Weight Loss - Obesity

[Michael Scally MD]

Garaulet M, Gomez-Abellan P, Alburquerque-Bejar JJ, Lee YC, Ordovas JM, Scheer FAJL. Timing of food intake predicts weight loss effectiveness. Int J Obes. http://www.nature.com/ijo/journal/vaop/ncurrent/full/ijo2012229a.html

Background: There is emerging literature demonstrating a relationship between the timing of feeding and weight regulation in animals. However, whether the timing of food intake influences the success of a weight-loss diet in humans is unknown.

Objective: To evaluate the role of food timing in weight-loss effectiveness in a sample of 420 individuals who followed a 20-week weight-loss treatment.

Methods: Participants (49.5% female subjects; age (mean±s.d.): 42±11 years; BMI: 31.4±5.4?kg?m?2) were grouped in early eaters and late eaters, according to the timing of the main meal (lunch in this Mediterranean population). 51% of the subjects were early eaters and 49% were late eaters (lunch time before and after 1500 hours, respectively), energy intake and expenditure, appetite hormones, CLOCK genotype, sleep duration and chronotype were studied.

Results: Late lunch eaters lost less weight and displayed a slower weight-loss rate during the 20 weeks of treatment than early eaters (P=0.002). Surprisingly, energy intake, dietary composition, estimated energy expenditure, appetite hormones and sleep duration was similar between both groups. Nevertheless, late eaters were more evening types, had less energetic breakfasts and skipped breakfast more frequently that early eaters (all; P<0.05). CLOCK rs4580704 single nucleotide polymorphism (SNP) associated with the timing of the main meal (P=0.015) with a higher frequency of minor allele (C) carriers among the late eaters (P=0.041). Neither sleep duration, nor CLOCK SNPs or morning/evening chronotype was independently associated with weight loss (all; P>0.05).

Conclusions: Eating late may influence the success of weight-loss therapy. Novel therapeutic strategies should incorporate not only the caloric intake and macronutrient distribution—as is classically done—but also the timing of food.

 

[Michael Scally MD]

Is Bariatric Surgery Worth It? Maybe not.

Livingston EH. Is Bariatric Surgery Worth It?: Comment on “Impact of Bariatric Surgery on Health Care Costs of Obese Persons”. JAMA Surg. 2013:1. JAMA Network | JAMA Surgery | Is Bariatric Surgery Worth It?Comment on “Impact of Bariatric Surgery on Health Care Costs of Obese Persons”Is Bariatric Surgery Worth It?

Is bariatric surgery worth it? Maybe not. Accumulating evidence suggests there is no economic benefit for weight loss surgery.

Long-term follow-up from the Swedish Obese Subjects study reported in JAMA showed that although fewer medications were used by bariatric patients compared with controls, the bariatric patients used substantially more hospital resources. A formal cost-effectiveness study using very high-quality data from the US Department of Veterans Affairs did not show a cost benefit for Roux-en-Y gastric bypass. In this issue of JAMA Surgery, an analysis of claims paid by BlueCross BlueShield for bariatric surgery patients for as long as 6 postoperative years failed to demonstrate a cost benefit for weight loss surgery.

Coupled with findings that bariatric surgery confers little to no long-term survival benefit, these observations show that bariatric surgery does not provide an overall societal benefit. In other words, the indications for bariatric surgery should be viewed in terms of individual patient benefit without anticipating that there will be cost savings to a health care system by offering this treatment.

Bariatric surgery clearly benefits some patients. Current data suggest that weight loss operations should be offered to highly selected patients. Patients considered for bariatric surgery should have a complication of obesity that is known to dramatically improve with weight loss surgery. Examples include diabetes and osteoarthritis. These operations should not be done for body mass index as an exclusive indication. Surgery should be offered only to patients with demonstrated compliance to medical and dietary treatment. Operations with questionable long-term effectiveness such as laparoscopic banding procedures should be avoided.

Bariatric surgery has dramatic short-term results, but on a population level its outcomes are far less impressive. In this era of tight finances and inevitable rationing of health care resources, bariatric surgery should be viewed as an expensive resource that can help some patients. Those patients should be carefully vetted and the operations offered only if there is an overwhelming probability of long-term success.


Weiner JP, Goodwin SM, Chang H, et al. Impact of Bariatric Surgery on Health Care Costs of Obese Persons: A 6-Year Follow-up of Surgical and Comparison Cohorts Using Health Plan Data. JAMA Surg. 2013:1-8. JAMA Network | JAMA Surgery | Impact of Bariatric Surgery on Health Care Costs of Obese PersonsA 6-Year Follow-up of Surgical and Comparison Cohorts Using Health Plan DataBariatric Surgery and Costs for Obese Persons

Importance - Bariatric surgery is a well-documented treatment for obesity, but there are uncertainties about the degree to which such surgery is associated with health care cost reductions that are sustained over time.

Objective - To provide a comprehensive, multiyear analysis of health care costs by type of procedure within a large cohort of privately insured persons who underwent bariatric surgery compared with a matched nonsurgical cohort.

Design - Longitudinal analysis of 2002-2008 claims data comparing a bariatric surgery cohort with a matched nonsurgical cohort.

Setting - Seven BlueCross BlueShield health insurance plans with a total enrollment of more than 18 million persons.

Participants - A total of 29 820 plan members who underwent bariatric surgery between January 1, 2002, and December 31, 2008, and a 1:1 matched comparison group of persons not undergoing surgery but with diagnoses closely associated with obesity.

Main Outcome Measures - Standardized costs (overall and by type of care) and adjusted ratios of the surgical group's costs relative to those of the comparison group.

Results - Total costs were greater in the bariatric surgery group during the second and third years following surgery but were similar in the later years. However, the bariatric group's prescription and office visit costs were lower and their inpatient costs were higher. Those undergoing laparoscopic surgery had lower costs in the first few years after surgery, but these differences did not persist.

Conclusions and Relevance - Bariatric surgery does not reduce overall health care costs in the long term. Also, there is no evidence that any one type of surgery is more likely to reduce long-term health care costs. To assess the value of bariatric surgery, future studies should focus on the potential benefit of improved health and well-being of persons undergoing the procedure rather than on cost savings.

 

[Michael Scally MD]

Hughes TE, Kim DD, Marjason J, Proietto J, Whitehead JP, Vath JE. Ascending Dose Controlled Trial of Beloranib, a Novel Obesity Treatment for Safety, Tolerability and Weight Loss in Obese Women. Obesity (Silver Spring). Ascending Dose Controlled Trial of Beloranib, a Novel Obesity Treatment for Safety, Tolerability and Weight Loss in Obese Women - Hughes - Obesity - Wiley Online Library

OBJECTIVE: Evaluate the safety and tolerability of beloranib, a fumagillin-class methionine aminopetidase-2 (MetAP2) inhibitor, in obese women over 4 weeks.

DESIGN AND METHODS: Thirty-one obese (mean BMI 38kg/m2 ) women were randomized to intravenous 0.1, 0.3, or 0.9mg/m2 beloranib or placebo twice weekly for 4 weeks (N=7, 6, 9, and 9).

RESULTS: The most frequent AEs were headache, infusion site injury, nausea, and diarrhea. Nausea and infusion site injury occurred more with beloranib than placebo. The most common reason for discontinuation was loss of venous access. There were no clinically significant abnormal laboratory findings. In subjects completing 4 weeks, median weight loss with 0.9mg/m2 beloranib was -3.8kg (95% CI -5.1, -0.9; N=8) vs. -0.6kg with placebo (-4.5, -0.1; N=6). Weight change for 0.1 and 0.3mg/m2 beloranib was similar to placebo. Beloranib(0.9mg/m2 ) was associated with a significant 42 and 18% reduction in triglycerides and LDL-cholesterol, as well as improvement in C-reactive protein and reduced sense of hunger. Changes in beta-hydroxybutyrate, adiponectin, leptin, and fibroblast growth factor-21 were consistent with the putative mechanism of MetAP2 inhibition. Glucose and blood pressure were unchanged.

CONCLUSIONS: Beloranib treatment was well tolerated and associated with rapid weight loss and improvements in lipids, C-reactive protein, and adiponectin.

 

[Michael Scally MD]

Liou AP, Paziuk M, Luevano J-M, Machineni S, Turnbaugh PJ, Kaplan LM. Conserved Shifts in the Gut Microbiota Due to Gastric Bypass Reduce Host Weight and Adiposity. Science Translational Medicine 2013;5(178):178ra41. Conserved Shifts in the Gut Microbiota Due to Gastric Bypass Reduce Host Weight and Adiposity

Roux-en-Y gastric bypass (RYGB) results in rapid weight loss, reduced adiposity, and improved glucose metabolism. These effects are not simply attributable to decreased caloric intake or absorption, but the mechanisms linking rearrangement of the gastrointestinal tract to these metabolic outcomes are largely unknown.

Studies in humans and rats have shown that RYGB restructures the gut microbiota, prompting the hypothesis that some of the effects of RYGB are caused by altered host-microbial interactions. To test this hypothesis, we used a mouse model of RYGB that recapitulates many of the metabolic outcomes in humans.

16S ribosomal RNA gene sequencing of murine fecal samples collected after RYGB surgery, sham surgery, or sham surgery coupled to caloric restriction revealed that alterations to the gut microbiota after RYGB are conserved among humans, rats, and mice, resulting in a rapid and sustained increase in the relative abundance of Gammaproteobacteria (Escherichia) and Verrucomicrobia (Akkermansia). These changes were independent of weight change and caloric restriction, were detectable throughout the length of the gastrointestinal tract, and were most evident in the distal gut, downstream of the surgical manipulation site.

Transfer of the gut microbiota from RYGB-treated mice to nonoperated, germ-free mice resulted in weight loss and decreased fat mass in the recipient animals relative to recipients of microbiota induced by sham surgery, potentially due to altered microbial production of short-chain fatty acids.

These findings provide the first empirical support for the claim that changes in the gut microbiota contribute to reduced host weight and adiposity after RYGB surgery.

 

[BBC3]

THis is a great point. I am not even getting into that awsome post below about CARBS.. Later. But on this one. ONE WOULD THINK, that the estrogen profile associated with being obese would be a major cancer trigger. And I do. Really though, I think of some really fat folks, ESPECIALLY WOMEN, and INDIANs (NAtive) which get away with it.

(Have we not taken a couple of those bastards under the microscope yet?? After all, we did everything else to them..) LOL

Is it that Fat MEN die of other disease before getting cancer? Specifically heart??

Final note. I have nothing against American Indians. In fact I married one and suggest everyone here should try some of that hot INJIN STANK. The BUSH is a BEATIFUL thing to BEHOLD and without a curl in that soft luvin LOCK..:drooling: The only problem is, that they dont truly love ya unless they have tried to kill you at least 3 times... LOL

Was that WRONG???!!! ????

Obesity & Cancer

The prevalence of obesity, a major risk factor for several chronic diseases, more than doubled between 1980 and 2000. The latest United States data suggest that the current prevalence of obesity in adults is leveling off around 35%, with another 33% of the adult population considered overweight. Approximately seven in 10 adults and three in 10 children in the United States exceed a healthy weight.

The obese phenotype often manifests in metabolic syndrome, which describes a state of metabolic dysregulation characterized by several factors: insulin resistance and hyperglycemia, dyslipidemia (higher triglycerides, lower high-density lipoprotein-cholesterol), increased waist circumference, and hypertension. We now know that this phenotype is associated with many types of cancer. In particular, study data sounded the alert to the magnitude of the obesity-cancer problem. In a very interesting article, authors found that 20% of cancer deaths can be attributed to overweight/obesity and 5% to lack of exercise. Thus, control of this one lifestyle-related risk factor has the potential to reduce the incidence of cancer by as much as a quarter.

The American Institute for Cancer Research and World Cancer Research Fund publishes systematic reviews, meta-analyses and recommendations based on the world’s cancer literature in their Expert Report on Food, Nutrition, Physical Activity, and the Prevention of Cancer, now in its second edition continuous updates online. As summarized in that report, many kinds of cancers are associated with obesity. Links have been established between obesity and with colorectal, kidney, liver/gall bladder, pancreatic, and esophageal cancers in both men and women; stomach and prostate cancers in men only; and postmenopausal breast, endometrial, uterine, and ovarian cancers in women only).

 

[Michael Scally MD]

Topiramate + phentermine. An excessively dangerous appetite-suppressant combination. Prescrire Int 2013;22(136):61-4. Topiramate + phentermine. An excessively dange... [Prescrire Int. 2013] - PubMed - NCBI

The cornerstones of treatment for obesity, and even more so for simple overweight, are dietary measures and physical exercise. There are no drugs with a favourable harm-benefit balance in this setting. A fixed-dose combination of topiramate, an antiepileptic drug, and phentermine, an appetite-suppressant amphetamine, has been refused marketing authorisation in the European Union, after being licensed in the United States. There are no randomised controlled trials of topiramate + phentermine in the prevention of complications of obesity.

In the three available placebo-controlled trials, patients treated with topiramate 46 mg per day + phentermine 7.5 mg per day for between 1 and 2 years lost about 6-8 kg more than patients who received a placebo. About one-quarter of this weight loss was regained within a year after treatment discontinuation. The known adverse effects of the two drugs composing this combination are additive, and include psychiatric disorders, cardiac arrhythmias and metabolic acidosis. The risk of serious cardiovascular disorders was not adequately studied during clinical trials. Many women of child-bearing age would be exposed to this combination, which can provoke fetal abnormalities, including cleft palate, if taken during pregnancy. In practice, the topiramate + phentermine combination has an unfavourable harm-benefit balance and has no place in the treatment of obesity.

 

[Michael Scally MD]

Gut Microbe May Fight Obesity And Diabetes
Gut microbe may fight obesity and diabetes : Nature News & Comment

The gut is home to innumerable different bacteria — a complex ecosystem that has an active role in a variety of bodily functions. In a study published this week in Proceedings of the National Academy of Sciences, a team of researchers finds that in mice, just one of those bacterial species plays a major part in controlling obesity and metabolic disorders such as type 2 diabetes. The bacterium, Akkermansia muciniphila, digests mucus and makes up 3–5% of the microbes in a healthy mammalian gut. But the intestines of obese humans and mice, and those with type 2 diabetes, have much lower levels.

Mice that were fed a high-fat diet, the researchers found, had 100 times less A. muciniphila in their guts than mice fed normal diets. The researchers were able to restore normal levels of the bacterium by feeding the mice live A. muciniphila, as well as 'prebiotic' foods that encourage the growth of gut microbes. The effects of this treatment were dramatic. Compared with untreated animals, the mice lost weight and had a better ratio of fat to body mass, as well as reduced insulin resistance and a thicker layer of intestinal mucus. They also showed improvements in a host of other indicators related to obesity and metabolic disorders.


Everard A, Belzer C, Geurts L, et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proceedings of the National Academy of Sciences. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity

Obesity and type 2 diabetes are characterized by altered gut microbiota, inflammation, and gut barrier disruption. Microbial composition and the mechanisms of interaction with the host that affect gut barrier function during obesity and type 2 diabetes have not been elucidated.

We recently isolated Akkermansia muciniphila, which is a mucin-degrading bacterium that resides in the mucus layer. The presence of this bacterium inversely correlates with body weight in rodents and humans. However, the precise physiological roles played by this bacterium during obesity and metabolic disorders are unknown.

This study demonstrated that the abundance of A. muciniphila decreased in obese and type 2 diabetic mice. We also observed that prebiotic feeding normalized A. muciniphila abundance, which correlated with an improved metabolic profile. In addition, we demonstrated that A. muciniphila treatment reversed high-fat diet-induced metabolic disorders, including fat-mass gain, metabolic endotoxemia, adipose tissue inflammation, and insulin resistance. A. muciniphila administration increased the intestinal levels of endocannabinoids that control inflammation, the gut barrier, and gut peptide secretion. Finally, we demonstrated that all these effects required viable A. muciniphila because treatment with heat-killed cells did not improve the metabolic profile or the mucus layer thickness.

In summary, this study provides substantial insight into the intricate mechanisms of bacterial (i.e., A. muciniphila) regulation of the cross-talk between the host and gut microbiota. These results also provide a rationale for the development of a treatment that uses this human mucus colonizer for the prevention or treatment of obesity and its associated metabolic disorders.

 

[Michael Scally MD]

Beloranib A Novel Methionine Aminopeptidase 2 (MetAP2) Inhibitor Appeared Safe and Showed Dose Responsive Weight Loss [~10 kg (22 pounds)] Over 12 Weeks in Interim Analysis of Ongoing Phase 2 Trial
ADA 2013

Beloranib is a MetAP2 inhibitor that increases fatty acid oxidation and reduces hunger. Previous proof of concept studies over 4 weeks showed ~4% weight loss with 1-3 mg subcutaneous (SC) beloranib in obese women. This is a double-blind placebo-controlled study to investigate the safety/tolerability PK/PD and metabolic effects of SC beloranib.

Obese men and women were randomized to 0.6 (n=37) 1.2 (n=36) or 2.4 mg (n=34) of SC beloranib vs. placebo (N=38) twice-weekly for 12wks. Body weight (BW) sense of hunger and cardiometabolic biomarkers were measured. Results are based on pre-specified interim analysis of first 19 patients who completed 12 weeks of treatment duration (n=5 6 3 and 5 for 0.6 1.2 2.4mg and placebo respectively). Patients were white females (mean age 40.3 yr BW 101.2 kg and BMI 37.9 kg/m2).

The most common adverse events (AEs) with higher incidence during beloranib treatment were sleep disturbance nausea and vomiting (resulting in 2 drop-outs from the 2.4 mg group). There were no severe AEs serious AEs or deaths. There were no clinically significant abnormal laboratory measures vitals or ECG findings.

After 12wks subjects on 0.6 1.2 or 2.4mg lost an average (±SEM) BW of -3.8±0.8 -6.1±1.5 and -9.9±2.3 kg vs. +1.8±0.4 kg for placebo (all p<0.005 vs. placebo). Hunger LDL-c TG and hs-CRP decreased in the beloranib groups vs. placebo.

Beloranib treatment for 12wks was generally well-tolerated by SC administration resulted in rapid and sustained clinically meaningful BW loss of up to ~10% improved sense of hunger and cardiometabolic risk markers in this interim analysis of an ongoing Phase 2 study which is scheduled to be completed by May 2013.

 

[Michael Scally MD]

Masters RK, Reither EN, Powers DA, Yang YC, Burger AE, Link BG. The Impact of Obesity on US Mortality Levels: The Importance of Age and Cohort Factors in Population Estimates. American Journal of Public Health 2013:e1-e7. An Error Occurred Setting Your User Cookie

Objectives. To estimate the percentage of excess death for US Black and White men and women associated with high body mass, we examined the combined effects of age variation in the obesity–mortality relationship and cohort variation in age-specific obesity prevalence.

Methods. We examined 19 National Health Interview Survey waves linked to individual National Death Index mortality records, 1986–2006, for age and cohort patterns in the population-level association between obesity and US adult mortality.

Results. The estimated percentage of adult deaths between 1986 and 2006 associated with overweight and obesity was 5.0% and 15.6% for Black and White men, and 26.8% and 21.7% for Black and White women, respectively. We found a substantially stronger association than previous research between obesity and mortality risk at older ages, and an increasing percentage of mortality attributable to obesity across birth cohorts.

Conclusions. Previous research has likely underestimated obesity’s impact on US mortality. Methods attentive to cohort variation in obesity prevalence and age variation in obesity’s effect on mortality risk suggest that obesity significantly shapes US mortality levels, placing it at the forefront of concern for public health action.

 

[Michael Scally MD]

[Mice] A Gut Lipid Messenger Links Excess Dietary Fat to Dopamine Deficiency - Why does ice cream taste so good? High-fat foods activate a reward circuit in the brain involving dopamine, a neurotransmitter that regulates pleasure. Overconsumption of high-fat foods is thought to dampen this dopamine-induced reward sensation, leading to compensatory consumption of even more high-fat foods.

The mechanisms by which dietary fat in the gut “talks” to the dopamine reward circuit are unclear. This study suggests that an intestinal lipid messenger called oleoylethanolamine (OEA) may play a role—at least in mice. Mice on a high-fat diet had unusually low levels of intestinal OEA and exhibited deficient dopaminergic responses to gut stimulation with high-fat lipids. Infusion of OEA into these mice restored the dopaminergic response, and mice that had been accustomed to a high-fat diet began to eat more low-fat foods.

Tellez LA, Medina S, Han W, et al. A Gut Lipid Messenger Links Excess Dietary Fat to Dopamine Deficiency. Science 2013;341(6147):800-2. A Gut Lipid Messenger Links Excess Dietary Fat to Dopamine Deficiency

Excessive intake of dietary fats leads to diminished brain dopaminergic function. It has been proposed that dopamine deficiency exacerbates obesity by provoking compensatory overfeeding as one way to restore reward sensitivity. However, the physiological mechanisms linking prolonged high-fat intake to dopamine deficiency remain elusive. We show that administering oleoylethanolamine, a gastrointestinal lipid messenger whose synthesis is suppressed after prolonged high-fat exposure, is sufficient to restore gut-stimulated dopamine release in high-fat–fed mice. Administering oleoylethanolamine to high-fat–fed mice also eliminated motivation deficits during flavorless intragastric feeding and increased oral intake of low-fat emulsions. Our findings suggest that high-fat–induced gastrointestinal dysfunctions play a key role in dopamine deficiency and that restoring gut-generated lipid signaling may increase the reward value of less palatable, yet healthier, foods.

 

[Michael Scally MD]

What Does the Average American Man Look Like Compared to Other Countries?
What Does the Average American Man Look Like Compared to Other Countries? &mdash; The Feed

From left to right: USA, Japan, Netherlands, and France

The 3D models were produced using the average waist, height, and BMI measurements of the average middle aged male.

The American male was just shy of OBESITY (BMI 30)!

USA
29 BMI
176.4 cm height
99.4 cm waist

Japan
23.7 BMI
171.4 cm height
82.9 cm waist

Netherlands
25.2 BMI
183.3 cm height
91 cm waist

France
25.55 BMI
174.4 cm height
92.3 cm waist

 

[Michael Scally MD]

Aspiration Therapy [Bulimia] Leads To Weight Loss in Obese Subjects

Sullivan S, Stein R, Jonnalagadda S, Mullady D, Edmundowicz S. Aspiration therapy leads to weight loss in obese subjects: a pilot study. Gastroenterology 2013;145(6):1245-52 e1-5. Elsevier

BACKGROUND & AIMS: Obese patients rarely achieve long-term weight loss with only lifestyle interventions. We evaluated the use of endoscopic aspiration therapy for obesity. Aspiration therapy involves endoscopic placement of a gastrostomy tube (A-Tube) and the AspireAssist siphon assembly (Aspire Bariatrics, King of Prussia, PA) to aspirate gastric contents 20 minutes after meal consumption.

METHODS: We performed a pilot study of 18 obese subjects who were randomly assigned (2:1) to groups that underwent aspiration therapy for 1 year plus lifestyle therapy (n = 11; mean body mass index, 42.6 +/- 1.4 kg/m(2)) or lifestyle therapy only (n = 7; mean body mass index, 43.4 +/- 2.0 kg/m(2)). Lifestyle intervention comprised a 15-session diet and behavioral education program.

RESULTS: Ten of the 11 subjects who underwent aspiration therapy and 4 of the 7 subjects who underwent lifestyle therapy completed the first year of the study. After 1 year, subjects in the aspiration therapy group lost 18.6% +/- 2.3% of their body weight (49.0% +/- 7.7% of excess weight loss [EWL]) and those in the lifestyle therapy group lost 5.9% +/- 5.0% (14.9% +/- 12.2% of EWL) (P < .04). Seven of the 10 subjects in the aspiration therapy group completed an additional year of therapy and maintained a 20.1% +/- 3.5% body weight loss (54.6% +/- 12.0% of EWL).

There were no adverse effects of aspiration therapy on eating behavior and no evidence of compensation for aspirated calories with increased food intake. No episodes of binge eating in the aspiration therapy group or serious adverse were reported.

CONCLUSIONS: In a pilot study, aspiration therapy appears to be a safe and effective long-term weight loss therapy for obesity.

 

[Michael Scally MD]

This Weight-Loss Pill Turns Into a Balloon to Fill Your Stomach
This Weight-Loss Pill Turns Into a Balloon to Fill Your Stomach - James Hamblin - The Atlantic

This is the Obalon system. http://www.obalon.com/hcp/en/

It is a pill that has a balloon inside. Obalon is a weight-loss device, marketed as an alternative to bariatric surgery, that claims to help people eat less and "push back from the table sooner."

Obalon begins to work when you swallow Obalon and it lands in your stomach. Obalon remains temporarily attached to a thin tube, through which doctors can inflate it.

They then remove the thin tube, and the balloon stays in your stomach for up to three months, bobbing around like buoy in gastric waters.

You can take up to three at a time, the manufacturers say. The ideas is that it partly fills the stomach to make the person feel full.

 

[Michael Scally MD]

Fan N, Sun H, Wang Y, et al. Midkine, a Potential Link between Obesity and Insulin Resistance. PLoS One 2014;9(2):e88299. PLOS ONE: Midkine, a Potential Link between Obesity and Insulin Resistance

Obesity is associated with increased production of inflammatory mediators in adipose tissue, which contributes to chronic inflammation and insulin resistance.

Midkine (MK) is a heparin-binding growth factor with potent proinflammatory activities. We aimed to test whether MK is associated with obesity and has a role in insulin resistance.

It was found that MK was expressed in adipocytes and regulated by inflammatory modulators (TNF-alpha and rosiglitazone). In addition, a significant increase in MK levels was observed in adipose tissue of obese ob/ob mice as well as in serum of overweight/obese subjects when compared with their respective controls.

In vitro studies further revealed that MK impaired insulin signaling in 3T3-L1 adipocytes, as indicated by reduced phosphorylation of Akt and IRS-1 and decreased translocation of glucose transporter 4 (GLUT4) to the plasma membrane in response to insulin stimulation. Moreover, MK activated the STAT3-suppressor of cytokine signaling 3 (SOCS3) pathway in adipocytes.

Thus, MK is a novel adipocyte-secreted factor associated with obesity and inhibition of insulin signaling in adipocytes. It may provide a potential link between obesity and insulin resistance.

 

[Michael Scally MD]

Orexigen Wins U.S. FDA Approval for Weight-Loss Pill
http://www.firstwordpharma.com/node/1234581

The FDA approved Orexigen Therapeutics and Takeda's Contrave (naltrexone/bupropion) as a treatment option for chronic weight management in addition to a reduced-calorie diet and physical activity.

The drug, which the agency rejected in 2011, is authorised for use in adults with a body mass index (BMI) of 30 or greater or those with a BMI of 27 or greater who have at least one weight-related condition such as hypertension, type 2 diabetes or dyslipidaemia.

According to the FDA, patients using a maintenance dose of Contrave should be evaluated after 12 weeks to determine if the treatment is working.

The agency indicated that if a patient has not lost at least 5 percent of baseline body weight at this time, the therapy should be discontinued, as it is unlikely that the patient will achieve and sustain clinically meaningful weight loss.

The FDA added that the product carries a warning about the increased risk of suicidal thoughts connected to the antidepressant bupropion and can causes seizures.

Further, the regulator said that Contrave can raise blood pressure and heart rate, so should not be used in patients with uncontrolled hypertension.

 

[sunnykmr234]

Paul L. Doering, a pharmacy professor at the University of Florida, said he doesn't "doubt for a minute that this drug will be wildly successful, at least at first," adding, "Time will ultimately tell if it is a good drug or not. In the meantime, I'm going to let somebody else be the first to take it."

 

[Michael Scally MD]

Legro RS, Kunselman AR, Meadows JW, et al. Time-related increase in urinary testosterone levels and stable semen analysis parameters after bariatric surgery in men. Reprod Biomed Online. http://www.rbmojournal.com/article/S1472-6483(14)00599-9/abstract

The aim of this prospective cohort study was to determine the time-course in androgen and semen parameters in men after weight loss associated with bariatric surgery. Six men aged 18-40 years, meeting National Institutes of Health bariatric surgery guidelines, were followed between 2005 and 2008. Study visits took place at baseline, then 1, 3, 6 and 12 months after surgery. All men underwent Roux-en-y gastric bypass (RYGB). At each visit, biometric, questionnaire, serum, and urinary specimens and seman analysis were collected. Urinary integrated total testosterone levels increased significantly (P < 0.0001) by 3 months after surgery, and remained elevated throughout the study. Circulating testosterone levels were also higher at 1 and 6 months after surgery, compared with baseline. Serum sex hormone-binding globulin levels were significantly elevated at all time points after surgery (P < 0.01 to P = 0.02). After RYGB surgery, no significant changes occurred in urinary oestrogen metabolites (oestrone 3-glucuronide), serum oestradiol levels, serial semen parameters or male sexual function by questionnaire. A threshold of weight loss is necessary to improve male reproductive function by reversing male hypogonadism, manifested as increased testosterone levels. Further serial semen analyses showed normal ranges for most parameters despite massive weight loss.

 

[Michael Scally MD]

FDA Approves Weight-Management Drug Saxenda
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm427913.htm

The U.S. Food and Drug Administration today approved Saxenda (liraglutide [rDNA origin] injection) as a treatment option for chronic weight management in addition to a reduced-calorie diet and physical activity.

The drug is approved for use in adults with a body mass index (BMI) of 30 or greater (obesity) or adults with a BMI of 27 or greater (overweight) who have at least one weight-related condition such as hypertension, type 2 diabetes, or high cholesterol (dyslipidemia).

Saxenda is a glucagon-like peptide-1 (GLP-1) receptor agonist and should not be used in combination with any other drug belonging to this class, including Victoza, a treatment for type 2 diabetes. Saxenda and Victoza contain the same active ingredient (liraglutide) at different doses (3 mg and 1.8 mg, respectively). However, Saxenda is not indicated for the treatment of type 2 diabetes, as the safety and efficacy of Saxenda for the treatment of diabetes has not been established.

Saxenda has a boxed warning stating that tumors of the thyroid gland (thyroid C-cell tumors) have been observed in rodent studies with Saxenda but that it is unknown whether Saxenda causes thyroid C-cell tumors, including a type of thyroid cancer called medullary thyroid carcinoma (MTC), in humans. Saxenda should not be used in patients with a personal or family history of MTC or in patients with multiple endocrine neoplasia syndrome type 2 (a disease in which patients have tumors in more than one gland in their body, which predisposes them to MTC).

 

[Michael Scally MD]

Liraglutide Facilitates Weight Reduction in Nondiabetic Patients

Liraglutide helps nondiabetic patients lose weight, but gastrointestinal side effects are common, according to an industry-supported study in the New England Journal of Medicine. The glucagon-like peptide-1 analogue, initially approved to treat type 2 diabetes (branded as Victoza), was approved for weight loss in nondiabetic patients in 2014 (as Saxenda).

Over 3700 nondiabetic patients with a body-mass index of at least 30 (or at least 27 if they also had dyslipidemia or hypertension) were randomized to receive liraglutide (3 mg/day) or placebo, injected subcutaneously. All patients also received lifestyle counseling.

At 56 weeks, mean weight loss was significantly greater with liraglutide than with placebo (8.4 vs. 2.8 kg). Gastrointestinal side effects occurred more commonly with liraglutide than with placebo (e.g., 40% vs. 15% for nausea, 16% vs. 4% for vomiting). Liraglutide recipients were also more likely to develop symptomatic gallbladder disease and pancreatitis.

A 1-year course of liraglutide resulted in moderate weight loss, at the expense of substantial gastrointestinal side effects. Of note, the cost of liraglutide will be prohibitive for many people: about US$1,100 monthly for those paying out of pocket.


Pi-Sunyer X, Astrup A, Fujioka K, Greenway F, Halpern A, et al. A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management. New England Journal of Medicine. 2015;373(1):11-22. http://www.nejm.org/doi/full/10.1056/NEJMoa1411892

BACKGROUND - Obesity is a chronic disease with serious health consequences, but weight loss is difficult to maintain through lifestyle intervention alone. Liraglutide, a glucagon-like peptide-1 analogue, has been shown to have potential benefit for weight management at a once-daily dose of 3.0 mg, injected subcutaneously.

METHODS - We conducted a 56-week, double-blind trial involving 3731 patients who did not have type 2 diabetes and who had a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of at least 30 or a BMI of at least 27 if they had treated or untreated dyslipidemia or hypertension.

We randomly assigned patients in a 2:1 ratio to receive once-daily subcutaneous injections of liraglutide at a dose of 3.0 mg (2487 patients) or placebo (1244 patients); both groups received counseling on lifestyle modification. The coprimary end points were the change in body weight and the proportions of patients losing at least 5% and more than 10% of their initial body weight.

RESULTS - At baseline, the mean (±SD) age of the patients was 45.1±12.0 years, the mean weight was 106.2±21.4 kg, and the mean BMI was 38.3±6.4; a total of 78.5% of the patients were women and 61.2% had prediabetes.

At week 56, patients in the liraglutide group had lost a mean of 8.4±7.3 kg of body weight, and those in the placebo group had lost a mean of 2.8±6.5 kg (a difference of −5.6 kg; 95% confidence interval, −6.0 to −5.1; P<0.001, with last-observation-carried-forward imputation).

A total of 63.2% of the patients in the liraglutide group as compared with 27.1% in the placebo group lost at least 5% of their body weight (P<0.001), and 33.1% and 10.6%, respectively, lost more than 10% of their body weight (P<0.001).

The most frequently reported adverse events with liraglutide were mild or moderate nausea and diarrhea. Serious events occurred in 6.2% of the patients in the liraglutide group and in 5.0% of the patients in the placebo group.

CONCLUSIONS - In this study, 3.0 mg of liraglutide, as an adjunct to diet and exercise, was associated with reduced body weight and improved metabolic control.

 

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There are different type of things someone can do. As we know there different types of obesity. The one can be more controlable is theone for eating to much inappropiate foods. Everything requires sacrifice and discipline


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