Body fat percentage, body mass index, skin thicknesses, and anthropomorphic measures


The central cannabinoid system and feeding disorders



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The central cannabinoid system and feeding disorders

The importance of the central cannabinoid system in the understanding and management of feeding disorders has increased.[45, 46, 47, 48]

In particular, activation of the cannabinoid type 1 (CB1) receptor is associated with increased appetite and appears to be the basis for the effectiveness of dronabinol in enhancing diet in AIDS and other wasting syndromes. CB1 antagonists showed great potential for weight management in several human trials.

Rimonabant, the most-developed CB1 antagonist, caused mean weight loss of 3-6 kg over 1-year follow-up at doses of 5-20 mg/d. Adverse effects, which were most prevalent at high doses, included dizziness, mood swings, headaches, nausea, vomiting, and diarrhea. Rimonabant may obtain FDA approval as an adjunct for weight loss in the next 2-3 years based on the accumulating data from phase 3 trials of human obesity.



Investigational drugs

Agents in early phases of investigation that may yet prove of use include ghrelin antagonists, alpha-MSH analogs, enterostatin, neuropeptide YY antagonists, beta3-adrenergic agonists, and various nutraceuticals and herbal products (including the extract from the African cactus Hoodia gordonii, which may cause clinically significant appetite suppression).

Metformin does not have an indication for obesity, but it was useful in preventing diabetes and improving insulin resistance in conditions such as polycystic ovary syndrome [PCOS]. Its use was associated with weight neutrality or mild weight loss.[49]

Gadde and colleagues reported that randomized use of the antiepileptic drug zonisamide in a cohort of 60 obese subjects was associated with a weight loss of about 6% of baseline weight, with few adverse effects.[50]

Lustig and colleagues reported the potential utility of octreotide in ameliorating the distinct subclass of hypothalamic obesity.[51]

The first glucagon-like peptide (GLP)-1 analog, exenatide, although not FDA approved for obesity management, has been associated with modest weight loss in subjects with type 2 diabetes.

Peptide YY (3-36) is being developed as a nasal inhaler. Preliminary, ongoing phase 1 and 2 trials yielded encouraging results.[52, 53, 54]

Amylin is the synthetic version of pramlintide and does not have an FDA indication for obesity management. However, this drug is clearly associated with variable weight loss in people with type 1 or 2 diabetes, while improving overall glycemic control.



Drugs no longer used

Some agents that initially showed promise were later demonstrated to be poor prospects in rigorous randomized intervention trials. These include guar gum, chitosan, axokine (or ciliary neurotrophic factor, the use of which was associated with development of autoantibodies and marked reduction in anorexiant potency in about 30% of subjects), leptin (except in the rare subclass of leptin-deficient obesity), St John's wort, psyllium, conjugated linoleic acid, chromium, and ginseng, among others.



Comorbidities

The management of obesity is not complete without attention being paid to various potential comorbidities.

Addressing these issues can have profound effects on the patient's well-being and risk of morbidity and mortality.

Public policy and obesity management

Although management of obesity in the individual subject is important, realizing that obesity is a public-health problem is vital. Successful management of the obesity pandemic requires public health professionals and administrators to make tough policy decisions.

The multibillion-dollar food industry and the link between this industry and the consumer (including retailers and caterers) must be included in this public-health effort. The high-density foods, snacks, and drinks that are so common in the developed world and that now are infiltrating developing countries must be recognized as major factors in this pandemic.

Large-scale public-health education aimed at all age groups must be implemented with the same fervor and zeal that characterized past advertisements for tobacco. Such public-health initiatives must be accompanied by an equally spirited effort to educate the public and to encourage regular participation in exercise and outdoor recreational activities among individuals of all ages.



Fat substitutes

One strategy to prevent obesity that is being explored in the dietary industry involves use of fat substitutes.

Olestra (Olean) has been approved for use as a dietary supplement and additive in various fast foods, such as potato chips and crackers. Olestra has a calorie value of 0 kcal/g, whereas fat has approximately 9.1 kcal/g. Olestra consists of a sucrose polyester backbone with 6-8 fatty-acid side chains; this structure making it too large for digestive enzymes of the gut to hydrolyze it. In many trials, olestra had fairly good tolerability, though it apparently is less tasty than materials cooked in regular fat. The major adverse effects reported were flatulence, bloating, diarrhea, and loose stools. Because of the concern for possible malabsorption of fat-soluble vitamins, the FDA requires all olestra-prepared foods to be supplemented with these vitamins.

Sitostanol (Benecol) is a plant stanol ester preparation that is used as a spread similar to margarine. It blocks cholesterol absorption in the intestine, with no clinically significant alterations in triglyceride or HDL-C values.

Preliminary reports suggest the potential utility of agents that impede dietary carbohydrate absorption. Tagatose is one of the agents in this class that is undergoing trials.

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author


Gabriel I Uwaifo, MBBS  Clinical Associate Professor of Medicine, Section on Endocrinology, Diabetes and Metabolism, Louisiana State University Health Sciences Center

Gabriel I Uwaifo, MBBS is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians-American Society of Internal Medicine, American Diabetes Association, American Medical Association, American Society of Hypertension, and Endocrine Society

Disclosure: Nothing to disclose.

Coauthor(s)



Elif Arioglu, MD  Assistant Professor of Medicine, Division of Endocrinology and Metabolism, University of Michigan

Elif Arioglu, MD is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine, American Diabetes Association, American Medical Association, and Endocrine Society

Disclosure: Nothing to disclose.

Specialty Editor Board



Harris C Taylor, MD  Clinical Professor of Medicine, Division of Clinical and Molecular Endocrinology, Case Western Reserve University School of Medicine

Harris C Taylor, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Thyroid Association, and Endocrine Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment



Romesh Khardori, MD, PhD, FACP  Former Professor, Department of Medicine, Former Chief, Division of Endocrinology, Metabolism, and Molecular Medicine, Southern Illinois University School of Medicine

Romesh Khardori, MD, PhD, FACP is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, and Endocrine Society

Disclosure: Nothing to disclose.

Mark Cooper, MBBS, PhD, FRACP  Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University

Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD  Professor of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

[CLOSE WINDOW]



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Central nervous system neurocircuitry for satiety and feeding cycles.



Comorbidities of obesity.

Energy balance equation.

Secondary causes of obesity.

Simplified scheme for the pathophysiology of type 2 diabetes mellitus.

Gastric electrical-stimulation device.

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