• 哈爾濱醫(yī)科大學(xué)附屬第二醫(yī)院內(nèi)分泌代謝病科（哈爾濱，150001）;

【摘要】　目的　 研究2型糖尿?。╰ype 2 diabetes mellitus，T2DM）合并非酒精性脂肪性肝?。╪on-alcoholic fatty liver disease， NAFLD）患者血漿脂肪細(xì)胞特異性脂肪酸結(jié)合蛋白（adipocyte-specific fatty acid-binding protein，A-FABP）的水平及其相關(guān)因素。　方法　 2009年10月—2010年10月選取T2DM合并NAFLD組（A組）60例，未合并NAFLD組56例（B組）為研究對象。測定體質(zhì)量指數(shù)（body mass index，BMI），檢測血脂、糖化血紅蛋白（hemoglobin A1c，HbA1c）等生化指標(biāo)。放射免疫法測定空腹胰島素（fasting insulin，F(xiàn)INS），空腹C肽水平（fasting C-peptide，F(xiàn)CP），計(jì)算胰島素抵抗指數(shù)（homeostasis model of assessment-insulin resistance，HOMA-IR）、胰島素敏感指數(shù)（insulin sensitivity index，ISI），測定A-FABP、C反應(yīng)蛋白（C-reaction protein，CRP）及腫瘤壞死因子-α（tumor necrosis factor-α，TNF-α）。　結(jié)果　 與B組患者相比，A組患者其血漿A-FABP水平、BMI、腰圍、腰臀比、丙氨酸氨基轉(zhuǎn)移酶、門冬氨酸氨基轉(zhuǎn)移酶、CRP、TNF-α、FCP、FINS、總膽固醇、甘油三酯、Ln（HOMA-IR）升高，Ln（ISI）降低，差異有統(tǒng)計(jì)學(xué)意義（P lt;0.05）；兩組HbA1c差異無統(tǒng)計(jì)學(xué)意義（P gt;0.05）。A-FABP水平變化與TNF-α、HOMA-IR、CRP呈正相關(guān)，與ISI呈負(fù)相關(guān)。　結(jié)論　 T2DM伴NAFLD中，A-FABP升高與胰島素抵抗是并存的，且存在明顯相關(guān)關(guān)系，二者在疾病的發(fā)生發(fā)展中均可能具有重要的作用。
【Abstract】　Objective　 To analyze the serum level of adipocyte-specific fatty acid-binding protein (A-FABP) in patients with type 2 diabetes mellitus (T2DM) complicated with non-alcoholic fatty liver disease (NAFLD), and its related factors.　Methods　 From October 2009 to October 2010, 112 patients with T2DM were categorized into two groups: the group with NAFLD (group A) with 60 patients, and the group without NAFLD (group B) with 56 patients. Body mass index (BMI), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and hemoglobin A1c (HbA1c) were detected. Radioimmunoassay was carried out to measure fasting insulin (FINS) and fasting C-peptide (FCP), and homeostasis model of assessment-insulin resistance (HOMA-IR) and insulin sensitivity index (ISI) were calculated. At the same time, A-FABP, C-reaction protein (CRP) and tumor necrosis factor-α (TNF-α) were also detected.　Results　 Compared with patients in group B, plasma levels of A-FABP, BMI, waistline, waist to hip ratio, ALT, AST, TG, TC, HDL-C, LDL-C, CRP, FCP, FINS, and HOMA-IR for patients in group A were all higher, while ISI was lower; and the differences in the above-mentioned parameters were statistically significant (P lt;0.05). The levels of HbA1c in the two groups were not significantly different (P gt;0.05). The change of A-FABP level was positively correlated with TNF-α, HOMA-IR and CRP, while it wasnegatively correlated with ISI.　Conclusions　 In patients with T2DM with NAFLD, there is an obvious correlation between the coexisting A-FABP rise and insulin resistance. Both of them played critical roles in the onset and developing of the disease.

引用本文： 郭琳,李強(qiáng),于萍,陳莉麗,崔璨,王薇,高萍,張巾超. 2型糖尿病合并非酒精性脂肪性肝病患者血漿脂肪細(xì)胞特異性脂肪酸結(jié)合蛋白水平的分析. 華西醫(yī)學(xué), 2011, 26(6): 815-818. doi: 復(fù)制

1. 　Leclercq I. Non-alcoholic fatty liver disease[J]. Bull Mem Acad R Med Belg, 2010, 165(3-4): 147-155.
2. 　Esteghamati A, Noshad S, Khalilzadeh O, et al. Insulin resistance is independently associated with liver aminotransferases in diabetic patients without ultrasound signs of nonalcoholic Fatty liver disease[J]. Metab Syndr Relat Disord, 2011, 9(2): 111-117.
3. 　Smith AJ, Sanders MA, Thompson BR, et al. Physical association between the adipocyte fatty acid-binding protein and hormone-sensitive lipase: a fluorescence resonance energy transfer analysis[J]. J Biol Chem. 2004, 279(50): 52399-52405.
4. 　Jin J, Peng DQ, Yuan SG, et al. Serum adipocyte fatty acid binding proteins and adiponectin in patients with coronary artery disease: the significance of A-FABP/adiponectin ratio[J]. Clin Chim Acta, 2010, 411(21-22): 1761-1765.
5. 　中華醫(yī)學(xué)會(huì)肝臟病學(xué)分會(huì)脂肪肝和酒精性肝病學(xué)組. 非酒精性脂肪肝病診斷標(biāo)準(zhǔn)[J]. 中華肝臟病雜志, 2003, 11(2): 71.
6. 　李光偉. 胰島素敏感性評估及其在臨床研究中的應(yīng)用[J]. 中華內(nèi)分泌代謝雜志, 2000, 16(3): 1981.
7. 　李光偉, 潘孝仁, Lilliojas S, 等. 檢測人群胰島素敏感性的一項(xiàng)新指數(shù)[J]. 中華內(nèi)科雜志, 1993, 32 (10): 6561.
8. 　Brunt EM. Non-alcoholic fatty liver disease: what’s new under the microscope? [J]. Gut, 2011 Feb 8, [Epub ahead of print].
9. 　Caballero F, Fernández A, De Lacy AM, et al. Enhanced free cholesterol, SREBP-2 and StAR expression in human NASH[J]. J Hepatol, 2009, 50(4): 789-796.
10. 　Kotronen A, Yki-Jarvinen H. Fatty liver: a novel component of the metabolic syndrome[J]. Arterioscler Thromb Vasc Biol, 2008, 28(1): 27-38.
11. 　Arrese M. Nonalcoholic fatty liver disease. liver disease: an overlooked complication of diabetes mellitus[J]. Nat Rev Endocrinol, 2010, 6(12): 660-661.
12. 　Ferreira DM, Castro RE, Machado MV, et al. Apoptosis and insulin resistance in liver and peripheral tissues of morbidly obese patients is associated with different stages of non-alcoholic fatty liver disease[J]. Diabetologia, 2011, 54(7): 1788-1798.
13. 　Chen SH, He F, Zhou HL, et al. Relationship between nonalcoholic fatty liver disease and metabolic syndrome[J]. J Dig Dis, 2011, 12(2): 125-130.
14. 　García-Monzón C, Lo Iacono O, Mayoral R, et al. Hepatic insulin resistance is associated with increased apoptosis and fibrogenesis in nonalcoholic steatohepatitis and chronic hepatitis C[J]. J Hepatol, 2011, 54(1): 142-152.
15. 　Xu A, Wang Y, Xu JY, et al. Adipocyte fatty acid-binding protein is a plasma biomarker closely associated with obesity and metabolic syndrome[J]. Clin Chem, 2006, 52(3): 405-413.
16. 　Tso AW, Xu A, Sham PC, et al. Serum adipocyte fatty acid binding protein as a new biomarker predicting the development of type 2 diabetes: a 10-year prospective study in a Chinese cohort[J]. Diabetes Care, 2007, 30(10): 2667-2672.
  1. 1. 　Leclercq I. Non-alcoholic fatty liver disease[J]. Bull Mem Acad R Med Belg, 2010, 165(3-4): 147-155.
  2. 2. 　Esteghamati A, Noshad S, Khalilzadeh O, et al. Insulin resistance is independently associated with liver aminotransferases in diabetic patients without ultrasound signs of nonalcoholic Fatty liver disease[J]. Metab Syndr Relat Disord, 2011, 9(2): 111-117.
  3. 3. 　Smith AJ, Sanders MA, Thompson BR, et al. Physical association between the adipocyte fatty acid-binding protein and hormone-sensitive lipase: a fluorescence resonance energy transfer analysis[J]. J Biol Chem. 2004, 279(50): 52399-52405.
  4. 4. 　Jin J, Peng DQ, Yuan SG, et al. Serum adipocyte fatty acid binding proteins and adiponectin in patients with coronary artery disease: the significance of A-FABP/adiponectin ratio[J]. Clin Chim Acta, 2010, 411(21-22): 1761-1765.
  5. 5. 　中華醫(yī)學(xué)會(huì)肝臟病學(xué)分會(huì)脂肪肝和酒精性肝病學(xué)組. 非酒精性脂肪肝病診斷標(biāo)準(zhǔn)[J]. 中華肝臟病雜志, 2003, 11(2): 71.
  6. 6. 　李光偉. 胰島素敏感性評估及其在臨床研究中的應(yīng)用[J]. 中華內(nèi)分泌代謝雜志, 2000, 16(3): 1981.
  7. 7. 　李光偉, 潘孝仁, Lilliojas S, 等. 檢測人群胰島素敏感性的一項(xiàng)新指數(shù)[J]. 中華內(nèi)科雜志, 1993, 32 (10): 6561.
  8. 8. 　Brunt EM. Non-alcoholic fatty liver disease: what’s new under the microscope? [J]. Gut, 2011 Feb 8, [Epub ahead of print].
  9. 9. 　Caballero F, Fernández A, De Lacy AM, et al. Enhanced free cholesterol, SREBP-2 and StAR expression in human NASH[J]. J Hepatol, 2009, 50(4): 789-796.
  10. 10. 　Kotronen A, Yki-Jarvinen H. Fatty liver: a novel component of the metabolic syndrome[J]. Arterioscler Thromb Vasc Biol, 2008, 28(1): 27-38.
  11. 11. 　Arrese M. Nonalcoholic fatty liver disease. liver disease: an overlooked complication of diabetes mellitus[J]. Nat Rev Endocrinol, 2010, 6(12): 660-661.
  12. 12. 　Ferreira DM, Castro RE, Machado MV, et al. Apoptosis and insulin resistance in liver and peripheral tissues of morbidly obese patients is associated with different stages of non-alcoholic fatty liver disease[J]. Diabetologia, 2011, 54(7): 1788-1798.
  13. 13. 　Chen SH, He F, Zhou HL, et al. Relationship between nonalcoholic fatty liver disease and metabolic syndrome[J]. J Dig Dis, 2011, 12(2): 125-130.
  14. 14. 　García-Monzón C, Lo Iacono O, Mayoral R, et al. Hepatic insulin resistance is associated with increased apoptosis and fibrogenesis in nonalcoholic steatohepatitis and chronic hepatitis C[J]. J Hepatol, 2011, 54(1): 142-152.
  15. 15. 　Xu A, Wang Y, Xu JY, et al. Adipocyte fatty acid-binding protein is a plasma biomarker closely associated with obesity and metabolic syndrome[J]. Clin Chem, 2006, 52(3): 405-413.
  16. 16. 　Tso AW, Xu A, Sham PC, et al. Serum adipocyte fatty acid binding protein as a new biomarker predicting the development of type 2 diabetes: a 10-year prospective study in a Chinese cohort[J]. Diabetes Care, 2007, 30(10): 2667-2672.