Sitting time linked to increased mortality in adults with diabetes, reveals research

Adults with diabetes who meet the recommended guidelines for physical activity may offset the risk of mortality that is associated with excessive sitting time, according to a new study at Columbia University Mailman School of Public Health. This is the first study to show that getting adequate exercise can counteract the elevated risk of mortality associated with sitting for long periods of time each day, even for people with diabetes. The findings are published in Diabetes Care.

“Managing the elevated mortality risk in this high-risk population is particularly pressing given the widespread diabetes epidemic and the tendency among adults with diabetes to sit more and move less,” said Wen Dai, PhD, first author who was a doctoral student in Epidemiology at Columbia Mailman School.

Excessive sedentary time is a significant public health issue with increased mortality risk for the general population.

The researchers analyzed data from the 2007-2018 National Health and Nutrition Examination Surveys (NHANES) for individuals 20 years of age or older with diabetes as defined by the American Diabetes Association. Individuals with diabetes were followed- through 2019 to determine mortality status. Sitting time and moderate-to-vigorous physical activity were self-reported. Data on sociodemographics, lifestyle factors and medical conditions were collected through computer-assisted personal interviews.

Physical activity was categorized as inactive (<10 min/week), insufficiently active (10-149 min/week), and active (≥150 min/week). Thirty-eight percent reported being physical active in the moderate to vigorous range for less than 10 minutes per week. Half of the respondents had diabetes for five years or less and 34 percent were diabetic for more than 10 years. Inactive individuals with diabetes or those recording physical activity of less than 10 minutes per week was associated with greater mortality risk from all causes.

Over approximately 6 years, there were 1,278 deaths from all causes and 354 deaths from heart disease for individuals 60 years old on average, 48 percent of whom were female and 61 percent non-Hispanic White. About one-quarter had less than a high school education, and approximately 12 percent lacked health insurance.

“Our findings support an emphasis on encouraging and supporting patients in adhering to guideline-recommended physical activity levels, particularly for individuals whose life circumstances necessitate prolonged sitting in particular, such as drivers or office workers,” said Sandra Albrecht, PhD, assistant professor of Epidemiology at Columbia Mailman School of Public Health, and senior author.

Reference:

Wen Dai, Sandra S. Albrecht; Sitting Time and Its Interaction With Physical Activity in Relation to All-Cause and Heart Disease Mortality in U.S. Adults With Diabetes. Diabetes Care 2024; dc240673. https://doi.org/10.2337/dc24-0673.

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Severe Aortic Wall Thrombus Predicts Higher Risks in transfemoral TAVR: Study reveals

France: A recent study has shown a strong association between aortic wall thrombus (AWT) presence on preprocedural multidetector computed tomography (CT) and thromboembolic complications, including mortality and stroke after transfemoral (TF) TAVR. The findings were published online in JACC: Cardiovascular Interventions.

Thromboembolic events, notably strokes, continue to pose significant challenges in transcatheter aortic valve replacement (TAVR), according to researchers. Despite efforts, embolic protection devices have not demonstrated substantial clinical benefits in extensive randomized clinical trials. Aortic wall thrombus is frequently detected on multidetector CT during TAVR evaluations, yet its prognostic implications remain uncertain. Considering this, Marc Bonnet, Cardiology Department, Hospital Annecy-Genevois, Metz-Tessy, France, and colleagues sought to evaluate the association between the AWT presence and the incidence of thromboembolic outcomes in patients undergoing TF TAVR for severe aortic stenosis.

For this purpose, the researchers conducted a prospective cohort study of consecutive patients who underwent TF TAVR for severe aortic stenosis between 2011 and 2022. A specific scale ranging from 0 to 10 was employed for qualitative assessment of aortic wall thrombus (AWT).

The primary outcome measured a composite of procedural thromboembolic events, including ischemic stroke, blue toe syndrome, bowel ischemia, or infarction of other solid organs. Secondary endpoints included ischemic strokes and procedural mortality.

The following were the key findings of the study:

  • Of the 641 patients included, severe AWT (score ≥8) was identified in 11.4%.
  • Severe AWT presence was strongly associated with an increase in the primary outcome (OR: 8.48).
  • This relationship persisted following multivariable analysis, which adjusted for comorbidities and procedural characteristics.
  • The presence of severe AWT was also associated with an increased incidence of stroke and procedural death (OR: 5.66 and OR: 4.66, respectively).

In their editorial accompanying the study, Yousif Ahmad, MD, PhD, and Alexandra J. Lansky, MD, from Yale School of Medicine in New Haven, CT, highlight that the Sentinel device (Boston Scientific) evaluated in PROTECTED TAVR is not the only option. They note that other cerebral embolic protection tools currently in development may offer improved efficacy.

The editorial introduces a new perspective, suggesting that rather than solely emphasizing new devices or technical aspects, an alternative global approach to reducing stroke and other embolic complications after TAVR could involve identifying high-risk patients who would derive the greatest benefit from protective measures.

Reference:

Bonnet M, Maxo L, Lohse T, et al. Association between aortic wall thrombus and thromboembolic events after transfemoral transcatheter aortic valve replacement. JACC Cardiovasc Interv. 2024;17:1680-1690.

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Data shows surge in new GLP-1RA prescriptions for obesity without type 2 diabetes, reveals study

A nationwide study found a marked increase in new GLP-1RA prescriptions over the last decade, particularly since 2020. Semaglutide was the most prescribed GLP-1RA, by far, in 2023. Notably, the proportion of new users with type 2 diabetes decreased whereas prescriptions among those with obesity or relevant comorbid conditions but without T2D spiked. According to the study authors, the high prevalence of obesity and the increasing demand for GLP-1RA prescriptions for obesity could contribute to drug shortages and may worsen existing racial and ethnic disparities in drug access. The brief research report is published in Annals of Internal Medicine.

Researchers from the Perelman School of Medicine at the University of Pennsylvania and Cedars-Sinai studied data from TriNetX, a federated health research network with records for 45 million individuals in the United States, to delineate the annual trend in new prescriptions of GLP-1RAs between 2011 and 2023, categorized by the presence of diabetes and comorbid conditions related to diabetes or obesity. New prescriptions were defined as users who received GLP-1RAs for the first time in their records in the TrinetX database.

The data showed that of the 1 million new GLP-1RA users identified during the study timeframe, users were disproportionately female, non-Hispanic White, and had a BMI of 30 kg/m2 or greater. During the same period, there was a 2-fold increase in the proportions of users without type 2 diabetes but with a BMI of 30 kg/m2 or greater, or in those with a BMI of 27 to 30 kg/m2 and an obesity-related comorbid condition. Additionally, the proportion of users without FDA-approved indications increased from 0.21% in 2019 to 0.37% in 2023. In 2019, semaglutide and liraglutide constituted 31.4% and 35.3% of all new GLP-1RA prescriptions, respectively. In 2023, these proportions increased to 88.1% for semaglutide, and decreased to 10.3% for liraglutide.

Reference:

Yee Hui Yeo, Ali Rezaie,  Tina Yi-Jin Hsieh, Xiaoqin Hu, Srinivas Gaddam, and Kevin Sheng-Kai Ma, Shifting Trends in the Indication of Glucagon-like Peptide-1 Receptor Agonist Prescriptions: A Nationwide Analysis, Annals of Internal Medicine, https://doi.org/10.7326/M24-0019.

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FDA approves Blood test for colon cancer

Washington: U.S. health regulators on Monday approved a first-of-its-kind blood test for colon cancer, offering a new way of screening for a leading cause of cancer deaths.

Test manufacturer Guardant said the Food and Drug Administration approved its Shield test for screening in adults 45 and older who have an average risk of colon cancer. The test isn’t a replacement for colonoscopies, but provides a noninvasive approach to screening.

Doctors can already order Shield for patients as a laboratory test with an out-of-pocket price of $895. But FDA approval is expected to increase coverage by private and government insurance.

The test looks for DNA fragments shed by tumor cells and precancerous growths. In a study published in March, the test caught 83% of the cancers but very few of the precancerous growths found by colonoscopy, the gold standard for colon cancer screening. The test missed 17% of cancers, performance that is on par with stool-based tests.

Besides spotting tumors, colonoscopies can prevent the disease by removing precancerous growths called polyps.

But some people avoid the exam because of the hassle of getting time off work or the day-ahead preparation that involves drinking a strong laxative to empty the bowels. In the U.S., screening is recommended for healthy adults ages 45 to 75 at average risk for colon cancer.

Physicians will be able to run the Shield test after taking a simple blood draw, Guardant said in a statement. The company plans to launch its product “in the near future.”

The annual rate of U.S. colon cancer screening is nearly 60%, well short of the 80% of age-eligible adults goal set by the American Cancer Society and other groups.

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Resistin Emerges as Key Predictor of Mortality and Disease Severity in Pulmonary Arterial Hypertension: Study

USA: Elevated levels of the cytokine resistin were strongly linked to a higher risk of mortality in adults with pulmonary arterial hypertension (PAH), new data from over 1,000 participants has shown.

“Our study establishes the significance of resistin in the pathobiology of human PAH. Consistent with its role observed in rodent studies, serum resistin emerges as a promising new biomarker for predicting outcomes in pulmonary arterial hypertension (PAH) and could open up new possibilities for treatment,” the researchers wrote in Respiratory Research.

They added, “Machine learning-based survival models have underscored the value of incorporating resistin levels to enhance predictive accuracy.”

Resistin, a cytokine produced by adipocytes, has been linked to adverse clinical outcomes in heart failure and cardiovascular disease, the researchers noted. Although studies in mice suggest that human resistin contributes to pulmonary vascular remodeling and the progression of pulmonary arterial hypertension, its potential as a biomarker for PAH is still not well-defined.

To fill this knowledge gap, Li Gao, Johns Hopkins University School of Medicine, Baltimore, MD, USA, and colleagues aimed to evaluate the potential for using the cytokine resistin as a biological and genetic marker for disease severity and survival in a large cohort of PAH patients.

For this purpose, the researchers obtained clinical, biospecimens, and genetic data for 1121 adults with PAH, including 313 with scleroderma-associated PAH (SSc-PAH) and 808 with idiopathic PAH (IPAH).

Serum resistin levels were quantified using ELISA, and their relationships with clinical variables and single nucleotide polymorphism genotypes were analyzed through multivariable regression models. Additionally, machine learning (ML) algorithms were utilized to create and evaluate risk models for predicting mortality.

The following were the key findings of the study:

  • Resistin levels were significantly higher in all PAH samples and PAH subtype (IPAH and SSc-PAH) samples than in controls and had significant discriminative abilities (AUCs of 0.84, 0.82, and 0.91, respectively).
  • High resistin levels (above 4.54 ng/mL) in PAH patients were associated with older age, shorter 6-minute walk distances, and reduced cardiac performance (cardiac index).
  • Mutant carriers of either rs3219175 or rs3745367 had higher resistin levels.
  • High resistin levels in PAH patients were also associated with an increased risk of death (hazard ratio: 2.6).
  • Comparisons of ML–derived survival models confirmed the satisfactory predictive value of the random forest model (AUC = 0.70) for PAH.

The findings revealed that serum resistin can serve as a biomarker for PAH prognosis and survival in a large cohort composed solely of patients with IPAH and SSc-PAH.

“Future research should focus on creating multi-marker assays to enhance noninvasive risk stratification,” the researchers concluded.

Reference:

Gao, L., Skinner, J., Nath, T. et al. Resistin predicts disease severity and survival in patients with pulmonary arterial hypertension. Respir Res 25, 235 (2024). https://doi.org/10.1186/s12931-024-02861-8

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Short-term vegan diet associated with reductions in biological age estimates, suggests study

Eating a vegan diet for eight weeks is associated with reductions in biological age estimations based on levels of DNA methylation-a type of chemical modification of DNA (known as an epigenetic modification) that alters gene expression but not DNA itself. Previous research has reported that increased DNA methylation levels are associated with ageing. The findings, which are based on a small randomised controlled trial of 21 pairs of adult identical twins, are published in BMC Medicine.

Varun Dwaraka, Christopher Gardner and colleagues investigated the molecular effects of a short-term vegan diet by instructing one half of each twin pair to eat an omnivorous diet for eight weeks-including between 170 and 225 grams of meat, one egg, and one and a half servings of dairy each day-and the other half to eat a vegan diet for the same length of time. The sample was 77 percent women (32), and participants were 40 years old on average and had an average body mass index of 26 kilograms per metres squared. For the first four weeks of the study participants ate meals that had been prepared for them and for the second four weeks participants ate meals that they had prepared themselves, after receiving nutrition classes from health educators.

The authors investigated the impacts of diet on levels of DNA methylation by analysing blood samples collected from participants at baseline, week four, and week eight of the study. They used DNA methylation levels to infer the biological ages of participants and their organ systems.

By the end of the study the authors observed decreases in estimates of biological age-known as epigenetic ageing clocks-in participants who ate a vegan diet but not among those that ate an omnivorous diet. They also observed decreases in the ages of the heart, hormone, liver, and inflammatory and metabolic systems of participants who ate a vegan, but not an omnivorous diet, for eight weeks.

The authors caution that the extent to which the differences observed between participants who ate different diets can be attributed to their dietary compositions is unclear. They note that participants who ate a vegan diet lost two kilograms more on average than those who ate an omnivorous diet due to differences in the calorie contents of meals provided during the initial four weeks of the study. They suggest that these weight loss variations could have contributed to the observed differences in epigenetic age between both groups. Further research is needed to investigate the relationship between dietary composition, weight and ageing, in addition to the long-term effects of vegan diets, they add.

Reference:

Dwaraka, V.B., Aronica, L., Carreras-Gallo, N. et al. Unveiling the epigenetic impact of vegan vs. omnivorous diets on aging: insights from the Twins Nutrition Study (TwiNS). BMC Med 22, 301 (2024). https://doi.org/10.1186/s12916-024-03513-w.

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Healthy Eating and Intermittent Fasting Boost Weight Loss and Brain Health in Older Adults: Study

USA: An article in Cell Metabolism examined the effects of intermittent fasting (IF) and healthy low-calorie (HL) diets over eight weeks on brain health in cognitively intact, late middle-aged, and older individuals with insulin resistance (IR).

The researchers revealed that both an intermittent fasting diet and a standard healthy living diet emphasizing nutritious foods result in weight loss, decreased insulin resistance (IR), and slower brain aging in older overweight adults with IR. However, neither diet influenced biomarkers associated with Alzheimer’s disease (AD).

The study presented a methodological framework that incorporates various brain and cognitive metrics to thoroughly evaluate the impact of diet on brain health. Results showed that both diets yielded similar benefits on neuronal insulin resistance biomarkers (NDEV), BrainAGE, and magnetic resonance spectroscopy (MRS) glucose levels, underscoring these measures as effective indicators of the brain’s dietary response.

In an eight-week randomized clinical trial, Dimitrios Kapogiannis, Intramural Research Program, Laboratory of Clinical Investigation, National Institute on Aging, and the Department of Neurology at Johns Hopkins University et. al. found 40 cognitively intact older adults with insulin resistance. The study assessed the effects of 5:2 intermittent fasting and a healthy living diet on brain health.

It was found that despite intermittent fasting leading to greater weight loss, both diets similarly improved insulin signaling biomarkers in neuron-derived extracellular vesicles, reduced the brain-age gap (indicating slower biological brain aging) on MRI, lowered brain glucose levels on magnetic resonance spectroscopy, and enhanced blood biomarkers for carbohydrate and lipid metabolism.

Changes in cerebrospinal fluid biomarkers for Alzheimer’s disease were minimal. Both diets enhanced executive function and memory, with intermittent fasting showing greater benefits in certain cognitive areas. Exploratory analyses revealed that sex, body mass index, and genotypes of apolipoprotein E and SLC16A7 influenced the diets’ effects.

The key findings of the research were:

  • The 5:2 intermittent fasting diet led to more weight loss in 8 weeks compared to a healthy living diet.
  • Both diets reduced neuronal insulin resistance and slowed brain aging.
  • Both diets improved memory and executive function, with greater improvement seen in the 5:2 intermittent fasting group.
  • Neither diet affected biomarkers of Alzheimer’s disease.

It was concluded that the study offers a framework for evaluating the impact of dietary interventions on the brain and encourages additional research on intermittent fasting and continuous diets to optimize brain health.

Reference 

Kapogiannis D, Manolopoulos A, Mullins R, Avgerinos K, Delgado-Peraza F, Mustapic M, Nogueras-Ortiz C, Yao PJ, Pucha KA, Brooks J, Chen Q, Haas SS, Ge R, Hartnell LM, Cookson MR, Egan JM, Frangou S, Mattson MP. Brain responses to intermittent fasting and the healthy living diet in older adults. Cell Metab. 2024 Jul 16:S1550-4131(24)00283-3. doi: 10.1016/j.cmet.2024.07.012. Epub ahead of print. Erratum for: Cell Metab. 2024 Jun 19:S1550-4131(24)00225-0. doi: 10.1016/j.cmet.2024.05.017. PMID: 39019039.

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Study suggests shorter duration of first line antibiotics for simple acute otitis media in children: Study

A new study by Sophie Katz and team suggests short term duration of first line antibiotics for children with simple acute otitis media (AOM). The findings of this study were published in Journal of the Pediatric Infectious Diseases Society. About 25% of children’s antibiotic prescriptions are for acute otitis media. Majority of the children with AOM who were over two years of age receive lengthy (10-day) regimens of antibiotics, even though national recommendations suggest shorter (5 to 7 days) treatments. Thus, this study was set out to compare the length of time antibiotics were given for children with uncomplicated AOM who were between the ages of 2 and 17 in two pediatric academic health systems, as well as to determine how long the prescriptions varied within each system.

This retrospective analysis was done on electronic medical record (EMR) data from 135 care sites across two health systems. The study encompassed outpatient interactions from 2019 to 2022 for children with an AOM. The percentage of 5-day prescriptions was the main result. The percentage of 7-day and 10-day prescriptions, instances linked to treatment failure, prescriptions for antibiotics other than first-line therapy, recurrence of AOM and adverse medication events were among the secondary outcomes.

A total of 61,612 (84%) of the 73,198 AOM visits involved children of 2 years and over ended in an antibiotic prescription. Only 5% of prescriptions (3,144) were for five days when compared to the majority (45,689; 75%) which were for seven days. It was uncommon for patients to experience treatment failure, recurrence of AOM, adverse medication events, hospital stays, and office, ER, or emergency room visits for AOM within 30 days following the index visit.

Overall, 75% of antibiotic prescriptions were given longer than necessary. There was little variation in the use of 5-day durations among individual practitioners and it was unusual to find them across all types of care sites. Reducing the length of therapy for AOM has the potential to significantly lower the exposure to antibiotics in children and this might have a significant impact on reducing the emergence of adverse events, antibiotic resistance, and other unintended effects of antibiotic use. Therefore, there is an urgent need for outpatient pediatric antibiotic stewardship to scale up initiatives to encourage the more general use of short treatment durations and first line antibiotics.

Reference:

Katz, S. E., Jenkins, T. C., Stein, A. B., Thomas, G., Koenig, N., Starnes, G. L., Newland, J. G., Banerjee, R., & Frost, H. M. (2024). urations of antibiotic treatment for acute otitis media and variability in prescribed durations across two large academic health systems. In Journal of the Pediatric Infectious Diseases Society. Oxford University Press (OUP). https://doi.org/10.1093/jpids/piae073

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Do non-statin cholesterol-lowering drugs affect liver cancer risk?

Past studies have suggested that taking cholesterol-lowering statin drugs may lower individuals’ risk of developing liver cancer. In a new study of non-statin cholesterol-lowering medications, one type was linked to lower risks of liver cancer. The findings are published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society.

Cholesterol absorption inhibitors, bile acid sequestrants, fibrates, niacin, and omega-3 fatty acids are types of non-statin cholesterol-lowering medications prescribed to manage cholesterol and lipid levels. The different classes of drugs work in different ways. A team led by Katherine A. McGlynn, PhD, MPH, of the National Cancer Institute, looked for associations between these five types of non-statin cholesterol-lowering medications and risk of liver cancer, the sixth most commonly occurring cancer globally and the third leading cause of cancer mortality.

The investigators used information from the Clinical Practice Research Datalink (CPRD), a primary care database that covers approximately 7% of the United Kingdom population. Their analysis included 3,719 liver cancer cases and 14,876 matched controls without cancer. Additional matches were also made based on individuals’ type 2 diabetes and chronic liver disease status.

Use of cholesterol absorption inhibitors was associated with 31% lower odds of liver cancer risk in the overall analysis. These medications were also linked with a lower risk of liver cancer in analyses based on diabetes and liver disease status. The study also confirmed that statins were associated with 35% lower odds of liver cancer.

No associations with liver cancer risk were observed for fibrates, omega-3 fatty acids, or niacin. While bile acid sequestrant use was associated with higher odds of liver cancer risk in the overall analysis, the results of analyses based on diabetes and liver disease status were inconsistent, suggesting that replication of these observations is important.

“As few studies have examined the effects of non-statin cholesterol-lowering drugs on liver cancer risk, the results of our study require replication in other populations. If our findings are confirmed in other studies, however, our results may inform liver cancer prevention research,” said Dr. McGlynn.

Reference:

Shahriar A. Zamani PhD, Barry I. Graubard PhD, Marianne Hyer MS, Emily Carver BS, Jessica L. Petrick PhD, MPH, Katherine A. McGlynn, Use of cholesterol-lowering medications in relation to risk of primary liver cancer in the Clinical Practice Research Datalink, https://doi.org/10.1002/cncr.35436. 

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Alveolar ridge preservation after extraction may obviate need for additional augmentation during implant placement: Study

Alveolar ridge preservation after extraction may obviate the need for additional augmentation during implant placement suggests a study published in the Clinical Oral Implant Research.

This systematic review and meta-analyses aimed to evaluate the outcomes of alveolar ridge preservation (ARP) following extraction of non-molar teeth in comparison to early implant placement (EIP) in terms of clinical and radiographic changes, need for additional augmentation at the time of implant placement, patient-reported outcomes, and implant failure rate. Electronic databases were searched to identify randomized and non-randomized studies that compared ARP to EIP. The risk of bias was assessed using the Cochrane Collaboration’s Risk of Bias tool. Data were analyzed using a statistical software program. Results: A total of 106 studies were identified, of which five studies with 198 non-molar extraction sockets in 198 participants were included. Overall meta-analysis showed significant differences in changes in midfacial mucosal margin (mean difference (MD) −0.09; 95% confidence interval (CI) −0.17 to −0.01; p = .03) and ridge width (MD −1.70; 95% CI −3.19 to −0.20; p = .03) in favor of ARP. The use of ARP was also associated with less need for additional augmentation at implant placement, but the difference was not statistically significant. Within the limitation of this review, ARP following extraction of non-molar teeth has short-term positive effects on soft tissue contour, mucosal margin and thickness, and alveolar ridge width and height. It can also simplify future implant treatment by minimizing the need for additional augmentation.

Reference:

Atieh, M. A., Shah, M., Hakam, A., AlAli, F., Aboushakra, I., & Alsabeeha, N. H. M. (2024). Alveolar ridge preservation versus early implant placement in single non-molar sites: A systematic review and meta-analysis. Clinical Oral Implants Research, 00, 1–17. https://doi.org/10.1111/clr.14314

Keywords:

Alveolar, ridge, preservation, extraction, obviate need, additional, augmentation, during, implant, placement, study, clinical oral implant research, Atieh, M. A., Shah, M., Hakam, A., AlAli, F., Aboushakra, I., & Alsabeeha, N. H. M.

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