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Overweight, obesity and the risk of LADA : results from a Swedish case–control study and the Norwegian HUNT Study

Hjort, Rebecka; Ahlqvist, Emma LU ; Carlsson, Per Ola; Grill, Valdemar; Groop, Leif LU ; Martinell, Mats; Rasouli, Bahareh; Rosengren, Anders; Tuomi, Tiinamaija LU and Åsvold, Bjørn Olav, et al. (2018) In Diabetologia 61(6). p.1333-1343
Abstract

Aims/hypothesis: Excessive weight is a risk factor for type 2 diabetes, but its role in the promotion of autoimmune diabetes is not clear. We investigated the risk of latent autoimmune diabetes in adults (LADA) in relation to overweight/obesity in two large population-based studies. Methods: Analyses were based on incident cases of LADA (n = 425) and type 2 diabetes (n = 1420), and 1704 randomly selected control participants from a Swedish case–control study and prospective data from the Norwegian HUNT Study including 147 people with LADA and 1,012,957 person-years of follow-up (1984–2008). We present adjusted ORs and HRs with 95% CI. Results: In the Swedish data, obesity was associated with an increased risk of LADA (OR 2.93, 95% CI... (More)

Aims/hypothesis: Excessive weight is a risk factor for type 2 diabetes, but its role in the promotion of autoimmune diabetes is not clear. We investigated the risk of latent autoimmune diabetes in adults (LADA) in relation to overweight/obesity in two large population-based studies. Methods: Analyses were based on incident cases of LADA (n = 425) and type 2 diabetes (n = 1420), and 1704 randomly selected control participants from a Swedish case–control study and prospective data from the Norwegian HUNT Study including 147 people with LADA and 1,012,957 person-years of follow-up (1984–2008). We present adjusted ORs and HRs with 95% CI. Results: In the Swedish data, obesity was associated with an increased risk of LADA (OR 2.93, 95% CI 2.17, 3.97), which was even stronger for type 2 diabetes (OR 18.88, 95% CI 14.29, 24.94). The association was stronger in LADA with low GAD antibody (GADA; <median) (OR 4.25; 95% CI 2.76, 6.52) but present also in LADA with high GADA (OR 2.14; 95% CI 1.42, 3.24). In the Swedish data, obese vs normal weight LADA patients had lower GADA levels, better beta cell function, and were more likely to have low-risk HLA-genotypes. The combination of overweight and family history of diabetes (FHD) conferred an OR of 4.57 (95% CI 3.27, 6.39) for LADA and 24.51 (95% CI 17.82, 33.71) for type 2 diabetes. Prospective data from HUNT indicated even stronger associations; HR for LADA was 6.07 (95% CI 3.76, 9.78) for obesity and 7.45 (95% CI 4.02, 13.82) for overweight and FHD. Conclusions/interpretation: Overweight/obesity is associated with increased risk of LADA, particularly when in combination with FHD. These findings support the hypothesis that, even in the presence of autoimmunity, factors linked to insulin resistance, such as excessive weight, could promote onset of diabetes.

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keywords
ANDIS, ANDiU, Body mass index, Case–control study, ESTRID, HUNT Study, LADA, Latent autoimmune diabetes in adults, Prospective study, Type 2 diabetes
in
Diabetologia
volume
61
issue
6
pages
11 pages
publisher
Springer
external identifiers
  • scopus:85044478822
ISSN
0012-186X
DOI
10.1007/s00125-018-4596-0
language
English
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yes
id
c67fe800-60e6-4a7c-9d24-52a40d7df9e7
date added to LUP
2018-05-22 12:57:59
date last changed
2019-04-10 04:08:31
@article{c67fe800-60e6-4a7c-9d24-52a40d7df9e7,
  abstract     = {<p>Aims/hypothesis: Excessive weight is a risk factor for type 2 diabetes, but its role in the promotion of autoimmune diabetes is not clear. We investigated the risk of latent autoimmune diabetes in adults (LADA) in relation to overweight/obesity in two large population-based studies. Methods: Analyses were based on incident cases of LADA (n = 425) and type 2 diabetes (n = 1420), and 1704 randomly selected control participants from a Swedish case–control study and prospective data from the Norwegian HUNT Study including 147 people with LADA and 1,012,957 person-years of follow-up (1984–2008). We present adjusted ORs and HRs with 95% CI. Results: In the Swedish data, obesity was associated with an increased risk of LADA (OR 2.93, 95% CI 2.17, 3.97), which was even stronger for type 2 diabetes (OR 18.88, 95% CI 14.29, 24.94). The association was stronger in LADA with low GAD antibody (GADA; &lt;median) (OR 4.25; 95% CI 2.76, 6.52) but present also in LADA with high GADA (OR 2.14; 95% CI 1.42, 3.24). In the Swedish data, obese vs normal weight LADA patients had lower GADA levels, better beta cell function, and were more likely to have low-risk HLA-genotypes. The combination of overweight and family history of diabetes (FHD) conferred an OR of 4.57 (95% CI 3.27, 6.39) for LADA and 24.51 (95% CI 17.82, 33.71) for type 2 diabetes. Prospective data from HUNT indicated even stronger associations; HR for LADA was 6.07 (95% CI 3.76, 9.78) for obesity and 7.45 (95% CI 4.02, 13.82) for overweight and FHD. Conclusions/interpretation: Overweight/obesity is associated with increased risk of LADA, particularly when in combination with FHD. These findings support the hypothesis that, even in the presence of autoimmunity, factors linked to insulin resistance, such as excessive weight, could promote onset of diabetes.</p>},
  author       = {Hjort, Rebecka and Ahlqvist, Emma and Carlsson, Per Ola and Grill, Valdemar and Groop, Leif and Martinell, Mats and Rasouli, Bahareh and Rosengren, Anders and Tuomi, Tiinamaija and Åsvold, Bjørn Olav and Carlsson, Sofia},
  issn         = {0012-186X},
  keyword      = {ANDIS,ANDiU,Body mass index,Case–control study,ESTRID,HUNT Study,LADA,Latent autoimmune diabetes in adults,Prospective study,Type 2 diabetes},
  language     = {eng},
  month        = {06},
  number       = {6},
  pages        = {1333--1343},
  publisher    = {Springer},
  series       = {Diabetologia},
  title        = {Overweight, obesity and the risk of LADA : results from a Swedish case–control study and the Norwegian HUNT Study},
  url          = {http://dx.doi.org/10.1007/s00125-018-4596-0},
  volume       = {61},
  year         = {2018},
}