Clinical trial NCT03909555: Effects of Short-term Intensive Insulin Therapy on Long-term Complications in Type 2 Diabetes
Official title: Effects of Short-term Intensive Insulin Therapy on Long-term Complications in Patients With Type 2 Diabetes
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Type 2 Diabetes Mellitus
Keywords: Type 2 diabetes mellitus
Continuous subcutaneous insulin infusion
chronic complications
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: Guangdong Provincial People's Hospital
name: Zhujiang Hospital
name: The Third Affiliated Hospital of Guangzhou Medical University
name: The Third Affiliated Hospital of Southern Medical University
name: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: The First Affiliated Hospital of Guangzhou Medical University
name: Nanfang Hospital, Southern Medical University
name: First Affiliated Hospital of Jinan University
name: Guangzhou Red Cross Hospital
name: Dongguan Kanghua Hospital
First posted: 2019-04-10
Enrollment: 777
Sex: ALL
Minimum age (years): 25
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with type 2 diabetes

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Difference in the proportions of chronic complications
timeFrame: 5 year
Secondary outcomes:
measure: Difference of glycosylated hemoglobin A1C
timeFrame: 5 year
measure: Difference of fast blood glucose
timeFrame: 5 year
measure: Difference of C-peptides
timeFrame: 5 year
measure: Difference of insulin resistance
timeFrame: 5 year
measure: Difference of insulin usage
timeFrame: 5 year
measure: Difference of oral anti-diabetic drugs usage
timeFrame: 5 year
measure: Difference of attitudes toward diabetes
timeFrame: 5 year
measure: Difference of quality of life
timeFrame: 5 year
Other outcomes:
measure: New biomarkers which may indicate the occurrence of chronic complications of diabetes
timeFrame: 5 year
Locations:
city: Guangzhou
country: China
facility: endocrinology department of the first affiliated hospital of Sun Yat-sen University
state: Guangdong
Study officials:
References: