Comparison Of Therapeutic Effects Of CSII And Combined With Biguanide Or TZD In Short-term T2DM

Background: Type 2 diabetes mellitus(T2DM)is considered as the result of combined effects of isletβ-cell dysfunction and insulin resistance (IR). IR takes through the whole process of T2DM, while gradual failure ofβ-cell function results in progress of T2DM.β-cell dysfunction is due to various reasons, such as glucose and lipid toxicity, various inflammatory factors (C-reactive protein, IL-6, SAA etc), glycation end products, primary factors and so on. C-reactive protein (CRP) is an important forecast indicator of T2DM, independent of other DM factors. However, the persistence of glucose toxicity is the major factor of inducingβ-cell dysfunction and it can aggravate IR further. The study about early application of insulin treatment in patients with T2DM has showed that not only it can reduce glucose toxicity, but also inhibit lipolysis, and has non-specific anti-inflammatory effect, and thus improved insulin sensitivity andβ-cell function. Metformin, as the biguanide representative of oral hypoglycemic agetens, can improve insulin sensitivity through decreasing FFA, TG and non-specific anti-inflammatory effect. Thiazolidinediones (TZD) such as pioglitazone, which belongs to Insulin-sensitizing agents can reduce IR. The study is aimed to find out the optional therapy by comparing the therapeutic effects of continuous subcutaneous insulin infusion (CSII) and combined with metformin or pioglitazone in patients with short-term T2DM.Methods: 73 hospitalized patients with short-term T2DM were divided randomly into three groups: simple CSII group, CSII combined with metformin group, CSII combined with pioglitazone group. Before the intensive therapy, fasting plasma glucose(FPG), high sensitivity CRP (hs-CRP), insulin(ins), C-peptide(CP)were measured and PG, Ins,.CP were measured in 2h after taking 75g glucose. Then MiniMed Paradigm insulin pump(Humalog) was used with initial dose of 0.7U/Kg/d in each group, and added Glucophage(850mg bid po) to metformin group, ActIns (15mg Qd po) to pioglitazone group. All the patients took the first affiliated hospital of dalian medical university standard caloric diet. We monitored capillary blood glucose for at least seven times daily and adjusted the Humalog dose accordingly. The control target was FBG<7mmol/L and 2hPBG<10mmol/L. The period of targeting and insulin dosage were recorded. Two weeks after intensive therapy, the above indicators were rechecked. Steady-state model(Homa)β-cell function[Homaβ= 20×Fins/(FPG-3.5)] and insulin resistance index(HomaIR=FPG×Fins/22.5) were calculated. At the same time, changes of the indicators before and after therapy and the treatment costs were compared among three groups. During intensive therapy, the patients whose blood glucose were difficult to target and need other hypoglycemic agents were not included in the study.Results: After two weeks of intensive treatment, FPG and HomaIR levels of three groups decreased significantly(P<0.05), Homaβ, Ins and CP response times levels were significantly higher(P<0.05); hs-CRP level of metformin group decreased significantly(P<0.05), hs-CRP levels in simply CSII and pioglitazone groups had downward trend, but not significant. Homaβlevels were significantly increased(P<0.05), HomaIR levels decreased significantly(P<0.05) in metformin and pioglitazone groups compared with the simple CSII one; The period of targeting and treatment costs were reduced, and insulin dosage decreased significantly in metformin group compared with the simple CSII and pioglitazone groups(P<0.05); FPG and hs-CRP descenting levels, Ins and CP response times increasing levels had no significant difference among three groups. Pearson's correlation analysis showed that FPG was negatively correlated with Homaβ, Ins response times, CP response times (r=0.76, 0.46 and 0.63 respectively, P<0.05) and positively with HomaIR (r=0.53, P<0.05).Conclusion: 1. FPG of T2DM patients were negatively correlated withβ-cell function, Ins reponse times, CP respose times and positively related with IR, the indicators mentioned above were significantly improved after intensive treatment of hypoglycemic, which suggested that glucose toxicity caused by hyperglycemia plays a dominent role in the progress of T2DM. 2. CSII combined with metformin or pioglitazone , compared with simple CSII, can improve the function ofβ-cell and reduce IR, and CSII combined with metformin can shorten hospitalization period, decrease insulin dosage and treatment costs especially.