| 1. |
- Edstorp, Jessica, et al.
(author)
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Does a prior diagnosis of infectious disease confer an increased risk of latent autoimmune diabetes in adults?
- 2024
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In: Diabetes/Metabolism Research and Reviews. - 1520-7552. ; 40:3, s. e3758-
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Journal article (peer-reviewed)abstract
- Aims: Infections are proposed risk factors for type 1 diabetes in children. We examined whether a diagnosis of infectious disease also confers an increased risk of latent autoimmune diabetes in adults (LADA). Materials and methods: We used data from a population-based Swedish case-control study with incident cases of LADA (n = 597) and matched controls (n = 2386). The history of infectious disease was ascertained through national and regional patient registers. We estimated adjusted odds ratios (OR) with 95% confidence intervals for ≥1 respiratory (any/upper/lower), gastrointestinal, herpetic, other or any infectious disease episode, or separately, for 1 and ≥2 infectious disease episodes, within 0–1, 1–3, 3–5 and 5–10 years before LADA diagnosis/matching. Stratified analyses were performed on the basis of HLA risk genotypes and Glutamic acid decarboxylase antibodies (GADA) levels. Results: Individuals who developed LADA did not have a higher prevalence of infectious disease 1–10 years before diabetes diagnosis. For example, OR was estimated at 0.87 (0.66, 1.14) for any versus no respiratory infectious disease within 1–3 years. Similar results were seen for LADA with high-risk HLA genotypes (OR 0.95 [0.64, 1.42]) or high GADA levels (OR 1.10 [0.79, 1.55]), ≥2 episodes (OR 0.89 [0.56, 1.40]), and in infections treated using antibiotics (OR 1.03 [0.73, 1.45]). The only significant association was observed with lower respiratory disease the year preceding LADA diagnosis (OR 1.67 [1.06, 2.64]). Conclusions: Our findings do not support the idea that exposure to infections increases the risk of LADA. A higher prevalence of respiratory infection in the year before LADA diagnosis could reflect increased susceptibility to infections due to hyperglycemia.
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| 2. |
- Edstorp, Jessica, et al.
(author)
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Incidence of lada and type 2 diabetes in relation to tobacco use and genetic susceptibility to type 2 diabetes and related traits : Findings from a swedish case-control study and the norwegian hunt study
- 2023
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 46:5, s. 1028-1036
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Journal article (peer-reviewed)abstract
- OBJECTIVE Smoking and Swedish smokeless tobacco (snus) are associated with latent autoimmune diabetes in adults (LADA) and type 2 diabetes (T2D). Our aim was to investigate whether genetic susceptibility to T2D, insulin resistance (IR), and insulin secretion (IS) aggravate these associations. RESEARCH DESIGN AND METHODS We used data from two population-based Scandinavian studies with case subjects with LADA (n = 839) and T2D (n = 5,771), matched control subjects (n = 3,068), and 1,696,503 person-years at risk. Pooled, multivariate relative risks (RR) with 95% CI were estimated for smoking/genetic risk scores (T2D-GRS, IS-GRS, and IR-GRS), and ORs for snus or tobacco/GRS (case-control data). We estimated additive (proportion attributable to interaction [AP]) and multiplicative interaction between tobacco use and GRS. RESULTS The RR of LADA was elevated in high IR-GRS heavy smokers (‡15 pack-years; RR 2.01 [CI 1.30, 3.10]) and tobacco users (‡15 box/pack-years; RR 2.59 [CI 1.54, 4.35]) compared with low IR-GRS individuals without heavy use, with evidence of additive (AP 0.67 [CI 0.46, 0.89]; AP 0.52 [CI 0.21, 0.83]) and multiplicative (P = 0.003; P = 0.034) interaction. In heavy users, there was additive interaction between T2D-GRS and smoking, snus, and total tobacco use. The excess risk conferred by tobacco use did not differ across GRS categories in T2D. CONCLUSIONS Tobacco use may confer a higher risk of LADA in individuals with genetic susceptibility to T2D and insulin resistance, whereas genetic susceptibility does not seem to influence the increased T2D incidence associated with tobacco use.
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| 3. |
- Edstorp, Jessica, et al.
(author)
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Smoking, use of smokeless tobacco, HLA genotypes and incidence of latent autoimmune diabetes in adults
- 2023
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In: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 66, s. 70-81
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Journal article (peer-reviewed)abstract
- Aims/hypotheses: Smoking and use of smokeless tobacco (snus) are associated with an increased risk of type 2 diabetes. We investigated whether smoking and snus use increase the risk of latent autoimmune diabetes in adults (LADA) and elucidated potential interaction with HLA high-risk genotypes. Methods: Analyses were based on Swedish case–control data (collected 2010–2019) with incident cases of LADA (n=593) and type 2 diabetes (n=2038), and 3036 controls, and Norwegian prospective data (collected 1984–2019) with incident cases of LADA (n=245) and type 2 diabetes (n=3726) during 1,696,503 person-years of follow-up. Pooled RRs with 95% CIs were estimated for smoking, and ORs for snus use (case–control data only). The interaction was assessed by attributable proportion (AP) due to interaction. A two-sample Mendelian randomisation (MR) study on smoking and LADA/type 2 diabetes was conducted based on summary statistics from genome-wide association studies. Results: Smoking (RRpooled 1.30 [95% CI 1.06, 1.59] for current vs never) and snus use (OR 1.97 [95% CI 1.20, 3.24] for ≥15 box-years vs never use) were associated with an increased risk of LADA. Corresponding estimates for type 2 diabetes were 1.38 (95% CI 1.28, 1.49) and 1.92 (95% CI 1.27, 2.90), respectively. There was interaction between smoking and HLA high-risk genotypes (AP 0.27 [95% CI 0.01, 0.53]) in relation to LADA. The positive association between smoking and LADA/type 2 diabetes was confirmed by the MR study. Conclusions/interpretation: Our findings suggest that tobacco use increases the risk of LADA and that smoking acts synergistically with genetic susceptibility in the promotion of LADA. Data availability: Analysis codes are shared through GitHub (https://github.com/jeseds/Smoking-use-of-smokeless-tobacco-HLA-genotypes-and-incidence-of-LADA). Graphical abstract: [Figure not available: see fulltext.]
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| 4. |
- Hjort, Rebecka, et al.
(author)
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Overweight, obesity and the risk of LADA : results from a Swedish case–control study and the Norwegian HUNT Study
- 2018
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In: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 61:6, s. 1333-1343
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Journal article (peer-reviewed)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 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;
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| 5. |
- Rasouli, Bahareh, et al.
(author)
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Alcohol and the risk for LADA: results based on the Swedish ESTRID study.
- 2014
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In: European Journal of Endocrinology. - 1479-683X. ; 171:5, s. 535-543
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Journal article (peer-reviewed)abstract
- Objective Moderate alcohol consumption is associated with a reduced risk of type 2 diabetes. Our aim was to investigate whether alcohol consumption is associated with risk of latent autoimmune diabetes in adults (LADA), an autoimmune form of diabetes with features of type 2 diabetes. Design Population-based case-control study Methods We used data from ESTRID case-control study carried out between 2010 and 2013, including 250 incident cases of LADA (glutamic acid decarboxylase antibodies [GADA] positive) and 764 cases of type 2 diabetes (GADA negative), and 1012 randomly selected controls aged ≥35. Logistic regression was used to estimate the odds ratios (OR) of diabetes in relation to alcohol intake, adjusted for age, sex, BMI, family history of diabetes, smoking, and education. Results Alcohol consumption was inversely associated with the risk of type 2 diabetes (OR 0.95, 95% confidence interval (CI); 0.92-0.99 for every 5-g increment in daily intake). Similar results were seen for LADA, but stratification by median GADA levels revealed that the results only pertained to LADA with low GADA (OR 0.85; 95% 0.76-0.94 per 5g alcohol/day), whereas no association was seen with LADA high GADA (OR 1.00, 95% CI; 0.94-1.06 per 5g/day). Every 5-g increment of daily alcohol intake was associated with a 10% increase in GADA levels (p=0.0312), and a10% reduction in HOMA-IR (p=0.0418). Conclusions Our findings indicate that alcohol intake may reduce risk of type 2 diabetes and type 2-like LADA, but has no beneficial effects on diabetes-related autoimmunity.
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| 6. |
- Rasouli, Bahareh, et al.
(author)
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Alcohol and the risk for latent autoimmune diabetes in adults : results based on Swedish ESTRID study
- 2014
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In: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 171:5, s. 535-543
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Journal article (peer-reviewed)abstract
- Objective: Moderate alcohol consumption is associated with a reduced risk of type 2 diabetes. Our aim was to investigate whether alcohol consumption is associated with the risk of latent autoimmune diabetes in adults (LADA), an autoimmune form of diabetes with features of type 2 diabetes. Design: A population-based case-control study was carried out to investigate the association of alcohol consumption and the risk of LADA. Methods: We used data from the ESTRID case-control study carried out between 2010 and 2013, including 250 incident cases of LADA (glutamic acid decarboxylase antibodies (GADAs) positive) and 764 cases of type 2 diabetes (GADA negative), and 1012 randomly selected controls aged >= 35. Logistic regression was used to estimate the odds ratios (ORs) of diabetes in relation to alcohol intake, adjusted for age, sex, BMI, family history of diabetes, smoking, and education. Results: Alcohol consumption was inversely associated with the risk of type 2 diabetes (OR 0.95, 95% CI 0.92-0.99 for every 5-g increment in daily intake). Similar results were observed for LADA, but stratification by median GADA levels revealed that the results only pertained to LADA with low GADA levels (OR 0.85, 95% CI 0.76-0.94/5 g alcohol per day), whereas no association was observed with LADA having high GADA levels (OR 1.00, 95% CI 0.94-1.06/5 g per day). Every 5-g increment of daily alcohol intake was associated with a 10% increase in GADA levels (P=0.0312), and a 10% reduction in homeostasis model assessment of insulin resistance (P=0.0418). Conclusions: Our findings indicate that alcohol intake may reduce the risk of type 2 diabetes and type 2-like LADA, but has no beneficial effects on diabetes-related autoimmunity.
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| 7. |
- Rasouli, Bahareh
(author)
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Alcohol, tobacco and the risk of LADA-latent autoimmune diabetes in adults
- 2016
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Doctoral thesis (other academic/artistic)abstract
- Diabetes is a common and increasing public health problem. Knowledge of risk factors is a prerequisite for efficient prevention; such knowledge is extensive for type 2 diabetes but limited for autoimmune forms of diabetes. LADA-latent autoimmune diabetes in adults is an autoimmune form of diabetes that develops in adults and has features of both type 1 and type 2 diabetes. It accounts for relatively large proportion of all diabetes patients, yet risk factors are largely unexplored. The aim of this thesis was to investigate the influence of tobacco exposure and alcohol consumption on the risk of LADA, and also to explore these factors in relation to type 2 diabetes, to compare the etiology of these adult onset forms of diabetes. Analyses were based on data from two large Scandinavian population-based studies; the Norwegian HUNT-study, a prospective cohort study conducted between 1984 and 2008, and ESTRID, an ongoing Swedish case-control study with incident cases. Information on lifestyle including alcohol consumption and tobacco use was collected by questionnaire. Cases of diabetes were identified by self-report (HUNT) or through the health care system (ESTRID). Patients with LADA had onset ≥35 years and were glutamic acid decarboxylase autoantibody (GADA) positive. Information on lack of insulin treatment (HUNT) or C-peptide levels (ESTRID) were used to indicate a slow onset. Alcohol consumption was associated with reduced risk of LADA in both HUNT and ESTRID. In ESTRID, stratification by GADA levels indicated that the reduced risk primarily pertained to LADA with low GADA levels (odds ratio [OR] 0.85, 95% confidence interval [CI] 0.76–0.94 for every 5-gram increase in daily alcohol intake). Smoking was associated with a reduced risk of LADA in HUNT which we could not confirm in ESTRID; in contrast we found an increased risk of LADA in heavy smokers (OR; 1.37, 95% CI; 1.02-1.84). With regard to type 2 diabetes, we could confirm that alcohol intake is associated with a reduced risk and smoking with an increased risk. There was no association between moist snuff use and type 2 diabetes or LADA in either the Swedish (type 2 diabetes: OR for >10 box-years; 1.00, 95% CI; 0.47-2.11, and LADA: 1.01, 95% CI; 0.45-2.29) or the Norwegian study. In conclusion, the results suggest that alcohol consumption reduces the risk of type 2 diabetes and type 2-like LADA. An increased risk of LADA was seen in smokers but results were contradictory and require further exploration. Finally the use of moist snuff was associated neither with type 2 diabetes nor LADA. These findings indicate that the etiology of LADA in part may be shared with type 2 diabetes and involve factors related to insulin sensitivity. Furthermore, they indicate that LADA may to some extent be preventable by lifestyle modification.
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| 8. |
- Rasouli, Bahareh, et al.
(author)
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Smoking and the risk of LADA : Results from a Swedish population-based case-control study
- 2016
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 39:5, s. 794-800
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Smoking is an established risk factor for type 2 diabetes. In contrast, it has been proposed that smoking may reduce the risk of latent autoimmune diabetes in adults (LADA), but studies are scarce. We aimed to study the impact of smoking on LADA and type 2 diabetes risks. RESEARCH DESIGN AND METHODS: We used data from a Swedish case-control study including incident case patients with LADA (GAD antibody [GADA] positive, n = 377) and type 2 diabetes (GADA negative, n = 1,188) and control subjects randomly selected from the population (n = 1,472). We calculated odds ratios (ORs) with 95% CIs by logistic regression, adjusted for age, sex, BMI, family history of diabetes, and alcohol consumption. RESULTS: There was no indication of reduced risk of LADA in smokers; instead, heavy smoking was associated with an increased risk of LADA (OR 1.37, 95% CI 1.02-1.84). Heavy smokers had higher levels of HOMA of insulin resistance (9.89 vs. 4.38, P = 0.0479) and HOMA of β-cell function (55.7 vs. 42.5, P = 0.0204), but lower levels of GADA (75 vs. 250, P = 0.0445), compared with never smokers. Smokers also displayedanincreased risk oftype2 diabetes (OR in eversmokers 1.53, 95% CI 1.25-1.88). CONCLUSIONS: In this large population of LADA patients, we did not observe a protective effect of smoking on autoimmunity and the risk of LADA. A protective effect could possibly be masked by a smoking-induced aggravation of insulin resistance, akin to the diabetogenic effect seen in individuals with type 2 diabetes.
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