Observatory and Fast Facts

June 23, 2021
Link between blood sugar and liver disease progression

There are no approved drugs to treat nonalcoholic fatty liver disease, but controlling blood sugar over time may help decrease the risk of liver scarring and disease progression, according to a study by Duke Health as reported in a news release.

In the study, the average three-month blood glucose levels of patients with non-alcoholic fatty liver disease influenced their chance of having more severe scarring in the liver, which can lead to liver failure.

Appearing online in the journal Hepatology, the study examined the documented glucose levels of 713 adult patients with fatty liver disease prior to a liver biopsy.

Researchers found that higher average blood glucose levels in the year leading up to a liver biopsy were associated with more severe swelling of liver cells. For every 1 percentage point increase in hemoglobin HbA1c (a measure of average glucose levels) in the year preceding biopsy, the chances for severe fibrosis rose by 15%.

Similarly, researchers also found that those with moderate glucose control over a period of five years, rather than good control, had more severe swelling of liver cells and a higher likelihood of having advanced liver scarring.

Lead author of the study, Duke Health endocrinologist Anastasia-Stefania Alexopoulos, MBBS, said severe liver disease related to fatty liver is on the rise. Alexopoulos says these findings are particularly significant for diabetes patients because a significant portion of the patient population also has nonalcoholic fatty liver disease.

Alexopoulos also said the findings may lead clinicians to reconsider their diabetes treatment approach to prescribe diabetes medications that are known to both improve glucose control and promote weight loss.

“A lot of the times in diabetes, we’re thinking about heart disease, high blood pressure, cholesterol — we’re thinking about all these complications,” Alexopoulos said. “I want fatty liver to be added in there.”

New bacterial weaknesses potentially targets AMR

In the perpetual arms races between bacteria and human-made antibiotics, there is a new tool to give human medicine the edge, in part, by revealing bacterial weaknesses and potentially by leading to more targeted or new treatments for bacterial infections.

A research team led by scientists at The University of Texas at Austin has developed chemical probes to help identify an enzyme, produced by some types of E. coli and pneumococcal bacteria, known to break down several common types of antibiotics, making these bacteria dangerously resistant to treatment.

“In response to antibiotic treatment, bacteria have evolved various mechanisms to resist that treatment, and one of those is to make enzymes that basically chew up the antibiotics, before they can do their job,” said Emily Que, Assistant Professor of Chemistry. “The type of tool we developed gives us critical information that could keep us one step ahead of deadly bacteria.”

In a paper published online in the Journal of the American Chemical Society, the researchers zeroed in on the threat posed by the bacterial enzyme called New Delhi metallo-beta-lactamase (NDM). They set out to create a molecule that glows when it comes into contact with the NDM enzyme. When these chemical probes are added to a test tube, they bind to the enzyme and glow. Such a tool could be used to alert doctors to what kind of bacterial threat is affecting their patients and tell them which antibiotics to use.

NDM breaks down antibiotics in the penicillin, cephalosporin and carbapenem classes, which are some of the safest and most effective treatments for bacterial infections. Other classes of antibiotics exist, but they may carry more side effects, have more drug interactions, and may be less available in some parts of the world.

In addition to indicating the presence of the NDM enzyme, the florescent chemical probe developed by Que and Walt Fast, Professor of Chemical Biology and Medicinal Chemistry, may help find a different way to combat these resistant bacteria. One treatment option that doctors use with resistant bacteria is to combine common antibiotics and an inhibitor. Although there is no known clinically effective inhibitor for NDM-producing bacteria, Que’s probe could help find one.

Once the probe has bound to the enzyme and begun to glow, if an effective inhibitor is introduced, it will knock the probe loose and the glow would stop. This allows scientists to test a high volume of potential drugs.

The study also examined a process called nutritional immunity, which comes from the human body’s production of proteins in response to an infection. The proteins snatch up all the available metals in the body, such as the zinc required to make NDM, rendering the bacteria more susceptible to attack.

Que’s probe can also be used to study nutritional immunity and NDM, because it will glow only in the presence of the zinc needed to form the enzyme.

Chip under skin may identify stroke

For patients who have experienced certain common types of stroke, a small chip inserted under the skin may help physicians predict their likelihood of experiencing a second stroke and, therefore, their likelihood of benefiting from preventive therapy, according to a news release from Massachusetts General Hospital.

The findings come from a recent clinical trial, which was supported by Medtronic and published in the Journal of the American Medical Association. It was led by investigators at Massachusetts General Hospital (MGH) and Northwestern University Feinberg School of Medicine.

Each year, approximately 800,000 strokes occur in the United States, and as many as one-fourth occur in people who experienced a previous stroke. Investigators have been searching for ways to identify patients who are likely to experience a recurrent stroke, as these individuals could be candidates for taking certain medications such as blood thinners. One group of patients who face an elevated risk of recurrent strokes are those with atrial fibrillation — an irregular and often rapid heart rate — that often goes undetected and untreated. (Irregular heartbeats can allow blood to pool in the heart, which can cause clots to form and travel to the brain.)

Recent research has shown that a small chip inserted under the skin can monitor the heart rate and rhythm, and help physicians detect atrial fibrillation in patients who previously experienced what’s called a cryptogenic stroke, one with no identified cause despite thorough patient testing. Now investigators have tested the chip — less than 1¾” long and 1/6” thick and called an insertable cardiac monitor — in patients who experienced a stroke caused by narrowing of a large artery like the carotid artery, or blockage of a small artery deep in the brain where atrial fibrillation would be unexpected.

In the Stroke of Known Cause and Underlying Atrial Fibrillation (STROKE AF) trial, 492 patients were randomized and completed 12 months of follow-up after receiving either an insertable cardiac monitor within 10 days of an initial stroke or usual care consisting of external cardiac monitoring through electrocardiograms or other tracking methods.

The chip detected atrial fibrillation in 12.1% of patients, compared with 1.8% detected through usual care. The team noted that the episodes of atrial fibrillation were not brief, with most lasting at least one hour. Most stroke experts would recommend that patients with this degree of atrial fibrillation start taking blood thinners to prevent a future stroke.

The FDA approves first Alzheimer’s drug since 2003

The U.S. Food and Drug Administration (FDA) approved Aduhelm (aducanumab) for the treatment of Alzheimer’s, a debilitating disease affecting 6.2 million Americans. This first new treatment approved for Alzheimer’s since 2003.

The agency granted approval of the drug even though its advisory committee and other experts voiced concerns about the drug’s efficacy and safety, based on the evidence produced during clinical trials.

The FDA said Aduhelm was approved using the accelerated approval pathway, which can be used for a drug that provides a meaningful therapeutic advantage over existing treatments for a serious disease. Under that pathway, the FDA said it is requiring the drug’s developer, Biogen, to conduct a new randomized, controlled clinical trial to verify the drug’s clinical benefit. If the trial fails to verify clinical benefit, the FDA said it may withdraw approval of the drug. 

Editors Clarification

Two Abbott hematology analyzers (CELL-DYN RUBY and Sapphire) were in the June issue feature on coagulation analyzers; however, neither perform coagulation tests. MLO regrets the error. 

Lung protein elevation may predict COPD

Airway mucus consists of various proteins, such as long mucins MUC5AC and MUC5B, both of which contribute greatly to the proper gel-like consistency of this most essential bodily fluid.

UNC School of Medicine researchers led by mucin expert Mehmet Kesimer, PhD, had previously discovered that the total mucin concentrations in the lungs are associated with COPD disease progression and could be used as diagnostic markers of chronic bronchitis, a hallmark condition for patients with COPD. Kesimer and colleagues now report that one of these mucins, MUC5AC, is more closely and reliably associated with the development of COPD than is its brother, MUC5B.

The research, published in The Lancet Respiratory Medicine, shows that MUC5AC is found at elevated levels in smokers who had not yet developed COPD but whose lung function wound up decreasing over the course of the three-year study. Former smokers at-risk for COPD, on the other hand, had normal levels of MUC5AC at the start of the study and maintained proper lung function over three years. MUC5AC hyper concentration in the lungs may be a key factor in predicting the risks and rates of progression to more severe disease, according to the study.

Recent nationwide efforts have focused on early- or pre-COPD to predict the risks of progression to COPD amongst smokers.

“Currently, we cannot forecast which individuals in the at-risk smokers group will progress to COPD, because we don’t have an objective biological marker to underpin the disease-causing pathways. Our research shows that MUC5AC could be a predictor of who will develop COPD from the large group of aging ‘at-risk’ smokers,” said Kesimer, Professor in the UNC Department of Pathology and Laboratory Medicine, and member of the UNC Marsico Lung Institute. “We think MUC5AC could be a new biomarker for COPD prognosis, and it could be a biomarker for testing the effectiveness of therapeutic strategies.”

MUC5AC could also become a target for pharmaceutical developers whose goal it is to halt COPD disease progression and help patients live more normal, active lives.

Smoking cigarettes has long been known to be a major risk factor for COPD, but Kesimer’s work suggests that quiting smoking decreases the odds of developing COPD as we age.