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.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
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).
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).
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).
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).
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).
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).
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).
R.A. DeFronzo, and E. Ferrannini, The pathogenesis of non-insulin-dependent diabetes, An Update, Medicine 61: 125–140 (1982)
R.B. Elliott, D. O’Brien, and C.C. Roy, An abnormal insulin in juvenile diabetes mellitus, Diabetes 14: 780 (1966).
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).
S.S. Fajans, Etiologic aspects of types of diabetes, Diabetes Care 4: 69–75 (1981).
S.S. Fajans, Unpublished Observations.
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).
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).
S.S. Fajans, M.C. Cloutier, and R.L. Crowther, Clinical and etiologic heterogeneity of idiopathic diabetes mellitus, Diabetes 27: 1112–1125 (1978).
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).
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).
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).
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).
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).
T. Gelehrter, Unpublished Observations.
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).
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).
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).
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).
K. Johansen, and G. Gregersen, A family with dominantly inherited mild juvenile diabetes, Acta Med. Scand. 201: 567–570 (1977).
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).
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).
J.R. Kimmel, and H.G. Pollock, Studies of human insulin from nondiabetic and diabetic pancreas, Diabetes 16: 687–694 (1967).
J. Köbberling, Studies on the genetic heterogeneity of diabetes mellitus, Diabetologia 7: 46–49 (1971).
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).
Kosaka, K., and Y. Akanuma, Heterogeneity of plasma IRI responses in patients with IGT, Letter to the Editor, Diabetologia 18: 347–348 (1980).
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).
R.D.G. Leslie, A.H. Barnett, D.A. Pyke, Chlorpropamide alcohol flushing and diabetic retinopathy, Lancet 1: 997–999 (1979).
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).
V. Mohan, C. Snehalatha, A. Ramachandran, R. Jayashree, and M. Viswanathan, Pancreatic beta-cell function in tropical pancreatic diabetes, Metabolism 32: 1091–1092 (1983).
National Diabetes Data Group, Classification of diabetes mellitus and other categories of glucose intolerance, Diabetes 28: 1039–1057 (1979).
P.G. Nelson, and D.A. Pyke, Genetic diabetes not linked to the HLA locus, Br. Med. J. 1: 196–197 (1976).
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).
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).
D. Owerbach, S. Poulsen, P. Billesblle, and J. Nerup, DNA sequence near the insulin gene affect glucose regulation, Diabetes 31: 65A (1982).
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).
G. Panzram, W. Adolph, Heterogeneity of maturity onset diabetes at young age (MODY), Lancet 2: 986 (1981).
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).
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).
D.A. Pyke, Diabetes: The genetic connections, Diabetologia 17: 333–343 (1979).
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)
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).
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).
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)
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).
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).
S. Seino, A. Funakoshi, A. Vinik, S.S. Fajans, Unpublished observations.
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).
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).
R.B. Tattersall, Mild familial diabetes with dominant inheritance, Quarterly J. Med. 43: 339 (1974).
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).
WHO expert Committee on Diabetes Mellitus, Second Report, World Health Organization Tech. Rep. Ser.:646 ( 1980, Geneva: WHO).
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).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1985 Springer Science+Business Media New York
About this chapter
Cite this chapter
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
Download citation
DOI: https://doi.org/10.1007/978-1-4757-1850-8_5
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4757-1852-2
Online ISBN: 978-1-4757-1850-8
eBook Packages: Springer Book Archive