Latent autoimmune diabetes in adults differs genetically from classical type 1 diabetes diagnosed after the age of 35 years

TY - JOUR

T1 - Latent autoimmune diabetes in adults differs genetically from classical type 1 diabetes diagnosed after the age of 35 years

AU - Andersen, Mette K.

AU - Lundgren, Virve

AU - Turunen, Joni A.

AU - Forsblom, Carol

AU - Isomaa, Bo

AU - Groop, Per Henrik

AU - Groop, Leif

AU - Tuomi, Tiinamaija

PY - 2010/9/1

Y1 - 2010/9/1

N2 - OBJECTIVE - We studied differences between patients with latent autoimmune diabetes in adults (LADA), type 2 diabetes, and classical type 1 diabetes diagnosed after age 35 years. RESEARCH DESIGN AND METHODS - Polymorphisms in HLA-DQB1, INS, PTPN22, and CTLA4 were genotyped in patients with LADA (n = 213), type 1 diabetes diagnosed at >35 years of age (T1D>35y; n = 257) or <20 years of age (T1D<20y; n = 158), and type 2 diabetes. RESULTS - Although patients with LADA had an increased frequency of HLA-DQB1 and PTPN22 risk genotypes and alleles compared with type 2 diabetic subjects, the frequency was significantly lower compared with T1D >35y patients. Genotype frequencies, measures of insulin secretion, and metabolic traits within LADA differed according to GAD antibody (GADA) quartiles, but even the highest quartile differed from type 1 diabetes. Having two or more risk genotypes was associated with lower C-peptide concentrations in LADA. CONCLUSIONS - LADA patients differed genetically and phenotypically from both T1D>35y and type 2 diabetic patients in a manner dependent on GADA levels.

AB - OBJECTIVE - We studied differences between patients with latent autoimmune diabetes in adults (LADA), type 2 diabetes, and classical type 1 diabetes diagnosed after age 35 years. RESEARCH DESIGN AND METHODS - Polymorphisms in HLA-DQB1, INS, PTPN22, and CTLA4 were genotyped in patients with LADA (n = 213), type 1 diabetes diagnosed at >35 years of age (T1D>35y; n = 257) or <20 years of age (T1D<20y; n = 158), and type 2 diabetes. RESULTS - Although patients with LADA had an increased frequency of HLA-DQB1 and PTPN22 risk genotypes and alleles compared with type 2 diabetic subjects, the frequency was significantly lower compared with T1D >35y patients. Genotype frequencies, measures of insulin secretion, and metabolic traits within LADA differed according to GAD antibody (GADA) quartiles, but even the highest quartile differed from type 1 diabetes. Having two or more risk genotypes was associated with lower C-peptide concentrations in LADA. CONCLUSIONS - LADA patients differed genetically and phenotypically from both T1D>35y and type 2 diabetic patients in a manner dependent on GADA levels.

UR - http://www.scopus.com/inward/record.url?scp=79951607479&partnerID=8YFLogxK

U2 - 10.2337/dc09-2188

DO - 10.2337/dc09-2188

M3 - Journal article

C2 - 20805278

AN - SCOPUS:79951607479

SN - 0149-5992

VL - 33

SP - 2062

EP - 2064

JO - Diabetes Care

JF - Diabetes Care

IS - 9

ER -