Derosa Giuseppe, Carbone Anna, D'Angelo Angela, Querci Fabrizio, Fogari Elena, Cicero Arrigo F G, Maffioli Pamela
Department of Internal Medicine and Therapeutics, University of Pavia, Italy.
Intern Med. 2013;52(19):2179-87. doi: 10.2169/internalmedicine.52.8175. Epub 2012 Mar 1.
The effects of dipeptidyl peptidase-4 (DPP-4) inhibition on adipose tissue inflammation remain obscure. The aim of this study was to evaluate the effects of the addition of sitagliptin on the β-cell function and various inflammatory biomarkers in type 2 diabetic patients.
After a run-in period of taking metformin, 178 diabetic patients with poor glycemic control were randomized to take sitagliptin at a dose of 100 mg once a day or a placebo in addition to metformin for 12 months. We evaluated the following parameters at three, six, nine and twelve months: body mass index (BMI), glycemic control, the homeostasis model assessment insulin resistance index (HOMA-IR), the homeostasis model assessment β-cell function index (HOMA-β), the proinsulin/fasting plasma insulin ratio (Pr/FPI ratio) and the levels of fasting plasma insulin (FPI), fasting plasma proinsulin (FPPr), C-peptide, glucagon, resistin, vaspin, omentin-1 and tumor necrosis factor-α (TNF-α). Before and twelve months after the addition of sitagliptin, the patients underwent combined euglycemic hyperinsulinemic and hyperglycemic clamping with subsequent arginine stimulation to assess insulin sensitivity and secretion.
Treatment with sitagliptin + metformin was more effective than placebo + metformin in improving glycemic control, the HOMA-IR and the glucagon level and increasing the HOMA-β and all β-cell measurements after combined euglycemic hyperinsulinemic and hyperglycemic clamping with subsequent arginine stimulation. Regarding inflammatory biomarkers, sitagliptin + metformin more effectively reduced the levels of resistin, vaspin and omentin-1 than placebo + metformin.
When treatment with metformin alone is not adequate for obtaining glycemic control, the addition of sitagliptin can be considered due to its actions in preserving the β-cell function and reducing the levels of biomarkers of inflammation.
二肽基肽酶-4（DPP-4）抑制对脂肪组织炎症的影响仍不清楚。本研究的目的是评估在2型糖尿病患者中添加西他列汀对β细胞功能和各种炎症生物标志物的影响。
在服用二甲双胍的导入期后，178例血糖控制不佳的糖尿病患者被随机分为两组，一组每天服用一次100mg西他列汀，另一组除二甲双胍外服用安慰剂，为期12个月。我们在3个月、6个月、9个月和12个月时评估了以下参数：体重指数（BMI）、血糖控制、稳态模型评估胰岛素抵抗指数（HOMA-IR）、稳态模型评估β细胞功能指数（HOMA-β）、胰岛素原/空腹血浆胰岛素比值（Pr/FPI比值）以及空腹血浆胰岛素（FPI）、空腹血浆胰岛素原（FPPr）、C肽、胰高血糖素、抵抗素、内脏脂肪素、网膜素-1和肿瘤坏死因子-α（TNF-α）的水平。在添加西他列汀之前和之后12个月，患者接受联合正常血糖高胰岛素血症和高血糖钳夹，随后进行精氨酸刺激，以评估胰岛素敏感性和分泌。
在联合正常血糖高胰岛素血症和高血糖钳夹并随后进行精氨酸刺激后，西他列汀+二甲双胍治疗在改善血糖控制、HOMA-IR和胰高血糖素水平以及增加HOMA-β和所有β细胞测量值方面比安慰剂+二甲双胍更有效。关于炎症生物标志物，西他列汀+二甲双胍比安慰剂+二甲双胍更有效地降低了抵抗素、内脏脂肪素和网膜素-1的水平。
当单独使用二甲双胍治疗不足以实现血糖控制时，由于西他列汀在保留β细胞功能和降低炎症生物标志物水平方面的作用，可以考虑添加西他列汀。
