Tag: Appetite and ingestive regulation

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Early Glucagon Elevation Linked to MASLD in Type 2 Diabetes

Researchers at the German Diabetes Centre have found that glucagon, a hormone that is considered to be a counterbalance to insulin, is elevated early in type 2 diabetes (T2D) and closely linked to the development of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). The findings, published in the journal Diabetes Care, indicate that dysregulation of glucagon occurs soon after diagnosis of type 2 diabetes and is associated with liver fat accumulation, information that could prompt a shift in the understanding of how MASLD progresses and suggesting new ways to treat it.

“Our findings highlight that type 2 diabetes should not be viewed solely from the perspective of insulin action. The liver and the regulation of glucagon play a special role in metabolism,” said senior author Michael Roden, MD, scientific director of the German Diabetes Centre.

The aim of the research was to address unresolved questions about the activity of glucagon in early type 2 diabetes and how it may influence the development of fatty liver disease (MASLD). While insulin resistance is central to diabetes research, glucagon is also known to contribute to elevated blood glucose by stimulating hepatic glucose production. MASLD is also common in people with type 2 diabetes, yet the interaction between liver fat and glucagon regulation is not well understood.

To investigate glucagon’s role in this regard, the researchers analyzed 50 adults with newly diagnosed type 2 diabetes and 50 people with normal glucose tolerance matched for age, sex, and body mass index. Participants underwent mixed-meal tolerance tests to assess glucagon and metabolites, hyperinsulinemic-euglycemic clamps to measure insulin sensitivity, and imaging using magnetic resonance spectroscopy and MRI to quantify hepatic lipid content and visceral fat.

The resulting data indicated that those people with newly diagnosed type 2 diabetes had significantly higher liver fat and elevated glucagon levels both when fasting and after meals.

“Individuals with T2D had an ∼65% higher HLC as well as higher fasting and postprandial glucagonemia (∼30% and ∼75%) than those with NGT,” the research noted. The presence of MASLD, rather than diabetes itself, was associated with higher fasting glucagon levels. Elevated glucagon levels after a meal were specifically linked to liver fat content in those people with type 2 diabetes.

These associations were independent of insulin sensitivity and visceral adipose tissue. “Hyperglucagonemia in the face of higher HLC in early T2D is not due to differences in insulin sensitivity or glucagonotropic metabolites but could suggest hepatic glucagon resistance,” the researchers wrote.

The study also addressed the role of amino acids and nonesterified fatty acids (NEFAs), which previous research has suggested serve as mediators of glucagon secretion. But the current research did not show this to be the case. “This study demonstrates that 1) fasting glucagon concentrations are elevated and tightly associated with MASLD already in newly diagnosed T2D and 2) increased postprandial glucagon levels are positively linked to HLC only in early T2D, but not NGT… but 3) neither amino acids nor NEFAs mediate this hepatopancreatic relationship,” the researchers wrote.

These findings could boost current development of glucagon-based drugs, including dual- and triple-agonists targeting incretin and glucagon receptors, which are already being studied for the treatment of MASLD. The study implicates that altered glucagon physiology in type 2 diabetes may influence how patients respond to drugs, and differences in glucagon signaling may help explain why some therapies appear less effective in individuals with diabetes compared to those without.

While this study was cross-sectional and does establish causality, the researchers pointed to the consistent associations across multiple metabolic measurements as evidence to support further investigation. Additional work could determine whether hepatic glucagon resistance can be directly measured and targeted. Future research will also focus on finding out whether modifying glucagon signaling can alter the progression of MASLD and type 2 diabetes, and how new therapies in development can be personalized for patients with different metabolic profiles.

The post Early Glucagon Elevation Linked to MASLD in Type 2 Diabetes appeared first on Inside Precision Medicine.

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Behavior Change Techniques in Digital Health Interventions for Promoting Adolescent Health Behaviors: Systematic Umbrella Review

Background: Digital health interventions (DHIs) using behavior change techniques (BCTs) show promise in addressing adolescent health behaviors, but evidence of their effectiveness across health behavior domains remains fragmented and poorly summarized. Objective: This systematic umbrella review synthesized evidence from existing systematic reviews on the effectiveness of BCTs within DHI targeting key adolescent health behavior domains: alcohol consumption, tobacco use, physical activity, dietary habits, and obesity management. Methods: We systematically searched PubMed, PsycInfo, Embase, and CINAHL in April 2024 for reviews of DHI for adolescents (10‐19 years old). We coded all identified BCTs using the Behavior Change Technique Taxonomy version 1 (BCTTv1). Data on BCT effectiveness, intervention characteristics, and review quality were extracted and narratively synthesized using AMSTAR-2 (A Measurement Tool to Assess Systematic Reviews 2). Results: A total of 20 reviews, comprising 224,135 participants, were included. These examined DHIs targeting physical activity (7 reviews), dietary habits (3 reviews), alcohol consumption (2 reviews), combined alcohol and nicotine use (1 review), and obesity management (1 review), with an additional 6 reviews covering multiple health behaviors. Across reviews, 65% (13/20) reported statistically significant positive effects on at least one health behavior outcome. “Social support (unspecified)” was the most consistently adopted and effective BCT, especially with parental/peer involvement. The combination of “self-monitoring,” “goal setting,” and “feedback” also commonly appeared in successful interventions. Intervention effectiveness appeared linked to strategic BCT selection and individualization rather than the total number of techniques. The methodological quality of included reviews was predominantly low, with only 2 rated high. Conclusions: This umbrella review identified “social support (unspecified)” as a consistently effective BCT across multiple adolescent health behavior domains, particularly with parental/peer involvement. Intervention success appears linked to targeted and individualized BCT use. Future research should prioritize clarifying the specific components and delivery methods of effective social support, rigorously evaluating BCT configurations in underexplored areas such as adolescent smoking cessation, and examining their long-term impact on behavior change.
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Glioblastoma: Testosterone Supplements Linked to 38% Lower Risk of Death

Researchers at Cleveland Clinic have discovered that androgen hormones such as testosterone can limit the growth of glioblastoma tumors in men. Results published today in Nature show that men receiving testosterone supplements for reasons unrelated to cancer showed a 38% lower risk of death compared to patients not taking these supplements. 

These findings are surprising because testosterone is known to contribute to the growth of other forms of cancer in men, such as prostate cancer, where hormone therapy is used routinely to decrease levels of androgen hormones and block cancer progression. However, these hormones were found to play a very different role in glioblastoma, an aggressive form of brain cancer that is more commonly diagnosed in men. 

“This outcome is a welcome surprise and may potentially offer a lead for new treatments for a kind of cancer that is deadlier in men,” said Anthony Letai, MD, PhD, director of NIH’s National Cancer Institute (NCI).  

In a mouse model of glioblastoma the researchers found that reducing levels of androgen hormones induced overdrive on the hypothalamus-pituitary-adrenal (HPA) axis, a brain circuit that controls reactions to stress and many physiological processes including hormone secretion. This caused a spike in stress hormones that led the brain to reinforce the protective function of the blood-brain barrier and create an immunosuppressive environment in the brain, reducing the ability of immune cells to fight against the tumor. 

“The brain has evolved to keep stuff out and that includes immune cells from elsewhere in the body. It’s a delicate tissue that often doesn’t want huge immune reactions,” said Justin D. Lathia, PhD, professor of cancer sciences and scientific director of the Brain Tumor Center at Cleveland Clinic.

Importantly, this effect was only observed in male mice. In females, changes in testosterone levels did not produce the same effects.

These findings were then confirmed in human samples obtained from 1,300 men with glioblastoma participating in the NIH database Surveillance, Epidemiology, and End Results (SEER). An analysis showed that men who received supplemental testosterone for reasons unrelated to their glioblastoma diagnosis had a 38% lower risk of death than other male patients. 

More research will be needed to better understand the complex pathway activated by testosterone and other androgen hormones. While the current study identified inflammation in the hypothalamus as a potential trigger of HPA axis activation, future work will look for the exact mechanism glioblastoma tumors employ to induce this reaction from an entirely different region of the brain.  

Lathia noted that, although these results do not establish a causal link between testosterone and patient outcomes for men diagnosed with glioblastoma, the study opens the door for future clinical trials that dive deeper into the link between androgen hormones and glioblastoma tumor growth. He added, “An obvious follow-up study would be to find out whether androgen deprivation, which is a common treatment for cancer, is actually detrimental for glioblastoma.” 

 

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Pancreatic Cancer Shares Genetic Drivers with Obesity and Diabetes

Researchers at the University of Birmingham have found that the same genes are active in pancreatic cancer, obesity, and diabetes. Their findings, published in Cancer Medicine, could finally provide an explanation to why metabolic disease is a major risk factor for pancreatic cancer. 

“We know that people with obesity or diabetes tend to have worse outcomes from pancreatic cancer, but the biological reasons have not been clear,” says Animesh Acharjee, PhD, associate professor of integrative analytics and AI at the University of Birmingham and senior author of the study. “Our study shows that the same genes and inflammatory pathways are active in both metabolic disease and pancreatic cancer, which helps explain this link and points to new opportunities for identifying high‑risk patients and developing more targeted treatments.”

Treatment options are currently limited for patients diagnosed with pancreatic cancer, a form of cancer that is often diagnosed at advanced stages. Only about 15% of patients are eligible for surgery, and about 80% of them relapse after treatment. 

Previously, the researchers had identified a series of genes that were consistently altered in metastatic pancreatic tumors. In the current study, they examined whether these same genes also play a role in metabolic disorders such as obesity and diabetes, which are increasingly recognized as risk factors for pancreatic cancer.  

First, the team analyzed genetic data from publicly available datasets to study how six key drivers of pancreatic cancer behave in healthy individuals compared to people with obesity. These included the ITGAM, PECAM1, CCL5, STAT1, STAT2, and CD44 genes, which are involved in inflammation, immune cell recruitment, and lipid metabolism processes. All six genes were found to be upregulated in individuals with obesity. 

Single-cell RNA sequencing of patient tumor samples revealed that a subset of immune cells, including macrophages and monocytes found within the tumor microenvironment, expressed these core six genes at higher levels than other cells. This discovery suggests this group of cells may be key drivers of tumor progression and recurrence and a potential therapeutic target for the development of targeted therapies.  

Taken together, these findings indicate that immune and inflammatory pathways that drive metabolic disease also play a major role in pancreatic cancer, where they could be involved in immune evasion and recurrence after surgery. Future work will investigate whether modulating the activity of these genes could reduce the chronic inflammation and immune dysregulation that drive the recurrence of pancreatic cancer to improve the success rate of this procedure. Targeting these pathways could offer new therapeutic strategies to manage pancreatic cancer, especially in patients with underlying metabolic conditions.

“This study highlights how chronic inflammation and metabolic dysfunction can intersect with cancer biology,” says Simon Jones, PhD, professor in musculoskeletal aging at the University of Birmingham and team lead for the NIHR Biomedical Research Centre. “Understanding these shared mechanisms is essential if we are to improve outcomes for patients who are living with multiple long‑term conditions alongside cancer.”

 

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Advanced Cardiovascular-Kidney-Metabolic Syndrome Linked to Increased Cancer Risk

Researchers from Japan are calling for increased cross-disciplinary collaboration after showing that people with advanced cardiovascular-kidney-metabolic (CKM) syndrome are at increased risk for cancer.

They explain in Circulation: Population Health and Outcomes that CKM syndrome is a conceptual framework, proposed by the American Heart Association (AHA) in 2023, that captures the interconnected nature of cardiovascular, kidney, and metabolic diseases and reflects the shared risk factors and pathophysiological mechanisms of these diseases.

The current study findings suggest that this framework could also “serve as a valuable, non-invasive stratification tool in precision oncology and preventive medicine,” said Hidehiro Kaneko, MD, PhD, the study’s lead author and associate professor in the department of cardiovascular medicine at the University of Tokyo in Japan.

He told Inside Precision Medicine: “By identifying individuals with advanced CKM (particularly stages 3 and 4), clinicians could tailor and potentially intensify cancer screening protocols for these high-risk patients. This enables more personalized surveillance and early detection strategies that bridge the gap between cardiometabolic management and cancer prevention.”

According to AHA statistics, nearly nine out of 10 adults in the United States have at least one component of CKM syndrome, which includes high blood pressure, abnormal cholesterol, diabetes, obesity, and reduced kidney function.

Although these components of CKM syndrome have each been associated with an increased risk for certain cancers, the relationship between CKM stage and the risk for incident cancer is unclear, as current knowledge is largely derived from studies of individual components rather than the integrated syndrome.

To address this, Kaneko and team analyzed administrative claims data for more than 1.3 million people living in Japan. Of these, 12.5% had CKM stage 0, 9.8% had stage 1, 31.7% had stage 2, 36.3% had stage 3, and 9.8% had stage 4.

The researchers report that, over a median follow-up of 3.4 years, increasing baseline CKM stages were associated with significantly greater cancer incidence.

Specifically, the incidence of cancer was 81.2 cases per 10,000 person–years in people with CKM stage 0, increasing to 97.2, 105.1, 250.9, and 257.7 cases per 10,000 person–years in those with CKM stages 1, 2, 3, and 4, respectively.

After adjustment for age, sex, alcohol consumption, and physical inactivity, individuals with CKM stage 1 or 2 at baseline did not have a significantly increased risk for cancer relative to those with CKM stage 0. However, people with CKM stages 3 and 4 had significant 25% and 30% higher risks for cancer, respectively, than those with stage 0.

When the team analyzed the data by cancer type, they found that the incidence of colorectal, stomach, lung, renal pelvis and ureter, pancreatic, non-Hodgkin lymphoma, bladder, liver, kidney, thyroid, leukemia, and gallbladder cancers increased progressively with higher baseline CKM stages. There was a similar pattern for prostate cancer in men and for breast, cervical, and uterine cancers in women.

Conversely, there was no clear association between baseline CKM stage and the incidence of esophageal cancer, malignant melanoma, or Hodgkin lymphoma.

The associations between CKM stage 3 or 4 and cancer risk were stronger in men than in women and in people younger than 65 years of age relative to older individuals. However, people aged 65 years and older were also at increased risk for cancer even when they had CKM stage 1 or 2 relative to stage 0, whereas younger individuals were not.

Kaneko said that the study highlights a critical need for increased awareness of the link between CKM syndrome and cancer.

“While physicians and the public generally understand that interconnected metabolic and kidney conditions lead to heart disease and stroke, the integrated CKM syndrome is rarely viewed as a significant driver of cancer,” he remarked. “Our study demonstrates a clear, stage-dependent increase in incident cancer risk as CKM progresses, underscoring the need to recognize cancer as a major potential consequence of this multisystem syndrome.”

Kaneko suggested that “this can be addressed by shifting public health messaging to emphasize that proactive lifestyle modifications—such as weight management, a healthy diet, and regular exercise—provide dual protection against both cardiovascular events and cancer.”

He added: “Within the medical community, we should promote the CKM staging framework as a comprehensive health assessment tool, encouraging cross-disciplinary collaboration among cardiologists, nephrologists, endocrinologists, and oncologists to manage these overlapping risks holistically.”

The post Advanced Cardiovascular-Kidney-Metabolic Syndrome Linked to Increased Cancer Risk appeared first on Inside Precision Medicine.

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STAT+: French regulator fines Novo and Lilly over weight loss ad campaigns

As competition mounts in the red-hot market for weight loss drugs, France’s medicines regulator fined Novo Nordisk approximately $2 million for running “misleading” advertisements for its Wegovy and Saxenda medications.

At the same time, the National Agency for Medicines and Health Products Safety also fined Eli Lilly roughly $127,000 over advertising for its Mounjaro obesity treatment that purportedly amounted to indirect promotion of a medicine for which a prescription is required.

The penalties reflect increasing concern among regulators that weight loss medicines may be misused and, as result, promotions run by pharmaceutical companies are being closely scrutinized. Two years ago, the regulator issued a bulletin on the risks associated with the drugs, especially inappropriate use.

Continue to STAT+ to read the full story…

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Biomarker of Epigenetic Aging Could Signal Depression

Research led by New York University suggests a marker of epigenetic aging could be linked to depression.

The team found that accelerated aging of a type of white blood cell called a monocyte was significantly associated with the psychological and cognitive expressions of depression in a group of women with and without HIV.

“Depression is not a one-size-fits-all disorder—it can look really different from person to person, which is why it’s so important to consider varied presentations and not just a clinical label,” said lead researcher Nicole Beaulieu Perez, PhD, assistant professor at NYU Rory Meyers College of Nursing, in a press statement.

“Our study reveals unique biological underpinnings of mental health that are often obscured by broad diagnostic categories.”

As reported in The Journals of Gerontology Series A, the researchers analyzed blood samples and depression scores from 440 women, 261 living with HIV and 179 without, from the Women’s Interagency HIV Study. They tested women with HIV as people with this disease and others affecting the immune system are at greater risk of depression than the general public.

The team looked at biological aging using two epigenetic clocks: a broad multi-tissue clock and a monocyte-specific clock that measures chemical modifications to DNA in these cells.

Depression was measured using the CES-D questionnaire, which separates physical, bodily expressions of depression such as fatigue, appetite loss, and agitation from psychological and cognitive expressions of the disorder such as hopelessness, anhedonia, and feelings of failure.

Accelerated monocyte aging was significantly associated with the psychological and cognitive expressions of depression and with anhedonia specifically, even after adjusting for HIV status, race, and ethnicity. The broader multi-tissue Horvath clock showed no association with any depression domain, suggesting it is the monocyte-specific aging signal, not generalized biological aging, that tracks with mood and cognitive symptoms.

Diagnosis of depression relies largely on self-reported symptoms and not a specific physiological test. The finding that monocyte aging maps onto cognitive and mood symptoms rather than physical ones is counterintuitive, since monocytes are inflammatory cells that one might expect to track physical, inflammation-driven complaints like fatigue.

The study is small and cross-sectional, so causality cannot yet be established, but if the claims of the study were validated it could help to personalize treatment for depression in the future.

“The dynamics of monocyte aging and depression warrant further study to clarify mechanistic links,” conclude the authors.

“Our findings bring us a step closer to this goal of precision mental health care, especially for high-risk populations, by providing a biological framework that could guide future diagnosis and treatment,” adds Beaulieu Perez.

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