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. 2010 Sep;33(9):2062-4.
doi: 10.2337/dc09-2188.

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

Mette K Andersen  1 , Virve Lundgren, Joni A Turunen, Carol Forsblom, Bo Isomaa, Per-Henrik Groop, Leif Groop, Tiinamaija Tuomi
Affiliations

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

Mette K Andersen et al. Diabetes Care. 2010 Sep.

Abstract

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.

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Figures

Figure 1
Figure 1
On the left, distribution of HLA-DQB1 genotypes and PTPN22 (rs2476601) alleles in type 1 diabetic patients (T1D<20y, n = 158) or after the age of 35 years (T1D>35y, n = 257), LADA patients (n = 213), and type 2 diabetic patients (T2D, n = 648). On the right, distribution of HLA-DQB1 genotypes and PTPN22 (rs2476601) alleles in LADA patients stratified according to GADA quartiles: the highest, LADAhigh (n = 52); the two middle quartiles pooled, LADAmid (n = 109); and the lowest, LADAlow (n = 52). Black columns represent risk genotypes and alleles, and white columns represent protective (HLA-DQB1) or nonrisk (PTPN22) genotypes and alleles. The χ2 test was applied to test differences between diabetic groups. Significant differences are indicated with asterisks. *P < 0.05. **P < 0.0001. HLA-DQB1: P = 0.01 across the GADA quartiles of LADA.
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