Advertisement

Syndromes of Extreme Insulin Resistance

  • George GrunbergerEmail author
  • Anjana Myneni
  • Bianca Alfonso
Reference work entry

Abstract

This group of syndromes shares severe insulin resistance and hyperinsulinemia with variable clinical manifestations (Kahn et al., N Engl J Med 294:739–745, 1976; Moller and Flier, N Engl J Med 325:938–948, 1991). Attention has been paid to these rare disorders because they provide insight into several aspects of insulin action at the molecular level and advance our understanding of the more common insulin-resistant disorders, such as polycystic ovarian syndrome (Barbieri et al., Fertil Steril 50:197–202, 1988) and type 2 diabetes mellitus (Barroso et al., Nature 402:880–883, 1999).

Keywords

Insulin resistance Hyperinsulinemia Plasma glucose Glucose tolerance test Serum insulin HOMA Glucose homeostasis Lipoatrophy Acanthosis nigricans Lipodystrophic Rabson-Mendenhall Thiazolidinediones Insulin Immunomodulation Chromium 

References

  1. 1.
    Kahn CR, Flier JS, Bar RS, et al. The syndrome of insulin resistance and acanthosis nigricans: insulin receptor disorders in man. N Engl J Med. 1976;294:739–45.PubMedCrossRefGoogle Scholar
  2. 2.
    Moller DE, Flier JS. Insulin resistance: mechanisms, syndromes, and implications. N Engl J Med. 1991;325:938–48.PubMedCrossRefGoogle Scholar
  3. 3.
    Barbieri RL, Smith S, Ryan KJ, et al. The role of hyperinsulinemia in the pathogenesis of ovarian hyperandrogenism. Fertil Steril. 1988;50:197–202.PubMedCrossRefGoogle Scholar
  4. 4.
    Barroso I, Curnell M, Crowley VE, et al. Dominant negative mutation in human PPAR gamma associated with severe insulin resistance, diabetes mellitus, and hypertension. Nature. 1999;402:880–3.PubMedGoogle Scholar
  5. 5.
    Borai A, Livingstone C, Ferns GA. The biochemical assessment of insulin resistance. Ann Clin Biochem. 2007;44:324–42.PubMedCrossRefGoogle Scholar
  6. 6.
    Tritos NA, Mantzoros CS. Syndromes of severe insulin resistance. J Clin Endocrinol Metab. 1998;83(9):3025–30.PubMedCrossRefGoogle Scholar
  7. 7.
    Legro RS, Finegood D, Dunaif A. A fasting glucose to insulin ratio is a useful measure of insulin sensitivity in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 1998;83:2694–8.PubMedGoogle Scholar
  8. 8.
    Vanhala P, Vanhala M, Kumpusalo E, et al. The quantitative insulin sensitivity check index QUICKI predicts the onset of type 2 diabetes better than fasting plasma insulin in obese subjects: a 5 year follow up study. J Clin Endocrinol Metab. 2002;87:5834–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Lee S, Choi S, Kim HJ, et al. Cut-off measures of surrogate measures of insulin resistance for metabolic syndrome in Korean non-diabetic adults. J Korean Med Sci. 2006;21:695–700.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Rabasa-Lhoret R, Bastard JP, Jan V, et al. Modified quantitative insulin sensitivity check index is better correlated to hyperinsulinemic glucose clamp than other fasting-based index of insulin sensitivity in different insulin resistant states. J Clin Endocrinol Metab. 2003;88:4917–23.PubMedCrossRefGoogle Scholar
  11. 11.
    Collinet M, Berthelon M, Benit P, et al. Familial hyperinsulinemia due to a mutation substituting histidine for arginine at position 65 in proinsulin: identification of the mutation by restriction enzyme mapping. Eur J Pediatr. 1998;157:450–60.CrossRefGoogle Scholar
  12. 12.
    Haned M, Polonsky KS, Bergenstal RM, et al. Familial hyperinsulinaemia due to a structurally abnormal insulin. Definition of an emerging new clinical syndrome. N Engl J Med. 1984;310:1288–94.CrossRefGoogle Scholar
  13. 13.
    Vinik A, Bell G. Mutant insulin syndromes. Horm Metab Res. 1988;20(1):1–10.PubMedCrossRefGoogle Scholar
  14. 14.
    Steiner DF, Tager HS, Chan SJ, et al. Lessons learned from molecular biology of insulin-gene mutations. Diabetes Care. 1990;13(6):600–9.PubMedCrossRefGoogle Scholar
  15. 15.
    Duckworth WC, Bennit RG, Hamel FG. Insulin degradation: progress and potential. Endocr Rev. 1998;19:608–24.PubMedGoogle Scholar
  16. 16.
    Francis A, Hanning I, Alberti KG. The influence of insulin antibody levels on the plasma profile and action of subcutaneously injected human and bovine short acting insulins. Diabetologia. 1985;28:330–4.PubMedCrossRefGoogle Scholar
  17. 17.
    Taylor SI, Grunberger G, Marcus-Samuels B, et al. Hypoglycemia associated with antibodies to the insulin receptor. N Engl J Med. 1982;307:1422–6.PubMedCrossRefGoogle Scholar
  18. 18.
    Virkamaki A, Ueki K, Kahn CR. Protein–protein interaction in insulin signaling and the molecular mechanisms of insulin resistance. J Clin Invest. 1999;103:931–43.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Gorden P, Carpentier JL, Frechet PO, et al. Internalization of polypeptide hormones: mechanism, intracellular localization and significance. Diabetologia. 1980;18:263–74.PubMedCrossRefGoogle Scholar
  20. 20.
    Grunberger G, Robert A, Carpentier JL, et al. Human circulating monocytes internalize 125I-insulin in a similar fashion to rat hepatocytes: relevance to receptor regulation in target and non-target tissue. J Lab Clin Med. 1985;106:211–7.PubMedGoogle Scholar
  21. 21.
    Flier JS, Minaker KL, Landsburg L, et al. Impaired in vivo insulin clearance in patients with target cell resistance to insulin. Diabetes. 1982;31:132–5.PubMedCrossRefGoogle Scholar
  22. 22.
    Flier JS. Metabolic importance of acanthosis nigricans. Arch Derm. 1985;121:193–4.PubMedCrossRefGoogle Scholar
  23. 23.
    Cruz PD, Hud JA. Excess insulin binding to insulin-like growth factor receptors: proposed mechanism for acanthosis nigricans. J Invest Dermatol. 1992;98(Suppl):82S–5.PubMedCrossRefGoogle Scholar
  24. 24.
    Fradkin JE, Eastman RC, Lesniak MA, et al. Specificity spillover at the hormone receptor: exploring its role in human disease. N Engl J Med. 1989;320:640–5.PubMedCrossRefGoogle Scholar
  25. 25.
    Rotman-Pikielny P, Andewelt A, Ozyavuzligil A, et al. Polycystic ovarian syndrome (PCOS): lessons from patients with severe insulin resistance syndromes. The Endocrine Society’s 83rd annual meeting; 2001. p. 80.Google Scholar
  26. 26.
    Premkumar A, Chow C, Bhandarkar P, et al. Lipoatrophic lipodystrophic syndromes – the spectrum of findings on MR imaging. AJR. 2002;178:311–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Cauble MS, Gilroy R, Sorrel MF, et al. Lipoatrophic diabetes and end-stage liver disease secondary to nonalcoholic steatohepatitis with recurrence after liver transplantation. Transplantation. 2001;71:892–5.PubMedCrossRefGoogle Scholar
  28. 28.
    Garg A. Acquired and inherited lipodystrophies. N Engl J Med. 2004;350(12):1220–34.PubMedCrossRefGoogle Scholar
  29. 29.
    Garg A, Wilson R, Barnes R, et al. A gene for congenital generalized lipodystrophy maps to human chromosome 9q34. J Clin Endocrinol Metab. 1999;84:3390–4.PubMedCrossRefGoogle Scholar
  30. 30.
    Magre J, Delepine M, Khallouf E, et al. Identification of the gene altered in Berardinelli-Seip congenital lipodystrophy on chromosome 11q13. Nat Genet. 2001;28:365–70.PubMedCrossRefGoogle Scholar
  31. 31.
    Peters JM, Barnes R, Bennet L, et al. Localization the gene for familial partial lipodystrophy (Dunnigan Variety) to chromosome 1q21-22. Nat Genet. 1998;18:292–5.PubMedCrossRefGoogle Scholar
  32. 32.
    Jackson SN, Pinkey J, Bargiotta A, et al. A defect in the regional deposition of adipose tissue (partial lipodystrophy) is encoded by a gene at chromosome 1q. Am J Hum Genet. 1998;63:534–40.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Cao H, Hegele RA. Nuclear lamin A/C R482Q mutations in Canadian kindreds with Dunnigan type familial partial lipodystrophy. Hum Mol Genet. 2000;9:109–12.PubMedCrossRefGoogle Scholar
  34. 34.
    Garg A, Vinaitheerthan M, Weatherall PT, et al. Phenotypic heterogeneity in patients with familial partial lipodystrophy (Dunnigan variety) related to the site of missense mutations in lamin A/C gene. J Clin Endocrinol Metab. 2001;86:59–65.PubMedGoogle Scholar
  35. 35.
    Simha V, Garg A. Body fat distribution and metabolic derangements in patients with familial partial lipodystrophy associated with mandibuloacral dysplasia. J Clin Endocrinol Metab. 2002;87:776–85.PubMedCrossRefGoogle Scholar
  36. 36.
    Simha V, Agarwal AK, Oral EA, Fryns J-P, Garg A, et al. Genetic and phenotypic heterogeneity in patients with mandibuloacral dysplasia-associated lipodystrophy. J Clin Endocrinol Metab. 2003;88:2821–4.PubMedCrossRefGoogle Scholar
  37. 37.
    Agarwal AK, Garg A. A novel heterozygous mutation in peroxisome proliferator-activated receptor-gamma gene in a patient with familial partial lipodystrophy. J Clin Endocrinol Metab. 2002;87:408–11.PubMedGoogle Scholar
  38. 38.
    Savage DB, Tan GD, Acerini CL, et al. Human metabolic syndrome resulting from dominant-negative mutations in the nuclear receptor peroxisome proliferator-activated receptor-gamma. Diabetes. 2003;52:910–7.PubMedCrossRefGoogle Scholar
  39. 39.
    George S, Rochford JJ, Wolfrum C, et al. A family with severe insulin resistance and diabetes due to a mutation in AKT2. Science. 2004;304:1325–8.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Misra A, Garg A. Clinical features and metabolic derangements in acquired generalized lipodystrophy: case reports and review of the literature. Medicine (Baltimore). 2003;82:129–46.CrossRefGoogle Scholar
  41. 41.
    Haque WA, Shimomura I, Matsuzawa Y, Garg A. Serum adiponectin and leptin levels in patients with lipodystrophies. J Clin Endocrinol Metab. 2002;87:2395–8.PubMedCrossRefGoogle Scholar
  42. 42.
    Billings JK, Milgraum SS, Gupta AK, et al. Lipoatrophic panniculitis: a possible autoimmune inflammatory disease of fat report of three cases. Arch Dermatol. 1987;123:1662–6.PubMedCrossRefGoogle Scholar
  43. 43.
    Hubler A, Abendroth K, Keiner T, et al. Dysregulation of insulin-like growth factors in a case of generalized acquired lipoatrophic diabetes mellitus (Lawrence syndrome) connected with autoantibodies against adipocytes membranes. Exp Clin Endocrinol Diabetes. 1998;106:79–84.PubMedCrossRefGoogle Scholar
  44. 44.
    Garg A. Lipodystrophies. Am J Med. 2000;108:143–52.PubMedCrossRefGoogle Scholar
  45. 45.
    Jasin HE. Systemic lupus erythematosus, partial lipodystrophy and hypocomplementemia. J Rheumatol. 1979;6:43–50.PubMedGoogle Scholar
  46. 46.
    Torrelo A, Espana A, Boixeda P, Ledo A. Partial lipodystrophy and dermatomyositis. Arch Dermatol. 1991;127:1846–7.PubMedCrossRefGoogle Scholar
  47. 47.
    Mathieson PW, Wurzner R, Oliveria DB, et al. Complement mediated adipocytes lysis by nephritic factor sera. J Exp Med. 1993;177:1827–31.PubMedCrossRefGoogle Scholar
  48. 48.
    Chen D, Misra A, Garg A. Lipodystrophy in human immunodeficiency virus-infected patients. J Clin Endocrinol Metab. 2002;87:4845–56.PubMedCrossRefGoogle Scholar
  49. 49.
    Tsiodras S, Mantzoros C, Hammer S, et al. Effects of protease inhibitors on hyperglycemia, hyperlipidemia and lipodystrophy. A five-year cohort study. Arch Intern Med. 2000;160:2050–6.PubMedCrossRefGoogle Scholar
  50. 50.
    Van Der Valk M, Gisolf EH, Reiss P, et al. Increased risk of lipodystrophy when nucleoside analogue reverse transcriptase inhibitors are included with protease inhibitors in the treatment of HIV infection. AIDS. 2001;15:847–55.PubMedCrossRefGoogle Scholar
  51. 51.
    Panse I, Vasseur E, Raffin-Manson ML, et al. Lipodystrophy associated with protease inhibitors. Br J Dermatol. 2000;142:496–500.PubMedCrossRefGoogle Scholar
  52. 52.
    Caron M, Auclair M, Vigouroux C, et al. The HIV protease inhibitor indinavir impairs sterol regulatory element-binding protein-1 intranuclear localization, inhibits preadipocyte differentiation, and induces insulin resistance. Diabetes. 2001;50:1378–88.PubMedCrossRefGoogle Scholar
  53. 53.
    Dowell P, Flexner C, Kwiterovich PO, et al. Suppression of preadipocyte differentiation and promotion of adipocytes death by HIV protease inhibitors. J Biol Chem. 2000;275:41325–32.PubMedCrossRefGoogle Scholar
  54. 54.
    Murata H, Hruz PW, Mueckler M. The mechanism of insulin resistance caused by HIV protease inhibitor therapy. J Biol Chem. 2000;275:20251–4.PubMedCrossRefGoogle Scholar
  55. 55.
    Meyer MM, Schuett M, Jost P, et al. Indinavir decreases insulin-stimulated phosphatidylinositol 3-kinase activity and stimulates leptin secretion in human adipocytes. Diabetes. 2001;50 Suppl 2:A414.Google Scholar
  56. 56.
    Bastard JP, Caron M, Vidal H, et al. Association between altered expression of adipogenic factor SREBP1 in lipoatrophic adipose tissue from HIV-1-infected patients and abnormal adipocyte differentiation and insulin resistance. Lancet. 2002;359:1026–31.PubMedCrossRefGoogle Scholar
  57. 57.
    Shimomura I, Hammer RE, Richardson JA, et al. Insulin resistance and diabetes mellitus in transgenic mice expressing nuclear SREBP-1c in adipose tissue: model for congenital generalized lipodystrophy. Genes Dev. 1998;12:3182–94.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    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;76:1533–41.PubMedGoogle Scholar
  59. 59.
    Martin XD, Zenobi PD. Type A syndrome of insulin resistance: anterior chamber anomalies of the eye and effects of insulin-like growth factor-1 on the retina. Ophthalmologica. 2001;215:117–23.PubMedCrossRefGoogle Scholar
  60. 60.
    Grunberger G, Zick Y, Gorden P. Defect in phosphorylation of insulin receptors in cells from an insulin-resistant patient with normal insulin binding. Science. 1984;223:832–934.CrossRefGoogle Scholar
  61. 61.
    Young J, Morbois-Trabut L, Couzinet B, et al. Type A insulin resistance syndrome revealing a novel lamin A mutation. Diabetes. 2005;54:1873–8.PubMedCrossRefGoogle Scholar
  62. 62.
    Maddux BA, Goldfine ID. Membrane glycoprotein PC-1 inhibition of insulin receptor function occurs via direct interaction with receptor alpha subunit. Diabetes. 2000;49:13–9.PubMedCrossRefGoogle Scholar
  63. 63.
    Krook A, Kumar S, et al. Molecular scanning of the insulin receptor gene in syndromes of insulin resistance. Diabetes. 1994;43:357–68.PubMedCrossRefGoogle Scholar
  64. 64.
    Moreira RO, Zagury RL, et al. Multidrug therapy in a patient with Rabson-Mendenhall syndrome. Diabetologia. 2010;53:2454–5.PubMedCrossRefGoogle Scholar
  65. 65.
    Thiel CT, Knebel B, Knerr I, et al. Two novel mutations in the insulin binding subunit of the insulin receptor gene without insulin binding impairment in a patient with Rabson-Mendenhall syndrome. Mol Genet Metab. 2008;94:356–62.PubMedCrossRefGoogle Scholar
  66. 66.
    Tuthill A, Semple RK, Day R, et al. Functional characterization of a novel insulin receptor mutation contributing to Rabson- Mendenhall syndrome. Clin Endocrinol. 2007;661:21–6.Google Scholar
  67. 67.
    Kim D, Cho SY, et al. Two novel insulin receptor gene mutations in a patient with Rabson- Mendenhall syndrome: the first Korean case confirmed by biochemical, and molecular evidence. J Korean Med Sci. 2012;27:565–8.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Mohanan S, Chandrashekar L, et al. Rabson-Mendenhall syndrome with recurrent cerebral infarcts caused by a novel INSR mutation. Int J Dermatol. 2013;52:182–5.PubMedCrossRefGoogle Scholar
  69. 69.
    Dutta D, Maisnam I, et al. Syndrome of extreme insulin resistance (Rabson- Mendenhall Phenotype) with atrial septal defect: clinical presentation and treatment outcomes. J Clin Res Pediatr Endocrinol. 2013;5(1):58–61.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Flier JS, Kahn CR, Roth J, et al. Antibodies that impair insulin receptor binding in an unusual diabetic syndrome with severe insulin resistance. Science. 1975;190:63–5.PubMedCrossRefGoogle Scholar
  71. 71.
    Arioglu E, Andewelt A, Diabo C, et al. Clinical course of autoantibody to the insulin receptor syndrome. The Endocrine Society’s 83rd annual meeting; 2001. p. 113.Google Scholar
  72. 72.
    Flier JS, Bar RS, Muggeo M, et al. The evolving clinical course of patients with insulin receptor autoantibodies: spontaneous remission or receptor proliferation with hypoglycemia. J Clin Endocrinol Metab. 1978;47:985–95.PubMedCrossRefGoogle Scholar
  73. 73.
    Bar RS, Levis WR, Rechler MM, et al. Extreme insulin resistance in ataxia telangiectasia: defect in affinity of insulin receptors. N Engl J Med. 1978;298:1164–71.PubMedCrossRefGoogle Scholar
  74. 74.
    Gama MPR, Jonasson TH, et al. Extreme insulin-resistance syndrome associated with alpha-1 antitrypsin deficiency. Endocrinologist. 2010;20:137–40.CrossRefGoogle Scholar
  75. 75.
    Burant CF, Sreenan S, Hirano K, et al. Troglitazone action is independent of adipose tissue. J Clin Invest. 1997;100:2900–8.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Arioglu E, Duncan-Morin J, Sebring N, et al. Efficacy and safety of troglitazone in the treatment of lipodystrophy syndrome. Ann Int Med. 2000;133:263–74.PubMedCrossRefGoogle Scholar
  77. 77.
    Hadigan C, Corcoran C, Basgoz N, et al. Metformin in the treatment of HIV lipodystrophy syndrome. JAMA. 2000;284:472–7.PubMedCrossRefGoogle Scholar
  78. 78.
    Di Paolo S. Metformin ameliorates extreme insulin resistance in a patient with anti-insulin receptor antibodies: description of insulin receptor and postreceptor effects in vivo and vitro. Acta Endocrinol. 1992;126:117–23.PubMedGoogle Scholar
  79. 79.
    Rique S, Ibanez L, Marcos MV, et al. Effect of metformin on androgen and insulin concentration in type A insulin resistance syndrome. Diabetologia. 2000;43:385–6.PubMedCrossRefGoogle Scholar
  80. 80.
    Dailey AM, Tannock LR. Extreme insuli resistance: indication and approaches to the use of u-500 insulin in type 2 diabetes mellitus. Curr Diab Rep. 2011;11:77–82.PubMedCrossRefGoogle Scholar
  81. 81.
    Nakae J, Kato M, Murashita M, et al. Long-term effect of recombinant human insulin-like growth factor1 on metabolic and growth control in a patient with leprechaunism. J Clin Endocrinol Metab. 1998;83:542–9.PubMedCrossRefGoogle Scholar
  82. 82.
    Morrow LA, O’Brien MB, Moller DE, et al. Recombinant human insulin like growth factor-1 therapy improves glycemic control and insulin action in type A syndrome insulin resistance. J Clin Endocrinol Metabol. 1994;79:205–10.Google Scholar
  83. 83.
    Quin JD, Fisher BM, Paterson KR, et al. Acute response to recombinant insulin-like growth factor 1 in a patient with Mendenhall’s syndrome. N Engl J Med. 1990;323:1425–6.PubMedCrossRefGoogle Scholar
  84. 84.
    Yamamoto T, Sato T, Mori T, et al. Clinical efficacy of insulin like growth factor 1 in a patient with auto-antibodies to insulin receptors: a case report. Diabetes Res Clin Pract. 2000;49:65–9.PubMedCrossRefGoogle Scholar
  85. 85.
    Torres RA, Unger KW, Cadman JA, et al. Recombinant human growth hormone improves truncal adiposity and buffalo humps in HIV positive patients on HAART. AIDS. 1999;13:2479–81.PubMedCrossRefGoogle Scholar
  86. 86.
    Schwarz JM, Mulligan K, Lee J, et al. Effects of recombinant human growth hormone on hepatic lipid and carbohydrate metabolism in HIV-infected patients with fat accumulation. J Clin Endocrinol Metab. 2002;87:942–5.PubMedCrossRefGoogle Scholar
  87. 87.
    Kramer N, Rosenstien ED, Schneider G. Refractory hyperglycemia complicating an evolving connective tissue disease: response to cyclosporin. J Rheumatol. 1998;25:816–8.PubMedGoogle Scholar
  88. 88.
    Eriksson JW, Bremell T, Eliasson B, et al. Successful treatment with plasmapheresis, cyclophosphamide, and cyclosporin A in type B syndrome of insulin resistance. Case report. Diabetes Care. 1998;21:1217–20.PubMedCrossRefGoogle Scholar
  89. 89.
    Manikas ED, Isaac I, et al. Successful treatment of Type B insulin resistance with rituximab. J Clin Endocrinol Metab. 2015;100:1719–22.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Coll AP, Thimas S, Mufti GJ. Rituximab therapy for the type B syndrome of severe insulin resistance. N Engl J Med. 2004;350:310–1.PubMedCrossRefGoogle Scholar
  91. 91.
    Malek R, Chong AY, Lupsa BC, et al. Treatment of type B insulin resistance: a novel approach to reduce insulin receptor autoantibodies. J Clin Endocrinol Metab. 2010;95:3641–7.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Gavrilova O, Marcus-Samuels B, Graham D, et al. Surgical implantation of adipose tissue reverses diabetes in lipotropic mice. J Clin Invest. 2000;105:271–8.PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Shimomura I, Hammer RE, Ikemoto S, et al. Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy. Nature. 1999;401:73–6.PubMedCrossRefGoogle Scholar
  94. 94.
    Reitman ML, Gavrilova O. A-ZIP/F-1 mice lacking white fat: a model for understanding lipoatrophic diabetes. Int J Obes Relat Metab Disord. 2000;24 Suppl 4:S11–4.PubMedCrossRefGoogle Scholar
  95. 95.
    Oral EA, Simha V, Ruiz E, et al. Leptin-replacement therapy for lipodystrophy. N Engl J Med. 2002;346:570–8.PubMedCrossRefGoogle Scholar
  96. 96.
    Petersen KF, Oral EA, Dufour S, et al. Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy. J Clin Invest. 2002;109:1345–50.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Simha V, Szczepaniak LS, Wagner AJ, et al. Effect of leptin replacement on intrahepatic and intramyocellular lipid content in patients with generalized lipodystrophy. Diabetes Care. 2003;26:30–5.PubMedCrossRefGoogle Scholar
  98. 98.
    Zhang B, Salituro G, Szalkowski D, et al. Discovery of a small molecule insulin mimetic with antidiabetic activity in mice. Science. 1999;284:974–7.PubMedCrossRefGoogle Scholar
  99. 99.
    Vincent JB. Elucidating a biological role for chromium at a molecular level. Acc Chem Res. 2000;33:503–10.PubMedCrossRefGoogle Scholar
  100. 100.
    Imparl-Radosevich J, Deas S, et al. Regulation of phosphotyrosine tyrosine phosphatase (PTP-1) and insulin receptor kinase by fractions from cinnamon: implications from cinnamon regulation of insulin signaling. Horm Res. 1998;50:177–82.PubMedGoogle Scholar
  101. 101.
    Martin J, Wang ZQ, Zhang XH, et al. Chromium picolinate supplementation attenuates body weight gain and increases insulin sensitivity in subjects with type 2 diabetes. Diabetes Care. 2006;29:1826–32.PubMedCrossRefGoogle Scholar
  102. 102.
    Ravina A, Slezak L, Rubal A, Mirsky N. Clinical use of the trace element chromium (III) in the treatment of diabetes mellitus. J Trace Elem Exp Med. 1995;8:183–90.Google Scholar
  103. 103.
    Via M, Scurlock C, et al. Chromium infusion reverses extreme insulin resistance in a cardiothoracic ICU patient. Nutr Clin Pract. 2008;23:325–8.PubMedCrossRefGoogle Scholar
  104. 104.
    Skarulis MC, Celi FS, Mueller E, et al. Thyroid hormone induced brown adipose tissue and amelioration of diabetes in a patient with extreme insulin resistance. J Clin Endocrinol Metab. 2010;95(1):256–62.PubMedCrossRefGoogle Scholar

Helpful Internet Sources for Additional Information on Insulin Resistance

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • George Grunberger
    • 1
    Email author
  • Anjana Myneni
    • 2
  • Bianca Alfonso
    • 3
  1. 1.Internal Medicine and Molecular Medicine and GeneticsGrunberger Diabetes Institute, Wayne State University School of MedicineBloomfield HillsUSA
  2. 2.Grunberger Diabetes InstituteBloomfield HillsUSA
  3. 3.Coral GablesUSA

Personalised recommendations