Anti-thyroid autoantibodies in children with insulin-dependent diabetes mellitus

The study was aimed at the assessment of frequency of occurrence of thyroid antimicrosomal and antithyreoglobuln autoantibodies in children with insulin-dependent diabetes and healthy control children. The occurrence of thyroid autoantibodies was analyzed with respect to the age and sex of children and the duration of the disease. The studied group was composed of 199 children of age between 2 and 17 years with insulin-dependent diabetes. Control group included 100 healthy children. Thyroid autoantibodies were determined by using a solid phase radioimmunoassay. Antimicrosomal antibodies were detected in 35% of diabetic children, but only in 1% of healthy children. Neither in diabetic nor in control children the occurrence of antithyreoglobulin antibodies was significant. The frequency of occurrence of antimicrosomal antibodies was not related to age of children or the duration of diabetes. The occurrence of these antibodies was significantly more frequent in girls (in 70% of cases) than in boys (30% of cases).     

Circulating immune complexes in the serum of diabetes mellitus in childhood by a modified 125I-C1q binding test.

The 125I-C1q binding test for the detection of soluble immune complexes in native unheated human serum was applied to the study of sera from 52 patients with diabetes mellitus in childhood. This radiolabeled C1q binding test is more sensitive and reproducible among the various methods proposed for the detection of immune complexes. The 125I-C1q binding activity in 52 sera from diabetes mellitus in childhood was 9.47 +/- 0.36% compared to 6.94 +/- 0.74% in normal controls. 125I-C1q binding values in diabetes mellitus in childhood were significantly higher than normal controls. Slight high values were seen in 3 patients with positive anti-DNA-antibodies in diabetes mellitus in childhood. 125I-C1q binding was not significantly increased in patients with positive antithyroid antibodies and insulin antibodies. There was no significant correlation between the duration of diabetes and 125I-C1q binding activity.     

Antinuclear antibodies in childhood diabetics

Antinuclear antibodies (ANA) were detected both in type 1 diabetic children and in control subjects. The incidence of ANA in eighty of these diabetics was 16.3%, as determined using two different substrates, human pancreas and human peripheral leucocytes. The incidence and the patterns in the detection of ANA were the same. Four hundred and seventy-three children and one thousand one hundred and twenty-five adults served as the controls. The incidence of ANA in non-diabetic children was 0.8% and that in one adult population was 1.1%. Therefore, the incidence of ANA in childhood diabetics was significantly higher. We studied autoantibodies in childhood diabetics, in normal children and in one adult population. Pancreatic islet cell antibodies (ICA) were detected in 29 out of 80 type 1 diabetics (36.3%) in two out of 473 normal children (0.4%) and in six cases in one population (0.5%). thyroid microsomal antibodies (MCHA) were detected in 9 out of 80 childhood diabetics and the incidence of MCHA in type 1 diabetics was significantly higher than in the controls.     

The combination of antibodies to GAD-65 and IA-2ic can replace the islet-cell antibody assay to identify subjects at risk of type 1 diabetes mellitus.

First-degree relatives of type 1 diabetic patients are at increased risk of developing diabetes and, until recently, islet cell antibodies (ICA) have represented the major risk marker used for identification of individuals at increased risk for subsequent progression to diabetes. In order to determine the value of antibodies to GAD-65 and IA-2ic to identify individuals at high risk for type 1 diabetes mellitus, we measured both autoantibodies and ICA in 1436 first-degree relatives of patients with type 1 diabetes. In addition, the sera were analyzed for thyroid, adrenal and gastric-parietal cell autoantibodies as markers for possible polyendocrine involvement. GAD-65 Abs were found in 135 out of 1436 (9.4%) first-degree relatives and in 57 of 98 (58.2%) ICA-positive subjects. IA-2ic were detected in 52 of 1436 (3.6%) first-degree relatives and in 44 of 98 (44.8%) ICA-positive relatives. IA-2ic and/or GAD-65 were detected in 73 of 98 (74.5%) ICA-positive relatives. Interestingly, antibodies to GAD-65 and/or IA-2ic were present in 91.2% of individuals with more than 20JDF-units. Anti-IA-2ic and GAD-65 were positively correlated with high levels of ICA. Anti-IA-2ic and GAD-65 were found in 19% and 48.5% of subjects with ICA levels of 5-20JDF-u but in 68.8% and 76.5% of individuals with ICA of 40JDF-u or more, respectively (p < 0.001), compared to subjects with ICA levels less than 5 JDF-u. When autoantibody frequencies among the relatives were analyzed according to relationship to the proband, the offspring and siblings had a higher frequency of ICA and IA-2ic (p<0.05) than the subgroup of parents. A significant association was observed between IA-2ic and thyroid antibodies. In addition, higher levels of IA-2ic were found in relatives with positive TPO antibodies (p < 0.001); this correlation was particularly strong in offspring and siblings (p < 0.01). Determination of GAD-65 and IA-2ic antibodies may be considered as an alternative to primary ICA-screening, enabling the screening of large populations.     

Antimicrosomal antibodies, gastric parietal cell antibodies and antinuclear factors in insulin dependent diabetes mellitus.

Thyroid antimicrosomal antibodies, gastric parietal cell antibodies (PCA) and antinuclear factors were studied in 208 insulin dependent diabetic (IDD) according to the duration of diabetes and patient's age at the time of testing. Antimicrosomal antibodies were found in 11 out of 47 (23.4%) IDD with the duration of less than one year, however this value declined to 13.1% at 1 to 3 years, 15.3% at 4 to 5 years, 10.8% at 6 to 10 years and 5.8% at more than 10 years. Of the 47 IDD, 7 (14.8%) were positive for gastric parietal cell antibodies. The prevalence of PCA declined with increasing duration of diabetes. However, this decrease in the prevalence of antimicrosomal antibodies and PCA was not so extreme as that of pancreatic islet cell antibodies. Antinuclear factors did not reveal a significant correlation with the duration of diabetes. In normal controls, the prevalence of antimicrosomal antibodies, PCA and the antinuclear factors increased progressively with age. In IDD, the prevalence of the antinuclear factors was also progressively greater with age. However, the prevalence of antimicrosomal antibodies in IDD decreased with age and those of PCA showed the lowest percent in the 40-69 year-age group.     

Enuresis: familial incidence and relationship to allergic disorders

An analysis is made of the incidence of allergic diseases in 105 enuretic boys and girls, in their parents and siblings, and in matched controls. There is an increased incidence of hay fever, urticaria and food and drug allergies in enuretic boys. There is an increased incidence of enuresis in the parents of enuretic children. Enuretic children and their fathers are significantly more prone to develop urinary infections than are controls; there is also an increased incidence in urinary infections in their mothers, but numbers are insufficient to indicate that this is significant.     

High frequency of diabetes-specific autoantibodies in parents of children with type 1 diabetes. DENIS study group.

Strategies to identify subjects at risk for type 1 diabetes are largely based on the detection of autoantibodies directed to various beta cell autoantigens. Most previous studies only comprise siblings and children of patients with type 1 diabetes; only scare data are available on the antibody profile in older relatives. In this study, we examined the prevalence of cytoplasmic islet cell antibodies (ICA), antibodies to glutamic acid decarboxylase (GADA), antibodies to the protein tyrosine phosphatase IA-2 (IA-2A) and IA-2beta (IA-2betaA) in 531 unaffected parents of patients with type 1 diabetes, and compared the results with antibody frequencies in 2425 siblings. The frequency of ICA, GADA and IA-2A was substantially higher among siblings as compared to parents of patients with type 1 diabetes (8.0% vs. 4.5%, 8.0% vs. 4.3%, and 4.5% vs. 1.9%, respectively; p<0.01). However, subdividing the probands according to age revealed a high prevalence of ICA (5.5 %), GADA (5.9 %), and IA-2A (3.1%) among parents aged 31 -40 years which was similar to that observed in siblings above 20 years of age (6.4%, 6.4%, and 3.1%). In both cohorts, GADA and IA-2A were significantly associated with the presence of ICA. The combined screening for GADA and IA-2A identified 100% of parents and 91.9% of siblings at high risk for type 1 diabetes (>10 JDF-U). Furthermore, the analysis of antibody combinations revealed that among antibody positive individuals the percentage of subjects with two or three antibodies was even higher in parents (69.0%) than in siblings (58.2%). The present study shows a high frequency of single and multiple autoantibodies in unaffected parents of patients with type 1 diabetes. Our data indicate that GAD and IA-2 not only represent the major target of autoantibodies in young siblings but also in adult relatives. These findings may be important for the design of future intervention studies.     

Stress in families of children who have ingested poisons.

One hundred families of children under 5 years admitted to Cardiff Hospitals after accidentally ingesting poisons were compared with 100 control families matched for socioeconomic class and age and sex of the child. Questioning about five major stress factors (serious family illness, pregnancy, recent family moves, one parent away from home, anxiety or depression in one or both parents) disclosed significantly more stress in the affected families than in the controls. Thirty of the affected families had more than one major stress factor compared with four of the controls, while 63 of the controls had no major stress factor compared with 24 of the affected families (P less than 0.001). In only four of the affected families was there no stress factor. Fifteen children took poisons in homes other than their own. Unemployment was significantly more prevalent in the affected families than in the general population, though apart from this the socioeconomic backgrounds were similar. There were significantly more accidents and childhood poisonings in the parents and siblings of affected children than in the control families. In 25% of the cases poisoning was with Angiers Junior Aspirin.     

Inheritance of acute appendicitis: familial aggregation and evidence of polygenic transmission.

We explored familiality as well as the heritability and possible mode(s) of inheritance of acute appendicitis in childhood and early adolescence. Our case-control study showed that a positive family history for reported appendectomy was significantly more frequent in families of 80 consecutive patients eventually proved to have histopathologic acute appendicitis than in families of surgical controls matched for sex, age, and number of siblings. The relative risk was 10.0 (95% confidence limits 4.7-21.4). The pattern of familial aggregation was further supported by the fact that the age-standardized morbidity ratio was four times greater among family members of cases than among controls. We then applied the unified mixed model of segregation analysis, as implemented in the computer program POINTER, to a new set of 100 multigenerational pedigrees of children with histopathologically confirmed acute appendicitis that were broken down into 674 nuclear families. Age-specific morbidity risk and lifetime incidence of acute appendicitis were estimated from relatives of controls matched for age and sex to probands. Complex segregation analysis supported a polygenic or multifactorial model with a total heritability of 56%. There was no evidence to support a major gene, although a rare gene could not be ruled out as the cause of a small proportion of cases. Specific studies to address genetic and environmental factors in this serious disease seem worthwhile; but, for now, a positive family history of appendicitis might join other evidence leading to improved clinical recognition of acute appendicitis.     

Occurrence of various autoantibodies in autoimmune diseases

The study aimed at determining the incidence of autoantibodies occurrence in the course of autoimmunological diseases of the thyroid gland and in healthy population. Autoantibodies against various structures were assayed, including: cellular nuclei, smooth muscles, mitochondria, biliary tubules, parietal cells, reticular fibres, striated muscles as well as thyroglobulin and thyroid microsomes. The study involved 63 patients with autoimmunological diseases of the thyroid gland (35 patients with Graves-Basedow disease and 28 patients with Hashimoto's disease) and 30 healthy individuals. Thyroid antimicrosomal and antithyroglobulin antibodies were assayed with RIA in stable phase whereas the remaining antibodies--with multifunctional indirect immunofluorescence test. The obtained results are the following: antimicrosomal antibodies were present in 68.3% cases while antithyroglobulin antibodies in 76.2% of the examined patients with autoimmunological diseases of the thyroid gland. Immunofluorescence tests performed in the same group have shown antinuclear antibodies in 13% of cases, antibodies against smooth muscles in 28.6%, antimitochondrial antibodies in 1.6%, antibodies against biliary tubules in 3.4%, antibodies against parietal cells in 11.1%, antibodies against reticular fibres in 7.9%, and antibodies against striated muscles in 9.5% of cases. Antinuclear antibodies, antibodies against smooth muscles, and antibodies against both thyroidal microsome and thyroglobulin (in 3.3%) were the only antibodies found in the control group.     

Thyroid cancer risk 40+ years after irradiation for an enlarged thymus: an update of the Hempelmann cohort

Although ionizing radiation is a known carcinogen, the long-term risk from relatively higher-dose diagnostic procedures during childhood is less well known. We evaluated this risk indirectly by assessing thyroid cancer incidence in a cohort treated with "lower-dose" chest radiotherapy more than 55 years ago. Between 2004 and 2008, we re-surveyed a population-based cohort of subjects treated with radiation for an enlarged thymus during infancy between 1926 and 1957 and their unexposed siblings. Thyroid cancer occurred in 50 irradiated subjects (mean thyroid dose, 1.29 Gy) and in 13 nonirradiated siblings during 334,347 person-years of follow-up. After adjusting for attained age, Jewish religion, sex and history of goiter, the rate ratio for thyroid cancer was 5.6 (95% CI: 3.1-10.8). The adjusted excess relative risk per gray was 3.2 (95% CI: 1.5-6.6). The adjusted excess absolute risk per gray was 2.2 cases (95% CI: 1.4-3.2) per 10,000 person-years. Cumulative thyroid cancer incidence remains elevated in this cohort after a median 57.5 years of follow-up and is dose-dependent. Although the incidence appeared to decrease after 40 years, increased risk remains a lifelong concern in those exposed to lower doses of medical radiation during early childhood.     

Thyroid disease and other maternal factors in mongolism

One hundred women, who at the age of 35 years or more had had a child with mongolism, were investigated to discover any relation between thyroid disease and autoimmunity and mongolism and to search for other possible etiological factors. They were compared with 100 matched controls. The mothers of mongoloid children had a higher incidence of thyroid disease, either hypo- or hyperactivity (11 compared with three in the control group). The proportion with thyroglobulin antibodies was the same (18.8%) in both groups and mean serum protein-bound iodine levels were similar. There was no difference in reproductive history, diseases other than of the thyroid, frequency of previous pelvic and abdominal x-rays or incidence of infectious hepatitis during the year prior to conception.     

IA-2 autoantibodies restricted to the IgG4 subclass are associated with protection from type 1 diabetes.

The tyrosine phosphatase-like protein IA-2 is a major target antigen for autoantibodies in the preclinical period of type 1 diabetes. In this study, we examined whether immunoglobulin isotypes and IgG subclass specific autoantibodies directed at IA-2 discriminate between children at risk of type 1 diabetes who progressed to diabetes vs. those who remained diabetes-free. IgG1-4, IgA and the IgE-specific IA-2 antibody (IA-2A) were measured by radioligand assays in 50 patients with type 1 diabetes and 41 ICA-positive siblings of patients with type 1 diabetes who were followed for diabetes development. Of 41 siblings, 32 were positive for IA-2A; of these, 59 % had IA-2 IgG1, 59 % IgG4, 16 % IgG3, 9 % IgG2, 16 % IgA and 13 % IgE antibodies. IA-2 IgG1 was the dominant isotype in prediabetic children (n = 14, 86 % positive) and patients with type 1 diabetes (98 % positive) whereas only 7 of 18 (39 %) non-progressors had antibodies of this isotype. In subjects that remained diabetes-free, a significantly higher frequency of IA-2 IgG4 in the absence of IgG1 was observed (50 %) compared to progressors (7 %) and patients with type 1 diabetes (0 %). Life-table analysis revealed that IA-2A restricted to IgG4 correlated with protection from type 1 diabetes (p < 0.003). In contrast, IA-2 IgG2, IgG3, IgE and IgA did not differ significantly between study groups. Our findings suggest that the measurement of IA-2 IgG1 and IgG4 subclass antibodies can serve as surrogate marker to discriminate between antibody positive subjects at high or low risk for rapid development of diabetes.     

Pertussis immunisation and serious acute neurological illnesses in children.

OBJECTIVE--To determine long term outcome in children who had a severe acute neurological illness in early childhood associated with pertussis immunisation. DESIGN--Follow up study of cases and matched controls. SETTING--Assessment of children at home and at school throughout Britain. SUBJECTS--Children recruited into the national childhood encephalopathy study in 1976-9 were followed up, with one of their two original matched controls, in 1986-9. MAIN OUTCOME MEASURES--Performance in educational attainment tests; behaviour problems reported by teachers and parents; continuing convulsions; evidence of other neurological or physical dysfunction. RESULTS--Over 80% of cases and controls were traced. Case children were significantly more likely than controls to have died or to have some form of educational, behavioural, neurological, or physical dysfunction a decade after their illness. The prevalence of one or more of these adverse outcomes in case children who had been immunised with diphtheria, tetanus, and pertussis vaccine within seven days before onset of their original illness was similar to that in case children who had not been immunised recently. The relative risk for recent diphtheria, tetanus, and pertussis immunisation in children who had died or had any dysfunction in comparison with controls was 5.5 (95% confidence interval 1.6 to 23.7). However, the number of cases associated with vaccine (12) was extremely small and statistically vulnerable, and other possible agents or predisposing factors could not be excluded. CONCLUSIONS--Diphtheria, tetanus, and pertussis vaccine may on rare occasions be associated with the development of severe acute neurological illnesses that can have serious sequelae. Some cases may occur by chance or have other causes. The role of pertussis vaccine as a prime or concomitant factor in the aetiology of these illnesses cannot be determined in any individual case. The balance of possible risk against known benefits from pertussis immunisation supports continued use of the vaccine.     

Higher Risk of Thyroid Disorders in Young Patients with Type 1 Diabetes: A 12-Year Nationwide,Population-Based,Retrospective Cohort Study

Background

The association between type 1 diabetes and thyroid autoimmunity has been studied in various populations, but seldom on Taiwanese children and adolescents. Therefore, the aim of this study was to examine the incidence of autoimmune thyroid disorders in Taiwanese children and adolescent patients with type 1 diabetes, based on data from a nationwide, population-based, health claims database.

Methods

Using Taiwan’s National Health Insurance Research Database, we identified 3,652 patients with type 1 diabetes between 2000 and 2012. A comparison cohort was assembled, which consisted of five patients without type 1 diabetes, based on frequency matching for sex and 3-year age interval, for each patient with type 1 diabetes. Both groups were followed until diagnosis of thyroid disorders or the end of the follow-up period. Poisson regression models were used to calculate incidence rate ratios for the thyroid disorders between the type 1 diabetes cohort and the comparison cohort.

Results

Simple and unspecified goiter (International Classification of Diseases, 9^th Revision, Clinical Modification [ICD-9-CM] code 240), thyrotoxicosis (ICD-9-CM code 242), unspecified hypothyroidism (ICD-9-CM code 244.9), and thyroiditis (ICD-9-CM code 245) showed significantly higher incidences in the type 1 diabetes cohort compared with the control cohort, with incidence rate ratios of 2.74, 6.95, 6.54, 16.07, respectively.

Conclusions

Findings from this nationwide, population-based cohort study showed that the incidences of autoimmune thyroid disorders were significantly higher in Taiwanese children and adolescents with type 1 diabetes compared with those without the disease.     

Immunoenzyme determination of antibodies to the surface of islands of Langerhans in autoimmune destruction of the insular apparatus

Enzyme-linked immunosorbent assay (ELISA) was applied for detection of human islet cell surface antibodies (ICSA) to rat islet target cells. In 23 healthy controls without hereditary diabetes the findings were on the upper normal limit (mean value of optical density + 3 SEM). The results above the limit were considered positive. 11 out of 18 insulin-dependent (Type I) diabetics with the disease duration less than 5 years were ICSA-positive. All 9 patients with insulin-independent (Type 2) diabetes were ICSA-negative. 3 out of 18 healthy subjects (siblings and children of probands with type II diabetes) were strongly ICSA-positive, although all the members of this risk group had unimpaired oral glucose tolerance test. Thus, ELISA screening of ICSA may be useful for discriminating patients with different types of diabetes and revealing nonaffected individuals at high risk according to their beta-cell integrity.     

Children at High Risk for Overweight: A Classification and Regression Trees Analysis Approach

Objective: Early identification of children at high risk for childhood overweight is a major challenge in fighting the obesity epidemic. We tried to identify the most powerful set of combined predictors for childhood overweight at school entry. Research Methods and Procedures: A classification and regression trees analysis on risk factors for childhood overweight in 4289 children 5 to 6 years of age participating in the obligatory school entry health examination 2001/2002 in Bavaria, Germany, was performed. Parental questionnaires asked for children's weight at birth and 2 years, breastfeeding history, maternal smoking in pregnancy, parental education, parental overweight/obesity, nationality, and number of older siblings. Overweight was defined according to sex‐ and age‐specific BMI cut‐points proposed by the International Obesity Task Force. Results: Prevalence of overweight was 11% among the entire study population. Although high early weight gain >10, 000 grams was found in about one‐half of the overweight children, its positive predictive value reached only 25%, indicating that one of four children with a high early weight gain is overweight at school entry. The best reliable set of predictors included high early weight gain and obese parents and accounted for a likelihood ratio of 3.6, with a corresponding positive predictive value of 40%, and was found in 4% of all children. Discussion: A combination of predictors available at 2 years of age could improve predictability of overweight at school entry. However, corresponding low positive predictive values indicate a precision of the prediction that might be insufficient for targeting intervention programs for identified high‐risk children.     

Cytoplasmic islet-cell antibodies (ICA) and cytoplasmic complement- fixing antibodies (CF-ICA) in patients with newly detected and short-lasting diabetes mellitus type 1

The study aimed at assessing ICA and CF-ICA in the serum of patients with newly diagnosed and short-lasting diabetes mellitus type 1. Sixty patients with newly diagnosed diabetes type 1 (39 patients) and short-lasting diabetes of the same type (21 patients) aged between 2 and 34 years were classified. Anti-islet antibodies were detected with indirect immunoflourescence in specimens of fresh, frozen human pancreast in the tested group ICA were found in 53% of cases. At the time of diagnosis, ICA were found in 76% of children and in 14% of adult patients whereas respective data for diabetes mellitus lasting up to 2 years were 40% and 64%. Complement-fixing islet cytoplasmatic antibodies were found only in patients with ICA (47% of such cases). These antibodies were found in children with newly diagnosed diabetes mellitus (36%). In case of adults CF-ICA were detected in 7% of newly diagnosed diabetes mellitus cases and in 45% of cases with the disease lasting for 2 years. Titres of ICA ranged from 1:1 to 1:128 whereas titres CF-ICA from 1:1 to 1:8. No correlation between ICA titre and CF-ICA titre was noted.     

Natural course of preclinical type 1 diabetes

The clinical presentation of type 1 diabetes is preceded by an asymptomatic latent period characterized by the presence of diabetes-associated autoantibodies in the peripheral circulation, reflecting beta-cell damage. This prediabetic period may last for months and years. Several studies observing genetically susceptible subjects from birth have shown that insulin autoantibodies (IAA) are the first or among the first autoantibodies to appear in young children, implying that insulin may be the primary autoantigen in most cases of childhood type 1 diabetes. About 12-16% of siblings of children with type 1 diabetes have been observed to test positive for at least one diabetes-associated autoantibody, whereas the risk of diabetes among siblings has been estimated to be 6-8%. In parallel, close to 4% of Finnish schoolchildren tested positive for at least one diabetes-associated autoantibody; the lifetime risk of type 1 diabetes in the Finnish population has been estimated to be close to 1%. These observations suggest that only 25-50% of those with signs of beta-cell autoimmunity eventually progress to clinical type 1 diabetes. Accordingly there is a considerable proportion of children in whom beta-cell autoimmunity remains subclinical or is aborted. Positivity for only one diabetes-associated autoantibody may actually represent innocent beta-cell autoimmunity, while positivity for two or more autoantibodies seems to mark a point of no return. The autoimmune response is very dynamic in the early phase of prediabetes, with spreading from one antigen to another and from one epitope to another within a given antigen. In addition both isotype spreading and switching can be observed in early prediabetes. This indicates that the early prediabetic process may be a suitable target for immunomodulation aimed at delaying or preventing progression to clinical diabetes.     

Anti-GAD-positive patients with type 1 diabetes mellitus have higher prevalence of autoimmune thyroiditis than anti-GAD-negative patients with type 1 and type 2 diabetes mellitus

The aim of our study was to evaluate antibodies against thyroglobulin (anti-TG) and thyroid peroxidase (anti-TPO) - markers of autoimmune thyroiditis - in several groups of adult patients with type 1 and type 2 diabetes mellitus (DM). We were particularly interested whether the presence of thyroid antibodies is related to the positivity of glutamic acid decarboxylase antibodies (anti-GAD). We found elevated anti-GAD in 46 % (97/210) patients with type 1 DM. All patients with type 2 diabetes were anti-GAD-negative. At least one thyroid antibody (anti-TG and/or anti-TPO) was found in 30 % (62/210) patients with type 1 DM and 27 % (22/83) type 2 diabetes patients. The patients with type 1 DM were further grouped according to their anti-GAD status. The anti-GAD-positive patients had a higher prevalence of anti-TG antibodies than the anti-GAD-negative patients (25 % vs. 12 %, p=0.03) as well as anti-TPO antibodies (32 % vs. 12 %, p<0.001). At least one thyroid antibody was detected in 39 % (38/97) of anti-GAD-positive but only in 21 % (24/113) of anti-GAD-negative patients with type 1 DM (p=0.006). No significant difference in the frequency of thyroid antibodies was found between anti-GAD-negative patients with type 1 and type 2 DM (21 % vs. 27 %, p=0.4). The groups with or without thyroid antibodies in both type 1 and type 2 diabetic patients did not differ in actual age, the age at diabetes onset, duration of diabetes, body mass index or HbA1c level. Patients with elevated thyroid antibodies had significantly higher levels of TSH than those without thyroid antibodies (1.86 vs. 3.22 mIU/l, p=0.04 in type 1 DM; 2.06 vs. 4.89 mIU/l, p=0.003 in type 2 DM). We conclude that there is a higher frequency of thyroid-specific antibodies in anti-GAD-positive adult patients with type 1 DM than in anti-GAD-negative patients or in patients with type 2 DM. Patients with or without thyroid antibodies do not differ in age, DM onset and duration, BMI or HbA1c. Thyroid antibodies-positive patients have higher levels of thyroid stimulating hormone (TSH).