Type 1 Diabetes Research

By Dr. Luis Vaschetto, Ph.D.Reviewed by Danielle Ellis, B.Sc.

Type 1 diabetes is a progressive autoimmune disorder that requires regular monitoring, insulin injections, and an awareness of potential complications. It generally begins in childhood, adolescence, or early youth and can significantly shorten lifespan.

Type 1 diabetes has a significant negative impact on an individual's quality of life as well as on the utilization of healthcare. People with the condition are at an increased risk of developing diabetic retinopathy, kidney damage, and cardiovascular disease.

Research into type 1 diabetes has focused on several areas, some of which include:

• Understanding exactly what happens when the body's immune system turns on the insulin-producing beta cells in the pancreas and attacks them. Understanding this may help to develop mechanisms for treating or even curing type 1 diabetes mellitus.
• Creating, regenerating or repairing the damaged or destroyed pancreatic beta cells. So far, research has involved replacing the islet cells using a specialized encapsulation technique, genetic engineering, and stem cell procedures. Creating genetically engineered viral vectors that trigger and produce insulin is fundamental in diabetes research. Gene therapy involves inserting genes or gene sequences into specific vectors, such as viral vectors, to protect beta cells from the attack of the immune system. In a proof-of-concept study, it has been shown that viral-vector based gene therapies can be used to reprogram alpha cells into functional beta cells in mice, which could be a potential new therapeutic approach for type 1 diabetes. Read more here.
• Developing improved techniques for monitoring and regulating blood sugar levels. One focus is the creation of non-invasive and pain-free methods for administering insulin that do not involve injections. New approaches to tone down the autoimmune reactions that cause type 1 diabetes include the BCG vaccine and other immunization techniques. Read more here.
• Type 1 diabetes is a highly inheritable disease, and researchers are actively working to identify genes and signaling pathways that play a role in its development. These studies could lead to new ways to predict and prevent type 1 diabetes and discover genetic markers associated with the disease.
• Prevention of damage to the parts of the body affected by diabetes, such as the blood vessels, eyes, kidneys, and heart.
• Improving understanding of the impact of diabetes on behavior and mental health to help enhance quality of life.

Epigenetics in type 1 diabetes: new pathways to understanding the disease

Epigenetic modifications are chemical changes to the DNA and associated histones that do not alter the DNA sequence. One of the most common epigenetic modifications is histone acetylation, which is generally associated with active gene expression patterns. Recently, researchers have discovered that the level of acetylation of lysine 9 on histone H3 protein (H3K9Ac) is increased in monocytes of people with Type 1 diabetes, and this high level can contribute to the metabolic memory of diabetes by upregulating critical genes involved in the clinical manifestation of the disease.

On the other hand, microRNAs (miRNAs) are small regulatory RNAs that regulate gene expression patterns. They do this, for example, by binding to the 3' untranslated region (UTR) of target mRNAs and thus repressing their translation. Interestingly, studies have recently shown that miRNAs are involved in the pathogenesis of type 1 diabetes, and they could also serve as diagnostic markers and therapeutic targets for patients with this disease.

Latest advances in type 1 diabetes research

Over the last few years, there have been many advances in type 1 diabetes research and treatment strategies, one of the most important being the introduction of novel insulin formulations such as ultra-rapid-acting insulins. These formulations are developed using EDTA to dissociate insulin hexamers and citrate to prevent reaggregation. Ultra-rapid-acting insulins have shown improved absorption and peak onset of action. However, it is worth highlighting that some of these formulations have been associated with injection site reactions.

Testing new immunotherapies to prevent type 1 diabetes

Researchers are developing new immunotherapies to prevent or delay the development of type 1 diabetes. These therapies target the immune system, stopping it from attacking the insulin-producing beta cells in the pancreas. Some of the most promising immunotherapies against type 1 diabetes include:

• T cell-targeting therapies block the activity of T cells that attack insulin-producing β cells. For example, a recently developed therapy uses genetically engineered T cells to target insulin-reactive CD8 T cells, reducing the incidence and delaying the onset of diabetes in animal models.
• Antibody-based therapies target T cells or other immune cells by using antibodies. For example, chimeric antigen receptor (CAR) T cells specific for an MHC class II-peptide complex can delay the onset of type 1 diabetes in mice.

 References

• Krasner, Alan, et al. "A review of a family of ultra-rapid-acting insulins: formulation development." Journal of Diabetes Science and Technology 6.4 (2012): 786-796.
• Miao, Chenggui, et al. "MicroRNAs in type 1 diabetes: new research progress and potential directions." Biochemistry and Cell Biology 96.5 (2018): 498-506.
• Miao, Feng, et al. "Evaluating the role of epigenetic histone modifications in the metabolic memory of type 1 diabetes." Diabetes 63.5 (2014): 1748-1762.
• Scott, Gwen S., et al. "Immunotargeting of insulin reactive CD8 T cells to prevent diabetes." Journal of autoimmunity 35.4 (2010): 390-397.
• Xiao, Xiangwei, et al. "Endogenous reprogramming of alpha cells into beta cells, induced by viral gene therapy, reverses autoimmune diabetes." Cell stem cell 22.1 (2018): 78-90.
• Zhang, Li, et al. "Chimeric antigen receptor (CAR) T cells targeting a pathogenic MHC class II: peptide complex modulate the progression of autoimmune diabetes." Journal of Autoimmunity 96 (2019): 50-58.
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