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Sunday, June 9, 2019

Health paradox: New US diabetes cases fall as obesity rises

The number of new diabetes cases among U.S. adults keeps falling, even as obesity rates climb, and health officials aren’t sure why.
New federal data released Tuesday found the number of new diabetes diagnoses fell to about 1.3 million in 2017, down from 1.7 million in 2009.
Earlier research had spotted a decline, and the new report shows it’s been going on for close to a decade. But health officials are not celebrating.
“The bottom line is we don’t know for sure what’s driving these trends,” said the lead author of the new report, Dr. Stephen Benoit of the Centers for Disease Control and Prevention. Among the possibilities: Changes in testing and getting people to improve their health before becoming diabetic.
The report was published by the journal BMJ Open Diabetes Research & Care. The statistics run through 2017. Last year’s numbers are not yet available, Benoit said.
Diabetes is a disease in which sugar builds up in the blood. The most common form is tied to obesity, and the number of diabetics ballooned as U.S. obesity rates increased.
But other factors also might have pushed up annual diabetes diagnoses from 2000 to 2010, and they may partly explain why the numbers have been going down since, some experts said.
First, the diagnostic threshold was lowered in the late 1990s. That caused more people to be counted as diabetics, but the impact of that may have played out.
“We might have mined out a lot of the previously unrecognized cases” and so new diagnoses in the last several years are more likely to be actual new illnesses, said Dr. John Buse, a University of North Carolina diabetes expert.
Meanwhile, doctors have increasingly used a newer blood test to diagnoses diabetes. It’s much easier than tests that required patients to fast for 12 hours or to undergo repeated blood draws over two hours.
The American Diabetes Association recommended the new test, known as the hemoglobin A1C blood test, for routine screening in 2010. Because it’s easier to do, it would be expected to lead to more diagnoses. But some experts say it may miss a large proportion of early cases in which people aren’t showing symptoms. “You may be missing people that would have been diagnosed” with older tests, Benoit said.
Another possibility: Increasingly, more doctors have been diagnosing “prediabetes,” a health condition in which blood sugar levels are high but not high enough to hit the diabetes threshold. Physicians typically push such patients into exercise programs and urge them to change their diet.
“Prediabetes is becoming a more accepted diagnosis” and may be causing an increasing number of patients to improve their health before becoming diabetic, said Dr. Tannaz Moin, a UCLA expert.
The new report is based on a large national survey conducted by the government every year. Participants were asked if they had been diagnosed with diabetes, and also if the diagnosis was made in the previous year.
It found the rate of new diabetes cases fell to 6 per 1,000 U.S. adults in 2017, from 9.2 per 1,000 in 2009. That’s a 35 percent drop, and marks the longest decline since the government started tracking the statistic nearly 40 years ago, according to the CDC.
The decrease was mainly seen among white adults, the researchers said.
Meanwhile, the overall estimate of how many Americans have diabetes — whether the diagnosis is recent or not — has been holding steady at 80 per 1,000 U.S. adults. That translates to about 21 million Americans.
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‘Mix and Match’ Options Emerging in Automated Insulin Delivery

As automated insulin delivery is rapidly evolving, interchangeability between insulin pumps and sensors on the various platforms is emerging as a key component to moving the field forward.
Here at the American Diabetes Association (ADA) 2019 Scientific Sessions, many attendees who follow the technology were surprised by the announcement that Medtronic will be working with the nonprofit Tidepool to create an interoperable automated insulin pump system, a category the US Food and Drug Administration (FDA) now calls “alternate controller enabled (ACE)” pumps.
Currently, Medtronic manufactures the only commercially available hybrid closed-loop system (previously known as the artificial pancreas) and is the only company to manufacture both the insulin pump and continuous glucose monitor (CGM) components of such automated insulin delivery systems.
Tidepool is a data hub for patients and clinicians to combine and view data from insulin pumps, CGMs, and blood glucose meters. It also stores information about meals, exercise, and other daily events. As a next step, the organization is now developing the Tidepool Loop app, which would serve as a platform allowing interoperability between various diabetes devices.
“Pairing our future Bluetooth-enabled MiniMed ACE pump with Tidepool Loop would enable an FDA-approved interoperable system — with pump and CGM components — that may be mixed and matched with the Tidepool Loop app as the person with diabetes chooses,” Medtronic announced on June 6, the day before the conference.

It’s Tough Being First…

Here at the meeting, an oral abstract session on automated insulin delivery held on June 8 included a presentation from Stanford University on real-world clinical experience with Medtronic’s hybrid MiniMed 670G system in which — similar to a report at ENDO 2019: The Endocrine Society Annual Meeting in March — clinical experience with this first commercially available artificial pancreas has been less than ideal, with many patients abandoning the system and frequently citing difficulties with the sensor as the reason.
“It’s always tough being first, from the standpoint of the 670G, and this cooperation [with Tidepool] is going to give folks all sorts of other options,” Rayhan Lal, MD, of Stanford University, California, told Medscape Medical News. “Other companies are starting to collaborate, and I think to stay in the space you have to cooperate with others in the field,” he added.
Indeed, session moderator Alanna Weisman, MD, University of Toronto, Ontario, Canada, told Medscape Medical News, “Interchangeability is a big issue…I think patients would like to be able to mix and match and choose the devices that work best for them.”
Weisman said she was surprised by the Medtronic announcement, but that “it’s very exciting.”
Also presented during the same abstract session were new data on the third generation of Beta Bionics’ investigational iLet system, including its use with two different sensors — the Dexcom G5 and implantable Eversense(Senseonics).

Real-World Results Differ From Research

Lal presented data from a 1-year prospective observational study of 79 adult and pediatric patients (aged 9-61 years) who started using the 670G system at Stanford between May 2017 and May 2018. Most (72%) had previously used a Medtronic pump, 51% had previously used a Dexcom sensor, and 33% had previously used a Medtronic CGM.
The proportions discontinuing the “auto mode” function of the 670G rose over time, from just 1% at week 1 to 40% at 6 months to 46% at 1 year. Compared to those who continued using auto mode, those who discontinued were significantly younger (22.3 vs 31.5 years; P = .02) and had been using the Medtronic Guardian 3 sensor for less time prior to entering auto mode (P = .001).
Of note, although it wasn’t significant due to low numbers, participants who were using a Dexcom along with the 670G – and feeding the numbers from the Dexcom into the 670G system – were also more likely to discontinue auto mode (31% vs 13%; 8 vs 4 patients; P = 0.11).
“Sensor issues” accounted for 60% of the reasons listed for abandoning auto mode at 1 year, including need for multiple daily calibrations, sensor alerts, and systems automatically exiting auto mode and requiring additional fingersticks. Other cited reasons, such as problems obtaining supplies and fear of hypoglycemia, were less common (17% and 10%, respectively).
“Education and adequate preparation are crucial in setting realistic expectations for closed-loop systems. A focus on usability and human factors is necessary to ensure patients stay on treatment,” Lal concluded.
In separate press releases issued on June 8, Medtronic announced enrolment of the first study participants in a pivotal trial of its Bluetooth-enabled 780G advanced hybrid closed-loop system, designed to automate the delivery of correction boluses to address current or anticipated high blood glucose levels based on sensor readings, and a next-generation Guardian CGM, designed to improve accuracy and system performance and reduce the number of calibrations.

iLet Works With Different Sensors, Ultimately to Include Glucagon

Rabab Z. Jafri, MD, a pediatric endocrinologist at Massachusetts General Hospital, Boston, presented the iLet data, the first on safety and efficacy of the Gen3 iLet, “a purpose-built bionic pancreas platform” designed to administer both insulin and glucagon, although the current data are for use with insulin alone.
The iLet uses only body weight to initialize and uses autonomous machine learning to adapt to the individual user. Unlike other closed-loop systems, it doesn’t require the user to enter carbohydrate counts, basal rates, or correction factors. It responds to input from the Dexcom G5 or Eversense CGM.
In the current study, 34 adult outpatients were enrolled who had type 1 diabetes. A random-order cross-over was used to compare the insulin-only mode of the iLet to usual care for 7 days each. Mean CGM glucose values were 155 mg/dL while wearing the insulin-only iLet versus 162 mg/dL with usual care (P = .09). Time spent with blood glucose < 54 mg/dL didn’t differ significantly (P = .64), but iLet did improve time spent in the 70-180 mg/dL range compared with usual care (70% vs 62%; P = .01).
Results didn’t differ between the 17 patients using the Dexcom G5 and the 17 patients using the Eversense.
Findings from this study have led to improvements in the design of the Gen4 iLet, Jafri noted.
Separately on June 6, Beta Bionics and Zealand Pharma announced resultsfrom the first home-use study of the Gen3 bihormonal configuration of iLet, using Zealand’s stable aqueous glucagon analog dasiglucagon.
Ten adults with type 1 diabetes wore the bihormonal and insulin-only iLet configurations for 1 week each. During the bihormonal period, they achieved a mean CGM glucose level of 139 mg/dL on days 2-7 of use compared with 149 mg/dL during the insulin-only period (P < .01).
During the bihormonal period, participants spent 79% of the time with CGM glucose levels in the range of 70-180 mg/dL on days 2-7 of use compared with 71% during the insulin-only period (P < .01).

iLet Available Soon; Patients Want Choices

Principal investigator Steven Russell, MD, Massachusetts General Hospital, Boston, told Medscape Medical News that Beta Bionics plans to start a pivotal study with the Gen4 version — the one they hope to bring to market — next year.
The company anticipates that the insulin-only configuration could be commercially available within 2 years, while the bihormonal version will take longer since it will involve a new drug approval.
Weisman, who published a meta-analysis of closed-loop systems in 2017, told Medscape Medical News that although her data show the dual-hormone version of iLet has some benefits over the single-hormone version, they also add complexity, so “it’s a trade-off.”
That’s part of the decision-making clinicians will need to help patients within the very near future as these systems reach the market, she noted.
Regarding interchangeability of devices in these systems, Weisman observed: “Patients want choices. I think being able to combine systems to fit their needs makes sense.”
Jafri and Weisman have reported no relevant financial relationships. Lal has reported being a consultant for Abbott Diabetes Care and receives research funding from Medtronic. Russell has reported being on advisory panels for Companion Medical and Unomedical, is a consultant for Flexion Therapeutics, and receives research support from Beta Bionics, MITRE Corporation, Novo Nordisk, and Zealand Pharma. He also has other relationships with ADOCIA, Ascensia Diabetes Care, Lilly Diabetes, Roche Diabetes Care, and Senseonics.
ADA 2019 Scientific Sessions. Presented June 8, 2019. Abstract 80-OR
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Sanofi Soliqua Phase 3 meets primary objective: American Diabetes Assn

Soliqua® Phase 3 results significantly lowered blood sugar levels compared to GLP-1 receptor agonist treatments
  • Patients switched to Soliqua reached an average blood sugar below the American Diabetes Association recommended level of 7%
  • Full Phase 3 data presented today at the American Diabetes Association (ADA) 79th Scientific Sessions

In a Phase 3 study[1] evaluating adults with type 2 diabetes inadequately controlled by GLP-1 receptor agonist (GLP-1 RA) treatments, Soliqua®/Suliqua®[2] (insulin glargine 100 Units/mL and lixisenatide) met the primary study objective by demonstrating a statistically superior reduction of average blood sugar level (HbA1c) after 26 weeks, compared with continuing GLP-1 RA treatment.
The LixiLan-G study included either a daily or once-weekly GLP-1 RA treatment as comparator. More patients who switched to Soliqua achieved HbA1c levels below 7%, a target recommended by the ADA, compared with those who stayed on previous GLP-1 RA therapy. More patients who switched to Soliqua also achieved the composite endpoint of HbA1c below 7% without documented symptomatic hypoglycemia (low blood sugar levels).
The study showed a safety profile consistent with the established profiles of the treatments studied: the most common classes of adverse event were gastrointestinal events (i.e., nausea, diarrhea and or vomiting) and hypoglycemia.
The full Phase 3 data results were presented today for the first time as an oral presentation at the 79th Scientific Sessions of the ADA in San Francisco.
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Abbott and Tandem in the spotlight at diabetes meeting

  • Leading medical device companies have arrived in San Francisco for the American Diabetes Association (ADA) meeting, setting the stage for updates that will shape the continuous glucose monitor (CGM) and insulin pump markets.
  • Companies including Dexcom and Roche released news ahead of the event. Roche partnered with diabetes care platform GlucoMe, while Dexcom entered into a diabetes data exchange with Companion Medical.
  • More significant updates are scheduled for the weekend, when Abbott will share details of its FreeStyle Libre 2 CGM system and Tandem Diabetes Care will present data from a pivotal trial of its automated insulin delivery system.

In a preview of the annual meeting, analysts at Cowen picked the Abbott and Tandem presentations as some of the most significant of the event. After a year of growth at its diabetes unit, Abbott will use the ADA meeting to share information on the second generation of FreeStyle Libre.
Libre 2 is under review at the FDA but Abbott CEO Miles White declined to predict when it will come to market in the U.S. when talking to investors in April. The Cowen analysts think the approval could be imminent but, even if Abbott is unable to launch the device at ADA, it is likely to share additional details of the device across multiple planned presentations.
Abbott filed for approval of Libre 2 as an interoperable continuous glucose monitoring (iCGM) system, meaning it will need to meet the special controls established by FDA when it authorized the Dexcom G6 last year. Libre 2 needs to exceed multiple performance standards to qualify as an iCGM but it is unclear whether Abbott will share detailed data at ADA.
“We may not get a comprehensive update on performance improvements vs. the current Libre system (which should be required to meet iCGM special controls), as headline mean absolute relative difference/outlier data may not tell the full story,” the Cowen analysts wrote.
The biggest news outside of the CGM space may come from Tandem, which is due to share data from a pivotal trial of its automated insulin delivery system, Control-IQ. Based on previous data, Cowen analysts expect patients using the system to achieve a time in range of over 75% and spend less than 2% of their time below the bottom end of the safe blood sugar range.
Tandem plans to submit a regulatory filing for Control-IQ to FDA next month and bring the device to market by the end of the year. The timeline for launch has slipped somewhat as it has taken Tandem longer than anticipated to access the study data.
Abbott and Tandem are both due to present information about their devices on Sunday. Some of their peers shared news ahead of the event.
Senseonics Holdings revealed FDA approved a dosing claim for Eversense that will enable patients who download an app to use the CGM system as a replacement for fingersticks.
T1D Exchange partnered with DreaMed Diabetes to provide its artificial intelligence-based decision support technology to six clinics. The technology, DreaMed Advisor Pro, is designed to help high-risk patients maintain balanced glucose levels.
Dexcom and Roche also shared their updates on the diabetes care platform GlucoMe and the diabetes data exchange with Companion Medical, respectively.
The Roche partnership with GlucoMe grew out of the startup hub it helped to set up last year and furthers its efforts to build a web of digital products around its diabetes devices.
The Dexcom agreement will enable users of Companion Medical’s smart insulin pen to display insulin data on Dexcom’s diabetes management software.
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Blue State Seniors Like Private Medicare, Complicating Single Payer

Seniors in progressive U.S. states are choosing private Medicare Advantage plans more so than the national average even as the politicians who want to represent them talk about getting rid of the insurer’s role in health coverage.
New data from the Kaiser Family Foundation shows more than 40% of new Medicare beneficiaries in Oregon and Minnesota chose Medicare Advantage plans in 2016. And more than 36% of new Medicare beneficiaries in New York and California chose Medicare Advantage plans in 2016.
The move toward privatized Medicare plans in Democratic-leaning states like these comes as many candidates for the party’s nomination for President are pushing a single payer version of “Medicare for All” that would bring an end to the private insurer’s role.
With two dozen Democrats running for President in 2020 to challenge Donald Trump should Republicans re-nominate him to run for re-election, the Democratic Party’s candidates are backing everything from a single payer approach to Medicare for All to efforts that allow Americans under the age of 65 to buy into Medicare coverage.
Democratic U.S. Sens. Cory Booker of New Jersey, Kirsten Gillibrand of New York, Kamala Harris of California, Bernie Sanders of Vermont and Elizabeth Warren of Massachusetts were among 17 Senators who introduced the Sanders-led Medicare for All Act of 2017. This legislation, which would expand Medicare more broadly to Americans of all ages, would have no premiums, limited cost-sharing and replaces all private insurance along with Medicaid and the Children’s Health Insurance Program.
Beyond those supporting single payer, others want to see coverage expanded to all through Medicare or a public option. Former U.S. Rep Beto O’Rourke of Texas has said in the past he would support Sanders’ Medicare for All proposal, but lately he’s talking about a more incremental approach to expanding health coverage as has former Vice President Joe Biden who has said he wants to preserve the private healthcare system. And Pete Buttigieg, the Mayor of South Bend, Indiana, is proposing a “Medicare for all who want it” solution that he says would put the U.S. on a path to universal coverage.
The Kaiser Family Foundation analysis seems to indicate those baby boomers who turn 65 and first become eligible for Medicare could be choosing private plans at a higher rate than they are given their experience with the private system.
“Twenty-nine percent of new beneficiaries chose to enroll in Medicare Advantage during their first year in Medicare in 2016,” the Kaiser analysis shows. “That level generally matches the overall share of beneficiaries who opted for Medicare Advantage that year, but does not support the view that the aging Baby Boom generation, having had more experience with HMOs and PPOs during their working years, would select the private plans over traditional Medicare at relatively high rates. In fact, the share of new beneficiaries choosing Medicare Advantage has increased only modestly over the years.”
But the numbers of total Medicare beneficiaries choosing Medicare Advantage is on the rise in the Kaiser study as well as other studies. Medicare Advantage plans provide extra benefits and services to seniors, such as disease management and nurse help hotlines, as well as some plans providing vision and dental care and wellness programs. The plans also are scored by a star-ratings system created under the Affordable Care Act.
Some industry analysts see Medicare Advantage penetration headed to 50% or more of the market in the next five years, particularly after the Trump administration changed regulation to allow Medicare Advantage plans to cover more supplemental benefits. Proponents of Medicare Advantage say enrollment among new beneficiaries if seniors had more education and better understood their options.
“The more educated older adults are about their choices, the more likely they are to make the best choice for themselves,” said Allyson Schwartz,President and CEO of the Better Medicare Alliance, which represents medical care providers and insurers including Humana, UnitedHealth Group, CVS Health and its Aetna health insurance business. “After one or two years in traditional Medicare, as people learn more about their options, they then enroll in Medicare Advantage. Enrollment in MA continues to grow as beneficiaries across the country regardless of political ideology seek lower cost, more benefits, and a coordinated system of care.”
Political battlegrounds like Florida, Georgia, Michigan, Pennsylvania and Wisconsin were states where the share of new Medicare beneficiaries was higher than the 29% national average outlined in the Kaiser study for 2016.
Backers of Medicare Advantage say insurers have attracted more than 22 million people to such plans because of the benefits the plans offer.
“About a third of people eligible for Medicare choose Medicare Advantage because it offers better service, care and value,” America’s Health Insurance Plans (AHIP) spokeswoman Kristine Grow said. AHIP represents several health insurers with Medicare Advantage business including Anthem, Cigna, Centene, Molina Healthcare and WellCare Health Plans.
“About 6 million of them are seniors who make less than $20,000 a year – many of whom might not be able to afford the out-of-pocket costs of traditional Medicare,” Grow added. “Medicare Advantage helps enrollees save money by capping out of pocket costs, offering additional benefits that traditional Medicare doesn’t cover, and for many plans including comprehensive drug coverage at no additional cost.”
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Fractyl procedure shows Type 2 diabetics going insulin-free for 6 months

Early clinical data from Fractyl Laboratories showed that its 40-minute outpatient procedure aimed at the gut could help eliminate several months’ worth of daily insulin injections for people with Type 2 diabetes.
The former Fierce 15 winner’s endoscopic Revita DMR procedure—for “duodenal mucosal resurfacing”—uses water and heat to strip away the inner lining of a portion of the small intestine, allowing it to regrow naturally.
This rejuvenating process seeks to reset the constant production of hormones within that part of the organ, the lion’s share of which are linked to metabolism and related diseases.
Years of dietary fats, sugars and other foods can cause the mucosal lining of the duodenum to become too thick, the company says, leading to imbalances and feedback loops that can contribute to insulin resistance, diabetes and other metabolic syndromes—including non-alcoholic fatty liver disease and steatohepatitis, known as NAFLD and NASH.
The therapy was inspired by the surprising results of certain gastric bypass surgeries for weight loss, which showed an almost immediate reversal of Type 2 diabetes when food was routed around the duodenum.

“This reversal was also totally weight independent, which was really striking and goes against everything that we learned in medical school about why you develop Type 2 diabetes or other metabolic diseases,” Fractyl co-founder and CEO Harith Rajagopalan told FierceMedTech.
“Because the way that we were taught is that you gain weight, and you become obese, and then that obesity causes you to get Type 2 diabetes—but here is the surgery where the diabetes is going away before people have even lost any weight,” Rajagopalan said.
In the company’s interim study results, presented at the annual Scientific Sessions of the American Diabetes Association in San Francisco, 11 out of 13 patients—with an average history of Type 2 diabetes spanning 10 years—reported being insulin-free after at least six months. Three additional participants have not yet reached the six-month mark.
The participants continued therapy with a GLP-1 agonist, with some not needing insulin injections for as long as a year. Additionally, patients saw a nearly 45% reduction in liver fat on an MRI scan plus improvements in weight and blood pressure, the company said.
“Type 2 diabetes is complicated with many severe comorbidities, often managed with multiple daily medications. But with Revita DMR, we continue to see positive clinical effects on diabetes, fatty liver and cardiovascular disease after treatment,” said Juan Carlos Lopez-Talavera, Fractyl’s chief medical officer.
A healthy mucosal layer regrows within one to two months following the procedure, though the beneficial effects appear to be lasting much longer than that, Rajagopalan said.
“Time will tell whether this procedure needs be repeated and at what frequency, but so far, I think it’s reasonable to say that the effects continue to look very promising one year after the procedure,” he said—with one of the most profound improvements being seen in quality-of-life and management of the disease by moving patients from calculating daily injections onto a fixed set of medications.
A separate, sham-controlled study is being currently performed in more than 100 patients with poorly controlled diabetes despite a number of treatments but are not yet receiving insulin.
Data from that randomized trial are expected later this summer. Combined with the results from the smaller study, Fractyl aims to use the two trials to help commercialize its CE marked Revita procedure outside the U.S., while also filing for pivotal studies with the FDA.
Earlier this year, the company presented NAFLD and NASH-focused data at the International Liver Congress in Vienna. In that study, measurements of liver fat were reduced by 36%, with 88% of patients showing improvements in both liver fat and glucose levels within three months of treatment.
Fractyl describes NAFLD, NASH and Type 2 diabetes reaching epidemic levels in the U.S. and internationally, with about 18 million Americans estimated to have more than one of the conditions.
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Chronic inflammation saps motivation by reducing dopamine in brain

Why do we feel listless when we are recovering from an illness? The answer is, apparently, that low-grade chronic inflammation interferes with the dopaminergic signaling system in the brain that motivates us to do things.
This was reported in a new paper published in the journal Trends in Cognitive Sciences.
The research carried out at Emory University explains the links between the reduced release of dopamine in the brain, the motivation to do things, and the presence of an inflammatory reaction in the body. It also presents the possibility that this is part of the body’s effort to optimize its energy expenditure during such inflammatory episodes, citing evidence gathered during their study.
The authors also published an experimental framework based on computational tools, devised to test the theory.
The underlying hypothesis is that the body needs more energy to heal a wound or overcome an infection, for instance, both of which are associated with low-grade inflammation. To ensure that energy is available, the brain uses an adaptive technique to reduce the natural drive to perform other tasks which could potentially drain away the energy needed for healing. This is essentially a recalibration of the specialized reward neurons in the motivation center of the brain, so that ordinary tasks no longer feel like they’re worth doing.
According to the new study, the mechanism of this recalibration is immune-mediated disruption of the dopamine pathway, reducing dopamine release.

The computational technique published by the scientists is designed to allow experimental measurements of the extent to which low-grade inflammation affects the amount of energy available, and the decision to do something based on the effort needed. This could allow us to better understand why and how chronic inflammatory states cause a lack of motivation in other disease conditions as well, including schizophrenia and depression.
Andrew Miller, co-author of the study, says, “If our theory is correct, then it could have a tremendous impact on treating cases of depression and other behavioral disorders that may be driven by inflammation. It would open up opportunities for the development of therapies that target energy utilization by immune cells, which would be something completely new in our field.”
It is already known that immune cells release cellular signaling molecules called cytokines, which affect the functioning of the dopamine-releasing neurons in the area of the brain called the mesolimbic system. This area enhances our willingness to work hard for the sake of a reward.
Dopamine
Image Copyright: Meletios, Image ID: 71648629 via shutterstock.com
Recently, it was discovered that immune cells also enjoy a unique capability to shift between various metabolic states, unlike other cells. This could affect cytokine release patterns in such a way as to signal the brain to conserve available energy for the use of the immune system.
These facts were the foundation of the new hypothesis, which explains it in terms of evolutionary adaptation. In the hypothetical early environment, the immune system, faced with abundant microbial and predatory challenges, needed tremendous amounts of energy. It therefore had its own mechanism to signal other body systems, via the mesolimbic dopamine system, to control the use of energy resources during periods when the organism was undergoing severe or sudden stress.
Modern life is relatively soft and less challenging. With less physical activity, low-grade inflammation is chiefly due to factors such as obesity, chronic stress, metabolic syndrome, aging and other lifestyle illnesses. This could mistakenly cause the mesolimbic dopamine neurons to produce less dopamine. Lower dopamine levels in turn decrease the motivation for work, by reducing the perception of reward while increasing the perception of effort involved. This ultimately conserves energy for use by the immune system.
Previous studies by Miller as well as other scientists have shown that a high level of immune functioning in association with low levels of dopamine and reduced motivation characterizes some cases of schizophrenia, depression and certain other mental health conditions.
The scientists do not think these disorders are caused by the low-grade inflammation, but that some people who have these illnesses are hypersensitive to immune cytokines. This could in turn cause them to lose motivation for daily living.
The scientists are currently performing a clinical trial on people with depression, to test the theory using the computational framework.
Source:
Treadway M. T. et al., (2019). Can’t or Won’t? Immunometabolic Constraints on Dopaminergic Drive. Trends in Cognitive Sciences. https://doi.org/10.1016/j.tics.2019.03.003
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