Related Mechanisms of RBP4 in Glycolipid Metabolism

Shanghai Tenth People's Hospital,School of Medicine,Tongji University

Retinol binding protein 4 ( RBP4 ) is a newly discovered adipokine secreted by adipose tissue, which leads to insulin resistance ( IR ) and participates in the occurrence of T2DM. At present, it's not clear whether RBP4 can cause islet β cell dysfunction. The purpose of this study is to explore the role of serum apo-RBP4 in the pathogenesis of newly diagnosed T2DM patients.

Study Overview

• Status: Completed
• Conditions: Beta Cell Dysfunction
• Intervention / Treatment: Biological: overexpression STRA6/miRNA3

Detailed Description

In recent years, with the improvement of living standards and lifestyle changes, the incidence of type II diabetes is increasing, and T2DM has become a worldwide disease that seriously endangers people ' s health. When patients with diabetes in the middle and late, the condition is often irreversible, and early if effective treatment, help to improve the condition in a timely manner, delay the development of the disease process. Therefore, early diagnosis and treatment is the key to prevention and treatment of diabetes. Years of studies have shown that insulin resistance and β-cell dysfunction are the two major mechanisms of type II diabetes. Previous studies on the pathogenesis of type II diabetes mostly focused on insulin resistance, and there are few studies on β-cell dysfunction. Therefore, the study of islet β-cell dysfunction is extremely important. According to previous studies, the investigator found that although insulin resistance exists in type II diabetes, also exists to the same extent in many people who do not have diabetes. These people may have or do not have metabolic syndrome. Therefore, insulin resistance alone cannot be the decisive pathogenic factor of type II diabetes, and the increasing facts indicate that the abnormality of islet cells, especially islet β cells, may be the central link in the pathogenesis of type II diabetes. Obviously, insulin resistance is the initiating factor of type II diabetes, and the normal function of islet β cells is the determinant of whether type II diabetes occurs : the occurrence of insulin resistance initiates the pathogenesis of type II diabetes, but if the islet β cells can maintain its compensatory ability, type II diabetes will not occur. Once its compensatory ability decreases, type II diabetes gradually occurs. Therefore, islet β cell dysfunction is the key to the pathogenesis of type II diabetes. Exploring the harmful factors that impair β-cell function is critical for early prevention and treatment of diabetes.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200072
      • Xiaoyun Cheng

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Prior to conducting any trial-related activities, including those conducted to assess the subject's eligibility Informed consent of the subject;
2. Aged 18-60 years at the time of screening;
3. The diagnosis of diabetes was defined as fasting blood glucose above 7.0mmol/ L twice on different days on a normal diet

Exclusion Criteria:

1. HIV, hepatitis B or C ( self-reported ) or active pulmonary tuberculosis history :
2. history of malignant tumor ;
3. Severe liver dysfunction or kidney disease ( AST or ALT > 3 times the normal upper limit, or eGFR < 30ml min 1.73 m2 ) ;
4. History of severe cardiovascular and cerebrovascular diseases ( angina pectoris, myocardial infarction or stroke ) in the past 6 months :
5. history of severe gastrointestinal disease or gastrointestinal surgery in the past 12 months ;
6. There are other diseases that affect glucose and lipid metabolism : hyperthyroidism, hypothyroidism, cortex Hyperalcoholism, etc. ;
7. Secondary diseases or drugs lead to obesity, including : elevated cortisol ( such as Cushing 's syndrome ), sagging Obesity caused by body and hypothalamus injury, obesity caused by weight loss drug reduction / discontinuation, etc.
8. Drugs affecting body weight or energy intake / energy expenditure were used within 3 months before screening, including :

Sex steroids ( intravenous, oral or intra-articular ), tricyclic antidepressants, for psychiatric disorders

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: T2DM group; patients with T2DM	Biological: overexpression STRA6/miRNA3; RBP4 express in patients with T2DM or not; Other Names: RBP4 express in T2DM patients
Active Comparator: control group; patients without T2DM	Biological: overexpression STRA6/miRNA3; RBP4 express in patients with T2DM or not; Other Names: RBP4 express in T2DM patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RBP4	Retinol binding protein 4	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FBG	fasting blood-glucose in mmol/L	3 years
FINS	fasting serum insulin in mU/L	3 years
ALT	alanine aminotransferase in U/L	3 years
AST	aspartate aminotransferase in U/L	3 years
UA	Uric acid in umol/L	3 years
HOMA-IR	Homeostatic model assessment insulin resistance index=FBG*FINS/22.5	3 years
FT	free testosterone (nmol/L)	3 years
LDL-C	low-density lipoprotein cholesterol in mmol/L	3 years
HDL-C	Hight-density lipoprotein cholesterol in mmol/L	3 years
BMI	BMI=weight(kg)/heihgt(m)^2	3 years
TT	total testosterone in mmol/L	3 years
PBG	postprandial blood-glucose in mmol-L	3 years
PINS	postprandial serum insulin in mU/L	3 years
HbA1c(%)	Glycated hemoglobin	3 years
FSH	follicle-stimulating hormone in IU/L	3 years
TC	Total Cholesterol(mmol/L)	3 years
TG	Triglyceride(mmol/L)	3 years

Collaborators and Investigators

• Sponsor: Shanghai 10th People's Hospital
• Investigators: Study Chair: Shen Qu, Dr, Department of Endocrinology,Shang hai Tenth People's Hostipal,Shang hai,Shanghai,China,200070

Publications and helpful links

General Publications

• Weng Q, Zhao M, Zheng J, Yang L, Xu Z, Zhang Z, Wang J, Wang J, Yang B, Richard Lu Q, Ying M, He Q. STAT3 dictates beta-cell apoptosis by modulating PTEN in streptozocin-induced hyperglycemia. Cell Death Differ. 2020 Jan;27(1):130-145. doi: 10.1038/s41418-019-0344-3. Epub 2019 May 16.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2018
• Primary Completion (Actual): June 1, 2020
• Study Completion (Actual): July 1, 2021

Study Registration Dates

• First Submitted: September 28, 2022
• First Submitted That Met QC Criteria: October 8, 2022
• First Posted (Actual): October 12, 2022

Study Record Updates

• Last Update Posted (Actual): October 12, 2022
• Last Update Submitted That Met QC Criteria: October 8, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Retinol binding protein 4; beta cell dysfunction; glycolipid metabolism
• Other Study ID Numbers: RBP4

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No