UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate®

胰岛素抵抗：定义及临床疾病谱

Author
Christos Mantzoros, MD, DSc
Section Editor
David M Nathan, MD
Deputy Editor
Jean E Mulder, MD
Translators
李启富, 主任医师，教授

引言

胰岛素抵抗的广义定义为机体对正常胰岛素浓度的生物反应低于正常水平。通过该定义可知，胰岛素抵抗可能涉及胰岛素在体内多种组织中的多种生物作用。但通常在临床实践中，胰岛素抵抗指的是一种状态，在该状态中某既定胰岛素浓度会产生正常水平以下的葡萄糖反应[1]。1922年引入胰岛素治疗，几年后，“胰岛素抵抗”这一术语首次被用于描述个别需要逐渐增大胰岛素剂量来控制高血糖的糖尿病患者。由于当时的治疗性胰岛素纯度不高且来源于非人类物种，大多数此类患者使用后会产生针对治疗性胰岛素的抗体，进而导致胰岛素抵抗[2]。使用重组人胰岛素治疗的患者很少产生抗胰岛素抗体，胰岛素抵抗发挥主要作用的临床疾病谱也就发生了显著的改变。胰岛素抵抗现已不被当做糖尿病治疗的罕见并发症，而被视为一组疾病，包括以下内容(表 1)：

  • 严重的胰岛素抵抗综合征，如B型胰岛素抵抗综合征(存在抗胰岛素受体[3]的自身抗体)，以及罕见的遗传性疾病，如矮妖精貌综合征(存在胰岛素受体突变[4])和脂肪营养不良状态[5]。
  • 葡萄糖耐量受损和2型糖尿病。
  • 导致继发性胰岛素抵抗的肥胖、应激、感染、尿毒症、肢端肥大症、糖皮质激素过量和妊娠。
  • 相关高胰岛素血症发病机制尚不明确的一些常见疾病，如代谢综合征、高血压、高脂血症、冠状动脉疾病、多囊卵巢综合征以及卵泡膜细胞增殖症。 (参见“代谢综合征(胰岛素抵抗综合征或X综合征)”和“成人多囊卵巢综合征的临床表现”和“卵巢卵泡膜细胞增生”)

发生胰岛素抵抗的可能机制将在别处讨论。 (参见“2型糖尿病的发病机制”)

定义及定量

胰岛素抵抗可被定义为对内源性和外源性胰岛素的葡萄糖反应均低于正常水平。

内源性胰岛素抵抗 — 血清胰岛素浓度高但血糖浓度正常或偏高可确定内源性胰岛素抵抗。在实践中，我们仅在评估具有严重胰岛素抵抗临床特征的患者时才检测其血清胰岛素水平(参见下文‘临床疾病谱’)。

            

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: 2017-06 . | This topic last updated: 2015-07-07.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
References
Top
  1. Moller DE, Flier JS. Insulin resistance--mechanisms, syndromes, and implications. N Engl J Med 1991; 325:938.
  2. Kahn CR, Rosenthal AS. Immunologic reactions to insulin: insulin allergy, insulin resistance, and the autoimmune insulin syndrome. Diabetes Care 1979; 2:283.
  3. Kahn CR, Flier JS, Bar RS, et al. The syndromes of insulin resistance and acanthosis nigricans. Insulin-receptor disorders in man. N Engl J Med 1976; 294:739.
  4. Musso C, Cochran E, Moran SA, et al. Clinical course of genetic diseases of the insulin receptor (type A and Rabson-Mendenhall syndromes): a 30-year prospective. Medicine (Baltimore) 2004; 83:209.
  5. Tsiodras S, Mantzoros C, Hammer S, Samore M. Effects of protease inhibitors on hyperglycemia, hyperlipidemia, and lipodystrophy: a 5-year cohort study. Arch Intern Med 2000; 160:2050.
  6. Steiner DF, Tager HS, Chan SJ, et al. Lessons learned from molecular biology of insulin-gene mutations. Diabetes Care 1990; 13:600.
  7. Bergman RN, Finegood DT, Ader M. Assessment of insulin sensitivity in vivo. Endocr Rev 1985; 6:45.
  8. Buchanan TA, Watanabe RM, Xiang AH. Limitations in surrogate measures of insulin resistance. J Clin Endocrinol Metab 2010; 95:4874.
  9. Tritos NA, Mantzoros CS. Clinical review 97: Syndromes of severe insulin resistance. J Clin Endocrinol Metab 1998; 83:3025.
  10. McLaughlin T, Abbasi F, Cheal K, et al. Use of metabolic markers to identify overweight individuals who are insulin resistant. Ann Intern Med 2003; 139:802.
  11. Ascaso JF, Pardo S, Real JT, et al. Diagnosing insulin resistance by simple quantitative methods in subjects with normal glucose metabolism. Diabetes Care 2003; 26:3320.
  12. Barb, D, Mantzoros, C. Diagnosing obesity, diabetes mellitus and the insulin resistance syndrome. In: Obesity and Diabetes, Mantzoros, C. (Eds), Humana Press, Inc., Totowa, NJ 2006. p.129.
  13. Taylor SI, Grunberger G, Marcus-Samuels B, et al. Hypoglycemia associated with antibodies to the insulin receptor. N Engl J Med 1982; 307:1422.
  14. Rogers DL. Acanthosis nigricans. Semin Dermatol 1991; 10:160.
  15. Poretsky L, Piper B. Insulin resistance, hypersecretion of LH, and a dual-defect hypothesis for the pathogenesis of polycystic ovary syndrome. Obstet Gynecol 1994; 84:613.
  16. Taylor SI, Dons RF, Hernandez E, et al. Insulin resistance associated with androgen excess in women with autoantibodies to the insulin receptor. Ann Intern Med 1982; 97:851.
  17. Taylor SI, Cama A, Accili D, et al. Mutations in the insulin receptor gene. Endocr Rev 1992; 13:566.
  18. Moller DE, Cohen O, Yamaguchi Y, et al. Prevalence of mutations in the insulin receptor gene in subjects with features of the type A syndrome of insulin resistance. Diabetes 1994; 43:247.
  19. Dunaif A, Hoffman AR, Scully RE, et al. Clinical, biochemical, and ovarian morphologic features in women with acanthosis nigricans and masculinization. Obstet Gynecol 1985; 66:545.
  20. Dunaif A, Segal KR, Shelley DR, et al. Evidence for distinctive and intrinsic defects in insulin action in polycystic ovary syndrome. Diabetes 1992; 41:1257.
  21. Dunaif A, Xia J, Book CB, et al. Excessive insulin receptor serine phosphorylation in cultured fibroblasts and in skeletal muscle. A potential mechanism for insulin resistance in the polycystic ovary syndrome. J Clin Invest 1995; 96:801.
  22. Cohen JC, Hickman R. Insulin resistance and diminished glucose tolerance in powerlifters ingesting anabolic steroids. J Clin Endocrinol Metab 1987; 64:960.
  23. Barbieri RL, Smith S, Ryan KJ. The role of hyperinsulinemia in the pathogenesis of ovarian hyperandrogenism. Fertil Steril 1988; 50:197.
  24. Nestler JE, Jakubowicz DJ. Decreases in ovarian cytochrome P450c17 alpha activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome. N Engl J Med 1996; 335:617.
  25. Dunaif A, Scott D, Finegood D, et al. The insulin-sensitizing agent troglitazone improves metabolic and reproductive abnormalities in the polycystic ovary syndrome. J Clin Endocrinol Metab 1996; 81:3299.
  26. Elders MJ, Schedewie HK, Olefsky J, et al. Endocrine-metabolic relationships in patients with leprechaunism. J Natl Med Assoc 1982; 74:1195.
  27. RABSON SM, MENDENHALL EN. Familial hypertrophy of pineal body, hyperplasia of adrenal cortex and diabetes mellitus; report of 3 cases. Am J Clin Pathol 1956; 26:283.
  28. Taylor SI. Lilly Lecture: molecular mechanisms of insulin resistance. Lessons from patients with mutations in the insulin-receptor gene. Diabetes 1992; 41:1473.
  29. Flier JS, Moller DE, Moses AC, et al. Insulin-mediated pseudoacromegaly: clinical and biochemical characterization of a syndrome of selective insulin resistance. J Clin Endocrinol Metab 1993; 76:1533.
  30. Flier JS, Young JB, Landsberg L. Familial insulin resistance with acanthosis nigricans, acral hypertrophy, and muscle cramps. N Engl J Med 1980; 303:970.
  31. Minaker KL, Flier JS, Landsberg L, et al. Phenytoin-induced improvement in muscle cramping and insulin action in three patients with the syndrome of insulin resistance, acanthosis nigricans, and acral hypertrophy. Arch Neurol 1989; 46:981.
  32. Fiorenza CG, Chou SH, Mantzoros CS. Lipodystrophy: pathophysiology and advances in treatment. Nat Rev Endocrinol 2011; 7:137.
  33. Björntorp P. "Portal" adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. Arteriosclerosis 1990; 10:493.
  34. Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 1993; 259:87.
  35. Ziemke F, Mantzoros CS. Adiponectin in insulin resistance: lessons from translational research. Am J Clin Nutr 2010; 91:258S.
  36. Oral EA, Simha V, Ruiz E, et al. Leptin-replacement therapy for lipodystrophy. N Engl J Med 2002; 346:570.
  37. Mantzoros CS. Whither recombinant human leptin treatment for HIV-associated lipoatrophy and the metabolic syndrome? J Clin Endocrinol Metab 2009; 94:1089.
  38. Brennan AM, Mantzoros CS. Leptin and adiponectin: their role in diabetes. Curr Diab Rep 2007; 7:1.
  39. Gavrila A, Chan JL, Yiannakouris N, et al. Serum adiponectin levels are inversely associated with overall and central fat distribution but are not directly regulated by acute fasting or leptin administration in humans: cross-sectional and interventional studies. J Clin Endocrinol Metab 2003; 88:4823.
  40. Fargnoli JL, Fung TT, Olenczuk DM, et al. Adherence to healthy eating patterns is associated with higher circulating total and high-molecular-weight adiponectin and lower resistin concentrations in women from the Nurses' Health Study. Am J Clin Nutr 2008; 88:1213.
  41. Blüher M, Williams CJ, Klöting N, et al. Gene expression of adiponectin receptors in human visceral and subcutaneous adipose tissue is related to insulin resistance and metabolic parameters and is altered in response to physical training. Diabetes Care 2007; 30:3110.
  42. Magkos F, Mantzoros CS. Body fat redistribution and metabolic abnormalities in HIV-infected patients on highly active antiretroviral therapy: novel insights into pathophysiology and emerging opportunities for treatment. Metabolism 2011; 60:749.
  43. Tsokos GC, Gorden P, Antonovych T, et al. Lupus nephritis and other autoimmune features in patients with diabetes mellitus due to autoantibody to insulin receptors. Ann Intern Med 1985; 102:176.