The effect of DPP-4 inhibition with sitagliptin on incretin secretion and on fasting and postprandial glucose turnover in subjects with impaired fasting glucose
The effect of DPP-4 inhibition with sitagliptin on incretin secretion and on fasting and postprandial glucose turnover in subjects with impaired fasting glucose
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DOI：
10.1111/j.1365-2265.2009.03764.x
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发表时间：
2010-08-01
影响因子：
3.2
通讯作者：
Vella, Adrian
中科院分区：
文献类型：
--
作者：
Bock, Gerlies;Man, Chiara Dalla;Vella, Adrian
目的观察到空腹血糖受损(IFG)患者血清胰高血糖素样肽-1(GLP-1)浓度降低。目前尚不确定这些异常是否直接参与了IFG和糖耐量受损的发病机制。二肽基肽酶-4(DPP-4)抑制剂可以提高IFG中的生长素激素浓度，从而能够检查它们对IFG中葡萄糖周转的影响。研究设计和方法我们采用双盲、安慰剂对照、平行组设计对22名IFG患者进行了研究。在登记时，受试者吃的是标有[1-13C]-葡萄糖的标准化膳食。输注[6-~3H]葡萄糖使能测量全身性进餐情况(MRA)。输注[6，6-2H(2)]葡萄糖可测量内源性葡萄糖生成量(EGP)和葡萄糖消失率(RD)。随后，受试者被随机分成两组，每天服用100毫克西格列汀或安慰剂。结果如预期的那样，接受安慰剂治疗的IFG受试者的血糖浓度没有任何变化。尽管西格列汀提高了完整的GLP-1浓度，但西格列汀治疗并没有改变空腹或餐后血糖、胰岛素或C肽浓度。餐后EGP(18中心点1+/-0中心点7 vs 17中心点6+/-0中心点8 mU/kg/min，P=0中心点53)，RD(55中心点6+/-4中心点3 vs 58中心点9+/-3中心点3 mU/kg/min，P=0中心点47)和MRA(6639+/-377 vs 6581+/-316 mU/kg/6h，P=0中心点85)。西格列汀与总GLP-1降低相关，提示胰岛素分泌减少。结论抑制DPP-4不会改变IFG患者的空腹或餐后糖转换。低浓度的INT不太可能参与IFG的发病机制。
P>ObjectiveLow glucagon-like peptide-1 (GLP-1) concentrations have been observed in impaired fasting glucose (IFG). It is uncertain whether these abnormalities contribute directly to the pathogenesis of IFG and impaired glucose tolerance. Dipeptidyl peptidase-4 (DPP-4) inhibitors raise incretin hormone concentrations enabling an examination of their effects on glucose turnover in IFG.Research design and methodsWe studied 22 subjects with IFG using a double-blinded, placebo-controlled, parallel-group design. At the time of enrolment, subjects ate a standardized meal labelled with [1-13C]-glucose. Infused [6-3H] glucose enabled measurement of systemic meal appearance (MRa). Infused [6,6-2H(2)] glucose enabled measurement of endogenous glucose production (EGP) and glucose disappearance (Rd). Subsequently, subjects were randomized to 100 mg of sitagliptin daily or placebo. After an 8-week treatment period, the mixed meal was repeated.ResultsAs expected, subjects with IFG who received placebo did not experience any change in glucose concentrations. Despite raising intact GLP-1 concentrations, treatment with sitagliptin did not alter either fasting or postprandial glucose, insulin or C-peptide concentrations. Postprandial EGP (18 center dot 1 +/- 0 center dot 7 vs 17 center dot 6 +/- 0 center dot 8 mu mol/kg per min, P = 0 center dot 53), Rd (55 center dot 6 +/- 4 center dot 3 vs 58 center dot 9 +/- 3 center dot 3 mu mol/kg per min, P = 0 center dot 47) and MRa (6639 +/- 377 vs 6581 +/- 316 mu mol/kg per 6 h, P = 0 center dot 85) were unchanged. Sitagliptin was associated with decreased total GLP-1 implying decreased incretin secretion.ConclusionsDPP-4 inhibition did not alter fasting or postprandial glucose turnover in people with IFG. Low incretin concentrations are unlikely to be involved in the pathogenesis of IFG.