There is a “new way” to delay the failure of islets β type 1 diabetes

Type 1 diabetes is an autoimmune disease in which immune cells attack and cause pancreatic islets β cell function to decrease until they fail. Pancreatic islet β cells can secrete insulin to lower blood sugar, so the treatment of type 1 diabetes mainly relies on insulin, and there is an urgent need to explore new treatment strategies that can prevent or slow down the function of pancreatic islet β cells.

The reporter of “China Science News” learned from the Second Xiangya Hospital of Central South University on April 24 that Professor Zhou Zhiguang, director of the National Clinical Research Center for Metabolic Diseases and director of the Key Laboratory of Diabetes Immunology of the Ministry of Education, led a multi-center clinical study completed by 36 hospitals across the country, and found a “new formula” to delay the failure of islet β cells in type 1 diabetes.

The picture shows Zhou Zhiguang (far left) guiding the team to carry out research work. Photo courtesy of interviewee

This result was published in Signal Transduction and Targeted Therapy on April 20, with Zhou Zhiguang and Professor David Leslie of the University of London as co-corresponding authors, Associate Professor Yan Xiang, Professor Li Xia, Dr. Liu Bingwen and Professor Huang Jiaqi of the Second Xiangya Hospital as the co-first authors, and the Second Xiangya Hospital as the first completion unit and corresponding author unit.

Preclinical studies have found that dipeptidyl peptidase IV inhibitors (DPP-4i) and vitamin D have certain immunomodulatory effects, and show certain islet function protection in NOD mice, an animal model of type 1 diabetes. Satagliptin belongs to DPP-4i and has been widely used in more than 60 countries, including China, to treat patients with type 2 diabetes.

Professor Zhou Zhiguang innovatively combined saxagliptin and vitamin D in the treatment of adult patients with type 1 diabetes, in order to explore a new solution to delay islet failure. The study group conducted a multicenter, randomized, controlled trial to explore the combination of saxagliptin and vitamin D to maintain β cell function in adult-onset type 1 diabetes (ADVENT study). The primary endpoint of the study was change in fasting C-peptide from baseline to 24 months; Secondary endpoints were area under the concentration-time curve (AUC), glycemic control, total daily insulin use, and safety of C-peptide levels in the 2-h mixed dietary tolerance test.

The ADVENT study is the first clinical trial in the world to evaluate the safety and efficacy of DPP-4i combined with vitamin D on the functional protection of islet β cells in adults with type 1 diabetes. The study showed that daily administration of 5 mg of satagliptin (DPP4i) and 2000 U of vitamin D had a good safety profile and delayed islet β cell failure in adults with type 1 diabetes receiving conventional treatment (metformin and insulin), especially in patients with high titers of glutamate decarboxylase antibody (GADA).

According to reports, the research results provide a new strategy for immunotherapy of adult type 1 diabetes and promote the precision treatment of type 1 diabetes based on GADA antibody levels.

The ADVENT study included 301 adults with type 1 diabetes who retained partial islet function and were GADA antibody-positive. It is worth noting that in patients with high GADA antibody titers, the C-peptide AUC decline rate in the saxagliptin plus vitamin D group was significantly slower than in the conventional treatment group, while there was no similar phenomenon in patients with low GADA antibody titer. The average daily insulin dose in the saxagliptin plus vitamin D group was significantly lower than in the usual care group.

The ADVENT study lasted 10 years from design to implementation, with more than 50 units participating in case screening, 36 centers entering intervention trials, and more than 400 people participating in the study, which is of great clinical significance. The “Guidelines for the Management of Type 1 Diabetes in Adults” recently released by ADA/EASD and the first “International Expert Consensus on the Treatment of Occult Autoimmune Diabetes (LADA) in Adults” both pointed out that the treatment of adult autoimmune type 1 diabetes is lacking and needs to be solved urgently. The publication of ADVENT research results undoubtedly provides new measures and new evidence for the treatment of autoimmune diabetes in adults. (Source: China Science News, Wang Haohao, Xie Zhiguo)

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