News from the latest research

EXPOSURE TO BISPHENOL A Linked to PROSTATE CANCER

It seems that people are exposed to bisphenol A (BPA) almost everywhere they go, and there’s no shortage of research linking the endocrine disruptor to myriad conditions. Now, research from PLOS ONE has shown that exposure to BPA is associated with early-onset prostate cancer.

According to the article, prostate cancer (PCa) is the second-most common cancer in North American men. BPA itself is not a known carcinogen, the scientists note, but exposure to BPA is “widespread, exceeding 90% of the general population.”

The study, led by Shuk-Mei Ho, director of the Cincinnati Cancer Center, involved 60 urology patients and found “higher levels of urinary BPA (creatinine-adjusted) in prostate cancer patients (5.74 µg/g [95% CI; 2.63, 12.51]) than in non-prostate cancer patients (1.43 µg/g [95% CI; 0.70, 2.88]) (p = 0.012).” The authors also wrote that the difference was even more pronounced in patients 65 and younger.

Ho and her team concluded that their findings provide the first evidence that “urinary BPA level may have prognostic value for PCa and that disruption of the centrosome duplication cycle by low-dose BPA may be a previously unknown mechanism underlying neoplastic transformation and cancer progression in the prostate.”

NIGHTTIME LIGHT EXPOSURE Linked to OBESITY

Nighttime exposure to artificial light — the glow from the TV or streetlights peeking through the windows — disrupts circadian rhythms, which may alter metabolic function and be a contributing factor to rising obesity rates, according to research recently published in Endocrine Reviews.

Researchers, led by Laura K. Fonken, of the University of Colorado, noted that since “the advent of electric lights around the turn of the 20th century, exposure to artificial and irregular light schedules has become commonplace” and has paralleled the “global increase in the prevalence of obesity and metabolic disorders.” In fact, from 2000 to 2005, the number of people with a BMI over 50 increased 75% in the United States.

Exposure to this artificial light creates a domino effect of sorts. People’s biological clocks work in coordination with the external environment, and light at night has been shown to reduce sleep quality and throw off circadian regulation. The authors point out that “appropriate circadian regulation is important for many homeostatic functions, including energy regulation.” They go on to write that multiple genes involved in nutrient metabolism and metabolically related hormones “such as glucagon, insulin, ghrelin, leptin, and corticosterone” follow circadian rhythms, meaning the oscillation of these genes and release of these hormones fall out of sync when sleep is disrupted or sleep quality is reduced.

The review first points to evidence in animal models to implicate “exposure to light at night in the growing obesity epidemic.” They found that mice “exposed to dimly lit, as compared to dark, nights impair glucose processing, increase white adipose tissue depots, and elevated body mass gain similarly to mice in constant light conditions.” The scientists go on to note that mice maintained on light cycles “incongruous with their endogenous ~24 hours circadian period” accelerate weight gain and alter metabolic hormones.

Fonken and her team looked at evidence in humans, especially shift workers, a population in which exposure to light at night has been linked to metabolic impairments, based on “mulitple epidemiological studies.” They then discussed the Old Order Amish population, where exposure to light at night is minimal and obesity prevalence is “far lower than the general population in the United States.” The authors concluded that these “converging lines of evidence indicate exposure to light at night may cause metabolic changes in mammals” and predict that circadian disruption caused by other factors could also affect metabolism. However, they note the need for further research to establish pathways for this phenomenon.

NOVEL THERAPEUTIC STRATEGY FOR NDI

Researchers in Hungary may have found a novel therapeutic strategy for patients suffering from nephorgenic diabetes insipidus (NDI), according to a study recently published in Molecular Endocrinology.

Laszlo Hunyady, MD, PhD, DSc, of Semmelweis University, and his team pointed out that mutations of the members of the G protein-coupled receptor (GPCR) superfamily are vital to physiological processes, as they are a major group of surface receptors, which recognize hormones, neurotransmitters, and sensory information. This importance means that mutations of these GPCRs “are responsible for numerous human diseases,” and more than 600 loss-of-function mutations have been identified.

The scientists specifically targeted one of these receptors — the type 2 vasopressin receptor (V2R) — as it is “one of the most extensively investigated” regarding inactivating mutations and can cause NDI “with different mechanisms.” They evaluated the properties of the mutant receptor (V2R becoming N321K missense mutation) and performed real-time cyclic adenosine monophosphate (cAMP) measurements “after agonist stimulation of transiently transfected HEK293 cells with V2Rs.”

As a result of the study, the authors wrote that they were able to demonstrate “N321K mutant V2R showed normal cell surface expression but the potency of argininevasopressin (AVP) for cAMP generation was low, while the clinically used desmopressin (dDAVP) was not efficient. The β-arrestin binding and internalization properties of the mutant receptor were also different compared to the wild type.”

However, they went on to write that the function of the mutant receptor can be “rescued” with administration of V2R receptor agonist Val4 -dDAVP (dVDAVP), “which had no detectable side effects on V1R in the effective cAMP signaling causing concentration,” pointing to a therapeutic strategy for NDI patients who express N321K mutation in the V2R.

LIFE EXPECTANCY NOT INCREASING FOR OVERWEIGHT TEENS

People are generally living longer today than they were in the 1960s, but a recent study published in the Journal of Clinical Endocrinology & Metabolism showed that individuals who were overweight or obese as teenagers aren’t seeing the same gains in life expectancy.

Researchers led by Amir Tirosh, MD, PhD, of the Division of Endocrinology at the Brigham and Women’s Hospital, used a nationwide longitudinal cohort study and analyzed records of 2,159,327 adolescents born between 1950 and 1993, who were medically evaluated for compulsory military service in Israel. They determined the teens’ BMI at the time of evaluation and recorded “incident cases of all-cause mortality before age 50.”

The authors wrote that during “43,126,211 person-year of followup, 18,530 deaths were recorded. As compared with rates observed in the 25th–50th BMI percentiles, all-cause mortality continuously increased across BMI range reaching rates of 8.90/104 and 2.90/104 person-years for men and women with BMI>97th percentile, respectively. A multivariate analysis adjusted for age, socio-economic status, education, and ethnicity demonstrated a significant increase in mortality at BMI>50th percentile (BMI>20.55 kg/m2 ) for men and ≥85th percentile in women (BMI>24.78 kg/m2 ).”

Over the past 40 years, mortality rates in normal-weight participants born between 1970 to 1980 significantly dropped, compared to those born between 1950 and 1960, but the scientists were able to demonstrate that there had been “no improvement in survival rate” among overweight and obese adolescents during the same time period. “Significant interaction between BMI and birth year was observed (p=0.007),” the authors wrote.

“In studying the rate of death among adults younger than age 50, we found that there was no improvement among men who were overweight or obese as teenagers,” Tirosh said. “In fact, the mortality rate among overweight and obese teenagers in the years 2000 to 2010 was as high as the rate observed in the 1960s and 1970s.” The authors concluded that based on these results, “pre-adulthood obesity may attenuate the progressive increase in life expectancy.”

You may also like

  • New App Helps Improve Diabetes Care in Patients with COVID-19

    Last month, Endocrine News ran a feature about the need optimal glycemic control in patients hospitalized with COVID-19, which could require physicians treating these patients to take different approaches than usual. Now, an international group of healthcare experts have developed an app to help the providers on the front lines of caring for patients with…

  • Consuming Sucralose with Carbohydrates May Impair Insulin Sensitivity, Study Finds

    Consuming sucralose-sweetened beverages with carbohydrates may impair insulin sensitivity, according to a study recently published in Cell Metabolism. Researchers led by Dana M. Small, PhD, director of the Modern Diet and Physiology Research Center at Yale University in New Haven, Conn., point out that there is still significant controversy surrounding the effects of no- or…