Volume 15 · Issue 05 · 2023

Patients with type 2 diabetes mellitus (T2DM) have a higher cardiovascular risk. In recent years, many studies have shown that glucagon-like peptide-1 receptor agonist (GLP-1RA) can not only reduce blood glucose and body weight in patients with T2DM, but more importantly, the results of cardiovascular outcome test (CVOT) of such preparations show that some GLP-1RA can reduce the incidence of major adverse cardiovascular events in patients with T2DM. However, the cardiovascular protection mechanism of GLP-1RA has not been fully elucidated. Glucagon-like peptide-1 receptor is at low expression levels in the heart and blood vessels, which suggests that Glucagon-like peptide-1 may exert direct and indirect effects on the cardiovascular system. Multiple CVOT data indicate that the drug molecular structure of GLP-1RA is also closely related to cardiovascular benefits. Therefore, a deep understanding of the cardiovascular protective molecular mechanism of GLP-1RA can not only better apply this class of drugs in clinical practice, but also provide important ideas for the future development of new drugs based on glucagon-like peptide-1.

To investigate the effect of baseline serum uric acid (SUA) on the incidence of macrovascular events in patients with type 2 diabetes mellitus (T2DM) without hyperuricemia.

Based on a ten-year cohort of Beijing Community Diabetes Study, using cluster random sampling, participants from 25 communities of 5 districts of Beijing were selected between August 2008 and July 2009. A total of 2 988 T2DM patients without hyperuricemia who completed 10-year follow-up were included. The clinical information was collected at baseline, and the occurrence of macrovascular events (cardiovascular events, cerebrovascular events, peripheral vascular events) were adjudicated by the expert diagnosis group. The total, male and female populations were divided into three groups according to the baseline SUA tertiles (T₁, T₂, and T₃ group), respectively. Differences among three groups were evaluated by one-way analysis of variance (ANOVA) or Kruskal-Wallis H test or χ² test. Cox regression analyses were applied to evaluate the relationship between the SUA tertiles and the risks of macrovascular events.

In the total population, the T₁ group (SUA≤252.00 μmol/L) consisted of 1 005 cases, T₂ group (252.00 μmol/L<SUA≤315.07 μmol/L) consisted of 988 cases, and T₃ group (SUA>315.07 μmol/L) consisted of 995 cases. In the male population, T₁ group (SUA≤266.33 μmol/L) included 404 cases, T₂ group (266.33 μmol/L<SUA≤332.22 μmol/L) included 405 cases, and T₃ group (SUA>332.22 μmol/L) included 404 cases. In the female population, T₁ group (SUA≤242.00 μmol/L) included 594 cases, T₂ group (242.00 μmol/L<SUA≤305.00 μmol/L) included 592 cases, and T₃ group (SUA>305.00 μmol/L) included 589 cases. In total, male and female populations, the incidence of cardiovascular events increased with the increasing of SUA level, and the difference among the three SUA tertiles groups was statistically significant (P<0.05), while there was no significant difference in the incidence of cerebrovascular events (P>0.05), and the incidence of peripheral vascular events was highest in T₃ group of the total population (P=0.044). In total population, compared with the T₁ group, Cox regression analysis indicated that the T₃ group had a significantly increased risk of cardiovascular events (HR=1.998, 95%CI 1.380-2.893, P<0.001) after adjustments for gender, age, body mass index, waist circumference, blood pressure, duration of diabetes, glycated hemoglobin A_1c, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, estimated glomerular filtration rate, anti-hyperglycemic therapy, income, education level and smoking habits. After stratification by gender, the risk of cardiovascular events was also significantly increased in T₂ and T₃ groups compared with those in T₁ groups in male and female (P<0.05). In total, male and female populations, the incidences of cerebrovascular events and peripheral vascular events were not significantly associated with the SUA tertiles after adjustment for multiple factors (P>0.05).

The SUA level was independently associated with the risk of cardiovascular events in the patients with T2DM even without hyperuricemia, suggesting that higher level of SUA may predict the new occurrence of cardiovascular events in T2DM patients with SUA levels in the normal range.

To explore the relationship between microvascular complications and subclinical carotid atherosclerosis in patients with type 1 diabetes mellitus (T1DM).

A total of 582 hospitalized T1DM patients from the Department of Endocrinology and Metabolism of Peking University People′s Hospital from January 2019 to December 2021 were screened consecutively, and 314 subjects who met the inclusion criteria were enrolled. The clinical data and laboratory results of the subjects were collected, including age, sex, diabetes duration, smoking history, height, weight, waist circumference, blood pressure, glycated hemoglobin A_1c (HbA_1c), and lipid profile. Body mass index (BMI) was calculated. All the subjects underwent photography to determine diabetes retinopathy. Urinary albumin to creatinine ratio and estimated glomerular filtration rate (eGFR) were taken out to define the diagnosis of diabetes nephropathy. Vibration sensation, 10 g nylon silk test, ankle reflex, temperature sensation and acupuncture pain sensation were used to determine the diagnosis of diabetes peripheral neuropathy. Carotid plaques were determined by carotid ultrasound, the patients were divided into group with carotid plaque and group without carotid plaque according to the presence or absence of carotid plaque. Chi-square test, t test or Mann-Whitney U test were used to compare the differences between groups, and logistic analysis was used to evaluate the relationship between microvascular complications and carotid plaques.

The average age of the subjects was (50±11) years, and the average duration of diabetes was (10±9) years. Among them, 162 were male (51.6%), and the average BMI was (23.1±3.3) kg/m², with and average HbA_1c of (9.4±2.1)%. One hundred and seventy-one (54.5%) had carotid plaques. Compared with the group without carotid plaques (143 cases), the group with carotid plaques had older age, longer duration of disease, higher waist circumference and systolic blood pressure, higher triglyceride levels, urinary microalbumin and creatinine ratios, and lower eGFR levels. Meanwhile, smoking, diabetes retinopathy and diabetes neuropathy were more common in the group with carotid plaques (P<0.05). The results of multivariate logistic regression analysis showed that age (OR=1.13, P=0.001), smoking (OR=2.93, P=0.006), eGFR (OR=0.94, P=0.015), and diabetes neuropathy (OR=1.84, P=0.049) were associated with carotid plaques.

Diabetes nephropathy and diabetes peripheral neuropathy are associated with the risk of cardiovascular complications in T1DM patients.

To investigate the correlation between fasting blood glucose (FPG) and neurological function in patients with acute ischemic stroke.

A retrospective analysis was performed on 3 338 stroke patients admitted to Xuanwu Hospital of Capital Medical University within 24 hours of onset from November 2013 to October 2016. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured. FPG, 2 hours postprandial-based blood glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), glycated hemoglobin A_1c (HbA_1c), serum creatinine (Scr), urea, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), homocysteine (Hcy), plasma fibrinogen (Fg) were detected. National institutes of health stroke scale (NIHSS), Glasgow coma index (GCS) and modified Rankin scale (MRS) were used to evaluate neurological function. Patients were divided into three groups according to different FPG levels on admission: normal blood glucose group (FPG<6.1 mmol/L, no history of diabetes, 1 507 cases), FPG impaired group (6.1 mmol/L≤FPG<7.0 mmol/L, 1 002 cases), diabetes group (FPG≥7.0 mmol/L or previous history of diabetes, 829 cases). According to NIHSS score, all patients were divided into neurological impairment group (NIHSS score>1 point, 1 906 cases) and normal neurological function group (NIHSS score≤1 point, 1 432 cases). The analysis of variance, t test, and χ² test were used for comparison between groups. Pearson correlation analysis was used to analyze the correlation between FPG and neural function score. Multivariate logistic regression analysis was used to analyze the influencing factors of neurological function in acute ischemic stroke patients.

Compared with the normal blood glucose group and the impaired FPG group, SBP, DBP, FPG, ALT and AST were increased and the indexes of Scr, urea and TG were decreased in the diabetic group, the differences were statistically significant (all P<0.05). Compared with the normal blood glucose group, the SBP, DBP, FPG and ALT in the FPG impaired group were increased, while the AST, Scr, urea and TG were decreased, and the differences were statistically significant (all P<0.05). There were statistically significant differences in NIHSS, MRS and GCS scores among the three groups (all P<0.001). NIHSS and MRS scores in the diabetic group were significantly higher than those in the FPG impaired group, and GCS scores were significantly lower than those in the FPG impaired group (all P<0.001). NIHSS and MRS scores in the FPG impaired group were significantly higher than those in the normal blood glucose group, and GCS scores were significantly lower than those in the FPG impaired group (all P<0.05). FPG was positively correlated with NIHSS and MRS scores (r=0.80, P<0.05; r=0.84, P<0.05), was negatively correlated with GCS scores (r=-0.83, P<0.05). Multivariate logistic regression analysis showed that age, 2 hours postprandial-based blood glucose, hypoglycemic agents and FPG were all related to neurological function in stroke patients (P<0.05).

There is a significant correlation between FPG and neurological function score in patients with acute ischemic stroke. Patients with high FPG have more severe neurological function injury, poorer neurological function recovery state and worse consciousness state.

To investigate the effect of glucagon-like peptide-1 (GLP-1) on advanced glycation end products (AGE)-induced ferroptosis in human aortic vascular endothelial cells (HAEC) and its possible mechanism.

HAEC was divided into 6 groups: control group, AGE group, ferrostatin-1 (Fer-1) group, AGE+GLP-1 (7-37) group, AGE+GLP-1 (9-36) group and AGE+GLP-1 (28-36) group. Each group has three parallel groups. After 48 h of culture, cell viability and malondialdehyde (MDA) content were detected by the kit, mRNA expression levels of ferroptosis related genes [prostaglandin-endoperoxide synthase 2 (PTGS2), acyl-CoA synthetase long-chain family member 4 (ACSL4), glutathione peroxidase 4 (GPX4)] were detected by real-time fluorescence quantitative polymerase linked reaction, and the protein levels of GPX4, ACSL4, liver kinase B1 (LKB1), phosphorylated LKB1 (p-LKB1), adenosine monophosphate-activated protein kinase (AMPK) and phosphorylated AMPK (p‐AMPK) were detected by Western blotting. One-way analysis of variance (ANOVA) and t-test were used for comparison between groups.

Compared with the control group, mitochondrial morphology was abnormal in the AGE group, and cell vitality was significantly inhibited (P<0.05),the cell viability of the AGE+Fer-1 group was significantly increased (P<0.05). In the AGE group, the mRNA level of the positive regulator of ferroptosis gene PTGS2 was up-regulated (P<0.05), the mRNA level of ACSL4 was increased (P<0.05), and the mRNA level of the negative regulator gene GPX4 was down-regulated (P<0.05). The expression of above genes was reversed in AGE+Fer-1 group (P<0.05). Compared to the AGE group, the viability of HAEC cells in GLP-1 and its small molecule fragment group was significantly increased (P<0.05), the content of MDA in cells was decreased, and the degree of lipid peroxidation was decreased (P<0.05). The expression of GPX4 was up-regulated (P<0.05), and the expression of ACSL4 was down-regulated (P<0.05). The expression of p-LKB1 and p-AMPK were significantly increased (P<0.05).

GLP-1 can reduce ferroptosis induced by AGE in HAEC, and the mechanism may be related to the activation of LKB1/AMPK signaling pathway.

To explore the effect of family history of diabetes millitus and hypertension on abnormal glucose metabolism and their interaction.

This study was a case-control study. The community residents with normal blood glucose who participated in the risk evaluation of cancers in Chinese diabetic individuals: a longitudinal (REACTION) study in Dalian from August to December 2011 were selected as the study subjects, and the subjects were followed up from July to December 2014. Family history of diabetes and hypertension at baseline were collected. All subjects who underwent oral glucose tolerance test were divided into case group and control group according to their glucose metabolism status at follow-up. Based on the multivariate logistic regression models, the effects of family history of diabetes and hypertension on the prevalence of abnormal glucose metabolism and their interactions were analyzed. The relative excess risk (RERI), attributable proportion of interactin (AP), and the synergy index (SI) of the interaction were calculated to evaluate the interaction effect on the addition scale.

A total of 2 597 subjects were included in the study. There were 526 cases in the case group and 2 071 cases in the control group. Multivariate logistic regression analysis showed that family history of diabetes (OR=1.387, 95%CI 1.133-1.699, P=0.002) and hypertension (OR=1.553, 95%CI 1.134-2.126, P=0.006) were still the independent influencine factors for abnormal glucose metabolism. The OR value of family history of diabetes multiplied by hypertension on the risk of abnormal glucose metabolism was 1.020 (95%CI 0.639-1.433, P=0.957). Taking patients without history of diabetes and hypertension as control group, the risk of abnormal glucose metabolism in those with hypertension but without a family history of diabetes was increased by 0.443 (OR=1.443, 95%CI 1.111-1.874, P<0.001). The risk of abnormal glucose metabolism in those with a family history of diabetes without hypertension increased by 0.379 (OR=1.379, 95%CI 1.042-1.824, P=0.024), and the risk of abnormal glucose metabolism in those with a family history of diabetes and hypertension increased by 0.998 (OR=1.998, 95%CI 1.467-2.722, P<0.001). Quantitative analysis of interaction showed that RERI=0.180 (95%CI -0.446-0.805), SI=1.222 (95%CI 0.595-2.509), AP=0.090 (95%CI -0.212-0.393).

Family history of diabetes, hypertension were independently associated with the prevalence of abnormal glucose metabolism, and the risk of abnormal glucose metabolism increased when both were present, but there was no significant multiplicative or additive interaction on abnormal glucose metabolism.

To investigate the effect of fasting plasma glucose (FPG) variability on hip fracture in men.

This study was a prospective study that included male employees of Kailuan Group Corporation who underwent physical examinations at a total of 11 hospitals in Kailuan General Hospital and its affiliated hospitals for three consecutive times in 2006, 2008, and 2010 as the study subjects. The annual physical examination in 2010 was used as the starting point for follow-up. All participants were followed from the date of the 3rd examination to December 31, 2021, or until the first occurrence of an endpoint event. The subjects were divided into three groups according to the standard deviation of FPG (FPG-SD) levels, namely, T1 group (FPG-SD<0.33 mmol/L), T2 group (FPG-SD between 0.33 and 0.59 mmol/L), and T3 group (FPG-SD≥0.60 mmol/L). The Kaplan-Meier method was used to calculate the cumulative incidence of endpoint events in each group. Cox proportional risk model was used to analyze the effects of PFG-SD groups on hip fracture.

A total of 43 969 subjects were included, and 177 hip fractures occurred during a median follow-up of 11.02 (10.60-11.33) years. The incidence of hip fracture in T1, T2 and T3 groups was 0.27% (40/14 630), 0.39% (57/14 695) and 0.55% (80/14 644), respectively. Cox regression analysis showed that the HR and 95%CI of hip fracture risk in T₂ and T₃ were 1.28 (0.85-1.92) and 1.64 (1.10-2.47), respectively, compared with T₁.

Increased FPG variability is an independent risk factor for hip fracture in men.

To investigate the awareness of knowledge of diabetic kidney disease (DKD) and related factors in six provinces in China.

From December 2021 to March 2022, a cross-sectional survey study using a structured questionnaire was conducted among 6 230 type 2 diabetes (T2DM) patients aged 18 years and above in six provinces in China (Heilongjiang Province, Hubei Province, Guangdong Province, Gansu Province, Tianjin City, and Chongqing City). The survey collected information on the patients′ general characteristics (gender, education level, region, residential area, and duration of diabetes), awareness of DKD prevention and treatment knowledge (including common symptoms of kidney disease, DKD risk factors, and DKD prevention and control measures), and self-assessment of DKD knowledge and skills. The Chi-square test was used for inter-group comparisons.

Only 18.15% (1 131/6 230) of patients were aware of anemia and fatigue as common symptoms of kidney disease, while 36.84% (2 295/6 230) had no knowledge of any common symptoms of kidney disease. In terms of awareness of DKD risk factors, only 17.61% (1 097/6 230), 16.95% (1 056/6 230), and 13.34% (831/6 230) of the respondents were aware of acute kidney injury, nephrotoxic substances, and excessive protein intake, respectively, while 32.81% (2 044/6 230) had no knowledge of any DKD risk factors. Regarding knowledge of DKD prevention and control measures, only 44.96% (2 801/6 230), 37.37% (2 328/6 230), 33.87% (2 110/6 230), and 25.81% (1 608/6 230) of patients were aware of medication adherence, regular follow-up and monitoring, blood pressure control, and lipid control, respectively, while 20.13% (1 254/6 230) had no knowledge of any DKD prevention and control measures. Comparison of the knowledge of DKD prevention and treatment among different groups showed that male patients, those from the northern regions, those with a higher level of education, and those with diabetes mellitus for 10 years or more had higher awareness rates of common symptoms, risk factors, and prevention and control measures for DKD (P<0.05). Compared with rural residents, urban residents had higher awareness rates of common symptoms and risk factors of kidney disease (P<0.01).

The awareness levels of common symptoms of kidney disease, DKD risk factors, and prevention and control measures among diabetes patients in six provinces in China are relatively low, and there are significant differences in awareness levels among diabetes patients of different genders, residential areas, regions, education levels, and disease courses.

To explore the potential target of unfolded protein response-protein kinase R-like endoplasmic reticulum kinase (UPR-PERK) pathway in the process of ER stress in liver, we also tested whether the UPR-PERK pathway could regulate the oxidative stress-induced growth inhibitor 1 (Osgin1) in the liver endoplasmic reticulum (ER) stress models.

Using GEO database as the source of analysis data, the differentially expressed genes were selected by GEO2R software, using Venn diagram, we identified Osgin1 as the gene with significant variation in the three physiological factors of fasting-refeeding, exercise, and age. The direct interaction between the UPR-PERK pathway and Osgin1 was verified using the GENEMANIA database. Subsequently, we used three different liver endoplasmic reticulum stress models (acute endoplasmic reticulum stress model, non-alcoholic fatty liver disease model and liver cancer model) in GEO Database and TCGA database to further verify the regulatory relationship of UPR-PERK pathway to Osgin1. GraphPadPrism 9.0.0 software was used for statistical analysis. Pearson correlation analysis was used to analyze the correlation between the transcriptional levels of UPR-PERK pathway genes and Osgin1.

Compared with the control group, fasting-refeeding, increased exercise and aging significantly changed the transcription level of Osgin1 (Osgin1 mRNA was up-regulated by 700%, down-regulated by 156% and 229%, respectively, P<0.05). The GENEMANIA database verified the direct interaction between the UPR-PERK pathway and Osgin1. In the model of endoplasmic reticulum (ER) stress, compared with control group, inhibition of UPR-PERK pathway related gene (Eif2ak3) could significantly reverse the up-regulation of Osgin1 mRNA induced by Tunicamycin (Osgin1 mRNA was downregulated by 87%, P<0.001). In the non-alcohol fatty liver model, compared with control group, when the UPR-PERK pathway was alleviated by the administration of drugs, the Osgin1 transcription level was also down-regulated by 48%, 43.3% and 56.6% with BI4556906, EX10970 and IXA4 interventions (P<0.05). In hepatic cancer cell tissues, compared with control group, the transcription levels of UPR-PERK pathway-related genes and Osgin1 were significantly up-regulated 109% (P<0.001).

The activation of UPR-PERK pathway upregulates Osgin1 transcription in physiological conditions and liver endoplasmic reticulum stress models.

Atherosclerotic cardiovascular disease (ASCVD) mainly includes coronary heart disease, stroke and peripheral vascular disease. Post-transplant diabetes mellitus (PTDM) refers to diabetes diagnosed after organ transplantation. At present, with the increase of kidney transplant recipients, the number of PTDM patients is increasing year by year. Diabetes-related ASCVD is one of the important causes of death and disability. Among the risk factors for ASCVD in PTDM patients, in addition to traditional risk factors such as age, smoking, obesity, dyslipidemia, hypertension, etc., there are also specific risk factors such as anti-rejection drug use and long-term renal function impairment. Therefore, PTDM patients face a greater risk of cardiovascular disease than ordinary type 2 diabetes mellitus (T2DM) patients. Current research shows that the application of new hypoglycemic drugs can significantly improve the cardiorenal outcomes of T2DM patients, and also bring hope to PTDM patients. The application of this type of drug in PTDM patients is worth looking forward to, and whether its cardiovascular benefits need further exploration. This article reviews the risk factors and treatment exploration of PTDM and ASCVD.

The increasing number of people with type 2 diabetes mellitus (T2DM) has become a global health problem. Sarcopenia is a disease characterized by a progressive decrease in skeletal muscle mass and strength, and its incidence is increasing year by year in patients with T2DM. The pathogenesis of sarcopenia in patients with T2DM is not clear, but may be related to insulin resistance, skeletal muscle lipid deposition, inflammation and peripheral neuropathy. Glucagon-like peptide-1 (GLP-1) receptor agonists are widely used in the treatment of diabetes. Besides the exact efficacy of lowering glucose and weight loss, they also have certain therapeutic effects on sarcopenia. This article mainly reviews the research progress of GLP-1 receptor agonists in the treatment of diabetic sarcopenia.

Dipeptidyl peptidase IV inhibitor (DPP-4i) is an oral hypoglycemic drug that increases insulin secretion, reduces glucagon secretion and improves hyperglycemia in a glucose concentration-dependent manner. DPP-4i combined with insulin therapy has been shown to further improve glycemic control in patients with type 2 diabetes mellitus (T2DM) without increasing the risk of hypoglycemia, having a neutral effect on body weight, and being well tolerated. Linagliptin is a DPP-4i that is mainly excreted through bile and intestines, and the excretion ratio is about 5% through the kidneys. Therefore, there is no need to adjust the dose in patients with renal insufficiency, and it can be widely used in T2DM patients receiving insulin therapy. As the study of linagliptin in patients with a variety of different types of T2DM deepens, new clinical evidence continues to emerge. Combined with the latest research progress in the field, from the perspective of insulin therapy regimen and clinical application population, this paper combs the relevant randomized controlled studies and real-world research data of linagliptin combined with insulin, and discusses the application of this combination therapy regimen in general patients and special patients. In addition to efficacy and safety, other benefits of this combination regimen are also explored to rationalize clinical treatment regimen development.

Diabetic foot is one of the serious complications of diabetes, and the high amputation rate and mortality rate caused by it seriously threaten the health of the population. The pathogenesis of diabetic foot is complicated, and the wound is repeatedly prolonged. It is recognized as one of the three chronic wounds. Mesenchymal stem cells, with their biological advantages of self-renewal and multidirectional differentiation, have shown good clinical application prospects in promoting diabetic foot wound healing. This paper reviews the role and mechanism of mesenchymal stem cells in the treatment of diabetic foot wounds. In addition, the latest clinical trial studies of mesenchymal stem cells in the treatment of diabetic foot at home and abroad are retrieved and listed, from basic to clinical, from preclinical research to clinical research, which comprehensively demonstrates the research progress of mesenchymal stem cells in the whole course of diabetic foot treatment and the problems existing in clinical application.

Artificial pancreas is a treatment option for type 1 diabetes by adjusting the infusion rate of insulin pump through core algorithm according to the glucose concentration sensed by sensor, and simulating physiological insulin secretion. The results show that the application of artificial pancreas can improve blood sugar control and improve the quality of life of patients with type 1 diabetes. This paper introduces the composition and classification of artificial pancreas, summarizes the clinical research progress of artificial pancreas in the treatment of type 1 diabetes, and makes a prospect of the challenges and future development of artificial pancreas.

Brain insulin signaling plays an important role in maintaining the niche of hippocampal neural stem cells and neuronal activity. Since hippocampus is an important brain region involved in the formation and regulation of learning, memory, cognition and other functions, insulin resistance (IR) in this brain region may be the key factor of cognitive abnormalities and even cognitive impairment in type 2 diabetes mellitus (T2DM). This paper summarizes the effects of normal/abnormal regulation of insulin signaling on cognitive function in adult hippocampal neurogenesis and molecular mechanism of hippocampal synaptic activity, in order to provide ideas for the prevention and treatment of cognitive impairment in diabetes mellitus.

Incretin is an important hormone that connects the intestine with the brain and pancreas, and plays a regulatory role in the body's energy metabolism. Glucose-dependent insulinotropic polypeptide (GIP) is an important component of incretin, and it complements with glucagon-like peptide-1 (GLP-1), another member of incretin, to regulate energy metabolism. In recent years, important breakthroughs have been made in the study of the mechanism of action of GIP and its receptors, which makes GIP an important target for improving glucose and energy metabolism. The newly developed GIP and GLP-1 receptor agonists have shown significant improvements in blood glucose and body weight in patients with type 2 diabetes, emerging as potentially attractive drug options. This article reviews the important research progress of GIP in basic and clinical aspects, in order to help the clinic deeply understand the regulatory mechanism of incretin on human energy metabolism, and better understand the drugs developed based on this target.