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Objective: To investigate whether the risk for autoimmune diabetes in adults differs between socioeconomic groups and to compare such risk with that for type 2 diabetes.Research Design and Methods: The inhabitants of the Norwegian county of Nord-Trøndelag were investigated by questionnaires and clinical examinations on three occasions during 1984-2008. We used information from a subset consisting of 56,296 subjects (participating in at least two surveys), including 122 incident cases of autoimmune diabetes in adults (aged ≥35 and anti-GAD positive) and 1,555 cases of type 2 diabetes (aged ≥35 and anti-GAD negative). Hazard ratios (HRs) of diabetes associated with self-reported education and occupation were estimated by Cox proportional hazards models.Results: High levels of education (university versus primary school) were associated with an increased risk of autoimmune diabetes (HR 1.98 [95% CI 1.21-3.26]), after adjustment for BMI, lifestyle factors, and family history of diabetes. Case subjects with high levels of education had lower levels of C-peptide, tended to have higher levels of anti-GAD, and were more often treated with insulin. Conversely, these subjects had a reduced risk of type 2 diabetes (HR 0.69 [95% CI 0.57-0.82]), a risk that was partly explained by lower BMI and more physical activity (adjusted HR 0.89 [95% CI 0.74-1.06]).Conclusions: High levels of education are associated with an increased risk of autoimmune diabetes in adults, a finding that may be mediated by effects on autoimmune activity. Because the association is not explained by traditional risk factors, other, currently unidentified, environmental factors are likely to be involved. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate alcohol consumption in relation to the incidence of type 2 diabetes.Research Design and Methods: The study population consisted of 22778 twins of the Finnish Twin Cohort. This cohort was compiled in 1975 and includes all same-sexed twins born in Finland before 1958. Information on alcohol, smoking, diet, physical activity, medical, and social conditions was obtained by questionnaires administered in 1975, 1981, and 1990. By record linkage to national registers of hospital discharge and prescribed medication, 580 incident cases of type 2 diabetes were identified during 20 years of follow-up.Results: Moderate alcohol consumption (5-29.9 g/day in men and 5-19.9 g/day in women) tended to be associated with a reduced incidence of type 2 diabetes compared with low consumption (<5 g/day). The estimates were lower in overweight (BMI >or=25.0 kg/m(2)) subjects (relative risk 0.7, 95% CI 0.5-1.0 [men]; 0.6, 0.3-1.1 [women]). High alcohol consumption (>or=20 g/day) was associated with an increased incidence of type 2 diabetes in lean women (2.9, 1.1-7.5) but not in overweight women or in men. In women, binge drinking was associated with an increased incidence of type 2 diabetes (2.1, 1.0-4.4). Analyses of alcohol-discordant twin pairs supported a reduced risk in moderate consuming twins compared with their low-consuming cotwins (odds ratio 0.5, 95% CI 0.2-1.5).Conclusions: The results of this study suggested that moderate alcohol consumption may reduce the risk of type 2 diabetes. On the other hand, binge drinking and high alcohol consumption may increase the risk of type 2 diabetes in women. [ABSTRACT FROM AUTHOR]

Objective: Childhood-onset type 1 diabetes (T1D) is associated with perinatal factors, but data related to adult-onset T1D are scarce. This study aimed at investigating the association between early-life factors and adult-onset T1D in a Swedish nationwide cohort and family-based study., Research Design and Methods: We included 1,813,415 individuals aged ≥18 years, born in Sweden 1983 to 2002, followed until 2020. T1D diagnosis (n = 3,283) was identified from the National Diabetes, Patient and Prescribed Drugs Registers, and perinatal exposures were obtained from the Medical Birth Register. We performed Cox proportional hazard (hazard ratio [95% CI]) regression with mutual adjustment for perinatal exposures, sex, birth year, and parental sociodemographic background and history of diabetes. We also compared T1D risks among siblings' groups identified from the Multiple Generation Register., Results: The incidence rate of adult-onset T1D was 18.8 per 100,000 person-years. Year of birth (1.06 [1.01-1.10], per five additional years) and history of maternal (4.10 [3.09-5.43]) and paternal (6.24 [5.10-7.64]) T1D were associated with a higher incidence of adult-onset T1D, whereas female sex (0.69 [0.64-0.74]) and having parents born outside Sweden were associated with a lower incidence. Regarding perinatal exposures, only non-full-term birth (<39 weeks vs. ≥39 weeks) was associated with a higher incidence of adult-onset T1D (1.12 [1.04-1.22]). The sibling cohort results were consistent with the full cohort analysis., Conclusions: Perinatal factors seem to play a minor role in the development of adult-onset T1D compared with childhood-onset T1D, suggesting that triggers or accelerators of autoimmunity occurring later in life are more significant., (© 2024 by the American Diabetes Association.)

Objective: Latent autoimmune diabetes in adults (LADA) is a heterogenous, slowly progressing autoimmune diabetes. We aim to contribute new knowledge on the long-term prognosis of LADA with varying degrees of autoimmunity by comparing it to type 2 diabetes and adult-onset type 1 diabetes., Research Design and Methods: This Swedish population-based study included newly diagnosed LADA (n = 550, stratified into LADAlow and LADAhigh by median autoimmunity level), type 2 diabetes (n = 2,001), adult-onset type 1 diabetes (n = 1,573), and control subjects without diabetes (n = 2,355) in 2007-2019. Register linkages provided information on all-cause mortality, cardiovascular diseases (CVDs), diabetic retinopathy, nephropathy, and clinical characteristics during follow-up., Results: Mortality was higher in LADA (hazard ratio [HR] 1.44; 95% CI 1.03, 2.02), type 1 (2.31 [1.75, 3.05]), and type 2 diabetes (1.31 [1.03, 1.67]) than in control subjects. CVD incidence was elevated in LADAhigh (HR 1.67; 95% CI 1.04, 2.69) and type 2 diabetes (1.53 [1.17, 2.00]), but not in LADAlow or type 1 diabetes. Incidence of retinopathy but not nephropathy was higher in LADA (HR 2.25; 95% CI 1.64, 3.09), including LADAhigh and LADAlow than in type 2 diabetes (unavailable in type 1 diabetes). More favorable blood pressure and lipid profiles, but higher HbA1c levels, were seen in LADA than type 2 diabetes at baseline and throughout follow-up, especially in LADAhigh, which resembled type 1 diabetes in this respect., Conclusions: Despite having fewer metabolic risk factors than type 2 diabetes, LADA has equal to higher risks of death, CVD, and retinopathy. Poorer glycemic control, particularly in LADAhigh, highlights the need for improved LADA management., (© 2023 by the American Diabetes Association.)

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., (© 2023 by the American Diabetes Association.)

Objective: Type 1 diabetes is described to have an acute onset, but autoantibodies can appear several years preceding diagnosis. This suggests a long preclinical phase, which may also include metabolic parameters. Here we assessed whether elevations in glycemic, lipid, and other metabolic biomarkers were associated with future type 1 diabetes risk in adults., Research Design and Methods: We studied 591,239 individuals from the Swedish AMORIS cohort followed from 1985-1996 to 2012. Through linkage to national patient, diabetes, and prescription registers, we identified incident type 1 diabetes. Using Cox regression models, we estimated hazard ratios for biomarkers at baseline and incident type 1 diabetes. We additionally assessed trajectories of biomarkers during the 25 years before type 1 diabetes diagnosis in a nested case-control design., Results: We identified 1,122 type 1 diabetes cases during follow-up (average age of patient at diagnosis: 53.3 years). The biomarkers glucose, fructosamine, triglycerides, the ratio of apolipoprotein (apo)B to apoA-I, uric acid, alkaline phosphatase, and BMI were positively associated with type 1 diabetes risk. Higher apoA-I was associated with lower type 1 diabetes incidence. Already 15 years before diagnosis, type 1 diabetes cases had higher mean glucose, fructosamine, triglycerides, and uric acid levels compared with control subjects., Conclusions: Alterations in biomarker levels related to glycemia, lipid metabolism, and inflammation are associated with clinically diagnosed type 1 diabetes risk, and these may be elevated many years preceding diagnosis., (© 2022 by the American Diabetes Association.)

Objective: Islet autoimmunity is associated with diabetes incidence. We investigated whether there was an interaction between dietary fish intake or plasma phospholipid n-3 polyunsaturated fatty acid (PUFA) concentration with the 65-kDa isoform of GAD (GAD65) antibody positivity on the risk of developing adult-onset diabetes., Research Design and Methods: We used prospective data on 11,247 incident cases of adult-onset diabetes and 14,288 noncases from the EPIC-InterAct case-cohort study conducted in eight European countries. Baseline plasma samples were analyzed for GAD65 antibodies and phospholipid n-3 PUFAs. Adjusted hazard ratios (HRs) for incident diabetes in relation to GAD65 antibody status and tertiles of plasma phospholipid n-3 PUFA or fish intake were estimated using Prentice-weighted Cox regression. Additive (proportion attributable to interaction [AP]) and multiplicative interactions between GAD65 antibody positivity (≥65 units/mL) and low fish/n-3 PUFA were assessed., Results: The hazard of diabetes in antibody-positive individuals with low intake of total and fatty fish, respectively, was significantly elevated (HR 2.52 [95% CI 1.76-3.63] and 2.48 [1.79-3.45]) compared with people who were GAD65 antibody negative and had high fish intake, with evidence of additive (AP 0.44 [95% CI 0.16-0.72] and 0.48 [0.24-0.72]) and multiplicative ( P = 0.0465 and 0.0103) interactions. Individuals with high GAD65 antibody levels (≥167.5 units/mL) and low total plasma phospholipid n-3 PUFAs had a more than fourfold higher hazard of diabetes (HR 4.26 [2.70-6.72]) and an AP of 0.46 (0.12-0.80) compared with antibody-negative individuals with high n-3 PUFAs., Conclusions: High fish intake or relative plasma phospholipid n-3 PUFA concentrations may partially counteract the increased diabetes risk conferred by GAD65 antibody positivity., (© 2020 by the American Diabetes Association.)

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 displayed an increased risk of type 2 diabetes (OR in ever smokers 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., (© 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Objective: Knowledge on mortality in autoimmune diabetes with adult onset is limited. We compared mortality in adult-onset autoimmune diabetes and type 2 diabetes, taking into account metabolic risk factors, HbA1c, lifestyle, and socioeconomic factors., Research Design and Methods: Participants of the population-based HUNT2 Study (second survey of the Norwegian HelseUndersøkelsen i Nord-Trøndelag Study; n = 64,264) were followed up prospectively for mortality in the Cause of Death Registry (1995-2009). Diabetes with onset ≥35 years was classified as autoimmune diabetes in adults if anti-GAD was positive (n = 208) and as type 2 diabetes if anti-GAD was negative (n = 2,425). Hazard ratios (HRs) of mortality from all-causes, cardiovascular disease (CVD), and ischemic heart disease (IHD) were calculated using the Cox proportional hazards model., Results: Prevalence of the metabolic syndrome was lower in autoimmune diabetes than in type 2 diabetes (55 vs. 77%, P < 0.001). Still, autoimmune diabetes was associated with an increased risks of mortality from all-causes (HR 1.55 [95% CI 1.25-1.92]), CVD (1.87 [1.40-2.48]), and IHD (2.39 [1.57-3.64]), equally high as in type 2 diabetes in analyses where individuals without diabetes were used as the reference group. The increased risk was not explained by overweight, lifestyle, socioeconomic position, or presence of the metabolic syndrome. Excess mortality was primarily observed in individuals with elevated HbA1c., Conclusions: Mortality in autoimmune diabetes was as high as in type 2 diabetes, despite a more favorable baseline metabolic risk profile. Excess risk was associated with poor glycemic control. The results from this study, the largest so far on mortality in autoimmune diabetes in adults, underscore the importance of optimal treatment modalities to improve survival in adult-onset autoimmune diabetes.

Objective: To investigate the association between smoking habits and risk of autoimmune diabetes in adults and of type 2 diabetes., Research Design and Methods: We used data from the three surveys of the Nord-Trøndelag Health Study, spanning 1984-2008 and including a cohort of 90,819 Norwegian men (48%) and women (52%) aged ≥20 years. Incident cases of diabetes were identified by questionnaire and classified as type 2 diabetes (n = 1,860) and autoimmune diabetes (n = 140) based on antibodies to glutamic decarboxylase (GADA) and age at onset of diabetes. Hazard ratios (HRs) adjusted for confounders were estimated by Cox proportional hazards regression models., Results: The risk of autoimmune diabetes was reduced by 48% (HR 0.52 [95% CI 0.30-0.89]) in current smokers and 58% in heavy smokers (0.42 [0.18-0.98]). The reduced risk was positively associated with number of pack-years. Heavy smoking was associated with lower levels of GADA (P = 0.001) and higher levels of C-peptide (964 vs. 886 pmol/L; P = 0.03). In contrast, smoking was associated with an increased risk of type 2 diabetes, restricted to overweight men (1.33 [1.10-1.61]). Attributable proportion due to an interaction between overweight and heavy smoking was estimated to 0.40 (95% CI 0.23-0.57)., Conclusions: In this epidemiological study, smoking is associated with a reduced risk of autoimmune diabetes, possibly linked to an inhibitory effect on the autoimmune process. An increased risk of type 2 diabetes was restricted to overweight men.

Objective: The aim of this study was to investigate the association between family history of diabetes (FHD) and prevalence and incidence of latent autoimmune diabetes of the adult (LADA), type 1 diabetes, and type 2 diabetes., Research Design and Methods: The results were based on cross-sectional data from 64,498 men and women (aged >or=20 years) who were in the Nord-Trøndelag Health Study, which included 128 cases of LADA, 1,134 cases of type 2 diabetes, and 123 cases of type 1 diabetes. In addition, prospective data on 46,210 subjects, which included 80 incident cases of LADA, observed between 1984 and 1986 and 1995 and 1997 were available. Patients with LADA had antibodies against GAD and were insulin independent at diagnosis., Results: FHD was associated with a four times (odds ratio [OR] 3.92 [95% CI 2.76-5.58]) increased prevalence of LADA. Corresponding estimates for type 2 and type 1 diabetes were 4.2 (3.72-4.75) and 2.78 (1.89-4.10), respectively. Patients with LADA who had FHD had lower levels of C-peptide (541 vs. 715 pmol/l) and were more often treated with insulin (47 vs. 31%) than patients without FHD. Prospective data indicated that subjects with siblings who had diabetes had a 2.5 (1.39-4.51) times increased risk of developing LADA during the 11-year follow-up compared with those without., Conclusions: This study indicates that FHD is a strong risk factor for LADA and that the influence of family history may be mediated through a heritable reduction of insulin secretion.