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Family history of type 1 and type 2 diabetes and risk of latent autoimmune diabetes in adults (LADA)

Hjort, Rebecka; Alfredsson, L; Andersson, T.; Carlsson, P. O.; Grill, V; Groop, L. LU ; Martinell, M.; Rasouli, B.; Storm, P. LU and Tuomi, T. LU , et al. (2017) In Diabetes and Metabolism
Abstract

Background: A family history of diabetes (FHD) is a strong predictor of diabetes risk, yet has rarely been investigated in latent autoimmune diabetes in adults (LADA). This study therefore investigated the risk of LADA and type 2 diabetes (T2D) in relation to FHD, taking into account the type of diabetes in relatives. Methods: Data from a population-based study were used, including incident cases of LADA [glutamic acid decarboxylase antibody (GADA)-positive, n = 378] and T2D (GADA-negative, n = 1199), and their matched controls (n = 1484). First-degree relatives with disease onset at age. <. 40 years and taking insulin treatment were classified as type 1 diabetes (T1D) or, if otherwise, as T2D. Odds ratios (ORs) were adjusted for... (More)

Background: A family history of diabetes (FHD) is a strong predictor of diabetes risk, yet has rarely been investigated in latent autoimmune diabetes in adults (LADA). This study therefore investigated the risk of LADA and type 2 diabetes (T2D) in relation to FHD, taking into account the type of diabetes in relatives. Methods: Data from a population-based study were used, including incident cases of LADA [glutamic acid decarboxylase antibody (GADA)-positive, n = 378] and T2D (GADA-negative, n = 1199), and their matched controls (n = 1484). First-degree relatives with disease onset at age. <. 40 years and taking insulin treatment were classified as type 1 diabetes (T1D) or, if otherwise, as T2D. Odds ratios (ORs) were adjusted for age, gender, BMI, education and smoking. Cases were genotyped for high- and low-risk HLA genotypes. Results: Both FHD-T1D (OR: 5.8; 95% CI: 3.2-10.3) and FHD-T2D (OR: 1.9; 95% CI: 1.5-2.5) were associated with an increased risk of LADA, whereas the risk of T2D was associated with FHD-T2D (OR: 2.7; 95% CI: 2.2-3.3), but not FHD-T1D. In LADA patients, FHD-T1D vs FHD-T2D was associated with higher GADA but lower C-peptide levels, lower prevalence of low-risk HLA genotypes (5.0% vs 28.6%, respectively; P = 0.038) and a tendency for higher prevalence of high-risk genotypes (90.0% vs 69.1%, respectively; P = 0.0576). Conclusion: The risk of LADA is substantially increased with FHD-T1D but also, albeit significantly less so, with FHD-T2D. This supports the idea of LADA as a mix of both T1D and T2D, but suggests that the genes related to T1D have greater impact. LADA patients with FHD-T1D had more T1D-like features, emphasizing the heterogeneity of LADA.

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epub
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keywords
Autoimmune diabetes, Case-control study, Family history of diabetes, Heredity, Latent autoimmune diabetes in adults, Type 2 diabetes
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Diabetes and Metabolism
publisher
Masson Editeur
external identifiers
  • scopus:85021314171
ISSN
1262-3636
DOI
10.1016/j.diabet.2017.05.010
language
English
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yes
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4106bb55-8869-4e85-8994-8f239929ac22
date added to LUP
2017-08-18 14:58:52
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2017-08-19 03:00:10
@article{4106bb55-8869-4e85-8994-8f239929ac22,
  abstract     = {<p>Background: A family history of diabetes (FHD) is a strong predictor of diabetes risk, yet has rarely been investigated in latent autoimmune diabetes in adults (LADA). This study therefore investigated the risk of LADA and type 2 diabetes (T2D) in relation to FHD, taking into account the type of diabetes in relatives. Methods: Data from a population-based study were used, including incident cases of LADA [glutamic acid decarboxylase antibody (GADA)-positive, n = 378] and T2D (GADA-negative, n = 1199), and their matched controls (n = 1484). First-degree relatives with disease onset at age. &lt;. 40 years and taking insulin treatment were classified as type 1 diabetes (T1D) or, if otherwise, as T2D. Odds ratios (ORs) were adjusted for age, gender, BMI, education and smoking. Cases were genotyped for high- and low-risk HLA genotypes. Results: Both FHD-T1D (OR: 5.8; 95% CI: 3.2-10.3) and FHD-T2D (OR: 1.9; 95% CI: 1.5-2.5) were associated with an increased risk of LADA, whereas the risk of T2D was associated with FHD-T2D (OR: 2.7; 95% CI: 2.2-3.3), but not FHD-T1D. In LADA patients, FHD-T1D vs FHD-T2D was associated with higher GADA but lower C-peptide levels, lower prevalence of low-risk HLA genotypes (5.0% vs 28.6%, respectively; P = 0.038) and a tendency for higher prevalence of high-risk genotypes (90.0% vs 69.1%, respectively; P = 0.0576). Conclusion: The risk of LADA is substantially increased with FHD-T1D but also, albeit significantly less so, with FHD-T2D. This supports the idea of LADA as a mix of both T1D and T2D, but suggests that the genes related to T1D have greater impact. LADA patients with FHD-T1D had more T1D-like features, emphasizing the heterogeneity of LADA.</p>},
  author       = {Hjort, Rebecka and Alfredsson, L and Andersson, T. and Carlsson, P. O. and Grill, V and Groop, L. and Martinell, M. and Rasouli, B. and Storm, P. and Tuomi, T. and Carlsson, S.},
  issn         = {1262-3636},
  keyword      = {Autoimmune diabetes,Case-control study,Family history of diabetes,Heredity,Latent autoimmune diabetes in adults,Type 2 diabetes},
  language     = {eng},
  publisher    = {Masson Editeur},
  series       = {Diabetes and Metabolism},
  title        = {Family history of type 1 and type 2 diabetes and risk of latent autoimmune diabetes in adults (LADA)},
  url          = {http://dx.doi.org/10.1016/j.diabet.2017.05.010},
  year         = {2017},
}