Skip to main content
SpringerLink
Log in

Diabetes and Insulin Resistance

  • Chapter
Genetic factors in coronary heart disease

Part of the book series: Developments in Cardiovascular Medicine ((DICM,volume 156))

Abstract

It has long been appreciated that individuals with diabetes mellitus are at a dramatically increased risk for coronary heart disease. Although the epidemiology of coronary heart disease in individuals with diabetes is well characterized, the mechanisms responsible for the association have not been completely delineated. In this chapter, the genetics of diabetes as currently understood will be discussed, along with ways in which the genes involved in diabetes may also be implicated in predisposition to CHD.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. WHO Expert Committee on Diabetes Mellitus. 1980 Second report on diabetes mellitus. Technical Report Series 646, Geneva, Switzerland: WHO; 1980.

    Google Scholar 

  2. Rotter JI, Vadheim CM, Rimoin DL. Diabetes mellitus. In: King RE, Rotter JI, Motulsky AG, eds. The genetic basis of common diseases. New York and Oxford: Oxford University Press; 1992:413–481.

    Google Scholar 

  3. Vadheim CM, Rotter JI. Genetics of diabetes mellitus. In: Alberti KGMM, Zimmet P, DeFronzo RA, Keen H, eds. International textbook of diabetes mellitus. Chichester, England: John Wiley & Sons; 1992:31–98.

    Google Scholar 

  4. Tattersall RB. The present status of maturity-onset type of diabetes mellitus. In: Kobberling J, Tattersall RB, eds. Genetics of diabetes mellitus. New York: Academic Press; 1982:261–70.

    Google Scholar 

  5. Rotter JI, Vadheim CM, Rimoin DL. Genetics of diabetes mellitus. In: Rifkin H, Porte D, eds. Diabetes mellitus. New York: Elsevier; 1990:378–413.

    Google Scholar 

  6. Hitman GA, Niven MJU. Genes and diabetes mellitus. Br Med Bull. 1989;45:191–205.

    PubMed  CAS  Google Scholar 

  7. Zimmet P. Type 2 (non-insulin-dependent) diabetes — An epidemiological overview. Diabetologia. 1982;22:399–411.

    Article  PubMed  CAS  Google Scholar 

  8. Rimoin DL, Rotter JI. Genetic syndromes associated with diabetes mellitus and glucose intolerance. In: Kobberling J, Tattersall R, eds. Genetics of diabetes mellitus. London: Academic Press; 1982:149–81.

    Google Scholar 

  9. Hitchcock CL, Riley WJ, Maclaren NK. Autoimmunity in insulin dependent diabetes mellitus: Its detection and prevention. Concepts Immunopathol. 1988;5:144–67.

    PubMed  CAS  Google Scholar 

  10. Nepom GT, Ehrlich H. MHC class-II molecules and autoimmunity. Annu Rev Immunol. 1991;9:493–525.

    Article  PubMed  CAS  Google Scholar 

  11. Thomson G, Robinson WP, Kuhner MK, et al. Genetic heterogeneity, modes of inheritance, and risk estimates for a joint study of Caucasians with insulin dependent diabetes mellitus. Am J Hum Genet. 1988;43:799–816.

    PubMed  CAS  Google Scholar 

  12. Rotter JI, Anderson CE, Rubin R, Congleton JE, Terasaki PI, Rimoin DL. HLA genotype study of insulin-dependent diabetes, the excess of DR3/DR4 heterozygotes allows rejection of the recessive hypothesis. Diabetes. 1983;32:169–74.

    Article  PubMed  CAS  Google Scholar 

  13. Erlich HA, Griffith RL, Bugawan TL, Ziegler CA, Eisenbarth G. Implication of specific DQB1 alleles in genetic susceptibility and resistance by identification of IDDM siblings with novel HLA-DQB1 allele and unusual DR2 and DR1 haplotypes. Diabetes. 1991;40:478–81.

    Article  PubMed  CAS  Google Scholar 

  14. Ludvigsson J, Samuelsson U, Beauforts C. HLA-DR3 is associated with a more slowly progressive form of type 1 (insulin-dependent) diabetes. Diabetologia. 1986;29:207–10.

    Article  PubMed  CAS  Google Scholar 

  15. Ludvigsson J, Lindblom B. Human lymphocyte antigen DR types in relation to early clinical manifestations in diabetic children. Pediatr Res. 1984;18:1239–41.

    Article  PubMed  CAS  Google Scholar 

  16. Rotter JI, Landaw EM. Measuring the genetic contribution of a single locus to a multilocus disease. Clin Genet. 1984;26:529–42.

    Article  PubMed  CAS  Google Scholar 

  17. Raffel LJ, Vadheim CM, Klein R, et al. HLA-DR and the 5’ insulin gene polymorphism in insulin dependent diabetes. Metabolism. 1991;40:1244–8.

    Article  PubMed  CAS  Google Scholar 

  18. Julier C, Hyer RN, Davies J, et al. The insulin-IGF2 region on chromosome 11p encodes a gene implicated in HLA-DR4 dependent diabetes susceptibility. Nature. 1991;354:155–9.

    Article  PubMed  CAS  Google Scholar 

  19. Bell GI, Horita S, Karam JH. A polymorphic locus near the human insulin gene is associated with insulin-dependent diabetes mellitus. Diabetes. 1984;33:176–83.

    Article  PubMed  CAS  Google Scholar 

  20. Owerbach D, Nerup J. Restriction fragment length polymorphism of the insulin gene in diabetes mellitus. Diabetes. 1982;21:275–7.

    Article  Google Scholar 

  21. Hitman GA, Tarn AC, Winter RM, et al. Type 1 (insulin dependent) diabetes and a highly variable locus close to the insulin gene on chromosome 11. Diabetologia. 1985;28:218–22.

    Article  PubMed  CAS  Google Scholar 

  22. Spielman RS, Bauer MP, Clerget-Darpoux F. Genetic analysis of IDDM: Summary of GAW5 IDDM results. Genet Epidemiol. 1989;6:43–58.

    Article  PubMed  CAS  Google Scholar 

  23. Thomson G, Robinson WP, Kuhner MK, Joe S, Klitz W. HLA and insulin gene associations with IDDM. Genet Epidemiol. 1989;6:155–60.

    Article  PubMed  CAS  Google Scholar 

  24. Raffel LJ, Hitman GA, Toyoda H, Karam JH, Bell GI, Rotter JI. The aggregation of the 5’ insulin gene polymorphism in type I (insulin-dependent) diabetes mellitus families. J Med Genet. 1992;29:447–50.

    PubMed  CAS  Google Scholar 

  25. Hoover ML, Black KE, Ball E, et al. Polymorphisms of the human T-cell receptor alpha and beta chain genes and their relationship to insulin dependent diabetes mellitus. In: Dupont B, ed. Immunobiology of HLA, Vol 2. New York: Springer; 1989:411–12.

    Google Scholar 

  26. Concannon P, Wright JA, Wright LG, Sylvester DR, Spielman RS. T cell receptor genes and insulin dependent diabetes mellitus (IDDM): no evidence for linkage from affected sib pairs. Am J Hum Genet. 1990;47:45–52.

    PubMed  CAS  Google Scholar 

  27. Pyke DA. The genetic connections. Diabetologia. 1979;17:333–43.

    Article  PubMed  CAS  Google Scholar 

  28. Barnett AH, Eff C, Leslie RDG, Pyke DA. Diabetes in identical twins: a study of 200 pairs. Diabetologia. 1981;20:87–93.

    Article  PubMed  CAS  Google Scholar 

  29. Taylor SI, Kadowaki T, Kadowaki H, Accili D, Cama A, McKeon C. Mutations in the insulin-receptor gene in insulin-resistant patients. Diabetes Care. 1990;13:257–79.

    Article  PubMed  CAS  Google Scholar 

  30. Moller DE, Yokota A, Flier JS. Normal insulin-receptor cDNA sequence in Pima Indians with NIDDM. Diabetes. 1989;38:1496–500.

    Article  PubMed  CAS  Google Scholar 

  31. O’Rahilly S, Choi WH, Patel P, Turner RC, Flier JS, Moller DE. Detection of mutation in insulin receptor gene in NIDDM patients by analysis of single stranded conformation polymorphisms. Diabetes. 1991;40:777–82.

    Article  CAS  Google Scholar 

  32. Kwok SCM, Steiner DF, Rubenstein AH, Tager HS. Identification of a point mutation in the human insulin gene giving rise to a structurally abnormal insulin (Insulin Chicago). Diabetes. 1983;32:872–5.

    Article  PubMed  CAS  Google Scholar 

  33. Haneda M, Polonsky KS, Bergenstal RM, et al. Familial hyperinsulinemia due to a structurally abnormal insulin. Definition of an emerging new clinical syndrome. N Engl J Med. 1984;310:1288–94.

    Article  PubMed  CAS  Google Scholar 

  34. Nanjo K, Miyano M, Kondo M, et al. Insulin Wakayama: Familial mutant insulin syndrome in Japan. Diabetologia. 1987;30:87–92.

    PubMed  CAS  Google Scholar 

  35. Elbein SC, Gruppuso P, Schwartz R, Skolnick M, Permutt MA. Hyperproinsulinemia in a family with proposed defect in conversion is linked to the insulin gene. Diabetes. 1985;34:821–4.

    Article  PubMed  CAS  Google Scholar 

  36. Gruppuso PA, Gorden P, Kahn CR, Cornblath M, Zeller WP, Schwartz R. Familial hyperproinsulinemia due to a proposed defect in conversion of proinsulin to insulin. N Engl J Med. 1984;311:629–34.

    Article  PubMed  CAS  Google Scholar 

  37. Sanz N, Karam JH, Horita S, Bell GI. Prevalence of insulin-gene mutations in non-insulin dependent diabetes mellitus. N Engl J Med. 1986;314:1322.

    PubMed  CAS  Google Scholar 

  38. Bell GI, Xiang KS, Newman MV, et al. Gene for non-insulin-dependent diabetes mellitus (maturity-onset diabetes of the young subtype) is linked to DNA polymorphism on human chromosome 20q. Proc Natl Acad Sci USA. 1991;88:1484–8.

    Article  PubMed  CAS  Google Scholar 

  39. Froguel Ph, Vaxillaire M, Sun F, et al. Close linkage of glucokinase locus on chromosome 7p to early-onset non-insulin-dependent diabetes mellitus. Nature. 1992;365:162–4.

    Article  Google Scholar 

  40. Hattersley AT, Turner RC, Permutt MA, et al. Linkage of type 2 diabetes to the glucokinase gene. Lancet. 1992;339:1307–10.

    Article  PubMed  CAS  Google Scholar 

  41. Vionnet N, Stoffel M, Takeda J, et al. Nonsense mutation in the glucokinase gene causes early-onset non-insulin-dependent diabetes mellitus. Nature. 1992;336:721–2.

    Article  Google Scholar 

  42. Sun F, Knebelmann B, Pueyo ME, et al. Deletion of the donor site of intron 4 in the glucokinase gene causes maturity-onset diabetes of the young. J Clin Invest. 1993;92:1174–80.

    Article  PubMed  CAS  Google Scholar 

  43. Permutt MA, Chiu KC, Tanizawa Y. Glucokinase and NIDDM. A candidate gene that paid off. Diabetes. 1992;41:1367–72.

    Article  PubMed  CAS  Google Scholar 

  44. Velho G, Froguel P, Clement K, et al. Primary pancreatic beta-cell secretory defect caused by mutations in glucokinase gene in kindreds of maturity onset diabetes of the young. Lancet. 1992;340:444–8.

    Article  PubMed  CAS  Google Scholar 

  45. Reaven GM. Role of insulin resistance in human disease. Diabetes. 1988;37:1595–607.

    Article  PubMed  CAS  Google Scholar 

  46. Manicardi V, Camellini L, Bellodi G, Coscelli C, Ferrannini E. Evidence for an association of high blood pressure and hyperinsulinemia in obese men. J Clin Endocrinol Metab. 1986;62:1302–4.

    Article  PubMed  CAS  Google Scholar 

  47. Ferrannini EF, Buzzigoli G, Bonadonna R, et al. Insulin resistance in essential hypertension. N Engl J Med. 1987;317:350–7.

    Article  PubMed  CAS  Google Scholar 

  48. DeFronzo RA, Ferrannini E. Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care. 1991;14:173–94.

    Article  PubMed  CAS  Google Scholar 

  49. Pyorala K, Laakso M, Unsitupa M. Diabetes and atherosclerosis: an epidemiologic view. Diabetes/Metab Rev. 1987;3:463–524.

    Article  CAS  Google Scholar 

  50. Eschwege E, Richard JL, Thibult N, et al. Coronary heart disease mortality in relation with diabetes, blood glucose and plasma insulin levels: the Paris prospective study, ten years later. Horm Metab Res. 1985;15(Suppl):41–6.

    CAS  Google Scholar 

  51. Jarrett RJ. Is insulin atherogenic? Diabetologia. 1988;31:71–5.

    Article  PubMed  CAS  Google Scholar 

  52. Stern MP, Haffner SM. Body fat distribution and hyperinsulinemia as risk factors for diabetes and cardiovascular disease. Arteriosclerosis. 1986;6:123–30.

    Article  PubMed  CAS  Google Scholar 

  53. HafTner SM, Stern MP, Hazuda HP, Mitchell BD, Patterson JK. Increased insulin concentrations in non-diabetic offspring of diabetic parents. N Engl J Med. 1988;319:1297–301.

    Article  Google Scholar 

  54. Lillioja S, Mott DM, Zawadzki JK, et al. In vivo insulin action is a familial characteristic in nondiabetic Pima Indians. Diabetes. 1987;35:1329–35.

    Article  Google Scholar 

  55. Bogardus C, Lillioja S, Nyomba BL, et al. Distribution of an in vivo insulin action in Pima Indians as mixture of three normal distributions. Diabetes. 1989;38:1423–32.

    Article  PubMed  CAS  Google Scholar 

  56. Iselius L, Lindsten J, Morton NE, et al. Genetic regulation of the kinetics of glucose-induced insulin release in man. Clin Genet. 1985;28:8–15.

    Article  PubMed  CAS  Google Scholar 

  57. O’Rahilly SP, Rudenski AS, Burnett MA, et al. Beta-cell dysfunction, rather than insulin insensitivity, is the primary defect in familial type 2 diabetes. Lancet. 1986;2:360–4.

    Article  CAS  Google Scholar 

  58. O’Rahilly SP, Turner RC, Matthews DR. Impaired pulsatile secretion of insulin in relatives of patients with non-insulin-dependent diabetes. N Engl J Med. 1988;318:1225–30.

    Article  CAS  Google Scholar 

  59. Eriksson J, Farnssila-Kallunki A, Ekstrand A, et al. Early metabolic defects in persons at increased risk for non-insulin-dependent diabetes mellitus. N Engl J Med. 1989;321:337–43.

    Article  PubMed  CAS  Google Scholar 

  60. Warram JH, Martin BC, Krolewski AS, Soeldner JS, Kahn CR. Slow glucose removal rate and hyperinsulinemia precede the development of type II diabetes in the offspring of diabetic parents. Ann Intern Med. 1990;113:909–15.

    Article  PubMed  CAS  Google Scholar 

  61. Olefsky JM, Molina JM. Insulin resistance in man. In: Rifkin H, Porte D, eds. Diabetes mellitus theory and practice. New York: Elsevier; 1990:121–51.

    Google Scholar 

  62. Bell GL Molecular defects in diabetes mellitus. Diabetes. 1991;40:413–22.

    Article  PubMed  CAS  Google Scholar 

  63. Reaven GM. Insulin resistance, hyperinsulinemia, hypertriglyceridemia, and hypertension. Diabetes Care. 1991;14:195–202.

    Article  PubMed  CAS  Google Scholar 

  64. Shohat T, Raffel LJ, Vadheim CM, Rotter JL Diabetes mellitus and coronary heart disease genetics. In: Lusis AJ, Rotter JI, Sparkes RS, eds. The molecular genetics of coronary heart disease: candidate genes and physiologic processes in atherosclerosis. Basel: S. Karger; 1992:272–310.

    Google Scholar 

  65. Jarrett RJ. Report on the multinational study of vascular disease in diabetics (WHO study No. 08). Internal WHO Document NCD/OND/79.4. WHO Geneva; 1982.

    Google Scholar 

  66. Chazan BI, Balodimos MC, Ryan JR, Marble A. Twenty-five to forty-five years of diabetes with and without vascular complications. Diabetologia. 1970;6:565–9.

    Article  PubMed  CAS  Google Scholar 

  67. Ryan RJ, Balodimos MC, Chazan BI, et al. Quarter century victory medal for diabetes: a follow up of patients one to 20 years later. Metabolism. 1970;19:493–501.

    Article  PubMed  CAS  Google Scholar 

  68. Lestradet H, Papoz L, Hellonin de Menibus C, et al. Long-term study of mortality and vascular complications in juvenile-onset (type 1) diabetes. Diabetes. 1981;30:175–9.

    Article  PubMed  CAS  Google Scholar 

  69. Paz-Guevara AT, Hsu T-H, White P. Juvenile diabetes after forty years. Diabetes. 1975;24:559–65.

    Article  PubMed  CAS  Google Scholar 

  70. Pirart J. Diabetes mellitus and its degenerative complications: a prospective study of 4,400 patients observed between 1947 and 1973. Diabetes Care. 1978;l:168–88, 252–63.

    Google Scholar 

  71. Dorman JS, Drash AL. Concordance of diabetic complications in multiple sibling case families. Diabetes. 1986;35:48A.

    Google Scholar 

  72. Nora JJ, Lortscher RH, Spangler RD, Nora AH, Kimberbling WJ. Genetic-epidemiologic study of early-onset ischemic heart disease. Circulation. 1980;61:503–8.

    Article  PubMed  CAS  Google Scholar 

  73. Krolewski AS, Czyzyk A, Kopczynski J, Rywik S. Prevalence of diabetes mellitus, coronary heart disease and hypertension in the families of insulin dependent and insulin independent diabetes. Diabetologia. 1981;21:520–4.

    PubMed  CAS  Google Scholar 

  74. Cohen AM. Prevalence of diabetes among different ethnic Jewish groups in Israel. Metabolism. 1961;10:50–8.

    PubMed  CAS  Google Scholar 

  75. Cohen AM, Fidel J, Cohen B, Furst A, Eisenberg S. Diabetes, blood lipids, lipoproteins, and change of environment: Restudy of the ‘new immigrant Yemenites’ in Israel. Metabolism. 1979;28:716–28.

    Article  PubMed  CAS  Google Scholar 

  76. Taylor R, Ram P, Zimmet P, Raper LR, Rigrose H. Physical activity and prevalence of diabetes in Melanesian and Indian men in Fiji. Diabetologia. 1984;27:578–82.

    Article  PubMed  CAS  Google Scholar 

  77. Zimmet P, Taylor R, King H. Diabetes in the Pacific — An epidemiological perspective. In: Eschwege E, ed. Advances in diabetes epidemiology. INSERM Symposium No. 22. New York: Elsevier; 1982:75–82.

    Google Scholar 

  78. O’Dea K. Marked improvement in carbohydrate and lipid metabolism in diabetic Australian Aborigines after temporary reversion to traditional lifestyle. Diabetes. 1984;33:596–603.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Common Disease Genetics Program, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA, 90048, USA

    Leslie J. Raffel (Assistant Professor of Pediatrics and Medicine Associate Director), Tamar Shohat & Jerome I. Rotter

Authors
  1. Leslie J. Raffel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tamar Shohat
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jerome I. Rotter
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Sackler Medical Faculty, Epidemiology and Biostatistics, the Neufeld Cardiac Research Institute, Sheba Medical Center and Tel Aviv University, Israel

    Uri Goldbourt (Professor of Epidemiology and Preventive Medicine, Head) (Professor of Epidemiology and Preventive Medicine, Head)

  2. Division of Epidemiology, Institute of Environmental Medicine, Karolinska Institute and Division of Cardiovascular Medicine, Department of Internal Medicine, Karolinska Hospital, Stockholm, Sweden

    Ulf de Faire (Professor) (Professor)

  3. Institute of Medical Genetics, Department of Medical Genetics, Ullevål University Hospital, Oslo, Norway

    KÃ¥re Berg (Professor of Medicine, Chairman, Director and Physician-in-Chief) (Professor of Medicine, Chairman, Director and Physician-in-Chief)

Rights and permissions

Reprints and permissions

Copyright information

© 1994 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Raffel, L.J., Shohat, T., Rotter, J.I. (1994). Diabetes and Insulin Resistance. In: Goldbourt, U., de Faire, U., Berg, K. (eds) Genetic factors in coronary heart disease. Developments in Cardiovascular Medicine, vol 156. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-1130-0_14

Download citation

  • DOI: https://doi.org/10.1007/978-94-011-1130-0_14

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-4494-3

  • Online ISBN: 978-94-011-1130-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation