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*For reference only for medical professionals, whether it is "promoting remodeling" or "unloading", it is necessary to rescue the pancreatic beta cells! Various risk factors such as genetic susceptibility and unhealthy life>
.
Therefore, the protection of islet β-cell function has become one of the most cutting-edge topics in the field of T2DM diagnosis and treatment.
Various explorations around this goal can be divided into "unloading" approaches aimed at reducing the burden on β-cells, and those aimed at promoting β-cell burden.
A "pro-remodeling" pathway that secretes more insulin
.
So what are the highlights in the field of islet beta cell protection today? The decline of pancreatic β-cell function occurs earlier, and effective early intervention methods are needed.
It is well known that the time point when a patient is diagnosed with T2DM is not the real start time of the disease
.
Studies have shown that as early as prediabetes, patients begin to experience a decline in the function of pancreatic β cells [2]: insulin resistance caused by various factors increases blood sugar, and β cells need to compensate by secreting more insulin to stabilize blood sugar.
, but the compensation is also limited.
With the gradual increase of the burden, the β cells will enter the decompensation period, and the insulin secretion function will begin to decline
.
Therefore, in the pre-diabetic stage, measures such as life>
.
It is worth noting that during the process from prediabetes to T2DM, the number and secretory function of β cells tend to increase first and then decrease (Figure 1) [3]
.
The number and secretory capacity of β cells together determine the overall function of pancreatic β cells, but the secretory capacity may be the real decisive factor in the two
.
Figure 1.
Changes in the number and secretory function of islet β cells during the development of T2DM.
Previous views believed that islet β cells decreased in number due to death, but the latest view suggests that β cells may have undergone "dedifferentiation" and transformed into loss of insulin Secretory function of endocrine precursor cells or other types of cells [4], therefore, reversing dedifferentiation and restoring β-cell secretion capacity through various therapeutic methods is an important way to protect β-cell function
.
In 2020, a study of 4792 T2DM patients in China showed that under the condition that traditional drugs such as metformin and insulin were mainly used, the β-cell function of Chinese patients decreased at a rate of 2% per year, and the β-cell function and HbA1c level.
All gradually deteriorated with the prolongation of the course of disease (Figure 2) [5]
.
In addition, the decline of β-cell function is first manifested by the loss of early-phase insulin secretion, and the patient's postprandial blood sugar rises [6], which is also in line with the blood sugar characteristics of Chinese patients
.
Therefore, based on these characteristics, seeking an effective early intervention strategy to protect the function of pancreatic β cells may be of great significance to diabetic patients in China
.
Figure 2.
The trend of changes in islet β-cell function in T2DM patients in China.
Various methods are used in a timely manner to accurately assess β-cell function.
To meet the different needs of clinical diagnosis and treatment and scientific research, the methods used by clinicians to evaluate the β-cell function of T2DM patients It is also diverse.
Commonly used indicators for evaluating β-cell function include insulin secretion index (HOMA-β), proinsulin/insulin ratio (PI/I), acute insulin response (AIR), and insulin secretion index (△I30/△G30).
), glucose disposal index (DI), etc.
[7-8], the specific meaning of each index is shown in Table 1
.
Table 1.
Commonly used β-cell function evaluation indicators in clinical research and their significance.
In different stages of the disease course of T2DM, the selection of pancreatic β-cell function evaluation methods should also be different.
As shown in Table 2, the evaluation suitable for different populations can be selected.
Methods; and for different research purposes and sample sizes, evaluation methods can also be optimized in time.
For example, the high-glucose clamp test is cumbersome and not suitable for epidemiological investigations, but it can be used for small-scale scientific research.
When conducting epidemiological surveys in the population, the simple intravenous glucose tolerance test (IVGTT) + oral glucose tolerance test (OGTT) method can be used [7-8]
.
Table 2.
Recommended methods for assessing islet β-cell function in different disease stages Evaluate the number of β cells in patients[9]; analyze the changes of β cells in real time with genomics, proteomics and other technologies, and discover potential targets for the protection of β cell therapy[10]; or perform single-cell RNA sequencing on β cells, from The cellular level reveals the characteristics of its functional changes, etc.
[11]
.
What are the ways to restore islet beta cell function? Islet β-cell failure is the core of T2DM disease [12], so it is also the focus of exploration in the field of diabetes treatment
.
Numerous researchers and medical workers are trying from different angles and using different means to achieve the goal of restoring beta cell function and then reversing the progression of diabetes
.
Most of the various hypoglycemic drugs currently in use can have a certain impact on β-cell function.
According to the mechanism of action, they can be divided into “unloading” pathways (such as insulin) that reduce insulin secretion requirements, reduce the burden on β-cells (such as insulin), and restore and enhance β-cell function.
The 'pro-remodeling' pathways of cellular insulin secretion capacity (eg, sulfonylureas) [13] are inconclusive
.
Existing clinical research evidence shows that insulin as an early intensive treatment plan is more effective than traditional oral hypoglycemic drugs in improving islet β-cell function
.
A study conducted by Chinese scholars in 2008 showed that continuous subcutaneous insulin infusion (CSII) or multiple insulin injections (MDI), supplemented with basal insulin and mealtime insulin at the same time, were evaluated by HOMA-β and acute insulin response (AIR).
The function of islet β-cells in the insulin group was significantly improved, and the improvement effect was maintained after 1 year, and the drug-free remission rate of the insulin group was 48.
2% (121/251) after 1 year, which was significantly higher than that of the oral drug group (p = 26.
7%).
0.
0012) (Fig.
3) [14]
.
Figure 3.
The remission rate and AIR status of patients in the Chinese study in 2008.
In addition, another study showed that in the case of little difference in HbA1c level and fasting blood glucose control, the glucose disposal index (DI) of patients receiving basal + mealtime insulin intensive therapy ) was higher than that in patients who received oral glimepiride + metformin, also suggesting that insulin has better β-cell protection [15]
.
While most hypoglycemic agents are used alone or in combination, short-term treatment does have evidence of improving β-cell function, but long-term treatment data are limited
.
In addition to existing drug treatments, non-drug treatments such as gastric volume reduction surgery and very low-calorie diet[16-17] can also improve the function of pancreatic β-cells in patients with T2DM.
The continuous progress of basic scientific research also provides new intervention methods.
For example, the application of new drugs targeting other sites in blood sugar regulation, bone marrow/umbilical cord blood cell transplantation, β-cell replacement with endogenous cells and pancreatic islet transplantation [18-20] provides the possibility, and the development of these methods in the future can also be expected.
.
Summary: The functional decline of pancreatic beta cells is the core problem of T2DM
.
At present, there is no effective treatment to reverse this process, but commonly used treatments such as insulin and oral hypoglycemic drugs can protect β-cell function to a certain extent by means of "unloading" and "promoting remodeling".
The protective effect is better than that of oral hypoglycemic drugs
.
In the future, new research and new technologies around the protection of β-cell function are expected to truly achieve the "ultimate goal" of reversing β-cell failure and treating diabetes from the source
.
References: [1] Park YJ, Woo M.
Journal of Cell Biology.
2019; 218(4): 1094-1095.
[2] Cersosimo E, et al.
Current Diabetes Reviews.
2014; 10(1): 2- 42.
[3] Chen C, et al.
Molecular Metabolism.
2017; 6(9): 943-957.
[4] Remedi MS, Emfinger C.
Diabetes, Obesity and Metabolism.
2016; 18: 110-116.
[5 ]Gao Z, et al.
Diabetes/Metabolism Research and Reviews.
2021;37(2):e3364.
[6]Seino S,et al.
The Journal of Clinical Investigation.
2011;121(6):2118-2125.
[ 7] Xiao Xinhua, Mao Lili.
Chinese Journal of Diabetes.
2009;1(3):218-221.
[8]Chen Chen.
Medical Review.
2014;20(9):1561-1564.
[9]Li Jiaying, Feng Lie.
Chinese Journal of Diabetes.
2011;03(2):178-181.
[10]Lytrivi M,et al.
BMC Genomics.
2020;21(1):1-15.
[11]Xin Y,et al.
Endocrinology.
2016;157(9):3431-3438.
[12]Saisho Y.
DIABETES.
2018.
[13]Salunkhe VA,et al.
Diabetologia.
2018;61(9):1895-1901.
[14]Weng J , et al.
The Lancet.
2008;371(9626):1753-1760.
[15]Chon S,et al.
Diabetes,Obesity and Metabolism.
2018;20(5):1121-1130.
[16]Jørgensen NB, et al.
American Journal of Physiology-Endocrinology and Metabolism.
2012;303(1):E122-E131.
[17]Malandrucco I, et al.
The American Journal of Clinical Nutrition.
2012;95(3):609-613.
[18] Salunkhe VA,et al.
Diabetologia.
2018;61(9):1895-1901.
[19]Sordi V,et al.
Nutr Metab Cardiovasc Dis.
2017;27(7):583-600.
[20]Farney AC, et al.
Pancreas.
2016;45(1):8-20.
- End - "This article is only used to provide scientific information to medical and health professionals, and does not represent the platform's position" Contribution / reprint / business cooperation, please contact: pengsanmei @yxj.
org.
cn
.
Therefore, the protection of islet β-cell function has become one of the most cutting-edge topics in the field of T2DM diagnosis and treatment.
Various explorations around this goal can be divided into "unloading" approaches aimed at reducing the burden on β-cells, and those aimed at promoting β-cell burden.
A "pro-remodeling" pathway that secretes more insulin
.
So what are the highlights in the field of islet beta cell protection today? The decline of pancreatic β-cell function occurs earlier, and effective early intervention methods are needed.
It is well known that the time point when a patient is diagnosed with T2DM is not the real start time of the disease
.
Studies have shown that as early as prediabetes, patients begin to experience a decline in the function of pancreatic β cells [2]: insulin resistance caused by various factors increases blood sugar, and β cells need to compensate by secreting more insulin to stabilize blood sugar.
, but the compensation is also limited.
With the gradual increase of the burden, the β cells will enter the decompensation period, and the insulin secretion function will begin to decline
.
Therefore, in the pre-diabetic stage, measures such as life>
.
It is worth noting that during the process from prediabetes to T2DM, the number and secretory function of β cells tend to increase first and then decrease (Figure 1) [3]
.
The number and secretory capacity of β cells together determine the overall function of pancreatic β cells, but the secretory capacity may be the real decisive factor in the two
.
Figure 1.
Changes in the number and secretory function of islet β cells during the development of T2DM.
Previous views believed that islet β cells decreased in number due to death, but the latest view suggests that β cells may have undergone "dedifferentiation" and transformed into loss of insulin Secretory function of endocrine precursor cells or other types of cells [4], therefore, reversing dedifferentiation and restoring β-cell secretion capacity through various therapeutic methods is an important way to protect β-cell function
.
In 2020, a study of 4792 T2DM patients in China showed that under the condition that traditional drugs such as metformin and insulin were mainly used, the β-cell function of Chinese patients decreased at a rate of 2% per year, and the β-cell function and HbA1c level.
All gradually deteriorated with the prolongation of the course of disease (Figure 2) [5]
.
In addition, the decline of β-cell function is first manifested by the loss of early-phase insulin secretion, and the patient's postprandial blood sugar rises [6], which is also in line with the blood sugar characteristics of Chinese patients
.
Therefore, based on these characteristics, seeking an effective early intervention strategy to protect the function of pancreatic β cells may be of great significance to diabetic patients in China
.
Figure 2.
The trend of changes in islet β-cell function in T2DM patients in China.
Various methods are used in a timely manner to accurately assess β-cell function.
To meet the different needs of clinical diagnosis and treatment and scientific research, the methods used by clinicians to evaluate the β-cell function of T2DM patients It is also diverse.
Commonly used indicators for evaluating β-cell function include insulin secretion index (HOMA-β), proinsulin/insulin ratio (PI/I), acute insulin response (AIR), and insulin secretion index (△I30/△G30).
), glucose disposal index (DI), etc.
[7-8], the specific meaning of each index is shown in Table 1
.
Table 1.
Commonly used β-cell function evaluation indicators in clinical research and their significance.
In different stages of the disease course of T2DM, the selection of pancreatic β-cell function evaluation methods should also be different.
As shown in Table 2, the evaluation suitable for different populations can be selected.
Methods; and for different research purposes and sample sizes, evaluation methods can also be optimized in time.
For example, the high-glucose clamp test is cumbersome and not suitable for epidemiological investigations, but it can be used for small-scale scientific research.
When conducting epidemiological surveys in the population, the simple intravenous glucose tolerance test (IVGTT) + oral glucose tolerance test (OGTT) method can be used [7-8]
.
Table 2.
Recommended methods for assessing islet β-cell function in different disease stages Evaluate the number of β cells in patients[9]; analyze the changes of β cells in real time with genomics, proteomics and other technologies, and discover potential targets for the protection of β cell therapy[10]; or perform single-cell RNA sequencing on β cells, from The cellular level reveals the characteristics of its functional changes, etc.
[11]
.
What are the ways to restore islet beta cell function? Islet β-cell failure is the core of T2DM disease [12], so it is also the focus of exploration in the field of diabetes treatment
.
Numerous researchers and medical workers are trying from different angles and using different means to achieve the goal of restoring beta cell function and then reversing the progression of diabetes
.
Most of the various hypoglycemic drugs currently in use can have a certain impact on β-cell function.
According to the mechanism of action, they can be divided into “unloading” pathways (such as insulin) that reduce insulin secretion requirements, reduce the burden on β-cells (such as insulin), and restore and enhance β-cell function.
The 'pro-remodeling' pathways of cellular insulin secretion capacity (eg, sulfonylureas) [13] are inconclusive
.
Existing clinical research evidence shows that insulin as an early intensive treatment plan is more effective than traditional oral hypoglycemic drugs in improving islet β-cell function
.
A study conducted by Chinese scholars in 2008 showed that continuous subcutaneous insulin infusion (CSII) or multiple insulin injections (MDI), supplemented with basal insulin and mealtime insulin at the same time, were evaluated by HOMA-β and acute insulin response (AIR).
The function of islet β-cells in the insulin group was significantly improved, and the improvement effect was maintained after 1 year, and the drug-free remission rate of the insulin group was 48.
2% (121/251) after 1 year, which was significantly higher than that of the oral drug group (p = 26.
7%).
0.
0012) (Fig.
3) [14]
.
Figure 3.
The remission rate and AIR status of patients in the Chinese study in 2008.
In addition, another study showed that in the case of little difference in HbA1c level and fasting blood glucose control, the glucose disposal index (DI) of patients receiving basal + mealtime insulin intensive therapy ) was higher than that in patients who received oral glimepiride + metformin, also suggesting that insulin has better β-cell protection [15]
.
While most hypoglycemic agents are used alone or in combination, short-term treatment does have evidence of improving β-cell function, but long-term treatment data are limited
.
In addition to existing drug treatments, non-drug treatments such as gastric volume reduction surgery and very low-calorie diet[16-17] can also improve the function of pancreatic β-cells in patients with T2DM.
The continuous progress of basic scientific research also provides new intervention methods.
For example, the application of new drugs targeting other sites in blood sugar regulation, bone marrow/umbilical cord blood cell transplantation, β-cell replacement with endogenous cells and pancreatic islet transplantation [18-20] provides the possibility, and the development of these methods in the future can also be expected.
.
Summary: The functional decline of pancreatic beta cells is the core problem of T2DM
.
At present, there is no effective treatment to reverse this process, but commonly used treatments such as insulin and oral hypoglycemic drugs can protect β-cell function to a certain extent by means of "unloading" and "promoting remodeling".
The protective effect is better than that of oral hypoglycemic drugs
.
In the future, new research and new technologies around the protection of β-cell function are expected to truly achieve the "ultimate goal" of reversing β-cell failure and treating diabetes from the source
.
References: [1] Park YJ, Woo M.
Journal of Cell Biology.
2019; 218(4): 1094-1095.
[2] Cersosimo E, et al.
Current Diabetes Reviews.
2014; 10(1): 2- 42.
[3] Chen C, et al.
Molecular Metabolism.
2017; 6(9): 943-957.
[4] Remedi MS, Emfinger C.
Diabetes, Obesity and Metabolism.
2016; 18: 110-116.
[5 ]Gao Z, et al.
Diabetes/Metabolism Research and Reviews.
2021;37(2):e3364.
[6]Seino S,et al.
The Journal of Clinical Investigation.
2011;121(6):2118-2125.
[ 7] Xiao Xinhua, Mao Lili.
Chinese Journal of Diabetes.
2009;1(3):218-221.
[8]Chen Chen.
Medical Review.
2014;20(9):1561-1564.
[9]Li Jiaying, Feng Lie.
Chinese Journal of Diabetes.
2011;03(2):178-181.
[10]Lytrivi M,et al.
BMC Genomics.
2020;21(1):1-15.
[11]Xin Y,et al.
Endocrinology.
2016;157(9):3431-3438.
[12]Saisho Y.
DIABETES.
2018.
[13]Salunkhe VA,et al.
Diabetologia.
2018;61(9):1895-1901.
[14]Weng J , et al.
The Lancet.
2008;371(9626):1753-1760.
[15]Chon S,et al.
Diabetes,Obesity and Metabolism.
2018;20(5):1121-1130.
[16]Jørgensen NB, et al.
American Journal of Physiology-Endocrinology and Metabolism.
2012;303(1):E122-E131.
[17]Malandrucco I, et al.
The American Journal of Clinical Nutrition.
2012;95(3):609-613.
[18] Salunkhe VA,et al.
Diabetologia.
2018;61(9):1895-1901.
[19]Sordi V,et al.
Nutr Metab Cardiovasc Dis.
2017;27(7):583-600.
[20]Farney AC, et al.
Pancreas.
2016;45(1):8-20.
- End - "This article is only used to provide scientific information to medical and health professionals, and does not represent the platform's position" Contribution / reprint / business cooperation, please contact: pengsanmei @yxj.
org.
cn
