Literature DB >> 8343743

Genetic susceptibility to non-insulin dependent diabetes mellitus and glucose intolerance are located in HLA region.

E Tuomilehto-Wolf1, J Tuomilehto, G A Hitman, A Nissinen, J Stengård, J Pekkanen, P Kivinen, E Kaarsalo, M J Karvonen.   

Abstract

OBJECTIVES: To test the hypothesis that the genetic susceptibility to non-insulin dependent diabetes mellitus is the same as that to insulin dependent disease and to see whether glucose intolerance is associated with specific HLA haplotypes.
DESIGN: Population based study of men in 1989 first tested for glucose tolerance in 1984. HLA haplotypes, including HLA-A, C, B, DR, and DQ, were defined serologically. HLA haplotype data from a population based Finnish study of childhood diabetes were used for predicting non-insulin dependent diabetes and impaired glucose tolerance.
SETTING: Two communities in Finland.
SUBJECTS: Representative cohort of Finnish men aged 70-89, comprising 98 men with non-insulin dependent diabetes mellitus and a randomly selected group of 74 men, who served as controls, who were tested for glucose tolerance twice within five years. MAIN OUTCOME MEASURES: Non-insulin dependent diabetes, impaired glucose tolerance, blood glucose concentration.
RESULTS: Diabetes associated HLA haplotypes were present in 94% (85/90) of diabetic subjects, 79% (27/34) of subjects with impaired glucose tolerance, and only 13% (3/23) of non-diabetic subjects. In this group of elderly men sensitivity of the diabetes associated HLA haplotypes for non-insulin dependent diabetes and impaired glucose tolerance was 90%, specificity 87%, and predictive power 97%. Mean fasting blood glucose concentration was only just significantly higher in men with diabetes associated haplotypes than in men with no such haplotypes, but there was a substantial difference in blood glucose values two hours after glucose loading (10.4 and 6.4 mmol/l in men with diabetes associated HLA haplotypes and men with no such haplotypes, respectively (p < 0.0001)).
CONCLUSIONS: These findings support the hypothesis that specific HLA haplotypes exhibit a common genetic determinant for insulin dependent and non-insulin dependent diabetes. Furthermore, HLA is a major genetic determinant of glucose intolerance in elderly Finnish men. The belief that the HLA predisposition to diabetes is specific for insulin dependent diabetes mellitus is largely incorrect.

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Year:  1993        PMID: 8343743      PMCID: PMC1678370          DOI: 10.1136/bmj.307.6897.155

Source DB:  PubMed          Journal:  BMJ        ISSN: 0959-8138


  22 in total

1.  Evidence for HL-A-linked genes in "juvenile" diabetes mellitus.

Authors:  A G Cudworth; J C Woodrow
Journal:  Br Med J       Date:  1975-07-19

Review 2.  Genetics of diabetes.

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Journal:  Clin Endocrinol Metab       Date:  1977-07

3.  Histocompatibility (HL-A) antigens, lymphocytotoxic antibodies and tissue antibodies in patients with diabetes mellitus.

Authors:  D P Singal; M A Blajchman
Journal:  Diabetes       Date:  1973-06       Impact factor: 9.461

4.  HL-A antigens and diabetes mellitus.

Authors:  J Nerup; P Platz; O O Andersen; M Christy; J Lyngsoe; J E Poulsen; L P Ryder; L S Nielsen; M Thomsen; A Svejgaard
Journal:  Lancet       Date:  1974-10-12       Impact factor: 79.321

5.  Diabetes in identical twins. A study of 200 pairs.

Authors:  A H Barnett; C Eff; R D Leslie; D A Pyke
Journal:  Diabetologia       Date:  1981-02       Impact factor: 10.122

6.  HLA factors in non-insulin-dependent diabetes mellitus.

Authors:  A Arnaiz-Villena; S Rodríguez de Córdoba; I L Dujovne; J R Regueiro; A Bootello; M Serrano-Rios
Journal:  N Engl J Med       Date:  1980-10-30       Impact factor: 91.245

7.  HLA haplotypes in type 1 (insulin-dependent) diabetes mellitus: molecular analysis of the HLA-DQ locus. The DIME Study Group.

Authors:  P J Tienari; E Tuomilehto-Wolf; J Tuomilehto; L Peltonen
Journal:  Diabetologia       Date:  1992-03       Impact factor: 10.122

8.  The histocompatibility (HLA) antigen distribution in diabetes in southern African Blacks (Xhosa).

Authors:  B R Briggs; W P Jackson; E D DuToit; M C Botha
Journal:  Diabetes       Date:  1980-01       Impact factor: 9.461

9.  HLA and non-insulin dependent diabetes in Fiji indians.

Authors:  S W Serjeantson; D P Ryan; P Ram; P Zimmet
Journal:  Med J Aust       Date:  1981-05-02       Impact factor: 7.738

10.  Non-insulin-dependent diabetes mellitus with early onset in Blacks and Indians.

Authors:  A C Asmal; B Dayal; I Jialal; W P Leary; M A Omar; N L Pillay; F T Thandroyen
Journal:  S Afr Med J       Date:  1981-07-18
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  15 in total

1.  HLA typing is not predictive of proliferative diabetic retinopathy in patients with younger onset type 2 diabetes mellitus.

Authors:  T Mimura; S Amano; S Kato; M Araie; H Funatsu; S Kitano; E Shimizu; H Noma; O Yoshino; S Hori
Journal:  Br J Ophthalmol       Date:  2004-02       Impact factor: 4.638

2.  The imbalance of Th17/Th1/Tregs in patients with type 2 diabetes: relationship with metabolic factors and complications.

Authors:  Chun Zeng; Xiaoyun Shi; Baojun Zhang; He Liu; Lianjun Zhang; Wenjun Ding; Yong Zhao
Journal:  J Mol Med (Berl)       Date:  2011-10-01       Impact factor: 4.599

3.  In Finland insulin gene region encoded susceptibility to IDDM exerts maximum effect when there is low HLA-DR associated risk. DiMe (Childhood Diabetes in Finland) Study Group.

Authors:  K A Metcalfe; G A Hitman; M J Fennessy; M I McCarthy; J Tuomilehto; E Tuomilehto-Wolf
Journal:  Diabetologia       Date:  1995-10       Impact factor: 10.122

Review 4.  An immune origin of type 2 diabetes?

Authors:  H Kolb; T Mandrup-Poulsen
Journal:  Diabetologia       Date:  2005-04-30       Impact factor: 10.122

5.  Type 1, type 1.5, and type 2 diabetes: NOD the diabetes we thought it was.

Authors:  Marc Y Donath; Jan A Ehses
Journal:  Proc Natl Acad Sci U S A       Date:  2006-08-07       Impact factor: 11.205

6.  Changing perspectives in diabetes: their impact on its classification.

Authors:  T J Wilkin
Journal:  Diabetologia       Date:  2007-04-25       Impact factor: 10.122

7.  A high incidence of type 1 diabetes and an alarming increase in the incidence of type 2 diabetes among young adults in Finland between 1992 and 1996.

Authors:  N Lammi; O Taskinen; E Moltchanova; I-L Notkola; J G Eriksson; J Tuomilehto; M Karvonen
Journal:  Diabetologia       Date:  2007-05-11       Impact factor: 10.122

Review 8.  The genetics of non-insulin-dependent diabetes mellitus: tools and aims.

Authors:  M I McCarthy; P Froguel; G A Hitman
Journal:  Diabetologia       Date:  1994-10       Impact factor: 10.122

9.  Genetic susceptibility to non-insulin dependent diabetes.

Authors:  L Groop; G F Bottazzo
Journal:  BMJ       Date:  1994-02-19

10.  A gene in the HLA class I region contributes to susceptibility to IDDM in the Finnish population. Childhood Diabetes in Finland (DiMe) Study Group.

Authors:  M Fennessy; K Metcalfe; G A Hitman; M Niven; P A Biro; J Tuomilehto; E Tuomilehto-Wolf
Journal:  Diabetologia       Date:  1994-09       Impact factor: 10.122

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