Archive for month: December, 2023

USA: In an article published in Andrology, the lab of Dr. Michael Golding has demonstrated that it takes much longer than previously believed, longer than a month, for the effects of alcohol consumption to leave the father’s sperm.

Researchers at Texas A&M University have already shown that paternal drinking habits before conception can harm fetal development semen from men who regularly consume alcohol impacting placenta development, fetal alcohol syndrome (FAS)-associated brain and facial defects, and even IVF outcomes.

“When someone is consuming alcohol on a regular basis and then stops, their body goes through withdrawal, where it has to learn how to operate without the chemical present,” said Golding, a professor in the School of Veterinary Medicine & Biomedical Sciences’ Department of Veterinary Physiology & Pharmacology. “What we discovered is that a father’s sperm are still negatively impacted by drinking even during the withdrawal process, meaning it takes much longer than we previously thought for the sperm to return to normal.”

The Dangers Of Paternal Drinking

One of the major risks associated with alcohol consumption before and during pregnancy is FAS, which causes abnormal facial features, low birth weight and/or height, attention and hyperactivity issues, and poor coordination.

Currently, doctors are required to confirm only that the mother has consumed alcohol-not the father-to diagnose a child with FAS.

“For years, there’s really been no consideration of male alcohol use whatsoever,” Golding said. “Within the last five to eight years, we’ve started to notice that there are certain conditions where there’s a very strong paternal influence when it comes to alcohol exposure and fetal development.

“With this project, we wanted to see how long it would take for the effects of alcohol on sperm to wear off,” he said. “We thought it would be a relatively quick change back to normal, but it wasn’t. The withdrawal process took over a month.”

When drinking alcohol, an individual’s liver experiences oxidative stress, leading the body to overproduce certain chemicals, which then interrupts normal cellular activity. Golding’s team discovered that withdrawal causes the same kind of oxidative stress, effectively lengthening the duration of alcohol’s effects on the body beyond what was previously thought.

“During withdrawal, the liver experiences perpetual oxidative stress and sends a signal throughout the male body,” Golding said. “The reproductive system interprets that signal and says, ‘Oh, we are living in an environment that has a really strong oxidative stressor in it. I need to program the offspring to be able to adapt to that kind of environment.’ But Golding suspects that the adaptations to the sperm aren’t beneficial-they lead to problems like FAS.”

He also noted that it doesn’t take excessive alcohol use for a person to experience withdrawal.

“In the models we’re using, even drinking three to four beers after work several days a week can induce withdrawal when the behavior ceases,” Golding said. “You may not feel inebriated, but your body is going through chemical changes.”

Changing The Narrative

Golding’s work is vital to improving pregnancy outcomes by changing the conversation about who is responsible for alcohol-related birth defects, since society has historically placed all blame on mothers, even when they do not consume alcohol during their pregnancy.

“There’s psychological trauma associated with the question, ‘Did you drink while you were pregnant?’ It’s also difficult for physicians to have that conversation,” he said. “But if they don’t, then FAS doesn’t get diagnosed right away and the child may not get the support that they need until later in life.”

Because of this, it’s crucial that couples planning on getting pregnant know how far in advance to stop drinking in order to prevent birth defects.

While Golding and his lab will continue to research the effects of paternal drinking to help doctors advise couples, he suggests that fathers abstain from alcohol at least three months prior to conceiving, given this groundbreaking discovery.

“There’s still a lot of work to be done to get a hard answer, but we know that sperm are made over the course of 60 days, and the withdrawal process takes at least one month,” he said. “So, my estimate would be to wait at least three months.”

Reference:

Roach AN, Bhadsavle SS, Higgins SL, Derrico DD, Basel A, Thomas KN, Golding MC. Alterations in sperm RNAs persist after alcohol cessation and correlate with epididymal mitochondrial dysfunction. Andrology. 2023 Dec 3. doi: 10.1111/andr.13566. 

USA: Adherence to second-line diabetes drugs can be hit or miss among patients with type 2 diabetes, a recent study has reported.

The findings published in the American Journal of Managed Care showed that two-thirds of patients discontinued their medication, switched to a different medication class or intensified their treatment. Discontinuation was higher (50%) among glucagon-like peptide-1 receptor agonists (GLP-1 RA) drugs, which are linked to gastrointestinal side effects. 

When patients discontinue their medication, switch to a different drug or intensify their treatment (either via an increased dose, adding a third medication or starting insulin), it wastes the doctor and patient’s time, costs the health system unnecessary expense and, in the case of discontinuation, can result in a patient not fully treating their Type 2 diabetes.

Most patients with Type 2 diabetes will end up needing to add a second-line medication after metformin — the go-to primary drug for glucose management — to control their blood sugar levels. 

The study of more than 82,000 patients between 2014 and 2017 found that within one year of their initial prescription, nearly two-thirds of patients either discontinued their medication, switched to a different medication class or intensified their treatment.

The scientists analyzed five non-insulin classes of diabetes medications. In four of the five classes, 38% of patients discontinued their medication. But among patients prescribed glucagon-like peptide-1 receptor agonists (GLP-1 RAs), half (50%) discontinued treatment.

“Discontinuation is bad. It is common in all five types of medications, but we see significantly more in those prescribed the GLP-1 RAs,” said corresponding author David Liss, research associate professor of general internal medicine at Northwestern University Feinberg School of Medicine.

“Presumably, the doctor is saying, ‘You need to start a new medication to control your Type 2 diabetes,’ and then within a year, half of them just stop and don’t start another one, and that’s not a good thing.”

Prior studies have shown that treatment discontinuation is common for Type 2 diabetes medications, but this is the first large American study to show such high discontinuation rates in second-line medications, Liss said.

“Our findings highlight the need for new prescribing approaches and to better understand the barriers patients face when taking these medications, to ultimately reduce wasting patients’ time, clinicians’ time and the health system’s money,” Liss said.

Association with gastrointestinal side effects

While the scientists did not have data on reasons why patients discontinued treatment, the particularly high discontinuation rate for GLP-1 RAs may have been due to adverse gastrointestinal side effects-such as nausea, vomiting and diarrhea-which have been observed in patients who take these medications for diabetes control and for weight loss, Liss said.

Originally approved by the U.S. Food and Drug Administration (FDA) for treating Type 2 diabetes, GLP-1 RAs (with brand names like Ozempic and Wegovy) are now used for weight loss, too. “We know there are gastrointestinal side effects for these drugs that are currently in the news, both for patients with diabetes and patients attempting to lose weight,” Liss said.

What happens after discontinuation?

For many patients in this study, discontinuing a second-line diabetes medication wouldn’t immediately lead to hyperglycemia (high blood sugar) symptoms or medical emergencies, Liss said.

“But discontinuation still puts these patients at greater risk for downstream hospitalizations related to diabetes,” Liss added.

Endocrinologist versus internal medicine prescribers

Discontinuation risk was lower and intensification risk was higher when an endocrinologist prescribed the medication, compared to when a family medicine or internal medicine physician prescribed the second-line drugs, the study found. Liss said this difference could be because endocrinologists had particular expertise in the newer classes of diabetes drugs, enhancing their ability to discuss the pros and cons of medications when making prescribing decisions with patients.

Importance of follow-ups on new drugs

The study retrospectively analyzed patients’ health insurance claims data, meaning the scientists could identify when a patient had been prescribed a medication; if the care provider switched their medication to a new class; or if they increased their dose.

The scientists assumed that patients who experienced a treatment switch or intensification did so after talking with their doctor. But the scientists suspect that many patients made the decision to discontinue their medication without having talked to a doctor.

“Our results may represent a ‘wake-up call’ for clinicians that many of their patients were not taking the medicines that were prescribed,” Liss said. “While we don’t know if providers were aware of the discontinuation events observed in this study, our results highlight the need for ongoing communication between patients and prescribers over time-around medication benefits, side effects and costs-not just at the time of prescribing.” 

Reference:

David T. Liss, Manisha Cherupally, Treatment Modification After Initiating Second-Line Medication for Type 2 Diabetes, The American Journal of Managed Care, DOI: 10.37765/ajmc.2023.89466

Adjunctive antimicrobial peptide was clinically efficacious for treatment of stage III grade B periodontitis suggests a new study published in the Oral Diseases.

China: A large cross-sectional study in Chongqing, China, has shed light on the association between alcohol consumption and the risk of hyperuricaemia among adults.

USA: Cord blood (CB) leptin may be a biomarker of future adiposity risk, a recent study has concluded. The research was a follow-up to the Hyperglycemia and Adverse Pregnancy Outcomes Follow-Up Study.