Risk Of Latent Autoimmune Diabetes Research Articles

Does a prior diagnosis of infectious disease confer an increased risk of latent autoimmune diabetes in adults?

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). 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 5-10years before LADA diagnosis/matching. Stratified analyses were performed on the basis of HLA risk genotypes and Glutamic acid decarboxylase antibodies (GADA) levels. Individuals who developed LADA did not have a higher prevalence of infectious disease 1-10years before diabetes diagnosis. For example, OR was estimated at 0.87 (0.66, 1.14) for any versus no respiratory infectious disease within 1-3years. 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]). 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.

Childhood adiposity and novel subtypes of diabetes in adults: a Mendelian randomisation and genome-wide genetic correlation study

BackgroundFive novel subtypes of adult-onset diabetes were identified in 2018. We aimed to investigate whether childhood adiposity increases the risks of these subtypes using a Mendelian randomisation design, and to explore genetic overlaps between body size (self-reported perceived body size [ie, thinner, about average, or plumper] in childhood, and BMI measured in adulthood) and these subtypes. MethodsThe Mendelian randomisation and genetic correlation analyses were based on summary statistics from European genome-wide association studies of childhood body size (n=453 169), adult BMI (n=359 983), latent autoimmune diabetes in adults (n=8581), severe insulin-deficient diabetes (n=3937), severe insulin-resistant diabetes (n=3874), mild obesity-related diabetes (n=4118), and mild age-related diabetes (n=5605). We identified 267 independent genetic variants as instrumental variables for childhood body size in the Mendelian randomisation analysis of latent autoimmune diabetes in adults and 258 independent genetic variants as instrumental variables for other diabetes subtypes. The inverse variance-weighted method was used as the primary estimator in the Mendelian randomisation analysis, supplemented by other Mendelian randomisation estimators. We calculated overall genetic correlations (rg) between childhood or adult adiposity and different subtypes using linkage disequilibrium score regression. FindingsA large childhood body size was associated with increased risk of latent autoimmune diabetes in adults (odds ratio [OR] 1·62, 95% CI 1·95–2·52), severe insulin-deficient diabetes (OR 2·45, 1·35–4·46), severe insulin-resistant diabetes (OR 3·08, 1·73–5·50), and mild obesity-related diabetes (OR 7·70, 4·32–13·7), but not mild age-related diabetes in the main Mendelian randomisation analysis. Other Mendelian randomisation estimators gave similar results and did not support the existence of horizontal pleiotropy. There was genetic overlap between childhood body size and mild obesity-related diabetes (rg 0·282; p=0·0003), and between adult BMI and all diabetes subtypes. InterpretationThis study provides genetic evidence that higher childhood adiposity is a risk factor for all subtypes of adult-onset diabetes, except mild age-related diabetes. It is therefore important to prevent and intervene in childhood overweight or obesity. There is shared genetic contribution to childhood obesity and mild obesity-related diabetes. FundingThe study was supported by the China Scholarship Council, the Swedish Research Council (grant number 2018-03035), Research Council for Health, Working Life and Welfare (grant number 2018-00337), and Novo Nordisk Foundation (grant number NNF19OC0057274).

Smoking, use of smokeless tobacco, HLA genotypes and incidence of latent autoimmune diabetes in adults

Aims/hypothesesSmoking 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.MethodsAnalyses 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.ResultsSmoking (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/interpretationOur findings suggest that tobacco use increases the risk of LADA and that smoking acts synergistically with genetic susceptibility in the promotion of LADA.Data availabilityAnalysis codes are shared through GitHub (https://github.com/jeseds/Smoking-use-of-smokeless-tobacco-HLA-genotypes-and-incidence-of-LADA).Graphical abstract

Birthweight, BMI in adulthood and latent autoimmune diabetes in adults: a Mendelian randomisation study

Aims/hypothesisObservational studies have found an increased risk of latent autoimmune diabetes in adults (LADA) associated with low birthweight and adult overweight/obese status. We aimed to investigate whether these associations are causal, using a two-sample Mendelian randomisation (MR) design. In addition, we compared results for LADA and type 2 diabetes.MethodsWe identified 43 SNPs acting through the fetal genome as instrumental variables (IVs) for own birthweight from a genome-wide association study (GWAS) of the Early Growth Genetics Consortium (EGG) and the UK Biobank. We identified 820 SNPs as IVs for adult BMI from a GWAS of the UK Biobank and the Genetic Investigation of ANthropometric Traits consortium (GIANT). Summary statistics for the associations between IVs and LADA were extracted from the only GWAS involving 2634 cases and 5947 population controls. We used the inverse-variance weighted (IVW) estimator as our primary analysis, supplemented by a series of sensitivity analyses.ResultsGenetically determined own birthweight was inversely associated with LADA (OR per SD [~500 g] decrease in birthweight 1.68 [95% CI 1.01, 2.82]). In contrast, genetically predicted BMI in adulthood was positively associated with LADA (OR per SD [~4.8 kg/m2] increase in BMI 1.40 [95% CI 1.14, 1.71]). Robust results were obtained in a range of sensitivity analyses using other MR estimators or excluding some IVs. With respect to type 2 diabetes, the association with birthweight was not stronger than in LADA while the association with adult BMI was stronger than in LADA.Conclusions/ interpretationThis study provides genetic support for a causal link between low birthweight, adult overweight/obese status and LADA.Graphical abstract

The Association of CTLA-4 rs231775 and rs3087243 Polymorphisms with Latent Autoimmune Diabetes in Adults: A Meta-Analysis.

Polymorphisms rs231775 and rs3087243 of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) gene have been associated with risk of latent autoimmune diabetes in adults (LADA). However, the results were inconsistent. The purpose of this study was to quantitatively assess the relationship between polymorphisms rs231775 and rs3087243 of CTLA-4 and LADA in a larger pooled population by performing a meta-analysis. Systematic search for eligible studies was conducted in PubMed, Web of Science, and Embase. Case-control studies containing genotype frequencies of polymorphisms rs231775 or rs3087243 were selected, and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the associations between polymorphisms of CTLA-4 and LADA in allelic, dominant and recessive genetic model. A total of eleven studies, in which five studies reported rs231775, two studies reported rs3087342, and four studies reported both rs231775 and rs3087243, were identified. Among them, one study wasn't included in the following meta-analysis because the distribution of genotypes in the control group didn't comply with Hardy-Weinberg equilibrium. Significant associations with susceptibility to LADA were detected for rs231775 (785 cases and 3435 controls) and for rs3087243 (820 cases and 4824 controls) in overall population. Further subgroup analyses for ethnicity (Asian, Caucasian, and African) have also indicated the positive association between rs231775 and LADA. As for rs3087243, subgroup analyses detected the association between polymorphism and LADA in Caucasian population under recessive model. Polymorphisms rs231775 and rs3087243 of CTLA-4 gene are potential risk factors for LADA and may serve as novel genetic biomarkers of LADA.

Combined lifestyle factors and the risk of LADA and type 2 diabetes – Results from a Swedish population-based case-control study

AimsWe investigated the risk of latent autoimmune diabetes in adults (LADA) and type 2 diabetes in relation to a healthy lifestyle, the proportion of patients attributable to an unhealthy lifestyle, and the influence of family history of diabetes (FHD) and genetic susceptibility. MethodsThe population-based study included incident LADA (n = 571), type 2 diabetes (n = 1962), and matched controls (n = 2217). A healthy lifestyle was defined by BMI < 25 kg/m2, moderate-to-high physical activity, a healthy diet, no smoking, and moderate alcohol consumption. We estimated odds ratios (OR) with 95% confidence intervals (CIs) adjusted for age, sex, education, and FHD. ResultsCompared to a poor/moderate lifestyle, a healthy lifestyle was associated with a reduced risk of LADA (OR 0.51, CI 0.34–0.77) and type 2 diabetes (OR 0.09, CI 0.05–0.15). A healthy lifestyle conferred a reduced risk irrespective of FHD and high-risk HLA genotypes. Having a BMI < 25 kg/m2 conferred the largest risk reduction for both LADA (OR 0.54, CI 0.43–0.66) and type 2 diabetes (OR 0.12, CI 0.10–0.15) out of the individual items. ConclusionPeople with a healthy lifestyle, especially a healthy body weight, have a reduced risk of LADA including those with genetic susceptibility to diabetes.

Physical Activity, Genetic Susceptibility, and the Risk of Latent Autoimmune Diabetes in Adults and Type 2 Diabetes.

PurposePhysical activity (PA) has been linked to a reduced risk of type 2 diabetes by reducing weight and improving insulin sensitivity. We investigated whether PA is associated with a lower incidence of latent autoimmune diabetes in adults (LADA) and whether the association is modified by genotypes of human leukocyte antigen (HLA), transcription factor 7-like 2 (TCF7L2)-rs7903146, or the fat mass and obesity-associated gene, FTO-rs9939609.MethodsWe combined data from a Swedish case-control study and a Norwegian prospective study including 621 incident cases of LADA and 3596 cases of type 2 diabetes. We estimated adjusted pooled relative risks (RRs) and 95% CI of diabetes in relation to high (≥ 30 minutes of moderate activity 3 times/week) self-reported leisure time PA, compared to sedentariness.ResultsHigh PA was associated with a reduced risk of LADA (RR 0.61; CI, 0.43-0.86), which was attenuated after adjustment for body mass index (BMI) (RR 0.90; CI, 0.63-1.29). The reduced risk applied only to noncarriers of HLA-DQB1 and -DRB1 (RR 0.49; CI, 0.33-0.72), TCF7L2 (RR 0.62; CI, 0.45-0.87), and FTO (RR 0.51; CI, 0.32-0.79) risk genotypes. Adjustment for BMI attenuated but did not eliminate these associations. For type 2 diabetes, there was an inverse association with PA (RR 0.49; CI, 0.42-0.56), irrespective of genotype.Main ConclusionsOur findings indicate that high PA is associated with a reduced risk of LADA in individuals without genetic susceptibility.

Consumption of red meat, genetic susceptibility, and risk of LADA and type 2 diabetes

PurposeRed meat consumption is positively associated with type 1 (T1D) and type 2 (T2D) diabetes. We investigated if red meat consumption increases the risk of latent autoimmune diabetes in adults (LADA) and T2D, and potential interaction with family history of diabetes (FHD), HLA and TCF7L2 genotypes.MethodsAnalyses were based on Swedish case–control data comprising incident cases of LADA (n = 465) and T2D (n = 1528) with matched, population-based controls (n = 1789; n = 1553 in genetic analyses). Multivariable-adjusted ORs in relation to self-reported processed and unprocessed red meat intake were estimated by conditional logistic regression models. Attributable proportion (AP) due to interaction was used to assess departure from additivity of effects.ResultsConsumption of processed red meat was associated with increased risk of LADA (per one servings/day OR 1.27, 95% CI 1.07–1.52), whereas no association was observed for unprocessed red meat. For T2D, there was no association with red meat intake once BMI was taken into account. The combination of high (> 0.3 servings/day vs. less) processed red meat intake and high-risk HLA-DQB1 and -DRB1 genotypes yielded OR 8.05 (95% CI 4.86–13.34) for LADA, with indications of significant interaction (AP 0.53, 95% CI 0.32–0.73). Results were similar for the combination of FHD-T1D and processed red meat. No interaction between processed red meat intake and FHD-T2D or risk variants of TCF7L2 was seen in relation to LADA or T2D.ConclusionConsumption of processed but not unprocessed red meat may increase the risk of LADA, especially in individuals with FHD-T1D or high-risk HLA genotypes.

Interaction Between Overweight and Genotypes of HLA, TCF7L2, and FTO in Relation to the Risk of Latent Autoimmune Diabetes in Adults and Type 2 Diabetes.

We investigated potential interactions between body mass index (BMI) and genotypes of human leukocyte antigen (HLA), TCF7L2-rs7903146, and FTO-rs9939609 in relation to the risk of latent autoimmune diabetes in adults (LADA) and type 2 diabetes. We pooled data from two population-based studies: (i) a Swedish study with incident cases of LADA [positive for glutamic acid decarboxylase autoantibodies (GADA); n = 394) and type 2 diabetes (negative for GADA; n = 1290) and matched controls without diabetes (n = 2656) and (ii) a prospective Norwegian study that included incident cases of LADA (n = 131) and type 2 diabetes (n = 1901) and 886,120 person-years of follow-up. Analyses were adjusted for age, sex, physical activity, and smoking. Interaction between overweight (BMI ≥ 25 kg/m2) and HLA/TCF7L2/FTO high-risk genotypes was assessed by attributable proportion due to interaction (AP). The combination of overweight and high-risk genotypes of HLA, TCF7L2, and FTO was associated with pooled relative risk (RRpooled) of 7.59 (95% CI, 5.27 to 10.93), 2.65 (95% CI, 1.97 to 3.56), and 2.21 (95% CI, 1.60 to 3.07), respectively, for LADA, compared with normal-weight individuals with low/intermediate genetic risk. There was a significant interaction between overweight and HLA (AP, 0.29; 95% CI, 0.10 to 0.47), TCF7L2 (AP, 0.31; 95% CI, 0.09 to 0.52), and FTO (AP, 0.38; 95% CI, 0.15 to 0.61). The highest risk of LADA was seen in overweight individuals homozygous for the DR4 genotype [RR, 26.76 (95% CI, 15.42 to 46.43); AP, 0.58 (95% CI, 0.32 to 0.83) (Swedish data)]. Overweight and TCF7L2 also significantly interacted in relation to type 2 diabetes (AP, 0.26; 95% CI, 0.19 to 0.33), but no interaction was observed with high-risk genotypes of HLA or FTO. Overweight interacts with HLA high-risk genotypes but also with genes associated with type 2 diabetes in the promotion of LADA.

Coffee consumption, genetic susceptibility and risk of latent autoimmune diabetes in adults: A population-based case-control study

AimCoffee consumption is inversely related to risk of type 2 diabetes (T2D). In contrast, an increased risk of latent autoimmune diabetes in adults (LADA) has been reported in heavy coffee consumers, primarily in a subgroup with stronger autoimmune characteristics. Our study aimed to investigate whether coffee consumption interacts with HLA genotypes in relation to risk of LADA. MethodsThis population-based study comprised incident cases of LADA (n=484) and T2D (n=1609), and also 885 healthy controls. Information on coffee consumption was collected by food frequency questionnaire. Odds ratios (ORs) with 95% CIs of diabetes were calculated and adjusted for age, gender, BMI, education level, smoking and alcohol intake. Potential interactions between coffee consumption and high-risk HLA genotypes were calculated by attributable proportion (AP) due to interaction. ResultsCoffee intake was positively associated with LADA in carriers of high-risk HLA genotypes (OR: 1.14 per cup/day, 95% CI: 1.02–1.28), whereas no association was observed in non-carriers (OR: 1.04, 95% CI: 0.93–1.17). Subjects with both heavy coffee consumption (≥4 cups/day) and high-risk HLA genotypes had an OR of 5.74 (95% CI: 3.34–9.88) with an estimated AP of 0.36 (95% CI: 0.01–0.71; P=0.04370). ConclusionOur findings suggest that coffee consumption interacts with HLA to promote LADA.

Overweight, obesity and the risk of LADA: results from a Swedish case\u2013control study and the Norwegian HUNT Study

Aims/hypothesisExcessive 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.MethodsAnalyses 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.ResultsIn 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/interpretationOverweight/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.

Serious life events and the risk of latent autoimmune diabetes in adults (LADA) and Type 2 diabetes.

It has been suggested that experiencing serious life events may promote Type1 diabetes in children. Studies in adults are lacking, as are studies on the interaction of life events with genetic factors. We aimed to investigate life events and the risk of latent autoimmune diabetes in adults (LADA) and Type 2 diabetes while taking into account HLA genotype. Analysis was based on 425 incident cases of LADA, 1417 incident cases of Type 2 diabetes and 1702 population-based controls recruited in Sweden between 2010 and 2016. Self-reported information on life events including conflicts, divorce, illness/accidents, death and financial problems experienced during the 5years preceding diagnosis/index year was used. Odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated by logistic regression and adjusted for age, sex, BMI, family history of diabetes, smoking, physical activity and education. Overall there was no association between experience of any life event and either LADA (OR 0.86, 95% CI 0.68-1.08) or Type2 diabetes (OR 1.00, 95% CI 0.83-1.21). The results were similar for individual events as well as in separate analysis of men and women. Similar results were seen in more autoimmune LADA (glutamic acid decarboxylase antibodies >median) [OR (any life event) 0.88, 95% CI 0.64-1.21] and in LADA carriers of the high-risk HLADR4-DQ8 genotype (OR 0.89, 95% CI 0.61-1.29). Our findings indicate that experience of a serious life event, including the death of a family member, divorce or financial problems, is not associated with an increased risk of LADA, overall or in genetically susceptible individuals.

Sweetened beverage intake and risk of latent autoimmune diabetes in adults (LADA) and type 2 diabetes.

Sweetened beverage intake is associated with increased risk of type 2 diabetes, but its association with autoimmune diabetes is unclear. We aimed to investigate sweetened beverage intake and risk of latent autoimmune diabetes in adults (LADA); autoimmune diabetes with features of type 2 diabetes. Data from a Swedish population-based study was used, including incident cases of LADA (n = 357) and type 2 diabetes (n = 1136) and randomly selected controls (n = 1371). Diabetes classification was based on onset age (≥35), glutamic acid decarboxylase autoantibodies (GADA) and C-peptide. Sweetened beverage intake information was derived from a validated food frequency questionnaire. ORs adjusted for age, sex, family history of diabetes, education, lifestyle, diet, energy intake and BMI were estimated using logistic regression. Daily intake of >2 servings of sweetened beverages (consumed by 6% of participants) was associated with increased risk of LADA (OR: 1.99, 95% CI: 1.11-3.56), and for each 200 mL daily serving, OR was 1.15 (95% CI: 1.02-1.29). Findings were similar for sugar-sweetened (OR: 1.18, 95% CI: 1.00-1.39) and artificially sweetened beverages (OR: 1.12, 95% CI: 0.95-1.32). Similarly, each daily serving increment in total sweetened beverage conferred 20% higher type 2 diabetes risk (95% CI: 1.07-1.34). In type 2 diabetes patients, high consumers displayed higher HOMA-IR levels (4.5 vs 3.5, P = 0.0002), but lower HOMA-B levels (55 vs 70, P = 0.0378) than non-consumers. Similar tendencies were seen in LADA. High intake of sweetened beverages was associated with increased risk of LADA. The observed relationship resembled that with type 2 diabetes, suggesting common pathways possibly involving insulin resistance.

Smoking and the Risk of LADA: Results From a Swedish Population-Based Case-Control Study.

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. 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. 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 displayed an increased risk of type 2 diabetes (OR in ever smokers 1.53, 95% CI 1.25-1.88). 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.

Fatty fish consumption and risk of latent autoimmune diabetes in adults.

Objective:It has been suggested that intake of fatty fish may protect against both type 1 and type 2 diabetes. Hypotheses rest on the high marine omega-3 fatty acid eicosapentaenoic acid+docosahexaenoic acid (EPA+DHA) and vitamin D contents, with possible beneficial effects on immune function and glucose metabolism. Our aim was to investigate, for the first time, fatty fish consumption in relation to the risk of latent autoimmune diabetes in adults (LADA).Methods:Analyses were based on data from a Swedish case–control study with incident cases of LADA (n=89) and type 2 diabetes (n=462) and randomly selected diabetes-free controls (n=1007). Diabetes classification was based on the onset of age (⩾35), glutamic acid decarboxylase autoantibodies, and C-peptide. A validated food frequency questionnaire was used to derive information on previous intake of fish, polyunsaturated long-chain omega-3 fatty acids (n-3 PUFA) and supplementation of fish oil and vitamin D. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using logistic regression, adjusted for age, gender, body mass index (BMI), family history of diabetes, physical activity, smoking, education, and consumption of alcohol, fruit, vegetables and red meat.Results:Weekly fatty fish consumption (⩾1 vs <1 serving per week), was associated with a reduced risk of LADA but not type 2 diabetes (OR 0.51, 95% CI 0.30–0.87, and 1.01, 95% CI 0.74–1.39, respectively). Similar associations were seen for estimated intake of n-3 PUFA (⩾0.3 g per day; LADA: OR 0.60, 95% CI 0.35–1.03, type 2 diabetes: OR 1.14, 95% CI 0.79–1.58) and fish oil supplementation (LADA: OR 0.47, 95% CI 0.19–1.12, type 2 diabetes: OR 1.58, 95% CI 1.08–2.31).Conclusions:Our findings suggest that fatty fish consumption may reduce the risk of LADA, possibly through effects of marine-originated omega-3 fatty acids.

Alcohol and the risk for latent autoimmune diabetes in adults: results based on Swedish ESTRID study.

ObjectiveModerate 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.DesignA population-based case–control study was carried out to investigate the association of alcohol consumption and the risk of LADA.MethodsWe 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.ResultsAlcohol 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).ConclusionsOur 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.

The association of PTPN22 rs2476601 polymorphism and CTLA-4 rs231775 polymorphism with LADA risks: a systematic review and meta-analysis.

Although the polymorphisms of PTPN22 and the variants of CTLA-4 have been reported to be the susceptibility genes, which increased risk of latent autoimmune diabetes in adults (LADA), the results remained inconclusive. The aim of this meta-analysis was to evaluate the association between the polymorphisms of two genes and LADA. We performed a systematic review by identifying relevant studies and applied meta-analysis to pool gene effects. Data from ten studies published between 2001 and 2013 were pooled for two polymorphisms: rs2476601 in the PTPN22 gene and rs231775 in the CTLA-4 gene. Data extraction and assessments for risk of bias were independently performed by two reviewers. Fixed-effect model and random-effect model were used to pool the odds ratios; meanwhile, heterogeneity test, publication bias and sensitive analysis were explored. The minor T allele at rs2476601 and the minor G at rs231775 carried estimated relative risks (odds ratio) of 1.52 (95 % CI 1.29–1.79) and 1.39 (95 % CI 1.11–1.74), respectively. These alleles contributed to an absolute lowering of the risk of all LADA by 4.88 and 14.93 % when individuals do not carry these alleles. The estimated lambdas were 0.49 and 0.63, suggesting a codominant model of effects was most likely for two genes. In summary, our systematic review has demonstrated that PTPN22 rs2476601 and CTLA-4 rs231775 are potential risk factors for LADA. An updated meta-analysis is required when more studies are published to increase the power of these polymorphisms and LADA. Electronic supplementary materialThe online version of this article (doi:10.1007/s00592-014-0613-z) contains supplementary material, which is available to authorized users.

Coffee consumption and the risk of latent autoimmune diabetes in adults--results from a Swedish case-control study.

Coffee consumption is associated with a reduced risk of Type2 diabetes. Our aim was to investigate if coffee intake may also reduce the risk of latent autoimmune diabetes in adults, an autoimmune form of diabetes with features of Type2 diabetes. We used data from a population-based case-control study with incident cases of adult onset (≥35years) diabetes, including 245 cases of latent autoimmune diabetes in adults (glutamic acid decarboxylase antibody positive), 759 cases of Type2 diabetes (glutamic acid decarboxylase antibody negative), together with 990 control subjects without diabetes, randomly selected from the population. Using questionnaire information on coffee consumption, we estimated the odds ratio of latent autoimmune diabetes in adults and Type2 diabetes adjusted for age, sex, BMI, smoking, physical activity, alcohol, education and family history of diabetes. Coffee intake was inversely associated with Type2 diabetes (odds ratio0.92, 95%CI 0.87-0.98 per cup/day). With regard to latent autoimmune diabetes in adults, the general trend was weak (odds ratio1.04, 95%CI 0.96-1.13), but stratification by degree of autoimmunity (median glutamic acid decarboxylase antibody levels) suggested that coffee intake may be associated with an increased risk of high glutamic acid decarboxylase antibody latent autoimmune diabetes in adults (odds ratio1.11, 95%CI 1.00-1.23 per cup/day). Furthermore, for every additional cup of coffee consumed per day, there was a 15.2% (P=0.0268) increase in glutamic acid decarboxylase antibody levels. Our findings confirm that coffee consumption is associated with a reduced risk of Type2 diabetes. Interestingly, the findings suggest that coffee may be associated with development of autoimmunity and possibly an increased risk of more Type1-like latent autoimmune diabetes in adults.

Comment on: Olsson et al. High Levels of Education Are Associated With an Increased Risk of Latent Autoimmune Diabetes in Adults: Results From the Nord-Trøndelag Health Study. Diabetes Care 2011;34:102–107

Olsson et al. (1) describe an association between high levels of education and an increased risk of autoimmune diabetes in adults. They propose “the hygiene hypothesis” as an explanation for their results indicating that childhood environment and a low prevalence of childhood infections might contribute to the evolution of autoimmune diabetes. We would like to draw the attention to …

Response to Comment on: Olsson et al. High Levels of Education Are Associated With an Increased Risk of Latent Autoimmune Diabetes in Adults: Results From the Nord-Trøndelag Health Study. Diabetes Care 2011;34:102–107

We appreciate the interest of Sawicki and Bastian (1) in our study. They propose an alternative explanation of our results, namely, that parents with a high education level would have better controlled diabetes, leading to lesser complications during pregnancy, which, in turn, would lead to stronger liability for …