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
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.
Intensive insulin therapy will be more effective at improving long-term diabetes remission and beta-cell function.
Patients Screened: 436
Patients Enrolled: 352
Mean Follow Up: 1 year
Mean Patient Age: 51 years
• 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
• Acute or chronic complication from diabetes
• Severe intercurrent illness
• Positive test for glutamic acid decarboxylase antibody
• Adolescent onset diabetes
• Mitochondrial diabetes
• Time of glycemic remission
• Diabetes remission rate at 1 year
Beta-cell function represented by HOMA B
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.
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.
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).
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.
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, Hemoglobin A, Glycosylated, Insulin Infusion Systems, Blood Glucose, Diabetes Mellitus, Type 2, Hypoglycemic Agents, Insulins, Fasting
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