The latest advancements in the treatment of diabetes in 2021.

This article will discuss the latest developments in the treatment of diabetes in 2021 and corresponding knowledge points, hoping to be helpful to you. Let's start the formal explanation! Oral insulin is here! Will the days of daily injections of insulin come to an end? Attention all diabetes patients...

It is gratifying that on May 15, 2021, at the 9th China Diabetes, Obesity, and Hypertension Debate to Consensus Conference, the oral insulin capsule (ORMD-0801) developed by China's Hefei Tianmai Biotech made its official debut, bringing new hope to diabetes patients. As of May 15th, when the conference was held, Phase III clinical trials of oral insulin capsules have been conducted domestically and internationally, with 36 hospitals in our country participating. We all hope that this drug can be successfully launched as soon as possible, benefiting more patients with diabetes.

Is it mainly targeted towards the treatment of type 2 diabetes? The treatment of type 2 diabetes has always been a challenge. Although there are various drugs and treatment methods available, there is no method that can completely cure this disease. Now, a gene-modified adipose stem cell therapy for type 2 diabetes has been approved for clinical trials, which is great news.

The time it takes for this treatment method to be popularized in various hospitals may vary due to factors such as treatment efficacy, safety, quality, and cost. However, it typically takes several years from registering clinical trials to obtaining approval, followed by additional time for promotion and popularization in hospitals and markets. Therefore, it generally takes several years or even longer to be widespread in various hospitals. If this treatment method achieves good results in clinical trials and is proven to be safe and effective, the time for its popularization may be shortened.

Science Advances | Tsinghua University's Du Yanan team explores new methods for treating diabetes The treatment of diabetes-related metabolic disorders using mesenchymal stem cells (MSCs) has been hindered by insufficient cell survival and limited therapeutic effects under high glucose stress. On July 2, 2021, Tsinghua University's Du Yanan team published a research paper titled "Exendin-4 gene modification and microscaffold encapsulation promote self-persistence and antidiabetic activity of MSCs" in Science Advances. The study used Exendin-4 (MSC-Ex-4), a glucagon-like peptide 1 (GLP-1) analog, to genetically engineer MSCs and demonstrated their enhanced cellular function and anti-diabetic effects in a type 2 diabetes (T2DM) mouse model.

Mechanistically, MSC-Ex-4 achieved self-enhancement and improved survival under high glucose stress through the autocrine activation of the AMPK signaling pathway mediated by GLP-1R. Additionally, the Exendin-4 secreted by MSC-Ex-4 inhibited the aging and apoptosis of pancreatic β cells through endocrine action, while the biologically active factors secreted by MSC-Ex-4, such as IGFBP2 and APOM, enhanced insulin sensitivity and reduced lipid accumulation in liver cells through paracrine activation of the PI3K-Akt pathway. Furthermore, the study encapsulated MSC-Ex-4 in a 3D gelatin microscaffold for single-dose administration, extending the therapeutic effect for three months. Overall, the study provides insights into the mechanisms of self-persistence and anti-diabetic activity mediated by Exendin-4 in MSCs, offering a more effective MSC-based treatment for T2DM.

Currently, there are over 436 million people worldwide with diabetes, and it is projected to reach 700 million by 2045. Type 2 diabetes (T2DM) accounts for approximately 90% of diabetes cases, characterized by insulin resistance and high blood sugar, which are caused by factors such as obesity, lack of exercise, unhealthy diet, and genetics. Insulin resistance occurs when cells in the liver, muscles, and adipose tissue fail to respond to insulin, leading to impaired glucose uptake. Pancreatic β cells compensate for insulin resistance by increasing insulin production, eventually resulting in β cell failure and irreversible hyperglycemia. Long-term exposure to chronic hyperglycemia inhibits proliferation and induces apoptosis in β cells, leading to a decrease in β cell mass and dysfunction.

Furthermore, T2DM is closely associated with liver dysfunction, with over 90% of obese T2DM patients also having metabolic-associated fatty liver disease (MAFLD). Liver cells play an important role in glucose and lipid homeostasis by storing nutrients as glycogen and triglycerides (TG). In a state of hepatic insulin resistance, insulin fails to inhibit hepatic gluconeogenesis but accelerates fatty acid synthesis in liver cells, leading to increased production of liver glucose and accumulation of TG. Despite β cell and liver cell dysfunction, the high blood glucose and hypertriglyceridemia exacerbate insulin resistance in muscles and adipose tissue, as well as impair the function of other organs and tissues. Therefore, T2DM is closely associated with various complications, including coronary heart disease, stroke, and retinopathy.

In addition to lifestyle modifications, the use of antidiabetic medications is necessary to maintain normal blood sugar levels in T2DM patients. Glucagon-like peptide-1 (GLP-1) is an incretin hormone that promotes insulin secretion and inhibits glucagon secretion by interacting with GLP-1 receptors (GLP-1R), thereby helping to control blood sugar fluctuations. However, GLP-1 is rarely used in T2DM treatment due to its short half-life and rapid degradation by dipeptidyl peptidase-4 within a few minutes. Exendin-4, the first GLP-1R agonist approved for T2DM treatment, is a 39-amino acid peptide and a GLP-1 analog with a longer half-life of 2.4 hours. It enhances β cell mass by inhibiting apoptosis and promoting cell proliferation, thereby increasing insulin secretion. Moreover, Exendin-4 has been proven to be an effective candidate drug for weight reduction and improvement of diabetes and MAFLD. Despite the improvements in blood sugar regulation and insulin response, the plasma half-life of Exendin-4 remains limited due to renal clearance. Therefore, twice-daily administration is required, resulting in unexpected fluctuations in plasma concentration and intermittent activation of GLP-1R.

Although the aforementioned antidiabetic drug therapies have brought benefits, some patients still cannot achieve normal blood sugar levels or experience various side effects such as hypoglycemia, diarrhea, nausea, and vomiting. In recent years, cell-based therapies have emerged as alternative approaches to combat various refractory diseases, including T2DM. Specifically, mesenchymal stem/stromal cells (MSCs) have shown therapeutic effects in improving hyperglycemia, insulin resistance, and systemic inflammation caused by T2DM in some preclinical and clinical trials, providing a new approach for T2DM treatment. However, technological advancements are still urgently needed to successfully translate MSC-based therapies into clinical treatments for T2DM. One of the major obstacles to overcome is the reduced proliferation and survival rate of MSCs after in vivo administration.

Therefore, various strategies have been studied to improve the survival rate, delay clearance kinetics, and maintain the secretion of MSC factors in vivo, such as biomaterial encapsulation, gene engineering, and MSC preconditioning. Furthermore, optimizing the administration route of MSCs is crucial, as intravenous administration of MSCs primarily results in their retention in the lungs and subsequent tissues, leading to reduced therapeutic effects. Additionally, a comprehensive understanding of the therapeutic mechanisms of MSCs in T2DM remains elusive. MSCs have been shown to promote endogenous insulin production and stimulate β cell proliferation. Moreover, MSCs are known for their ability to modulate immune responses, which is crucial for improving systemic inflammation caused by T2DM.

Given the aforementioned limitations of Exendin-4 and MSCs in the treatment of T2DM, researchers have explored the therapeutic benefits of combining Exendin-4 and MSCs. MSCs have also been genetically modified with GLP-1 and demonstrated superior therapeutic efficacy in T2DM treatment compared to wild-type MSCs. However, it should be emphasized that these combination therapies inherit many limitations. For example, the therapeutic effects and duration of single-dose free Exendin-4 administration are limited when co-administered with MSCs. Moreover, considering the short half-life of GLP-1 at only 2 minutes and the need for high effective doses for T2DM treatment, it is expected to be challenging to significantly improve the therapeutic effects of MSCs through GLP-1-modified MSCs.

In this study, based on the discovery that human MSCs express GLP-1R, the researchers constructed Exendin-4 gene-engineered MSCs (MSC-Ex-4) through a lentiviral transduction system to verify whether the Exendin-4 secreted by MSC-Ex-4 can potentially promote self-persistence by activating the AMPK signaling pathway through GLP-1R-mediated autocrine activation. The study also explored the potential mechanisms of MSC-Ex-4's endocrine action in protecting pancreatic β cells and its paracrine action in improving liver cell function. In addition to the Exendin-4 secreted by MSC-Ex-4, it is speculated that other secreted components of MSC-Ex-4 can reduce cell aging and apoptosis, promote β cell proliferation, enhance insulin sensitivity, and reduce lipid accumulation. Finally, the study systematically provided multi-dose administration of free MSC-Ex-4 and utilized injectable three-dimensional (3D) gelatin microscaffolds (GMs) as cell encapsulation and delivery carriers to assist MSC-Ex-4 in achieving long-lasting therapeutic effects through single-dose local administration.

In conclusion, this study provides insights into the mechanisms of self-persistence and anti-diabetic activity mediated by Exendin-4 in MSCs, offering a more effective MSC-based treatment for T2DM. WOSCI, a team of doctoral graduates from Yale University, specializes in the latest scientific developments and provides various academic guidance, including cutting-edge scientific news, publishing information, journal analysis, SCI paper writing techniques, academic lectures, and SCI paper polishing.

Why can't type 2 diabetes be cured? Generally speaking, diabetic patients rarely achieve recovery through drug treatment, and the vast majority of patients can only control their blood sugar through medication. Textbooks also describe diabetes as a chronic non-communicable disease that can only be controlled and not cured.

In recent years, with the development of medicine, metabolic surgery has gradually become one of the methods for treating diabetes. In early 2021, an important article on the progress of diabetes treatment was published online in The Lancet. A 10-year follow-up study showed that for severe type 2 diabetes patients, metabolic surgery is more effective in long-term control of the condition compared to medication and lifestyle interventions, and more than one-third of surgical patients achieved long-term relief. This means that "curing" type 2 diabetes is possible.

The above is the explanation given by the editor about the latest developments in the treatment of diabetes in 2021. If you would like to learn more about the latest developments in the treatment of diabetes in 2021 and other related information, please follow and bookmark our website.