BB&T Contributing Editor

BOSTON — Obesity is the most prevalent, fatal, chronic, relapsing disease of the 21st century, a fact highlighted by a variety of unhappy statistics.

The fact that obesity is growing in epidemic proportions is seen most obviously in the United States, where there has been a rapid rise since 1960 in the number of those who are overweight. According to the Centers for Disease Control and Prevention (Atlanta), 66% of the U.S. adult populations are either overweight or obese, and 15% of children and adolescents ages 6 to 19 are overweight. The number of Americans and Europeans defined as "clinically" obese is estimated to be 100 million. And this trend is spreading around the globe with the increased Westernization of diets and the parallel increase in sedentary work habits.

Estimates put the number of overweight adults — defined as having a body mass index (BMI, calculated by dividing a person's body weight in kilograms by their height in meters squared) of 24.5 or greater — at 1 billion worldwide (see Table 1 below for categories of BMI).

Perhaps the most concerning is the increasing number of children in both the U.S. and the UK who are overweight, an indicator that this trend represents a clinical firestorm set to become worse.

People defined simply as overweight have increased health risks. A study published in the Aug. 26 issue of the New England Journal of Medicine demonstrated increased risk of death. And being obese creates much greater risks, in terms of both morbidity and mortality. Obesity is closely linked to increased incidence of Type II diabetes, heart attack and stroke, as reported in a study published in the January issue of the Journal of the American Medical Association. The North American Association for the Study of Obesity (NAASO; Silver Spring, Maryland) reports that obesity causes 112,000 excess deaths in the U.S. annually.

The range of these problems and the various solutions were the focus of more than 2,100 scientists, physicians and dietician attendees at this year's annual NAASO meeting in October.

Surgical interventions

Diet and exercise — and more recently the use of drugs — have been the main weapons in the weight-loss arsenal. And the presentations, exhibits and informal discussions in the meeting rooms and hallways of the NAASO meeting demonstrated that the armamentarium available to fight this epidemic is expanding in a variety of interesting ways.

Bariatric surgery has been shown in clinical trials to result in substantial weight loss and resolution of some co-morbidities such as diabetes, but associated with important costs and consequences. For instance, because of its high cost — $15,000 to $20,000 — many insurers do not cover the surgery.

A study conducted by Derek Brown and Eric Finkelstein of RTI International (Research Triangle Park, North Carolina) explored whether savings resulting from improved health following two bariatric procedures, gastric bypass and gastric banding, offset the cost of the procedures. The results were mixed.

The authors looked at the differences in mean quarterly costs, inpatient hospitalization rates and number of prescription drug payments before and after surgery, using medical claims for the procedures from more than 100 insurance plans during the period 2001 to 2004. The data showed that both gastric banding and gastric bypass achieved modest reductions in prescription drug use and post surgical costs.

However, the net effect on costs was different between the two procedures. Gastric banding resulted in a mean total savings of about $1,400 per year. On average, no savings were achieved from gastric bypass because of increased hospitalization rates resulting from surgical complications. The study concluded that for payers to achieve savings from gastric bypass it is critical to reduce the incidence of adverse events of this procedure.

In February 2006, Medicare reimbursement for bariatric surgery covered morbidly obese people over the age of 65 who have tried and failed other weight-loss options, have at least one co-morbid condition related to obesity, and have a BMI of 35 or greater.

The decision was seen as a substantial and important reversal of previous Department of Health and Human Services policy which has stated that obesity is not a disease.

Analyzing, measuring body composition

Determining the amount of weight — and the amount of weight to lose — is a critical step in this effort.

The Plusavis 333 analyzer from Jawon Medical in Korea measures body fat composition using conductivity to calculate a biological factor representing different types of body tissue that is based on five factors, weight, height, impedance, age and gender.

ImpediMed (Queensland, Australia/Rochester, New York) featured Imp SFB7, a tetra polar bioimpedance spectroscopy device that scans 256 frequencies from 4 kHz to 1000 kHz to determine the total body water and extracellular fluid from impedance data. Fat-free mass and fat mass are calculated on the device. Similar data are obtained from its Imp DF50 instrument which uses a single frequency at 50 kHz to analyze body composition.

Life Measurement (Concord, California) displayed its Pea Pod and Bod Pod body composition tracking systems that use air displacement plethysmography to measure percent fat and lean body mass in infants and adults, respectively. Clinical assessment of infant growth and nutritional status is enhanced by the accurate measurement of body fat and its changes over time.

Echo Medical Systems (Houston) markets Echo-MRI and LaTheta equipment for body composition analysis of total fat, lean muscle and total body water. It is used in mice, rats and humans during preclinical and clinical research.

Bruker Optics (Billerica, Massachusetts) markets the minispec equipment which utilizes a benchtop magnetic resonance unit and provides body composition analysis with precise measurements of lean tissue, fat and fluid in live mice, rats and other small animals.

Devices weigh in

Innovative device systems are among the most recent developments in the weight-loss sector.

ObesiTx (Kiryat Shemona, Israel) is a start-up company developing a volume reducing implantable intragastric device which is designed to restrict and/or reduce the volume of the stomach with a ring, placed around the stomach with anchors, through a minimally invasive endoscopic procedure. The device can be retrieved or readjusted for different gastric volumes throughout its period of use. This approach offers the prospect that stomach stapling surgery to combat obesity may be done in the future by using a tube that is inserted through the mouth.

Satiety (Palo Alto, California) reported at recent gastroenterology conferences on its 21-patient pilot trial at Erasme University Hospital (Brussels, Belgium) that used a transoral gastroplasty procedure which does not require any abdominal incisions and was claimed to be much less invasive and have fewer complications than bariatric surgery (see sidebar, p. 4). Using a small plastic hose and an endoscope to view the procedure, the sides of the obese patient's stomach are vacuumed and two staple lines are applied to make the stomach smaller. After one month, patients on the trial lost between 9 and 28 pounds, representing 7% to 25% of their weight.

StimPulse (Kiryat, Shemona, Israel) is developing a sensing and stimulating implantable device that senses food intake into the digestive system and applies electrical stimulation to the digestive system in order to reduce the ability for further intake of food.

Monitoring physical activity

Weight-loss efforts are typically linked to increased exercise, with the strategies in this sector becoming more sophisticated.

Suzuken Company, a Japanese manufacturer of pharmaceuticals and medical equipment, featured the Kenz Lifecorder EX monitor for clinical and health/fitness professionals to monitor the physical activity of their patients. It analyzes exercise intensity, time, frequency, energy expenditure and steps. The company also markets under its Kenz brand a line of electrocardiographs and Holter monitors.

Mini Mitter (Bend, Oregon), acquired by Respironics (Murrysville, Pennsylvania) in August 2005, markets the Actical, a small, omni-directional accelerometer that accurately measures the level of the subject's physical activity and step count. Actiheart is a wireless heart rate, physical activity and caloric expenditure recording system. The company says it is the only heart-rate recorder with an integrated accelerometer that can calculate energy expenditure for ambulatory activities.

ActiGraph (Fort Walton Beach, Florida) markets the Actiwatch, a small electronic device for 24-hour activity monitoring, used for diagnosing sleep disorders, an obesity-related problem. It collects the user's physical activity, limb movements, or sleep levels. Its rechargeable lithium battery provides power for 14 days. Actiware-PLM is used for assessing the magnitude and periodicity of limb movements during sleep. The ActiWeb software offers analytical processing options including cardiovascular, limb and extremity, and sleep reports. The device can be used in weight loss/management programs to accurately determine caloric expenditure versus caloric intake.

Seahorse Bioscience (North Billerica, Massachusetts) exhibited its XF24 extracellular flux analyzer for determining energy expenditure, fatty acid oxidation and cell signaling in mammalian cells. The instrument works with standard microplates and allows reuse of the cells for other assays.

Aestis (Boulder, Colorado) has patents on the use of controlled hypoxia for the treatment and prevention of obesity. It is known that hypoxia causes mountain climbers to experience weight. The reduced amount of inspired oxygen induces physiological changes equivalent to those seen at high altitudes. Aestis is seeking to use this method for treating obesity by having the person sleep in a tent with low oxygen concentration. A small feasibility study on its Thin Air system was conducted at Maastricht University (the Netherlands) which showed weight loss of about one pound per week with no significant side effects. Currently, hypoxia therapy is used by athletes for their training.

Obesity-related diagnostics

Diagnostic Systems Laboratories (Webster, Texas), acquired by Beckman Coulter (Fullerton, California) in October 2005, Alpco Diagnostics (Salem, New Hampshire), and Phoenix Pharmaceuticals (Belmont, California) provide a wide range of kits for homeostasis and metabolism immunoassays. These include obesity-related peptides such as ghrelin, PYY, adiponectin and leptin. Phoenix also featured its test kit for nesfatin-1, a newly discovered obesity peptide that is a satiety molecule found in the hypothalamus, and obestatin, a new peptide encoded by the ghrelin gene that opposes ghrelin effects on food intake.

Interleukin Genetics (Waltham, Massachusetts) has licensed technology from GeneOb (Amherst, New York) that uses specific genetic markers as the basis for determining the risk of an individual's weight gain and response to weight loss programs. The company plans to launch its weight management genetic test in North America next year through its commercialization partner, Alticor (Ada, Michigan).

Quantomix (Nes-Ziona, Israel) has developed a method for high-resolution imaging and quantitative measurement of lipid accumulation in cells and tissues using its proprietary Wetsem technology. It provides images and data that reveal tissue morphology and visualization of precise intracellular structure. At the cellular level, obesity is caused by an increase in the number and size of adipocytes (fat cells), and the measurement of fat cell size can therefore serve as an accurate indicator of the effectiveness of intervention.

Assisting weight-loss efforts

A variety of systems were being showcased at the meeting focused on providing aids to weight-loss efforts.

Novartis Medical Nutrition (Minneapolis) was promoting its Optifast diet as a useful regimen six to eight weeks prior to bariatric surgery as a way of shrinking the size of the liver and reducing blood sugar levels, as well as its Resource and Optisource post-bariatric surgery products which are specially formulated to meet the patient's needs for proteins, vitamins and minerals. It featured two poster presentations on its Boost Diabetic diet (40% carbohydrates, 20%-30% protein and 30%-35% fat), based on new nutrition guidelines from the Joslin Clinic (Boston).

Phoenix Care, a unit of Estenda Solutions (Conshohocken, Pennsylvania), provides patient and practice management services for the bariatric surgery marketplace. It recently launched software that can be used to improve patient outcomes and clinic efficiency by combining optimized access to traditional healthcare metrics. It is designed to assess and manage the long-term behavioral changes required of bariatric patients.

Key drugs in the fight

Two drugs currently approved in the U.S. for obesity are Xenical from Hoffmann-La Roche (Basel, Switzerland) and Meridia from Abbott Laboratories (Abbott Park, Illinois). Although these products have been shown have safety and/or compliance issues, they have achieved annual sales of $480 million and $200 million, respectively. A drug that acts on the brain to reduce appetite is Acomplia from Sanofi-Aventis (Paris), approved in Europe in June 2006.

Alizyme (Cambridge, UK) sponsored a symposium on the use of lipase inhibitors for obesity management. The company has completed a Phase II trial on Cetilistat, a drug that acts by inhibiting gastrointestinal lipases, thereby blocking fat absorption and digestion. It differs from other anti-obesity agents because it does not act on the brain to reduce appetite.

Orexigen (San Diego) is investigating rationally selected drug combinations to increase satiety and decrease appetite, while at the same time avoiding the plateau and/or rebound that occurs with most diet regimens by neutralizing the neuro-pathways that compensate for the resulting weight loss. Its two lead compounds in clinical trials are Contrave in Phase III and Excalia in Phase IIb. These drugs are engineered to act on specific groups of neurons in the central nervous system.