Effect of UDCA on the New Onset Diabetes and Glucose Intolerance Induced by Statin

Study Overview
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Brief Summary
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At present, it is recognized that statins are the cornerstone of treatment for the prevention of major cardiovascular events in patients with atherosclerotic cardiovascular disease (ASCVD); However, at the same time, the increased risk of long-term glucose tolerance and type 2 diabetes mellitus caused by statin therapy has attracted wide attention. The investigators' recent study found that the levels of glycosylated hemoglobin, insulin and C-peptide increased significantly with the extension of follow-up time in patients with hyperlipidemia. At the same time, serum and fecal bile acid metabolism profiles, especially secondary bile acid metabolism, were extensively changed, especially in ursodeoxycholic acid (UDCA), suggesting that the decrease of UDCA is a possible mechanism for statins to induce side effects of diabetes. According to this hypothesis, ursodeoxycholic acid combined with statins may improve the abnormal glucose tolerance caused by statins and maximize the benefit of statins. This study is a multicenter, prospective, randomized, parallel, double-blind placebo-controlled, cohort study. Taking ASCVD patients as the research object, the investigators will compare the changes of glycosylated hemoglobin, fasting blood glucose, fasting insulin, C-peptide and metabolomic indexes before and after the use of ursodeoxycholic acid combined with atorvastatin and atorvastatin alone and during follow-up, Further evaluate the changes of blood glucose related indexes before and after the use of ursodeoxycholic acid combined with atorvastatin and atorvastatin alone, clarify the possible mechanism and specific treatment targets of abnormal glucose tolerance caused by statin, and put forward a possible alternative treatment for the disorder of glucose metabolism caused by statin.

Official Title
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Effect of UDCA on the New Onset Diabetes and Glucose Intolerance Induced by Statin-A Multicenter, Prospective, Random Controlled Trial

Conditions
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Diabetes Mellitus

Intervention / Treatment
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* Drug: UDCA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years old and < 80 years old, regardless of gender; For those who had indications for taking statins for more than half a year, glycosylated hemoglobin increased by more than 0.5 and > 6.1% compared with half a year ago; Agree to accept the study treatment plan and voluntarily sign the informed consent form. Exclusion Criteria: previous diagnosis of diabetes mellitus; Received hypoglycemic drug treatment; The level of abdominal blood glucose at baseline was ≥ 7mmol / L; Need to take glucocorticoids for a long time; Acute myocardial infarction and stroke occurred in the last 6 months; Severe liver dysfunction; Glomerular filtration rate (EGFR) < 30ml / min / 1.73m2 (MDRD formula); Malignant tumor; Blood system diseases; Acute or severe systemic infection; Women during pregnancy, lactation and preparation for pregnancy; Alcohol and other drug addicts and mental patients; Patients who are participating in other clinical studies or withdraw from less than 1 month;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: UDCA 500mg per day<br>This group of participants receive UDCA 500mg per day. | Drug: UDCA<br>* UDCA vs. placebo together with statin in ASCVD patients<br>* Other names: Ursodeoxycholic acid;|
| Placebo Comparator: Placebo<br>This group of participants receive placebo. | Drug: UDCA<br>* UDCA vs. placebo together with statin in ASCVD patients<br>* Other names: Ursodeoxycholic acid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of HbA1c | Changes of glycosylated hemoglobin after taking ursodeoxycholic acid for half a year | 12 months after enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of blood lipid |  | 12 months after enrollment | 
| Concentration of fasting blood glucose |  | 12 months after enrollment | 
| Concentration of fasting islets |  | 12 months after enrollment | 
| Concentration of bile acids |  | 12 months after enrollment | 
| Rate of MACE |  | 12 months after enrollment |