Comparison of Diabetes Retinopathy Among Type 2 Diabetic Patients Treated With Different Regimens

Study Overview
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Brief Summary
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Diabetic retinopathy (DR) is an important cause of blindness.

Detailed Description
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Diabetic retinopathy (DR) is an important cause of blindness, and its development of an irreversible process. DR is not only the overall progress and the level of blood sugar, and blood glucose fluctuations more closely, is the key to a smooth hypoglycemic delay DR progression.Diabetes control and complication trail(DCCT) study shows that even though glycemic control was no significant difference in blood glucose fluctuations ,DR also have a significant difference. In this study, three different glucose-lowering program for: (A) a single oral anti-diabetic drugs, (B) basal insulin and oral anti-diabetic drugs, (C) premixed insulin and oral anti-diabetic drugs for comparison. Focus on the stability and the impact of these three programs hypoglycemic long-term prognosis of the DR, and thus affect the molecular mechanisms of DR-based exploration of glucose fluctuations, to optimize blood glucose solutions, lower blood sugar steady, slow progression of DR ultimate clinical purposes. The multi-center study is to cooperate, enrolled 600 cases of type 2 diabetes, observe the effects of different solutions on blood sugar glucose fluctuations and retinopathy, a total of 5 years of follow-up. This will be the first at home and abroad to compare the incidence of hypoglycemic effect programs on DR large multi-center, randomized, controlled clinical studies, clinical practice will optimize the treatment of type 2 diabetes theoretical and evidence-based medicine.

Official Title
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Comparison of Diabetes Retinopathy Among Type 2 Diabetic Patients Treated With Different Regimens: a Multicentre Randomized Parallel-group Clinical Trial

Conditions
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Diabetic Retinopathy

Intervention / Treatment
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* Drug: Metformin
* Drug: Lantus
* Drug: Novomix30


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: aged 30-65; diagnosed to be type 2 diabetes in accordance with the WHO diagnostic criteria in 1999 . diabetes duration for 5 years or less; the glycosylated hemoglobin (HbA1c) is higher than or equal to7.0% ; body mass index (BMI) 20-35 kg/m2; fluorescein fundus angiography (FFA) showed no diabetic retinopathy; women of childbearing-age have birth control plan for 5 years plan; Exclusion Criteria: pregnant or lactating women; diabetes autoantibodies (GAD) antibodies positive; occurred state of diabetic ketoacidosis, diabetes, high permeability, diabetes lactic acidosis within a half years ; aspartate aminotransferase (AST), alanine aminotransferase (ALT) 2.5 times higher than normal ceiling, and/or serum creatinine (Cr) or 133 umol/l (1.5 mg/dl); hemoglobin disease history which can affect determination of HbA1c; have received a coronary angioplasty, coronary artery stent implantation, coronary artery bypass surgery, there was myocardial infarction, unstable angina, and clinical significance of abnormal ecg, cerebrovascular accident, or transient ischemic attack. psychiatric patients; any eye eyesight < 0.1 patients (WHO blind eye disease: keratitis, need serious cataract surgery, glaucoma, uveitis, high myopia shaft > 26.5 mm, history of ocular trauma;Other ophthalmology medical history: the central vein occlusion, branch vein occlusion, wet sex senile macular degeneration, etc.; in eye surgery history, history of cataract surgery, and three months; Other serious diseases, the researchers think that don't fit into the patients

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 65 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: oral drugs<br>oral anti-diabetic drugs only.metformin,start from 500mg bid,if blood glucose dose not reach the standard，added to 500mg tid→1000mg bid.if metformin reach the biggest dosage，added gliclazide modified release tablets，from 30mg qd,if blood glucose dose not reach the standard,add dosage 30mg qd→60 mg qd→90mg qd→120mg qd(max).if still not reach the target，add acarbose 50mg tid | Drug: Metformin<br>* start with metformin，from 500mg bid,if metformin reach the biggest dosage，added gliclazide modified release tablets，afterthat，add acarbose<br>* Other names: acarbose;|
| Experimental: lantus<br>basal insulin combine with oral drugs,started with insulin glargine 0.2 u/kg subcutaneous injection at 10pm（at 8am if patients are night workers）,add dosage if glucose dose not reach the target.after that,you can add oral drugs ,as Group Oral Drugs. | Drug: Lantus<br>* started with insulin glargine 0.2 u/kg subcutaneous injection ，add dosage if glucose dose not reach the target.after that,you can add oral drugs（like oral drug group）<br>* Other names: acarbose;|
| Experimental: Novomix30<br>premixed insulin combine with oral drugs,started with premixed insulin subcutaneous injection(0.4-0.6 u/kg divided into half before breakfast and dinner),and add dosage if glucose dose not reach the target.after that,you can add oral drugs ,as Group Oral Drugs . | Drug: Novomix30<br>* started with premixed insulin subcutaneous injection(0.4-0.6 u/kg divided into half before breakfast and dinner),and add dosage if glucose dose not reach the target.after that,you can add oral drugs ,as Group Oral Drugs<br>* Other names: acarbose;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of diabetic retinopathy | 5-year incidence rate of diabetic retinopathy（%） | 5years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cardiovascular events | myocardial infarction, angina,or cardiac insufficiency with other causes | 5 years | 
| renal failure | use urinary protein excretion rate（%） evaluate clinical course of diabetic nephropathy | 5years | 
| glucose fluctuation | we use continuous glucose monitoring system（CGMS）,made by Medtronic company USA,and assess within-day blood glucose excursions,Daytime blood sugar stability and the stability of postprandial blood glucose,including Standard Deviation Of Blood Glucose（SDBG）in mmol/L, largest amplitude of glycemic excursions(LAGE)in mmol/L, mean amplitude of glycemic excursions(MAGE) in mmol/L,low glycemic index(LBMI),coefficient variation fasting glucose parameters,Mean Of Daily Differences(MODD)in mmol/L. | every one year in 5years | 
| oxidative stress | Glyoxalase 1(GLO-1)in pg/ml,Advanced glycation end products(AGEs）in pg/ml,Soluble Receptor for advanced glycation end products(sRAGE）in pg/ml. | every one year in 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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type 2 diabetes mellitus, Diabetic Retinopathy, glucose fluctuation, oxidative stress, Insulin, Oral drugs