Effects of Short-term Intensive Insulin Therapy on Long-term Complications in Type 2 Diabetes

Type 2 Diabetes Mellitus Clinical Trial

Official title:

Effects of Short-term Intensive Insulin Therapy on Long-term Complications in Patients With Type 2 Diabetes

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03909555
• Other study ID #: 20181015
• Status: Not yet recruiting
• Start date: June 1, 2019
• Est. completion date: December 31, 2021

Study information

• Verified date: March 2019
• Source: Sun Yat-sen University
• Contact: Jiewen Jin, Ph.D.
• Phone: +8615298386724
• Email: jiewenjin_med[@]163.com
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Short-term intensive insulin therapy (SIIT) is able to reverse β cell dysfunction and induce glycemic remission in patients with newly diagnosed type 2 diabetes. On the other hand, intensive control of glucose and lifestyle modification are two key elements in preventing chronic complications, especially microvascular neuropathy. However, no study reported the long-term effect of SIIT on the chronic complications. In this multi-center, case-control study, effects of SIIT on the proportion of long-term chronic complications as well as potential biomarkers were investigated.

In total, 777 patients with type 2 diabetes, including 259 patients who participated SIIT when diabetes was newly diagnosed and 518 patients who received routine diabetic therapy will be enrolled in 12 centers in China. After baseline assessments, all patients will undergo complications assessment, including records of cardiovascular diseases (CVD), carotid ultrasonography, electrocardiogram, echocardiography, fundus photography, urinary albumin excretion, Toronto Clinical Neuropathy Scale and Composite Autonomic Symptom Score. Primary endpoint is the difference in the proportions of macrovascular and microvascular complications between groups. Secondary endpoints include the difference of glucose control, insulin resistance, complexity of anti-diabetic therapy and self-management skills and quality of life between two groups. What's more, new biomarkers, which may indicate the occurrence of chronic complications of diabetes, such as circulating endothelial progenitor, β cell dysfunction, and T cells.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 777
• Est. completion date: December 31, 2021
• Est. primary completion date: June 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years and older

Eligibility

Inclusion Criteria:

1. Diagnosed as type 2 diabetes for at least 5 years;

2. When diagnosed as diabetes for the first time, aged between 25 and 65 years, body mass index (BMI) 22-35 kg/m2, fasting plasma glucose (FPG) between 7.0 mmol/l (126 mg/dl) and 16.7 mmol/l (300 mg/dl);

3. Short-term intensive insulin therapy group: Patients received short-term intensive insulin therapy for 14 days when newly diagnosed as type 2 diabetes and induce glycemic remission.

4. Routine diabetic therapy group: Patients received routine diabetic therapy as guideline indicated and never induce glycemic remission.

Exclusion Criteria:

1. Type 1 diabetes or special type of diabetes;

2. Acute complications of diabetes (including DKA, HHS and lactic acidosis) when diagnosed as diabetes;

3. Serious microvascular complications: proliferative stage of retinopathy; urine AER >300 mg/g or urine protein positive, quantification >0.5 g/d; uncontrolled painful diabetic neuropathy and significant diabetic autonomic neuropathy when diagnosed as diabetes;

4. Severe macrovascular complications: acute cerebrovascular accident, acute coronary syndrome, vascular intervention for peripheral arterial disease or amputation requiring hospitalization within 12 months prior to enrollment when diagnosed as diabetes;

5. Blood creatinine clearance less than 50 ml/min, alanine aminotransferase =2.5×upper limit of normal, total bilirubin =1.5×upper limit of normal; Hemoglobin <100 g/L or need regular blood transfusion;

6. Use of drugs that may influence blood glucose within 12 weeks;

7. Systemic infection or serious concomitant disease; patients with malignancy or chronic diarrhea;

8. Uncontrolled endocrine gland dysfunction;

9. Patients with mental or communication disorders;

10. Chronic cardiac insufficiency, heart function class III and above;

11. Pregnant women, lactating women and women of child bearing age who are not willing to take contraception during the study;

12. Subjects who don't cooperate, cannot be followed up or have difficulty in completing the study considered by the investigator.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Other:
• Complications assessment
Records of cardiovascular diseases (CVD), carotid ultrasonography, electrocardiogram, echocardiography, fundus photography, urinary albumin excretion, Toronto Clinical Neuropathy Scale and Composite Autonomic Symptom Score.

Locations

Country	Name	City	State
China	endocrinology department of the first affiliated hospital of Sun Yat-sen University	Guangzhou	Guangdong

Sponsors (11)

Lead Sponsor

Collaborator

Sun Yat-sen University

Dongguan Kanghua Hospital, First Affiliated Hospital of Jinan University, Guangdong General Hospital, Guangzhou Red Cross Hospital, Nanfang Hospital of Southern Medical University, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, The First Affiliated Hospital of Guangzhou Medical University, The Third Affiliated Hospital of Guangzhou Medical University, The Third Affiliated Hospital of Southern Medical University, Zhujiang Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	New biomarkers which may indicate the occurrence of chronic complications of diabetes	Proportion of circulating endothelial progenitor cells between groups. Low level of circulating endothelial progenitor cells indicating a worse outcome.	5 year
Primary	Difference in the proportions of chronic complications	Difference in the proportions of macrovascular and microvascular complications between groups	5 year
Secondary	Difference of glycosylated hemoglobin A1C	Difference of glycosylated hemoglobin A1C between groups	5 year
Secondary	Difference of fast blood glucose	Difference of fast blood glucose between groups	5 year
Secondary	Difference of C-peptides	Difference of fast C-peptides between groups.	5 year
Secondary	Difference of insulin resistance	Difference of HOMA2-IR between groups. HOMA2-IR is calculated by fast blood glucose and C-peptide according to formula proposed by DR Matthew (the software can be accessed at http://www.ocdem.ox.ac.uk).	5 year
Secondary	Difference of insulin usage	Compare the proportion of insulin usage (including rapidly acting insulin, regular insulin, long-acting insulin and premixed insulin) between groups	5 year
Secondary	Difference of oral anti-diabetic drugs usage	Compare the proportion of oral anti-diabetic drugs usage (including biguanides, sulfonylureas, Glinides, glucosidase inhibitors, thiazolidinediones, DPP 4 inhibitors, SGLT-2 inhibitor and their combination) between groups	5 year
Secondary	Difference of attitudes toward diabetes	Compare the score of Diabetes Care Profile questionnaire between groups. Patients were questioned about five aspects, including positive attitude, negative attitude, ability to care for their diabetes, belief in importance of care, and self-care adherence. Each statement included a 5-point ranking scale, ranging from strongly disagree (never) to strongly agree (always), with 3 points as neutral. Items under the subscales of positive attitude, care ability, importance of care, and self-care adherence scoring =4 points and items of negative attitude scoring=2 points were designated as good performance, whereas the opposites were poor.	5 year
Secondary	Difference of quality of life	Compare the score of Diabetes quality of life (DQOL) between groups. The DQOL contains a total of 46 items, and all the items are categorized into one of the following four domains: life satisfaction (15 items), diabetes impact (20 items), social/vocational related worries (7 items), and diabetes related worries (4 items). The DQOL adopts a 5-point Likert scale for its response options. The scores range from 1, labeled as "very satisfied," to 5, labeled as "very dissatisfied," for items in the life satisfaction domain; from 1, labeled as "never impacted," to 5, labeled as "always impacted," for items in the diabetes impact domain; and from 1, labeled as "never worried," to 5, labeled as "always worried," for the social/vocational related and diabetes related worries domains. Higher score indicating better outcome.	5 year