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HLA class II alleles specify phenotypes of ketosis-prone diabetes

Nalini, Ramaswami; Gaur, Lakshmi K; Maldonado, Mario; Hampe, Christiane S; Rodriguez, Lucille; Garza, Gilberto; Lernmark, Ake LU and Balasubramanyam, Ashok (2008) In Diabetes Care 31(6). p.1195-1200
Abstract

OBJECTIVE - Ketosis-prone diabetes (KPD) comprises four subgroups based on the presence or absence of β-cell autoantibodies (A+ or A-) and β-cell functional reserve (β + or β-). Genetic factors could contribute to their distinctive phenotypes. Our aim was to specify the role of HLA class II alleles associated with susceptibility or resistance to autoimmune type 1 diabetes in determining KPD phenotypes. RESEARCH DESIGN AND METHODS - A total of 185 adults presenting with diabetic ketoacidosis were followed longitudinally for a mean of 5.5 years, with measurements of auto- antibodies, β-cell functional reserve, insulin sensitivity, and insulin requirement. Frequencies of susceptibility and resistance alleles at HLA DQA1, DQB1, and DRB1... (More)

OBJECTIVE - Ketosis-prone diabetes (KPD) comprises four subgroups based on the presence or absence of β-cell autoantibodies (A+ or A-) and β-cell functional reserve (β + or β-). Genetic factors could contribute to their distinctive phenotypes. Our aim was to specify the role of HLA class II alleles associated with susceptibility or resistance to autoimmune type 1 diabetes in determining KPD phenotypes. RESEARCH DESIGN AND METHODS - A total of 185 adults presenting with diabetic ketoacidosis were followed longitudinally for a mean of 5.5 years, with measurements of auto- antibodies, β-cell functional reserve, insulin sensitivity, and insulin requirement. Frequencies of susceptibility and resistance alleles at HLA DQA1, DQB1, and DRB1 loci were correlated with clinical and phenotypic features of KPD subgroups and compared with those of ethnic-specific population control subjects. RESULTS - Susceptibility alleles were more frequent (P < 0.0001) in the two A+ than the two A- KPD subgroups; in the latter, the frequency was no greater than in population control subjects (except for DQB1 *0302). Susceptibility alleles differentiated the two clinically similar β- subgroups (more frequent in A+β - than A-β - KPD; P < 0.01). Resistance alleles were more frequent in the two β+ than the two β- KPD subgroups (P < 0.01). The frequencies of certain susceptibility (e.g., DQB1 *02) and resistance (DQB1 *0602) alleles were higher in African-American A-β+ KPD patients than in African-American control subjects. DQB1 *0302 was more frequent in all KPD subgroups compared with control subjects. CONCLUSIONS - HLA class II alleles associated with susceptibility or resistance to autoimmune type 1 diabetes help specify the four subgroups of KPD. Inheritance of these alleles may influence long-term β-cell functional reserve. © 2008 by the American Diabetes Association.

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author
publishing date
type
Contribution to journal
publication status
published
in
Diabetes Care
volume
31
issue
6
pages
6 pages
publisher
American Diabetes Association
external identifiers
  • scopus:48649088094
ISSN
0149-5992
DOI
10.2337/dc07-1971
language
English
LU publication?
no
id
80d44276-9e22-4c48-81ee-e1e7d896794c
date added to LUP
2017-09-07 11:21:46
date last changed
2017-09-07 11:21:46
@article{80d44276-9e22-4c48-81ee-e1e7d896794c,
  abstract     = {<p>OBJECTIVE - Ketosis-prone diabetes (KPD) comprises four subgroups based on the presence or absence of β-cell autoantibodies (A+ or A-) and β-cell functional reserve (β + or β-). Genetic factors could contribute to their distinctive phenotypes. Our aim was to specify the role of HLA class II alleles associated with susceptibility or resistance to autoimmune type 1 diabetes in determining KPD phenotypes. RESEARCH DESIGN AND METHODS - A total of 185 adults presenting with diabetic ketoacidosis were followed longitudinally for a mean of 5.5 years, with measurements of auto- antibodies, β-cell functional reserve, insulin sensitivity, and insulin requirement. Frequencies of susceptibility and resistance alleles at HLA DQA1, DQB1, and DRB1 loci were correlated with clinical and phenotypic features of KPD subgroups and compared with those of ethnic-specific population control subjects. RESULTS - Susceptibility alleles were more frequent (P &lt; 0.0001) in the two A+ than the two A- KPD subgroups; in the latter, the frequency was no greater than in population control subjects (except for DQB1 *0302). Susceptibility alleles differentiated the two clinically similar β- subgroups (more frequent in A+β - than A-β - KPD; P &lt; 0.01). Resistance alleles were more frequent in the two β+ than the two β- KPD subgroups (P &lt; 0.01). The frequencies of certain susceptibility (e.g., DQB1 *02) and resistance (DQB1 *0602) alleles were higher in African-American A-β+ KPD patients than in African-American control subjects. DQB1 *0302 was more frequent in all KPD subgroups compared with control subjects. CONCLUSIONS - HLA class II alleles associated with susceptibility or resistance to autoimmune type 1 diabetes help specify the four subgroups of KPD. Inheritance of these alleles may influence long-term β-cell functional reserve. © 2008 by the American Diabetes Association.</p>},
  author       = {Nalini, Ramaswami and Gaur, Lakshmi K and Maldonado, Mario and Hampe, Christiane S and Rodriguez, Lucille and Garza, Gilberto and Lernmark, Ake and Balasubramanyam, Ashok},
  issn         = {0149-5992},
  language     = {eng},
  number       = {6},
  pages        = {1195--1200},
  publisher    = {American Diabetes Association},
  series       = {Diabetes Care},
  title        = {HLA class II alleles specify phenotypes of ketosis-prone diabetes},
  url          = {http://dx.doi.org/10.2337/dc07-1971},
  volume       = {31},
  year         = {2008},
}