Tag: diabetes

Treating Periodontitis can Reduce Risks of Certain Other Diseases

A steadily growing body of evidence points to a two-way connection between oral health and systemic disease.

Periodontitis, the inflammation and disease of tissues surrounding the teeth, is already known to be a result of type 2 diabetes, but there is research to suggest that it may also cause diabetes—as well as certain other diseases.

“What happens in your body impacts your mouth, and that in turn impacts your body. It’s truly a cycle of life,” said Professor Purnima Kumar of The Ohio State University. “What is more dynamic than the gateway to your body – the mouth?” she continued. “It’s so ignored when you think about it, and it’s the most forward-facing part of your body that interfaces with the environment, and it’s connected to this entire tubing system. And yet we study everything but the mouth.”

The link between oral health and type 2 diabetes was first established in the 1990s, and Prof Kumar has led many investigations into this area. She was lead author in a study published last year that investigated the oral microbiomes of people with and without type 2 diabetes, and the effects of nonsurgical periodontitis treatment.

“Our studies have led up to the conclusion that people with diabetes have a different microbiome from people who are not diabetic,” Prof Kumar said. “We know that changing the bacteria in your mouth and restoring them back to what your body knows as healthy and friendly bacteria actually improves your glycemic control.”

The rough picture that has emerged is that oral bacteria are aerobic, but even small changes such as a few days of not brushing teeth can trigger a cascade that results in the bacteria shifting to an anaerobic, fermentative state producing toxins and byproducts. It becomes, as Prof Kumar puts it, “a septic tank” that stimulates the immune system and causes an inflammatory state, producing signalling products that bacteria then feed on.

“Then this community – it’s an ecosystem – shifts. Organisms that can break down protein start growing more, and organisms that can breathe in an oxygen-starved environment grow. The bacterial profile and, more importantly, the function of the immune system changes,” she explained.

The inflammation causes pores to open in the lining of the mouth, allowing the bacteria entry to the body.

“The body is producing inflammation in response to these bacteria, and those inflammatory products are also moving to the bloodstream, so now you’re getting hammered twice. Your body is trying to protect you and turning against itself,” Prof Kumar said. “And these pathogens are having a field day, crossing boundaries they were never supposed to cross.”

Though the relationship between oral health and certain disease is a complex one, Prof Kumar said prevention was exceedingly simple. Daily brushing and flossing with twice-yearly dentist visits for cleaning were sufficient.

Source: News-Medical.Net

Journal information: Kumar, P. S., et al. (2020) Subgingival Host-Microbial Interactions in Hyperglycemic Individuals. Journal of Dental Research. doi.org/10.1177/0022034520906842. 

Large Study Casts Doubt on “Fat but Fit”

New Spanish research casts doubt on the “fat but fit” paradox, where it is thought that physical fitness is enough to eliminate cardiovascular disease (CVD) risk.

Overweight and obesity is a worldwide problem that is greatly contributing to the burden of noncommunicable diseases, including CVD. A high body mass index (BMI) is strongly associated with CVD risk factors, such as hypercholesterolaemia, hypertension and diabetes. The cardiovascular complications arising from overweight and obesity are driven by processes such as inflammation, insulin resistance, endothelial dysfunction, coronary calcification. Some evidence suggested that physical activity was cardioprotective, partly or completely eliminating the CVD risk from disease – the “fat but fit” paradox.

A recent meta-analysis showed that cardiovascular fitness was a better predictor of cardiovascular disease over overweight/obesity, suggesting that perhaps public health programmes should emphasise fitness over control of body weight. To this end, the researchers sought to confirm if the “fat but fit” paradox was real.

The researchers gathered data from workers’ health insurance, with participants aged 18-64 grouped into normal weight, overweight and obesity by BMI, and into regularly active ( >150 min moderate physical activity or equivalent per week), insufficiently active (less than regularly active) and inactive (no physical activity at all). They were further separated by age, sex, smoking status and residential address.

Approximately 42%, 41%, and 18% of participants had normal weight, overweight, or obesity, respectively; 63.5%, 12.3%, and 24.2% were inactive, insufficiently active, and regularly active; and 30%, 15%, and 3% had hypercholesterolaemia, hypertension, and diabetes.

However, the protective effect of physical activity was far less than the excess risk from overweight/obesity. So much so that even regularly active obese participants had two to five-fold risk increases over their inactive but normal weight peers in the risk factors.

The protective effect of physical activity in overweight/obesity remains controversial. Shortcomings of the study were that they did not control for diet, and only accounted for self-reported leisure time activities. However, the large study size, with over 500 000 participants, should put paid to the theory that a physically active lifestyle can completely eliminate the deleterious effects of overweight/obesity.

The researchers concluded that, “weight loss per se should remain a primary target for health policies aimed at reducing CVD risk in people with overweight/obesity.”

Journal article source: European Journal of Protective Cardiology

Journal information: Pedro L Valenzuela, et al., Joint association of physical activity and body mass index with cardiovascular risk: a nationwide population-based cross-sectional study, European Journal of Preventive Cardiology, 2021;, zwaa151, https://doi.org/10.1093/eurjpc/zwaa151

Brown Fat May Protect Against Multiple Chronic Diseases

Brown fat, which is found around the neck and shoulders, was once thought only to be beneficial to newborns, but has more recently been thought to have beneficial health effects in humans. However, it has been challenging to study since it is so deeply buried.

In mouse models, brown fat is known to be thermogenic, significantly improving glucose and lipid homeostasis, but in humans its role in metabolism and cardiovascular disease was still unclear. The prevalence of brown fat is difficult to measure in humans, since the only noninvasive way to detect it is with expensive PET scans. However, radiologists have to distinguish brown fat from tumours in PET scans, and this provided a valuable resource to establish the prevalence of brown fat in the population. The researchers used 134 529 PET scans of 52 487 patients.

Brown fat was found in some 10% of the population, which may be an underestimate since individuals undergoing the scans were told to avoid cold, exercise and caffeine, which are all known to increase the activity of brown fat.

“For the first time, it reveals a link to lower risk of certain conditions,” said Paul Cohen, Assistant Professor at The Rockefeller University Hospital. “These findings make us more confident about the potential of targeting brown fat for therapeutic benefit.”

Despite this new evidence, exactly how brown fat contributes to health is still unclear, although there are some clues. Brown fat uses glucose to generate energy, and this may help lower blood glucose levels. The role hat brown fat plays in hypertension, which is tightly connected to the hormonal system, is less clear.”We are considering the possibility that brown fat tissue does more than consume glucose and burn calories, and perhaps actually participates in hormonal signaling to other organs,” Cohen says.

The researchers plan to investigate the biology of brown fat, such as by looking for genetic variations to explain why some have it and others do not, which may lead to pharmacological treatments.

“The natural question that everybody has is, ‘What can I do to get more brown fat?'” Cohen said. “We don’t have a good answer to that yet, but it will be an exciting space for scientists to explore in the upcoming years.”

Source: Medical Xpress

Journal information: Becher, T., Palanisamy, S., Kramer, D.J. et al. Brown adipose tissue is associated with cardiometabolic health. Nat Med (2021). doi.org/10.1038/s41591-020-1126-7

2020 Saw Huge Growth in Metformin Recalls

The year 2020 saw huge numbers of metformin products being removed from shelves due to contamination concerns. Metformin is an antidiabetic agents used to treat type 2 diabetes mellitus, and comes as immediate-release and extended-release products.

In May 2020, the US Food and Drug Administration (FDA) announced that it had recommended certain extended-release metformin products to be removed from shelves, as they were contaminated with N-nitrosodimethylamine (NDMA), a potential carcinogen. This followed a December 2019 announcement that the FDA was aware of there being low levels of NDMA in metformin products outside of the US. Lab studies showed NDMA in US products in February, although the FDA only recommended voluntary recalls of metformin products on May 28. Participating in the recall of extended-release metformin were five companies, of which one, Apotex and Amneal, recalled all of its lots.

Whilst NDMA is ubiquitous in daily life, found in cured and grilled foods as well as contaminated water, the daily limit was set at 96ng, specifically because such a dose would lead to a 1 in 100 000 increase in cancer risk after 70 years of exposure.

Prompted by a report from a private laboratory stating that 16 of 38 metformin products tested exceeded the daily NDMA limit, the FDA released its own article in the journal American Association of Pharmaceutical Scientists, stating the reasoning behind its recommendation for voluntary recall. The FDA noted that its own testing only found eight products of the 38 exceeded the NDMA limit, and explained that N,N-dimethylformamide (DMF) conflated levels in mass spectrometry measurements.

However, this was followed in July by an additional set of recalls, and yet more in August and October. Separately, Sun Pharmaceuticals issued a recall for its relatively new extended-release oral suspension (brand name Riomet ER; 500 mg/5 mL) which had only received approval in February.However, none of the FDA’s recalls have extended to immediate-release metformin, which is the most commonly prescribed form of the drug.

Source: MedPage Today

Exenatide and Dapagliflozin Outlast Metformin for Diabetes Treatment

An AstraZeneca-funded trial called DURATION-8 has shown a viable alternative for metformin with a combination of two medications, exenatide and dapagliflozin.

The standard treatment for type 2 diabetes is metformin, but for many patients it loses its effectiveness over time. To get around this, a combination of exenatide (a glucagon-like peptide-1 receptor agonist) and dapagliflozin (sodium-glucose cotransporter-2 inhibitor) was trialled.

Originally a 28 week trial, DURATION-8 was extended to 52 weeks on the strength of its initial results.

“Many therapies in diabetes management are short-lived, which is why it is useful to test for long-term effect,” says first author Dr Serge Jabbour, director of the division of endocrinology and the Diabetes Center at Thomas Jefferson University.

The trial, with 695 participants, compared the two medications, either individually with a placebo or in combination. The combination group saw the greatest drop in glycated hemoglobin (HbA1c) levels. This was accompanied by drops in systolic blood pressure and body weight.

The authors note the need for a follow-on study to determine if there were protective effects against cardiovascular and renal events with the combination.

Source: Medical News Today

Electromagnetic fields treat diabetes in animal models

According to Medial Express, electromagnetic fields (EMF) may be a new way to modulate blood glucose levels. Scientists found that when drawing blood from mice borrowed from an experiment which had them to low level EMF, the typical high blood sugar in these animals was found to be lowered. 

Carter and Huang are energized by the possibility of translating the findings to human patients with type 2 diabetes. In terms of safety, the World Health Organization considers low energy EMFs safe for human health. The UI study also found no evidence of any adverse side effects in mice.

The team is now working on a larger animal model to see if the EMFs produce similar effects in an animal that has a more similar size and physiology to humans. They also plan to conduct studies to understand the redox mechanism underlying the effects of EMFs. Their ultimate goal is to move into clinical trials with patients to translate the technology into a new class of therapies. With that goal in mind, Carter, Huang, and Carter’s twin brother, Walter, have created a startup company called Geminii Health, with help from the UI Office for the Vice President of Research.

“Our dream is to create a new class of non-invasive medicines that remotely take control of cells to fight disease,” Carter says.

The multidisciplinary research team also included scientists from the UI Departments of Radiology, Neuroscience and Pharmacology, Molecular Physiology and Biophysics, and Physics and Astronomy, as well as colleagues from Vanderbilt University.