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More Reflections on Obesity

      For many people, obesity is a sensitive topic. I include myself in that cohort. When I entered college, I was a skinny 108 lb (49 kg). That weight allowed me to go out for freshman crew and to enjoy the coxswainʼs seat and megaphone. Now, some 60 years later, I would call myself “pleasingly plump.” My cardiologist and others might rightly say, “You need to lose weight.” I believe that my watermelon-like belly stems from my being congenitally swaybacked (more properly known as lumbar hyperlordosis). True, but am I in denial?
      Like others, I have tried exercise and diet, but nothing has meaningfully worked. I sustain my current weight at an intake of 2000 kcal/d—any less and I no longer enjoy eating. Losing weight is easier said than done. Those of you who have read my previous notes may remember that an analysis of my genetic makeup suggests a preference for sweet over savory foods.
      • Shader R.I.
      Some reflections on the microbiome and obesity.
      The cards are stacked against me, since I really like ice cream.
      Also from my previous notes you may recognize my belief that, when appropriate, scientific reporting and communication may benefit by adding a pinch of humor. Before enlarging on this weighty topic, I want to whet your appetite by sharing a soupçon of saucy tidbits. Here are 2 relevant puns I recently discovered: (1) “There is a growing body of obesity research,” and (2) a recruitment advertisement: “New study on obesity looks for larger test group.” Enough silliness.
      Historically, prescription weight-loss aids have generally been amphetamine variants. Another option is surgical reduction of the absorbing surface of the stomach, through either diversion or banding. Until recently, there were no new alternatives. In the past several years, however, the US Food and Drug Administration (FDA) has approved 4 medicinal remedies and 1 device, a vagus nerve stimulator. I will briefly annotate these five new options.
      • 1.
        Lorcaserin
        Trademark: Belviq (Eisai Inc, Woodcliff Lake, New Jersey).
        was approved in June 2012. It is indicated, as an adjunct to increased physical activity in conjunction with a reduction in caloric intake, for weight loss. It is thought to work by a serotonergic mechanism.
        *Trademark: Belviq (Eisai Inc, Woodcliff Lake, New Jersey).
      • 2.
        In July 2012, a combination of phentermine/topiramate
        Trademark: Qsymia (Vivus Inc, Mountain View, California).
        was approved for similar indications. It is a combination of a stimulant and an antiepileptic agent.
        Trademark: Qsymia (Vivus Inc, Mountain View, California).
      • 3.
        Then in September 2014, another combination, naltrexone/bupropion,
        Trademark: Contrave (Takeda Pharmaceuticals Inc, Lincolnshire, Illinois).
        was similarly approved. It is a combination of an opioid antagonist and a prodopaminergic antidepressant.
        Trademark: Contrave (Takeda Pharmaceuticals Inc, Lincolnshire, Illinois).
        These first 3 agents are all given by the oral route.
      • 4.
        In December 2014, the FDA approved the use of liraglutide
        Trademark: Saxenda (Novo Nordisk Inc, Princeton, New Jersey).
        as an additional option. In contrast to the oral agents, liraglutide is given by subcutaneous injection. Liraglutide is thought to reduce caloric intake and appetite through agonist activity at glucagon-like peptide 1 receptors in the brain.
        §Trademark: Saxenda (Novo Nordisk Inc, Princeton, New Jersey).
      • 5.
        More recently, in January 2015, FDA approval was granted for the use of the Maestro Rechargeable System (EnteroMedics Inc, St. Paul, Minnesota), a surgically implanted vagus nerve stimulator. In pacemaker-like fashion, this device periodically blocks the vagus nerve (5 minutes of blocking, then 5 minutes off, all day during waking hours). The intermittent blockade avoids gastroparesis, while weight loss is promoted through the blockade of vagal involvement with oneʼs sense of fullness and hunger. This device is indicated for use in persons with a body mass index of ≥40 kg/m2 (ie, morbidly obese) or ≥35 kg/m2 in those with a comorbid medical condition (eg, type 2 diabetes mellitus, hypertension).
      The other agents are to be used for persons with a body mass index of ≥30 kg/m2 (ie, obese) or ≥27 kg/m2 (ie, overweight) if a contributing medical condition is comorbid.
      None of these treatments has been shown to work in the majority of patients, and generally the weight loss is up to 5%. This figure is the usual target for efficacy in randomized clinical studies of weight-loss strategies. Although at best this amount may seem minimal or modest, a 5% reduction in weight can be clinically meaningful, particularly in persons with comorbid medical problems. It is important to note that these treatment approaches are currently FDA approved solely for use in adults, although studies of the use of these agents in children and adolescents are under way.
      Obesity in children and adolescents is a multifactorial problem. Although genetic and hormonal factors may be contributory, other determinants also account for the growing epidemic of weight problems in these age groups. The major ones include family eating habits; insufficient physical activity; low availability of affordable, nourishing, nonfatty or low-caloric food choices; a lack of parental knowledge about healthy dietary practices; and maternal gestational diabetes.
      The dilemma is that children actually need adequate fuel from food to provide them with the energy needed for growth and functioning. Therefore, parents, schools, legislators, and food manufacturers need to join together to solve this significant public health problem. Globally, the number of children with weight problems increased from 32 million in 1990 to 42 million in 2013.

      Commission on Ending Childhood Obesity. Facts and figures on childhood obesity. www.who.int/end-childhood-obesity/facts/en. Accessed August 1, 2015.

      In the United States, an estimated one fifth to one fourth of children and adolescents are overweight, and an additional 16% to 18% are obese.
      • Ogden C.L.
      • Carroll M.D.
      • Kit B.K.
      • et al.
      Prevalence of childhood and adult obesity in the United States, 2011–2012.
      • Skinner A.C.
      • Skelton J.
      Prevalence and trends in obesity and severe obesity among children in the United States, 1999–2012.
      Data from the National Health and Nutrition Survey

      National Health and Nutritional Examination Survey. http://www.cdc.gov/nchs/nhanes.htm. Accessed August 1, 2015.

      suggest that the prevalence of obesity is expanding across all age groups of children and adolescents. This finding should serve as a warning about what is to come: These children and adolescents will be at a greater-than-average risk for hypertension, type 2 diabetes mellitus, and other health problems later in life.
      Racial and ethnic factors also contribute. Compared with the white population in the United States, Latino and African-American children and adolescents experience greater rates of obesity. From a global perspective, there are more obese children in developing countries than in developed countries.
      It should be obvious that we need more research on this at-risk population, including not only treatment studies but, perhaps even more importantly, prevention strategies that involve parents, schools, and food manufacturers as well as community leaders and both local and national legislators. Without a massive and sustained effort, there is little likelihood that meaningful change will occur. One prediction, from the Commission on Ending Childhood Obesity,

      Commission on Ending Childhood Obesity. Facts and figures on childhood obesity. www.who.int/end-childhood-obesity/facts/en. Accessed August 1, 2015.

      is indeed ominous: “If current trends continue the number of overweight or obese infants and young children globally will increase to 70 million by 2025.”
      Dr. Philip D. Walson, our former Editor-in-Chief and our current Topic Editor at Large, has collected a group of 4 papers
      • Walson P.D.
      Pediatric obesity.
      • Kendrick J.G.
      • Carr R.R.
      • Ensom M.H.
      Pediatric obesity: pharmacokinetics and implications for drug dosing.
      • Siegel R.M.
      • Anneken A.
      • Duffy C.
      • et al.
      Emoticon use increases plain milk and vegetable purchase in a school cafeteria without adversely affecting total milk purchase.
      • Rowe S.
      • Siegel D.
      • Benjamin Jr, D.K.
      Gaps in drug dosing for obese children: a systematic review of commonly prescribed acute care medications.
      • Mihalopoulos N.L.
      • Spigarelli M.G.
      Co-management of pediatric depression and obesity: a systematic review.
      focusing on the problems of obesity in children and adolescents. Three papers in the collection cover topics including the dosing of medication in obese children and depression as a comorbidity in obese adolescents.
      • Kendrick J.G.
      • Carr R.R.
      • Ensom M.H.
      Pediatric obesity: pharmacokinetics and implications for drug dosing.
      • Rowe S.
      • Siegel D.
      • Benjamin Jr, D.K.
      Gaps in drug dosing for obese children: a systematic review of commonly prescribed acute care medications.
      • Mihalopoulos N.L.
      • Spigarelli M.G.
      Co-management of pediatric depression and obesity: a systematic review.
      The fourth paper describes the results from a study that determined whether a simple intervention could encourage children to make better food choices in a school cafeteria setting.
      • Siegel R.M.
      • Anneken A.
      • Duffy C.
      • et al.
      Emoticon use increases plain milk and vegetable purchase in a school cafeteria without adversely affecting total milk purchase.
      Youth and Children Specialty Updates are published annually and are available as FREE ACCESS content on the journal’s website. The previous Youth and Children Update, entitled “Pediatric Clinical Trials and Drug Development” was published in Volume 36, Number 2 of Clinical Therapeutics. To view the previous Youth and Children Update, see the articles below:

      References

        • Shader R.I.
        Some reflections on the microbiome and obesity.
        Clin Ther. 2015; 37: 925-927
      1. Pun of the day. http://www.punoftheday.com/cgi-bin/findpuns.pl?q=obesity&submit=Search. Accessed August 1, 2015.

      2. Commission on Ending Childhood Obesity. Facts and figures on childhood obesity. www.who.int/end-childhood-obesity/facts/en. Accessed August 1, 2015.

        • Ogden C.L.
        • Carroll M.D.
        • Kit B.K.
        • et al.
        Prevalence of childhood and adult obesity in the United States, 2011–2012.
        JAMA. 2014; 311: 806-814
        • Skinner A.C.
        • Skelton J.
        Prevalence and trends in obesity and severe obesity among children in the United States, 1999–2012.
        JAMA Pediatr. 2014; 168: 561-566
      3. National Health and Nutritional Examination Survey. http://www.cdc.gov/nchs/nhanes.htm. Accessed August 1, 2015.

        • Walson P.D.
        Pediatric obesity.
        Clin Ther. 2015; 37: 1895-1896
        • Kendrick J.G.
        • Carr R.R.
        • Ensom M.H.
        Pediatric obesity: pharmacokinetics and implications for drug dosing.
        Clin Ther. 2015; 37: 1897-1923
        • Siegel R.M.
        • Anneken A.
        • Duffy C.
        • et al.
        Emoticon use increases plain milk and vegetable purchase in a school cafeteria without adversely affecting total milk purchase.
        Clin Ther. 2015; 37: 1938-1943
        • Rowe S.
        • Siegel D.
        • Benjamin Jr, D.K.
        Gaps in drug dosing for obese children: a systematic review of commonly prescribed acute care medications.
        Clin Ther. 2015; 37: 1924-1932
        • Mihalopoulos N.L.
        • Spigarelli M.G.
        Co-management of pediatric depression and obesity: a systematic review.
        Clin Ther. 2015; 37: 1933-1937