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The Effect Of Repaglinide On β-cell Function Of Newly Diagnosed Type 2 Diabetes Mellitus Evaluated By True Insulin

Posted on:2011-09-26Degree:MasterType:Thesis
Country:ChinaCandidate:X Y ShiFull Text:PDF
GTID:2144360305950730Subject:Endocrine and metabolic diseases
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BackgroundIn clinical practice, oral glucose tolerance-insulin release test (OG-IRT) is used to evaluate pancreaticβ-cell function in type 2 diabetes mellitus(T2DM). Due to the inhibition of glucose toxicity, routine OG-IRT can not reflect the reserve function of residual P-cell objectively. With the development of monoclonal-antibody technology, there are various specific methods to detect insulin. Insulin determinated with these methods is bioactive, called as true insulin or specific insulin. In addition to impaired rhythm of insulin secrete, patients with T2DM accompanied with descending quality of insulin, which is shown as increased ratio of proinsulin and lower true insulin. Repaglinide is a non-sulfonylurea insulin secretagogue agent, which can combine with 36KD subunit of insulin receptor on surface of P-cell. Because of short peak time, half-life time and the specific character which can close K+ channel quickly, repaglinide can increase insulin in early phase and recover the physiogenic rhythm of insulin secrete in T2DM.PurposeTo explore the role of repaglinide combined with OG-IRT (RG-OG-IRT) in estimating P-cell function of newly diagnosed T2DM and evaluate the differences of repaglinide and glibenclamide onβ-cell function of newly diagnosed T2DM.Subjects and Methods66 newly diagnosed T2DM patients were randomly divided into 2 groups: repaglinide group (RG, n=36) and glibenclamide group (GB, n=30). As a baseline, OGTT was performed when the patients entered the group. In repaglinide group, OGTT was repeated 15 minutes after 2.0mg repaglinide was taken on the second day's morning, defined as RG-OG-IRT. RG-OG-IRT was performed on the eighth day's morning after taking 2.0mg of repaglinide orally three times a day for 7 days. In glibenclamide group, OGTT was performed on the eighth day's morning after taking 2.5mg of glibenclamide twice a day for 7 days. The blood were collected in all the groups before taking drugs and anhydrous dextrose,30 minutes and 120 minutes after taking anhydrous dextrose. Plasma glucose (PG) was measured with glucose oxidase method, true insulin (TI) with ELISA and immunoreactive insulin (IRI) with radioimmunoassay. The ratio of true insulin to immunoreactive insulin and insulin secrete index of early phase (△Ins30/△G30) were calculated.Results1. In repaglinide group, TI of 3 steps at 30 minutes was 17.65±9.10mIU/L, 21.19±14.30 mIU/L and 23.69±16.39mIU/L respectively. There were statistical differences among them (P<0.05). TI/IRI of 3 steps at 30 minutes were 0.65±0.06, 0.69±0.02 and 0.73±0.03 respectively, and their differences are significant(P<0.05).△Ins30/△G30 of latter 2 steps were 6.54±5.41,9.02±6.03 respectively, which both apparently increased compared with that of baseline(2.75±4.46, both P<0.01).2. In glibenclamide group, TI of post-treatment at 30 minutes was 18.88±9.73mIU/L, without statistical significance compared with baseline. While TI at 120 minutes had statistical significance compared with baseline (P<0.05). TI/IRI of post-treatment at 30 minutes was 0.66±0.01, the baseline was 0.64±0.09, with no clearly statistical differences between them. There was no statistical distinction between△Ins30/△G30 before and after treatment.Conclusions1. Repaglinide can ameliorate the rhythm of insulin release in early phase in T2DM.2. Repaglinide can increase true insulin secretion and its ratio to IRI, showing improvements on quantity and quality of early-phase insulin release in T2DM.3. OG-IRT combined with repaglinide may reflect the reserve and secrete function of (3-cell better than routine OG-IRT in newly diagnosed T2DM.4. For the newly diagnosed T2DM patients with higher PG, OG-IRT combined with repaglinide may better reflect the reserve and secrete function ofβ-cell after short-term intensive treatment with repaglinide.
Keywords/Search Tags:Type 2 diabetes mellitus, β-cell function, True insulin, Repaglinide
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