Abstract
Objective
Thyroid diseases are common in individuals with type 1 diabetes mellitus (T1DM) and should be investigated annually in these individuals. The aim of this study was to evaluate the frequency of thyroid diseases in first degree relatives (FDR) of patients with T1DM.
Subjects and methods
Eighty individuals (40 patients with T1DM and 40 FDR) were interviewed and blood was sampled for thyroid-stimulating hormone (TSH), free thyroxine (FT4) and thyroid peroxidase (TPO) antibodies measurement. Autoantibodies against glutamic acid decarboxylase 65 (GAD65), islet antigen-2 (IA2) and autoantibodies against insulin (AAI) were measured in FDR.
Results
We found a similar prevalence of thyroid dysfunction in patients with T1DM and their FDR (22.5% vs. 27.5%; p = 0,79). There were no differences in serum TSH levels (p = 0.29), FT4 (p = 0,45), frequency of abnormal TSH (p = 0.28), positive TPO antibodies (p = 0.13), titers of TPO antibodies (in positive cases) between patients with T1DM and their FDR (p = 0.94).
Conclusions
Thyroid abnormalities seem to be common not only in patients with T1DM but also in their FDR, which suggests that screening strategies for thyroid diseases might also be useful to these individuals.
Autoimmunity; diabetes; thyroid dysfunction
INTRODUCTION
Patients with type 1 diabetes mellitus (T1DM) are at increased risk
for other autoimmune disorders, such as autoimmune thyroid disease (ATD), celiac
disease and Addison’s disease (11 Winter WE, Schatz DA. Autoimmune markers in diabetes. Clin Chem.
2011;57(2):168-75.
2 Bonifacio E, Mayr A, Knopff A, Ziegler AG. Endocrine autoimmunity in
families with type 1diabetes: frequent appearance of thyroid autoimmunity during
late childhood and adolescence. Diabetologia.
2009;52(2):185-92.-33 Hanukoglu A, Mizrachi A, Dalal I, Admoni O, Rakover Y, Bistritzer Z,
et al. Extrapancreatic autoimmune manifestations in type 1 diabetes patients and
their first degree relatives. Diabetes Care.
2003;26(4):1235-40.). The most prevalent autoimmune disease in
patients with T1DM is ATD. Although quite a variable frequency of thyroid antibodies
(thyroglobulin antibody – TgAb and thyroid peroxidase antibody – TPOAb) and thyroid
dysfunction (TD) has been reported in patients with T1DM among different populations
(from 3 to 50%), a high prevalence of ATD has been reported in most cases. This
suggests that both diseases share etiopathogenic mechanisms (22 Bonifacio E, Mayr A, Knopff A, Ziegler AG. Endocrine autoimmunity in
families with type 1diabetes: frequent appearance of thyroid autoimmunity during
late childhood and adolescence. Diabetologia.
2009;52(2):185-92.
3 Hanukoglu A, Mizrachi A, Dalal I, Admoni O, Rakover Y, Bistritzer Z,
et al. Extrapancreatic autoimmune manifestations in type 1 diabetes patients and
their first degree relatives. Diabetes Care.
2003;26(4):1235-40.
4 Kordonouri O1, Klinghammer A, Lang EB, Grüters-Kieslich A, Grabert
M, Holl RW. Thyroid autoimmunity in children and adolescents with type 1
diabetes. Diabetes Care. 2002;25:1346-50.
5 Ramos AJS, Costa ADM, Benicio AVL, Ramos ALC, Silva ARA, de Carvalho
CR, et al. Prevalência de doença tireoideana em pacientes com diabetes tipo 1.
Arq Bras Endocrinol Metab. 2003;47(2):177-82.-66 Mantovani RM, Mantovani LM, Dias VMA. Thyroid autoimmunity in
children and adolescents with type 1 diabetes mellitus: prevalence and risk
factors. J Pediatr Endocrinol Metab. 2007;20(6):669-75.). Current guidelines
recommend that all patients with T1DM should undergo an annual screening for thyroid
disease with at least a serum TSH measurement (22 Bonifacio E, Mayr A, Knopff A, Ziegler AG. Endocrine autoimmunity in
families with type 1diabetes: frequent appearance of thyroid autoimmunity during
late childhood and adolescence. Diabetologia.
2009;52(2):185-92.,66 Mantovani RM, Mantovani LM, Dias VMA. Thyroid autoimmunity in
children and adolescents with type 1 diabetes mellitus: prevalence and risk
factors. J Pediatr Endocrinol Metab. 2007;20(6):669-75.
7 Roldan MB, Alonso M, Barrio R. Thyroid autoimmunity in children and
adolescents with type 1 diabetes mellitus. Diabetes Nutr Metab.
1999;12:27-31.-88 Souza OLR, Diehl A, Carleto Jr LD, Garcia V, Carrilho AJF, Oliveira
ML, et al. Prevalência de auto-imunidade tireoidiana em um grupo de pacientes
com diabetes mellitus tipo 1 em Londrina, PR. Arq Bras Endocrinol Metab.
2005;49(2):228-33.).
Clustering of autoimmune disorders is commonly observed in families of patients that
have autoimmune diseases. Previous studies have shown that first degree relatives
(FDR) of patients with T1DM have an increased prevalence of thyroid abnormalities
than the general population (22 Bonifacio E, Mayr A, Knopff A, Ziegler AG. Endocrine autoimmunity in
families with type 1diabetes: frequent appearance of thyroid autoimmunity during
late childhood and adolescence. Diabetologia.
2009;52(2):185-92.,33 Hanukoglu A, Mizrachi A, Dalal I, Admoni O, Rakover Y, Bistritzer Z,
et al. Extrapancreatic autoimmune manifestations in type 1 diabetes patients and
their first degree relatives. Diabetes Care.
2003;26(4):1235-40.,99 Mohn A, Di Michele S, Faricelli R, Martinotti S, Chiarelli F.
Increased frequency of subclinical hypothyroidism and thyroid-associated
antibodies in siblings of children and adolescents with type 1 diabetes
mellitus. Eur J Endocrinol. 2005;153:717-8.
10 Villano MJ1, Huber AK, Greenberg DA, Golden BK, Concepcion E, Tomer
Y. Autoimmune thyroiditis and diabetes: dissecting the joint genetic
susceptibility in a large cohort of multiplex families. J Clin Endocrinol Metab.
2009;94(4):1458-66.
11 Barone B, Dantas JR, Almeida MH, Anna-Gomes BS, Bencke-Gongalves MD,
Albernaz MS, et al. Pancreatic autoantibodies, HLA DR and PTPN22 polymorphisms
in first degree relatives of patients with type 1 diabetes and multiethnic
background. Exp Clin Endocrinol Diabetes. 2011;119(10):618-20.-1212 Rodrigues R, Gonçalves FT, Jorge PT. Prevalência de disfunção
tireoidiana e anticorpos antitireoidianos em pacientes portadores de diabetes
melito tipo 1 e em seus familiares de primeiro grau. Arq Bras Endocrinol Metab.
2008;52(6):985-93.), ranging from 8 to 25% (22 Bonifacio E, Mayr A, Knopff A, Ziegler AG. Endocrine autoimmunity in
families with type 1diabetes: frequent appearance of thyroid autoimmunity during
late childhood and adolescence. Diabetologia.
2009;52(2):185-92.,33 Hanukoglu A, Mizrachi A, Dalal I, Admoni O, Rakover Y, Bistritzer Z,
et al. Extrapancreatic autoimmune manifestations in type 1 diabetes patients and
their first degree relatives. Diabetes Care.
2003;26(4):1235-40.).
However, these studies have included mostly Caucasians, very little is known about
the prevalence of ATD in other ethnic groups and thyroid disease often remains
undiagnosed in this group (1212 Rodrigues R, Gonçalves FT, Jorge PT. Prevalência de disfunção
tireoidiana e anticorpos antitireoidianos em pacientes portadores de diabetes
melito tipo 1 e em seus familiares de primeiro grau. Arq Bras Endocrinol Metab.
2008;52(6):985-93.,1313 Anaya JM, Castiblanco J, Tobón GJ, García J, Abad V, Cuervo H, et
al. Familial clustering of autoimmune diseases in patients with type 1 diabetes
mellitus. J Autoimmun. 2006;26(3):208-14.). The aim of this study was to investigate
the frequency of thyroid diseases and thyroid autoimmunity in FDR of patients with
T1DM from the Brazilian multiethnic population.
SUBJECTS AND METHODS
Eighty individuals were enrolled in this study, 40 patients with T1D (group 1) and their respective FDR (group 2). Patients were randomly selected, in order of appearance. All patients were followed at the Diabetes and Nutritional Diseases Section at Clementino Fraga Filho University Hospital (HUCFF) of Federal University of Rio de Janeiro (UFRJ), and at the State Institute of Diabetes and Endocrinology Luiz Capriglione (IEDE) in Rio de Janeiro, Brazil. The project was approved by the institutional review board and all participants signed an informed consent.
T1D was defined according to the American Diabetes Association criteria. One participant per family was included, and they were siblings or children of the index patient.
All subjects were interviewed and blood was sampled for thyroid stimulating hormone (TSH), free thyroxine (FT4) and thyroid peroxidase (TPO) antibodies measurement. Autoantibodies against glutamic acid decarboxylase 65 (GAD65), islet antigen-2 (IA2A) and autoantibodies against insulin (IAA) were also measured in the FDR. Thyroid dysfunction was defined by the presence of abnormal TSH levels and/or previous known thyroid disorder.
Serum TSH and TPO antibody were measured with a Chemiluminescence method according to the manufacturer’s instructions (Immulite – Diagnostic Products Corporation). For FT4, GADA, IA2A and IAA antibodies a direct radiobinding assay (Immulite-Diagnostic Products Corporation) was used. All analyses were performed at Clementino Fraga Filho University Hospital, Rio de Janeiro, Brazil. The sera were stored at -80°C degrees after sampling. Cut-off values for the test were set to 0.4 – 4.0 µlU/mL for TSH, 0.8 – 1.8 ng/dl for FT4, > 35 UI/mL for the positive TPO antibody, and ≥ 1.0 Ui/ml for positive GADA, IA2A and IAA antibodies.
All statistical analyses were performed using the Statistical Package for Social Science (SPSS). Mann-Whitney U test and Chi-Square were used for comparison between groups. A p-value < 0.05 was considered significant.
RESULTS
Characteristics of the study group
Among TIDM patients and their FDR, there was a higher prevalence of women (57.5% vs. 70%, respectively) and Whites (62.5% vs. 60%, respectively). T1DM subjects were older than their FDR (30.83 ± 10.57 years vs. 19.45 ± 9.77 years, respectively). In patients, the mean duration of diabetes was 13.1 ± 7.5 years. The characteristics of the study group are shown in table 1.
ATD in T1DM patients and their FDR
The prevalence of thyroid dysfunction (altered TSH and/or previous known thyroid disorder) did not differ between the groups (22.5% x 27.5%; p = 0.79). A total of 8 subjects had primary hypothyroidism and were treated with levothyroxine (five patients and three FDR). These FDR had previous thyroid disease. In two of them, the correspondent index case with TIDM also had hypothyroidism. The prevalence of TSH levels ≥ 2.5 µlU/ml was also similar in both groups (33.3% vs. 37.5% respectively, p = 0.81).
There were no significant differences in serum TSH levels (p = 0.29), FT4 (p = 0,45), abnormal TSH (p = 0.28), positive TPO antibodies (p = 0.13) and titers of TPO antibodies (in positive cases) between patients with T1DM and their FDR (p = 0.94). Abnormal TSH levels were observed in patients and their FDR, as shown in table 1, and were independent of TPO antibody status (p = 0.67). FT4 levels were normal in all patients with high TSH levels.
We found no association between TSH levels and gender (p = 0.31), ethnicity (p = 1.00) or age (p = 0.08) in the group as a whole or with the positivity for pancreatic autoantibodies (GADA p = 1.00, IA2A p = 0.49 and IAA p = 1.00) in the FDR.
The prevalence of GADA in FDR was 17.5% (n = 7). There was a positive association between positive titers of GADA, positive TPO antibodies (p = 0.00), and abnormal TSH levels (p = 0.01).
CONCLUSIONS
In this study, we identified a similar frequency of thyroid dysfunction and
autoimmunity in patients with T1DM and their FDR. Current guidelines indicate that
thyroid disorders should be screened annually in individuals with T1DM based on the
high risk of the development of these abnormalities (1414 van Belle TL, Coppieters KT, von Herrath MG. Type 1 diabetes:
etiology, immunology, and therapeutic strategies. Physiol Rev.
2011;91(1):79-118.
15 de Graaff LC, Martín-Martorell P, Baan J, Ballieux B, Smit JW,
Radder JK. Long-term follow-up of organ-specific antibodies and related organ
dysfunction in type 1 diabetes mellitus. Neth J Med.
2011;69(2):66-71.-1616 Barker JM, Barriga KJ, Yu L, Miao D, Erlich HA, Norris JM, et al.;
Diabetes Autoimmunity Study in the Young. Prediction of autoantibody positivity
and progression to type 1 diabetes: Diabetes Autoimmunity Study in the Young
(DAISY). J Clin Endocrinol Metab. 2004;89(8):3896-902.). Our data suggests that a
significant proportion of FDR also develop thyroid autoimmunity and thyroid
dysfunction.
Thyroid diseases may present with non-specific signs and symptoms and may remain undiagnosed for long periods of time. Untreated thyroid diseases may increase the risk of cardiovascular diseases through inter-relationships with dyslipidemia, insulin resistance and vascular endothelial dysfunction (1717 Waring AC, Cappola AR. Thyroid and cardiovascular risk. Thyroid and Heart Failure. 2009;151-65.,1818 Cappola AR, Fried LP, Arnold AM, Danese MD, Kuller LH, Burke GL, et al. Thyroid status, cardiovascular risk, and mortality in older adults. JAMA. 2006;295(9):1033-41.). Therefore, it is probable that FDR of patients with T1DM would also benefit by the current screening strategy for thyroid diseases that are applied for patients with T1DM.
Although we did not find any case of undiagnosed overt hypothyroidism in this study,
subclinical hypothyroidism was quite common. There is increasing evidence of the
role of subclinical asymptomatic hypothyroidism in the risk for cardiovascular
diseases (1717 Waring AC, Cappola AR. Thyroid and cardiovascular risk. Thyroid and
Heart Failure. 2009;151-65.
18 Cappola AR, Fried LP, Arnold AM, Danese MD, Kuller LH, Burke GL, et
al. Thyroid status, cardiovascular risk, and mortality in older adults. JAMA.
2006;295(9):1033-41.-1919 Jin P, Huang G, Lin J, Yang L, Xiang B, Zhou W, et al. High titre of
antiglutamic acid decarboxylase autoantibody is a strong predictor of the
development of thyroid autoimmunity in patients with type 1 diabetes and latent
autoimmune diabetes in adults. Clin Endocrinol (Oxf).
2011;74(5):587-92.) and even TSH levels between 2.5 and 4.0 mU/liter have been linked to
cardiovascular risk. The National Academy of Clinical Biochemistry has suggested
that the cutoff for TSH levels should be < 2.5 mU/liter, based on the observation
that 95% of the normal population has TSH levels within this range (2020 Kratzsch J, Fiedler GM, Leichtle A, Brügel M, Buchbinder S, Otto L,
et al. New reference intervals for thyrotropin and thyroid hormones based on
National Academy of Clinical Biochemistry criteria and regular ultrasonography
of the thyroid. Clin Chem. 2005;51(8):1480-6.). In this study, we did not find any
difference in the proportion of individuals with TSH levels < 2.5 mU/liter in
patients with T1DM and FDR.
Although this study had a modest sample size, other small studies have identified
similar results (22 Bonifacio E, Mayr A, Knopff A, Ziegler AG. Endocrine autoimmunity in
families with type 1diabetes: frequent appearance of thyroid autoimmunity during
late childhood and adolescence. Diabetologia.
2009;52(2):185-92.,33 Hanukoglu A, Mizrachi A, Dalal I, Admoni O, Rakover Y, Bistritzer Z,
et al. Extrapancreatic autoimmune manifestations in type 1 diabetes patients and
their first degree relatives. Diabetes Care.
2003;26(4):1235-40.,99 Mohn A, Di Michele S, Faricelli R, Martinotti S, Chiarelli F.
Increased frequency of subclinical hypothyroidism and thyroid-associated
antibodies in siblings of children and adolescents with type 1 diabetes
mellitus. Eur J Endocrinol. 2005;153:717-8.,1919 Jin P, Huang G, Lin J, Yang L, Xiang B, Zhou W, et al. High titre of
antiglutamic acid decarboxylase autoantibody is a strong predictor of the
development of thyroid autoimmunity in patients with type 1 diabetes and latent
autoimmune diabetes in adults. Clin Endocrinol (Oxf).
2011;74(5):587-92.,2121 Lam-Tse WK, Batstra MR, Koeleman BP, Roep BO, Bruining MG, Aanstoot
HJ, et al. The association between autoimmune thyroiditis, autoimmune gastritis
and type 1 diabetes. Pediatr Endocrinol Rev. 2003;1(1):22-37.
22 Jaeger C, Hatziagelaki E, Petzoldt R, Bretzel RG. Comparative
analysis of organ-specific autoantibodies in type 1 diabetic patients, their
first-degree relatives, and healthy control subjects. Diabetes Care.
2001;24(1):27-32.
23 Kordonouri O, Hartmann R, Deiss D, Wilms M, Grüters-Kieslich A.
Natural course of autoimmune thyroiditis in type 1 diabetes: association with
gender, age, diabetes duration, and puberty. Arch Dis Child.
2005;90(4):411-4.-2424 Bilimoria KY, Pescovitz OH, DiMeglio LA. Autoimmune thyroid
dysfunction in children with type 1 diabetes mellitus: screening guidelines
based on a retrospective analysis. J Pediatr Endocrinol Metab.
2003;16(8):1111-7.), including one in another sample of the
Brazilian population (1212 Rodrigues R, Gonçalves FT, Jorge PT. Prevalência de disfunção
tireoidiana e anticorpos antitireoidianos em pacientes portadores de diabetes
melito tipo 1 e em seus familiares de primeiro grau. Arq Bras Endocrinol Metab.
2008;52(6):985-93.). According to these
authors, thyroid autoantibodies occur in 8% to 25% of FDR of T1DM patients. The
prevalence of thyroid dysfunction is also high in this group (25%), being similar to
the prevalence found in patients. These data confirm the high frequency of thyroid
abnormalities in FDR of patients with T1DM and reinforce the relevance of
investigating thyroid disorders in family members of individuals with T1DM.
This study has also other limitations, besides its size. First, an ultrasound of the thyroid gland was not performed. Moreover, only one measurement of TSH was performed for each individual, without a confirmation of the TSH levels above the reference range. In addition, this was a cross-sectional study and information about the proportion of first degree relatives of patients with T1DM that develop clinical thyroid disease over the years is still lacking.
We did not observe any characteristic that would help to identify the FDR of T1DM
that are at an increased risk of thyroid abnormalities (age, gender, family member
with ATD, positive GADA, IA2 or IAA). However, some authors have found a positive
association between GADA and ATD (22 Bonifacio E, Mayr A, Knopff A, Ziegler AG. Endocrine autoimmunity in
families with type 1diabetes: frequent appearance of thyroid autoimmunity during
late childhood and adolescence. Diabetologia.
2009;52(2):185-92.,33 Hanukoglu A, Mizrachi A, Dalal I, Admoni O, Rakover Y, Bistritzer Z,
et al. Extrapancreatic autoimmune manifestations in type 1 diabetes patients and
their first degree relatives. Diabetes Care.
2003;26(4):1235-40.,77 Roldan MB, Alonso M, Barrio R. Thyroid autoimmunity in children and
adolescents with type 1 diabetes mellitus. Diabetes Nutr Metab.
1999;12:27-31.,1010 Villano MJ1, Huber AK, Greenberg DA, Golden BK, Concepcion E, Tomer
Y. Autoimmune thyroiditis and diabetes: dissecting the joint genetic
susceptibility in a large cohort of multiplex families. J Clin Endocrinol Metab.
2009;94(4):1458-66.,2222 Jaeger C, Hatziagelaki E, Petzoldt R, Bretzel RG. Comparative
analysis of organ-specific autoantibodies in type 1 diabetic patients, their
first-degree relatives, and healthy control subjects. Diabetes Care.
2001;24(1):27-32.
23 Kordonouri O, Hartmann R, Deiss D, Wilms M, Grüters-Kieslich A.
Natural course of autoimmune thyroiditis in type 1 diabetes: association with
gender, age, diabetes duration, and puberty. Arch Dis Child.
2005;90(4):411-4.
24 Bilimoria KY, Pescovitz OH, DiMeglio LA. Autoimmune thyroid
dysfunction in children with type 1 diabetes mellitus: screening guidelines
based on a retrospective analysis. J Pediatr Endocrinol Metab.
2003;16(8):1111-7.-2525 Bottini N, Vang T, Cucca F, Mustelin T. Role of PTPN22 in type 1
diabetes and other autoimmune diseases. Semin Immunol.
2006;18(4):207-13.). Bonifacio and cols. found
a positive association between the risk of developing TPOAbs and the presence of
GADA, whereas IA2A and IAA were not associated with TPOAb risk in relatives of T1DM
patients.
Further larger longitudinal studies are necessary to clarify if a universal screening for thyroid diseases should be recommended for FDR of patients with T1DM or if there are clinical or immunogenetic characteristics that could identify the individuals that are more prone to develop thyroid dysfunction and who should therefore undergo this investigation.
Acknowledgements:
we thank the participants and their families in this study as well as the nursing and medical staff for their help. We thank Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Capes) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for funding.
REFERENCES
-
1Winter WE, Schatz DA. Autoimmune markers in diabetes. Clin Chem. 2011;57(2):168-75.
-
2Bonifacio E, Mayr A, Knopff A, Ziegler AG. Endocrine autoimmunity in families with type 1diabetes: frequent appearance of thyroid autoimmunity during late childhood and adolescence. Diabetologia. 2009;52(2):185-92.
-
3Hanukoglu A, Mizrachi A, Dalal I, Admoni O, Rakover Y, Bistritzer Z, et al. Extrapancreatic autoimmune manifestations in type 1 diabetes patients and their first degree relatives. Diabetes Care. 2003;26(4):1235-40.
-
4Kordonouri O1, Klinghammer A, Lang EB, Grüters-Kieslich A, Grabert M, Holl RW. Thyroid autoimmunity in children and adolescents with type 1 diabetes. Diabetes Care. 2002;25:1346-50.
-
5Ramos AJS, Costa ADM, Benicio AVL, Ramos ALC, Silva ARA, de Carvalho CR, et al. Prevalência de doença tireoideana em pacientes com diabetes tipo 1. Arq Bras Endocrinol Metab. 2003;47(2):177-82.
-
6Mantovani RM, Mantovani LM, Dias VMA. Thyroid autoimmunity in children and adolescents with type 1 diabetes mellitus: prevalence and risk factors. J Pediatr Endocrinol Metab. 2007;20(6):669-75.
-
7Roldan MB, Alonso M, Barrio R. Thyroid autoimmunity in children and adolescents with type 1 diabetes mellitus. Diabetes Nutr Metab. 1999;12:27-31.
-
8Souza OLR, Diehl A, Carleto Jr LD, Garcia V, Carrilho AJF, Oliveira ML, et al. Prevalência de auto-imunidade tireoidiana em um grupo de pacientes com diabetes mellitus tipo 1 em Londrina, PR. Arq Bras Endocrinol Metab. 2005;49(2):228-33.
-
9Mohn A, Di Michele S, Faricelli R, Martinotti S, Chiarelli F. Increased frequency of subclinical hypothyroidism and thyroid-associated antibodies in siblings of children and adolescents with type 1 diabetes mellitus. Eur J Endocrinol. 2005;153:717-8.
-
10Villano MJ1, Huber AK, Greenberg DA, Golden BK, Concepcion E, Tomer Y. Autoimmune thyroiditis and diabetes: dissecting the joint genetic susceptibility in a large cohort of multiplex families. J Clin Endocrinol Metab. 2009;94(4):1458-66.
-
11Barone B, Dantas JR, Almeida MH, Anna-Gomes BS, Bencke-Gongalves MD, Albernaz MS, et al. Pancreatic autoantibodies, HLA DR and PTPN22 polymorphisms in first degree relatives of patients with type 1 diabetes and multiethnic background. Exp Clin Endocrinol Diabetes. 2011;119(10):618-20.
-
12Rodrigues R, Gonçalves FT, Jorge PT. Prevalência de disfunção tireoidiana e anticorpos antitireoidianos em pacientes portadores de diabetes melito tipo 1 e em seus familiares de primeiro grau. Arq Bras Endocrinol Metab. 2008;52(6):985-93.
-
13Anaya JM, Castiblanco J, Tobón GJ, García J, Abad V, Cuervo H, et al. Familial clustering of autoimmune diseases in patients with type 1 diabetes mellitus. J Autoimmun. 2006;26(3):208-14.
-
14van Belle TL, Coppieters KT, von Herrath MG. Type 1 diabetes: etiology, immunology, and therapeutic strategies. Physiol Rev. 2011;91(1):79-118.
-
15de Graaff LC, Martín-Martorell P, Baan J, Ballieux B, Smit JW, Radder JK. Long-term follow-up of organ-specific antibodies and related organ dysfunction in type 1 diabetes mellitus. Neth J Med. 2011;69(2):66-71.
-
16Barker JM, Barriga KJ, Yu L, Miao D, Erlich HA, Norris JM, et al.; Diabetes Autoimmunity Study in the Young. Prediction of autoantibody positivity and progression to type 1 diabetes: Diabetes Autoimmunity Study in the Young (DAISY). J Clin Endocrinol Metab. 2004;89(8):3896-902.
-
17Waring AC, Cappola AR. Thyroid and cardiovascular risk. Thyroid and Heart Failure. 2009;151-65.
-
18Cappola AR, Fried LP, Arnold AM, Danese MD, Kuller LH, Burke GL, et al. Thyroid status, cardiovascular risk, and mortality in older adults. JAMA. 2006;295(9):1033-41.
-
19Jin P, Huang G, Lin J, Yang L, Xiang B, Zhou W, et al. High titre of antiglutamic acid decarboxylase autoantibody is a strong predictor of the development of thyroid autoimmunity in patients with type 1 diabetes and latent autoimmune diabetes in adults. Clin Endocrinol (Oxf). 2011;74(5):587-92.
-
20Kratzsch J, Fiedler GM, Leichtle A, Brügel M, Buchbinder S, Otto L, et al. New reference intervals for thyrotropin and thyroid hormones based on National Academy of Clinical Biochemistry criteria and regular ultrasonography of the thyroid. Clin Chem. 2005;51(8):1480-6.
-
21Lam-Tse WK, Batstra MR, Koeleman BP, Roep BO, Bruining MG, Aanstoot HJ, et al. The association between autoimmune thyroiditis, autoimmune gastritis and type 1 diabetes. Pediatr Endocrinol Rev. 2003;1(1):22-37.
-
22Jaeger C, Hatziagelaki E, Petzoldt R, Bretzel RG. Comparative analysis of organ-specific autoantibodies in type 1 diabetic patients, their first-degree relatives, and healthy control subjects. Diabetes Care. 2001;24(1):27-32.
-
23Kordonouri O, Hartmann R, Deiss D, Wilms M, Grüters-Kieslich A. Natural course of autoimmune thyroiditis in type 1 diabetes: association with gender, age, diabetes duration, and puberty. Arch Dis Child. 2005;90(4):411-4.
-
24Bilimoria KY, Pescovitz OH, DiMeglio LA. Autoimmune thyroid dysfunction in children with type 1 diabetes mellitus: screening guidelines based on a retrospective analysis. J Pediatr Endocrinol Metab. 2003;16(8):1111-7.
-
25Bottini N, Vang T, Cucca F, Mustelin T. Role of PTPN22 in type 1 diabetes and other autoimmune diseases. Semin Immunol. 2006;18(4):207-13.
Publication Dates
-
Publication in this collection
Apr 2015
History
-
Received
31 Jan 2014 -
Accepted
11 Dec 2014