BBI Contributing Editor

LAS VEGAS Attendance at the North American Association for the Study of Obesity's (NAASO; Silver Spring, Maryland) 2004 annual meeting, held here in mid-November, increased by 40% over the prior year to 2,000 attendees. There were 898 abstracts, a 38% increase and an indication of the growing interest in this subject area. The NAASO gathering is co-sponsored by the American Diabetes Association (Alexandria, Virginia) due to the co-morbidity of diabetes and obesity. The American Obesity Association (Washington) estimates that 127 million adults in the U.S. are overweight, of which 60 million are obese and 9 million are severely obese, and Americans are growing heavier each year. Overweight is defined as having a body mass index (BMI) of 25 to 29.9 kg/m2, and obese is defined as having a BMI of 30 kg/m2 and greater.

Obesity is the leading modifiable risk factor for Type 2 diabetes and, according to the Centers for Disease Control and Prevention (CDC; Atlanta), the incidence of diabetes has jumped nearly 50% in the past 10 years. Currently, nearly 18.2 million Americans have diabetes. A study released earlier this year by the CDC estimates that, if the current trends continue, as many as 30 million Americans may have diabetes by 2030.

Mailie Gammon, PhD, associate professor of epidemiology at the University of North Carolina (Chapel Hill), gave a review of her epidemiologic research on obesity in relation to cancer risk and survival and also presented her research, as yet unpublished, that focused on adult weight, weight gain and fat distribution in relation to breast cancer risk and survival. A recent report published in Neurology by a Swedish researcher suggests that lifelong obesity among women may lead to brain atrophy that is linked to impaired brain function and dementia.

Interest in drugs for weight loss has blossomed in recent years. Decision Resources (Waltham, Massachusetts) has estimated more than 100 weight-loss drugs in the early stages of research. Two prescription drugs are currently marketed: Meridia (sibutramine) from Abbott Laboratories (Abbott Park, Illinois), an appetite suppressant, and Xenical (orlistat) from F. Hoffmann-La Roche (Basel, Switzerland), which blocks the absorption of fat. Sales of these drugs has declined in recent years.

Merck (Whitehouse Station, New Jersey) has entered into a global alliance with Nastech Pharmaceutical (Bothell, Washington) to develop and commercialize peptide YY 3-36 (PYY) nasal spray, which is in Phase I trials as a treatment for obesity. PYY is a hormone produced by the small intestine and sent to the hypothalamus of the brain to signal the feeling of fullness. There is some evidence that obese people produce less of this hormone than leaner people and that their brains are receiving only a weak signal to stop eating.

Sanofi-Aventis (Paris) had a high profile at the meeting due to its weight-loss drug, Acomplia (rimonabant), which is being evaluated in four clinical trials (the Rio-Lipids trial) in a total of 6,600 patients. The drug is the first selective cannabinoid type 1 receptor blocker being developed to manage cardiovascular risk factors such as obesity and smoking. Initial results from a Phase III trial have shown that the drug also helps people quit smoking and prevent the excess weight gain that often plagues ex-smokers. This is the first of three Phase III smoking cessation trials that will include 6,500 smokers. Acomplia functions by reducing overactivity in the body's system that regulates food intake and energy expenditure. Sanofi-Aventis plans to file a new drug application with the FDA in mid-2005 and to seek drug approval in Europe at the same time. The drug needs to be taken chronically that is, continued after patients have reached their goal weight.

Alizyme (Cambridge, UK) was recently granted a Clinical Trial Authorization from the UK Medicines and Healthcare Products and Regulatory Agency to undertake a Phase IIb clinical trial of ATL-962 for the treatment of obesity in up to 600 clinically obese diabetic patients in a comparison against Hoffmann-LaRoche's Xenical weight loss drug. ATL-962 is an inhibitor of gastrointestinal lipases and causes weight loss by blocking the digestion and absorption of fat and acts in a similar way to Xenical.

Manhattan Pharmaceuticals (New York) presented a poster on oleoyl estrone, an orally administered steroid ester that occurs naturally in blood and was shown in rat studies to markedly reduce caloric intake and achieve a 15% to 20% loss in body mass without adverse effects. The weight loss was limited to reduction in fat, and there was no rebound weight gain when treatment was discontinued. The company said it plans to submit an IND to the FDA by year-end and to commence this year a Phase I safety and tolerability study on 36 patients that are given a single dose of oleoyl estrone. This will be followed by a second (Phase Ib) trial on 24 patients that receive a daily dose of the drug for seven days. A Phase II three-month efficacy trial also is planned by the end of 2005.

ADM Kao, a joint venture between ADM (Decatur, Illinois) and Kao Corp. (Tokyo), promoted Enova oil, a cooking oil that is a blend of soy and canola oils and contains 80% diacylglycerol oil by weight. Clinical trials in the U.S. and Japan have shown that fat mass and body weight may be reduced as well as a lowering of post-meal blood triglyceride levels by substituting Enova oil for conventional vegetable oil in a sensible daily diet. National rollout in the U.S. was expected to begin early this year.

Slim-Fast Foods (West Somerset, Kentucky), a subsidiary of the Anglo-Dutch firm Unilever and a leading provider of weight loss products to consumers, featured its new Optima Diet line of meal replacements and snack bars sweetened with Splenda.

Weight loss studies

A study of the eating and lifestyle habits of 28,700 adult American men and women who completed a 500-question survey was reported by WebMD's (Elmwood Park, New Jersey) Weight Loss Clinic. The research showed a strong correlation between increased fat consumption, both in terms of total fat consumed, percentage of daily caloric intake and increased BMI. The study found no correlation between daily carbohydrate consumption and protein intake and being overweight.

Two studies reported by researchers at Penn State University (College Park, Pennsylvania) showed that people who pursue a healthy, low-fat, low-energy-density diet that includes water-rich foods (such as fruits and vegetables) can consume more food but weigh less than people who eat a more energy-dense diet. The studies looked at the eating patterns of 7,500 men and women.

Nutrition 21 (Purchase, New York) reported that the results of a study on 36 subjects that showed that combining chromium picolinate and biotin (marketed as Diachrome) reduced the glycemic response in moderately obese individuals with Type 2 diabetes when given an oral carbohydrate solution.

A study conducted by researchers at the Mailman School of Public Health and the Obesity Research Center, both at Columbia University (New York), demonstrated a clear link between the risk of being obese and the number of hours of sleep each night. The study concluded that the less you sleep, the more likely you are to become obese. These results appear to be counterintuitive, since people who sleep less are burning more calories. It suggests that what happens to your body when you deprive it of sleep is of greater consequence than the amount of increased physical activity.

Three clinical studies undertaken by the Rippe Lifestyle Institute (Shrewsbury, Massachusetts), a research, communications and health promotion organization, investigated the relationship between aspects of cardiovascular disease risk factors linked to obesity. They included total cholesterol, ratio of cholesterol to HDL, HDL and glucose levels. They found a relationship between fat and a range of cardiovascular risk factors and that abdominal fat has a higher risk associated with it than overall fatness due to the stronger correlation between risk factors and waist circumference than with BMI. Also, waist circumference can be used as a strong diagnostic criterion for metabolic syndrome a set of disorders that is characterized by insulin resistance, abdominal fat, high blood sugar levels, dyslipidemia (high levels of triglycerides and low levels of high-density lipoproteins in blood), high blood cholesterol and high blood pressure. The metabolic syndrome increases the risk of heart disease.

In a separate study conducted by the Rippe Lifestyle Institute, it was found that elevated C-reactive protein in blood is a strong indicator of cardiovascular risk and one aspect of metabolic syndrome, diastolic blood pressure. It was concluded that the measurement of C-reactive protein may be useful to practitioners for assessing the risk for cardiovascular disease and metabolic syndrome. The study lends further support to the concept that obesity stimulates an inflammatory response in the body that may contribute to chronic diseases.

Monitoring aids for weight loss

Several companies exhibited products that utilize a breath test to measure oxygen consumption for calculating resting metabolic rate (RMR), also called resting energy expenditure, and thereby enabling patients to determine if their metabolism (the rate at which food is converted into energy) is normal, slow or fast. Knowing one's metabolic rate is helpful in planning caloric intake.

HealtheTech (Golden, Colorado) featured its MedGem and BodyGem handheld indirect calorimeters and its BalanceLog software that helps individuals create a personalized diet plan for reaching their desired weight that is based on their metabolism. The devices are sold to hospitals and fitness centers for weight management and include single-use mouthpieces. They are loaded with either 20 RMR or 100 RMR measurements.

Korr Medical Technologies (Salt Lake City) markets to physicians the ReeVue indirect portable calorimeter that measures RMR for weight loss counseling. According to the CDC, individuals are three times more likely to lose weight when the advice comes from their doctor.

Monitors for recording physical activity and calculating caloric expenditure also were on display. These products are used for improving physical fitness and as an aid in a weight loss program. The BioTrainer product line from IM Systems (Baltimore) and the Actical device from Mini Meter (Bend, Oregon) use accelerometer motion sensors for determining energy expenditure. IM Systems also markets instruments for monitoring sleep and movement disorders. Mini Meter offers for research use (not yet FDA-approved) the stick-on Actiheart heart rate and physical activity monitor that weights 10 grams and includes an omnidirectional accelerometer and an ECG signal processor. AEI Technologies (Naperville, Illinois) recently introduced a wristwatch-like upper armband that measures physical activity as well as heat flux, body temperature and skin resistance. The company also markets ergometers and the Moxus Modular V02 system, a metabolic cart for measuring oxygen and carbon dioxide.

Body composition analyzers that measure body fat and lean body mass also were on display. Life Measurement (Concord, California) featured the Bod Pod system for tracking body fat and lean mass. The person sits in an enclosed chamber and computerized sensors are used to determine the amount of air displaced by the body. In the past, underwater weighing (the "dunk tank") was the standard method for body composition analysis. The company's newly introduced Pea Pod infant body composition system offers information on infant growth and nutrition.

Tanita (Tokyo) uses bioelectrcial impedance measurements for body composition analysis. Its body fat monitoring scales are sold for home use. The person stands barefoot on the scale which has built-in electrodes. Their gender, height and weight are factored into the baseline measurement of the signal's impedance. The greater amount of lean muscle, the lower the impedance, and the more body fat, the higher the impedance.

Echo Medical Systems (Houston) displayed its EchoMRI quantitative magnetic resonance whole body composition analyzer for animals. It measures total body fat, lean mass, free fluids and total body water. These measurements are used to monitor metabolic disorders such as abnormal lipid levels, diabetes, insulin resistance and obesity.

Several firms exhibited ELISA test kits and radioimmunoassays for biomarkers that stimulate or inhibit food intake. The stimulants are: neuropeptide Y, hypocretins, ghrelin, dynorphin and -endorphin. The inhibitors are: neuropeptide K, leptin, cholecystokinin, neurotensin, urocortin, somatostatin and prolactin-releasing peptide. These companies include Alpco Diagnostics (Windham, New Hampshire), Phoenix Pharmaceuticals (Belmont, California), LINCO Research (St. Charles, Missouri), B-Bridge International (Sunnyvale, California) and Kamiya Biomedical (Seattle). Diagnostic Systems Laboratories (Webster, Texas) markets more than 200 esoteric endocrine assays as well as the ActiveGLO microplate luminometer for chemiluminescence measurements. It is a lower-cost unit that replaces single-well gamma counters.

QuantomiX (Nes Ziona, Israel) markets in the U.S. and Japan a system that enables scanning electron microscopes to image and analyze wet samples of cells and tissue biopsies in their native environment without compromising sample integrity. It can be used to image lipids in cells and tissues for quantitative analysis in metabolic syndrome research. For treating obese and diabetic patients, the system is used to monitor the accumulation of lipids in the tissues at the cellular and subcellular levels.

Pearson Assessments (Bloomington, Minnesota) markets psychological tests to health practitioners for use in presurgical and for follow-up evaluations of bariatric surgery patients. The tests are used to determine the patient's emotional readiness for this surgery and to assess the presence of depression, anxiety or other factors that may indicate a need for psychological treatment, as well as to track treatment outcomes.

No Comments