SCR ATCHING TH E SU RFACE : Q& A WITH EVAN D. ROSEN , MD, PHD

MARCH 2024

THE LEADING MAGAZINE FOR

ENDOCRINOLOGISTS

A Special Focus
on Treating
Pediatric Obesity
Andrew O. Agbaje, MD, MPH, FESC,
speaks to Endocrine News about his researchthat examines how obesity in adolescence
has far-reaching impacts well into adulthood
as well as why late adolescence could be themost critical time to interrupt the potential
comorbidities so often associated with obesity.

I Need To Fight
“FOR
THE
”
KIDS.
BAD RECEPTION:
Unlocking a confounding enigma behindmonogenic obesity in children.

•MASS HYSTERIA:
How obesity in adolescence impacts
cardiovascular and bone health•HAVING A BALL:
An examination of pediatricdyslipidemia and how
routine lipid screening
could play a role

THE US ENDOCRINOLOGY PIPELINEI S FA C I N G U N P R E C E D E N T E D C H A L L E N G E S .
In 2010, endocrinology was one of internal medicine’s most competitive specialties.
In 2024 it’s one of the least.

SINCE 2010,
THERE HAS BEEN
NO GROWTH IN
THE NUMBER
OF US MEDICALG R A D U AT E S
ENTERING
E N D O C R I N O L O G Y.

NUMBER OF FELLOWSHIP POSITIONS

400

300

BETWEEN 2010 AND 2024

78%

200

25%

100
DO GRADUATESINTERNATIONAL MEDICAL GRADUATES

0

US MEDICAL GRADUATES

2010

ENDOCRINEFELLOWSHIP SPOTSINCREASED BY 78%

US MEDICALGRADUATESAPPLYING TO
ENDOCRINOLOGYFELL BY 4%

US MEDICALGRADUATES
INCREASED BY 25%

4%

2024

TOGETHER, WE CAN MEET THIS CHALLENGE.
Our Medical School Engagement Program (MSEP) provides a way for leaders like you to pique
medical student interest in endocrinology and recognize your best and brightest learners with
opportunities to engage with leaders in our field.

STUDENTSLEADERSHIP

Access to networking
opportunities with endocrinology
faculty, funded excellence
awards, and complimentarySociety membership.

Build lasting relationships
with promising students, offer
rewarding teaching opportunities
to faculty, and increase thenumber of medical students
electing endocrinology rotations.

APPLICATIONS ARE NOW BEING ACCEPTED FOR THE 2024-2025 ACADEMIC YEAR.

S UBM I T Y OUR S T ODAY AT ENDOCRINE.ORG/MSEP© 2024 ENDOCRINE SOCIETYIN THIS ISSUE

MARCH 2024

28 |Having a Ball

Can Solving
Pediatric
Dyslipidemia
Really Be as Simple
as Child’s Play?
As parents constantly
tell their kids to “gooutside and play,” newresearch published in
The Journal of Clinical
Endocrinology &Metabolism basically
proves that mothers
and fathers really
do know best, evenwhen it comes to goodcardiovascular health!
BY KELLY HORVATHFEATURES

16 | Bad Reception

22 | Critical Mass

When two very different pediatric patients with obesity presented withunusually high leptin levels, endocrine researchers took notice and discoveredthat leptin was not adequately binding with receptors. When the young
patients’ familial history was considered, solutions were finally forthcoming.

Findings continue to emphasize the negative metabolic effects of fat masscompared with lean muscle mass. While the effects of too much fat mass on
cardiovascular health are well known, one study looks at the adverse impact
on adolescent bone health.

BY DEREK BAGLEYBY ERIC SEABORG

Unlocking a Confounding Enigma Behind Monogenic
Obesity in Children

Recent Research Emphasizes More Dangers of Obesityin Adolescence

ENDOCR INE NEWS | M A RC H 2 0 2 4 |1IN THIS ISSUE
16

13

13 | DASHBOARD

ENDO 2024 Highlights

Highlights from the world of
endocrinolgy

Mom was Right...

14 | ENDOCRINE ITINERARY

8 | INTOUCH

Scientific meetings of interest
to endocrinologists from aroundthe world

New Position Statement Focuseson Patient Experience inDiabetes Care.

10 | TRENDS & INSIGHTSHigh fat diet influences milk
lipids in lactating women;
Potential link between
high maternal cortisol andunpredicted birth complications;and Women exposed to toxic
metals may experience earlier
aging of their ovaries.
BY DEREK BAGLEY

10

34 22

4 | PRESIDENT’S VIEWPOINT
6 | FROM THE EDITOR

MARCH 2024

34 | LABORATORY NOTESSCRATCHING THE
SURFACE Q&A WITH 2024
ROY O. GREEP LAUREATEFOR OUTSTANDING
RESEARCH EVAN D.
ROSEN, MD, PHD
When Evan D. Rosen, MD, PhD,
first began researching adipose
biology many years ago, notmuch was known about it and its
impacts on so many diseases. He
talks to Endocrine News about
how far the science has advanced
regarding adipose tissue as wellas his own lab’s research, the2 | M A RC H 2 0 2 4 | ENDOCR INENEWS.ORG

importance of collaboration, andwhy a laboratory is a lot like asubmarine!

BY GLENDA FAUNTLEROY SHAW

38 | ADVOCACY
Endocrine Society Advances
Women’s Health ThroughResearch and Advocacy; Clinical
Endocrinology Mentorship
Opportunity at ENDO 2024;
Endocrine Society Advocates toProtect and Increase Funding for
the NIH; EU Proposes ScienceBased Restrictions on Bisphenols;and How to Incorporate the New
Medicare Complex Code G2211
into Your Practicewww.endocrine.org
Follow us on Twitter:@Endocrine_NewsR EAC H T H E WO RL D W I T H Y O U R W ORKP U B L I S H

I N

E N D O C R I N E

S O C I E T Y

J O U R N A L S

For more information about publishing with the Endocrine Society, please visit
academic.oup.com/endocrinesociety.

© 2024 ENDOCRINE SOCIETYPRESIDENT’S VIEWPOINT

ENDO 2024
HighlightsW

ith springtime just around the corner (or perhaps still alittle further around the corner if you live in Rochester,N.Y., like I do), our thoughts once again turn to sunshine,
flowers, and ENDO!
This year’s annual meeting in Boston, Massachusetts, June 1 – 4, promises tobe one of our best yet. Members of the dedicated Annual Meeting Steering
Committee, along with the Society’s hardworking education and meetings
staff, once again have outdone themselves in developing a program of
cutting-edge educational sessions and exciting networking opportunities.
It’s my pleasure to share a few highlights of this year’s program. Right off thebat, it’s instructive to see the numbers. This year’s ENDO will include:u6,000-plus attendees from around the world;u160-plus education sessions;u40-plus Meet the Professor sessions;uFour basic science pathways: Diabetes and Metabolism;
Neuroendocrinology; Nuclear Receptors and Signaling; andReproduction;u

30 oral abstract sessions and a poster hall with more than 2,200
scientific abstracts; andu

72 industry exhibitors supporting our field in the ENDOExpo hall.

Such programming alone will keep you busy from morning until evening.
But you also won’t want to miss our three plenary sessions taking place at
8:00 AM on the ENDO Main Stage. These unopposed sessions have been
specially curated to offer the broadest appeal and insights into some of thehottest topics affecting endocrinology and the medical/science fields atlarge. They are:June 1: Cardiovascular Disease in Diabetes: From Molecular Pathways
to Populations — This session gets to the heart of the matter. Among other

4 | M A RC H 2 0 2 4 | ENDOCR INENEWS.ORG

things, this session will review advances in knowledge aroundmechanisms responsible for cardiometabolic disorders, which
are informing novel approaches to therapy.
June 2: Artificial Intelligence (AI) in Health and Biomedical
Research: The Future Is Now — Who doesn’t both fear andrespect AI? This session will include a discussion on ways that“

Our meeting presents an excellent
opportunity for these young professionals to
kickstart their careers, whether they decideto focus on amazing clinical care, teaching
the next generation of physicians andscientists, or doing cutting-edge research.

”AI-based methods are being used to advance research and care.
Hear from two experts on computational biology, precision
medicine, genetics of complex traits, and machine learning.
June 3: Hormones and the Aging Brain — We aren’t getting
any younger! At this session, you will hear from experts leading
initiatives to accelerate the advancement of evidence-based
clinical care of brain disorders caused by disease, genetics, ortrauma. Other areas of expertise include early detection andprevention of cognitive aging and Alzheimer’s disease in at-risk
individuals, especially women.
These plenaries are marque events that present the very latest
in scientific knowledge. They also give us an opportunity torecognize leading figures in our field through the presentationof our Laureate Awards. I’m always inspired to see and hearfrom the “rock stars of endocrinology!” These are the people
who have made significant contributions to improving thecare and knowledge of hormone health, improving the lives of
millions of patients.

attending ENDO. Our meeting presents an excellent
opportunity for these young professionals to kickstart theircareers, whether they decide to focus on amazing clinical care,teaching the next generation of physicians and scientists, ordoing cutting-edge research.
The Endocrine Society takes seriously the need to prepare thenext generation of practitioners in our field. This was evident
at ENDO 2023, when we held the inaugural Endocrinology
Mentor Day. The program is designed to stoke interestin endocrinology among medical students and residents.
Mentors introduced their mentees to ENDO’s signature
programs, including poster presentations, interesting casestudies, and a plenary session. Already we’re seeing a hugedemand for the second iteration of Mentoring Day, so staytuned to upcoming Society communications if you want tobecome a mentor or mentee.
Clearly, ENDO provides an intense dose of knowledge sharing
and career betterment. But it’s also a lot of fun! The meetingprovides many opportunities to catch up with old friends andmake new ones.
Networking, in fact, has always been a major component of
ENDO. I can say, without a doubt, that I have met some of mybest friends and colleagues at ENDO, and every year I lookforward to seeing them again. I love the energy that comesfrom bumping into colleagues and peers in the hallways andat organized social events. One that you won’t want to miss isthe Opening Reception in the ENDOExpo, Saturday, June 1,
from 6:15 PM to 7:45 PM. An even more targeted opportunity
to network is at our Career Fair in the ENDOExpo, on Sunday,
June 2, from 2:00 PM to 4:00 PM.
Bottom line: ENDO is far and away the best meeting for
endocrine clinicians and researchers in the world. Stay abreastof the latest offerings and updates by visiting the ENDO 2024
website at: www.endocrine.org/ENDO2024. I will see you in
Boston, and, if you run into me wandering through the halls,
please take a moment to come and introduce yourself!
Stephen R. Hammes, MD, PhD
President, Endocrine Society

At the same time, I’m even more inspired to meet the upand-coming generation of endocrine clinicians and scientists

ENDOCR INE NEWS | M A RC H 2 0 2 4 |5FROM THE EDITOR

MARCH 2024

THE LEADING MAGAZINE FOR ENDOCRINOLOGISTS

Executive Editor: Mark A. Newman
mnewman@endocrine.org
Senior Editor: Derek Bagleydbagley@endocrine.org
Art Director/Production: Anthony S. Picco
Art Director/Design: Catherine C. Neill,
CNJ Creative, saLLC
www.cnjcreative.com
Designer: Petra Domingo
Prepress & Printing: The Sheridan Groupwww.sheridan.com
Endocrine News is a registered trademark owned by the
Endocrine Society.

Mom Was Right…

M

Endocrine News informs and engages the global endocrine
community by delivering timely, accurate, and trusted
content covering the practice, research, and profession of
endocrinology.

y mother was a nurse. She had a tendency to look at the world
two ways: her way and the wrong way. The problem, such as it
was, typically turned out to be that her way was the right way. It
was both comforting and infuriating all at once. I feel like there are many of
you out there who totally get where I’m coming from.
During the hot summers in southwest Alabama, when she would see mesitting on the couch, watching Good Times reruns with my hand jammed
into a Golden Flake potato chip bag up to my elbow, she would encourage
me to “go outside and play!” She told me I would feel better, and it wassuch nice weather, and it would be good for me, etc. To be honest, I didn’t
realize how wise she was until after the summer of my freshman year inhigh school wrapped up and I experienced my first band camp. I started mysophomore year lean, tanned, and only a marginally better trumpet player!
I relate this youthful tale of an abruptly ended life of sloth because so muchof this issue focuses on the dangers of adolescent obesity, not to mention
too much sedentary time for many adolescents with obesity. This month’s
cover features Andrew O. Agbaje, MD, MPH, FESC, from the Institute of
Public Health and Clinical Nutrition, School of Medicine, Faculty of Health
Sciences, at the University of Eastern Finland in Kuopio, whose research
figures prominently in two studies published in the January 2024 issue of
The Journal of Clinical Endocrinology & Metabolism that both address thedangers of the many complications associated with obesity in youth.
In “Having a Ball” on page 28, Kelly Horvath talks to Agbaje about his
JCEM paper, “Associations of Sedentary Time and Physical Activity FromChildhood With Lipids: A 13-Year Mediation and Temporal Study,” andhe details the study’s findings, why some of the official guidelines arewildly arbitrary, and the need for more regular lipid screenings in pediatricpatients. According to Agbaje, one out of five adolescents with obesity who
eventually develop heart disease is “one too many, when this is preventable,”

6 | M A RC H 2 0 2 4 | ENDOCR INENEWS.ORG

President: Stephen Hammes, MD, PhD
president@endocrine.org
President-Elect: John Newell-Price, MD, PhD, FRCP
j.newellprice@sheffield.ac.uk
Past-President: Ursula B. Kaiser, MDukaiser@bwh.harvard.edu
Secretary-Treasurer: Jeffrey Boord, MD
jeffrey.boord@parkview.com
Chief Communications Officer: Aaron Lohralohr@endocrine.org
The mission of the Endocrine Society is to advance excellencein endocrinology and promote its essential and integrative rolein scientific discovery, medical practice, and human health.

Endocrine News® is published 12 times a yearby the Endocrine Society, 2055 L Street, NW,
Suite 600, Washington, DC 20036
Phone 202-971-3636 • Fax 202-736-9708
www.endocrine.org.
Print ISSN 2157-2089 Online ISSN 2157-2097
Copyright © 2024 by the Endocrine Society.
All rights reserved.
• Please send letters to the editor, comments, and suggestions for EndocrineNews® to mnewman@endocrine.org.
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The statements and opinions expressed in Endocrine News®
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Advertising appearing in this publication does not constitute endorsementof its content by Endocrine News® or the Endocrine Society.

Editor's mom (center) helpng to prepare for ahealth fair in Jackson, Ala., sometime in the 1980s.

he says. “Also, when many of these heart diseases eventuallyoccur, we can’t cure them, we can only manage them forlife, which increases healthcare costs, yet it’s so cheap tomeasure cholesterol levels.” Current guidelines recommending
cholesterol screening at age 40 are woefully misguided
because by the time middle age rolls around, the damage
has already been done to the cardiovascular system, and thehealthcare cost burden spirals.
In “Critical Mass” on page 22, Eric Seaborg speaks to Agbaje
about his other JCEM study, “DXA-based Fat Mass With Risk
of Worsening Insulin Resistance in Adolescents: A 9-Year
Temporal and Mediation Study,” where he says that body massindex (BMI) measurements only tell part of the story; BMI
does not give a true measure of the dangers of abdominal fat“

It’s not an antibody.
It’s not an autoimmune antibody.
It’s a naturally occurring protein working
as antagonist when you treat the patientwith wild-type leptin, then you will
see that it’s blocking the receptor.

”

nor does it elucidate the benefits of muscle mass. “Fat mass
drives insulin resistance, but muscle mass appears to reverse it
in a very small way,” Agbaje says. “If we only use BMI, we will
not be able to see that muscle mass is beneficial in lowering
insulin resistance. … Abdominal fat is twice as dangerous
as total body fat. Every increase in abdominal fat raised
the risk of insulin resistance, not just at the time point but
progressively from age 15 to 24.”in Obese Boys: A Cross-Sectional Study,” which details theimpact of pediatric obesity on bone mineral density andcontent compared to average-weight children. The study
shows that those children with obesity have a 25% higher riskof extremity fracture than children of average weight.
Senior Editor Derek Bagley examines a New England Journalof Medicine study that looked into the cases of two very
different children — one from Qatar and one from Austria— who presented with unusually high leptin levels that the
researchers discovered were due to inadequate binding withreceptors (“Bad Reception,” p. 16). It wasn’t until the young
patients’ family history was considered that the researchers
were finally able to put the pieces of the puzzle together.
Once this binding “defect” was realized, it was like a totallynew idea from a biological point of view that had never been
described before, according to researcher Martin Wabitsch,
MD, PhD, head of the Division of Pediatric Endocrinology
and Diabetes, at Ulm University Medical Center in Germany.
“It’s not an antibody. It’s not an autoimmune antibody. It’s anaturally occurring protein working as antagonist when you
treat the patient with wild-type leptin, then you will see thatit’s blocking the receptor. And that’s what we saw also in thepatients.”
I hope you enjoy this issue with a special focus on adolescentobesity. It’s such an important issue that can be addressedin so many cases that will not only improve the current
and future health of these kids but take the strain off of thehealthcare systems around the world.
Just wish my mom was here to say, “I told you so!”— Mark A. Newman, Executive Editor, Endocrine NewsThe article also reports on a second JCEM study, “Insufficient
Bone Mineralization to Sustain Mechanical Load of Weight

ENDOCR INE NEWS | M A RC H 2 0 2 4 |7INTOUCH

New Position
Statement
Focuses
on Patient
Experience inDiabetes Care

Healthcare providers who treat diabetes need to think beyond the clinical numbers,
such as solely focusing on a person’s glucose goals. Taking the patient experience
into account can improve the quality of care and facilitate attainment of treatment
goals, according to a new position statement published in the Endocrine Society’s Journal of
Clinical Endocrinology & Metabolism.
The position statement reflects the consensus of two virtual roundtables the Endocrine Society
held in 2022. Participants included representatives from the American College of Cardiology;
American College of Physicians; American Diabetes Association®; Association of Diabetes
Care & Education Specialists; Diabetes Technology Society; the U.S. Centers for Disease
Control and Prevention; the diabetes research organization dQ&A; and patient advocacy
organizations DiabetesSisters, Close Concerns, and Taking Control of Your Diabetes.
More than 500 million people worldwide have diabetes. Managing this chronic diseaserequires making lifestyle changes throughout life, which can be burdensome for people
living with diabetes and their caregivers. Daily tasks such as blood glucose monitoring,dietary and exercise management, routine preventive care scheduling, and medication
management must be overseen by people living with diabetes themselves.
Effective two-way communication between people with diabetes and their healthcare
providers helps establish a shared understanding of the treatment plan and goals. Healthcare
providers who take the time to explain treatment options and discuss potential barriers canimprove patient satisfaction and clinical outcomes. In addition, healthcare providers needto consider each individual patient’s level of health literacy and cultural background when
discussing treatment options.

8 | M A RC H 2 0 2 4 | ENDOCR INENEWS.ORG

INTOUCH“Many existing educational resources are available to help
healthcare providers think through ways they can discuss
diabetes treatment in a neutral and nonjudgmental way andpractice using those strategies,” says Rita R. Kalyani, MD,
MHS, professor of medicine in the Division of Endocrinology,
Diabetes, and Metabolism at Johns Hopkins University
School of Medicine, who chaired the position statement andrepresented the Endocrine Society during the consensus
roundtables. “However, in the ever-changing landscape of
diabetes and its management, both health care providers andpeople with diabetes will continue to need new and evolving
tools to help address the common challenges they face.”u Discussing strategies for assessment of hypoglycemia — low

People with diabetes face an elevated risk of developing
depression, anxiety, and other mental health disorders. This
makes understanding the psychosocial impact of diabetes
important. Addressing stressors in the healthcare setting andensuring timely mental health referrals, when appropriate, canhelp individuals with diabetes feel more comfortable and help
them participate more fully in their appointments and care.

The other authors of this study are Myriam Allende-Vigoof the University of Puerto Rico, Humacao, Puerto Rico,representing the American College of Physicians; Kellie
Antinori-Lent of the University of Pittsburgh Medical Center
Shadyside in Pittsburgh, Pa., representing Association of
Diabetes Care & Education Specialists (ADCES); Kelly
L. Close of Close Concerns, Inc., in San Francisco, Calif.;
Sandeep R. Das of UT Southwestern Medical Center in Dallas,
Texas, representing the American College of Cardiology;
Phyllisa Deroze of dQ&A, The Diabetes Research Company
in San Francisco, Calif.; Steven Edelman of the Universityof California at San Diego in San Diego, Calif., representing
Taking Control of Your Diabetes (TCOYD); Nuha A. El Sayedof the American Diabetes Association of Arlington, Va., andHarvard Medical School in Boston, Mass.; David Kerr of the
Diabetes Technology Society in Santa Barbara, Calif.; Joshua
J. Neumiller of Washington State University of Spokane,
Wash., representing the American Diabetes Association; andAnna Norton, on behalf of DiabetesSisters of Raleigh, N.C.

Each section in the position statement begins with a common
clinical scenario that illustrates key gaps in diabetes care.
Readily accessible graphics and tools that can be used byhealthcare providers to deliver patient-centered care in practice
are also included.
The position statement offers a framework for leveraging
the experiences of people with diabetes to optimize healthoutcomes in several important areas, including:u Use of person-centered language in the healthcare settingu Ensuring that referrals to diabetes self-management andsupport service programs are timely and accessible to all
people with diabetes.

u Effectively navigating available therapeutic options together
and explaining complex regimens to people with diabetes toencourage them to take medication as prescribed.

blood glucose episodes that can be dangerous — as well as
prevention and treatment of hypoglycemia.

u Improving cardiovascular and renal outcomes using newer
therapeutic options.

u Using telehealth in the appropriate clinical setting.
u Using and incorporating diabetes technologies such as
insulin pumps and continuous glucose monitoring systems
into the diabetes management plan, when appropriate.

The roundtable meetings were supported by educational
grants to the Endocrine Society from Abbott, Medtronic,
Novo Nordisk, and Vertex. The position statement, which isa summary of the findings from those consensus roundtables,
was developed by the authors independently.

u Considering ways to adjust an individual’s treatment plan ina timely manner if they aren’t meeting therapeutic goals toprevent therapeutic inertia.

ENDOCR INE NEWS | M A RC H 2 0 2 4 |9TRENDS & INSIGHTSBY DEREK BAGLEY
Senior Editor

High Fat Diet Influences Milk Lipids in
Lactating WomenM

aternal exposure to a high fat diet
(HFD) alters milk lipids in lactating
women, enhancing adiposity andmyeloid inflammation in offspring, even inearly life, according to an animal study recently
published in Endocrinology.

“

While animbalance ofnutrition intake
and energy
expenditure isa primary causeof obesity, we are
now aware thatthe perinatal andearly postnatal
environments
can play asignificant role inmodifying disease
risk.

”

Researchers led by Kanakadurga Singer, MD,
and Brigid Gregg, MD, both of the University ofMichigan in Ann Arbor, point out that as of 2018,
43.4% of American adults over 20 years of age haveobesity. And as the obesity epidemic grows, sodoes our knowledge and awareness of the complex
disease. “While an imbalance of nutrition intake
and energy expenditure is a primary cause ofobesity, we are now aware that the perinatal andearly postnatal environments can play a significant
role in modifying disease risk,” the authors write.
The researchers write that infants are susceptible
to programming effects through signals conveyed
during lactation — the lactational programming
hypothesis. “In both humans and mice, thelactation period is a time when adipocytes and theimmune system continue to develop,” the authors
write. “These systems then play a role in governing
global metabolism. Suboptimal development of
immune and adipose cells can put individuals at
higher risk for obesity and its comorbidities, as wellas impaired immune function.”
Previous studies have shown connections between
maternal diet and how it affects adiposity inoffspring. Indeed, the authors’ prior studies
demonstrated that the adult meta-inflammation
exaggerated by HFD during the postnatal lactation
window (PN) was predominantly a phenotype ofmale offspring. “However, it is not clear if these
programmed effects manifest early at the time of
weaning,” the authors write.

10 | M A RC H 2 0 2 4 | ENDOCR INENEWS.ORG

For this study, the researchers hypothesized thataltering the milk fat profile via changes in thematernal diet favoring omega-6 fatty acids would
promote a pro-inflammatory milieu in offspring.
“Previous lactational exposure studies have not
performed detailed immune phenotyping in theoffspring,” the authors write. “Our findings showthat even early in life offspring of HFD dams had
more adiposity and increased [bone marrow (BM)]myeloid inflammation with serum from these micedirectly stimulating myelopoiesis.”
Mice were fed a high fat diet during the postnatal
lactation window (HFD PN mice). Their offspringwere evaluated at postnatal days 16 to 19 fortissue weight and gene expression. Profiling of
adipose tissue and bone marrow immune cells was
conducted through lipidomics, in vitro myeloid
colony forming unit assays, and flow cytometry.
“HFD PN mouse infants showed not only heavier
body and organ weights, but also presented withlarger adipocyte sizes than control infants,”
the authors write. “Lipidomic analysis revealed
increased n6:n3 ratios and increased linoleic acidin milk from HFD dams as well as serum fromsuckling HFD PN mice. HFD PN mice also showedaltered BM and adipose tissue immune cell profiles.
Together, these results demonstrate a significant
change in infant health profiles upon exposure to amaternal HFD, which can have detrimental effects
toward their future health.”
The authors go on to conclude that these findings
may hold significant implications for nutritionalguidelines for pregnant women and nursing
mothers. “Future studies are needed to understandthe mechanisms driving this pro-inflammatory
state of both BM and [adipose tissue macrophages],the causes of the sexually dimorphic phenotypes,
and the feasibility of intervening in this window to
improve metabolic health,” they write.

Potential Link Between High Maternal Cortisoland Unpredicted Birth ComplicationsAsnippet of hair can reveal a pregnant
person’s stress level and may one day
help warn of unexpected birth problems,
according to a study recently published in
Psychoneuroendocrinology.

months prior to collection. These women also
reported feelings of stress, anxiety, and depression,but on average, only high cortisol levels during
pregnancy showed a strong link to adverse birthoutcomes.

Washington State University researchers measured
the stress hormone cortisol in hair samples of 53
women in their third trimester. Of that group,
13 women who had elevated cortisol levels later
experienced unpredicted birth complications, suchas an early birth or hemorrhaging.

Throughout pregnancy, cortisol levels naturally
rise two to four times and peak during the third
trimester, but the measurements in this study
showed even more pronounced elevated cortisol
levels among the women who had unexpectedbirth complications.

While more research is needed with larger groups,
this preliminary finding could eventually lead to

Two months after giving birth, the group thatexperienced birth complications continued“

The U.S. also
notoriously
has one of thehighest maternalmortality rates
among developed
countries,
with deaths
disproportionately
impactingBlack womenand other peopleof color.

”a non-invasive way to identify those at risk forsuch complications. “There was otherwise nothing
about these women that would suggest a diseaseor anything else complicating the pregnancy.
This confirmed some hypotheses that levels ofstress, related specifically to cortisol levels, might
be associated with adverse birth outcomes,” says
Erica Crespi, PhD, a WSU developmental biologist
and the study’s corresponding author.
As part of the study, the participants all
answered survey questions about their levelsof psychological distress in addition to having
cortisol measurements taken in the third trimesterof pregnancy and after they gave birth. The women
who experienced unexpected birth complications
had elevated cortisol concentrations in their hair,a measure that indicates the stress hormone’s
circulating levels in the body during the three

to show elevated cortisol and gave survey
answers indicating continued stress, anxiety,and depression. At six months, their cortisol
remained elevated, but they started to report lower
psychological distress on the survey, which theauthors noted might be a sign of recovery.
Finding ways to reduce stress around birth could
help improve outcomes for both infants andmothers, the researchers say. They point out thatadverse birth outcomes are rising in the country.
The U.S. also notoriously has one of the highest
maternal mortality rates among developed
countries, with deaths disproportionately
impacting Black women and other people of color.

ENDOCR INE NEWS | M A RC H 2 0 2 4 |11Women Exposed to Toxic Metals May
Experience Earlier Aging of Their Ovaries

M“

Metals, including
arsenic andcadmium, possess
endocrinedisrupting
characteristics andmay be potentially
toxic to the ovaries.
We need to study
the younger
population as
well to fully
understand therole of chemicals
in diminishedovarian reserve andinfertility.

”

iddle-age women who are exposed
to toxic metals may have fewer eggs
in their ovaries as they approachmenopause, according to new research publishedin The Journal of Clinical Endocrinology &Metabolism.
Researchers led by Sung Kyun Park, ScD,
MPH, associate professor of epidemiology andenvironmental health sciences at the Schoolof Public Health at the
University of Michigan in
Ann Arbor, point out that
Anti-Müllerian
hormone(AMH) is a member of
the TGF-β superfamily
produced by granulosa
cells of preantral andearly antral follicles and is
detectable in circulation.
AMH is a promising serum
biomarkerofovarianreserve, since measuring AMH has the advantage
of being noninvasive and relatively stable overthe menstrual cycle, contrary to antral follicle
count and ovarian morphology, which are best
measured during the follicular phase. “Although
genetic and lifestyle factors, such as smoking, are
known to affect ovarian reserve, the impact ofenvironmental exposures remains inconclusive,”the authors write.
Studies have linked heavy metals measured inurine with women’s reproductive aging anddiminished ovarian reserve. Heavy metals
such as arsenic, cadmium, mercury, and leadare commonly found in our drinking water,
air pollution, and food contamination and areconsidered endocrine-disrupting chemicals.
“We attempted to address this gap by examining
the associations of heavy metals including arsenic,
cadmium, mercury, and lead, with longitudinal
trajectories of serum AMH concentrations as

12 | M A RC H 2 0 2 4 | ENDOCR INENEWS.ORG

markers of ovarian reserve during the menopausal
transition from samples collected in the Study of
Women’s Health Across the Nation (SWAN),” theauthors write. “We hypothesized that higher metal
concentrations were associated with lower AMH
concentrations and accelerated rates of decline in
AMH during the menopausal transition.”
The researchers studied 549 middle-age womenfrom the Study of Women’s Health Across the
Nation (SWAN) who weretransitioning to menopause
and had evidence of heavy
metals — including arsenic,
cadmium, mercury, or lead— in their urine samples.
They analyzed data from
AMH blood tests from up to
10 years before the women’s
final menstrual periods. They
found women with higher
levels of metal in their urine
were more likely to have lower AMH levels, anindicator of diminished ovarian reserve.
“Widespread exposure to toxins in heavy metals
may have a big impact on health problems linked
to earlier aging of the ovaries in middle-aged
women, such as hot flashes, bone weakening andosteoporosis, higher chances of heart disease, andcognitive decline,” Park says. “Our study linked
heavy metal exposure to lower levels of AMH in
middle-aged women. AMH tells us roughly how
many eggs are left in a woman’s ovaries — it’s likea biological clock for the ovaries that can hint at
health risks in middle age and later in life.”“Metals, including arsenic and cadmium, possess
endocrine-disrupting characteristics and may bepotentially toxic to the ovaries,” Park continues.
“We need to study the younger population as
well to fully understand the role of chemicals in
diminished ovarian reserve and infertility.”DASHBOARD“

Adipose tissue impacts so many diseases — type 2 diabetes, of course, butalso obesity, lipodystrophy, MASLD, hyperlipidemia, atherosclerosis, cancer, andmore. All of these conditions could potentially benefit from therapies that manipulate
adipose tissue biology. Despite the fact that there are already many medications for these
diseases, they continue to cause a huge amount of suffering. So, there is absolutely a needfor new treatments, and adipose tissue offers potential opportunities for tissue-based
therapeutics. In many ways, we have just scratched the surface of what’s possible.”– 2024 Roy O. Greep Laureate for Outstanding Research recipient Evan D. Rosen, MD, PhD, on better options for treating diabetes in “Scratching the Surface,” on page 34.

The percentageof adults with
type 2 diabetes
who discontinued
their secondline medication
within a year ofstarting it.

40%— SOURCE: AMERICAN
JOURNAL OF MANAGED CARE

65

Patients thisage and older
who receive
thyroid hormone
therapy andexperience low
thyrotropin are
at increased riskfor dementia andother cognitive
problems.

58

%

5

%

Number of U.S.-based
medical and nursing
students who view theircurrent studies as a“steppingstone” to ahealthcare career that
does not involve treating
patients.
— SOURCE: CLINICIAN OF THE FUTURE
2023 EDUCATION EDITION/ELSEVIERThe percentage
by whichtelehealthutilization
increasedin three outof four U.S.
census regions.

— SOURCE: FAIR HEALTH’SMONTHLY TELEHEALTHREGIONAL TRACKER.

— SOURCE: JAMA
INTERNAL MEDICINE

8x

PCOS-diagnosed
patients had
an 8.47-foldhigher riskof attemptedsuicidecomparedwith women
without PCOS.
— SOURCE: ANNALS OF
INTERNAL MEDICINEThe number of patients
removed from Medicaid overthe past year in a process
known as the “unwinding,”
which is aimed to bring thenumber of Medicaid enrollees
back to pre-pandemic levels.
— SOURCE: KFF HEALTH NEWS

16,000,000+
ENDOCR INE NEWS | M A RC H 2 0 2 4 |13

ENDOCRINE ITINERARY

June 1 – 4, 2024 • Boston, Mass.

AAES 2024 Annual Meeting
Dallas, Texas
April 20 – 22, 2024

American Association of Endocrine
Surgeons 2024 Annual Meeting attendees
can look forward to dynamic speakers,
presentations of innovative research,

We hope to see you at ENDO 2024, taking place
June 1 – 4, 2024, in Boston, Mass. With morethan 7,000 attendees, nearly 2,000 abstracts,and more than 200 other sessions, ENDO is the
top global meeting on endocrinology researchand clinical care. ENDO provides the opportunity
to collaborate with an unparalleled list of
endocrinologists, healthcare practitioners, andleading scientists from around the world. Throughsharing our experience, advice on patient care,and new advances in research, we move theneedle forward in hormone health and science.
Our outstanding slate of world-renowned speakers
will showcase the most cutting-edge advancesin research and medicine, with presentations
spanning the spectrum of science, clinical care,and social implications. https://www.endocrine.
org/meetings-and-events/endo-2024

Meeting is dedicated to the advancementof the science and art of endocrine
surgery through exchange of knowledge
and fostering collaboration. The upcoming
2024 event promises to deliver innovative
programming that will enrich attendees’
clinical practices, provide networking
opportunities, and facilitate scholarly
pursuits. We cordially invite you to join us
in Dallas for this exciting event. It will be
an excellent opportunity to dive into new
topics, share expertise, and connect withpeers who share similar interests.

https://www.endocrinesurgery.
org/2024-annual-meeting2024 Lab Manager
Leadership Summit

Denver, Colorado
April 29 – May 1, 2024
opportunities to connect with colleagues,
and informative panel discussions. This
year’s pre-meeting Advanced Course in
Endocrine Surgery will include outstanding
faculty and a wide range of topics. In
addition, sponsors will be on site toshowcase cutting-edge technologicaladvancements pertinent to the practiceof endocrine surgery. The AAES Annual

14 | M A RC H 2 0 2 4 | ENDOCR INENEWS.ORG

The Lab Manager 2024 Leadership
Summit will offer actionable advice on
the management, business, safety, andstaffing challenges facing today’s lab
managers. The program’s expert speakers
will provide you with the tools you needto reach higher levels of engagement andefficiency among your lab teams. Topics
will range from dealing with burnout, toincorporating automation into your lab, tolab operations, to effective communication,and much more — an interactive Q&A will
follow each session. Attendees will also beable to participate in hands-on workshops
and roundtable discussions, where they will
receive focused advice and learn from reallife examples of leadership success.

https://www.labmanager.com/labmanager-leadership-summit-30946

Pediatric Endocrine Society2024 Annual Meeting
Chicago, Illinois
May 2 – 5, 2024

The Pediatric Endocrine Society’s Annual
Meeting brings together our diverse
international community of over 1,000
clinicians, researchers, and trainees to share

ENDOCRINE ITINERARY

the excitement of new ideas, establish new friendships, and learn the latest
insights covering the wide scope of our diverse field.

INTERNATIONAL ITINERARY

https://pedsendo.org/education-events/pes-2024-annualmeeting/Diabetes Meet 2024

19th International Adrenal Meeting

This Diabetes Meet 2024 Conference invites all theacademic scientists, endocrinologists, surgeons,primary healthcare specialists, pediatricians,
pharmaceutical industrial delegates, talented young
scientists, and student communities across theglobe to attend this meeting where all the aspects ofdiabetes mechanism, disorders, and treatment will be
discussed under a single roof.

Boston, Masachusetts
May 29 – 31, 2024

Adrenal researchers and clinicians from around the world will convene
for the 19th International Adrenal meeting, which will feature the Keith
Parker Memorial Award and Lecture and the Alastair Brownie and Bernie
Schimmer Early Career Awards & Lectures. This year’s conference
will see the addition of pheochromocytoma and paraganglioma to
the program along with presentations in each session selected from
submitted abstracts.

https://www.eventsquid.com/mobileapp.cfm?id=22293

ADA 84th Scientific Sessions
Orlando, Florida
June 21 – 24, 2024

The American Diabetes Association’s (ADA) Scientific Sessions offers
researchers and healthcare professionals the unique opportunity toshare ideas and learn about the significant advances and breakthroughs
in diabetes. Participants will receive exclusive access to more than 190
sessions and 2,000 original research presentations, take part in provocativeand engaging exchanges with leading diabetes experts, expand theirprofessional networks, and so much more.

https://professional.diabetes.org/scientific-sessions

ADCES24

New Orleans, Louisiana
August 9 – 12, 2024
The Association of Diabetes Care & Education Specialists (ADCES) Annual
Conference is the premier diabetes care and educational event of theyear. More than 3,000 diabetes care and education specialists and other
healthcare professionals are expected to participate at ADCES24 in New
Orleans, La. Connect, collaborate, and educate yourself and others on thelatest in diabetes care and education.

https://www.diabeteseducator.org/home

ASBMR 2024

Toronto, Ontario, Canada
September 27 – 30, 2024
The ASBMR Annual Meeting boasts nearly 100 education sessions and1,100 poster presentations in four information-filled days. The conference
includes hands-on workshops focused on the latest technologies andresearch tools using model data sets, meet-the-professor sessions, the
ASBMR Discovery Hall, an exhibition hall that provides attendees with atruly immersive experience, with access to new science, new knowledge,
new tools, and new contacts all in one location.

https://www.asbmr.org/annual-meeting

Rome, Italy/Virtual
March 11 – 12, 2024

https://www.diabetesmeet.com

12th Seoul International Congressof Endocrinology and Metabolism(SICEM 2024)
Seoul, Korea
April 11 – 13, 2024

The Korean Endocrine Society (KES) will explore newfrontiers in the realms of endocrinology and metabolism
at SICEM 2024, the 12th Seoul International Congressof Endocrinology and Metabolism, in conjunction withthe 43rd Annual Scientific Meeting of the KES. This
prestigious congress will take place at Grand Walkerhill
Seoul in Korea and is hosted by KES. This year, there will
be joint symposiums in the SICEM program: ESROC-KES
will explore the intricate nuances of the thyroid; JES-KES
will concentrate on the field of bone; AFES-KES will
delve into the clinical aspects of diabetes, obesity, andlipid disorders; and ENDO-ESE-KES will provide valuable
insights into the field of pituitary, adrenal, and gonad
studies.

https://www.sicem.kr/about/overview.php

ECE 2024: 26th European Congressof Endocrinology
Stockholm, Sweden
May 11 – 14, 2024

Attracting more than 4,000 delegates, from morethan 100 countries, ECE continues to develop as aworld-leading congress for endocrine specialists. Given
that our community works on diverse research topics
and sees patients with a wide range of conditions,
ECE enables access to a comprehensive program,covering the breadth of endocrinology. Whatever
your area of interest, there will be sessions that areof direct relevance, as well as extensive networking
opportunities.

https://www.ese-hormones.org/
events-deadlines/european-congress-ofendocrinology/ece-2024

ENDOCR INE NEWS | M A RC H 2 0 2 4 |15BY DEREK BAGLEY
Obesity is anextremely complex
disease, especiallyin young children.
If a child younger
than the age of fivehas severe obesity,
it’s highly probablethat the cause is
genetic rather thanbeing overfed by
the parents.

BAD
reception

Unlocking a Confounding
Enigma Behind Monogenic
Obesity in Children

When two very different pediatric patientswith obesity presented with unusually highleptin levels, endocrine researchers took
notice and discovered that leptin was notadequately binding with receptors. When theyoung patients’ familial history was considered,solutions were finally forthcoming.

16 | M A RC H 2 0 2 4 | ENDOCR INENEWS.ORG

About three years ago, a 19-month-old
girl presented to Sidra Medicine — awomen’s and children’s hospital, medical
education, and biomedical research center locatedin Doha, Qatar — with severe obesity, the signs ofwhich began developing at just three months of age.
Khalid Hussain, MD, division chief ofEndocrinology at Sidra Medicine, which is amember of the Qatar Foundation, and his team
took on the case of this child who weighed almost
60 pounds before reaching the age of two. Hussain
says the child could hardly walk or even breathe,
so she also came under the care of a respiratory
team since the physicians thought her asthma may
be related to the obesity as well.
“I became very interested,” Hussain says. “I wanted
to understand why she had such severe obesity atthis age. We did some tests in Qatar, and I think the family atsome stage went to the U.K., as well. To cut a very long story short,between the U.K., Qatar, and Germany, we found that this child
had a genetic cause for the obesity — a defect in the hormone
called leptin, which regulates your feeding satiety.”
Monogenic obesity is a rare early-onset, and severe form ofobesity resulting from a mutation or deficiency of a single gene,e.g., leptin.
But this case was unusual in that children who have problems
with leptin have a deficiency; this child had very high levels of
leptin. After running some tests at the University Medical Centerin Ulm, Germany, Hussain and his team were able to show thatthe child was producing leptin, but it wasn’t working as well in the
body because it would not properly activate the leptin receptor.

An Increase in Pediatric Leptin Deficiency
In June 2023, Hussain and his colleagues and co-authors publisheda paper in the New England Journal of Medicine, detailing the caseof the above patient (Patient B) and another unrelated adolescent, a14-year-old boy (Patient A), who also had characteristics of leptin
dysfunction including intense hyperphagia, impaired satiety, andsevere, early-onset obesity. The authors point out that Patient A isof European descent, while Patient B is of Arab descent.
Martin Wabitsch, MD, PhD, head of the Division of PediatricEndocrinology and Diabetes at Ulm University Medical Centerin Ulm, Germany, and senior author of the NEJM paper tells

Wabitsch says that 2015 was a milestone because that’s when he and his
team found that even though high levels of leptin are secreted in the body,there was a defect in binding.

MARTIN WABITSCH,
MD, PHD
HEAD, DIVISION
OF PEDIATRIC
ENDOCRINOLOGY AND
DIABETES,ULM UNIVERSITY
MEDICAL CENTER,
ULM, GERMANY“This is, from a biologicalpoint of view, a totally newidea, new finding, neverbeen described before, thathuman nature can present
a mutated protein which isacting as an antagonist. It’s
not an antibody. It’s not an
autoimmune antibody. It’s anaturally occurring protein
working as antagonist when
you treat the patient withwild-type leptin, then you
will see that it’s blocking thereceptor. And that’s what wesaw also in the patients.”

ENDOCR INE NEWS | M A RC H 2 0 2 4 |17

Endocrine News that after the first description of congenital
leptin deficiency by Stephen O’Rahilly and Sadaf Farooqi,
most experts agreed that leptin deficiency was only found in
consanguineous families from Pakistan, Turkey, and possibly
some Arabic countries.
But then an adolescent girl from a family in Austria without
known consanguinity with severe, early-onset obesity and leptin
deficiency presented to the clinic in Ulm. Wabitsch runs a labthat focuses on children and adolescents with genetic obesity andleptin deficiency. He and his team tested this girl’s adipose tissuederived stem cells and differentiated adipocytes, and found proof
that the patient did indeed have adipocytes that do not secrete
leptin. Congenital leptin deficiency in this girl has been shown
to be due to a biallelic variant in the leptin gene.
“The phenotype was different to the Pakistani patients,”
Wabitsch says, “no immunological phenotype at all and theweight was much lower than that of the published patients. We
treated the patient with metreleptin, which was very difficult to
get at the time.”
Wabitsch says that from that point on, they had several new
patients with congenital leptin deficiency. Then in 2015, a twoyear-old patient from Germany presented with the classicalphenotype of leptin deficiency — severe obesity, hyperphagia —so the team measured serum leptin levels, but this time foundthe patient had high levels of leptin, in the 40s. “After excluding
other forms of genetic obesity, we said, ‘We don’t know what thispatient has,’ ” he recalls.
Around that time, another colleague of Wabitsch’s did leptin
sequencing in this child (which Wabitsch admits he wouldn’t
have done because the leptin levels were so high) and detected abiallelic variant in the leptin gene. “I was reminded of Kowarski
syndrome,” Wabitsch says, “growth hormone deficiency with

Once the young Qatari girlwas treated with high-dose
exogenous metreleptin,
Hussain says “eventually we
noticed that her appetite
was reduced, and overthe next several weeks,
the weight also started
coming down.” Not only has
her asthma disappeared
but she started walking
normally and even dancing,to her parents’ delight.

18 | M A RC H 2 0 2 4 | ENDOCR INENEWS.ORG

high growth hormone levels due to a defect in the binding of the growth hormone,so bio-inactive growth hormone. And then I said, ‘It seems to me that we havecongenital leptin deficiency with high leptin levels due to bio-inactive leptin.’”A “Eureka!” Moment
Wabitsch marks 2015 as a milestone — the time they found that even though highlevels of leptin are secreted in the body but there’s a defect in binding. They also
found that these patients could be treated with metreleptin as well. (These results
were also published in NEJM in 2015.) Wabitsch and his team screened morepatients and found they had bio-inactive leptin.
Wabitsch explains that bio-inactive hormones have been known to
endocrinologists for a while, from the aforementioned growth hormone toluteinizing hormone to thyroid-stimulating hormone. But this was new for
leptin, and it told the researchers that leptin measurements are not enough; genesequencing to exclude leptin was also required.
The team in Ulm also looked at the interaction between leptin and its receptor.
There are three binding sites with which leptin engages with its receptor. Wabitsch
says that binding site one’s function is unclear; site two is for high-affinity bindingof leptin to its receptor; and site three is for receptor activation. They theorizedthat a genetic variant could also affect the code for binding site three, and thus anaturally occurring antagonist could be impacting the receptor.

Factoring in Family History
That brings us back to the most recent NEJM paper. Hussain, Wabitsch, and theco-authors of the paper found that while both Patient A and Patient B had highlevels of leptin, they both had variants in binding site three. “That’s what we were
waiting for, humans with variants in this binding site, and both of them, in our invitro assessments, showed that these variants behaved as antagonists on the levelof the leptin receptor,” Wabitsch says. “And we needed much higher amounts ofmetreleptin to overcome the antagonism.”
From a biological point of view, this is a totally new finding that has never been
described before where “human nature can present a mutated protein which isacting as an antagonist,” according to Wabitsch. “It’s not an autoimmune antibody,”
he says. “It’s a naturally occurring protein working as antagonist when you treat thepatient with wild-type leptin, then you will see that it’s blocking the receptor. And
that’s what we saw in the two patients.”“We realized that we needed to treat the children with high dose exogenous
metreleptin,” Hussain says. “We admitted [Patient B], and we followed a particular
protocol by escalating the dose of metreleptin every few days. And eventually we
noticed that her appetite was reduced, and over the next several weeks, the weight

AT A

GLANCEX Monogenic obesity can
result from rare mutationsin the leptin gene usually
resulting in congenital
leptin deficiency, which
can be treated with thehuman leptin analogon
metreleptin.
X Young children who
presented with severe
obesity and high leptin
levels, which is unusual,
led researchers to discover
leptin was not binding withreceptors as it should.
X Recent study findings detailtwo cases of children withsevere obesity and highleptin levels treated withhigh doses of metreleptin.

ENDOCR INE NEWS | M A RC H 2 0 2 4 |19

KHALID HUSSAIN, MD
DIVISION CHIEF OF
ENDOCRINOLOGY,
SIDRA MEDICINE,
DOHA, QATAR“If they present extremely
early, that’s mostly suggestiveof a genetic cause. And
they should either discuss
this with a specialist, an
endocrinologist, or a geneticist
who has an interest in thisarea, because if you find thecause, you can actually makea complete difference to thechild’s management.”“They’re being treated by my adult colleagues in the adulthospital here in Qatar,” he says. “They’re responding very well, so
it’s not just the child. We eventually managed to treat the rest of
the family here, and they’re doing extremely well.”Indeed, both patients experienced a return to normal weight,
and Patient A reached mature Tanner stage at age 16.5. “After thetwo patients had extensive weight loss, which was presumably
accompanied by reductions in the endogenous productionof leptin variants, we reduced the metreleptin dose in bothpatients,” the NEJM paper authors write.
“Here, we provide in vitro and in vivo evidence for the existenceof leptin variants that orthosterically bind to, but do not fully
activate the leptin receptor, hence acting as competitive
antagonists in the presence of non-variant leptin,” Wabitsch says.

Overcoming the Antagonist
also started coming down. She’s down to about 18 or 19 kilos at
the age of about four or five now.”
Hussain says that the girl’s asthma has disappeared, she’s walking
normally and even dancing, with no medical issues at all. “It’sbeen absolutely revolutionary managing her and seeing her gofrom a child that couldn’t breathe in my clinic to someone who isstarting to dance around,” he says.
The girl’s parents are delighted, and Hussain says that theinteresting thing was that there were three other aunts in thisfamily who are adults and have severe obesity, so clinicians
investigated them, and the aunts have the same genetic problem.

20 | M A RC H 2 0 2 4 | ENDOCR INENEWS.ORG

And again, these findings speak to the absolute complexity ofa disease like obesity. If a child younger than the age of five has
severe obesity, it’s highly probable that the cause is genetic. The
general tendency is to think the parents are over-feeding thechild, but that tendency falls apart in the case of a 19-month-old.
“If they present extremely early, that’s mostly suggestive of agenetic cause.” Hussain says. “And they should either discuss
this with a specialist, an endocrinologist, or a geneticist who has
an interest in this area, because if you find the cause, you canactually make a complete difference to the child’s management. If
we had not discovered the cause, this poor child would continue
to gain weight, suffer from asthma, unable to walk or participate
in any of her life activities.”– BAGLEY IS THE SENIOR EDITOR OF ENDOCRINE NEWS. IN THE FEBRUARY ISSUE, HE SPOKE TO ENDOCRINE
SOCIETY MEMBER KEMAL AGBAHT, MD, ABOUT HOW HE MANAGED TO PRACTICE ENDOCRINOLOGY IN THE
WAKE OF THE 2023 EARTHQUAKE THAT DEVASTATED PORTIONS OF TURKEY.

COMPREHENSIVE CARE
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Critical

Recent Research
Emphasizes
More Dangers
of Obesity in
AdolescenceMASS

BY ERIC SEABORG

22 | M A RC H 2 0 2 4 | ENDOCR INENEWS.ORG

Two recent
studies fromThe Journalof Clinical
Endocrinology& Metabolism
underscore
the negative
metaboliceffects of fat
mass comparedwith leanmuscle masson adolescentcardiovascular
health as well asbone health.

S

everal recent studies have highlighted the importance of lean muscle mass versus
the dangers of fat mass in children and adolescents — and suggest that adolescence
could be a particularly important time to interrupt an individual’s trend toward themorbidities associated with obesity.
Studies often rely on body mass index (BMI) alone as a measure of obesity, but BMI can bemisleading because it does not differentiate lean mass from fat mass, according to Andrew
O. Agbaje, MD, MPH, a pediatric clinical epidemiologist at the Institute of Public Healthand Clinical Nutrition at the University of Eastern Finland.
To differentiate the effects of muscle mass versus fat mass, Agbaje led a team that studied
more than 3,000 adolescents from the U.K. Avon Longitudinal Study of Parents andChildren (ALSPAC) who had complete dual-energy x-ray absorptiometry measurements
and fasting blood samples taken at ages 15, 17, and 24 years.
The study, “DXA-based Fat Mass With Risk of Worsening Insulin Resistance in
Adolescents: A 9-Year Temporal and Mediation Study,” was published in the January 2024
issue of The Journal of Clinical Endocrinology & Metabolism and analyzed the longitudinalassociation of total fat mass, trunk fat mass, lean mass, and BMI with the cumulative riskof hyperglycemia, hyperinsulinemia, and high insulin resistance at those ages.
“Each 1-kilogram cumulative increase in total fat mass from ages 15 through 24 years
was associated with a progressively worsening risk of high insulin resistance as well as
hyperglycemia and hyperinsulinemia,” the study found.
“Fat mass drives insulin resistance, but muscle mass appears to reverse it in a very smallway,” Agbaje says. “If we only use BMI, we will not be able to see that muscle mass isbeneficial in lowering insulin resistance.”
Agbaje added that the study was also able to differentiate the effects of kinds of fat, suchthat “abdominal fat is twice as dangerous as total body fat. Every increase in abdominal fat
raised the risk of insulin resistance, not just at the time point but progressively from age
15 to 24.”

A Key Time to Intervene?
The temporal nature of the study — following each subject for nine years — enabled
Agbaje to conclude that “this age 15 to 17 is a very critical point, where physiology appears
to become pathology. The vicious cycle of insulin resistance and fat mass reinforcing eachother begins at the age of 17 years.”
The timing of the start of this “vicious cycle” led the study authors to conclude: “Midadolescence may be an optimal time for interrupting the worsening fat mass-insulin
resistance pathologic cycle and attenuating the risk of progressively worsening metabolic
dysfunction before young adulthood.”

ENDOCR INE NEWS | M A RC H 2 0 2 4 |23

Cardiovascular Evidence
Agbaje says that a study he published in Atherosclerosis on the effects oflipids on the cardiovascular system provides further evidence of how
early pathological damage can begin.

“

One critical point isthat when people withobesity lose weight, it is very
important that they do so by
exercise to keep up the lean bodymass. By keeping the lean bodymass, they will protect theirbones.”— REGIS COUTANT, MD, SPECIALIZED CENTER FOR OBESITY,
UNIVERSITY HOSPITAL, ANGERS, FRANCE

This study analyzed findings from almost 1,600 adolescents in the
ALSPAC cohort who had their lipids levels measured at ages 17 and
24 along with echocardiography measurements. The study found that“each 1 mmol increase in total cholesterol was associated with higher
odds of worsening left ventricular hypertrophy progression over sevenyears.”The study concluded: “Increasing lipid levels from adolescence throughyoung adulthood independently associated with the risk of progressively
worsening changes in cardiac structure and function and premature
cardiac damage in asymptomatic youth. Evidence of cardiac damage
attributable to high lipid levels may be seen two decades earlier in the
mid-twenties than the current level of evidence in the mid-forties.
Increased fat mass, systolic blood pressure, and insulin are potential
pathways through which increased lipids may contribute to cardiac
damage.”Agbaje noted that these findings could indicate a need for lipid screening
to begin at a much earlier age than called for in current guidelines.

Bone Mass Can’t Keep Up
Looking at another part of the body that obesity can affect, children withobesity have higher bone mineral density and bone mineral content
compared with children of average weight, yet those with obesity havea 25% higher risk of extremity fracture than children of average weight.

RESOURCES
Agbaje AO, Saner C, Zhang J, et al. DXA-based fat mass with risk ofworsening insulin resistance in adolescents: A 9-year temporal andmediation study. J Clin Endocrinol Metab. 2024 Jan 4:dgae004. doi:
10.1210/clinem/dgae004. Online ahead of print.
Emeriau F, Amsellem-Jager J, Bouhours-Nouet N, et al. Insufficient bonemineralization to sustain mechanical load of weight in obese boys: across-sectional study. J Clin Endocrinol Metab. 2024 Jan 2:dgad760. doi:
10.1210/clinem/dgad760. Online ahead of print.
Agbaje AG. Increasing lipids with risk of worsening cardiac damage in 1595
adolescents: a 7-year longitudinal and mediation study. Atherosclerosis.
2024 Feb:389:117440. doi: 10.1016/j.atherosclerosis.2023.117440.
Epub 2023 Dec 27.

24 | M A RC H 2 0 2 4 | ENDOCR INENEWS.ORG

Intrigued by this paradox, researchers led by pediatric endocrinologist Regis Coutant,MD, of the Specialized Center for Obesity at University Hospital in Angers, France,
explored the underlying mechanisms in “Insufficient Bone Mineralization to Sustain
Mechanical Load of Weight in Obese Boys: A Cross-Sectional Study,” also published in
the January 2024 JCEM.
The researchers used dual energy x-ray absorptiometry (DXA) to measure the bonemineral content and bone mineral density of about 250 boys with obesity between
the ages of 8 and 18 years at Angers Hospital.
They matched them by height and age with boys without obesity (whom the researchers
termed “lean boys”) using data from the U.S. National Health and Nutrition Examination
Study (NHANES).
The study found that each 1-point increase in BMI (1 kg/m2) was associated with anaverage 39-gram increase in bone mineral content in lean boys compared with a 25-gramincrease in boys with obesity — a 40% difference. Each 1-point increase in lean BMI was

AT A

GLANCEX Late adolescence
could be a criticaltime to interrupt
the march toward
the comorbidities
associated withobesity.
X Too much fat mass
could begin affecting
the cardiovascularsystem at an earlyage.

While fat mass drives insulin resistance, muscle mass appears to reverse it, albeit ina seemingly small way, according to Agbaje. He adds that if BMI is the only tool used
to measure fat mass, it’s difficult to see the benefits of muscle mass or the dangers ofabdominal fat.

X Children with obesity
do not add bone mass
at a rate adequate
to keep up with theadded load caused bytheir weight.

ENDOCR INE NEWS | M A RC H 2 0 2 4 |25

Andrew O. Agbaje, MD, MPH, FESC“

Fat mass drives insulin
resistance, but muscle
mass appears to reverse it in avery small way. If we only use
BMI, we will not be able to seethat muscle mass is beneficial
in lowering insulin resistance.
Abdominal fat is twice as
dangerous as total body fat.
Every increase in abdominal
fat raised the risk of insulin
resistance, not just at the time
point but progressively fromage 15 to 24.”
— ANDREW O. AGBAJE, MD, MPH, FESC, INSTITUTE OF PUBLIC HEALTH
AND CLINICAL NUTRITION, SCHOOL OF MEDICINE, FACULTY OF HEALTHSCIENCES, UNIVERSITY OF EASTERN FINLAND, KUOPIOChildren with obesity tend to have a higher bone mineral densityand bone mineral content than children of average weight.
However, those with obesity could have a 25% higher risk ofextremity fracture than average-weight children.

associated with an average 78-gram increase in bone mineral content inboth boys of average weight and boys with obesity, whereas a 1-point
increase in fat mass index was associated with an average decrease of 9grams of bone mineral content.
“When you increase the mechanical load with the weight, you have toincrease the bone mineral content,” Coutant says. “But the increase in
the bone mineral content in boys with obesity is significantly less than
it is in lean boys. So our study suggests that the increase in the bonemineral content associated with the increased weight in obese boys
is not enough to support the mechanical load, so it may explain therelative bone frailty of obese boys.”
Although the study did not address treatment, Coutant says that theresults suggest the importance of ensuring that children with obesity
receive enough calcium and vitamin D to support bone health.
He also highlighted the important association between lean body massand bone mineral content:“One critical point is that when people with obesity lose weight, it isvery important that they do so by exercise to keep up the lean bodymass. By keeping the lean body mass, they will protect their bones.”

26 | M A RC H 2 0 2 4 | ENDOCR INENEWS.ORG– SEABORG IS A FREELANCE WRITER BASED IN CHARLOTTESVILLE, VA. IN THE NOVEMBER
2023 ISSUE, HE WROTE ABOUT EFFORTS TO REDUCE THE RISK OF HYPOGLYCEMIA IN
OLDER ADULTS WITH DIABETES.

ENDO 2023
SESSION RECORDINGSVIEW MORE THAN 150 SESSIONSAND EARN UP TO 110 CME CREDITSP U R C H A S E T O D AY

© 2023 ENDOCRINE SOCIETYHAVINGa
Can Solving Pediatric Dyslipidemia
Really Be as Simple as Child’s Play?
BY KELLY HORVATH

28 | M A RC H 2 0 2 4 | ENDOCR INENEWS.ORG

As parents constantly telltheir kids to “go outside andplay,” new research published inBallF

or generations, moms and dads have been urging theirchildren to “go outside and play!” Although those wellmeaning parents probably just wanted to get their kids
out into the fresh air, little did they know that they were also
giving their kids sound cardiovascular health tips.

The Journal of Clinical Endocrinology& Metabolism basically proves thatmothers and fathers really do know
best, even when it comes to goodcardiovascular health!

However, what a study published in the December 2023
issue of The Journal of Clinical Endocrinology & Metabolism
does show for certain is that high levels of cholesterol duringchildhood have been associated with early signs of heartdisease when sedentary kids reach their mid-twenties, as well

ENDOCR INE NEWS | M A RC H 2 0 2 4 |29

“We [recently]
found that increasingcholesterol level within
the space of seven years[between ages 17 and24 years] increased therisk of premature heartdamage by 20%. We now
realize that sedentary
time was at the rootof all of the problems,
not even the cholesterol
itself. The cholesterol
now looks like anintermediate.”— ANDREW O. AGBAJE, MD, MPH, FESC, INSTITUTE OF
PUBLIC HEALTH AND CLINICAL NUTRITION, SCHOOL OF
MEDICINE, FACULTY OF HEALTH SCIENCES, UNIVERSITYOF EASTERN FINLAND, KUOPIO

Andrew O. Agbaje, MD, MPH,
FESC, questioned the WHO’s 2020
guidelines stating that children
should get at least an hour of
exercise every day. “Why 60
minutes?” he asks. “Why not 75?
Or 50? Then I also recognized thattelling adolescents that 80% of you
do not meet the guideline is tellingthem that they are failures, when
they are not.”as an increased risk of premature cardiovascular death when they are in their midforties. Furthermore, several clinical trials aimed at lowering cholesterol levels in the
youth population have had minimal or no effect.
In “Associations of Sedentary Time and Physical Activity From Childhood With
Lipids: A 13-Year Mediation and Temporal Study,” study author Andrew O. Agbaje,
MD, MPH, FESC, of the Institute of Public Health and Clinical Nutrition, School of
Medicine, Faculty of Health Sciences, University of Eastern Finland in Kuopio, and a
Harvard-certified clinical researcher makes child’s play of how to prevent dyslipidemia.
In the process, Agbaje turns entrenched beliefs about physical activity on their heads.

Origin Story
Using data from 792 “children of the ‘90s” from the University of Bristol’s Avon
Longitudinal Study of Parents and Children (ALSPAC), in England, Agbaje’s study
aims to fill a gap in the current understanding of the relationship between physicalactivity in childhood and adult cardiovascular health. While we have long suspectedthat sedentary time has deleterious effects on lipid indices, insufficient research has
been done on the optimal way to reduce sedentary time (i.e., increase physical activity).
According to the World Health Organization’s (WHO’s) “WHO guidelines on physicalactivity and sedentary behaviour,” from 2020, “Children and adolescents should do
at least an average of 60 minutes per day of moderate-to-vigorous-intensity, mostly
aerobic, physical activity, across the week.” The Centers for Disease Control andPrevention recommend the same.
The WHO also points out that current evidence suggests that 80% of children andadolescents do not meet this guideline. These metrics sent Agbaje on a quest. “Why30 | M A RC H 2 0 2 4 | ENDOCR INENEWS.ORG

To restrict dangerous sedentary time
for children, a combination of light andmoderate-to-vigorous-intensity physicalactivity could be the perfect solution.

60 minutes?” he asked. “Why not 75? Or 50? Then I also
recognized that telling adolescents that 80% of you do notmeet the guideline is telling them that they are failures, when
they are not. People don’t naturally accumulate 60 min/day
of moderate-to-vigorous-intensity physical activity (MVPA).
Specialized athletes choose to do this, but we are not designed
to do this. What we are designed to do is to walk.” Agbaje
says that in addition to the adolescent mental health hit thismessage delivers, it also affects parents, who likewise feel like
failures for not succeeding in pushing their children to achieve
60 min/day of MVPA.
“I began to see the problems of the 60-minutes-per-day
guideline — how ineffective, arbitrary, and unsustainable it isand the consequences of this negative publicity to adolescents.
So what is the benefit? There must be a paradigm shift,” heconcludes, “but before I can speak about paradigm shifts, there
must be evidence.”
Another problem with the WHO guideline — one they cite asa limitation — is that the threshold at which sedentary time
becomes harmful is not known, so they simply advise reducing
it. “This is not a guideline,” Agbaje says. “You don’t leave people
in limbo; we must be concrete.”

Universal Pediatric Lipid Screening
Agbaje says that ALSPAC data showed sedentary timemeasured by accelerometer worn for seven days at threetime points increasing from six hours per day in childhood
to eight hours per day in adolescence and to nine hours per
day by young adulthood, an increase driven largely — nosurprise — by screen time. He also analyzed measurementsof complete fasting plasma high-density lipoproteincholesterol, low-density lipoprotein cholesterol, triglycerides,
and total cholesterol taken at each of three follow-up visits
at ages 15, 17, and 24 years. “When we cumulatively lookedat that sedentary time and its impact on cholesterol level,
it was alarming to see that sedentary time independently
contributed nearly 70% to the total increase in cholesterollevel from the age of 15 to the age of 24.”
Add this to the findings from Agbaje’s previous studies that:
1) elevated pediatric lipid levels are linked to subclinicalatherosclerosis in the mid-twenties; 2) a simulated intervention
in late adolescence (around age 17) was shown to ameliorate
the pathophysiologic mechanisms driving atherosclerosis; and3) other researchers have reported pediatric dyslipidemia–
related premature cardiovascular mortality in the mid-forties,
and an important takeaway for clinicians emerges: “there
should be universal pediatric lipid screening,” Agbaje says.
But there’s more. “We [recently] found that increasing cholesterollevel within the space of seven years [between ages 17 and 24
years] increased the risk of premature heart damage by 20%,”
Agbaje says. The current study, however, revealed some additional
unpleasant surprises. “We now realize that sedentary time was at
the root of all of the problems, not even the cholesterol itself. The
cholesterol now looks like an intermediate,” he explains.
“The one out of five who develop heart disease is one too many,
when this is preventable. Also, when many of these heartdiseases eventually occur, we can’t cure them, we can only
manage them for life, which increases healthcare costs, yet it’s

ENDOCR INE NEWS | M A RC H 2 0 2 4 |31

so cheap to measure cholesterol levels.” Current guidelines recommending cholesterol
screening at age 40 are woefully misguided. At that point, any damage to thecardiovascular system that has occurred is probably irreversible, and the healthcare
cost burden spirals.

Finding Middle Ground

Andrew O. Agbaje,
MD, MPH, FESC“

I began to see theproblems of the
60-minutes-per-day
guideline — how
ineffective, arbitrary, andunsustainable it is andthe consequences ofthis negative publicity toadolescents. So what isthe benefit? There must
be a paradigm shift, but
before I can speak aboutparadigm shifts, there
must be evidence.

”— ANDREW O. AGBAJE, MD, MPH, FESC,INSTITUTE OF PUBLIC HEALTH AND CLINICALNUTRITION, SCHOOL OF MEDICINE, FACULTY
OF HEALTH SCIENCES, UNIVERSITY OF
EASTERN FINLAND, KUOPIO

32 | M A RC H 2 0 2 4 | ENDOCR INENEWS.ORG

So, sedentary time is profoundly harmful, yet 60 min/day of MVPA is an unrealistic
target — where do we go from here? Fortunately, there is an extremely effective —yet systematically overlooked — middle ground: light physical activity (LPA). For
children and adolescents, LPA can take many easy-to-come-by forms like walking,riding a bike, and even playing on the playground. The irony will be lost on no one
that this is precisely what childhood used to look like.
Agbaje’s study showed that time spent in MVPA does not change significantly fromchildhood to young adulthood, but what does change is the amount of time spentsedentary, and this extra time has been “stolen” from time that had been spent in
LPA. “Our study showed that we need at least three to four hours of light exercise
every day to be able to counter the effects of sedentary time. Up to six hours oflight exercise every day is the optimal amount, but, realistically, as we grow and get
involved in classes and work, our time is being fought for by many responsibilities.
So our studies have shown that if we can get three to four hours of light exercise
every day, we can antagonize all the negative effects of sedentary time.” In otherwords, LPA completely reverses that 70% increase in total cholesterol level fromage 15 to 24 and therefore also obviates its negative downstream effects, such as
subclinical atherosclerosis and premature heart damage.
LPA has other advantages as well, such as being accessible to most people, whereas
not everyone can participate in MVPA for various health reasons. LPA also can be
implemented gradually and systematically until it becomes what Agbaje called an“autopilot of positivity” (as compared to the “autopilot of negativity” that sedentary
time induces).
That this is great news is clear, but why no recommendation exists for a specificsedentary threshold, which equates to increasing LPA, is not. This is where Agbaje’s
paradigm shift is critical. “What we have been pushing does not work. MVPA is not
the right solution for sedentary time.”“I Need to Fight for the Kids”
To be clear, Agbaje is not decrying MVPA, which certainly has many overall healthbenefits, but he is saying that it is not going to improve cholesterol parameters
as effectively as LPA can because increased sedentary time is driving cholesterol
increases, and the increase in sedentary time was bought at the expense of time spentin LPA. LPA also has the upper hand because its effects on cholesterol reduction
are long-lasting, whereas the effects of MVPA diminish soon after exercise ceases,
mediated by fat mass.

While too much sedentary time is harmful and 60 minutes of physicalactivity is unrealistic, the middle ground appears to be light physicalactivity such as walking, bike riding, or playing on the playground.

Ultimately, spending time in both MVPA and LPA while
reducing time spent sedentary is the optimal approach tooverall health from a physical activity standpoint. Thesefindings are also true for adults — increasing LPA improves
several health parameters and lowers the risk of various
diseases — but Agbaje will keep his research focus on younger
populations. “They don’t have many voices. I need to fightfor the kids.” Prevention, he believes, through decreasing
sedentary time and instituting pediatric cholesterol screening,is the turning point in this fight against dyslipidemia.
The study was funded by the Finnish Cultural Foundation,
the Finnish Foundation for Cardiovascular Research, theYrjö Jahnsson Foundation, the Jenny and Antti Wihuri
Foundation, the Orion Research Foundation, the Aarne
Koskelon Foundation, the Paulo Foundation, the Paavo
Nurmi Foundation, and the Ida Montinin Foundation.

– HORVATH IS A FREELANCE WRITER BASED IN BALTIMORE, MD. IN THE
FEBRUARY ISSUE, SHE TALKED WITH 2024 TRANSATLANTIC AWARD WINNERFELIX BEUSCHLEIN, MD, ABOUT HIS CAREER AND RESEARCH.

At A Glance• In a 13-year study of activity and lipid levels
in participants ages 11 through 24, increasing
sedentary time was associated with increasing
low-density lipoprotein cholesterol, triglyceride, andtotal cholesterol.

• Increased light physical activity (LPA) (i.e., reduced
sedentary time) reduced total cholesterol by five- toeight-fold and was significantly less subject to theeffect of fat mass than was moderate-to-vigorous
intensity exercise.

• Recommending instituting cholesterol screening inadolescence, when reversing damage is still possible,
and engaging in at least three to four hours per day of
LPA could be helpful to include in future guidelines.

ENDOCR INE NEWS | M A RC H 2 0 2 4 |33

LABORATORY NOTES

Adipose tissue as seen from under a microscope lens.

Evan D. Rosen, MD, PhD

Scratching the SURFACE
Q&A with
2024 Roy O. Greep
Laureate for
Outstanding Research
Evan D. Rosen,
MD, PhD

BY GLENDA FAUNTLEROY SHAW

34 | M A RC H 2 0 2 4 | ENDOCR INENEWS.ORG

H

is significant contributions to unlocking the mysteries of adipose biology
are numerous, yet Evan D. Rosen, MD, PhD, offers that he and his fellow
researchers have just scratched the surface of possibilities in treating thediseases most impacted by adipose tissues.
Rosen has been recognized as the Endocrine Society’s 2024 Laureate for Outstanding
Research — an annual award that honors the work of the late Roy O. Greep, PhD,
recognizing meritorious contributions to research in endocrinology.
Rosen is the chief of the Division of Endocrinology, Diabetes, and Metabolism at
Beth Israel Deaconess Medical Center and professor of medicine at Harvard Medical
School in Boston, Mass. His team of laboratory researchers aim to define novel
targets that can be manipulated to improve outcomes in metabolic disease. They
research the transcriptional pathways that underlie metabolic diseases like obesity
and type 2 diabetes. They use genomic and epigenomic approaches to identify novel

When Evan D. Rosen, MD, PhD,
first began researching adipose
biology many years ago, not much
was known about it and its impacts

In Honor of
Roy O. Greep, PhD

on so many diseases. He talks to
Endocrine News about how far thescience has advanced regarding
adipose tissue as well as his own
lab’s research, the importance ofcollaboration, and why a laboratory
is a lot like a submarine!
transcription factors and pathways that regulate processes
such as adipogenesis, lipid handling, insulin resistance, andmetabolic memory. His lab also created many mouse models
that are widely used by the research community to study
adipose tissue.

The Endocrine Society honors Roy Orval
Greep, PhD, (1905 – 1997) a Harvard
University endocrinologist and scholar
renowned for his seminal observations related
to reproduction. Greep spent most of his
career at Harvard, teaching anatomy, dental
science, and endocrinology and histology,
and serving as dean of the Graduate Schoolof Dental Health. He was editor-in-chief ofEndocrinology and edited two widely used
textbooks on endocrinology and histology.
Greep served as the 45th president of the
Endocrine Society from 1965 to 1966.

Endocrine News wanted to learn more about Rosen’slaboratory’s goals and the future of adipose research.

Endocrine News: What did hearing the newsof the recognition for Outstanding Researchmean to you?
Evan D. Rosen: It was such a lovely feeling — so muchof our work as scientists can feel isolating and self-contained.
In many ways, the lab is like a submarine. We go dark forlong periods of time as we puzzle through a project, surfacing
every so often to communicate our results to the rest of thecommunity. Winning the Greep award meant that someone
was tracking our submarine, which is very gratifying andvalidating.

EN: Your work in helping to understandadipose biology is well recognized. How did
you find yourself delving into this type of
research?

ENDOCR INE NEWS | M A RC H 2 0 2 4 |35

LABORATORY NOTES

Rosen: I was attracted to adipose biology because, when
I started working in the field, so little was known. The
first scientific meetings I attended only had a hundred
people or so (compared to thousands now), and there wasa sense that this was a really important area that had been
overlooked for a long time.

EN: I’m curious about your view on the
progress that has been made since yourearly scientific meeting experience? Is
it correct that the growth in numbersof researchers has led to promisingcollaborations, both nationally and globally?
Are young researchers in your lab excitedabout their future in the field?
Rosen: Yes, there have been some terrific and productive
collaborations, both within the adipose community andbetween adipose researchers and workers in other fields.
One example of the former is the Human Cell Atlas
Adipose Bionetwork (which I co-lead), and which ispulling the community together to develop standards formethodology and nomenclature. A lot of young scientists
are interested in adipose tissue, so it certainly seems thereis excitement in the field.

EN: We know how to treat diabetes (and, inmost cases, prevent it), but what is the mostimportant discovery still to be unlocked
in treating the disease? Meaning, is therea need for better medications or better
treatment options?
Rosen: Adipose tissue impacts so many diseases — type2 diabetes, of course, but also obesity, lipodystrophy,
MASLD, hyperlipidemia, atherosclerosis, cancer, andmore. All of these conditions could potentially benefit
from therapies that manipulate adipose tissue biology.
Despite the fact that there are already many medications
for these diseases, they continue to cause a huge amount ofsuffering. So, there is absolutely a need for new treatments,
and adipose tissue offers potential opportunities for tissuebased therapeutics. In many ways, we have just scratched
the surface of what’s possible.

– FAUNTLEROY SHAW IS A FREELANCE WRITER BASED IN CARMEL, IND.
SHE WRITES THE MONTHLY LABORATORY NOTES COLUMN.

36 | M A RC H 2 0 2 4 | ENDOCR INENEWS.ORG

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ADVOCACY

Endocrine
Society
Advances
Women’s
HealthThrough
Research
andAdvocacyAs leaders in women’s healthresearch, our members appreciate
how persistent underinvestment in
women’s health research has impacted ourability to understand and treat conditions
that only affect women such as polycystic
ovarian syndrome and menopause; and thosethat affect men and women differently suchas thyroid disease, osteoporosis, diabetes,
and infertility. We also know how basic
science can help us understand how diseases
may affect women differently through sex
differences. We are therefore encouraged by
the establishment of an ad hoc committeeof the National Academies of Sciences,
Engineering, and Medicine (NASEM) charged
with addressing the persistent gaps that remainin the knowledge of women’s health researchacross all National Institutes of Health (NIH)
institutes and centers (ICs).
The NASEM Committee has ambitious
objectives and sought expertise from our Society
to inform their discussions and thinking as
they develop recommendations for the NIH toconsider and potentially adopt. Working witha group of member women’s health experts, wedeveloped a detailed statement delivered to thecommittee in which we emphasized important
endocrine-relevant issues. For instance, we
urged the committee to consider a life course
approach to the definition of women’s healthfrom in utero development through advanced
age; to consider gender and biological sex as
essential components of women’s health; and toencourage the NIH to encourage and support
women’s health researchers in fields across all
institutes and centers at the NIH.
NASEM also invited us to deliver prepared
remarks during the committee’s open session
on March 7. Research Affairs Core Committee
member Monica Laronda, PhD, shared the
Endocrine Society’s priorities and insights,
giving committee members the opportunity to
ask questions and engage with us further as it
seeks to fulfill its charge. We look forward tocontinuing to share our members’ perspective

38 | M A RC H 2 0 2 4 | ENDOCR INENEWS.ORG

with the committee and working with the NIH
to implement the recommendations arisingfrom the report.
The week prior to the NASEM meeting saw theEndocrine Society participate in another event
emphasizing women’s health. On February
29, during the 6th session of the United
Nations Environment Assembly (UNEA6), theEndocrine Society participated in a meetingsponsored by the Women’s Major Group on
how chemicals are affecting women’s health.
Recognizing endocrine-disrupting chemicals(EDCs) as major contributors to women’s
health issues such as breast and ovarian cancer,
Marina Fernandez, PhD, was invited to sharethe latest scientific information about the
impacts of EDCs in plastic on women’s healthand our recommendations on how member
states can improve public health by limiting
exposure to hazardous chemicals.
Following this event, the Endocrine Society
and the International Pollutants Elimination
Network (IPEN) joined together to announce
the launch of our latest collaborative report,“Endocrine-Disrupting Chemicals: Threatsto Human Health.” The report summarizes
the latest scientific information on EDCs andtheir links to disease, including information
on regulatory policies that have been updated
in recent years to reduce exposures. The
lead author on the report, Endocrine Society
member Andrea Gore, PhD, participated in amedia event during UNEA6 to share some of
the key points raised in the report. The reportis intended to inform policymakers and civilsociety organizations in their work to raiseawareness and develop policies to minimize
exposures to hazardous chemicals.
UNEA is the world’s most influential decisionmaking body on environmental issues, and weare thrilled to collaborate with the Women’s
Major Group and IPEN to share our members’scient i f ic ex per t ise w it h t he assembled
delegations.

ADVOCACY

Clinical Endocrinology
Mentorship Opportunity at
ENDO 2024
Endocrine Society
Advocates to Protect
and Increase Funding
for the NIH
On March 5, the Endocrine Society conducted a
Researcher Hill Day to advocate for the importanceof the National Institutes of Health (NIH).
Endocrine Society past-president Carol Wysham, MD, was anactive participant in Endocrinology Mentor Day at ENDO 2023
in Chicago, here instructing a mentee on the proper placementof a continuous glucose monitor (CGM).

The Endocrine Society will host the second annual
Endocrinology Mentor Day (eMD) at ENDO 2024
in Boston, on Sunday, June 2.

During the event, medical students and residents will be pairedwith an Endocrine Society member as their “mentor” for theday. Mentors will guide attendees around ENDO and introduce
them to ENDO’s signature programs, including poster
presentations, interesting case studies, and a plenary session.
The event at ENDO 2023 in Chicago last year was a big success,due in large part to our terrific mentors.
If you are interested in joining us for this program as a mentor,
or would like to learn more about the event, please email Ellie
Cliff at: ecliff@endocrine.org.

We asked Congress to complete work on afunding bill for the remainder of fiscal year (FY)
2024, before funding expires March 8, thatwill maintain paylines and protect early-stage
investigators and trainees, and for $51.3 billion
for the NIH in FY 2025. On Hill Day, we will
also advocate for the extension of the Special
Diabetes Program (SDP) for two years with a
13% increase in funding.

Take Action

Amplify our message by joining in our online
campaigns for research funding and SDP byvisiting: endocrine.org/advocacy/take-action.
Even if you cannot join us in Washington, D.C.,
for Hill Day, you can make your voice heard
by your congressional delegation. In just threeclicks, you can send a letter template to yoursenators and representatives and support
Endocrine Society priorities.

ENDOCR INE NEWS | M A RC H 2 0 2 4 |39

ADVOCACY

EU Proposes Science-Based Restrictions on Bisphenols

F

ollowing the European Food Safety Authority’s (EFSA)
updated opinion on bisphenol-A (BPA), which indicateda concern for human health at extremely low levels of
exposure, the European Commission announced a proposal
to ban BPA in food contact materials (FCM) including plastic
packaging and coatings. The Commission’s proposal also goesa step further by introducing restrictions on derivatives of BPA
to prevent substitutions with other bisphenols with potentiallysimilar hazardous properties.
The Endocrine Society welcomes the new proposal, which
is based on a systematic review of the latest science on BPA,
including results from the Consortium Linking Academic and“

We enthusiastically support theprovisions to address BPA derivatives,
which is consistent with ourrecommended approach for group-based
restrictions on similar chemicals.

”

Regulatory Insights on BPA Toxicity (CLARITY-BPA). The
Society’s EU EDCs Task Force has provided expert guidance
to European agencies and the Commission on every stepof this process, from suggesting studies to inform EFSA’s
systematic review, to providing commentary on the draft
opinion, and finally encouraging the Commission to prioritize
this important regulation. We enthusiastically support theprovisions to address BPA derivatives, which is consistent with
our recommended approach for group-based restrictions on
similar chemicals.
The proposal is open for a public consultation through early
March, and our task force will carefully review the draft
regulation and offer further suggestions to ensure that the final
restrictions achieve the intended health protections and can beswiftly implemented.

How to Incorporate the New Medicare
Complex Code G2211 into Your PracticeT

he Endocrine Society has long advocated the need for
Medicare to pay endocrinologists appropriately.

Due to our advocacy efforts, the 2024 Physician Fee Schedule
includes an increase for endocrinology partly because of theopportunity to use a new complex add-on code. On January
29, the Endocrine Society hosted a members-only webinar

40 | M A RC H 2 0 2 4 | ENDOCR INENEWS.ORG

explaining how clinicians can integrate the G2211 code into
their practices. The recording of the webinar and additional
resources can be found on our Physician Payment web pageat: www.endocrine.org/improving-practice/macra. We alsocollected the questions asked during the webinar and created a“FAQ” document that can be found on the Physician Payment
web page as well.

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