Effects Of Early Intensive Insulin Therapy On The Immunoloregulation On T Lymphocyte Subgroups And Endogenous β-cell Regeneration In Non-obese Diabetic Mice And Type 1 Diabetic Children

ObjectivesTo investigate the immunoloregulation effects of early intensive insulin therapy on T lymphocyte subgroups in nonobese diabetic(NOD) mice.MethodsThirty (12～14 weeks old)female NOD mice were randomized into early intensive therapy(EIT) group, early conventional therapy(ECT) group, late intensive therapy(LIT) group, late conventional therapy(LCT) group, and no-therapy (DM)group. Also, age-matched female NOD mice, without the advent of diabetes, was included in the study as the normal control(NC) group. The changes of weight and blood glucose in EIT group and other groups were observed and the ratio of T lymphocytes of spleen and thymus was analyzed by flow cytometer.ResultsThe weight of EIT group increased with the age compared with that in the LIT,LCT and DM groups (P<0.001) and the average 24-hour blood glucose sustained at (5.758±1.515) mmol/L, which was significantly lower than that in the LITn LCT and DM groups(P<0.001) but was higher than that in the NC group. As for the T cell from spleen, the percentage in the EIT group of CD4+ and CD3+ was low, and CD4+/CD8+ ratio decreased significantly compared with those of LCT and DM groups(all P<0.001). Compared with LIT,LCT and DM groups, the percentage of CD4+CD8-T cells from thymus in the EIT group was significantly lower(all P<0.001), while CD4+CD8+ was higher markedly(all P<0.001).ConclusionsEarly intensive insulin therapy can effectively control the blood glucose, keep normal weight gain, and decrease the host autoimmunity, which relate to the changes of T lymphocytes subsets. ObjectivesCompare the influence to the endogenousβ-cells function and regeneration of continuous subcutaneous insulin infusion with aspart (CSII-A) with twice daily injection (BDI)therapy of insulin Novolin 30R and multiple daily insulin injection (MDI) therapy of bolus insulin aspart and basal insulin glargine in new-onset of type 1 diabetes mellitus (T1DM).Research design and methodsSeventy-five patients with new-onset of T1DM within recent three years were enrolled in a open-label, parallel-group,3-month study. After intravenous administration of insulin corrected ketoacidosis,12 subjects were assigned to CSII-A therapy,30 subjects were assigned to BDI therapy (Novolin 30R before breakfast and dinner) and 33 patients were assigned to MDI therapy (aspart immediately before each meal and glargine at bedtime).1. Efficacy was assessed with eight-point blood glucose fluctuation (BG-F), he-moglobin A 1c(HbA1c) at 3-month.2. Total daily insulin dosage, C-peptide, honeymoon period beginning time and duration were compared as assessed the endogenousβ-cells function and regeneration.3. Linear correlation analysis was made between serum C-peptide and HbA1c at 3 month, BG-F.Results1. All groups had similar total daily insulin dosage at baseline, while at three-month, which in the CSII group was lower than that in the BDI and MDI groups (0.36±0.10u/kg·d vs 0.51±0.22u/kg·d; P=0.036 and 0.36±0.10u/kg·d vs 0.39±0.17 u/kg·d; P=0.43, CSII-A vs BDI,CSII-A vs MDI respectively).2. The CSII-A group showed a tend toward lower BG-F at three month (2.37±0.80mmol/L vs 5.9±2.89 mmol/L and 3.50±1.64 mmol/L for CSII-A and BDI, MDI; P=0.001,0.014, respectively).3. HbA1c values decreased significantly for the CSII group from baseline (13.4±2.2%) to end of study (6.19±0.63%) compared with other groups (from 13.1±2.0% to 7.61±0.93% for BDI, from 13.5±2.7% to 6.93±0.62 for MDI), (CSII-A vs BDI and MDI,P=0.000 and 0.002, respectively).4. As for the C-peptide, it was improved in CSII-A,BDI and MDI groups and significantly higher after CSII-A therapy than after BDI and MDI therapys (1.86±0.55ng/mL vs 0.78±0.45 ng/mL and 1.86±0.55ng/mL vs 1.10±0.54 ng/mL, CSII-A vs BDI,CSII-A vs MDI respectively; all P=0.000).5. Compared with BDI and MDI groups, the beginning of honeymoon period in CSII-A group was significantly earlier (CSII-A:0.75±0.16 month, BDI: 1.56±0.44 months, MDI:1.36±0.49 months; vs BDI and MDI, P= 0.000,0.003, respectively), while the duration of honeymoon period was longer markedly (CSII-A:18.75±6.00 months, BDI:8.74±3.06 months, MDI:11.14±5.60 months; respectively vs BDI and MDI,P=0.001,0.013, respectively).6. There was a significantly negative linear correlation between C peptide and BG-F(r=-0.54, P<0.01),HbA1c(r=-0.65, P<0.01) respectively.ConclusionsIn a trial of short duration, insulin aspart in CSII therapy provide efficacy and show apparent earlier beginning and longer duration of the honeymoon period, and ameliorate endogenousβcell regeneration better as compared with BDI and MDI therapys for new-onset pediatric patients with type 1 diabetes.