Archive for category: News

A recent prospective cohort study investigated the potential link between the gestational diabetes mellitus (GDM) and long-term mortality. The major highlights of this study were published in the BMC Cardiovascular Diabetology.

This study was conducted from October 2022 to April 2023 and involved a total of 10,327 women with a pregnancy history to discern whether GDM, without subsequent overt diabetes, had any significant association with all-cause and cardiac mortality. The findings revealed critical insights into the health outcomes of women with a history of GDM. 5.3% of the participants had GDM alone, while 14.1% had overt diabetes. 758 deaths were recorded over a median follow-up period of 6.7 years.

This crucial findings of this study uncovered that GDM alone did not increase the risk of either all-cause or cardiac mortality. The participants in the GDM group showed comparable mortality rates to those without diabetes. Also, the group with overt diabetes faced a significantly higher risk of both all-cause and cardiac mortality when compared to their counterparts without diabetes.

The sensitivity analysis focused on women aged 50 or above and reinforced these findings. Among this subgroup, a history of GDM did not show any association with increased mortality risks. Overt diabetes remained significantly linked to heightened all-cause and cardiac mortality rates.

These findings challenge previous assumptions regarding the long-term health implications of gestational diabetes. While overt diabetes poses substantial risks, this research suggests that GDM alone may not contribute to the heightened mortality rates. These insights underscore the importance of distinguishing between different forms of diabetes and their respective impacts on long-term health outcomes.

Source: 

Ying, Q., Xu, Y., Zhang, Z., Cai, L., Zhao, Y., & Jin, L. (2024). Gestational diabetes mellitus and risk of long-term all-cause and cardiac mortality: a prospective cohort study. In Cardiovascular Diabetology (Vol. 23, Issue 1). Springer Science and Business Media LLC. https://doi.org/10.1186/s12933-024-02131-3

Turkey: Prolidase activity may, in part, play a role in the pathogenesis of prostate cancer, a recent study has shown.

In a recent study published in the Frontiers in Medicine underscore the significant impact of neuropathic pain (NP) on disease activity assessment in patients with psoriatic arthritis (PsA). 

This study was conducted as a cross-sectional analysis which involved a total of 246 PsA patients and excluded the individuals with prior diagnoses of fibromyalgia, depression, anxiety, diabetes or dyslipidemia under treatment. Utilizing the painDETECT questionnaire Esther Toledano and team identified NP in 17.1% of the participants.

The results revealed several correlations in which the patients with NP showed higher levels of leptin. Leptin is commonly associated with obesity which indicates a potential link between NP and metabolic health. Also, poor sleep quality was significantly associated with NP that suggests a bidirectional relationship between sleep disturbances and neuropathic pain.

Fatigue levels were markedly higher in patients with NP when compared to those without by indicating the debilitating impact of NP on daily functioning. NP was found to be correlated with worse disease activity as measured by the clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) by highlighting the need for comprehensive pain management strategies in PsA patients.

This study emphasized the importance of recognizing and addressing NP in PsA management by underscoring the complex relationship between pain, comorbidities and disease severity in Psoriatic Arthritis patients. This research provides valuable insights into the multifaceted nature of pain in PsA and calls for an inclusive approach to patient care. Addressing neuropathic pain and its related factors will help healthcare providers to potentially enhance the quality of life and overall outcomes for individuals with Psoriatic Arthritis.

Source: 

Toledano, E., Queiro, R., Gómez-Lechón, L., Chacón, C. C., Hidalgo, C., Ibañez, M., Díaz-Álvarez, A., & Montilla, C. (2024). Influence of comorbidities not associated with fibromyalgia on neuropathic pain in patients with psoriatic arthritis: relationship with clinical parameters. In Frontiers in Medicine (Vol. 11). Frontiers Media SA. https://doi.org/10.3389/fmed.2024.1331761

Autosomal dominant polycystic kidney disease (ADPKD), the most common form of polycystic kidney disease, can lead to kidney enlargement and eventual loss of function. The disease affects more than 12 million people worldwide, and many patients end up needing dialysis or a kidney transplant by the time they reach their 60s.

Researchers at MIT and Yale University School of Medicine have now found that a compound originally developed as a potential cancer treatment holds promise for treating ADPKD. The drug works by exploiting kidney cyst cells’ vulnerability to oxidative stress-a state of imbalance between damaging free radicals and beneficial antioxidants.

In a study employing two mouse models of the disease, the researchers found that the drug dramatically shrank kidney cysts without harming healthy kidney cells.

“We really believe this has potential to impact the field and provide a different treatment paradigm for this important disease,” says Bogdan Fedeles, a research scientist and program manager in MIT’s Center for Environmental Health Sciences and the lead author of the study, which appears this week in the Proceedings of the National Academy of Sciences.

John Essigmann, the William R. and Betsy P. Leitch Professor of Biological Engineering and Chemistry at MIT; Sorin Fedeles, executive director of the Polycystic Kidney Disease Outcomes Consortium and assistant professor (adjunct) at Yale University School of Medicine; and Stefan Somlo, the C.N.H. Long Professor of Medicine and Genetics and chief of nephrology at Yale University School of Medicine, are the senior authors of the paper.

Cells under stress

ADPKD typically progresses slowly. Often diagnosed when patients are in their 30s, it usually doesn’t cause serious impairment of kidney function until patients reach their 60s. The only drug that is FDA-approved to treat the disease, tolvaptan, slows growth of the cysts but has side effects that include frequent urination and possible liver damage.

Essigmann’s lab did not originally set out to study PKD; the new study grew out of work on potential new drugs for cancer. Nearly 25 years ago, MIT research scientist Robert Croy, also an author of the new PNAS study, designed compounds that contain a DNA-damaging agent known as an aniline mustard, which can induce cell death in cancer cells.

In the mid 2000s, Fedeles, then a grad student in Essigmann’s lab, along with Essigmann and Croy, discovered that in addition to damaging DNA, these compounds also induce oxidative stress by interfering with mitochondria-the organelles that generate energy for cells.

Tumor cells are already under oxidative stress because of their abnormal metabolism. When they are treated with these compounds, known as 11beta compounds, the additional disruption helps to kill the cells. In a study published in 2011, Fedeles reported that treatment with 11beta compounds significantly suppressed the growth of prostate tumors implanted in mice.

A conversation with his brother, Sorin Fedeles, who studies polycystic kidney disease, led the pair to theorize that these compounds might also be good candidates for treating kidney cysts. At the time, research in ADPKD was beginning to suggest that kidney cyst cells also experience oxidative stress, due to an abnormal metabolism that resembles that of cancer cells.

“We were talking about a mechanism of what would be a good drug for polycystic kidney disease, and we had this intuition that the compounds that I was working with might actually have an impact in ADPKD,” Bogdan Fedeles says.

The 11beta compounds work by disrupting the mitochondria’s ability to generate ATP (the molecules that cells use to store energy), as well as a cofactor known as NADPH, which can act as an antioxidant to help cells neutralize damaging free radicals. Tumor cells and kidney cyst cells tend to produce increased levels of free radicals because of the oxidative stress they’re under. When these cells are treated with 11beta compounds, the extra oxidative stress, including the further depletion of NADPH, pushes the cells over the edge.

“A little bit of oxidative stress is OK, but the cystic cells have a low threshold for tolerating it. Whereas normal cells survive treatment, the cystic cells will die because they exceed the threshold,” Essigmann says.

Shrinking cysts

Using two different mouse models of ADPKD, the researchers showed that 11beta-dichloro could significantly reduce the size of kidney cysts and improve kidney function.

The researchers also synthesized a “defanged” version of the compound called 11beta-dipropyl, which does not include any direct DNA-damaging ability and could potentially be safer for use in humans. They tested this compound in the early-onset model of PKD and found that it was as effective as 11beta-dichloro.

In all of the experiments, healthy kidney cells did not appear to be affected by the treatment. That’s because healthy cells are able to withstand a small increase in oxidative stress, unlike the diseased cells, which are highly susceptible to any new disturbances, the researchers say. In addition to restoring kidney function, the treatment also ameliorated other clinical features of ADPKD; biomarkers for tissue inflammation and fibrosis were decreased in the treated mice compared to the control animals.

The results also suggest that in patients, treatment with 11beta compounds once every few months, or even once a year, could significantly delay disease progression, and thus avoid the need for continuous, burdensome antiproliferative therapies such as tolvaptan.

“Based on what we know about the cyst growth paradigm, you could in theory treat patients in a pulsatile manner-once a year, or perhaps even less often-and have a meaningful impact on total kidney volume and kidney function,” Sorin Fedeles says.

The researchers now hope to run further tests on 11beta-dipropyl, as well as develop ways to produce it on a larger scale. They also plan to explore related compounds that could be good drug candidates for PKD.

Reference:

Bogdan I. Fedeles, Rishi Bhardwaj, Yasunobu Ishikawa, Stefan Somlo, A synthetic agent ameliorates polycystic kidney disease by promoting apoptosis of cystic cells through increased oxidative stress, Proceedings of the National Academy of Sciences, https://doi.org/10.1073/pnas.2317344121.