type 1 diabetes

How does type 1 diabetes alter muscle structure and blood supply?

Posted by

0


How Type 1 Diabetes Alters Muscle Structure and Blood Supply?
Expression of myosin heavy chain isoforms 1 (A, E), 2a (B, F), 2x/d (C, G), and 2b (D, H) in successive cross-sections of gluteus maximusmuscle of streptozotocin-induced diabetic mice (A–D) and age-matched non-diabetic mice (E–H). The scale bar indicates 50 μm.

In a recent study conducted by the Institute of Anatomy, Faculty of Medicine, University of Ljubljana, researchers have provided new insights into the detrimental effects of type 1 diabetes mellitus (T1DM) on skeletal muscle structure and capillary networks. Utilizing state-of-the-art 3D imaging technology, this comprehensive study marks a significant leap in understanding the multifaceted impact of T1DM on the body’s muscular system.

Diabetes mellitus disrupts the regulation of glucose levels, leading to high blood sugar and a myriad of related health issues. T1DM, characterized by the immune-mediated destruction of insulin-producing pancreatic β cells, has profound effects on various organs, especially skeletal muscles, which play a crucial role in glucose uptake and regulation.

This study, published in the journal Biomolecules and Biomedicine, aimed to explore the structural and functional adaptations of skeletal muscles to the metabolic disturbances caused by T1DM.

The hidden changes in muscle and blood vessels

Conducted on female C57BL/6J-OlaHsd mice using a streptozotocin (STZ)-induced model to simulate T1DM, the research focused on critical muscles like the soleus, gluteus maximus, and gastrocnemius. Researchers meticulously analyzed the expression of myosin heavy chain (MyHC) isoforms and the intricacies of the 3D capillary network.

“Our study provides a deeper understanding of how type 1 diabetes not only affects muscle fiber composition but also significantly alters the capillary networks that are essential for muscle health,” explained Nejc Umek, the study’s lead author.

How Type 1 Diabetes Alters Muscle Structure and Blood Supply?
Numerical density and diameter of (A,D) gluteus maximus,(B,E) soleus, and (C,F) gastrocnemius muscle fibers. Comparison between type 1 diabetes mellitus mice (black columns; n=12) and non-diabetic mice (gray columns; n=12). Data are presented as mean±standard deviation. *P<0.05.

The research revealed that, despite the composition of fast-twitch type 2b fibers remaining consistent, notable differences were observed in the diabetic mice’s soleus muscle, which showed a reduced proportion of type 2a fibers and diminished fiber diameters across all muscles analyzed.

Additionally, an intriguing increase in capillary length per muscle volume was discovered in the gluteus maximus of diabetic mice, suggesting an adaptive mechanism to counterbalance muscle fiber atrophy induced by diabetes.

Methodological advances and key discoveries

The study utilized female mice, addressing a gap in diabetes research that often overlooks gender differences in disease progression and response to treatment. Through a single intraperitoneal administration of STZ, researchers successfully induced T1DM, confirmed by significantly elevated fasting glucose levels. This model allowed for an in-depth examination of diabetes-induced changes in a controlled environment.

By employing antibodies specific to different MyHC isoforms and cutting-edge 3D imaging, the team could precisely quantify changes in muscle fiber types and the capillary network. “The advanced 3D imaging techniques we used represent a significant improvement over traditional 2D analyses, offering a more detailed and accurate depiction of the capillary network changes in diabetic muscle tissue,” stated Erika Cvetko, the study’s senior author.

How Type 1 Diabetes Alters Muscle Structure and Blood Supply?
Capillaries and muscle fibers in gluteus maximus muscle of streptozotocin-induced diabetic mice (B, D) and age-matched non-diabeticmice (A, C).(A and B) Immunofluorescent staining with volume rendering of capillaries; (C and D) Reconstructed muscle fibers with supplying capillaries. The scale bar indicates 50μm.

Implications for diabetes management and future directions

The findings from this collaborative research effort highlight the necessity for comprehensive diabetes management plans that encompass not only glucose regulation but also the preservation of muscle structure and function. “Understanding the specific alterations in muscle tissue due to type 1 diabetes paves the way for developing targeted therapies that could significantly improve patient outcomes,” Cvetko added.

The study’s revelations about the increased capillary length per muscle volume in diabetic mice underscore the body’s potential compensatory responses to the structural changes induced by diabetes. These insights are crucial for designing interventions that aim to mitigate muscle deterioration and enhance overall diabetes care.

This novel study contributes significantly to the body of knowledge on diabetes and its systemic effects, particularly on skeletal muscle health. By highlighting the critical role of maintaining muscle integrity and vascular supply in the management of T1DM, the research opens new avenues for therapeutic strategies and underscores the importance of multidisciplinary approaches in tackling this complex disease.

Ozempic May Reduce Insulin Needs in People With Type 1 Diabetes

Posted by

0


Early research suggests that people with type 1 diabetes who started semaglutide within three months of diagnosis were able to stop taking mealtime insulin. 

The benefits of Ozempic (semaglutide) continue to stack up for people with type 2 diabetes and obesity, with the latest data showing that it reduces heart disease and stroke in people with obesity who don’t have diabetes. 

Semaglutide is also being studied for other conditions, such as fatty liver disease and addiction. However, people with type 1 diabetes have largely been left out of the conversation as there have been fewer studies on semaglutide as a treatment for type 1. 

However, this could change in the coming years. New research suggests that semaglutide may in fact have benefits in early type 1 diabetes – specifically, the potential to reduce insulin needs. 

What was the study testing? 

This study looked at the effects of semaglutide on new-onset type 1 diabetes. 

Most people with type 1 diabetes have some intact beta cells when they are first diagnosed, meaning that they may still produce insulin. A drug like semaglutide that could stimulate insulin secretion among the remaining beta cells might help people with newly diagnosed type 1 diabetes manage their glucose levels. 

The researchers analyzed whether semaglutide, a GLP-1 agonist, could help reduce blood glucose. The study evaluated data that was previously collected from 10 adults, ages 21-39, who had started taking semaglutide within three months of their diagnosis. At diagnosis, all the participants were taking basal and mealtime insulin.

Participants had started taking 0.125 mg semaglutide per week, which was then adjusted to a maximum of 0.5 mg semaglutide per week, while mealtime insulin dose was lowered. The basal insulin dose was reduced based on continuous glucose monitoring (CGM) data.

What were the key findings? 

Within three months, participants no longer needed mealtime insulin. At six months, seven out of 10 no longer needed basal insulin. That means the majority of people in the study were able to stop taking any insulin after six months of treatment with semaglutide. 

Researchers also noted improvements in participants’ glycemic control. For example, A1C levels fell from an average of 11.7% at diagnosis to 5.9% at six months and 5.7% at one year, indicating that participants were in the prediabetes range. Participants also achieved a time in range of 89%.

In terms of safety, some participants experienced mild hypoglycemia (low blood sugar) while the semaglutide dose was increased. Once the semaglutide dose stabilized, there were no problems with hypoglycemia. There were no reports of diabetic ketoacidosis or other serious side effects. 

The bottom line

This study shows possible benefits for semaglutide in new-onset type 1 diabetes – both to manage blood sugar and reduce insulin needs. Although the study size was small and not randomized, semaglutide may reduce blood glucose levels and eliminate the need for mealtime insulin in some people with type 1 diabetes. 

Previous research has shown benefits of a similar GLP-1 drug, liraglutide, on glucose, weight, and insulin doses in larger samples of people with type 1 diabetes. 

Another small study suggested that semaglutide may be beneficial for people with longstanding type 1 diabetes. Among 10 adults who had type 1 diabetes for an average of 20 years, semaglutide led to 14% weight loss over six months. Beyond weight loss, participants saw a 25% reduction in daily carbohydrate intake and a 26% reduction in insulin doses per day at six months.

Going forward, a larger, better-designed randomized study will be needed to understand the full picture of the safety and efficacy of semaglutide in type 1 diabetes.

Adding Splenda to your drink may prevent Type 1 diabetes and rheumatoid arthritis

Posted by

0


Artificial sweetener Splenda may hold the key to curing Type 1 diabetes and rheumatoid arthritis, a new study explains. High doses of sucralose, the basis for the popular sweetener, prevents cells from attacking healthy body tissue in mice — the same thing that happens to humans who have an autoimmune disease.

There are over 100 autoimmune diseases where a person’s built-in defense system accidentally attacks instead of protects the body. These include lupus, Crohn’s disease, ulcerative colitis, and multiple sclerosis.

“We’re hoping to piece together a bigger picture of the effects of diet on health and disease, so that one day we can advise on diets that are best suited to individual patients, or find elements of our diet that doctors can exploit for treatment,” says Karen Vousden, a senior study author and principal group leader at the Francis Crick Institute, in a media release.

“More research and studies are needed to see whether these effects of sucralose in mice can be reproduced in humans. If these initial findings hold up in people, they could one day offer a way to limit some of the harmful effects of autoimmune conditions.”

Artificial Sweetener Splenda
Artificial Sweetener – Splenda by Bukowsky18 is licensed under CC BY-NC-SA 2.0.

Are there safety concerns surrounding Splenda?

Sucralose, is an ingredient in many processed foods and drinks. It’s calorie-free, but 600 times sweeter than sugar. While the popular opinion is that Splenda is safe, there are some concerns about long-term consumption disrupting gut bacteria and even increasing the risk of certain cancers.

Now, experiments on lab rodents showed that consuming large amounts lowered activation of T-cells that fight disease and infections. The findings open the door to treating patients in whom immune responses become uncontrolled — sometimes triggering life-threatening conditions.

“We do not want people to take away the message that sucralose is harmful if consumed in the course of a normal balanced diet, as the doses we used in mice would be very hard to achieve without medical intervention,” says Fabio Zani, the study’s co-first author and a postdoctoral training fellow at the Crick.

“The impact on the immune system we observed seems reversible and we believe it may be worth studying if sucralose could be used to ameliorate conditions such as autoimmunity, especially in combinational therapies.”

Researchers fed animals levels of the sweetener equivalent to the acceptable daily intake recommended by food safety authorities in Europe and the United States. Relatively similar doses would not typically be unreachable by people adding it to food or drinks as part of a normal diet.

The mice were less able to activate T-cells in response to cancer or infection. The team did not see an effect on other types of immune cells either. Further analysis revealed sucralose dampened cell function by reducing the release of calcium due to stimulation.

Health officials say sucralose is ‘not harmful to the immune system’

Prof. Vousden says the results demonstrate how high doses of sucralose can alter immune responses in mammals. However, it should not sound alarm bells for those wanting to ensure they have a healthy immune system or properly recover from disease, as the quantities mice consumed were higher than what humans normally ingest.

The researchers hope the findings could lead to a new way to control the harm caused by overactive immune cells.

“We’ve shown that a commonly used sweetener, sucralose, is not a completely inert molecule and we have uncovered an unexpected effect on the immune system. We are keen to explore whether there are other cell types or processes that are similarly affected by this sweetener,” explains Julianna Blagih, co-first author and former postdoctoral training fellow at the Crick, now an assistant professor at the Maisonneuve-Rosemont Hospital Research Center at the University of Montreal.

U.S. manufacturers Heartland Food Products Group promotes Splenda as a healthier alternative to sugar, which studies have linked to obesity and the onset of Type 2 diabetes. It was approved for use in 2000 after the EU’s Scientific Committee on Food declared it is “not harmful to the immune system, does not cause cancer, infertility, pose a risk to pregnancy or affect blood sugar levels.”

“This study begins to explore how high doses of sucralose could potentially be used in new treatment options for patients, but it’s still early days,” concludes Karis Betts, a senior health information manager at Cancer Research UK.

“The results of this study don’t show harmful effects of sucralose for humans so you don’t need to think about changing your diet to avoid it.”

Pancreas gene finding gives new insights into human development and aids search for type 1 diabetes cure

Posted by

0


The Bashir Twins

Understanding how the human pancreas develops is crucial to allow scientists to make insulin producing–beta cells in the quest to cure Type 1 diabetes. Now, scientists have made a unique and surprising discovery – a gene that is essential for making the pancreas in humans is not present in almost all other animals.

Beta cells within the pancreas produce insulin that regulate blood sugar. Every mammal needs the pancreatic beta-cells to survive. In established Type 1 diabetes there are no, or very few, working beta-cells.

The new finding, published in Nature Genetics, challenges assumptions about how the regulation of development evolves. Until now, scientists had assumed that genes essential for development of key organs and functions were highly conserved through evolution, meaning the genetic pathway remains the same between different species, from fish to humans. However, the gene, called ZNF808, is only found in humans, other apes such as chimpanzees and gorillas, and in some monkeys, such as macaques.

This Wellcome Trust-funded research was carried out by researchers at the University of Exeter Medical School, the University of Cambridge and the University of Helsinki in Finland. The study shows just how different humans can be to other animals often used in research, such as mice, emphasising the importance of studying the human pancreas.

Lead author Dr Elisa De Franco, of the University of Exeter Medical School, said: “Our finding is really surprising – this is the only example we know of where a gene that is fundamental to the development of an organ in humans and primates is not present in other animals. You’d expect a gene only found in primates to regulate a feature that is specific to primates, such as brain size, but it is not the case for this gene, which instead is involved in development of an organ shared by all vertebrates! We think this shows that there must have been an evolutionary shift in higher primates to serve a purpose.”

Senior author Professor Andrew Hattersley, of the University of Exeter Medical School, said: “One hypothesis that we are exploring is that the evolutionary benefit is to the pancreas in the fetus. Human babies are born through the pelvis, so they cannot stay in the uterus for a longtime as they would grow too large for birth. Instead to cope with being born early and needing to survive without continual feeding they need to be born with more fat than any other animal.  This fat is laid down when the fetus’ pancreas produces more insulin. Our research has shown that human fetuses have more insulin-related growth than other animals.

Dr Nick Owens, of the University of Exeter Medical School, remarked “This research really emphasises the importance of studying the human pancreas in order to understand and find new treatments for diabetes. Animal research is important, but it can only tell us so much. We know there are fundamental differences between humans and other animals, such as mice which are often the subject of research in this field. The human pancreas is different in how it looks, works and develops. Our genetic finding could help us understand why that’s the case.”

ZNF808 belongs to a family of recently evolved proteins which bind and ‘switch off’ specific regions of the DNA which have also developed recently in evolutionary terms. These DNA regions were among the regions considered “junk” DNA with no meaningful purpose for decades, but new technology have recently allowed us to discover their functions. Our findings confirm that these regions of our DNA are playing important roles during human development.

Dr Michael Imbeault, from the University of Cambridge, said “These findings show that genes like ZNF808, even if relatively ‘recent’ in evolution, can have a crucial role in human development. ZNF808 is a member of the largest, but also least studied family of proteins that regulate our genome. There are hundreds of genes like ZNF808 in our DNA, many primate or even human specific, and our results demonstrate how these can be key players in human health.”.

The identification of ZNF808 as being involved in human pancreas development occurred after researchers at the University of Exeter examined genetic samples from patients recruited across the world who were born without a pancreas and found that they all had genetic changes resulting in loss of ZNF808. They then teamed up with colleagues at the University of Cambridge and Helsinki University to study the effect of ZNF808 loss using stem cells in the lab. The results showed that ZNF808 plays an important function early during human development when cells need to ‘decide’ whether to become pancreas or liver.

Among those who shared their genetic samples was Tania Bashir, aged 12, from Luton. Her father Imran Bashir welcomed the Exeter team’s progress. “Having an answer to why this happened is important. We’ve always wanted to know – now we do. The next important step is to understand what this means to the future of science. My dream is that one day, scientists will be able to genetically modify a stem cell and grow a human pancreas, and implant that into Tania, and potentially cure her. I don’t know if that will ever be possible, but I do know that this understanding is a crucial step forward.”

Professor Timo Otonkoski from University of Helsinki remarked “The input of people born without a pancreas was fundamental to this discovery. Nobody would have ever thought that ZNF808 played a role in pancreatic development if we hadn’t found the changes in this gene in these patients. The ultimate goal of our research is for this knowledge to be translated into being able to manipulate stem cells to produce beta cells that can produce insulin in the laboratory. That could be the key to curing type 1 diabetes. Our finding is a significant step in understanding what makes the human pancreas unique, which could help progress this area.”

How Having Diabetes Impacts Romantic Relationships

Posted by

0


Wanting to learn more about the impact that diabetes can have on someone’s love life, we asked people with diabetes about their successes as well as heartbreaks. We were flooded with comments from people wanting to share their experiences.

A diabetes diagnosis undoubtedly impacts the person diagnosed, but it also impacts that person’s loved ones and romantic relationships. Many of us forget or maybe never realize how the people around us support, or don’t, our journey with this disease. 

Wanting to learn more about the impact that diabetes can have on someone’s love life, I reached out to various people with diabetes, looking for stories of success as well as heartbreak. I was flooded with comments from people wanting to share their experiences. 

I presented a few questions to the willing participants.

  • Has diabetes impacted your romantic relationship and how did it make you feel?
  • How did you and your partner address the challenges?
  • What strategies have you developed to deal with these situations?
  • What advice would you give to others struggling with similar challenges?

As someone who has never been married, I have often questioned whether my type 1 diabetes has been the reason why I’ve remained single. I’ve spent many hours in therapy discussing the impact diabetes has had on me, but until lately I have not spent much time considering how it has affected my relationships. 

Kathlin Gordon from Virginia Beach, Virginia, shared this with me: “Diabetes is not only a burden on me, but also my partner. They’re forever in a position of being a safety net and caretaker because they are forced into that role. This unfortunate stress is an additional hurdle that is never easy in a relationship. It’s hard to put energy into loving someone when your energy is spent on hating type 1 diabetes.”

Gordon’s statement breaks my heart partly because I know she is not alone in this mindset. Then you have someone like Craig Le Fevre from Boise, Idaho, who has been in two very different relationship scenarios. Le Fevre shared with me how his now ex-wife addressed his new diagnosis of diabetes when they were married. 

“My ex-wife didn’t take much time or put any effort into learning about diabetes or how it was for me,” he said. “After about a year, I explained that in watching things come up with our kids’ health and other situations I had seen her do research into what would be going on with them. This never happened with my diagnosis, and it made me feel like it wasn’t important to her and that I was carrying the burden alone. It became a bit of a recurring issue. It wasn’t what led to us getting divorced, but it contributed, being a consistent thing leading to feelings of not being cared for.”

Compassion is key to any healthy relationship, but Le Fevre said he felt he wore that burden alone. He hasn’t given up. Recently, he put himself back on the dating market. 

“When meeting new people, just deciding when to reveal having diabetes can be stressful,” he said. “When wearing a pump, it’s probably going to come out on the first date. As a relationship progresses, trying to decide what role that person is going to play in my management takes a lot of thought.”

In a new relationship for more than a year, Lefevre said his condition is still an aspect they are trying to work through together.

“Her interest in my diabetes from the start was a big deal,” Le Fevre said. “She gets up without asking when I have a late night low, even if it’s just to sit there so I’m not alone. This kind gesture makes me feel good, but it doesn’t mean it’s without its stressors because it’s causing her to lose sleep, and she worries about what level of intervention she should take.” 

Le Fevre said that it has been challenging for both of them to find that balance of letting him care for himself and not leaving him to feel alone. “It’s almost a dance we are always doing,” he said, “so that is always an extra thing to navigate within our relationship. And then understanding how a high blood sugar, or a lack of sleep, can affect my mood later on.”

Le Fevre said he wants to be careful his diabetes doesn’t put too much stress on the relationship. “Diabetes is something that takes a great deal of mental work for me and permeates every aspect of my life,” he explains. “I worry that it’s going to negatively impact a relationship and that I’m burdening the people who care about me. So it’s an extra thing to think about and make me feel guilty at times.”

Le Fevre’s story is a reminder of the fine line our loved ones walk in our diabetes management and that we sometimes walk in trying to care for them back. 

Karen Weinstock, of Westfield, New Jersey, offered this perspective: “Many glucose tabs have been ingested [for hypoglycemia] over my 30 years of marriage. Learning how to be a loving partner in the dance of diabetes has been a long road, but my husband has joined me as a willing partner. We have shared many of the challenges of life with type 1 diabetes together. Less judgment, and more willingness is my aim. Just being human with an open heart is our goal.”

As a nurse specializing in diabetes and a person living with type 1 diabetes, Patricia Daiker of Dallas, Texas,shared some enlightening insights on diabetes and relationships.

“When you live with diabetes, you have a unique set of emotions and beliefs that color your intimate relationships,” she said. “It’s not part of the standard diabetes education plan. It happens to each of us on some level, but it always happens. I am talking about grief and trauma.”

When you “get” diabetes you lose the life you “thought” you would have, Daiker said. That “ideal” life was supposed to be one without insulin, tech devices, constant vigilance, and the freedom to just go about your business without feeling like you might be causing some future problems. And with that grief, she said, “you get anger, frustrations, remorse, depression, and a whole slew of emotions.”


“When it comes to relationships, I think trauma is the elephant in the room,” Daiker continued. “As a nurse, trauma has meant car accidents, stab wounds, and other life-threatening injuries. Well, diabetes is a life-threatening injury that we face each day.” 

This, and the sense of shame that sometimes accompanies it, can’t help but have a powerful impact on our relationships, she said.

Daiker shared a few suggestions on how to handle these emotions when it came to building strong relationships, either with a longtime partner or someone you’ve just started dating.  

  • Realize you have experienced trauma and likely you have some shameful thoughts rolling around in there. It’s not your fault and it’s normal.   
  • Challenge those shaming thoughts. Look at the situation as if you were a stranger. The distance can help you feel safe and gain perspective.
  • Embrace and welcome the part of you that is so afraid. Self-compassion is key to healing trauma and building positive relationships. We have to learn to love ourselves first, diabetes and all.   
  • Be brave and speak your truth. You’ll find out quickly if this other person is someone you can trust and value.
  • Remember that “you” are the only “you” on the planet. You matter. You are worthy.  You are loveable. Period. Diabetes is irrelevant. 

These testimonials of people willing to share their love stories remind us that diabetes isn’t going anywhere. It’s a disease that impacts every aspect of our lives, including relationships. We need to love ourselves, face the trauma, shame and guilt to build soulful and loving relationships.

Are Immune Therapies for Type 1 Diabetes Worthwhile?

Posted by

0


The oral Janus kinase inhibitor baricitinib (Olumiant) preserved beta-cell function in people with new-onset type 1 diabetes over 48 weeks, new phase 2 data show. 

But, as with the intravenously administered monoclonal antibody teplizumab (Tzield), there were no significant improvements in A1c and all study participants continued to require exogenous insulin. Both drugs are currently on the US market — baricitinib for rheumatoid arthritis, alopecia areata, and COVID-19 and teplizumab for delaying the onset of type 1 diabetes in those with preclinical (stage 2) disease. 

A randomized, placebo-controlled trial examined baricitinib vs placebo in 91 people with type 1 diabetes onset during the previous 100 days. Published in The New England Journal of Medicine (NEJM) on December 7, 2023, the research was performed by Michaela Waibel, PhD, of St. Vincent’s Institute of Medical Research, Melbourne, Australia, and colleagues. 

A phase 3 teplizumab trial, of two 12-day courses or placebo given to 328 young people with new-onset type 1 diabetes, was also published in the December 7, 2023, issue of NEJM. That study appeared online on October 18, 2023, and was reported by Medscape Medical News. 

In an editorial in the same issue, Johnny Ludvigsson, MD, PhD, of Crown Princess Victoria Children’s Hospital and the Division of Pediatrics, Linköping University, Linköping, Sweden, writes that the two trials together “indicate that, finally, we have promising treatments that may soon be offered to patients with type 1 diabetes at the onset of their disease. With sufficient health care resources, these treatments will be pragmatically feasible.”

Ludvigsson also points out that even though thus far, these interventions aren’t cures and patients must still administer exogenous insulin, preserved residual beta-cell secretion of even small amounts of insulin can help minimize glucose fluctuations and thereby potentially reduce the risk for long-term complications. 

However, he questions whether clinicians, patients, or their parents will see these treatments as justified because other options for improving glycemia are available. “For patients with type 1 diabetes, immunologic interventions to preserve β-cell function arrive in parallel with glucose sensors, smart insulin pumps, and even closed-loop systems…immunologic interventions can be expected to be accepted and successful if clinicians are able to explain the great value for the patient of residual insulin secretion.”

At the same time, he notes, “the interventions to preserve β-cell function must be proved to be safe and to not cause serious adverse events in both the short and the long term. If patients with type 1 diabetes, who already have a chance for a good-quality, long life with modern conventional treatment, are to start receiving such therapy, it should not add to their already heavy burden.”

In the baricitinib study, 60 patients were randomly assigned to receive the drug at 4 mg/da and 31 to receive matched oral placebo. The primary outcome, mean C-peptide level determined by area under the curve during a 2-hour mixed meal tolerance test at week 48, was 0.65 nmol/L/min with baricitinib vs 0.43 nmol/L/min with placebo — a significant difference (P = .001). 

There were no significant differences in daily insulin dose or A1c, but the mean coefficient of variation in glucose levels, as measured by continuous glucose monitoring, was lower with baricitinib: 29.6% vs 33.8% with placebo. 

Waibel and colleagues write, “We speculate that the initiation of baricitinib earlier, when the C-peptide level is higher, either immediately after the diagnosis of symptomatic clinical type 1 diabetes or during presymptomatic stage 2 or stage 3A disease identified through the screening of relatives of patients with type 1 diabetes or through the screening of the general population, may be more effective in decreasing the need for injected insulin.”

Adverse event frequency and severity didn’t differ between the two groups, and there were no severe treatment-associated adverse events.

In the teplizumab trial, participants randomly assigned to receive teplizumab had significantly higher stimulated C-peptide levels than did those assigned to placebo at week 78, with a difference of 0.13 pmol/mL (P <  .001).

There were no significant differences in other endpoints, including insulin doses required to meet glycemic goals, A1c, time in range, or significant hypoglycemic events. 

And with teplizumab, despite premedication in anticipation of discomfort and adverse events, some patients still experienced headache, gastrointestinal symptoms, rash, lymphopenia, and mild cytokine release syndrome. Two patients had severe cytokine release syndrome that resolved within a week but led to treatment discontinuation. 

Ludvigsson concludes, “As clinicians, we need to learn how best to combine therapies to preserve β cells and to control type 1 diabetes. Furthermore, we must learn to which patient a certain immunologic therapy should be given, and for how long. With increasing knowledge from treatment trials involving patients with early stage 3 (clinical) diabetes, we should learn whether such therapy can contribute to a cure and possibly prevent clinical disease if used in earlier stages of type 1 diabetes.”

Uncovering Disease-Driving Events that Lead to Type 2 Diabetes

Posted by

0


an arrow goes from the pancreas to a pancreatic islet, then to a beta cell. RFX6 gene activity is beta cells is decreased. DNA regions are enriched for type 2 diabetes signals
Researchers found lower levels of the protein RFX6 led to beta cells in the pancreas releasing less insulin. Lower RFX6 levels also led to structural changes in the DNA, specifically in sites that have known links to diabetes risk. Credit Donny Bliss/NIH

Nearly 35 million people in communities across the U.S. have type 2 diabetes (T2D), putting them at increased risk for a wide range of serious health complications, including vision loss, kidney failure, heart disease, stroke, and premature death.1 While we know a lot about the lifestyle and genetic factors that influence diabetes risk and steps that can help prevent or control it, there’s still a lot to learn about the precise early events in the body that drive this disease.

When you have T2D, the insulin-producing beta cells in your pancreas don’t release insulin in the way that they should. As a result, blood sugar doesn’t enter your cells, and its levels in the bloodstream go up. What’s less clear is exactly what happens to cause beta cells and the cell clusters where they’re found (called islets) to malfunction in the first place. However, I’m encouraged by some new NIH-supported research in Nature that used various large datasets to identify key signatures of islet dysfunction in people with T2D.2

Earlier studies have linked about 400 sites in the human genome to an increased risk for T2D. But most of them—more than 9 in 10—are primarily in noncoding stretches of DNA that control genes. As a result, it’s been hard to figure out exactly how those genetic variants that increase risk in the general population lead to the changes in individuals who go on to develop T2D.

In the new study, a team led by Marcela Brissova and Alvin C. Powers , Vanderbilt University Medical Center, Nashville, and Stephen C.J. Parker , University of Michigan, Ann Arbor, used sophisticated analytic approaches to study changes within pancreatic tissues and islets taken from donors who’d had early-stage T2D at the time of their death. They included tissues from donors without T2D to serve as a comparison.

To get a better understanding, they looked at the tissues in multiple ways, studying differences in their basic physiology, gene activity, and cellular-level structures. By integrating data on these observed differences with other types of data from prior studies, they showed that impaired function of beta cells is a hallmark of early T2D, reinforcing prior evidence. Other pancreatic islet cell types appeared mostly unchanged.  

Their studies also showed that alterations in a particular gene network are key in early-stage T2D. The network, controlled by a protein called RFX6, cause pancreatic beta cells to malfunction. The researchers performed additional studies that showed lowering RFX6 levels led beta cells to secrete less insulin. Lower RFX6 levels also led to structural changes in the DNA, specifically in sites that have known links to diabetes risk. They expanded this finding by doing a population-scale genetic analysis. Using genetic information for more than 500,000 volunteers available in the UK biobank, they showed a causal link between lower levels of RFX6 and T2D.

Further study is needed to understand what’s behind the initial changes in RFX6. The researchers also want to explore further whether RFX6 might be a promising target for new treatments to prevent or reverse early-stage molecular and functional defects in the beta cell that underlie T2D. The researchers note that they have made all the data publicly available through user-friendly and interactive web portals, in hopes it will lead to more answers for the millions already affected by T2D and so many others who may be at risk.

How Often Should I Check My Blood Sugar?

Posted by

0


If you’re using a blood glucose meter or glucometer (BGM) to manage your diabetes, checking your blood sugar is critical — and if you take insulin, you’ll need to check several times per day. The numbers on your BGM can tell you how well your body is handling the food you eat and if your medication dosages need to be adjusted. Checking your blood sugar every day is also for your immediate and long-term safety. 

Things to consider about when and often you should check your blood sugar:

  • What the American Diabetes Association (ADA) says: The ADA’s recommendation is broad but includes a few critical points: If you take insulin, you should be monitoring your blood sugar daily. Overall, blood sugar monitoring frequency should be tailored to each individual based on goals, current blood sugar levels, changes in medications, etc.
  • If you take insulin via injections or pump, your healthcare team should prescribe a BGM and/or CGM (continuous glucose monitor) to help you monitor your blood sugars. When taking insulin, your blood sugars can fluctuate quickly and dramatically if your doses aren’t fine-tuned for your body’s needs! If your BGM says your blood sugar spikes 100 points after breakfast, for example, that tells you and your healthcare team that your insulin doses need a major adjustment!
  • If you don’t take insulin, checking your blood sugar every day is still very important. Your levels could be creeping up gradually or quickly, but you’re not feeling the symptoms or aware of the fluctuations. If your healthcare team feels comfortable with the stability of your blood sugar levels — meaning you are maintaining your A1C goal — you might be given the green light to cut back significantly on regular monitoring.

You can’t manage what you don’t know! Here’s a look at what times of day you might consider checking your blood sugar.

Tired of pricking your finger?

The tedious (and painful) act of pricking your finger can get tiring. If you’re tired of pricking your finger, definitely check out today’s continuous glucose monitoring options:

While you might feel hesitant about wearing something in your skin all day, today’s CGM technology is pretty darn comfortable. In fact, you’ll likely forget it’s even in your skin. 

CGMs give you more data than a BGM or A1C test ever could, like time-in-range (TIR). TIR tells you what percentage of the day you are within, above, or below your target blood sugar ranges.

Research continues to demonstrate that using a CGM — even in people who aren’t taking insulin — improves A1c levels and decreases the frequency and severity of low blood sugars. Recent research from T1D Exchange found significant benefits of using a CGM within six months of being diagnosed with type 1 diabetes.

You can try the Libre or Dexcom sensors for free with the Hello, Dexcom and trial programs.

Okay, let’s take a look at important times of day to check the ol’ blood sugar.

When you wake up

Your blood sugar first thing in the morning says a lot about how your body and medications are working. It’s been at least eight hours since you ate anything, so that removes the biggest variable: food! This is probably the most important time of the day to check your blood sugar, especially if you have type 2 diabetes and do not use insulin.

If you’re consistently waking up above your target blood sugar range, that’s a clear sign for you and your healthcare team. While being a little bit above your target range isn’t necessarily cause for alarm, being significantly above your target range means it’s time to take action.

It could mean you need to adjust existing medication dosages, consider starting a new medication, or make some adjustments in your overall lifestyle habits that impact insulin resistance. 

On the other hand, if you’re waking up low, it could suggest you’re getting too much of a medication — specifically insulin or sulfonylureas! Keep in mind that if you start another medication, like Ozempic or Mounjaro, this could mean you need to adjust your insulin doses to prevent lows, even though Ozempic and Mounjaro do not cause hypoglycemia on their own. Either way, it’s time to chat with your healthcare team.

Before eating

Checking before every meal sounds tedious, but it’s very important — especially if you take insulin or your A1c is higher than your goal.

It’s important to know what your blood sugar is before eating because we’re also going to talk about checking your blood sugar after eating! If your blood sugar was high before the meal, that’s critical information for you and your healthcare team.

Heading into a meal with a high blood sugar could mean a few things:

  • You didn’t get enough insulin with your last meal.
  • You aren’t getting enough basal/background insulin.
  • You need to consider starting insulin therapy or another diabetes medication.
  • Your body, generally speaking, needs more support managing your blood sugar.

Checking your blood sugar before eating sets you up for success!

Two hours after eating 

While it can certainly take more than two hours for a meal to digest, this is a good indicator of how well your body is handling the meal you ate.

  • If you take insulin, high or low blood sugars after eating suggest you’re getting too little or too much insulin. This tells your healthcare team your doses and insulin-to-carbohydrate ratio need fine-tuning!
  • If you don’t take insulin, high blood sugars after eating suggests your body needs more support from diabetes medications or you might consider making changes in your meal choices.

The information you get from that post-meal BGM check can also motivate you to make some adjustments in what you’re eating. That giant bowl of cereal or pasta might be more than your body can handle. When you see the evidence on your BGM, it’s hard to ignore. That doesn’t mean you can’t ever eat pasta, but it might mean you want to consider reducing the portion size.

Before and after physical activity 

Exercise can cause rapid changes in your blood sugar level because your body needs more fuel to perform!

Aerobic exercise: Also known as “cardio exercise,” this type of physical activity increases how quickly your cells take up glucose to use that glucose for energy. If you take insulin, this means your blood sugar can drop very quickly. Aerobic exercise includes walking, jogging, vacuuming the house, gardening, cycling, etc

Anaerobic exercise: Anaerobic exercise is different! It can actually cause your blood sugar to rise thanks to “gluconeogenesis” — when your body converts lactic acid into glucose to use for fuel! Your liver can also release stored glucose during and after anaerobic exercise. Anaerobic exercise includes things like strength training, CrossFit, and sprinting.

Learning how to manage your blood sugar during exercise — especially if you take insulin — takes time. Work with your healthcare team and take good notes!

Regardless of what type of exercise you’re doing, always carry fast-acting carbohydrates with you to treat potential hypoglycemia.

Before bed

Before you settle in for the night, it’s critical for your health and safety to give that ol’ blood sugar level a look. You’re going to be snoozing for eight hours! 

Check your blood sugar before bed is critical because:

  • If you take insulin or other diabetes medications, you’ll want to make sure you’re in a safe range before falling asleep. If you’re low, you’ll need a small snack. If you’re high, you may need a correction dose. This time of day also lets you know how well your insulin dose covered your dinner and/or dessert.
  • If you don’t take insulin, that pre-snooze blood sugar tells you how well your body is handling dinner and/or dessert. If you’re consistently above your target range, it’s a clear sign that your food choices might need some adjusting or that you need support from diabetes medications.

That 8-hour snooze is 25% of your entire day’s worth of blood sugar levels! Getting your blood sugar into your goal range throughout the night can have a big impact on your A1c, too. But you can’t manage what you don’t know — so you’ve gotta start checking your blood sugar before bed.

The bottom line

Collect that data and talk to your healthcare team! The more often you check your blood sugar, the better you will understand your condition and how to manage it.

If you don’t use insulin, your doctor may recommend only checking once a day or a few times a week, but the more data you gather, the more you know about your diabetes health. You might also find you just need to check more often for a week or two to see how things are going. Get that data, talk to your healthcare team, and never give up!

Artificial Pancreas Improves Blood Glucose Control in Young Kids with Type 1 Diabetes

Posted by

0


Smiling young girl with a photo of an insulin pump

Last week brought some great news for parents of small children with type 1 diabetes (T1D). It involved what’s called an “artificial pancreas,” a new type of device to monitor continuously a person’s blood glucose levels and release the hormone insulin at the right time and at the right dosage, much like the pancreas does in kids who don’t have T1D.

Researchers published last week in the New England Journal of Medicine [1] the results of the largest clinical trial yet of an artificial pancreas technology in small children, ages 2 to 6. The data showed that their Control-IQ technology was safe and effective over several weeks at controlling blood glucose levels in these children. In fact, the new device performed better than the current standard of care.

Two previous clinical trials of the Control-IQ technology had shown the same in older kids and adults, age 6 and up [2,3], and the latest clinical trial, one of the first in young kids, should provide the needed data for the U. S. Food and Drug Administration (FDA) to consider whether to extend the age range approved to use this artificial pancreas. The FDA earlier approved two other artificial pancreas devices—the MiniMed 770G and the Insulet Omnipod 5 systems—for use in children age 2 and older [4,5].

The Control-IQ clinical trial results are a culmination of more than a decade-long effort by the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and many others to create technologies, such as an artificial pancreas, to improve blood glucose control. The reason is managing blood glucose levels remains critical for the long-term health of people with T1D.

What exactly is an artificial pancreas? It consists of three fully integrated components: a glucose monitor, an insulin pump, and a computer algorithm that allows the other two components to communicate. This automation frees people with T1D from checking their blood glucose levels multiple times a day and from many insulin dosing decisions, though they still interact with the system at mealtimes.

Abdomen of a young child. A glucose sensor, attached to the skin sends a signal to an insulin pump which is hanging from the child's pants. A tube runs to a another adhesive on the abdomen to deliver insulin.

In this clinical trial, led by Marc D. Breton, University of Virginia School of Medicine, Charlottesville, researchers tested their Control-IQ technology (manufactured by Tandem Diabetes Care, San Diego, CA), also known as a hybrid closed-loop control system. Thanks to an algorithm developed at the University of Virginia Center for Diabetes Technology, insulin doses are administered automatically every few minutes based on readings from a continuous glucose monitor.

But treating younger children with T1D presents its own set of age-specific challenges. Younger kids generally require smaller doses of insulin more frequently. They also tend to have a more unpredictable schedule with lots of small snacks and random bursts of physical activity.

On top of all that, these young children have a tougher time than kids a few years older when it comes to understanding their own needs and letting the adults around them know when they need help. For all these reasons, young children with T1D tend to spend a greater proportion of time than older kids or adults do with blood glucose levels that are higher, or lower, than they should be. The hope was that the artificial pancreas might help to simplify things.

To find out, the trial enrolled 102 volunteers between ages 2 and 6. Sixty-eight were randomly assigned to receive the artificial pancreas, while the other 34 continued receiving insulin via either an insulin pump or multiple daily injections. The primary focus was on how long kids in each group spent in the target blood glucose range of 70 to 180 milligrams per deciliter, as measured using a continuous glucose monitor.

During the trial’s 13 weeks, participants in the artificial pancreas group spent approximately three more hours per day with their blood glucose in a healthy range compared to the standard care group. The greatest difference in blood glucose control was seen at night while the children should have been sleeping, from 10 p.m. to 6 a.m. During this important period, children with the artificial pancreas spent 18 percent more time in normal blood glucose range than the standard care group. That’s key because nighttime control is especially challenging to maintain in children with T1D.

Overall, the findings show benefits to young children similar to those seen previously in older kids. Those benefits also were observed in kids regardless of age, racial or ethnic group, parental education, or family income.

In the artificial pancreas group, there were two cases of severe hypoglycemia (low blood glucose) compared to one case in the other group. One child in the artificial pancreas group also developed diabetic ketoacidosis, a serious complication in which the body doesn’t have enough insulin. These incidents, while unfortunate, happened infrequently and at similar rates in the two groups.

Interestingly, the trial took place during the COVID-19 pandemic. As a result, much of the training on use of the artificial pancreas system took place virtually. Breton notes that the success of the artificial pancreas under these circumstances is an important finding, especially considering that many kids with T1D live in areas that are farther from endocrinologists or other specialists.

Even with these clinical trials now completed and a few devices on the market, there’s still more work to be done. The NIDDK has plans to host a meeting in the coming months to discuss next steps, including outstanding research questions and other priorities. It’s all very good news for people with T1D, including young kids and their families.

References:

[1] Trial of hybrid closed-loop control in young children with type 1 diabetes. Wadwa RP, Reed ZW, Buckingham BA, DeBoer MD, Ekhlaspour L, Forlenza GP, Schoelwer M, Lum J, Kollman C, Beck RW, Breton MD; PEDAP Trial Study Group. N Engl J Med. 2023 Mar 16;388(11):991-1001.

[2] A randomized trial of closed-loop control in children with type 1 diabetes. Breton MD, Kanapka LG, Beck RW, Ekhlaspour L, Forlenza GP, Cengiz E, Schoelwer M, Ruedy KJ, Jost E, Carria L, Emory E, Hsu LJ, Oliveri M, Kollman CC, Dokken BB, Weinzimer SA, DeBoer MD, Buckingham BA, Cherñavvsky D, Wadwa RP; iDCL Trial Research Group. N Engl J Med. 2020 Aug 27;383(9):836-845.

[3] Six-month randomized, multicenter trial of closed-loop control in type 1 diabetes. Brown SA, Kovatchev BP, Raghinaru D, Lum JW, Buckingham BA, Kudva YC, Laffel LM, Levy CJ, Pinsker JE, Wadwa RP, Dassau E, Doyle FJ 3rd, Anderson SM, Church MM, Dadlani V, Ekhlaspour L, Forlenza GP, Isganaitis E, Lam DW, Kollman C, Beck RW; N Engl J Med. 2019 Oct 31;381(18):1707-1717.

[4] MiniMed 770G System-P160017/S076. U. S. Food and Drug Administration, December 23, 2020.

[5] FDA authorizes Omnipod 5 for ages 2+ in children with type 1 diabetes . Juvenile Diabetes Research Foundation news release, August 22, 2022

Another Artificial Pancreas a Success in Tots With Type 1 Diabetes

Posted by

0


Kids ages 2 to 5 saw significant benefits with hybrid closed-loop system

A photo of the t:slim X2 insulin pump

Very young children with type 1 diabetes saw glycemic benefits when using a hybrid closed-loop system, the randomized PEDAP trial showed.

Among 102 children ages 2 to 5 years, the mean percentage of time that the glucose level was within the target range increased by 12.4 percentage points with the closed-loop system — also known as an artificial pancreas — versus standard of care by week 13 of follow-up (95% CI 9.5-15.3, P<0.001), reported Marc D. Breton, PhD, of the University of Virginia Center for Diabetes Technology in Charlottesville, and colleagues.

This was equivalent to about 3 hours more per day spent in the target range of 70 to 180 mg/dL, the group noted in the New England Journal of Medicineopens in a new tab or window.

In the closed-loop group, the mean percentage of time that the glucose level was within the target range increased from 56.7±18.0% at baseline to 69.3±11.1% during follow-up, while those receiving standard-of-care — consisting of either an insulin pump or multiple daily injections of insulin plus a continuous glucose monitor — went from spending 54.9±14.7% of time in range at baseline to 55.9±12.6% at week 13.

The benefits of the closed-loop system were evident within the first day of use and were maintained consistently throughout the trial, Breton’s group pointed out.

During the daytime (6 a.m. to 9:59 p.m.), the closed-loop group spent 67% of time in target range versus 56% in the standard-care group. At night (10 p.m. to 5:59 a.m.), time spent in range was 74% and 56%, respectively. The biggest between-group difference was at 5 a.m.

Compared with standard care, closed-loop users also spent significantly less time in hyperglycemia, with a mean difference of -5.4 percentage points (95% CI -7.3 to -3.6, P<0.001), and had significantly lower mean glucose levels (mean difference -17.7 mg/dL, 95% CI -23.2 to -12.2) and HbA1c levels (-0.42%, 95% CI -0.62 to -0.22).

There were no between-group differences when it came to time spent in hypoglycemia. Two cases of severe hypoglycemia occurred in the closed-loop group and one occurred in the standard-care group. There was also one case of diabetic ketoacidosis that occurred in the closed-loop group.

Overall, 48% of the closed-loop group achieved an HbA1c under 7%, as recommended by the American Diabetes Association, compared with only 30% of the standard-care group.

In an accompanying editorialopens in a new tab or window, Daniela Bruttomesso, MD, PhD, of the University of Padua in Italy, called it “remarkable” that 81% of all training for the closed-loop system was done virtually, as were 91% of all follow-up visits.

The researchers explained that the trial took place in the U.S. during the COVID-19 pandemic, which forced the research group to pivot away from face-to-face visits.

“Successful use of the closed-loop system under these conditions is an important finding that could affect the approach to initiating and monitoring the use of the closed-loop system and expand the use of such systems, particularly in patients living in areas without an endocrinologist but with reliable internet access,” Breton and team wrote.

Bruttomesso noted that a “virtual approach has several advantages over in-person visits, including a more relaxed environment, lower travel costs, and greater ease of contact with clinicians,” but “patient preferences, possible legal issues, and accessibility to technology (the families of the patients in this trial had above-average incomes) are all important considerations in choosing the most appropriate way to communicate with patients at the initiation of a closed-loop system or during routine follow-up.”

Bruttomesso instead recommended a mix of in-person and virtual clinic meetings with these very young patients to establish this diabetes management.

The 68 kids randomly assigned to the closed-loop group were fitted with Tandem Diabetes Care’s t:slim X2 insulin pump with Control-IQ Technology system. This system enables automated basal adjustments every 5 minutes and bolus corrections delivered from an insulin pump. The insulin pump was paired with a Dexcom G6 continuous glucose monitoropens in a new tab or window that sent glucose values to the pump.

The average age of PEDAP trial participants was 4 years, and baseline HbA1c was 7.6%. About 75% of patients were white, and the majority had an annual household income of $100,000 or more. At baseline, most were using an insulin pump but nearly none were using a continuous glucose monitoring system.

Currently, the insulin pump is FDA clearedopens in a new tab or window for adults and children ages 6 and up.

This isn’t the first hybrid closed-loop system to demonstrate success in this very young age group. Medtronic’s MiniMed 770G systemopens in a new tab or window was the first to be approved by the FDA for kids ages 2 to 6 years with type 1 diabetes, back in September 2020.

And in another similar trial, the KidsAP studyopens in a new tab or window published in the New England Journal of Medicine in early 2022, kids ages 1 to 7 spent a significantly longer time in target range with a closed-loop system. Here, kids were fitted with the Dana Diabecare RS insulin pump, the Dexcom G6 transmitter, and the CamAPS FX novel phone application, which ran an algorithm to predict glycemic control.