Weight Loss - Obesity

[Michael Scally MD]

Re: Weight-Loss/Obesity

[The very company making the product EMPLOYS the authors. It sounds very similar to the product by Gelesis - Gelesis | About Gelesis .]

Experimental Drink Could Help Dieters Feel Full
Medical News: Experimental Drink Could Help Dieters Feel Full - in Primary Care, Obesity from MedPage Today

With the growing epidemic of obesity, Dutch researchers may have come up with a way for people to stick to their diets and lose weight -- an experimental meal replacement drink that seems to reduce hunger pangs and help dieters feel full longer.

A study conducted among 23 volunteers found that the drink reduced their hunger by as much as 30%, five hours (P< 0.001) after drinking it, reported Harry Peters, a manager-scientist of Unilever Research & Development in Vlaardingen, the Netherlands, and colleagues.

The secret ingredient: a strongly gelling dietary fiber called alginate.

"The drink was designed in such a way that it only gels under gastric conditions and not in the product before consumption," Peters and co-authors explained online in the journalObesity. They theorized that a drink of this kind "would dose-dependently decrease hunger responses at relatively low alginate levels."

A drink containing the gelling fiber that was palatable and able to delay the return of hunger could potentially increase consumer satisfaction with weight control programs and low-calorie food products, and thus encourage long-term compliance, the Dutch team suggested.

"Satiety feelings on a meal-to-meal basis are partly determined by gastrointestinal (GI) stimuli," they wrote. "One way to increase satiety is by formation of gels within the stomach. However, the viscosity of drinks needs to be high to increase satiety, and this may reduce consumer acceptance for many (e.g., fluid) types of products."

But producing a palatable drink based on post-consumption gelatin stimulated by gastric conditions might therefore be a preferred option, they suggested.

So they whipped up an experimental low-viscosity breakfast drink -- a prototype ready-to-drink chocolate-flavored meal replacement shake containing 190 calories in 325 ml (around 10 oz) -- using two concentrations of alginate (0.6% and 0.8%) designed to turn into a satiating gel only after it was consumed. Controls consumed the shake without added alginate.

A group of healthy volunteers were recruited from around the Unilever research site in Vlaardingen; 23 completed the study.

The volunteers (mean age around 53) consumed the drink containing various levels of alginate in place of a meal and reported their levels of hunger and fullness over the next five hours.

Volunteers who had the highest level of alginate in their drinks reported less hunger than the control group, with both "hunger" and "fullness" reduced robustly (20% and 34% lower area under the curve, respectively) with 0.8% alginate (both P<0.001, analysis of covariance). This effect was consistent across all six appetite scales used, Peters and co-authors wrote.

Most effects were also significant with 0.6% alginate, and a clear dose-response was observed.

"Although self-reported decreases in hunger are robustly reported in this study, further studies are needed to establish its implications for food intake, compliance to weight-loss programs, and long-term effects on weight loss or weight maintenance," Peters and colleagues concluded.


Peters HP, Koppert RJ, Boers HM, et al. Dose-Dependent Suppression of Hunger by a Specific Alginate in a Low-Viscosity Drink Formulation. Obesity (Silver Spring). Dose-Dependent Suppression of Hunger by a Specific... [Obesity (Silver Spring). 2011] - PubMed result

Addition of specific types of alginates to drinks can enhance postmeal suppression of hunger, by forming strong gastric gels in the presence of calcium. However, some recent studies have not demonstrated an effect of alginate/calcium on appetite, perhaps because the selected alginates do not produce sufficiently strong gels or because the alginates were not sufficiently hydrated when consumed. Therefore, the objective of the study was to test effects on appetite of a strongly gelling and fully hydrated alginate in an acceptable, low-viscosity drink formulation. In a balanced order crossover design, 23 volunteers consumed a meal replacement drink containing protein and calcium and either 0 (control), 0.6, or 0.8% of a specific high-guluronate alginate. Appetite (six self-report scales) was measured for 5 h postconsumption. Relevant physicochemical properties of the drinks were measured, i.e., product viscosity and strength of gel formed under simulated gastric conditions. Hunger was robustly reduced (20-30% lower area under the curve) with 0.8% alginate (P < 0.001, analysis of covariance), an effect consistent across all appetite scales. Most effects were also significant with 0.6% alginate, and a clear dose-response observed. Gastric gel strength was 1.8 and 3.8 N for the 0.6 and 0.8% alginate drinks, respectively, while product viscosity was acceptable (<0.5 Pa.s at 10 s(-1)). We conclude that strongly gastric-gelling alginates at relatively low concentrations in a low-viscosity drink formulation produced a robust reduction in hunger responses. This and other related studies indicate that the specific alginate source and product matrix critically impacts upon apparent efficacy.


But, the following study does not conclude that alginate is effective.

Odunsi ST, Vazquez-Roque MI, Camilleri M, et al. Effect of alginate on satiation, appetite, gastric function, and selected gut satiety hormones in overweight and obesity. Obesity (Silver Spring) 2010;18(8):1579-84. Effect of alginate on satiation, appetite, gastric... [Obesity (Silver Spring). 2010] - PubMed result

Lack of control of food intake, excess size, and frequency of meals are critical to the development of obesity. The stomach signals satiation postprandially and may play an important role in control of calorie intake. Sodium alginate (based on brown seaweed Laminaria digitata) is currently marketed as a weight loss supplement, but its effects on gastric motor functions and satiation are unknown. We evaluated effects of 10 days treatment with alginate or placebo on gastric functions, satiation, appetite, and gut hormones associated with satiety in overweight or obese adults. We conducted a randomized, 1:1, placebo-controlled, allocation-concealed study in 48 overweight or obese participants with excluded psychiatric comorbidity and binge eating disorder. All underwent measurements of gastric emptying (GE), fasting, and postprandial gastric volumes (GVs), postprandial satiation, calorie intake at a free choice meal and selected gut hormones after 1 week of alginate (three capsules vs. matching placebo per day, ingested 30 min before the main meal). Six capsules were ingested with water 30 min before the GE, GV, and satiation tests on days 8-10. There were no treatment group effects on GE or volumes, gut hormones (ghrelin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), peptide YY (PYY)), satiation, total and macronutrient calorie intake at a free choice meal. There was no difference detected in results between obese and overweight patients. Alginate treatment for a period of 10 days showed no effect on gastric motor functions, satiation, appetite, or gut hormones. These results question the use of short-term alginate treatment for weight loss.

 

[Michael Scally MD]

Re: Weight-Loss/Obesity

Hungary Introduces 'Fat Tax'
Battling the Couch Potatoes
Battling the Couch Potatoes: Hungary Introduces 'Fat Tax' - SPIEGEL ONLINE - News - International

09/01/2011
By Catherine Cheney

In an effort to address rising obesity rates and health care costs, Hungary on Thursday implemented a law imposing special taxes on foods with high fat, salt and sugar content. The move comes as other European countries also consider policies to fight obesity.

The dobostorta cake, a five-layer vanilla and chocolate buttercream dessert with a caramel-glazed top layer, is probably Hungary's best-known treat -- at least after goulash. The cake can be seen in the vitrines of coffee houses and bakery shops lining the streets of Budapest.

"Hungarians are really into desserts," said Carolyn Banfalvi, co-founder of Taste Hungary. The tour company operator describes Hungarian food in general as "very fatty," with traditional cooking ingredients that include pork and goose fat. "What they call bacon here is often pieces of pure lard," she said.

The Hungarian government argues that this kind of diet is also leading to obesity and increased health problems, and that those who partake in indulgences like sweets should also pay a premium to help offset those costs. Enter the "fat tax."

Beginning Sept. 1, Hungarians will have to pay a 10 forint (€ 0.37) tax on foods with high fat, sugar and salt content, as well as increased tariffs on soda and alcohol. The expected annual proceeds of €70 million will go toward state health care costs, including those associated with addressing the country's 18.8 percent obesity rate, which is more than 3 percent higher than the European Union average of 15.5 percent according to a 2010 report by the Organization for Economic Cooperation and Development. In Germany, by comparison, 13.6 percent of adults are obese, with Romania at the bottom of the list with 7.9 percent.

Hungarian Prime Minister Viktor Orban has said, "Those who live unhealthily have to contribute more." In other words, the new law is based on the idea that those whose diets land them in the hospital should help foot the bill, particularly in a country with a health care deficit of €370 million.

Governments Take on Girth

The controversial "fat tax" is the most comprehensive on unhealthy foods in the world to date; but with other European countries closely watching Hungary's move, it is unlikely to be the last. Obesity rates are rising across Europe, and several countries are already taxing unhealthy foods to tackle plunging budgets and expanding waistlines.

Denmark is one of several European countries to tax sodas, and it has imposed a levy on candy for nearly 90 years. The country was the first in the world to pass a law banning trans fats, with Austria and Switzerland following closely after. Later this year, Denmark also plans to levy a sin tax on foods with high saturated fat content.

"What Denmark plans to do interests us," Finnish Prime Minister Jyrki Katainen said this spring, hinting at the domino effect the introduction of these taxes can have in other European countries. "Finland and Denmark have introduced taxes on sugared products such as soft drinks, ice cream and chocolate. A saturated fat tax is a logical next step."

Romania also considered a "fat tax" early last year, expanding beyond sodas and candies and trans fats to tackle junk food more broadly. Romanian Health Minister Attila Cseke said the tax would "be a percentage of the sale of fast-food products" and that the revenue would be used "to increase the budgets of health programs and fund investments into the system's infrastructure."

The idea was axed after the government considered its potential impact on consumers, particularly given rising food prices. There were also concerns that the tax might lead low-income Romanians to resort to even cheaper products, potentially worsening their diets.

But the Hungarian parliament seemed to believe that the benefits outweighed the risks when, on July 12, it passed a tax very similar to the one rejected in Romania.

Will Tax Put Poor at Disadvantage?

Initially dubbed the "hamburger tax," the new legislation is now referred to as the "chip tax" or "fat tax," because it applies to products like packaged snacks and sugary drinks rather than fast food.

"The Hungarian tax is a tax on products with high sugar, salt, and/or caffeine; taxable products include soft drinks with added sugar, energy drinks with added sugar and caffeine, pre-packaged sweetened products, salty snacks, high salt content condiments, soup mixes, gravy mixes and bases," explained Lisa McCooey, director of communications for Food Drink Europe, an industry lobby group.

Hungarians already spend 17 percent of their income on food, and they pay an extra 25 percent tax on most of the food and drink products they consume -- one of the highest rates within the EU. A major criticism of the new tax is that it will hit low-income groups the hardest, given their higher consumption, on average, of processed foods. "The economic situation here is really pretty bad. A lot of people don't have any extra money to spend on anything," said Banfalvi. "Life here is not cheap if you're an average Hungarian making an average salary."

While generally supportive of the new tax, Archie Turnbull of the Brussels-based European Public Health Alliance, a network of public health NGOs, suggested in a letter to the Hungarian government that it "consider using other pricing mechanisms or subsidies to make the healthy options" of fresh fruits and vegetables "more widely available and affordable."

'Not An Effective Instrument'

There are also questions over the effectiveness of fat-tax legislation. The growing list of taxes on unhealthy foods is leading to a debate on whether an increase in taxes can actually translate to a decrease in obesity.

"Scientific research shows that taxation is not an effective instrument in addressing consumer behavior and will have no impact on obesity rates," McCooey argued. "Consumer information and education, not tax, is the way to advance consumer understanding of healthy eating."

"The link between the price of a product and its purchase is clear and has been well substantiated," countered EPHA's Turnbull. But, he added, taxes alone cannot lead to healthier habits. "Combined with health promotion measures designed to increase awareness of the health issues associated with a poor diet, the impact of fiscal measures applied to food policy can be significant."

But in a country where goose fat is common in cooking and where, as Banfalvi says, "the salads are just different plates of pickled vegetables," an increase in prices for unhealthy foods is no small change.

 

[Michael Scally MD]

Re: Weight-Loss/Obesity

Weight Loss Surgery to Combat Type 2 Diabetes in Obese Patients
Allergan - Weight Loss Surgery to Combat Type 2 Diabetes in Obese Patients

LOS ANGELES, Sept. 20, 2011 (GLOBE NEWSWIRE) -- According to the International Diabetes Federation, bariatric surgery should be considered earlier in the treatment of eligible patients to help curb the complications that can be caused by diabetes. According to its position statement, under certain circumstances, the health of obese people with type 2 diabetes can substantially benefit from bariatric surgery under certain circumstances, including their glucose control and other obesity related comorbid conditions.

Obesity can affect how long a person can live. Carrying excess weight increases the risk of developing life-threatening medical conditions including cancer, heart disease and diabetes. Studies demonstrate that significant weight loss can improve, and in some cases even resolve, these conditions.

LAP-BAND Adjustable Gastric Banding system, which is an alternative to gastric bypass surgery, has a history of proven success in helping patients reach their long-term weight loss goals.

LAP-BAND surgery, which is offered at many weight loss clinics across the country, is approved by FDA for persons with a body mass index (BMI) of more than 30, who are at least 30 pounds over their ideal weight and suffer from one or more obesity-related comorbid health conditions.

For these patients, LAP-BAND system may be able to help them lose weight, have a more active lifestyle and avoid weight related health conditions.

LAP-BAND effectively reduces the amount of the food that your stomach can hold at one time, which helps to gradually lose weight and keep it off. The procedure, which is performed by a trained and certified surgeon at a weight loss clinic, is up to 10 times safer than more extensive weight loss surgeries such as gastric bypass and gastric sleeve and has fewer risks. The recovery time for the procedure is generally faster as well, and patients are able to get back to their normal activities in about one week. LAP-BAND system reduces the capacity of the stomach, restricting the amount of food consumed at one time, so patients feel full faster, feel full for a longer time, and end up eating less food.

 

[Michael Scally MD]

Re: Weight-Loss/Obesity

Denmark taxes fatty products
Denmark is to impose the world's first "fat tax" in a drive to slim its population and cut heart disease.
http://www.telegraph.co.uk/health/healthnews/8796522/Denmark-taxes-fatty-products.html

The move may increase pressure for a similar tax in the UK, which suffers from the highest levels of obesity in Europe.

Starting from this Saturday, Danes will pay an extra 30p on each pack of butter, 8p on a pack of crisps, and an extra 13p on a pound of mince, as a result of the tax.

The tax is expected to raise about 2.2bn Danish Krone (£140m), and cut consumption of saturated fat by close to 10pc, and butter consumption by 15pc.

"It's the first ever fat-tax," said Mike Rayner, Director of Oxford University's Health Promotion Research Group, who has long campaigned for taxes on unhealthy foods.

"It's very interesting. We haven't had any practical examples before. Now we will be able to see the effects for real." The tax will be levied at 2.5 per Kg of saturated fat and will be levied at the point of sale from wholesalers to retailers.

Hungary at the start of this month imposed a tax is on all packaged foods containing unhealthy levels of sugar, salt, and carbohydrates, as well as products containing more than 20 milligrams of caffeine per 100 milliliters of the product.

Less than 10pc of Danes are clinically obese, putting them slightly below the European average.
But researchers at Denmark's Institute for Food and Economic estimate that close to 4pc of the country's premature deaths are a result of excess consumption of saturated fats.

For Britain, where more than 20pc of the population is obese, the number will be considerably higher.
A 2007 study by Mr Rayner's group concluded that a combination of taxes on healthy foods and tax breaks on fruit and vegetables could save 3,200 lives a year in the UK.

Health Minister Andrew Lansley has up until now resisted calls for taxes on unhealthy foods, but Mr Rayner said they were the only credible way to combat Britain's obesity problem.

"I think we're going to have them in Britain whether Mr Lansley wants them or not, because the obesity crisis in the UK is such that we need to take more action.

 

[Michael Scally MD]

Re: New Weight Loss Drugs

This drug is TOAST! IMO, the same can be said for the others.

Vivus Shares Plunge After Diet Drug’s Ingredient Linked to Oral Clefts
Vivus Shares Plunge After Diet Drug’s Ingredient Linked to Oral Clefts - Bloomberg

Vivus Inc. (VVUS), maker of an experimental weight-loss pill, plunged 20 percent in early trading after an ingredient in the medicine was shown to be associated with oral clefts in babies whose mothers took it in pregnancy.

 

[Michael Scally MD]

Re: Weight-Loss/Obesity

U.S. to Review Diet Treatment Once Rejected
http://www.nytimes.com/2012/02/17/business/diet-treatment-already-in-use-to-get-fda-review.html

LOS OSOS, Calif. — Next week, advisers to the Food and Drug Administration will recommend whether the agency should approve the first new prescription diet pill in 13 years.

The F.D.A. rejected the drug under review, Qnexa, in 2010, amid safety concerns, and the drug’s manufacturer is now presenting additional data to argue its case.

 

[Michael Scally MD]

Re: Weight-Loss/Obesity

Federal Panel Approves Weight-Loss Drug Qnexa
Federal Panel Approves Weight-Loss Drug Qnexa - WSJ.com

A federal advisory panel on Wednesday overwhelmingly backed Vivus Inc.'s weight loss drug Qnexa, boosting the chance the Food and Drug Administration could approve a new prescription weight-loss drug for the first time in more than a decade.

Qnexa and two other weight-loss drugs were rejected by the agency in the past two years on concerns about potential safety risks of the products. Two-thirds of Americans are overweight or obese.

Vivus submitted additional clinical data to the FDA that was reviewed Wednesday by the FDA's endocrinologic and metabolic drugs advisory committee, which is made up of non-FDA medical experts.

The panel voted 20 to 2 in favor of a question that asked whether the "overall benefit-risk assessment" supports approval of Qnexa. The vote amounts to a recommendation that the FDA approve the drug. The FDA usually follows the advice of its panels but isn't required to. The FDA is expected to make a final decision by April 17.

Qnexa is a controlled-release formulation that combines low doses of two older drugs: the stimulant phentermine, which cuts appetite, and topiramate, which increases the sense of feeling full. Topiramate is sold under the brand name Topamax by Johnson & Johnson to treat migraines and seizures.

The development of obesity compounds has been a tough area for companies since the fen-phen drug combination was taken off the U.S. market in 1997 after one of the medication's components was linked to heart-valve damage. Abbott Laboratories removed its weight-loss drug Meridia from the U.S. market in 2010 amid concerns about the drug's risk of side effects like heart attack and stroke.

 

[Michael Scally MD]

Re: Weight-Loss/Obesity

Lemoine AY, Ledoux Sv, Queguiner I, et al. Link between Adipose Tissue Angiogenesis and Fat Accumulation in Severely Obese Subjects. Journal of Clinical Endocrinology & Metabolism. Link between Adipose Tissue Angiogenesis and Fat Accumulation in Severely Obese Subjects

Background: White adipose tissue (WAT) can rapidly expand or regress under different nutritional conditions. The role of angiogenesis in the expandability of human adipose tissue is established. However, whether sc and omental WAT (scWAT and oWAT) angiogenesis could influence fat distribution and metabolic diseases is not known.

Aim: The aim of this study was to analyze whether the capacity of angiogenesis in scWAT and oWAT correlates with fat accumulation and fat loss, fat distribution, adipocyte hypertrophy, and metabolic disorders in obese subjects.

Methods: Samples of scWAT and oWAT were obtained during bariatric surgery in 29 obese nondiabetic subjects. Vascular density and inflammatory infiltrate were analyzed by immunohistochemistry, and expression of angiogenic genes was analyzed by quantitative PCR. These parameters were correlated with anthropometric and metabolic parameters.

Results: Vascular density of scWAT correlated positively with body mass index, whereas vascular density of the oWAT correlated with waist circumference. There was no correlation of markers of angiogenesis and metabolic disorders. The number of vessels per adipocyte and the expression level of receptor 2 of vascular endothelial growth factor correlated with adipocyte area in scWAT and oWAT. Finally, weight loss after bariatric surgery correlated negatively with adipocyte hypertrophy and vascular density and positively with inflammation and angiogenesis of WAT.

Conclusion: Angiogenesis may influence WAT expansion and plasticity but does not appear to be involved in the development of insulin resistance in subjects with severe obesity.

 

[Michael Scally MD]

Re: Weight-Loss/Obesity

The OECD predicts that 75% of the US population will be overweight/obese by 2020.

Obesity and the Economics of Prevention: Fit not Fat - United States Key Facts
Obesity and the Economics of Prevention: Fit not Fat - United States Key Facts

 

[Michael Scally MD]

Re: Weight-Loss/Obesity

Bariatric Surgery versus Medical Therapy

Mingrone G, Panunzi S, De Gaetano A, et al. Bariatric Surgery versus Conventional Medical Therapy for Type 2 Diabetes. New England Journal of Medicine. MMS: Error

BACKGROUND - Roux-en-Y gastric bypass and biliopancreatic diversion can markedly ameliorate diabetes in morbidly obese patients, often resulting in disease remission. Prospective, randomized trials comparing these procedures with medical therapy for the treatment of diabetes are needed.

METHODS - In this single-center, nonblinded, randomized, controlled trial, 60 patients between the ages of 30 and 60 years with a body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) of 35 or more, a history of at least 5 years of diabetes, and a glycated hemoglobin level of 7.0% or more were randomly assigned to receive conventional medical therapy or undergo either gastric bypass or biliopancreatic diversion. The primary end point was the rate of diabetes remission at 2 years (defined as a fasting glucose level of <100 mg per deciliter [5.6 mmol per liter] and a glycated hemoglobin level of <6.5% in the absence of pharmacologic therapy).

RESULTS - At 2 years, diabetes remission had occurred in no patients in the medical-therapy group versus 75% in the gastric-bypass group and 95% in the biliopancreatic-diversion group (P<0.001 for both comparisons). Age, sex, baseline BMI, duration of diabetes, and weight changes were not significant predictors of diabetes remission at 2 years or of improvement in glycemia at 1 and 3 months. At 2 years, the average baseline glycated hemoglobin level (8.65±1.45%) had decreased in all groups, but patients in the two surgical groups had the greatest degree of improvement (average glycated hemoglobin levels, 7.69±0.57% in the medical-therapy group, 6.35±1.42% in the gastric-bypass group, and 4.95±0.49% in the biliopancreatic-diversion group).

CONCLUSIONS - In severely obese patients with type 2 diabetes, bariatric surgery resulted in better glucose control than did medical therapy. Preoperative BMI and weight loss did not predict the improvement in hyperglycemia after these procedures.


Schauer PR, Kashyap SR, Wolski K, et al. Bariatric Surgery versus Intensive Medical Therapy in Obese Patients with Diabetes. New England Journal of Medicine. MMS: Error

BACKGROUND - Observational studies have shown improvement in patients with type 2 diabetes mellitus after bariatric surgery.

METHODS - In this randomized, nonblinded, single-center trial, we evaluated the efficacy of intensive medical therapy alone versus medical therapy plus Roux-en-Y gastric bypass or sleeve gastrectomy in 150 obese patients with uncontrolled type 2 diabetes. The mean (±SD) age of the patients was 49±8 years, and 66% were women. The average glycated hemoglobin level was 9.2±1.5%. The primary end point was the proportion of patients with a glycated hemoglobin level of 6.0% or less 12 months after treatment.

RESULTS - Of the 150 patients, 93% completed 12 months of follow-up. The proportion of patients with the primary end point was 12% (5 of 41 patients) in the medical-therapy group versus 42% (21 of 50 patients) in the gastric-bypass group (P=0.002) and 37% (18 of 49 patients) in the sleeve-gastrectomy group (P=0.008). Glycemic control improved in all three groups, with a mean glycated hemoglobin level of 7.5±1.8% in the medical-therapy group, 6.4±0.9% in the gastric-bypass group (P<0.001), and 6.6±1.0% in the sleeve-gastrectomy group (P=0.003). Weight loss was greater in the gastric-bypass group and sleeve-gastrectomy group (?29.4±9.0 kg and ?25.1±8.5 kg, respectively) than in the medical-therapy group (?5.4±8.0 kg) (P<0.001 for both comparisons). The use of drugs to lower glucose, lipid, and blood-pressure levels decreased significantly after both surgical procedures but increased in patients receiving medical therapy only. The index for homeostasis model assessment of insulin resistance (HOMA-IR) improved significantly after bariatric surgery. Four patients underwent reoperation. There were no deaths or life-threatening complications.

CONCLUSIONS - In obese patients with uncontrolled type 2 diabetes, 12 months of medical therapy plus bariatric surgery achieved glycemic control in significantly more patients than medical therapy alone. Further study will be necessary to assess the durability of these results.

 

[Michael Scally MD]

Re: Weight-Loss/Obesity

The Role of Obesity in Cancer Survival and Recurrence - Workshop Summary
The Role of Obesity in Cancer Survival and Recurrence - Workshop Summary - Institute of Medicine

Recent research suggests that excess weight and obesity can influence cancer survival and recurrence. Given the increasing rate of obesity and an aging population more susceptible to cancer, there is mounting concern about obesity’s role in fueling tumor growth. Additionally, there is interest in exploring ways to break the obesity-cancer link, especially in patients already diagnosed with cancer who are more susceptible to new cancers as well as a cancer progression or recurrence.

At a workshop October 31-November 1, 2011, held by the IOM’s National Cancer Policy Forum, experts presented the latest laboratory and clinical evidence on the obesity-cancer link and the possible mechanisms underlying that link. Clinicians, researchers, cancer survivors, and policy makers also discussed potential interventions to mitigate the effects of obesity on cancer, and research and policy measures needed to counter the expected rise of cancer incidence mortality due to an increasingly overweight and older population. This document summarizes the workshop.

 

[Michael Scally MD]

IMO, this is tantamount to a FDA approval! We will see. Stay Tuned. This would be the first weight loss drug in over a decade.

VIVUS Receives Notification of Qnexa(R) PDUFA Date Extension
Three-Month Extension for REMS Review
VIVUS, Inc. - VIVUS Receives Notification of Qnexa(R) PDUFA Date Extension

MOUNTAIN VIEW, Calif., April 9, 2012 (GLOBE NEWSWIRE) -- The U.S. Food and Drug Administration (FDA) informed VIVUS (Nasdaq:VVUS) of an extended Prescription Drug User Fee Act (PDUFA) date for its review of the Qnexa New Drug Application (NDA) from April 17 to July 17, 2012. The three-month extension is a standard extension period.

On April 4, 2012, following the FDA's request, VIVUS submitted the Qnexa Risk Evaluation and Mitigation Strategy (REMS), which was considered a major amendment to the NDA. The submission consisted of proposed REMS materials. Since the receipt date was within three months of the user fee goal date, the FDA is extending the PDUFA date by three months to provide time for a full review of the submission.

"The Qnexa REMS submission is comprehensive, with materials based on ongoing feedback from the FDA since our advisory committee meeting in February," stated Leland F. Wilson, chief executive officer of VIVUS. "We look forward to finalizing our REMS with the FDA while we move forward with our commercialization plans."

The Qnexa NDA seeks approval for the treatment of obesity, including weight loss and maintenance of weight loss for obese patients (BMI ? 30 kg/m2), or overweight patients (BMI ? 27 kg/m2) with weight-related co-morbidities such as hypertension, type 2 diabetes or dyslipidemia. Obesity is the second leading cause of preventable death and directly contributes to numerous life-threatening conditions including diabetes, cardiovascular disease, hypertension and stroke.

 

[Michael Scally MD]

A Weight Loss Surgery Sends Some to Canada
Impatience to Get Thin Sends Some to Canada - NYTimes.com

Tammy Kwarciak, a 44-year-old nurse whose weight had been creeping up for years, was determined to lose 50 pounds. So in February, she drove from her home in Port Huron, Mich., across the border into Canada and had a small balloonlike device inserted into her stomach.

The intragastric balloon, filled with liquid and left in the stomach for up to six months, is not approved for use in the United States, though it’s available in Europe, South America and other parts of the world. Clinical trials required to win federal Food and Drug Administration approval are being initiated, but many Americans aren’t waiting.

Since the balloon’s introduction in Canada in 2006, people like Mrs. Kwarciak have been streaming north in growing numbers. Drawn by the relative ease of balloon placement, Americans account for nearly a third of patients undergoing the procedures in Canadian clinics just over the border.

 

[Michael Scally MD]

A Novel Therapeutic Approach to Treating Obesity through Modulation of TGF? Signaling

Obesity is a worldwide epidemic and is driving increases in the development of type 2 diabetes, cardiovascular disease, and certain cancers. Compelling research demonstrates that even moderate weight loss can provide significant protection from cardiovascular disease and type 2 diabetes. Traditional obesity treatments are aimed at preventing further accumulation of chemical energy in the form of fat by reducing appetite or nutrient uptake; however, treatments that positively affect peripheral energy use still offers great promise.

For example, alterations in body composition to increase muscle mass could, in the absence of increased food intake, reduce adiposity and help reduce the risk of obesity-related cardiovascular and metabolic diseases. Brown adipocytes are of special interest in that they have the ability to decrease obesity through thermogenesis mediated by uncoupling protein 1 (UCP1). It has recently been shown that there are two types of brown fat that have distinctly different origins. The classical brown fat depots typified by the interscapular depot in mice arises from a common precursor with skeletal muscle. Brown fat-like cells (also called brite cells or beige cells) can also appear in white fat depots when an animal is exposed to ?3-adrenergic agonists or prolonged cold temperatures. Brown fat cells of both types are certainly novel and appealing targets for the development of antiobesity therapeutics.

Multiple members of the growth and differentiation factor (GDF) family, including myostatin (GDF-8), signal through activin receptor type IIB (ActRIIB). These factors have been shown to negatively regulate muscle mass and may also be involved in the regulation of adipose tissue mass. Previous research in rodents demonstrates that inhibition of ActRIIB signaling with a chimeric ActRIIB derivative (ActRIIB-mFc), consisting of the extracellular domain of murine ActRIIB fused to a murine IgG2a Fc domain, results in greatly increased muscle mass in healthy mice, mice with amyotrophic lateral sclerosis, and mice exposed to a hypoxic environment.

In addition, inhibition of ActRIIB signaling using a soluble receptor approach protected mice fed a high-fat diet (HFD) from developing diet-induced obesity (DIO). The reduced susceptibility of mice with diminished ActRIIB signaling to DIO has been mainly attributed to inhibition of myostatin signaling and secondary to increased muscle. Importantly, ActRIIB is a signaling receptor for TGF? ligands other than myostatin, many that are expressed in adipose tissue and may also be targets for the soluble ActRIIB-driven effect of protection from DIO.

Researchers have developed the novel, human therapeutic ActRIIB- Fc to inhibit ActRIIB signaling. This soluble ActRIIB- Fc is comprised of a form of the ActRIIB extracellular domain fused to a human IgG Fc domain and acts as a soluble, decoy receptor to the endogenous ActRIIB. HFD feeding in mice results in adverse changes in body composition and metabolic parameters similar to those reported in obese human subjects.

Therefore, they investigated the effects of ActRIIB-Fc on muscle mass, adiposity, and adiposity-related systemic physiological changes, such as changes in circulating concentrations of lipids and adipokines as well as lipid accumulation in liver and brown adipose tissue in mice fed a HFD. In this paper, researchers report striking effects of this novel therapeutic on preventing obesity induced in mice by HFD. This reagent induces many changes in the gene expression pattern of adipose tissues, including the induction of a brown fat-like gene program in the white fat, and these changes correlate with an increase in whole body energy expenditure. They also characterize ligands of theTGF? superfamily that regulate thermogenesis in primary adipocyte cultures and identify ligands that are potentially targeted by ActRIIB-Fc to elicit its effect on white fat.

These findings identify a novel potential mechanism for induction of thermogenic profile in predominantly WAT and provide grounds for the use of ActRIIB-Fc in treatment of obesity and obesity-related metabolic disorders.


Koncarevic A, Kajimura S, Cornwall-Brady M, et al. A Novel Therapeutic Approach to Treating Obesity through Modulation of TGF? Signaling. Endocrinology. A Novel Therapeutic Approach to Treating Obesity through Modulation of TGF? Signaling

Obesity results from disproportionately high energy intake relative to energy expenditure. Many therapeutic strategies have focused on the intake side of the equation, including pharmaceutical targeting of appetite and digestion. An alternative approach is to increase energy expenditure through physical activity or adaptive thermogenesis. A pharmacological way to increase muscle mass and hence exercise capacity is through inhibition of the activin receptor type IIB (ActRIIB). Muscle mass and strength is regulated, at least in part, by growth factors that signal via ActRIIB. Administration of a soluble ActRIIB protein comprised of a form of the extracellular domain of ActRIIB fused to a human Fc (ActRIIB-Fc) results in a substantial muscle mass increase in normal mice. However, ActRIIB is also present on and mediates the action of growth factors in adipose tissue, although the function of this system is poorly understood. In the current study, we report the effect of ActRIIB-Fc to suppress diet-induced obesity and linked metabolic dysfunctions in mice fed a high-fat diet. ActRIIB-Fc induced a brown fat-like thermogenic gene program in epididymal white fat, as shown by robustly increased expression of the thermogenic genes uncoupling protein 1 and peroxisomal proliferator-activated receptor-? coactivator 1?. Finally, we identified multiple ligands capable of reducing thermogenesis that represent likely target ligands for the ActRIIB-Fc effects on the white fat depots. These data demonstrate that novel therapeutic ActRIIB-Fc improves obesity and obesity-linked metabolic disease by both increasing skeletal muscle mass and by inducing a gene program of thermogenesis in the white adipose tissues.


Note: Acceleron Pharma, Inc. - Acceleron Pharma

 

[Michael Scally MD]

Obesity and Severe Obesity Forecasts through 2030 - >50%

Finkelstein EA et al. Obesity and Severe Obesity Forecasts through 2030. American Journal of Preventative Medicine, 2012. http://www.ajpmonline.org/webfiles/images/journals/amepre/AMEPRE_33853-stamped2.pdf

Background: Previous efforts to forecast future trends in obesity applied linear forecasts assuming that the rise in obesity would continue unabated. However, evidence suggests that obesity prevalence may be leveling off.

Purpose: This study presents estimates of adult obesity and severe obesity prevalence through 2030 based on nonlinear regression models. The forecasted results are then used to simulate the savings that could be achieved through modestly successful obesity prevention efforts.

Methods: The study was conducted in 2009–2010 and used data from the 1990 through 2008 Behavioral Risk Factor Surveillance System (BRFSS). The analysis sample included nonpregnant adults aged _18 years. The individual-level BRFSS variables were supplemented with state-level variables from the U.S. Bureau of Labor Statistics, the American Chamber of Commerce Research Association, and the Census of Retail Trade. Future obesity and severe obesity prevalence were estimated through regression modeling by projecting trends in explanatory variables expected to influence obesity prevalence.

Results: Linear time trend forecasts suggest that by 2030, 51% of the population will be obese. The model estimates a much lower obesity prevalence of 42% and severe obesity prevalence of 11%. If obesity were to remain at 2010 levels, the combined savings in medical expenditures over the next 2 decades would be $549.5 billion.

Conclusions: The study estimates a 33% increase in obesity prevalence and a 130% increase in severe obesity prevalence over the next 2 decades. If these forecasts prove accurate, this will further hinder efforts for healthcare cost containment.

 

[Michael Scally MD]

FDA advisers recommend approval of lorcaserin; could be first new weight loss drug in a decade
FDA advisers recommend approval of lorcaserin; could be first new weight loss drug in a decade - The Washington Post

WASHINGTON — Advisers to government health regulators have recommended that that they approve sales of what would be the first new prescription weight-loss drug in the U.S. in more than a decade, despite concerns over cardiac risks.

A panel of expert advisers to the Food and Drug Administration voted 18-4 to recommend approval of lorcaserin, developed by Arena Pharmaceuticals Inc. They concluded that its benefits “outweigh the potential risks when used long term” in overweight and obese people. One panel member abstained from voting.

 

[Michael Scally MD]

Alliances for Obesity Prevention: Finding Common Ground - Workshop Summary
Alliances for Obesity Prevention: Finding Common Ground - Workshop Summary - Institute of Medicine

 

[Michael Scally MD]

The Global Diabetes Tsunami... And Why America Actually Has It Good
The Global Diabetes Tsunami... And Why America Actually Has It Good | ZeroHedge

 

[Michael Scally MD]

From white to brown fat through the PGC-1?-dependent myokine irisin: implications for diabetes and obesity
From white to brown fat through the PGC-1?-dependent myokine irisin: implications for diabetes and obesity

 

[Michael Scally MD]

Marik PE. The malignant obesity hypoventilation syndrome (MOHS). Obesity Reviews. The malignant obesity hypoventilation syndrome (MOHS) - Marik - 2012 - Obesity Reviews - Wiley Online Library

We have coined the term ‘malignant obesity hypoventilation syndrome’ (MOHS) to describe a severe multisystem disease due to the systemic effects of obesity. Patients with this syndrome have severe obesity-related hypoventilation together with systemic hypertension, diabetes and the metabolic syndrome, left ventricular hypertrophy with diastolic dysfunction, pulmonary hypertension and hepatic dysfunction. This syndrome is largely unrecognized as physicians do not make the association between the patients' multiple medical problems and obesity. Because of the delayed diagnosis and progressive morbidities of this condition, all patients with a body mass index of more than 40 kg m?2 should be screened for MOHS. The management of patients with MOHS includes short-term measures to improve the patients' medical condition and long-term measures to achieve enduring weight loss. Bariatric surgery reverses or improves the multiple metabolic and organ dysfunctions associated with MOHS and should be strongly considered in these patients.