insulin

Posted on Diabetes

New procedure may eliminate insulin dependency in type 2 diabetes

a promising new treatment strategy for type 2 diabetes (T2D) that could significantly reduce or even eliminate the need for insulin therapy.
A promising new treatment strategy for type 2 diabetes (T2D) that could significantly reduce or even eliminate the need for insulin therapy.

Groundbreaking research presented at UEG Week 2024 reveals a promising new treatment for type 2 diabetes (T2D) that could significantly reduce or eliminate the need for insulin therapy.

This innovative approach combines a novel procedure called ReCET (Re-Cellularization via Electroporation Therapy) with semaglutide, resulting in the elimination of insulin therapy for 86% of patients.

Globally, type 2 diabetes (T2D) affects 422 million people, and obesity is recognized as a significant risk factor. While insulin therapy is commonly used to manage blood sugar levels in T2D patients, it can lead to side effects such as weight gain and further complicate diabetes management.

In the initial human trial, 14 participants between the ages of 28 and 75, with body mass indices ranging from 24 to 40 kg/m², underwent the ReCET procedure while under deep sedation. This treatment aims to enhance the body’s responsiveness to its own insulin. After the procedure, the participants followed a two-week isocaloric liquid diet, and then the dosage of semaglutide was gradually increased to 1mg per week.

At the 6- and 12-month follow-up, 86% of participants (12 out of 14) no longer needed insulin therapy, and this positive outcome persisted through the 24-month follow-up. During this time, all patients were able to maintain glycemic control, with HbA1c levels staying below 7.5%.

The maximum dose of semaglutide was well-tolerated by 93% of participants, one individual could not increase to the maximum dose due to nausea. All patients successfully completed the ReCET procedure, and no serious adverse effects were reported.

Dr Celine Busch, lead author of the study, commented, “These findings are very encouraging, suggesting that ReCET is a safe and feasible procedure that, when combined with semaglutide, can effectively eliminate the need for insulin therapy.”

“Unlike drug therapy, which requires daily medication adherence, ReCET is compliance-free, addressing the critical issue of ongoing patient adherence in the management of T2D. In addition, the treatment is disease-modifying: it improves the patient’s sensitivity to their own (endogenous) insulin, tackling the root cause of the disease, as opposed to currently available drug therapies, that are at best disease-controlling.”

Looking ahead, the researchers plan to conduct larger randomised controlled trials to further validate these findings. Dr Busch added, “We are currently conducting the EMINENT-2 trial with the same inclusion and exclusion criteria and administration of semaglutide, but with either a sham procedure or ReCET. This study will also include mechanistic assessments to evaluate the underlying mechanism of ReCET.”

Posted on Diabetes

A new injectable to prevent and treat hypoglycemia

A new injectable to prevent and treat hypoglycemia

Encapsulated glucagon for insulin-induced hypoglycemia dissolves when sugar levels get seriously low (less than 60 milligrams per deciliter, mg/dL), releasing the hormone into the bloodstream and triggering the liver to release glucose. The micelles remain intact at normal sugar levels (more than 100 mg/dL), keeping glucagon inactive. Credit Adapted from ACS Central Science 2024, DOI: 10.1021/acscentsci.4c00937

People with diabetes take insulin to lower high blood sugar. However, if glucose levels plunge too low — from taking too much insulin or not eating enough sugar — people can experience hypoglycemia, which can lead to dizziness, cognitive impairment, seizures or comas. Researchers in ACS Central Science report encapsulating the hormone glucagon to prevent and treat this condition. In mouse trials, the nanocapsules activated when blood sugar levels dropped dangerously low and quickly restored glucose levels.

Glucagon is a hormone that signals the liver to release glucose into the bloodstream. It’s typically given by injection to counteract severe hypoglycemia in people who have diabetes. While an emergency glucagon injection can correct blood sugar levels in about 30 minutes, formulations can be unstable and insoluble in water. Sometimes, the hormone quickly breaks down when mixed for injections and clumps together to form toxic fibrils. Additionally, many hypoglycemic episodes occur at night, when people with diabetes aren’t likely to test their blood sugar. To improve commercial glucagon stability and prevent hypoglycemia, Andrea Hevener and Heather Maynard looked to micelles: nanoscale, soap-like bubbles that can be customized to assemble or disassemble in different environments and are used for drug delivery. They developed a glucose-responsive micelle that encapsulates and protects glucagon in the bloodstream when sugar levels are normal but dissolve if levels drop dangerously low. To prevent hypoglycemia, the micelles could be injected ahead of time and circulate in the bloodstream until they are needed.

In lab experiments, the researchers observed that the micelles disassembled only in liquid environments mimicking hypoglycemic conditions in human and mice bodies: less than 60 milligrams of glucose per deciliter. Next, when mice experiencing insulin-induced hypoglycemia received an injection of the specialized micelles, they achieved normal blood sugar levels within 40 minutes. The team also determined that glucagon-packed micelles stayed intact in mice and didn’t release the hormone unless blood glucose levels fell below the clinical threshold for severe hypoglycemia. From additional toxicity and biosafety studies in mice, the researchers note that empty micelles didn’t trigger an immune response or induce organ damage.

Posted on Diet

How Sugar & Processed Foods Impact Your Health

“In this episode, my guest is Dr Robert Lustig, M.D., a neuroendocrinologist and professor of paediatrics at the University of California, San Francisco (UCSF). He is also a bestselling author on nutrition and metabolic health. We discuss the “calories in calories out” (CICO) model of metabolism and weight regulation and how specific macronutrients (protein, fat, carbohydrates), fibre, and sugar can modify the CICO equation. We cover the impact of different types of sugars, particularly fructose, sugars found in liquid form, taste intensity, and other factors on insulin levels, liver, kidney, and metabolic health. We also explore how fructose in non-fruit sources can be addictive, similar to drugs of abuse, and how sugar alters brain circuits related to food cravings and satisfaction. Additionally, we discuss the role of sugar in childhood and adult obesity, gut health and disease, and mental health. Furthermore, we delve into how the food industry uses refined sugars to create pseudo foods and their effects on the brain and body. This episode provides actionable information about sugar and metabolism, weight control, brain health, and body composition. It should be of interest to anyone seeking to understand how specific food choices impact the immediate and long-term health of the brain and body.”

Posted on Diabetes

Potential strategy against blood glucose drops in type 1 diabetes

Benrick and Rorsman

Anna Benrick and Patrik Rorsman, Sahlgrenska Academy at the University of Gothenburg, Credit Photo: University of Gothenburg.

New research suggests that inhibiting the hormone somatostatin could be a promising treatment approach for preventing severe drops in blood glucose levels in individuals with type 1 diabetes. A study conducted at the University of Gothenburg and other institutions has demonstrated the potential of this strategy to save lives.

When blood glucose levels decrease in healthy individuals, the pancreas releases a hormone called glucagon. This hormone prompts the liver to produce glucose, which helps to normalize the blood glucose levels. Glucagon has the opposite effect to insulin, another hormone that lowers blood glucose levels. Both insulin and glucagon are produced in the pancreas.

Individuals with type 1 diabetes have insufficient insulin as well as glucagon. When glucagon is not released during a drop in blood glucose, it results in dangerously low blood sugar levels, a condition that accounts for approximately 10% of all deaths in individuals with type 1 diabetes.

Restored ability to fend off drops in blood sugar

The latest study, published in the journal Nature Metabolism, introduces a potential new treatment approach for preventing dangerous blood sugar drops in individuals with type 1 diabetes. Patrik Rorsman, a leading researcher and Professor of Cellular Endocrinology at the Sahlgrenska Academy at the University of Gothenburg, as well as an active member of the University of Oxford, is one of the key contributors to this study.

The researchers examined groups of hormone-producing cells from the pancreas of humans and mice. They showed that in type 1 diabetes, these islets are unable to release glucagon when blood sugar is low. This is because the hormone somatostatin is released in greater amounts in type 1 diabetes and inhibits the release of glucagon.

Meanwhile, experiments showed that blocking somatostatin in mice with type 1 diabetes could restore the pancreas’s ability to release glucagon in the event of low blood sugar, thus preventing dangerously low blood sugar levels. The blocking was done pharmacologically.

Mapping of previously unknown signalling

Using genetically modified mice in which beta cells were activated by light, known as optogenetics, the interaction between different cell types in the pancreatic islets was also mapped: alpha cells that release glucagon, beta cells that release insulin and delta cells that release somatostatin.

The results provide an underlying explanation for how the reduced proportion of functioning beta cells in type 1 diabetes can be linked to the increased risk of blood sugar drops, something that has so far been unclear.

Anna Benrick is an Associate Professor of Physiology at the Sahlgrenska Academy at the University of Gothenburg and one of the co-authors.

“The new findings highlight an important and previously unknown role of electrical signaling that occurs through open cell connections between beta cells and delta cells,” she says. “If the electrical connections are lost, then the release of glucagon is reduced and the risk of a drop in blood pressure increases. The fact that this can be restored pharmacologically by blocking somatostatin opens up the possibility of preventing dangerous blood sugar drops in type 1 diabetes.”

Posted on Diabetes, Patient Talk

Once-weekly insulin as effective as daily injections for type 2 diabetics

a new class of insulin that is injected once a week is as effective as daily insulin injections for effective and safe blood sugar management in patients with type 2 diabetes
A new class of insulin that is injected once a week is as effective as daily insulin injections for effective and safe blood sugar management in patients with type 2 diabetes

When individuals with type 2 diabetes discover that their oral medications are no longer effective in controlling their blood sugar, insulin therapy is introduced. The frequency of insulin injections (such as daily injections) is one of the primary factors that can lead to difficulties in adhering to the treatment. Other factors include concerns about weight gain and experiencing hypoglycemic episodes, also known as “hypos.”

Insulin efsitora alfa (efsitora) is a new basal insulin designed for once-weekly administration. Clinical data on its safety and effectiveness so far have been limited to small phase 1 or phase 2 trials. This new phase 3 study compared the effectiveness of once-weekly visitors to daily injections of insulin degludec (standard insulin) in adult patients who had not yet started insulin therapy despite being on multiple oral diabetes medications and still not reaching their glycemic goals.

The authors state: “Among adults with type 2 diabetes who had not previously received insulin, once-weekly efsitora was found to be as effective as once-daily degludec in controlling high blood sugar by reducing glycated hemoglobin levels.”

“The potential of a once-weekly insulin is to simplify dose administration and reduce barriers to starting insulin therapy by decreasing injection frequency compared to a once-daily insulin. A recent study on preferences for once-weekly basal insulin in adults with type 2 diabetes showed that both patients and providers would favor once-weekly basal insulin over current basal insulin preparations.”