Effect Of Insulin Therapy On T2DM Patients With A Secondary Failure To Oral Antidiabetic Therapy

Objective By administrating continuously subcutaneous insulin infusion (CSII) or conventional subcutaneous insulin therapy (CIT), the Type 2 Diabetes Mellitus (T2DM) patients with a secondary failure to oral antidiabetic therapy had improved control of blood glucose level. We monitored the serum insulin (INS), C-peptide (C-P), glucagon (GLC) and somtostatin (SS) level between patients who received those two different treatments in order to indentify the physiological response to insulin therapy and select the better therapeutic regime.Methods We randomly divided 40 T2DM patients with a secondary failure to oral antidiabetic therapy into two groups. One group received continuously subcutaneous insulin infusion (CSII) treatment, while another group received conventional subcutaneous insulin therapy (CIT). We sampled plasma glucose (PG) before and after treatment in all subjects. All subjects have been fasting for 10 hours, and received oral 75g glucose at 07:00hrs. Then PG, serum insulin, C-peptide, glucagon and somtostatin level was sampled at baseline, 30 minutes and 120 minutes post oral glucose intake for the 40 T2DM patients. The same procedure applied to 19 healthy subjects in the control group. The laboratory test methods are listed as following: PG– glucose oxidase method, C-P– straight chemiluminometry, INS– straight chemiluminometry, GLU– enzyme-linked immunosorbent assay (ELISA), SS– ELISA. The level of PG, INS, C-P, GLC and SS is compared among those 3 groups statistically.Results1. Compared to the control group, the level of PG and GLC and fasting SS increased significantly in both CSII and CIT groups, while the level of INS and C-P decreased significantly (P<0.05).2. The PG before and post 75g oral glucose intake and the area under glucose curve (AUCg) decreased dramatically in both CSII and CIT groups post intensive insulin therapy. However, there is no significant difference between those two groups. On the other hand, INS, C-P, the area under insulin curve (AUCins) and the area under C-peptide curve (AUCcp) increased significantly. HOMA-IR reduced, while the HOMA-IS increased post treatment (P<0.05). The INS level at 120 minutes post oral glucose intake is distinguishably higher in CSII group than that in CIT group (P<0.05). 3. The GLC level at 30 minutes and 120 minutes post oral 75g glucose intake is higher than the fasting level among T2DM patients and healthy subjects. However, the level of GLC at different sample timing is outstanding higher among the T2DM patients than that in the control group (P<0.01). The level of GLC and the area under glucagon curve (AUCglc) notably decreased after intensive insulin therapy (P<0.01). There is no significant difference between CSII group and CIT group. There is a positive correlation between the GLC level and HOMA-IR, while there is a negative correlation between the GLC level and HOMA-IS.4. The fasting SS level and the SS level at 120 minutes post glucose intake (SS120) among the T2DM patients are significantly higher than that of the healthy subjects in the control group. However, the SS level of T2DM patients at 30 minutes (SS30) is lower (P<0.01). There is no significant difference between CSII group and CIT group. There is a positive correlation between SS30 and HOMA-IS(P<0.01).There is a negative correlation between SS30 and HOMA-IR(P<0.05).Conclusions The level of the INS and C-P decreased in the T2DM patients with a secondary failure to oral antidiabetic therapy compared with the healthy subjects in the control group.The level of the fasting glucagon increased in the T2DM patient groups, and the glucagon level did not reduce even when the serum glucose level was rising. The level of the fasting somtostatin and SS120 in T2DM patient groups is significantly higher than that in the control group, while the level of SS30 and the secretion peak is lower in the T2DM patient groups. Short-term intensive insulin therapy including CSII and CIT can decrease the serum glucose level,insulin resistance, and glucagon production. It also improves the function ofβ-cell. It is better to use CSII than CIT in the control of glucose level and the improvement ofβ-cell function.