• 1 四川大學(xué)華西醫(yī)院內(nèi)分泌代謝科（成都，610041）;2 成都市龍泉驛區(qū)第一人民醫(yī)院內(nèi)分泌科;3 四川大學(xué)華西醫(yī)院內(nèi)分泌代謝病實驗室;

【摘要】　目的　 探討胰島素強化治療對2型糖尿?。╰ype 2 diabetes mellitus，T2DM）患者血清脂聯(lián)素（adiponectin，APN）的影響。　方法　 2007年7—12月，研究納入連續(xù)使用胰島素治療至少3個月但血糖控制欠佳[6.5%≤糖化血紅蛋白（hemoglobin A1c， HbA1c）≤11.0%]的T2DM患者40例，其中男18例，女22例；年齡29~〖JP2〗69歲；平均診斷T2DM病史11年。治療方案為進行16周的胰島素強化治療，血糖控制目標為空腹血糖≤7 mmol/L，〖JP〗餐后2 h血糖≤8 mmol/L。分別于強化治療前、強化治療4周后及強化治療16周后測定HbA1c以及血清APN水平。　結(jié)果　 與強化治療前相比，胰島素治療4周后空腹及三餐后2 h血糖明顯下降（P lt;0.05），但HbA1c和血清APN水平差異無統(tǒng)計學(xué)意義（P gt;0.05）；強化16周后，HbA1c水平明顯低于治療前和治療4周后且差異具有統(tǒng)計學(xué)意義（P lt;0.05），APN水平高于治療前和治療4周后且差異有統(tǒng)計學(xué)意義（P lt;0.05）。體質(zhì)量指數(shù)在強化治療16周后明顯增加且與強化治療前和強化治療后4周相比差異具有統(tǒng)計學(xué)意義（P lt;0.05）。APN與空腹血糖（b=-0.225，P=0.013）、早餐后2 h血糖（b=-0.229，P=0.012）呈負相關(guān)。　結(jié)論　 胰島素強化治療可以提高T2DM患者血清APN水平。
【Abstract】　Objective　 To investigate the effect of intensive insulin therapy on serum adiponectin (APN) level in patients with type 2 diabetes mellitus (T2DM).　Methods　 Forty patients with T2DM who had undergone insulin therapy for at least three months but with their blood glucose poorly controlled [glycosylated hemoglobin Alc (HbA1c) level ranged from 6.5% to 10.0%] from July to December 2007 were enrolled in this study. There were 18 males and 22 females with their age ranged from 29 to 69 years. They had an average time of T2DM history of 11 years. Intensive insulin therapy was carried out for 16 weeks with a target of less than 7 mmol/L for fasting blood glucose and 8 mmol/L for postprandial blood glucose. HbA1c and serum adiponectin concentrations were detected at baseline, at week 4 after intensive therapy and at the end of the study.　Results　 After 4 weeks of intensive blood glucose control, fasting and postprandial blood glucose levels decreased significantly (P lt;0.05), but the HbA1c and serum APN concentrations did not reduce remarkably (P gt;0.05). After 16 weeks of treatment, the level of HbA1c was significantly lower than those at baseline and 4 weeks after treatment (P lt;0.05), and serum APN concentration increased significantly (P lt;0.05), compared with those two time points. However, an evident increase of body mass index (BMI) was found while compared with BMI at baseline and 4 weeks after treatment (P lt;0.05). The linear regression analysis indicated that APN was negatively associated with fasting blood glucose (b=-0.225,P=0.013) and blood glucose level 2 hours after breakfast (b=-0.229,P=0.012).　Conclusion　 Intensive insulin therapy can improve serum adiponectin level in type-2 diabetic patients.

引用本文： 崔利娜,余婷婷,王椿,鐘莉,張祥迅,龍洋,喻紅玲,冉興無. 胰島素強化治療對2型糖尿病患者血清脂聯(lián)素的影響. 華西醫(yī)學(xué), 2011, 26(6): 823-827. doi: 復(fù)制

1. 　The Diabetes Control and Complications Trial Research Group. The relationship of glycemic exposure (HbA1c) to the risk of development and progression of retinopathy in the diabetes control and complications trial[J]. Diabetes, 1995, 44(8): 968-983.
2. 　UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34)[J]. Lancet, 1998, 352(9131): 854-865.
3. 　ADVANCE Collaborative Group, Patel A, MacMahon S, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes[J]. N Engl J Med, 2008, 358(24): 2560-2572.
4. 　Duckworth W, Abraira C, Moritz T, et al. Glucose control and vascular complications in veterans with type 2 diabetes[J]. N Engl J Med, 2009, 360(2): 129-139.
5. 　ACCORD Study Group, Gerstein HC, Miller ME, et al. Long-term effects of intensive glucose lowering on cardiovascular outcomes[J]. N Engl J Med, 2011, 364(9): 818-828.
6. 　Ziegler D. Type 2 diabetes as an inflammatory cardiovascular disorder[J]. Curr Mol Med, 2005, 5(3): 309-322.
7. 　Weyer C, Funahashi T, Tanaka S, et al. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia[J]. J Clin Endocrinol Metab, 2001, 86(5): 1930-1935.
8. 　Daimon M, Oizumi T, Saitoh T, et al. Decreased serum levels of adiponectin are a risk factor for the progression to type 2 diabetes in the Japanese Population: the Funagata study[J]. Diabetes Care, 2003, 26(7): 2015-2020.
9. 　Lindsay RS, Funahashi T, Hanson RL, et al. Adiponectin and development of type 2 diabetes in the Pima Indian population[J]. Lancet, 2002, 360(9326): 57-58.
10. 　Spranger J, Kroke A, Möhlig M, et al. Adiponectin and protection against type 2 diabetes mellitus[J]. Lancet, 2003, 361(9353): 226-228.
11. 　張春秀, 張喜鳳, 石紅蕾, 等. 胰島素強化治療對2型糖尿病兒童血清脂聯(lián)素與胰島素抵抗的影響[J]. 實用兒科臨床雜志, 2009, 24(20): 1620-1621.
12. 　郭紅霞, 任巧華, 王戰(zhàn)建, 等. 胰島素泵強化治療對初診2型糖尿病血清內(nèi)脂素、脂聯(lián)素的影響[J]. 臨床薈萃, 2009, 24(20): 1816-1818.
13. 　Knobler H, Benderly M, Boyko V, et al. Adiponectin and the development of diabetes in patients with coronary artery disease and impaired fasting glucose[J]. Eur J Endocrinol, 2006, 154(1): 87-92.
14. 　Berg AH, Scherer PE. Adipose tissue, inflammation, and cardiovascular disease[J]. Circ Res, 2005, 96(9): 939-949.
15. 　Combs TP, Berg AH, Obici S, et al. Endogenous glucose production is inhibited by the adipose-derived protein Acrp30[J]. J Clin Invest, 2001, 108(12): 1875-1881.
16. 　Kurzer E, Leveillee R, Bird V. Obesity as a risk factor for complications during laparoscopic surgery for renal cancer: Multivariate analysis[J]. J Endourol, 2006, 20(10): 794-799.
17. 　Takahashi M, Arita Y, Yamagata K, et al. Genomic structure and mutations in adiposespeci?c gene, adiponectin[J]. Int J Obes Relat Metab Disord, 2000, 24(7): 861-868.
18. 　Kissebah AH, Sonnenberg GE, Myklebust J, et al. Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of the metabolic syndrome[J]. Proc Natl Acad Sci USA, 2000, 97(26): 14478-14483.
19. 　Stumvoll M, Tschritter O, Fritsche A, et al. Association of the T-G polymorphism in adiponectin (exon 2) with obesity and insulin sensitivity: interaction with family history of type 2 diabetes[J]. Diabetes, 2002, 51(1): 37-41.
20. 　Stefan N, Vozarova B, Funahashi T, et al. Plasma adiponectin concentration is associated with skeletal muscle insulin receptor tyrosine phosphorylation, and low plasma concentration precedes a decrease in whole-body insulin sensitivity in humans[J]. Diabetes, 2002, 51(6): 1884-1888.
21. 　Ouchi N, Kihara S, Arita Y, et al. Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages[J]. Circulation, 2001, 103(8): 1057-1063.
22. 　Yamauchi T, Kamon J, Waki H, et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity[J]. Nat Med, 2001, 7(8): 941-946.
23. 　Hernandez-Morante JJ, Milagro FI, Lujan JA, et al. Insulin effect on adipose tissue (AT) adiponectin expression is regulated by the insulin resistance status of the patients[J]. Clin Endocrinol (Oxf), 2008, 69(3): 412-417.
24. 　Festa A, D’Agostino R Jr, Tracy RP, et al. Elevated levels of acute phase proteins and plasminogen activeat or inhibitor-1 predict the development of type 2 diabetes: the insulin resistance atherosclerosis study[J]. Diabetes, 2002, 51(4): 1131-1137.
25. 　Dandona P, Aljada A, Mohanty P, et al. Insulin inhibits intranuclear nuclear factor kappa B and stimulates Ikappa B in mononuclear calls in obse subjects: evidence for an anti-inflammatory effect[J]. J Clin Endocrinol Metab, 2001, 86(7): 3257-3265.
  1. 1. 　The Diabetes Control and Complications Trial Research Group. The relationship of glycemic exposure (HbA1c) to the risk of development and progression of retinopathy in the diabetes control and complications trial[J]. Diabetes, 1995, 44(8): 968-983.
  2. 2. 　UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34)[J]. Lancet, 1998, 352(9131): 854-865.
  3. 3. 　ADVANCE Collaborative Group, Patel A, MacMahon S, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes[J]. N Engl J Med, 2008, 358(24): 2560-2572.
  4. 4. 　Duckworth W, Abraira C, Moritz T, et al. Glucose control and vascular complications in veterans with type 2 diabetes[J]. N Engl J Med, 2009, 360(2): 129-139.
  5. 5. 　ACCORD Study Group, Gerstein HC, Miller ME, et al. Long-term effects of intensive glucose lowering on cardiovascular outcomes[J]. N Engl J Med, 2011, 364(9): 818-828.
  6. 6. 　Ziegler D. Type 2 diabetes as an inflammatory cardiovascular disorder[J]. Curr Mol Med, 2005, 5(3): 309-322.
  7. 7. 　Weyer C, Funahashi T, Tanaka S, et al. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia[J]. J Clin Endocrinol Metab, 2001, 86(5): 1930-1935.
  8. 8. 　Daimon M, Oizumi T, Saitoh T, et al. Decreased serum levels of adiponectin are a risk factor for the progression to type 2 diabetes in the Japanese Population: the Funagata study[J]. Diabetes Care, 2003, 26(7): 2015-2020.
  9. 9. 　Lindsay RS, Funahashi T, Hanson RL, et al. Adiponectin and development of type 2 diabetes in the Pima Indian population[J]. Lancet, 2002, 360(9326): 57-58.
  10. 10. 　Spranger J, Kroke A, Möhlig M, et al. Adiponectin and protection against type 2 diabetes mellitus[J]. Lancet, 2003, 361(9353): 226-228.
  11. 11. 　張春秀, 張喜鳳, 石紅蕾, 等. 胰島素強化治療對2型糖尿病兒童血清脂聯(lián)素與胰島素抵抗的影響[J]. 實用兒科臨床雜志, 2009, 24(20): 1620-1621.
  12. 12. 　郭紅霞, 任巧華, 王戰(zhàn)建, 等. 胰島素泵強化治療對初診2型糖尿病血清內(nèi)脂素、脂聯(lián)素的影響[J]. 臨床薈萃, 2009, 24(20): 1816-1818.
  13. 13. 　Knobler H, Benderly M, Boyko V, et al. Adiponectin and the development of diabetes in patients with coronary artery disease and impaired fasting glucose[J]. Eur J Endocrinol, 2006, 154(1): 87-92.
  14. 14. 　Berg AH, Scherer PE. Adipose tissue, inflammation, and cardiovascular disease[J]. Circ Res, 2005, 96(9): 939-949.
  15. 15. 　Combs TP, Berg AH, Obici S, et al. Endogenous glucose production is inhibited by the adipose-derived protein Acrp30[J]. J Clin Invest, 2001, 108(12): 1875-1881.
  16. 16. 　Kurzer E, Leveillee R, Bird V. Obesity as a risk factor for complications during laparoscopic surgery for renal cancer: Multivariate analysis[J]. J Endourol, 2006, 20(10): 794-799.
  17. 17. 　Takahashi M, Arita Y, Yamagata K, et al. Genomic structure and mutations in adiposespeci?c gene, adiponectin[J]. Int J Obes Relat Metab Disord, 2000, 24(7): 861-868.
  18. 18. 　Kissebah AH, Sonnenberg GE, Myklebust J, et al. Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of the metabolic syndrome[J]. Proc Natl Acad Sci USA, 2000, 97(26): 14478-14483.
  19. 19. 　Stumvoll M, Tschritter O, Fritsche A, et al. Association of the T-G polymorphism in adiponectin (exon 2) with obesity and insulin sensitivity: interaction with family history of type 2 diabetes[J]. Diabetes, 2002, 51(1): 37-41.
  20. 20. 　Stefan N, Vozarova B, Funahashi T, et al. Plasma adiponectin concentration is associated with skeletal muscle insulin receptor tyrosine phosphorylation, and low plasma concentration precedes a decrease in whole-body insulin sensitivity in humans[J]. Diabetes, 2002, 51(6): 1884-1888.
  21. 21. 　Ouchi N, Kihara S, Arita Y, et al. Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages[J]. Circulation, 2001, 103(8): 1057-1063.
  22. 22. 　Yamauchi T, Kamon J, Waki H, et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity[J]. Nat Med, 2001, 7(8): 941-946.
  23. 23. 　Hernandez-Morante JJ, Milagro FI, Lujan JA, et al. Insulin effect on adipose tissue (AT) adiponectin expression is regulated by the insulin resistance status of the patients[J]. Clin Endocrinol (Oxf), 2008, 69(3): 412-417.
  24. 24. 　Festa A, D’Agostino R Jr, Tracy RP, et al. Elevated levels of acute phase proteins and plasminogen activeat or inhibitor-1 predict the development of type 2 diabetes: the insulin resistance atherosclerosis study[J]. Diabetes, 2002, 51(4): 1131-1137.
  25. 25. 　Dandona P, Aljada A, Mohanty P, et al. Insulin inhibits intranuclear nuclear factor kappa B and stimulates Ikappa B in mononuclear calls in obse subjects: evidence for an anti-inflammatory effect[J]. J Clin Endocrinol Metab, 2001, 86(7): 3257-3265.