Advertisements
Feeds:
Posts
Comments

Archive for the ‘Diabetes Mellitus’ Category


Will Lab-Grown Insulin-Producing Cells be the Next Insulin Pill?

Reporter: Irina Robu, PhD

Type 1 diabetes is an autoimmune disorder that destroys the insulin-producing beta cells of the pancreas, typically in childhood. Starved of insulin’s ability to regulate glucose levels in the blood, spikes in blood sugar can cause serious organ damage and eventually death. Replacing insulin cells lost in patients with Type 1 diabetes, has been a goal in regenerative medicine, but until now researchers had not been able to figure out how to produce cells in a lab dish that work as they do in healthy adults.

Dr. Matthias Hebrok, director of Diabetes Center at UCSF published a study on Feb 1, 2019 in Nature Cell Biology looked into generating insulin-producing cells that look and act a lot like the pancreatic beta cell. Hebrok and colleagues replicated the physical process by which the cells separate from the rest of the pancreas and form the so-called islets of Langerhans in the lab.

When the researchers replicated that process in lab dishes by artificially separating partially differentiated pancreatic stem cells and reforming them into islet-like clusters, the cells’ development unexpectedly leap forward. Not only did the beta cells begin responding to blood sugar more like mature insulin-producing cells, but similarly appeared to develop in ways that had never been realized in a laboratory setting. The scientist then transplanted these lab-grown islets into healthy mice and found that that in a matter of days, they produce more insulin than the animals’ own islets.

In partnership with bioengineers, geneticists, and other colleagues at UCSF, Hebrok’s team is by now working to move regenerative therapies to reality by using CRISPR gene editing to make these cells transplantable into patients without the necessity for immune-suppressing drugs or by screening drugs that could reinstate proper islet function in patients with Type 1 diabetes by protecting and expanding the few remaining beta cells to restart pancreatic insulin production.

SOURCE
https://www.universityofcalifornia.edu/news/functional-insulin-producing-cells-grown-lab?utm_source=fiat-lux

 

Advertisements

Read Full Post »


Google, Verily’s Uses AI to Screen for Diabetic Retinopathy

Reporter : Irina Robu, PhD

Google and Verily, the life science research organization under Alphabet designed a machine learning algorithm to better screen for diabetes and associated eye diseases. Google and Verily believe the algorithm can be beneficial in areas lacking optometrists.

The algorithm is being integrated for the first time in a clinical setting at Aravind Eye Hospital in Madurai, India where it is designed to screen for diabetic retinopathy and diabetic macular edema. After a patient is imaged by trained staff using a fundus camera, the image is uploaded to the screening algorithm through management software. The algorithm then analyzes the images for the diabetic eye diseases before returning the results.

Numerous AI-driven approaches have lately been effective in detecting diabetic retinopathy with high accuracy. An AI-based grading system was able to effectively diagnose two patients with the disease. Furthermore, an AI-driven approach for detecting an early sign of diabetic retinopathy attained an accuracy rate of more than 98 percent.

According to the R. Usha Kim, Chief of retina services at the Aravind Eye Hospital the algorithm permits physicians to work closely with patients on treatment and management of their disease, whereas increasing the volume of screenings we can perform. Automated grading of diabetic retinopathy has possible benefits such as increasing efficiency, reproducible, and coverage of screening programs and improving patient outcomes by providing early detection and treatment.

Even if the technology sounds promising, current research show there are long way until it can directly transfer from the lab into clinic.

SOURCE
https://www.healthcareitnews.com/news/google-verily-using-ai-screen-diabetic-retinopathy-india

Read Full Post »


Reprogrammed Human Pancreatic Cells Reprogrammed to Create Insulin

Reporter: Irina Robu, PhD

A  new study proposes that various cells can be modified to take a place of an insulin producing cell to help control sugar levels.  Researchers from University of Lincoln, UK report coaxing human pancreatic cells that don’t normally make insulin (a hormone that regulates the amount of glucose in the blood), to change their identity and begin producing the hormone. When implanted in mice, these reprogrammed cells relieved symptoms of diabetes, raising the opportunity that the method could one day be used as a treatment in people.

It is known that beta cells normally respond by releasing insulin when blood sugar levels rise after eating, which in turn stimulates to start absorbing sugars. In people with diabetes, this system breaks down, leading to high blood sugar levels that can harm the body and cause illness. In type 1 diabetes, the immune system attacks and destroys β-cells; in type 2, the β-cells do not produce enough of the hormone, or the body becomes resistant to insulin.

Scientists have previously revealed in mouse studies that if β-cells are destroyed, alternative type of pancreatic cell, called α-cells become more β-like and start making insulin. These α-cells normally yield the hormone glucagon which are originate together with β-cells in clumps of hormone-secreting cells called pancreatic islets or islets of Langerhans. Preceding studies showed that two proteins that control gene expression seemed to have an important role in coaxing α-cells to produce insulin in mice: Pdx1 and MafA.

At the same time as researchers from University of Lincoln, researchers from Pedro Herrera group at University of Geneva, wondered whether producing more of these proteins in human α-cells would have a similar result. They first took islet cells from human pancreases, and separated out the individual cell types which were then introduced DNA that encoded Pdx1 and MafA proteins into the α-cells, before clumping them back together.

After one week in culture, almost 40% of the human α-cells were producing insulin, while control cells that hadn’t been reprogrammed were not. The reprogrammed cells showed an increase in the expression of other genes related to β-cells, which were then implanted into diabetic mice, which had their β-cells destroyed and found that blood-sugar levels went down to normal levels. When the cell grafts were removed, the mice’s blood sugar shot back up.

Results of the experiment show that if α-cells or other kinds of islet cells could be made to start producing insulin in this way in diabetes patients’ quality of life will improve. According to Herrera before drawing conclusions about the efficacy of their approach, they will need to test the hybrid cells with other antibodies present in type-1 diabetes that could potentially attack those cells. But the research demonstrates that there is a lot of plasticity in the hormonal system of the human pancreas.

SOURCE

https://www.nature.com/articles/d41586-019-00578-z

Read Full Post »

Digital Therapeutics: A Threat or Opportunity to Pharmaceuticals


Digital Therapeutics: A Threat or Opportunity to Pharmaceuticals

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

Digital Therapeutics (DTx) have been defined by the Digital Therapeutics Alliance (DTA) as “delivering evidence based therapeutic interventions to patients, that are driven by software to prevent, manage or treat a medical disorder or disease”. They might come in the form of a smart phone or computer tablet app, or some form of a cloud-based service connected to a wearable device. DTx tend to fall into three groups. Firstly, developers and mental health researchers have built digital solutions which typically provide a form of software delivered Cognitive-Behaviour Therapies (CBT) that help patients change behaviours and develop coping strategies around their condition. Secondly there are the group of Digital Therapeutics which target lifestyle issues, such as diet, exercise and stress, that are associated with chronic conditions, and work by offering personalized support for goal setting and target achievement. Lastly, DTx can be designed to work in combination with existing medication or treatments, helping patients manage their therapies and focus on ensuring the therapy delivers the best outcomes possible.

 

Pharmaceutical companies are clearly trying to understand what DTx will mean for them. They want to analyze whether it will be a threat or opportunity to their business. For a long time, they have been providing additional support services to patients who take relatively expensive drugs for chronic conditions. A nurse-led service might provide visits and telephone support to diabetics for example who self-inject insulin therapies. But DTx will help broaden the scope of support services because they can be delivered cost-effectively, and importantly have the ability to capture real-world evidence on patient outcomes. They will no-longer be reserved for the most expensive drugs or therapies but could apply to a whole range of common treatments to boost their efficacy. Faced with the arrival of Digital Therapeutics either replacing drugs, or playing an important role alongside therapies, pharmaceutical firms have three options. They can either ignore DTx and focus on developing drug therapies as they have done; they can partner with a growing number of DTx companies to develop software and services complimenting their drugs; or they can start to build their own Digital Therapeutics to work with their products.

 

Digital Therapeutics will have knock-on effects in health industries, which may be as great as the introduction of therapeutic apps and services themselves. Together with connected health monitoring devices, DTx will offer a near constant stream of data about an individuals’ behavior, real world context around factors affecting their treatment in their everyday lives and emotional and physiological data such as blood pressure and blood sugar levels. Analysis of the resulting data will help create support services tailored to each patient. But who stores and analyses this data is an important question. Strong data governance will be paramount to maintaining trust, and the highly regulated pharmaceutical industry may not be best-placed to handle individual patient data. Meanwhile, the health sector (payers and healthcare providers) is becoming more focused on patient outcomes, and payment for value not volume. The future will say whether pharmaceutical firms enhance the effectiveness of drugs with DTx, or in some cases replace drugs with DTx.

 

Digital Therapeutics have the potential to change what the pharmaceutical industry sells: rather than a drug it will sell a package of drugs and digital services. But they will also alter who the industry sells to. Pharmaceutical firms have traditionally marketed drugs to doctors, pharmacists and other health professionals, based on the efficacy of a specific product. Soon it could be paid on the outcome of a bundle of digital therapies, medicines and services with a closer connection to both providers and patients. Apart from a notable few, most pharmaceutical firms have taken a cautious approach towards Digital Therapeutics. Now, it is to be observed that how the pharmaceutical companies use DTx to their benefit as well as for the benefit of the general population.

 

References:

 

https://eloqua.eyeforpharma.com/LP=23674?utm_campaign=EFP%2007MAR19%20EFP%20Database&utm_medium=email&utm_source=Eloqua&elqTrackId=73e21ae550de49ccabbf65fce72faea0&elq=818d76a54d894491b031fa8d1cc8d05c&elqaid=43259&elqat=1&elqCampaignId=24564

 

https://www.s3connectedhealth.com/resources/white-papers/digital-therapeutics-pharmas-threat-or-opportunity/

 

http://www.pharmatimes.com/web_exclusives/digital_therapeutics_will_transform_pharma_and_healthcare_industries_in_2019._heres_how._1273671

 

https://www.mckinsey.com/industries/pharmaceuticals-and-medical-products/our-insights/exploring-the-potential-of-digital-therapeutics

 

https://player.fm/series/digital-health-today-2404448/s9-081-scaling-digital-therapeutics-the-opportunities-and-challenges

 

Read Full Post »


Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

Stroke is a leading cause of death worldwide and the most common cause of long-term disability amongst adults, more particularly in patients with diabetes mellitus and arterial hypertension. Increasing evidence suggests that disordered physiological variables following acute ischaemic stroke, especially hyperglycaemia, adversely affect outcomes.

 

Post-stroke hyperglycaemia is common (up to 50% of patients) and may be rather prolonged, regardless of diabetes status. A substantial body of evidence has demonstrated that hyperglycaemia has a deleterious effect upon clinical and morphological stroke outcomes. Therefore, hyperglycaemia represents an attractive physiological target for acute stroke therapies.

 

However, whether intensive glycaemic manipulation positively influences the fate of ischaemic tissue remains unknown. One major adverse event of management of hyperglycaemia with insulin (either glucose-potassium-insulin infusions or intensive insulin therapy) is the occurrence of hypoglycaemia, which can also induce cerebral damage.

 

Doctors all over the world have debated whether intensive glucose management, which requires the use of IV insulin to bring blood sugar levels down to 80-130 mg/dL, or standard glucose control using insulin shots, which aims to get glucose below 180 mg/dL, lead to better outcomes after stroke.

 

A period of hyperglycemia is common, with elevated blood glucose in the periinfarct period consistently linked with poor outcome in patients with and without diabetes. The mechanisms that underlie this deleterious effect of dysglycemia on ischemic neuronal tissue remain to be established, although in vitro research, functional imaging, and animal work have provided clues.

 

While prompt correction of hyperglycemia can be achieved, trials of acute insulin administration in stroke and other critical care populations have been equivocal. Diabetes mellitus and hyperglycemia per se are associated with poor cerebrovascular health, both in terms of stroke risk and outcome thereafter.

 

Interventions to control blood sugar are available but evidence of cerebrovascular efficacy are lacking. In diabetes, glycemic control should be part of a global approach to vascular risk while in acute stroke, theoretical data suggest intervention to lower markedly elevated blood glucose may be of benefit, especially if thrombolysis is administered.

 

Both hypoglycaemia and hyperglycaemia may lead to further brain injury and clinical deterioration; that is the reason these conditions should be avoided after stroke. Yet, when correcting hyperglycaemia, great care should be taken not to switch the patient into hypoglycaemia, and subsequently aggressive insulin administration treatment should be avoided.

 

Early identification and prompt management of hyperglycaemia, especially in acute ischaemic stroke, is recommended. Although the appropriate level of blood glucose during acute stroke is still debated, a reasonable approach is to keep the patient in a mildly hyperglycaemic state, rather than risking hypoglycaemia, using continuous glucose monitoring.

 

The primary results from the Stroke Hyperglycemia Insulin Network Effort (SHINE) study, a large, multisite clinical study showed that intensive glucose management did not improve functional outcomes at 90 days after stroke compared to standard glucose therapy. In addition, intense glucose therapy increased the risk of very low blood glucose (hypoglycemia) and required a higher level of care such as increased supervision from nursing staff, compared to standard treatment.

 

References:

 

https://www.nih.gov/news-events/news-releases/nih-study-provides-answer-long-held-debate-blood-sugar-control-after-stroke

 

https://www.ncbi.nlm.nih.gov/pubmed/27873213

 

https://www.ncbi.nlm.nih.gov/pubmed/19342845

 

https://www.ncbi.nlm.nih.gov/pubmed/20491782

 

https://www.ncbi.nlm.nih.gov/pubmed/21211743

 

https://www.ncbi.nlm.nih.gov/pubmed/18690907

 

Read Full Post »


Hypertriglyceridemia: Evaluation and Treatment Guideline

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

Severe and very severe hypertriglyceridemia increase the risk for pancreatitis, whereas mild or moderate hypertriglyceridemia may be a risk factor for cardiovascular disease. Individuals found to have any elevation of fasting triglycerides should be evaluated for secondary causes of hyperlipidemia including endocrine conditions and medications. Patients with primary hypertriglyceridemia must be assessed for other cardiovascular risk factors, such as central obesity, hypertension, abnormalities of glucose metabolism, and liver dysfunction. The aim of this study was to develop clinical practice guidelines on hypertriglyceridemia.

The diagnosis of hypertriglyceridemia should be based on fasting levels, that mild and moderate hypertriglyceridemia (triglycerides of 150–999 mg/dl) be diagnosed to aid in the evaluation of cardiovascular risk, and that severe and very severe hypertriglyceridemia (triglycerides of >1000 mg/dl) be considered a risk for pancreatitis. The patients with hypertriglyceridemia must be evaluated for secondary causes of hyperlipidemia and that subjects with primary hypertriglyceridemia be evaluated for family history of dyslipidemia and cardiovascular disease.

The treatment goal in patients with moderate hypertriglyceridemia should be a non-high-density lipoprotein cholesterol level in agreement with National Cholesterol Education Program Adult Treatment Panel guidelines. The initial treatment should be lifestyle therapy; a combination of diet modification, physical activity and drug therapy may also be considered. In patients with severe or very severe hypertriglyceridemia, a fibrate can be used as a first-line agent for reduction of triglycerides in patients at risk for triglyceride-induced pancreatitis.

Three drug classes (fibrates, niacin, n-3 fatty acids) alone or in combination with statins may be considered as treatment options in patients with moderate to severe triglyceride levels. Statins are not be used as monotherapy for severe or very severe hypertriglyceridemia. However, statins may be useful for the treatment of moderate hypertriglyceridemia when indicated to modify cardiovascular risk.

 

References:

 

https://www.medpagetoday.com/clinical-connection/cardio-endo/77242?xid=NL_CardioEndoConnection_2019-01-21

https://www.ncbi.nlm.nih.gov/pubmed/19307519

https://www.ncbi.nlm.nih.gov/pubmed/23009776

https://www.ncbi.nlm.nih.gov/pubmed/6827992

https://www.ncbi.nlm.nih.gov/pubmed/22463676

https://www.ncbi.nlm.nih.gov/pubmed/17635890

 

Read Full Post »


Cardiovascular (CV) Disease and Diabetes: New ACC Guidelines for use of two major new classes of diabetes drugs — sodium-glucose cotransporter type 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1RAs) for reduction of adverse outcomes

Reporter: Aviva Lev-Ari, PhD, RN

 

“The main aim for this report is to educate cardiologists, who might not otherwise think about prescribing diabetes drugs, about these two new classes of medications that have important cardiovascular benefits for their patients,” cochair of the writing committee for the new consensus document, Brendan Everett, MD, assistant professor of medicine, Brigham and Women’s Hospital, Boston, commented to theheart.org | Medscape Cardiology.

We hope to help them understand which of their patients might benefit, and to help them understand how to prescribe these new drugs appropriately to their patients with both atherosclerotic cardiovascular disease and diabetes.”

The document is published online November 26 in the Journal of the American College of Cardiology, and is endorsed by the American Diabetes Association.

Journal of the American College of Cardiology

2018 ACC Expert Consensus Decision Pathway on Novel Therapies for Cardiovascular Risk Reduction in Patients With Type 2 Diabetes and Atherosclerotic Cardiovascular Disease

A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways Writing Committee: 

4 Pathway Summary Graphic

Figure 1 provides an overview of what is covered in the Expert Consensus Decision Pathway. See each section for more detailed considerations and guidance.

Figure 1

Summary Graphic

Figure 2 offers 1 approach to deciding which drug to use in which patient, Table 11 outlines patient and clinician preferences to consider when selecting an SGLT2 inhibitor or GLP-1RA. Table 12 provides an overview of considerations for initiating and monitoring an SGLT2 inhibitor. Table 13 provides an overview of considerations for initiating and monitoring a GLP-1RA.

Figure 2

Approach to Managing Patients With Established ASCVD and T2D

SOURCE

Read Full Post »

Older Posts »