Relationship between ß-Cell Autoantibodies and Their Combination with Anthropometric and Metabolic Components and Microvascular Complications in Latent Autoimmune Diabetes in Adults.

AIMS: Our study aimed to investigate the relationship between three autoantibodies and their combination with anthropometric and metabolic components and microvascular complications in patients with latent autoimmune diabetes in adults (LADA). METHODS: Our study included 189 LADA patients divided into four subgroups according to the autoantibodies present: glutamic acid decarboxylase autoantibodies (GADA) only; zinc transporter-8 autoantibodies (ZnT8A)+GADA; insulinoma-associated-2 autoantibodies (IA-2)+GADA; and ZnT8+IA-2+GADA. RESULTS: Compared to GADA positivity only, patients with ZnT8+GADA positivity and ZnT8+IA-2+GADA positivity had a shorter diabetes duration and lower body mass index (BMI); patients with ZnT8+GADA positivity were younger and showed an increase in glomerular filtration rate, while those with ZnT8+IA-2+GADA positivity had lower C-peptide and lower insulin resistance measured with HOMA2-IR. In a multiple regression analysis, ZnT8 positivity was associated with lower BMI (p = 0.0024), female sex (p = 0.0005), and shorter duration of disease (p = 0.0034), while IA-2 positivity was associated with lower C-peptide levels (p = 0.0034) and shorter diabetes duration (p = 0.02). No association between antibody positivity and microvascular complications of diabetes, including retinopathy, neuropathy, and microalbuminuria, as well as with variables of glucose control and ß-cell function were found. CONCLUSION: The results of our study suggest that ZnT8 and IA-2 autoantibodies are present in a significant number of LADA patients and associated with clinical and metabolic characteristics resembling classic type 1 diabetes. Due to increased LADA prevalence, earlier identification of patients requiring frequent monitoring with the earlier intensification of insulin therapy might be of special clinical interest.

Relative Frequency of Islet Autoimmunity in Children and Adolescents with Autoimmune Thyroid Disease

Objective: The aim of the present study was to investigate islet autoimmunity and susceptibility to type 1 diabetes (T1D) in children/adolescents with autoimmune thyroid disease (AITD, and in family members of AITD patients with islet autoimmunity. Methods: Islet-cell cytoplasmic, glutamic-acid decarboxylase, and tyrosine-phosphatase autoantibodies (AAbs) were measured in 161 AITD patients [127 with autoimmune thyroiditis (AT); 34 with Graves' disease (GD)], 20 family members of AITD patients with islet autoimmunity, and 155 age-matched controls. Results: Islet autoimmunity was found in 10.6% of AITD patients, significantly more frequent than in controls (1.9%; p=0.002). A higher prevalence of islet AAbs was found in females with AITD (p=0.011) but not in males (p=0.16) and in AT (p=0.013) but not in GD patients (p=0.19), compared to corresponding controls. Two or three islet AAbs were found concurrently in six AITD patients with islet autoimmunity. They all developed T1D and had significantly higher islet AAbs titers (p=0.01) than AITD patients with single islet AAbs but normal glucose metabolism. T1D was found in 3.7% of AITD patients compared to 0.2% of the age-matched, general Croatian population. Islet AAbs were found in 5/20 family members of AITD patients with islet autoimmunity, among whom two developed T1D. None of the controls was positive for more than one islet AAb or developed T1D. Conclusion: Children/adolescents with AITD, particularly females and patients with AT, appear to represent a risk group for islet autoimmunity and T1D, as do family members of AITD patients with positive islet AAbs. However, these findings should be validated in larger studies.

Human Leukocyte Antigen class II polymorphisms among Croatian patients with type 1 diabetes and autoimmune polyglandular syndrome type 3 variant.

This study included 161 patients: 92 patients had type 1 diabetes (T1D) while 69 patients had a combination of T1D and autoimmune thyroiditis, the so-called autoimmune polyglandular syndrome type 3 variant (APS3v). Those patients, as well as 93 controls, were typed for HLA-DRB1 and -DQB1 genes to assess their possible contribution to the development/protection of T1D with/without autoimmune thyroiditis. Both HLA-DRB1*04 and -DRB1*03 frequencies were significantly higher among T1D and APS3v patients than in controls. The frequencies of HLA-DRB1*11 and -DRB1*15 were lower among T1D patients, while HLA-DRB1*07 and -DRB1*11 occurred significantly less frequently among APS3v patients in comparison to controls. HLA-DQB1*03:01 and -DQB1*03:02 were associated with a higher risk of developing T1D and APS3v; HLA-DQB1*02 was significantly more present among APS3v patients while HLA-DQB1*03:03 was observed with a significantly lower frequency only among T1D patients. HLA-DRB1*03~DQB1*02 and HLA-DRB1*04~DQB1*03:02 were associated with both diseases. The higher frequency of HLA-DRB1*03/DRB1*03 among APS3v patients was the only significant difference in genotype frequency when compared to T1D patients, while high risk (HLA-DRB1*03/DRB1*04) and medium risk genotypes for T1D (HLA-DRB1*04/DRB1*04) occurred with similar frequencies in both patient groups. Although some of the results point toward shared genetic susceptibility of T1D and APS3v, observed differences in both susceptible/protective HLA profiles indicate the necessity of further studies in order to elucidate the pathogenesis of these diseases.

Fasting serum dipeptidyl peptidase-4 activity is independently associated with alanine aminotransferase in type 1 diabetic patients.

OBJECTIVES: Dipeptidyl peptidase-4 (DPP4) was recently proposed as a novel adipokine linked to insulin resistance (IR). As IR represents a cluster of disorders in hepatic and muscle cell insulin signalisation, we aimed to assess the possible correlation between fasting serum DPP4 activity, IR and liver enzymes in order to elucidate the question of hepatic contribution to serum DPP4 activity. DESIGN AND METHODS: This cross-sectional study comprised 44 T1DM patients aged 18 to 65years. IR was estimated using the equation derived from euglycemic-hyperinsulinemic clamp studies-estimated glucose disposal rate (eGDR). DPP4 serum activity was determined spectrophotometrically as a rate of cleavage of 7-amino-4-methyl coumarin (AMC) from H-Gly-Pro-AMC. The patients were divided into two groups according to the mean value of fasting serum DPP4 activity (31.42U/L). RESULTS: The group with lower fasting serum DPP4 activity had lower mean rate of liver biomarkers alanine aminotransferase (ALT) (p=0.001) and aspartate aminotransferase (AST) (p=0.002) while higher eGDR (p=0.003) compared to group with higher DPP4 activity. DPP4 activity showed positive correlation with AST (r=0.358, p=0.017) and ALT (r=0.364, p=0.015) while negative correlation with eGDR (r=-0.612, p<0.001). ALT remained positively associated with fasting serum DPP4 activity after controlling for age, gender, diabetes duration, the use of statins and antihypertensives (p=0.025). CONCLUSIONS: Fasting serum DPP4 activity might be associated with hepatic IR in T1DM patients and a part of soluble DPP4 activity might be of a hepatic origin. Further study investigation is warranted to elucidate this topic.

Relationship between autoantibodies combination, metabolic syndrome components and diabetic complications in autoimmune diabetes in adults.

The aim of our study was to establish the possible association between double or triple antibody positivity and latent autoimmune diabetes (LADA) phenotype in the context of metabolic syndrome (MS) prevalence and its individual components. This cross-sectional study population comprised 69 islet cell antibody-positive patients coming for their comprehensive annual review. They were divided into three groups according to antibody positivity. Twenty-five (36.2 %) were male, mean age of 51 years with disease duration of 8 years. Twenty-eight (40.58 %) were positive only for GAD Abs, 26 (37.68 %) were positive for ICA and GAD Abs and 15 (21.74 %) were positive for GAD, ICA, and IA2 Abs. The lowest value of waist circumference, MS, and artherial hypertension prevalence was found in the group positive for all three antibodies. In the multinomial multivariate logistic regression model, MS was negatively associated with triple Abs positivity compared to single Ab positivity and double Abs positivity. Our results highlight the importance of inverse association between simultaneous Abs positivity for ICA, GAD, and IA2 with the MS and its components present in LADA patients. This inverse relationship might implicate that LADA patients are phenotypically closer to T1DM. The contribution of IA2 Ab positivity merits is to be considered in the determination of LADA phenotypes, while its diagnostic value needs to be clarified in future follow-up studies.