Insulin Resistance in Chronic Disease

  • Uri Hamiel
  • Orit Pinhas-Hamiel
Part of the Contemporary Endocrinology book series (COE)


Patients with chronic diseases may develop, in addition to their underlying disease, insulin resistance, and the metabolic syndrome (MetS). The MetS is a cluster of conditions—hypertension, central obesity, dyslipidemia, and insulin resistance—that increases the risk for coronary heart disease, type 2 diabetes, and stroke. In this chapter, we aim to review the prevalence of the MetS in several chronic diseases and its impact on long-term morbidity. Bidirectional relationships between obesity and chronic diseases may exist, such as obesity predating the development of the disease, while medications and disability further increase the risk of developing the MetS. Patients with chronic disease may develop components of the MetS, even with normal body mass index (BMI). Patients with chronic disease carry an increased risk of morbidity due to coronary heart disease. A beneficial effect of metformin on glycemic control has been demonstrated, and this may be a promising drug for preventing metabolic side effects in some chronic diseases.


Chronic disease Metabolic syndrome Insulin resistance Sarcopenic obesity Glucocorticoid therapy 


  1. 1.
    Gingras V, Leroux C, Fortin A, Legault L, Rabasa-Lhoret R. Predictors of cardiovascular risk among patients with type 1 diabetes: a critical analysis of the metabolic syndrome and its components. Diabetes Metab. 2017;43:217–22. Scholar
  2. 2.
    Baker KS, Chow E, Steinberger J. Metabolic syndrome and cardiovascular risk in survivors after hematopoietic cell transplantation. Bone Marrow Transplant. 2012;47:619–25. Scholar
  3. 3.
    Gilliland FD, Berhane K, Islam T, McConnell R, Gauderman WJ, Gilliland SS, et al. Obesity and the risk of newly diagnosed asthma in school-age children. Am J Epidemiol. 2003;158:406–15. Scholar
  4. 4.
    Guerra S, Wright AL, Morgan WJ, Sherrill DL, Holberg CJ, Martinez FD. Persistence of asthma symptoms during adolescence. Am J Respir Crit Care Med. 2004;170:78–85. Scholar
  5. 5.
    Wilson PWF, D’Agostino RB, Parise H, Sullivan L, Meigs JB. Metabolic syndrome as a precursor of cardiovascular disease and type 2 diabetes mellitus. Circulation. 2005;112:3066–72. Scholar
  6. 6.
    Rzehak P, Wijga AH, Keil T, Eller E, Bindslev-Jensen C, Smit HA, et al. Body mass index trajectory classes and incident asthma in childhood: results from 8 European Birth Cohorts–a Global Allergy and Asthma European Network initiative. J Allergy Clin Immunol. 2013;131:1528–36. Scholar
  7. 7.
    Wiesenthal EN, Fagnano M, Cook S, Halterman JS. Asthma and overweight/obese: double trouble for urban children. J Asthma. 2016;53:485–91. Scholar
  8. 8.
    Farahmand M, Ramezani Tehrani F, Rostami Dovom M, Hashemi S, Azizi F. The impact of oral contraceptives on cardiometabolic parameters. J Endocrinol Investig. 2016;39:277–83. Scholar
  9. 9.
    Thuesen BH, Husemoen LL, Hersoug LG, Pisinger C, Linneberg A. Insulin resistance as a predictor of incident asthma-like symptoms in adults. Clin Exp Allergy. 2009;39:700–7. Scholar
  10. 10.
    Husemoen LLN, Glümer C, Lau C, Pisinger C, Mørch LS, Linneberg A. Association of obesity and insulin resistance with asthma and aeroallergen sensitization. Allergy. 2008;63:575–82. Scholar
  11. 11.
    Al-Shawwa BA, Al-Huniti NH, DeMattia L, Gershan W. Asthma and insulin resistance in morbidly obese children and adolescents. J Asthma. 2007;44:469–73. Scholar
  12. 12.
    Arshi M, Cardinal J, Hill RJ, Davies PS, Wainwright C. Asthma and insulin resistance in children. Respirology. 2010;15:779–84. Scholar
  13. 13.
    Baffi CW, Wood L, Winnica D, Strollo PJ Jr, Gladwin MT, Que LG, et al. Metabolic syndrome and the lung. Chest. 2016;149:1525–34. Scholar
  14. 14.
    Lee EJ, In KH, Ha ES, Lee KJ, Hur GY, Kang EH, et al. Asthma-like symptoms are increased in the metabolic syndrome. J Asthma. 2009;46:339–42. Scholar
  15. 15.
    Brumpton BM, Camargo CA, Romundstad PR, Langhammer A, Chen Y, Mai XM. Metabolic syndrome and incidence of asthma in adults: the HUNT study. Eur Respir J. 2013;42(6):1495–502. Accessed 29 Jul 2017.CrossRefGoogle Scholar
  16. 16.
    Forno E, Han YY, Muzumdar RH, Celedón JC. Insulin resistance, metabolic syndrome, and lung function in US adolescents with and without asthma. J Allergy Clin Immunol. 2015;136:304–11.e8. Scholar
  17. 17.
    Rastogi D, Bhalani K, Hall CB, Isasi CR. Association of pulmonary function with adiposity and metabolic abnormalities in urban minority adolescents. Ann Am Thorac Soc. 2014;11:744–52. Scholar
  18. 18.
    Adeniyi FB, Young T. Weight loss interventions for chronic asthma. Cochrane Database Syst Rev. 2012;(7):CD009339.
  19. 19.
    Al Khalifah RA, Alnhdi A, Alghar H, Alanazi M, Florez ID. The effect of adding metformin to insulin therapy for type 1 diabetes mellitus children: a systematic review and meta-analysis. Pediatr Diabetes. 2017;18(7):664–73. Scholar
  20. 20.
    Cardwell CR, Stene LC, Joner G, Davis EA, Cinek O, Rosenbauer J, et al. Birthweight and the risk of childhood-onset type 1 diabetes: a meta-analysis of observational studies using individual patient data. Diabetologia. 2010;53:641–51. Scholar
  21. 21.
    Magnus MC, Olsen SF, Granström C, Joner G, Skrivarhaug T, Svensson J, et al. Infant growth and risk of childhood-onset type 1 diabetes in children from 2 Scandinavian birth cohorts. JAMA Pediatr. 2015;169:e153759. Scholar
  22. 22.
    Verbeeten KC, Elks CE, Daneman D, Ong KK. Association between childhood obesity and subsequent type 1 diabetes: a systematic review and meta-analysis. Diabet Med. 2011;28:10–8. Scholar
  23. 23.
    Pinhas-Hamiel O, Levek-Motola N, Kaidar K, Boyko V, Tisch E, Mazor-Aronovitch K, et al. Prevalence of overweight, obesity and metabolic syndrome components in children, adolescents and young adults with type 1 diabetes mellitus. Diabetes Metab Res Rev. 2015;31:76–84. Scholar
  24. 24.
    Liu LL, Lawrence JM, Davis C, Liese AD, Pettitt DJ, Pihoker C, et al. Prevalence of overweight and obesity in youth with diabetes in USA: the SEARCH for Diabetes in Youth study. Pediatr Diabetes. 2010;11:4–11. Scholar
  25. 25.
    Bielorai B, Weintraub Y, Hutt D, Hemi R, Kanety H, Modan-Moses D, et al. The metabolic syndrome and its components in pediatric survivors of allogeneic hematopoietic stem cell transplantation. Clin Transpl. 2017;31(3). Scholar
  26. 26.
    Paris C, Yates L, Lama P, Zepeda AJ, Gutiérrez D, Palma J. Evaluation of metabolic syndrome after hematopoietic stem cell transplantation in children and adolescents. Pediatr Blood Cancer. 2012;59:306–10. Scholar
  27. 27.
    Oudin C, Auquier P, Bertrand Y, Contet A, Kanold J, Sirvent N, et al. Metabolic syndrome in adults who received hematopoietic stem cell transplantation for acute childhood leukemia: an LEA study. Bone Marrow Transplant. 2015;50:1438–44. Scholar
  28. 28.
    Baker KS, Ness KK, Steinberger J, Carter A, Francisco L, Burns LJ, et al. Diabetes, hypertension, and cardiovascular events in survivors of hematopoietic cell transplantation: a report from the bone marrow transplantation survivor study. Blood. 2007;109:1765–72. Scholar
  29. 29.
    Bajwa R, Skeens M, Garee A, Miao Y, Soni S, Pietryga D, et al. Metabolic syndrome and endocrine dysfunctions after HSCT in children. Pediatr Transplant. 2012;16:872–8. Scholar
  30. 30.
    Bizzarri C, Pinto RM, Ciccone S, Brescia LP, Locatelli F, Cappa M. Early and progressive insulin resistance in young, non-obese cancer survivors treated with hematopoietic stem cell transplantation. Pediatr Blood Cancer. 2015;62:1650–5. Scholar
  31. 31.
    Saultier P, Auquier P, Bertrand Y, Vercasson C, Oudin C, Contet A, et al. Metabolic syndrome in long-term survivors of childhood acute leukemia treated without hematopoietic stem cell transplantation: an L.E.A. study. Haematologica. 2016;101(12):1603–10. Scholar
  32. 32.
    Tichelli A, Bucher C, Rovó A, Stussi G, Stern M, Paulussen M, et al. Premature cardiovascular disease after allogeneic hematopoietic stem-cell transplantation. Blood. 2007;110(9):3463–71.CrossRefGoogle Scholar
  33. 33.
    Penfold RB, Stewart C, Hunkeler EM, Madden JM, Cummings JR, Owen-Smith AA, et al. Use of antipsychotic medications in pediatric populations: what do the data say? Curr Psychiatry Rep. 2013;15:426. Scholar
  34. 34.
    Petry NM, Barry D, Pietrzak RH, Wagner JA. Overweight and obesity are associated with psychiatric disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Psychosom Med. 2008;70:288–97. Scholar
  35. 35.
    Rajan T, Menon V. Psychiatric disorders and obesity: a review of association studies. J Postgrad Med. 2017;63:182. Scholar
  36. 36.
    Landau Z, Hadi-Cohen R, Boaz M, Krivoy A, Amit BH, Zalsman G, et al. Risk factors for weight gain and metabolic syndrome in adolescents with psychiatric disorders: a historical prospective study. J Child Adolesc Psychopharmacol. 2015;25:160–7. Scholar
  37. 37.
    Hung CI, Liu CY, Hsiao MC, Yu NW, Chu CL. Metabolic syndrome among psychiatric outpatients with mood and anxiety disorders. BMC Psychiatry. 2014;14:185. Scholar
  38. 38.
    Alosaimi FD, Abalhassan M, Alhaddad B, Alzain N, Fallata E, Alhabbad A, et al. Prevalence of metabolic syndrome and its components among patients with various psychiatric diagnoses and treatments: a cross-sectional study. Gen Hosp Psychiatry. 2017;45:62–9. Scholar
  39. 39.
    Kawada T. Relationship between metabolic syndrome and psychiatric disorders in patients with bipolar disorder or schizophrenia. Bipolar Disord. 2015;17:233–4. Scholar
  40. 40.
    Bioque M, García-Portilla MAP, García-Rizo C, Cabrera B, Lobo A, González-Pinto A, et al. Evolution of metabolic risk factors over a two-year period in a cohort of first episodes of psychosis. Schizophr Res. 2018;193:188–96.CrossRefGoogle Scholar
  41. 41.
    Galling B, Roldán A, Nielsen RE, Nielsen J, Gerhard T, Carbon M, et al. Type 2 diabetes mellitus in youth exposed to antipsychotics: a systematic review and meta-analysis. JAMA Psychiat. 2016;73(3):247–59. Scholar
  42. 42.
    DE Hert M, Correll CU, Bobes J, Cetkovich-Bakmas M, Cohen D, Asai I, et al. Physical illness in patients with severe mental disorders. I. Prevalence, impact of medications and disparities in health care. World Psychiatry. 2011;10:52–77. Accessed 5 Aug 2017.CrossRefGoogle Scholar
  43. 43.
    de Silva VA, Suraweera C, Ratnatunga SS, Dayabandara M, Wanniarachchi N, Hanwella R. Metformin in prevention and treatment of antipsychotic induced weight gain: a systematic review and meta-analysis. BMC Psychiatry. 2016;16:341. Scholar
  44. 44.
    Almandil NB, Liu Y, Murray ML, Besag FM, Aitchison KJ, Wong IC. Weight gain and other metabolic adverse effects associated with atypical antipsychotic treatment of children and adolescents: a systematic review and meta-analysis. Paediatr Drugs. 2013;15:139–50. Scholar
  45. 45.
    Anagnostou E, Aman MG, Handen BL, Sanders KB, Shui A, Hollway JA, et al. Metformin for treatment of overweight induced by atypical antipsychotic medication in young people with autism spectrum disorder: a randomized clinical trial. JAMA Psychiat. 2016;73:928–37. Scholar
  46. 46.
    Janszky I, Hallqvist J, Tomson T, Ahlbom A, Mukamal KJ, Ahnve S. Increased risk and worse prognosis of myocardial infarction in patients with prior hospitalization for epilepsy-the Stockholm Heart Epidemiology Program. Brain. 2009;132:2798–804. Scholar
  47. 47.
    Daniels ZS, Nick TG, Liu C, Cassedy A, Glauser TA. Obesity is a common comorbidity for pediatric patients with untreated, newly diagnosed epilepsy. Neurology. 2009;73:658–64. Scholar
  48. 48.
    Grosso S, Mostardini R, Piccini B, Balestri P. Body mass index and serum lipid changes during treatment with valproic acid in children with epilepsy. Ann Pharmacother. 2009;43:45–50. Scholar
  49. 49.
    Verrotti A, di Corcia G, Salladini C, Trotta D, Morgese G, Chiarelli F. Serum insulin and leptin levels and valproate-associated obesity. Epilepsia. 2003;44:1606. Scholar
  50. 50.
    Corman CL, Leung NM, Guberman AH. Weight gain in epileptic patients during treatment with valproic acid: a retrospective study. Can J Neurol Sci. 1997;24:240–4. Scholar
  51. 51.
    Abaci A, Saygi M, Yis U, Demir K, Dirik E, Bober E. Metabolic alterations during valproic acid treatment: a prospective study. Pediatr Neurol. 2009;41:435–9. Scholar
  52. 52.
    Pylvänen V, Pakarinen A, Knip M, Isojärvi J. Characterization of insulin secretion in valproate-treated patients with epilepsy. Epilepsia. 2006;47:1460–4. Scholar
  53. 53.
    Rakitin A, Eglit T, Kõks S, Lember M, Haldre S. Comparison of the metabolic syndrome risk in valproate-treated patients with epilepsy and the general population in Estonia. PLoS One. 2014;9:e103856. Scholar
  54. 54.
    Fang J, Chen S, Tong N, Chen L, An D, Mu J, et al. Metabolic syndrome among Chinese obese patients with epilepsy on sodium valproate. Seizure. 2012;21:578–82. Scholar
  55. 55.
    Pylvänen V, Pakarinen A, Knip M, Isojärvi J. Insulin-related metabolic changes during treatment with valproate in patients with epilepsy. Epilepsy Behav. 2006;8:643–8. Scholar
  56. 56.
    Nair SS, Harikrishnan S, Sarma PS, Thomas SV. Metabolic syndrome in young adults with epilepsy. Seizure. 2016;37:61–4. Scholar
  57. 57.
    Virkamäki 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. Scholar
  58. 58.
    Kohen-Avramoglu R, Theriault A, Adeli K. Emergence of the metabolic syndrome in childhood: an epidemiological overview and mechanistic link to dyslipidemia. Clin Biochem. 2003;36:413–20. Accessed 24 Jul 2017.CrossRefGoogle Scholar
  59. 59.
    Verrotti A, Manco R, Agostinelli S, Coppola G, Chiarelli F. The metabolic syndrome in overweight epileptic patients treated with valproic acid. Epilepsia. 2010;51:268–73. Scholar
  60. 60.
    Pinhas-Hamiel O, Livne M, Harari G, Achiron A. Prevalence of overweight, obesity and metabolic syndrome components in multiple sclerosis patients with significant disability. Eur J Neurol. 2015;22:1275–9. Scholar
  61. 61.
    Sicras-Mainar A, Ruíz-Beato E, Navarro-Artieda R, Maurino J. Comorbidity and metabolic syndrome in patients with multiple sclerosis from Asturias and Catalonia, Spain. BMC Neurol. 2017;17:134. Scholar
  62. 62.
    Falhammar H, Frisén L, Hirschberg AL, Norrby C, Almqvist C, Nordenskjöld A, et al. Increased cardiovascular and metabolic morbidity in patients with 21-hydroxylase deficiency: a Swedish population-based national cohort study. J Clin Endocrinol Metab. 2015;100:3520–8. Scholar
  63. 63.
    van Staa TP, Leufkens HGM, Abenhaim L, Begaud B, Zhang B, Cooper C. Use of oral corticosteroids in the United Kingdom. QJM. 2000;93:105–11. Scholar
  64. 64.
    van Raalte DH, Ouwens DM, Diamant M. Novel insights into glucocorticoid-mediated diabetogenic effects: towards expansion of therapeutic options? Eur J Clin Investig. 2009;39:81–93. Scholar
  65. 65.
    Lambillotte C, Gilon P, Henquin JC. Direct glucocorticoid inhibition of insulin secretion. An in vitro study of dexamethasone effects in mouse islets. J Clin Invest. 1997;99:414–23. Scholar
  66. 66.
    Larsson H, Ahrén B. Insulin resistant subjects lack islet adaptation to short-term dexamethasone-induced reduction in insulin sensitivity. Diabetologia. 1999;42:936–43. Scholar
  67. 67.
    Wang M. The role of glucocorticoid action in the pathophysiology of the metabolic syndrome. Nutr Metab. 2005;2(1):3. Scholar
  68. 68.
    Dessein PH, Joffe BI, Stanwix AE, Christian BF, Veller M. Glucocorticoids and insulin sensitivity in rheumatoid arthritis. J Rheumatol. 2004;31:867–74. Scholar
  69. 69.
    de Souza FHC, Shinjo SK. The high prevalence of metabolic syndrome in polymyositis. Clin Exp Rheumatol. 2014;32:82–7. Scholar
  70. 70.
    Seelig E, Meyer S, Timper K, Nigro N, Bally M, Pernicova I, et al. Metformin prevents metabolic side effects during systemic glucocorticoid treatment. Eur J Endocrinol. 2017;176:349–58. Scholar
  71. 71.
    Kershaw EE, Morton NM, Dhillon H, Ramage L, Seckl JR, Flier JS. Adipocyte-specific glucocorticoid inactivation protects against diet-induced obesity. Diabetes. 2005;54:1023–31. Scholar
  72. 72.
    Wofford MR, King DS, Harrell TK. Drug-induced metabolic syndrome. J Clin Hypertens (Greenwich). 2006;8:114–9. Accessed 3 Aug 2017.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Uri Hamiel
    • 1
    • 2
  • Orit Pinhas-Hamiel
    • 3
  1. 1.Department of PediatricsAssaf Harofeh Medical CenterZerifinIsrael
  2. 2.Sackler School of Medicine, Tel-Aviv UniversityTel Aviv-YafoIsrael
  3. 3.Sackler School of Medicine, Tel Aviv University, Israel, Pediatric Endocrine and Diabetes Unit, Edmond and Lily Safra Children’s Hospital, Sheba Medical CenterTel-HashomerIsrael

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