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Heterogeneity within Type II and Mody Diabetes

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 189))

Abstract

The heterogeneity within Type II diabetes (NIDDH) and within Maturity-Onset type Diabetes of Young people (MODY), a subset of NIDDM which is inherited in an autosomal dominant fashion, is discussed. Aspects of the definition and phenotypic expression of MODY are reviewed. Within NIDDM there are differences in patterns of inheritance between subgroups. HLA antigen associations are not found in most NIDDH populations but exist in three specific population groups with Type II diabetes. Within NIDDH and within MODY there are differences in the magnitude of insulin responses to glucose, differences in target tissue responsiveness to insulin in vivo, and differences in receptor and post-receptor effects of insulin. Structurally abnormal variant and biologically defective insulin molecules have been found in some Type II diabetic patients and in members of certain MODY families. The presence or absence of obesity may mark heterogeneous groups of Type II diabetic patients, in addition to the importance of obesity in uncovering an insulin secretory defect by causing insulin resistance. There is heterogeneity in susceptibility to vascular disease within NIDDM and MODY. The natural history of carbohydrate metabolism and of insulin secretory responses to glucose in early Type I diabetes and in MODY with low insulin secretory responses are illustrated and similarities and dissimilarities compared and contrasted. Failure to recognize young patients with MODY may contribute to incorrect diagnosis, management, and assignment of prognosis of this form of diabetes in the young by many practicing physicians.

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References

  1. A. Arnaiz-Villena, R.B. Castellanos, J.A. Oliver, and M.A. Blanco, HLA and maturity onset diabetes of the young, Letter to the Editor, Diabetologia 24: 460 (1983).

    Article  PubMed  CAS  Google Scholar 

  2. J. Barbosa, R. King, F.C. Goetz, H. Noreen, and E.J. Yuns, HLA in maturity-onset type of hyperglycemia in the young, Arch. Intern. Med. 138: 90–93 (1978).

    Article  CAS  Google Scholar 

  3. J. Barbosa, R. Ramsay, and F.C. Goetz, Plasma glucose, insulin glucagon and growth hormone in kindreds with maturity-onset type of hyperglycemia in young people, Ann. Intern. Med. 88: 595 (1978).

    Article  PubMed  CAS  Google Scholar 

  4. G.I. Bell, S. Horita, and J.H. Karam, A polymorphic locus adjacent to the human insulin gene and diabetes mellitus, Diabetes 31: 65A (1982).

    Google Scholar 

  5. J.I. Bell, J.S. Wainscoat, J.H. Old, C. Chlouverakis, H. Keen, R.C. Turner, and D.J. Weatherall, Maturity onset diabetes of the young is not linked to the insulin gene, Br. Med. J. 286: 590–592 (1983).

    Article  CAS  Google Scholar 

  6. B.R. Briggs, W.P.U. Jackson, E.D. Dutoit, and M.C. Botha, The histocompatibility (HLA) antigen distribution in diabetes in Southern African Blacks (Xhosa), Diabetes 29: 68–71 (1980).

    Article  PubMed  CAS  Google Scholar 

  7. J.W. Conn, and S.S. Fajans, The prediabetic state, A concept of dynamic resistance to a genetic diabetogenic influence, Am. J. Med., 31: 839–850 (1961).

    Article  PubMed  CAS  Google Scholar 

  8. R.A. DeFronzo, and E. Ferrannini, The pathogenesis of non-insulin-dependent diabetes, An Update, Medicine 61: 125–140 (1982)

    Article  PubMed  CAS  Google Scholar 

  9. R.B. Elliott, D. O’Brien, and C.C. Roy, An abnormal insulin in juvenile diabetes mellitus, Diabetes 14: 780 (1966).

    Google Scholar 

  10. O.K., Faber, M. Thomsen, C. Binder, P. Platz, and A. Svejgaard, HLA antigens in a family with maturity-onset type diabetes mellitus, Acta Endocrinologica 88: 329–338 (1978).

    Google Scholar 

  11. S.S. Fajans, Etiologic aspects of types of diabetes, Diabetes Care 4: 69–75 (1981).

    PubMed  CAS  Google Scholar 

  12. S.S. Fajans, Unpublished Observations.

    Google Scholar 

  13. S.S. Fajans, The natural history of idiopathic diabetes mellitus, Heterogeneity of insulin responses in latent diabetes. in: “The Genetics of Diabetes Mellitus,” W. Crutzfeldt, J. Köbberling, and J.V. Neel, eds., Springer-Verlag, Heidelberg, pp. 64–78 (1976).

    Chapter  Google Scholar 

  14. S.S. Fajans, Heterogeneity between various families with non-insulin-dependent diabetes of the MODY type. in: “The Genetics of Diabetes Mellitus,” J. Köbberling, and R. Tattersall, eds., Serono Symposium No. 47, Academic Press, London and New York, pp. 251–260 (1982).

    Google Scholar 

  15. S.S. Fajans, M.C. Cloutier, and R.L. Crowther, Clinical and etiologic heterogeneity of idiopathic diabetes mellitus, Diabetes 27: 1112–1125 (1978).

    PubMed  CAS  Google Scholar 

  16. S.S. Fajans, and J.W. Conn, Prediabetes, subclinical diabetes, and latent clinical diabetes: Interpretation, diagnosis and treatment, in: On the Nature and Treatment of Diabetes, B.S. Leibel, and G.S. Wrenshall, eds, Amsterdam, Excerpta Medica International Congress Series 84, pp. 641–656 (1965).

    Google Scholar 

  17. S.S. Fajans, and J.W. Conn, Tolbutamide-induced improvement in carbohydrate tolerance of young people with mild diabetes mellitus, Diabetes 9: 83–88 (1960).

    PubMed  CAS  Google Scholar 

  18. S.S. Fajans, J.C. Floyd Jr., C.I. Taylor, and S. Pek, Heterogeneity of insulin responses in latent diabetes, Trans. Assoc. Am. Phys. 87: 83–94 (1974).

    PubMed  CAS  Google Scholar 

  19. S.N.T. Fui, H. Keen, J. Jarrett, V. Gossain, and P. Marsden, Test for chlorpropamide-alcohol flush becomes positive after prolonged chlorpropamide treatment in insulin-dependent diabetics, N. Engl. J. Med. 309: 93–96 (1983).

    Article  PubMed  CAS  Google Scholar 

  20. T. Gelehrter, V. Dilworth, B. Balka, R. McDonald, and E. Schorry, Insulin binding and insulin action in fibroblasts from patients with maturity-onset diabetes of the young, Diabetes 30: 940–946 (1981).

    PubMed  CAS  Google Scholar 

  21. T. Gelehrter, Unpublished Observations.

    Google Scholar 

  22. M. Haneda, K.S. Polonsky, R.M. Bergenstal, J.B. Jaspan, S.E. Shoelson, P.M. Blix, S.J. Chan, S.C.M. Kwok, W.B. Wishner, A. Zeidler, J.M. Olefsky, G. Freidenberg, H.S. Tager, D.F. Steiner, and A.H. Rubenstein, Familial hyperinsulinemia due to a structurally abnormal insulin, N. Engl. J. Med. 1288–1294 (1984).

    Google Scholar 

  23. M. Haneda, S.J. Chan, S.C.M. Kwok, A.H. Rubenstein, and D.F. Steiner, Studies on mutant human insulin genes: Identification and sequence analysis of a gene encoding (SerB24) insulin, Proc. Natl. Acad. Sci. USA 80: 6366–6370 (1983).

    Article  PubMed  CAS  Google Scholar 

  24. B.V. Howard, H. Hidaka, F. Ishibashi, R.M. Fields, and P.H. Bennett, Type II diabetes and inherent cellular defects in insulin sensitivity, Diabetes 30: 562–567 (1981).

    Article  PubMed  CAS  Google Scholar 

  25. I. Jialal, and S.M. Joubert, Obesity does not modulate insulin secretion in Indian patients with non-insulin-dependent diabetes in the young, Diabetes Care 7: 77–79 (1984).

    Article  PubMed  CAS  Google Scholar 

  26. K. Johansen, and G. Gregersen, A family with dominantly inherited mild juvenile diabetes, Acta Med. Scand. 201: 567–570 (1977).

    CAS  Google Scholar 

  27. C. Johnston, D. Owerbach, R.D.G. Leslie, D.A. Pyke, and J. Nerup, Mason-type diabetes and DNA insertion polymorphism. Lancet 1: 280 (1984).

    Article  PubMed  CAS  Google Scholar 

  28. H. Keen, Problems in the definition of diabetes mellitus and its subtypes, in: “The Genetics of Diabetes Mellitus,” J. Köbberling, and R. Tattersall, eds, Serono Symposium, V. 47, Academic Press, London and New York, pp. 1–11 (1982).

    Google Scholar 

  29. J.R. Kimmel, and H.G. Pollock, Studies of human insulin from nondiabetic and diabetic pancreas, Diabetes 16: 687–694 (1967).

    PubMed  CAS  Google Scholar 

  30. J. Köbberling, Studies on the genetic heterogeneity of diabetes mellitus, Diabetologia 7: 46–49 (1971).

    Article  PubMed  Google Scholar 

  31. J. Köbberling, N. Bengsch, B. Brüggeboes, H. Schwarck, H. Tillil, and M. Weber, The chlorpropamide alcohol flush, Lack of specificity for familial non-insulin dependent diabetes, Diabetologia 19: 359–363 (1980).

    Article  PubMed  Google Scholar 

  32. Kosaka, K., and Y. Akanuma, Heterogeneity of plasma IRI responses in patients with IGT, Letter to the Editor, Diabetologia 18: 347–348 (1980).

    PubMed  CAS  Google Scholar 

  33. T. Kuzuya, and A. Matsuda, Family histories of diabetes among Japanese patients with type I (insulin-dependent) and type 2 (noninsulin-dependent) diabetes, Diabetologia 22: 372–374 (1982).

    Article  PubMed  CAS  Google Scholar 

  34. R.D.G. Leslie, A.H. Barnett, D.A. Pyke, Chlorpropamide alcohol flushing and diabetic retinopathy, Lancet 1: 997–999 (1979).

    Article  PubMed  CAS  Google Scholar 

  35. H. Lestradet, I. Deschamps, and B. Giron, Insulin and free fatty acid levels during oral glucose tolerance tests and their relation to age in 70 healthy children, Diabetes 25: 505 (1976).

    Article  PubMed  CAS  Google Scholar 

  36. V. Mohan, C. Snehalatha, A. Ramachandran, R. Jayashree, and M. Viswanathan, Pancreatic beta-cell function in tropical pancreatic diabetes, Metabolism 32: 1091–1092 (1983).

    Article  PubMed  CAS  Google Scholar 

  37. National Diabetes Data Group, Classification of diabetes mellitus and other categories of glucose intolerance, Diabetes 28: 1039–1057 (1979).

    Google Scholar 

  38. P.G. Nelson, and D.A. Pyke, Genetic diabetes not linked to the HLA locus, Br. Med. J. 1: 196–197 (1976).

    Article  PubMed  CAS  Google Scholar 

  39. J. Nerup, K. Johansen, P. Aaby Svendsen, P. Billesblle, S. Poulsen, B. Thomsen, and D. Owerbach, DNA sequences flanking the insulin gene and the genetics of diabetes syndrome, Diabetologia 23: 188 (1982).

    Google Scholar 

  40. J.M. Okefsky, and O.G. Kolterman, Mechanisms of insulin resistance in obesity and noninsulin-dependent (Type II) diabetes, Am. J. Med. 70: 151 (1981).

    Article  Google Scholar 

  41. D. Owerbach, S. Poulsen, P. Billesblle, and J. Nerup, DNA sequence near the insulin gene affect glucose regulation, Diabetes 31: 65A (1982).

    Google Scholar 

  42. D. Owerbach, B. Thomsen, K. Johansen, L.U. Lamm, and J. Nerup, DNA insertion sequences near the insulin gene are not associated with maturity-onset diabetes of young people, Diabetologia 25: 18–20 (1983).

    Article  PubMed  CAS  Google Scholar 

  43. G. Panzram, W. Adolph, Heterogeneity of maturity onset diabetes at young age (MODY), Lancet 2: 986 (1981).

    Article  PubMed  CAS  Google Scholar 

  44. P. Platz, B.K. Jakobsen, A. Svejgaard, B.S. Thomsen, K.B. Jensen, K. Henningsen, and L.U. Lamm, No evidence for linkage between HLA and maturity onset type of diabetes in young people, Diabetologia 23: 16–18 (1982).

    Article  PubMed  CAS  Google Scholar 

  45. H.J. Prince, P. Tsai, and J.H. Olefsky, Insulin binding, internalization, and insulin receptor regulation in fibroblasts from Type II, non-insulin-dependent diabetes subjects, Diabetes 30: 596–600 (1981).

    Article  PubMed  CAS  Google Scholar 

  46. D.A. Pyke, Diabetes: The genetic connections, Diabetologia 17: 333–343 (1979).

    Article  PubMed  CAS  Google Scholar 

  47. G.M. Reaven, and J.M. Olefsky, Relationship between heterogeneity of insulin responses and insulin resistance in normal subjects and patients with chemical diabetes, Diabetologia 13: 201–206 (1977)

    Article  PubMed  CAS  Google Scholar 

  48. A.L. Rosenbloom, L. Wheeler, R. Bianchi, F.T. Chin, C.M. Tiwary and A. Grgic, Age-related analysis of insulin responses during normal and abnormal glucose tolerance tests in children and adolescents, Diabetes 24: 820 (1975).

    Article  PubMed  CAS  Google Scholar 

  49. P. Rotwein, R. Chyn, J. Chirgwin, B. Cordell, H.M. Goodman, and M.A. Permutt, Polymorphism in the 5’-flanking region of the human insulin gene and its possible relation to Type 2 Diabetes, Science 213: 1117–1120 (1981).

    Article  PubMed  CAS  Google Scholar 

  50. S.W. Sarjeantson, D.P. Ryan, P. Ram, and P. Zimmet, HLA and non-insulin dependent diabetes in Fiji Indians, Med. J. Aust. 1: 462–463 (1981)

    Google Scholar 

  51. P.J. Savage, R.F. Hamman, and P.H. Bennett, Prediabetes in the Pima Indians, In: “Advances in Experimental Medicine and Biology: Treatment of Early Diabetes,“ edited by Camerini-Davalos, R.A., and Hanover, B., Plenum Press, New York, pp. 13–19 (1979).

    Google Scholar 

  52. J.A. Scarlett, 0.G. Kolterman, P. Moore, M. Saekow, J. Insel, J. Griffin, M. Mako, A.H. Rubenstein, and J.H. Olefsky, Insulin resistance and diabetes due to a genetic defect in insulin receptors, J. Clin. Endo. and Metab. 55: 123–132 (1982).

    Article  CAS  Google Scholar 

  53. S. Seino, A. Funakoshi, A. Vinik, S.S. Fajans, Unpublished observations.

    Google Scholar 

  54. S. Shoelson, M. Haneda, P. Blix, A. Nanjo, T. Sanke, K. Inouye, D. Steiner, A. Rubenstein, and H. Tager, Three mutant insulins in man, Nature 302: 540–543 (1983).

    Article  PubMed  CAS  Google Scholar 

  55. S. Shoelson, M. Fickova, M. Haneda, A. Nahum, G. Musso, E.T. Kaiser, A.H. Rubenstein, and H. Tager, Identification of a mutant human insulin predicted to contain a serine for phenyl-alanine substitution, Proc. Natl. Sci. USA. 80: 7390–7394 (1983).

    Article  CAS  Google Scholar 

  56. R.B. Tattersall, Mild familial diabetes with dominant inheritance, Quarterly J. Med. 43: 339 (1974).

    CAS  Google Scholar 

  57. R.B. Tattersall, and S.S. Fajans, A difference between the inheritance of classic juvenile-onset and maturity-onset type diabetes of young people, Diabetes 24: 44–53 (1975).

    Article  PubMed  CAS  Google Scholar 

  58. WHO expert Committee on Diabetes Mellitus, Second Report, World Health Organization Tech. Rep. Ser.:646 ( 1980, Geneva: WHO).

    Google Scholar 

  59. R.C. Williams, W.C. Knowler, W.J. Butler, D.J. Pettitt, J.R. Lisse, P.H. Bennett, D.L. Mann, A.N. Johnson, and P.I. Terasaki, HLA-A2 and type 2 (insulin dependent) diabetes mellitus in Pima Indians: An association of allele frequency with age, Diabetologia 21: 460–463 (1981).

    Article  PubMed  CAS  Google Scholar 

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Fajans, S.S. (1985). Heterogeneity within Type II and Mody Diabetes. In: Vranic, M., Hollenberg, C.H., Steiner, G. (eds) Comparison of Type I and Type II Diabetes. Advances in Experimental Medicine and Biology, vol 189. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-1850-8_5

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  • DOI: https://doi.org/10.1007/978-1-4757-1850-8_5

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