Effect of Intensive Insulin Therapy on Beta-Cell Function and Glycemic Control in Patients With Newly Diagnosed Type 2 Diabetes - Effect of Intensive Insulin Therapy on Beta-Cell Function and Glycemic Control in Patients With Newly Diagnosed Type 2 Diabetes

May 27, 2008
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Trial Sponsor:
973 Programme from the Chinese Government, the Natural Science Foundation of Guangdong Province Government, Novo Nordisk (China), and Roche Diagnostics (Shanghai)
Date Published:
01/01/2008
Date Updated:
05/27/2008
Original Posted Date:
05/27/2008
References

Description:

The goal of the trial was to evaluate the effect of short-term intensive diabetes therapy (continuous insulin, divided dose insulin, or oral hypoglycemic medications) on long-term diabetes remission rates and beta-cell function.

Hypothesis:

Intensive insulin therapy will be more effective at improving long-term diabetes remission and beta-cell function.

Study Design

Study Design:

Patients Screened: 436
Patients Enrolled: 352
Mean Follow Up: 1 year
Mean Patient Age: 51 years
Female: 23

Patient Populations:

• Patients with newly diagnosed type 2 diabetes who were not on diabetic medications
• Ages 25-70 years
• Fasting plasma glucose 7-16.7 mmol/L

Exclusions:

• Acute or chronic complication from diabetes
• Severe intercurrent illness
• Positive test for glutamic acid decarboxylase antibody
• Adolescent onset diabetes
• Mitochondrial diabetes

Primary Endpoints:

• Time of glycemic remission
• Diabetes remission rate at 1 year

Secondary Endpoints:

Beta-cell function represented by HOMA B

Drug/Procedures Used:

Patients with newly diagnosed type 2 diabetes were randomized to continuous subcutaneous insulin injection by implantable pump (CSII) (n = 133), multiple daily insulin injections (MDI) (n = 118), or oral hypoglycemics (n = 101). Treatment was maintained for 2 weeks after glycemic goal was attained, at which time patients were continued on diet and physical therapy.

The glycemic goal (target) was defined as a fasting blood glucose of <6.1 mmol/L and a blood glucose of <8.0 mmol/L at least 2 hours after meals. Patients who could not reach goal within 2 weeks or had intolerable side effects were excluded from the analysis.

Concomitant Medications:

Patients in the CSII group received human insulin through an implantable insulin pump. Patients in the MDI group received divided doses of Novolin-R and human insulin NPH. Patients in the oral hypoglycemic group received gliclazide (80-160 mg twice daily) if their body mass index (BMI) was 20-25 kg/m2. Patients with a BMI between 25 and 35 kg/m2 received metformin (0.5-1 g twice daily). Patients who could not reach glycemic control were treated with a combination of gliclazide and metformin. Insulin was titrated daily and oral diabetic medications were titrated every 3 days until glycemic goal (target) was reached.

Principal Findings:

Target glycemic control was achieved in 4.0 days in 97.1% of the CSII group, in 5.6 days in 95.2% of the MDI group, and in 9.3 days in 83.5% of the oral hypoglycemic group (p < 0.0001 for CSII vs. oral hypoglycemics). Remission at 1 year was observed in 51.1% of the CSII group, 44.9% of the MDI group, and 26.7% of the oral hypoglycemic group (p = 0.0012 for insulin vs. oral hypoglycemics).

After intensive therapy, there was no difference between the groups in the fasting plasma glucose (6.6 mmol/L for CSII, 6.8 mmol/L for MDI, and 6.5 mmol/L for oral hypoglycemics), 2-hour post-prandial plasma glucose (7.5 mmol/L, 8.1 mmol/L, and 8.2 mmol/L, respectively), or glycated hemoglobin (HbA1c) % (8.0, 8.0, and 7.9, respectively), although these parameters and low-density lipoprotein cholesterol improved from baseline among each group. HOMA B was significantly increased in all patients (87.5, 78.9, and 102.3, respectively).

Interpretation:

Among newly diagnosed type 2 diabetic patients, the use of short-term intensive therapy restores glycemic control in 7.9 days for most patients. The restoration of glycemic control occurs faster and in a higher proportion of patients who receive insulin compared with oral hypoglycemic medications. Short-term intensive therapy improves fasting and post-prandial blood glucose levels and HbA1c to a similar degree; however, there was a higher proportion of diabetes remission at 1 year with insulin therapy. Beta-cell function (HOMA B) was significantly increased in all groups. The implication is that 2-5 weeks of intensive therapy could result in sustained diabetes remission at 1 year in approximately one-half of the patients.

The authors postulated that removing the glucotoxicity of uncontrolled diabetes may preserve and even rescue beta-cell function. Although the patients in this study had newly diagnosed type 2 diabetes, their actual onset of diabetes is unknown. It is possible that the patients who responded most favorably to intensive therapy had a shorter duration of diabetes.

References:

Weng J, Li Y, Xu W, et al. Effect of intensive insulin therapy on beta-cell function and glycaemic control in patients with newly diagnosed type 2 diabetes: a multicentre randomised parallel-group trial. Lancet 2008;371:1753-60.

Keywords: Lipoproteins, LDL, Glycated Hemoglobin A, Insulin Infusion Systems, Blood Glucose, Diabetes Mellitus, Type 2, Hypoglycemic Agents, Insulins, Fasting


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