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Abstract Aim Coffee 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. Methods This 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. Results Coffee 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). Conclusion Our findings suggest that coffee consumption interacts with HLA to promote LADA. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

OBJECTIVE: H. pylori infection is reportedly associated with autoimmune diseases such as chronic thyroiditis and autoimmune diabetes. The aim of this study is to determine the association between H. pylori infection and its virulent strain CagA with antibodies against thyroperoxidase (TPO Ab) and thyrotropin (TSH) in a cohort of latent autoimmune diabetes in adult (LADA) patients. PATIENTS AND METHODS: We included 234 LADA patients (53.8% women). Antibodies against H. pylori whole antigens and CagA, TPO Ab and TSH were assessed in all patients. RESULTS: Prevalence of IgG against H. pylori and GagA was 52.1% and 20.9% respectively. Antibodies against H. pylori were not associated with TPO Ab and TSH (rho = 0.067, p = 0.620 and rho = 0.156, p = 0.099, respectively). Antibodies against CagA showed a positive association with TSH and TPO Ab (respectively rho = 0.309, p = 0.036 and rho = 0.419, p = 0.037). Subjects with hypothyroidism (TSH ≥ 3.5 μU/ml) had an increased frequency of Ab anti CagA (p = 0.059). CONCLUSIONS: The infection by H. pylori strains expressing CagA is associated with increased TPO Ab and TSH levels in LADA patients, suggesting a possible mechanism involved in thyroid autoimmunity and dysfunction of the gland. Further research is needed to test this hypothesis. [ABSTRACT FROM AUTHOR]

Aims The aim was to investigate the frequency and characteristics of persons with latent autoimmune diabetes in adults (LADA) amongst patients who had been clinically diagnosed as type 2 diabetes mellitus (CT2DM) in a tertiary care centre. Methodology One hundred and sixty patients with CT2DM participated in this cross-sectional study following selection by systematic random sampling. Demographic data, relevant clinical history and anthropometric measurements (weight, height, waist circumference and hip circumference) were taken and blood samples were obtained for analysis of fasting blood glucose, glycated haemoglobin (HbA1c) and glutamic acid decarboxylase antibodies (GADA). The results were analysed using SPSS version 16. Results Nineteen (11.9%) out of 160 persons with CT2DM were positive for GADA. 95(59.4%) of the total study population were females. The mean (SD) age, BMI, waist circumference, were 60.49 (10.37) years, 26.47 (4.80) kg/m 2 , 92.16 (11.50) cm respectively. Subjects with CT2DM who were GADA positive had trend towards lower mean BMI (25.64 kg/m 2 vs. 26.59 kg/m 2 ) and waist circumference (89.80 kg/m 2 vs. 92.47 kg/m 2 ) than GADA negative subjects. GADA positive subjects also had a trend showing higher mean fasting blood glucose (144 mg/dl vs. 125 mg/dl, t = 2.20, p = 0.14), higher mean HbA1c (7% vs. 6.1%, t = 3.19, p = 0.077) and a higher proportion on insulin (31.6% vs. 22%, χ 2 = 0.07, p = 0.25) when compared with GADA negative patients. Conclusion The prevalence of LADA amongst a subset of Nigerians with CT2DM was 11.9%. There were no distinguishing clinical features to help characterize persons with LADA. The above finding emphasizes the importance of GADA testing for appropriate classification of persons with CT2DM. Early diagnosis of LADA would help direct appropriate therapy to optimize glycaemic control. [ABSTRACT FROM AUTHOR]

• First study on early life BCG vaccination and incidence of diabetes in adults. • BCG vaccination was not associated with type 1 diabetes incidence before age 30. • After 30 years old, the risk of type 1 diabetes was lower among the BCG vaccinated. • Early life BCG vaccination was protective against type 2 diabetes in adulthood. • No association was observed with latent autoimmune diabetes in adulthood. Bacillus Calmette-Guerin (BCG) vaccination limits blood sugar elevations and autoimmunity. Previous studies focused on type 1 diabetes among children, despite possible effects on other phenotypes later in life. We studied associations between BCG vaccination and type 1, type 2 and latent autoimmune diabetes (LADA) in adulthood. A 1970–1974 birth cohort was linked with the BCG vaccination registry and administrative health data of Quebec. 396,118 people aged 22–44 years were followed-up for diabetes mellitus (DM) onset. Incident DM cases were subjects with ≥1 hospitalization or ≥2 physician claims related to DM over a 2-year period. Type 1 diabetes, type 2 diabetes, and LADA cases were individuals with ≥1 reimbursement of insulin, oral antidiabetic agent, or both. Cox proportional regressions were used to estimate hazard ratios (HR), adjusting for potential confounders. Forty-four percent of subjects were BCG vaccinated, 88% of these before age 1. For type 1 diabetes, no association was found before 30 years old, but vaccinated subjects had a lower risk of this phenotype after age 30 (HRadj= 0.65, 95% CI: 0.44–0.95). BCG vaccination was associated with a lower risk of type 2 diabetes (HRadj=0.85, 95% CI: 0.79–0.92), whereas no association was observed for LADA (HRadj=1.30, 95% CI: 0.71–2.38). Results did not differ by sex. Early life BCG vaccination was associated with lower risks of both type 1 and type 2 diabetes from early to middle adulthood, but not of LADA. Future studies should explore these long-term associations, while distinguishing diabetes phenotypes. [ABSTRACT FROM AUTHOR]

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Abstract: Background: Latent autoimmune diabetes in adults (LADA) represents a subgroup of diabetes mellitus. LADA is characterised by adult-onset diabetes and circulating autoimmune antibodies. LADA patients may need a different therapeutic approach than the usual type 2 diabetes mellitus. When LADA is inadequately diagnosed as type 2 diabetes mellitus, LADA patients will mistakenly be exposed to a high dose of oral glucose lowering drugs and their possible side effects. Aim: To assess which clinical features predict the presence or absence of LADA in patients older than 25 years presenting with hyperglycemia. Methods: A structured Medline and Embase search was conducted. Titles and abstracts were screened using predetermined selection criteria. Critical appraisal was based on standardized validity criteria for diagnostic research. Results: One-hundred and eighty-four papers were retrieved of which after assessment of relevance and validity 2 studies remained for further analysis. One study reported a probability of LADA of 0.99 with one or two out of the following five clinical features: age at onset <50 years; acute symptoms; BMI<25kg/m2; a history of autoimmune disease; a family history positive for diabetes mellitus. The other study reported a probability of LADA of zero with none of the following clinical features and of 0.32 with one out of three: fasting blood glucose≥15mmol/l and/or HbA1c ≥10%; 10% reduction in body weight in the previous 3 months; BMI<25kg/m2. Conclusion: Further testing for LADA by measurement of autoimmune antibodies appears to be unnecessary in the absence of a specific set of clinical features. Before initiating therapy applying the above criteria may help to separate LADA from usual type 2 diabetes. [Copyright &y& Elsevier]

Abstract: This review considers the current knowledge and practice of GADA testing people with diabetes in Europe and the UK. Important issues are raised, including interpretation of the results and the clinical relevance of the GADA titre. Recommendations are made towards standardising GADA testing, using World Health Organization units. [Copyright &y& Elsevier]