Insufficient insulin processing leads to obesity

 Obesity increases the risk of an imbalance in sugar metabolism and even of diabetes. A research group at the University of Basel has now shown the opposite is true as well: deficits in the body's insulin production contribute to obesity.

Poor nutrition, too little movement and too many pounds on the scale—lifestyle influences the risk of metabolic diseases like diabetes. But the relationship works the other way around as well, as a research group led by Dr. Daniel Zeman-Meier of the university's Department of Biomedicine and the University Hospital of Basel reports. If insulin production is compromised, as is the case in the early stages of type 2 diabetes, this can contribute to obesity. The researchers report their findings in the journal Nature Communications.

The research team focused on protease PC1/3, a key enzyme in the body that transforms various inactive hormone precursors into the final, active forms. If this enzyme isn't functioning properly in a person, the result can be severe endocrine disorders. The consequences include a feeling of uncontrollable hunger and severe obesity.

"Until now, it was assumed that this dysregulation is caused by a lack of activation of satiety hormones," explains the study's leader, Dr. Zeman-Meier. "But when we turned off PC1/3 in the brains of mice, the animals' body weight did not change significantly." The researchers concluded from this that something other than a brain malfunction must be responsible.

Incorrect activation of insulin leads to hunger and obesity

In their next step, they tested whether obesity could be caused by incorrect activation of other hormones. PC1/3 activates insulin, among other things. Insulin plays a key role in the regulation of blood sugar and fat metabolism. "Investigating the role of insulin production as a cause of obesity was obvious," says Dr. Zeman-Meier.

The researchers shut off PC1/3 specifically in the insulin-producing beta cells of the pancreas in mice. The animals consumed significantly more calories and soon became obese and diabetic.

"These results are also interesting because PC1/3 is reduced in the pancreas of patients with prediabetes," says Professor Marc Donath, the research group leader and final author of the study. This indicates that incorrect insulin activation could be not only a consequence, but also a cause of obesity.

But PC1/3 is also important in the weight regulation of healthy individuals, Donath says. The researchers were able to show that the gene expression of PC1/3 in the pancreas is negatively correlated with body weight in the general population—meaning that sufficient PC1/3 promotes a healthy body weight.

The finding that a defect in the insulin-producing beta cells is a trigger of obesity opens up new therapeutic possibilities. For example, it is conceivable that medications could be used to reduce the production of immature insulin precursors, creating a new tool in the fight against obesity and diabetes.

More information: Daniel T. Meier et al, Prohormone convertase 1/3 deficiency causes obesity due to impaired proinsulin processing, Nature Communications (2022). DOI: 10.1038/s41467-022-32509-4

https://medicalxpress.com/news/2022-09-insufficient-insulin-obesity.html

ICER reaffirms Qsymia as most cost-effective obesity treatment

 Last July, the cost-effectiveness drug watchdog ICER released a preliminary draft report that Vivus’ Qsymia was the most cost-effective option for weight loss. That decision has now been validated.

ICER made its final determination Wednesday that Qsymia, the brand name for the appetite suppressant phentermine combined with anticonvulsant topiramate, was more cost-effective for weight loss than other competitors such as Novo Nordisk’s Saxenda (liraglutide) and Wegovy (semaglutide) or Currax Pharmaceuticals’ Contrave (bupropion/naltrexone).

Vivus’ Qsymia beats out weight loss competitors in pricing watchdog's latest cost-effectiveness analysis

Per ICER:

At current prices and with commonly accepted cost-effectiveness benchmarks, results suggest that phentermine/topiramate in addition to lifestyle modification is cost effective compared with lifestyle modification alone. The cost effectiveness of treatment of obesity with semaglutide or liraglutide, in patients without diabetes mellitus, exceeds commonly used thresholds.

The watchdog mentioned that the health-benefit price benchmark for the more famous semaglutide, which also was more effective than the other Novo Nordisk drug and Contrave, is $7,500 to $9,800 per year. But at its current price point, it would require the drug be discounted somewhere between 44-57% of its wholesale price.

ICER reviewers also added that if Qsymia wasn’t performing well in certain patients, Contrave may be the next best cost-effective option. The reviewers noted in their report that there were a few limitations to analysis, including the full impact of the drugs in patients with chronic kidney diseases or conditions where weight loss may be beneficial.

Vivus nabbed approval for Qsymia in adults in 2012, followed by a tumultuous history that ended up with Vivus filing for bankruptcy. Years later, the FDA expanded Qsymia’s weight loss indication from just adults to use in adolescents. However, the regulatory agency added the condition that the drug is given on top of both a reduced-calorie diet and increased physical activity.

Vivus CEO John Amos told Endpoints News last month after ICER’s draft report that so far, Qsymia is averaging around $40 million to $42 million in annual sales and in the range of 400,000 scripts every year. And in approvals, Qsymia has been approved outside the US in South Korea, the five Nordic countries and Poland — with more approvals pending in other European countries such as the UK.

ICER’s decision comes the same week Currax launched a new ad campaign for Contrave, focused on the drug as a choice for emotional eating connected to obesity and overweight conditions.

https://endpts.com/icer-reaffirms-qsymia-as-most-cost-effective-obesity-treatment-in-final-report/

Cal. judge tosses FDA lawsuit targeting a clinic offering unproven stem cell treatments

 A federal judge in Riverside declared a California stem cell treatment firm to be exempt from Food and Drug Administration regulations, opening the door to the further proliferation of clinics offering therapies the FDA says are scientifically unproven and potentially dangerous.

In the ruling issued late Tuesday, Judge Jesus G. Bernal of Riverside declined to block California Stem Cell Treatment Center from continuing to offer purported stem cell treatments to customers.

Bernal accepted the center’s position that its treatments qualified for an exception from FDA regulations, in part because they were tantamount to surgical procedures.

Bernal’s ruling, which came more than a year after a seven-day trial in May 2021 and closing arguments last August, potentially undermines a years-long FDA crackdown on clinics claiming that stem cells can treat or cure conditions including orthopedic injuries, Alzheimer’s and Parkinson’s diseases, multiple sclerosis, and erectile dysfunction.

The “defendants are engaged in the practice of medicine,” Bernal ruled, “not the manufacture of pharmaceuticals.”

The FDA regulations, however, define drugs much more broadly than the “manufacture of pharmaceuticals” — rather, as any article that is “intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease.” Any such articles, the agency says, must have agency approval — and the California center’s treatments do not.

“To me, the language of his ruling sounded almost like it was written by the defendants,” Paul S. Knoepfler, a UC Davis stem cell biologist who has been tracking the proliferation of such clinics for years, observed in his laboratory blog.

“The Bernal ruling will not be a good thing for careful oversight of stem cell clinic practices,” Knoepfler said. “It’s concerning to think about more people being put at risk.”

Knoepfler suggested that the FDA would feel duty-bound to appeal Bernal’s ruling in order to protect its regulatory campaign, and because it conflicts with federal court rulings in a nearly identical case the FDA brought against Florida clinics in Miami federal court.

The agency told me by email that it is “reviewing the court’s decision and does not have further comment at this time.”

Bioethicist Leigh Turner of UC Irvine, who has collaborated with Knoepfler on tracking the growth of the stem cell clinic industry, agreed that Bernal’s ruling is “an enormous setback for the FDA in an area where they’ve struggled for many years.... For people who work in this industry, it’s great news. But not for anyone concerned about patient safety, misinformation or disinformation.”

As part of its crackdown, the FDA has written hundreds of letters warning stem cell clinics that they’re violating the law, and has pursued some in court.

After issuing regulations in 2017 declaring that treatments using unproven stem cell therapies were illegal, the FDA suspended its enforcement for more than three years to give clinic operators time to comply with FDA rules. The agency’s forbearance, however, opened the door to a further proliferation of suspect clinics.

By March 2021, according to a survey by Turner, nearly 1,500 U.S. businesses were pitching the suspect treatments at more than 2,700 clinics, reflecting a torrent of openings since 2016, when Turner and Knoepfler jointly started tracking the field.

“More than four times as many businesses than were identified five years ago are selling stem cell products that are not FDA-approved and lack convincing evidence of safety and efficacy,” Turner wrote last year.

Some clinics have charged customers more than $10,000 for the unproven treatments, plying the customers with unsupported claims of medical success. The fees are seldom, if ever, covered by health insurance. Some treatments resulted in serious medical complications.

The FDA also has warned the public that “some patients seeking cures and remedies are vulnerable to stem cell treatments that are illegal and potentially harmful.”

The FDA has approved stem cell treatments only for disorders of the blood-producing, or hematopoietic, system. No other stem cell treatment claims have been scientifically validated, the agency says.

“Stem cells have been called everything from cure-alls to miracle treatments,” the agency says in its public warning. “But don’t believe the hype.”

Bernal’s ruling conflicts with a 2019 decision by U.S. District Judge Ursula Ungaro of Miami, who ordered a Florida clinic shut down after the FDA asserted that its purported stem cell therapies were scientifically unproven and illegal.

Ungaro’s decision was upheld last year by the 11th Circuit U.S. Court of Appeals, which found that the clinic’s claim of exemption from FDA regulation on grounds similar to those claimed by the California center, didn’t apply. “No reasonable fact-finder could disagree,” the three-judge appellate panel ruled.

As it happens, in its finding the appellate panel specifically rejected an earlier ruling by Bernal, in which he denied the FDA’s request for a preliminary injunction against the California center and set the case for trial. The appellate ruling isn’t binding precedent for federal courts outside the 11th Circuit, which covers parts of the Southeast.

The FDA’s lawsuits against the Florida clinic and the California center were almost identical and filed on the same day, May 9, 2018. In both cases, the agency asserted that the clinics were in effect purveying illegal drugs as defined by federal law.

The lawsuits were part of an agency effort to clamp down on the burgeoning trade in stem cell-related therapies. The California lawsuit named the center’s founders, Elliott Lander and Mark Berman, as defendants. Berman died in April

The California Stem Cell Treatment Center has operated clinics in Beverly Hills and Rancho Mirage, and provides treatment protocols and other assistance to other clinics around the country.

In its Florida and California lawsuits, the FDA targeted a widespread practice utilized by both clinics in which fat cells are extracted from a customer by liposuction. The extraction is treated to produce a fluid purportedly rich in stem cells known as a “stromal vascular fraction” or SVF, which is injected back into the same subject.

Both sets of defendants asserted in their defense that their activities qualified for exceptions from FDA drug regulations afforded to surgical procedures involving the use of a patient’s own tissues as well as the use of “minimally manipulated” tissues. The agency’s position is that the fat extractions are so heavily treated before the reinjections that the treatments fall outside those exceptions.

In his ruling, Bernal drew extensively and verbatim from California Stem Cell Treatment Center’s proposed findings of facts and scarcely at all from the FDA’s proposal. His ruling incorporated several scientific errors, according to Knoepfler.

For example, Bernal accepted the center’s assertion that “unlike manufactured drugs, the SVF Surgical Procedure does not create any cellular or tissue-based product that did not previously exist within the patient.”

In fact, Knoepler says, “there is no equivalent of SVF already in the body.”

https://www.latimes.com/business/story/2022-08-31/federal-judge-tosses-lawsuit-targeting-stem-cell-clinic

Intellia Genome Candidate Receives FDA's Orphan Drug Designation

 

Intellia Therapeutics Inc. said Thursday that the Food and Drug Administration granted NTLA-2002 orphan drug designation. The clinical stage genome editing company said NTLA-2002, its genome editing candidate, is currently being evaluated in a Phase 1/2 study in adults with Type I or Type II hereditary angioedema, a genetic disorder characterized by recurring and unpredictable inflammatory attacks. Intellia said NTLA-2002 is designed to knock out the target gene kallikrein B1 to reduce plasma kallikrein activity and thus prevent hereditary angioedema attacks. Chief Executive John Leonard said the company will present interim data on safety, kallikrein reduction and hereditary angioedema attack rate data on Sept. 16 at the 2022 Bradykinin Symposium. https://www.marketscreener.com/quote/stock/INTELLIA-THERAPEUTICS-IN-27506682/news/Intellia-Therapeutics-NTLA-2002-Genome-Candidate-Receives-FDA-s-Orphan-Drug-Designation-41675278/

FEMA To Cover El Paso Costs Of Busing Illegal Immigrants To New York, Official Says

 by Caden Pearsen via The Epoch Times,

The Biden administration will reimburse El Paso city, which is following the lead of other border cities in Texas and Arizona to transport illegal immigrants to New York on buses, according to a city official.

El Paso officials this week sent 35 Venezuelans to New York City on chartered buses as they moved to address the growing number of illegal immigrants arriving via the U.S. southern border from South America, local media reported.

The Federal Emergency Management Agency (FEMA) has said it will reimburse local governments and NGOs for the cost of aiding and transporting the illegal aliens, according to Mario D’Agostino, the deputy city manager of El Paso.

“OEM has sponsored and provided transportation services for migrants out of El Paso, which is reimbursable through FEMA,” D’Agostino said in a statement obtained by El Paso Matters, referring to the city’s Office of Emergency Management.

“OEM has sponsored charter buses to include a recent transport to New York City, this was the preferred destination for those without any means to travel.”

FEMA did not immediately respond to a request for comment.

D’Agostino said that the last time El Paso officials arranged a charter bus to transport illegal immigrants elsewhere was on June 21, when 50 individuals were sent to Dallas to be aided by a group of area faith leaders, El Paso Matters reported.

The mayors of New York City and Washington, Eric Adams and Muriel Bowser, both Democrats, have criticized the busing program as politically motivated.

However, Gov. Greg Abbott (R-Texas) has said that individuals apprehended along the U.S. southern border voluntarily chose to go to their cities.

More than 8,900 illegal aliens have been bused out of Texas border cities to New York City and Washington, according to Abbott’s office. Both New York City and Washington are sanctuary cities.

DC, New York ‘Ideal Destinations’ for Illegal Immigrants

Around 4.9 million people have illegally entered the United States from Mexico since President Joe Biden took office in January 2021, according to a report released by the Federation for American Immigration Reform on Aug. 16.

Abbott has previously said that Biden’s “open border policies” and “refusal to acknowledge the crisis” they are causing forced him to take “unprecedented action,” which includes sending illegal immigrants to New York City and Washington.

“In addition to Washington, D.C., New York City is the ideal destination for these migrants, who can receive the abundance of city services and housing that Mayor Eric Adams has boasted about within the sanctuary city,” Abbott said earlier in August.

The Pentagon has denied requests from both Adams and Bowser for federal support, including National Guard deployments, to help their cities cope with the influx of illegal immigrants.

Abbott’s office has said that the busing mission, called “Operation Lone Star,” provides “much-needed relief to our overwhelmed border communities” in Texas.

“Operation Lone Star continues to fill the dangerous gaps left by the Biden Administration’s refusal to secure the border,” Abbott’s office said in a statement.

In addition to the constant stream of illegal immigrants, U.S. authorities along the border with Mexico have stopped the “smuggling of drugs, weapons, and people” into the United States, as well as “transnational criminal behavior between ports of entry,” according to the statement. This includes over 335.5 million “lethal fentanyl doses,” Abbott said on Twitter.

https://www.zerohedge.com/political/fema-cover-el-paso-costs-busing-illegal-immigrants-new-york-official-says

America, Exporter of the Gender Revolution

 Is the U.S. State Department about to classify Sweden, Finland, and the U.K. as human rights abusers? According to an internal memo from Secretary Antony Blinken (leaked to me by an officer in the department’s Foreign Service) and circulated among employees last week, the answer might be yes.

The memo represents an effort by Secretary Blinken to carry out President Biden’s Executive Order 14075 from last June. That order instructs agencies of the federal government to do what they can to stop “conversion therapy” for “LGBTQI+” people. Following its release, Biden appointed Jessica Stern as Special Envoy to Advance the Human Rights of LGBTQI+ Persons, a position created by the Obama administration but left unfilled under Donald Trump. Stern, who goes by “all pronouns,” had previously served as executive director at OutRight Action International, an advocacy organization with a permanent presence at United Nations headquarters in New York. OutRight has borrowed arguments against “conversion therapy” for sexual orientation (where the evidence against the practice is strong) and applied them, unscientifically, to “gender identity” (where studies have consistently shown that cross-gender identification in children is, for the vast majority of those who experience it, a passing phase). This strategy of piggybacking off public ignorance about the difference between homosexuality and transgenderism is by now familiar. And lest it be thought that politicians know better, Biden himself seems unable to differentiate between sexual orientation and gender identity.

The Biden administration has defined “conversion therapy” as any effort to “suppress or change an individual’s . . . gender identity.” The Blinken memo cites as an authority the American Academy of Child and Adolescent Psychiatry, an organization that, like the American Academy of Pediatrics, has fallen victim to capture by a small but vocal and well-organized group of ideologues, among them Jack Turban. The memo relies on the United Nations Independent Expert on sexual orientation and gender identity, Victor Madrigal-Borloz, to clarify that “conversion” means only efforts to change a transgender identity into a “cisgender one.” Thus, a hypothetical scenario in which a child is put under intense pressure to become trans, even if this means medicalization, would technically not count as “conversion.” At the first signs of a child’s gender distress or confusion, the only legitimate, “human rights”-respecting outcome of treatment, according to the Biden administration, is social transition followed, in most cases, by body modification.

Predictably, the Blinken memo contains no evidence or arguments for its claims about “conversion therapy,” but instead defers to “every major medical and mental health association in the United States.” In fact, however, medical groups like the AAP and AACAP have not followed the science on this issue, instead allowing activists to dictate policy positions based on pseudoscientific claims, egregious mischaracterizations of available studies, and, in some cases, outright fabrications of data. Anyone with above-average intelligence, a basic grasp of scientific methods, and enough time and patience to master the literature on this issue will easily come to the same conclusion. Medical authorities in Sweden, Finland, and the U.K. have already done so, as has Florida. France and Australia may soon follow suit.

Ominously, the Blinken memo defines “conversion therapy” to include not only “electric shock” and “corrective rape” but also “talk therapy.” That’s right: using psychotherapy to help a child in distress about her changing body feel more comfortable in it rather than undergo expensive, risky, and irreversible hormonal and surgical interventions is, according to the State Department, no different from electrocuting gays and lesbians in order to “liberate” them from their innate sexual attractions.

The problem, for countries like Sweden, Finland, and the U.K., is that medical authorities in these places have concluded over the past two years that the evidence for pediatric “gender affirming care” is extremely weak and that, as a result, hormonal and surgical interventions are (as Finland’s COHERE put it) “experimental.” Sweden and Finland are now instructing clinicians who deal with minors to utilize an approach that emphasizes talk therapy as the first line of defense and “affirming” drugs only in extreme situations, if ever. Sweden has banned gender surgeries for minors—surgeries that are practiced in the United States, notwithstanding the repeated gaslighting of gender clinics and left-of-center media outlets.

The Blinken directive effectively turns American consulates and embassies into global “gender affirming” spies. Embassies are instructed to “submit robust information on the so-called ‘conversion therapy’ practices” of host countries “as part of the annual Human Rights Reports.” Jessica Stern’s office will then devise an “action plan to combat the practice across foreign policy and foreign assistance lines of effort.”

The harms from the new policy will be tangible. First, bullying countries into not providing talk therapy to youth in distress over their developing bodies will, if successful, harm gay youth. Gender nonconformity and associated distress are very common phases of gay and lesbian youth development, as confirmed by research, clinical experience, and many firsthand accounts. If not allowed to talk about their feelings, these teenagers will be pumped full of synthetic hormones; some will find themselves under the surgeon’s knife. In Iran, being gay is punishable by death, but the condemned can avoid this fate by agreeing to “sex change” procedures. It is a sad irony that under the new Biden-Blinken policy, the Ayatollahs’ attitude toward homosexuality is now considered more in line with human rights than Europe’s most progressive welfare states. The Biden administration’s manipulation of American public solicitude for gay people in the interest of radical gender policies is nothing short of cynical.

Second, making “gender affirming care” a foreign policy requirement will dilute the moral authority of America’s broader commitment to human rights. Are foreign leaders now to believe that China’s persecution of its Uyghur minority, Venezuela’s use of arbitrary detentions and torture against regime dissidents, and the Taliban’s systematic oppression of women and girls are all on par with, say, Sweden urging its psychologists to help kids feel comfortable in their own bodies? Transgender activists will argue that ending “conversion therapy” and pushing back against other state-sponsored abuses are not mutually exclusive, but of course they are—and pretending otherwise will empower critics of the United States to argue that our understanding of human rights is absurd.

Third, even taking at face value the Biden administration’s own goal of promoting the wellbeing of transgender-identified people, it is hard to see how the new directive accomplishes that. What happens when an impoverished Sudanese teenager begins hormone therapy or gets a mastectomy and serious complications arise, as they so often do for these procedures? Medical services in many developing countries are notoriously subpar, and if risk of serious complications from specialized and as-yet experimental hormonal and surgical interventions is high in the United States, that risk is compounded where transitioned minors have no access to specially trained doctors with adequate medical equipment. It’s hard to see how rushing kids to experimental gender transition in countries without proper medical infrastructure serves their health needs.

Further, for countries with deep suspicions toward the West—countries, in other words, likely to be the most intolerant of transgender-identified people—the association of cross-gender identification with American foreign policy enables traditionalists to frame social change as cultural imperialism. Even assuming, for the sake of argument, youth medical transgenderism is a worthy goal, it defies reason that American soft power can aptly promote it.

In line with Tip O’Neill’s famous observation that “all politics is local,” Biden’s order to the State Department and Secretary Blinken’s interpretation of that order are, in all likelihood, driven more by domestic political calculation than by strategic consideration about protecting human rights abroad. As Biden himself made clear at the time, EO 14075 was a response to Republican-held states passing laws like Florida’s Parental Rights in Education Act (mischaracterized as “Don’t Say Gay”) and various bans on pediatric medical transition. This development in American foreign policy is a sobering (if haphazard) example of policy expansion.

Other implications of the new “human rights” policy are anyone’s guess. Will the United States use its long financial arm to pressure Sweden, Finland, and the U.K. to restore “affirmative care,” against the judgment of experts in those countries that—unlike here—have conducted systemic evidentiary reviews? Will economic and cultural cooperation between the U.S. and other Western nations be made contingent on these countries demonstrating that a sufficient number of teenagers every year are medically transitioned? (Bureaucrats like to define objectives and measure outcomes numerically.) Or will the harm be largely symbolic and reputational, underscoring the extent to which American elites are willing to sacrifice reason and common sense to the ever-proliferating and increasingly destructive demands of wokeness?

In 2009, Barack Obama notoriously kicked off his presidency with an “apology tour” in which he lamented American “arrogance” in foreign policy. Speaking to the Muslim world from a podium in Cairo, Obama implied that “colonialism” was to blame for Muslim nations’ failings. The president assured his audience that “America does not presume to know what is best for everyone,” and that “it is important for Western countries to avoid impeding Muslim citizens from practicing religion as they see fit.” Under President Biden, it would appear that cultural arrogance and “colonialism” (as defined in the contemporary academy) are once again staples of American foreign policy.

Leor Sapir is a fellow at the Manhattan Institute.

https://www.city-journal.org/state-dept-launches-international-gender-pressure-campaign

With seatbelt use down, car crash fatalities have risen 20%

 According to a new federal government study, seatbelt use is down and fatality crashes are up, with the number of deaths involving people thrown from a vehicle rising by 20% nationally from 2019 to 2020.

Traffic fatalities regardless of whether or not people were using seatbelts were up 7.2% in 2020 compared to 2019.

According to Pemco Insurance spokesperson Allison Leep, “National Highway Traffic Safety Administration (NHTSA) fatality statistics, which compare 2021 to 2020, show deaths increased.” Here are the numbers:

   .    16% increase in multi-vehicle crashes

• 14% increase among drivers 65 and older
• 13% increase among pedestrians
• 13% increase in crashes involving at least one large truck.

Leep says that last year was the deadliest year on our roads in 16 years here in Washington state. The Pacific Northwest overall was much worse for traffic fatalities, which saw a 10.5% increase in 2021 compared to 2020. NHTSA released those numbers in spring 2022 and noted they were partially based on statistical projections.

KIRO Newsradio asked Leep why drivers aren’t wearing their seatbelts, and she said the study finds that drivers are more than likely impaired and just don’t buckle up.

https://mynorthwest.com/3615138/with-seatbelt-use-down-car-crash-fatalities-have-risen-20/