Endocr Pract. 2018 Dec;24(12):1063-1072. doi: 10.4158/EP-2018-0287. Epub 2018 Oct 5.
The aim of this study was to investigate the effects of sitagliptin on the regulation of free fatty acid (FFA) and other metabolic parameters in drug-naïve subjects with type 2 diabetes mellitus (T2DM).
This was a prospective, nonrandomized, observational study. Drug-naïve subjects with T2DM received 25 to 50 mg/day sitagliptin monotherapy (n = 64). At 3 months, FFA and other metabolic parameters were compared with those at baseline. FFA was measured by colorimetry with enzymatic reactions. As a comparator, 12.5 to 25 mg/day alogliptin monotherapy was given to drug-naïve subjects with T2DM (n = 55).
Significant reductions in FFA (-13.2%, P<0.01) levels were observed with sitagliptin but not alogliptin. Both drugs showed similar glycemic efficacies. Significant correlations were observed between the changes (Δ) of FFA and Δglycated hemoglobin A1c (HbA1c), Dtotal cholesterol (TC), Δnon-high-density lipoprotein cholesterol (HDL-C), or Δlow-density lipoprotein cholesterol (LDL-C), and significant negative correlations were seen between ΔFFA and Δhomeostasis model assessment-B (HOMA-B), ΔC-peptide immunoreactivity (CPR)-index or Δbody mass index (BMI) in the sitagliptin group. The subjects in the sitagliptin group were further divided into 2 subgroups (n = 32 each) according to the changes of FFA (group B [above the median] ΔFFA = 23.1 %, P<.0005; group A [below the median] ΔFFA = -37.3 %, P<.00001). At baseline, FFA levels were significantly higher in group A versus group B ( P<.001). Higher degrees of reductions of FBG (-14.6% vs. -9.3%, P<0.05) or HbA1c (-20.6% vs. -16.9%, P<.05), and increases of HOMA-B (52.7% vs. 38.3%, P<.03) or CPR-index (37.5% vs. 18.8%, P<.02) were observed in group A versus group B. Significant reductions of TC (-5.8%, P<.002), non-HDL-C (-7.8%, P<.001) or LDL-C (-6.3%, P<.02), and significant increases of C-peptide (11.3%, P<.05) were seen only in group A.
Sitagliptin could downregulate high FFA levels. Subjects with reductions of FFA levels had better glycemic efficacies and higher degrees of enhancement of beta-cell function than others. Reductions of atherogenic cholesterols were seen in these populations.
CPR = C-peptide immunoreactivity; DPP-4 = dipeptidyl peptidase 4; FBG = fasting blood glucose; FFA = free fatty acid; HbA1c = glycated hemoglobin A1c; HDL-C = high-density lipoprotein cholesterol; HOMA-R = homeostasis model assessment-R; HOMA-B = homeostasis model assessment-B; non-HDL-C = non-HDL-cholesterol; LDL-C = low-density lipoprotein cholesterol; TC = total cholesterol; T2DM = type 2 diabetes; TG = triglyceride; UA = uric acid.
本研究旨在探讨西格列汀对初治 2 型糖尿病（T2DM）患者游离脂肪酸（FFA）及其他代谢参数的调节作用。
这是一项前瞻性、非随机、观察性研究。初治 T2DM 患者接受西格列汀 25-50mg/天单药治疗（n=64）。在 3 个月时，比较 FFA 与基线时的其他代谢参数。FFA 采用酶反应比色法测定。作为对照，给予初治 T2DM 患者 12.5-25mg/天阿格列汀单药治疗（n=55）。
西格列汀可显著降低 FFA（-13.2%，P<0.01）水平，但阿格列汀无此作用。两种药物均具有相似的降糖效果。FFA 的变化（Δ）与糖化血红蛋白 A1c（HbA1c）、总胆固醇（TC）、非高密度脂蛋白胆固醇（HDL-C）或低密度脂蛋白胆固醇（LDL-C）的变化呈显著正相关，与空腹胰岛素（FINS）、稳态模型评估-β（HOMA-β）、C 肽免疫反应性（CPR）-指数或体重指数（BMI）的变化呈显著负相关。在西格列汀组中，根据 FFA 的变化将患者进一步分为 2 个亚组（每组 n=32）：FFA 变化（组 B [中位数以上]ΔFFA=23.1%，P<.0005；组 A [中位数以下]ΔFFA=-37.3%，P<.00001）。基线时，组 A 患者的 FFA 水平显著高于组 B（P<.001）。与组 B 相比，组 A 患者的 FPG（-14.6% vs.-9.3%，P<.05）或 HbA1c（-20.6% vs.-16.9%，P<.05）降低程度更大，HOMA-B（52.7% vs.38.3%，P<.03）或 CPR-指数（37.5% vs.18.8%，P<.02）升高程度更大。仅在组 A 中观察到 TC（-5.8%，P<.002）、非 HDL-C（-7.8%，P<.001）或 LDL-C（-6.3%，P<.02）降低，以及 C 肽（11.3%，P<.05）升高。
西格列汀可下调高 FFA 水平。FFA 水平降低的患者比其他患者具有更好的降糖效果，β细胞功能增强程度更高。这些患者的致动脉粥样硬化胆固醇降低。
CPR=C 肽免疫反应性；DPP-4=二肽基肽酶 4；FBG=空腹血糖；FFA=游离脂肪酸；HbA1c=糖化血红蛋白 A1c；HDL-C=高密度脂蛋白胆固醇；HOMA-R=稳态模型评估-R；HOMA-B=稳态模型评估-B；非 HDL-C=非高密度脂蛋白胆固醇；LDL-C=低密度脂蛋白胆固醇；TC=总胆固醇；T2DM=2 型糖尿病；TG=甘油三酯；UA=尿酸。
