a national emergency. Although obesity may not attract the degree of attention that heart disease and cancer do, it is a serious public health issue. Experts agree that, as more and more obese children become obese adults, the diseases associated with obesity, such as heart disease, cancer, and particularly diabetes, will surge.The obesity epidemic in the United States is an unintended consequence of the economic, social, and technologic advances realized during the past several decades. The food supply is abundant and low in cost, and palatable foods with high caloric density are readily available in prepackaged forms and at fast-food restaurants. Laborsaving technologies have greatly reduced the amount of physical activity that used to be part of everyday life, and the widespread availability of electronic devices in the home, school, and office has promoted a sedentary lifestyle, particularly among children.A recent study estimated that medical expenditures attributed to overweight and obesity accounted for 9.1% of total US medical expenditures in 1998, and might have reached $78.5 billion dollars.² Today, the healthcare costs attributed to obesity are estimated to be $190 billion—nearly 21% of total US healthcare costs.³ Expenditures will continue to rise, particularly due to increases in the prevalence of obesity and the cost of related healthcare.Total healthcare costs attributable to this obesity epidemic are expected to double every decade, reaching $860.7 to $956.9 billion by 2030, accounting for 16% to 18% of total US healthcare costs, or 1 in every 6 dollars spent on healthcare. ⁴ In addition, obesity is likely to result in a decreased life expectancy for our population. Current US generations may have a shorter life expectancy than their parents if this obesity epidemic cannot be controlled.⁵ Based on nationally representative data and the assumptions of a future of increased obesity rates, along with increased healthcare costs, this paints an alarming picture of the future obesity epidemic. Projections show that if the trends continue, in 15 years, 80% of all American adults will be overweight or obese.⁶     

Why do we need drugs to treat the patient with obesity?

Objective:

Obesity is a public health problem, which increases the risk of chronic diseases and mortality. Weight loss can reduce mortality and improve most of the detrimental health consequences of obesity.

Design and Methods:

This paper was developed from two presentations to the US Food and Drug Administration (FDA), which has responsibility for reviewing and approving drugs to treat obesity.

Results:

A weight loss of 5% or more is sufficient to significantly reduce health risks in individuals with impaired glucose tolerance, hypertension, or nonalcoholic fatty liver disease. Slightly more weight loss (16% on average, achieved by surgery) reduces mortality. The goal of medicating for obesity is to help more patients achieve more weight loss. A barrier to drug approval has been the concern that weight loss medications might be used by individuals with little or no health risks, thus mandating a low side effect profile for approval of any drug. This limits the options for patients who have obesity‐related health problems that could improve with weight loss. Recently the FDA signaled interest in identifying health benefits in higher risk patients that might justify medications with higher risk; however, the potential impact on a large segment of the population has led the FDA to consider requiring a cardiovascular outcome trial for all obesity medications, either prior to or after approval.

Conclusion:

This review argues that drugs are needed for obesity because they enhance behaviorally induced weight loss and that new medications for obesity are needed in the approval process.     

Preventing and Treating Obesity in Girls and Young Women to Curb the Epidemic

Obesity and its serious comorbidities, type 2 diabetes, coronary heart disease, hypertension, and dyslipidemia, have reached epidemic proportions in adults and children. Female obesity is more prevalent and, thus, has greater epidemiological importance: Mothers transmit the disease epigenetically and genetically. Maternal obesity affects maternal health, pregnancy outcome, and fetal, neonatal, childhood, and ultimately adult morbidity and mortality. Obesity is easy to diagnose, as are most of its risk factors, yet very little progress has been made in preventing the disease. During a brief period of rapid early growth, there is imprinting of antecedents of adult obesity and obesity‐related disease. Because of the rapidity of this early growth and the relative brevity of the critical period, early recognition and prompt intervention are necessary and possibly sufficient to prevent the development of obesity. Identification of inappropriate rapid weight gain through frequent weighing should trigger immediate adjustment of energy intake, a simple intervention in bottle‐fed infants, the ones at greatest risk for becoming obese. This review presents a step‐care strategy with fail‐safe action levels starting with maternal education and diet, exercise, and behavior modification for mother and child and progressing to drug treatment and, in selected cases, laparoscopic surgery for young women of childbearing age in whom other measures have failed. This approach is predicated on the assumption that careful monitoring and responsive supplementation of potential deficiencies is easier to achieve, more cost‐effective, and safer than effectively treating manifest obesity and its comorbidities in adults.     

Willingness to pay for obesity pharmacotherapy

Several treatments for obesity have received regulatory approval, but health insurers and other payers typically refuse to support access to them. Thus, patients are left to bear significant out-of-pocket costs for obesity pharmacotherapy. This study aimed to assess preferences and willingness to pay (WTP) for obesity medications among people seeking weight loss in the United States and United Kingdom. An online survey was developed based on literature review, clinician interviews, and profiles of available therapies. Participants indicated their preference for hypothetical treatments which varied by seven attributes: percentage of weight loss, long-term health risk reduction, time to noticeable weight loss, delivery mode, side effects, lifestyle modification, and cost; 502 obese participants completed the survey (mean BMI 37.12 kg/m(2) (±4.63); 73.5% female; 47.7 (±12.9) years of age). The participants deemed weight loss of >21 kg (United Kingdom) and >28 kg (United State) as "acceptable". All treatment attributes were important (P < 0.001) except "time to noticeable weight loss." The survey found that percentage weight loss was the most important factor for patients and a reduction in long-term health risk was relatively less important. Patients were willing to pay ￡6.51/$10.49 per month per percentage point of weight loss that a pharmacotherapy could provide. Participants also highly valued therapies that did not require substantial lifestyle modifications and were willing to pay ￡17.78/$30.77 more per month for a one-pill-per-day treatment vs. a weekly injectable. Participants placed a high value on weight loss and avoiding changes to their lifestyle, and less value on reducing long-term risks to health.     

Escalating coverage of obesity in UK newspapers: the evolution and framing of the "obesity epidemic" from 1996 to 2010

Obesity is one of the fastest growing and most serious public health challenges facing the world in the 21st century. Correspondingly, over the past decade there has been increased interest in how the obesity epidemic has been framed by the media. This study offers the first large-scale examination of the evolution and framing of the obesity epidemic in UK newspapers, identifying shifts in news coverage about the causal drivers of and potential solutions to the obesity epidemic. Seven UK newspapers were selected and 2,414 articles published between 1 January 1996 and 31 December 2010 were retrieved from electronic databases using keyword searches. The thematic content of articles was examined using manifest content analysis. Over the 15-year period there was an increase in media reporting on obesity and in particular on childhood obesity. There was evidence of a trend away from a focus on individuals towards a greater level of reporting on societal solutions such as regulatory change, with the greatest shift in reporting occurring in mid-market and serious newspapers. Given that the media have a huge influence in shaping public opinion, this shift in reporting might be an early indicator to policymakers of a growing public discourse around a need for regulatory change to tackle the obesogenic environment.     

Sorghum phytochemicals and their potential impact on human health

Sorghum is a rich source of various phytochemicals including tannins, phenolic acids, anthocyanins, phytosterols and policosanols. These phytochemicals have potential to significantly impact human health. Sorghum fractions possess high antioxidant activity in vitro relative to other cereals or fruits. These fractions may offer similar health benefits commonly associated with fruits. Available epidemiological evidence suggests that sorghum consumption reduces the risk of certain types of cancer in humans compared to other cereals. The high concentration of phytochemicals in sorghum may be partly responsible. Sorghums containing tannins are widely reported to reduce caloric availability and hence weight gain in animals. This property is potentially useful in helping reduce obesity in humans. Sorghum phytochemicals also promote cardiovascular health in animals. Such properties have not been reported in humans and require investigation, since cardiovascular disease is currently the leading killer in the developed world. This paper reviews available information on sorghum phytochemicals, how the information relates to current phytonutrient research and how it has potential to combat common nutrition-related diseases including cancer, cardiovascular disease and obesity.     

Vaccination against GIP for the treatment of obesity

Background

According to the WHO, more than 1 billion people worldwide are overweight and at risk of developing chronic illnesses, including cardiovascular disease, type 2 diabetes, hypertension and stroke. Current therapies show limited efficacy and are often associated with unpleasant side-effect profiles, hence there is a medical need for new therapeutic interventions in the field of obesity. Gastric inhibitory peptide (GIP, also known as glucose-dependent insulinotropic polypeptide) has recently been postulated to link over-nutrition with obesity. In fact GIP receptor-deficient mice (GIPR^−/−) were shown to be completely protected from diet-induced obesity. Thus, disrupting GIP signaling represents a promising novel therapeutic strategy for the treatment of obesity.

Methodology/Principal Findings

In order to block GIP signaling we chose an active vaccination approach using GIP peptides covalently attached to virus-like particles (VLP-GIP). Vaccination of mice with VLP-GIP induced high titers of specific antibodies and efficiently reduced body weight gain in animals fed a high fat diet. The reduction in body weight gain could be attributed to reduced accumulation of fat. Moreover, increased weight loss was observed in obese mice vaccinated with VLP-GIP. Importantly, despite the incretin action of GIP, VLP-GIP-treated mice did not show signs of glucose intolerance.

Conclusions/Significance

This study shows that vaccination against GIP was safe and effective. Thus active vaccination may represent a novel, long-lasting treatment for obesity. However further preclinical safety/toxicology studies will be required before the therapeutic concept can be addressed in humans.     

Metabolic Determinants of Weight Gain in Humans

One of the fundamental challenges in obesity research is to identify subjects prone to weight gain so that obesity and its comorbidities can be promptly prevented or treated. The principles of thermodynamics as applied to human body energetics demonstrate that susceptibility to weight gain varies among individuals as a result of interindividual differences in energy expenditure and energy intake, two factors that counterbalance one another and determine daily energy balance and, ultimately, body weight change. This review focuses on the variability among individuals in human metabolism that determines weight change. Conflicting results have been reported about the role of interindividual differences in energy metabolism during energy balance in relation to future weight change. However, recent studies have shown that metabolic responses to acute, short‐term dietary interventions that create energy imbalance, such as low‐protein overfeeding or fasting for 24 hours, may reveal the underlying metabolic phenotype that determines the degree of resistance to diet‐induced weight loss or the propensity to spontaneous weight gain over time. Metabolically “thrifty” individuals, characterized by a predilection for saving energy in settings of undernutrition and dietary protein restriction, display a minimal increase in plasma fibroblast growth factor 21 concentrations in response to a low‐protein overfeeding diet and tend to gain more weight over time compared with metabolically “spendthrift” individuals. Similarly, interindividual variability in the causal relationship between energy expenditure and energy intake (“energy sensing”) and in the metabolic response to cold exposure (e.g., brown adipose tissue activation) seems, to some extent, to be indicative of individual propensity to weight gain. Thus, an increased understanding and the clinical characterization of phenotypic differences in energy metabolism among individuals (metabolic profile) may lead to new strategies to prevent weight gain or improve weight‐loss interventions by targeted therapies on the basis of metabolic phenotype and susceptibility to obesity in individual persons.     

Severe Obesity in Young Women and Reproductive Health: The Danish National Birth Cohort

Background

Little is known about reproductive health in severely obese women. In this study, we present associations between different levels of severe obesity and a wide range of health outcomes in the mother and child.

Methods

From the Danish National Birth Cohort, we obtained self-reported information about prepregnant body mass index (BMI) for 2451 severely obese women and 2450 randomly selected women from the remaining cohort who served as a comparison group. Information about maternal and infant outcomes was also self-reported or came from registers. Logistic regression was used to estimate the association between different levels of severe obesity and reproductive outcomes.

Principal Findings

Subfecundity was more frequent in severely obese women, and during pregnancy, they had an excess risk of urinary tract infections, gestational diabetes, preeclampsia and other hypertensive disorders which increased with severity of obesity. They tended to have a higher risk of both pre- and post-term birth, and risk of cesarean and instrumental deliveries increased across obesity categories. After birth, severely obese women more often failed to initiate or sustain breastfeeding. Risk of weight retention 1.5 years after birth was similar to that of other women, but after adjustment for gestational weight gain, the risk was increased, especially in women in the lowest obesity category. In infants, increasing maternal obesity was associated with decreased risk of a low birth weight and increased risk of a high birth weight. Estimates for ponderal index showed the same pattern indicating an increasing risk of neonatal fatness with severity of obesity. Infant obesity measured one year after birth was also increased in children of severely obese mothers.

Conclusion

Severe obesity is correlated with a substantial disease burden in reproductive health. Although the causal mechanisms remain elusive, these findings are useful for making predictions and planning health care at the individual level.     

Virginity Testing: Managing Sexuality in a Maturing HIV/AIDS Epidemic

KwaZulu-Natal province in South Africa is currently the site of the world's fastest growing HIV/AIDS epidemic, where it is estimated that between 30 and 40 percent of the adult population is seropositive for HIV. With support from local politicians and members of various government ministries, several self-styled guardians of tradition have emerged to form organizations that advocate and conduct regular virginity testing of girls. Reference to the current HIV/AIDS epidemic is central to calls for greater support of this practice. Drawing on original research among Zulu-speaking people in the periurban communities of Durban, this article examines the sociocultural construction of HIV/AIDS and locates the growing popularity of virginity testing within a gendered meaning-making process consistent with commonly held beliefs that the epidemic is the result of women being sexually "out of control." With the social impact of AIDS starting to take its toll in the forms of increasing AIDS-related deaths and a growing population of orphans, I argue that virginity testing is an attempt to manage the epidemic by exerting greater control over women and their sexuality. In addition, virginity testing of girls helps to draw attention away from the role of men in the maturing epidemic, consideration of which has been conspicuously absent in the popular discourse on AIDS at all levels of South African society.     

Examining the temporal relationships between childhood obesity and asthma

Childhood obesity has become an issue of increasing concern to health researchers and policymakers in the United States. One important chronic health condition linked to obesity is pediatric asthma. Although researchers have speculated that both conditions may have common origins, the majority of research in this area has focused on a unidirectional relationship between obesity and later asthma. However, much of the literature is limited by its reliance on cross-sectional data and its failure to examine the possibility that asthma may influence weight fluctuations through changes in physical and sedentary activity. Using data from the Early Childhood Longitudinal Study-Kindergarten Cohort (ECLS-K), I explore the bidirectional relationships between childhood obesity and asthma. The results in this paper suggest that past asthma levels are positively correlated with changes in BMI and the onset of obesity. However, only new onset asthma is positively correlated with subsequent changes in BMI. The potential mechanisms are unclear, as I find little evidence that asthma is structurally related to changes in physical or sedentary activity over time. When testing the prevailing hypothesis that obesity is related to subsequent asthma, I find that lagged weight status is strongly related to asthma prevalence levels but that the onset of overweight or obesity is not associated with the subsequent onset of asthma. These results suggest that the onset of asthma may be related to subsequent weight gain over time.     

Sleep and circadian rhythms: key components in the regulation of energy metabolism

In this review, we present evidence from human and animal studies to evaluate the hypothesis that sleep and circadian rhythms have direct impacts on energy metabolism, and represent important mechanisms underlying the major health epidemics of obesity and diabetes. The first part of this review will focus on studies that support the idea that sleep loss and obesity are "interacting epidemics." The second part will discuss recent evidence that the circadian clock system plays a fundamental role in energy metabolism at both the behavioral and molecular levels. These lines of research must be seen as in their infancy, but nevertheless, have provided a conceptual and experimental framework that potentially has great importance for understanding metabolic health and disease.     

Sleep loss: a novel risk factor for insulin resistance and Type 2 diabetes.

Chronic sleep loss as a consequence of voluntary bedtime restriction is an endemic condition in modern society. Although sleep exerts marked modulatory effects on glucose metabolism, and molecular mechanisms for the interaction between sleeping and feeding have been documented, the potential impact of recurrent sleep curtailment on the risk for diabetes and obesity has only recently been investigated. In laboratory studies of healthy young adults submitted to recurrent partial sleep restriction, marked alterations in glucose metabolism including decreased glucose tolerance and insulin sensitivity have been demonstrated. The neuroendocrine regulation of appetite was also affected as the levels of the anorexigenic hormone leptin were decreased, whereas the levels of the orexigenic factor ghrelin were increased. Importantly, these neuroendocrine abnormalities were correlated with increased hunger and appetite, which may lead to overeating and weight gain. Consistent with these laboratory findings, a growing body of epidemiological evidence supports an association between short sleep duration and the risk for obesity and diabetes. Chronic sleep loss may also be the consequence of pathological conditions such as sleep-disordered breathing. In this increasingly prevalent syndrome, a feedforward cascade of negative events generated by sleep loss, sleep fragmentation, and hypoxia are likely to exacerbate the severity of metabolic disturbances. In conclusion, chronic sleep loss, behavioral or sleep disorder related, may represent a novel risk factor for weight gain, insulin resistance, and Type 2 diabetes.     

Thinking Evolutionarily About Obesity

Obesity, diabetes, and metabolic syndrome are growing worldwide health concerns, yet their causes are not fully understood. Research into the etiology of the obesity epidemic is highly influenced by our understanding of the evolutionary roots of metabolic control. For half a century, the thrifty gene hypothesis, which argues that obesity is an evolutionary adaptation for surviving periods of famine, has dominated the thinking on this topic. Obesity researchers are often not aware that there is, in fact, limited evidence to support the thrifty gene hypothesis and that alternative hypotheses have been suggested. This review presents evidence for and against the thrifty gene hypothesis and introduces readers to additional hypotheses for the evolutionary origins of the obesity epidemic. Because these alternate hypotheses imply significantly different strategies for research and clinical management of obesity, their consideration is critical to halting the spread of this epidemic.     

Role of hereditary factors in weight loss and its maintenance

The prevalence of obesity is increasing worldwide at an alarming rate in both developed and developing countries. Obesity is a chronic complex disease of multifactorial origin resulting from a long-term positive energy balance, in which both genetic and environmental factors are involved. Genetically prone individuals are the first to accumulate fat in the present obesogenic environment. Obesity increases the risks of type 2 diabetes, hypertension, cardiovascular disease, dyslipidemia, arthritis, and several cancers and reduces the average life expectancy. Implementation of effective strategies in prevention and management of obesity should become an important target in health care systems. Weight changes throughout life depend on the interaction of behavioral, genetic and environmental factors. Weight loss in response to weight management shows a wide range of interindividual variation which is largely influenced by genetic determinants. The strong control of weight loss by genotype was confirmed by twin and family studies. Recently, special attention has been paid to nutritional, hormonal, psychobehavioral and genetic factors which can predict the response to weight reduction programme. In this article currently available data on the role of obesity candidate gene polymorphisms in weight loss and maintenance are reviewed. It is believed that an elucidation of the genetic component in the prognosis of weight management could assist in the development of more effective and individually tailored therapeutic strategies.     

Nanomedicine for obesity treatment

Obesity, as a chronic condition, has been a serious public health issue over the last decades both in the affluent Western world and developing countries. As reported, the risk of several serious diseases increases with weight gain, including type 2 diabetes, coronary heart disease, cancer, and respiratory diseases. In addition to lifestyle modifications, pharmacotherapy has become an important strategy to control weight gain. However, most of the anti-obesity drugs often show poor outcome for weight-loss and cause severe adverse effects. This review surveys recent advances in nanomedicine as an emerging strategy for obesity treatment with an emphasis on the enhanced therapeutic efficiency and minimized side effects. The insights for future development are also discussed.     

The Controversy Over Pediatric Bariatric Surgery

Despite the reported limited success of conventional treatments and growing evidence of the effectiveness of adult bariatric surgery, weight loss operations for (morbidly) obese children and adolescents are still considered to be controversial by health care professionals and lay people alike. This paper describes an explorative, qualitative study involving obesity specialists, morbidly obese adolescents, and parents and identifies attitudes and normative beliefs regarding pediatric bariatric surgery. Views on the etiology of obesity—whether it should be considered primarily a medical condition or more a psychosocial problem—seem to affect the specialists’ normative opinions concerning the acceptability of bariatric procedures as a treatment option, the parents’ feelings regarding both being able to influence their child’s health and their child being able to control their own condition, and the adolescents’ sense of competence and motivation for treatment. Moreover, parents and adolescents who saw obesity as something that they could influence themselves were more in favor of non-surgical treatment and vice versa. Conflicting attitudes and normative views—e.g., with regard to concepts of disease, personal influence on health, motivation, and the possibility of a careful informed consent procedure—play an important role in the acceptability of bariatric surgery for childhood obesity.