Natural history of preclinical IDDM in high risk siblings

Knip, Mikael; Vähäsalo, Paula; Karjalainen, J.; Lounamaa, R; Åkerblom, Hans K.; Tuomilehto, Jaakko; Toivanen, Liisa; Virtala, Esa; Pitkäniemi, Janne; Fagerlund, Åse; Flittner, M.; Gustafsson, B.; Häggquist, C.; Hakulinen, A.; Herva, L.; Hiltunen, Pauliina; Huhtamäki, T.; Huttunen, N. P.; Huupponen, T; Hyttinen, Marko; Joki, T.; Jokisalo, R.; Käär, M.‐L.; Kallio, Suvi; Kaprio, Eero A.; Kaski, U.; Laine, Loren; Lappalainen, Jani; Mäenpää, J; Mäkelä, Anna‐Liisa; Niemi, Katri; Niiranen, A.; Nuuja, A.; Ojajärvi, P.; Otonkoski, Timo; Pihlajamäki, K.; Pöntynen, S.; Rajantie, Jukka; Sankala, J.; Schumacher, J.; Sillanpää, Markus; Ståhlberg, Marja‐Riitta; Stråhlmann, C. H.; Uotila, T.; Väre, M.; Varimo, P.; Wetterstrand, G.; Aro, Antti; Hurme, H.; Höyty, H.; Ilonen, Jorma; Leinikki, Pauli; Miettinen, Aaro; Rásänen, Leena; Reunanen, Antti; Savilahti, Erkki; Tuomilehto‐Wolf, Eva; Virtanen, S. M.

doi:10.1007/bf00408476

Cited by 47 publications

(16 citation statements)

References 23 publications

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“…It is also noteworthy that despite lower insulin levels during the IVGTT, the relatives of diabetic patients -especially these with positive autoantibodies -had significantly higher fasting insulin concentrations and higher HOMA-IR index than had the controls. Moreover, a positive correlation between IAA levels and HOMA-IR was found in the study group, confirming the previous observations suggesting that not only decreased beta-cell secretory reserve, but also increased insulin resistance, impact upon the progression of the autoimmune process, especially in subjects with auto-antibodies directed against pancreatic islet antigens [17][18][19]. Abnormal sensitivity to insulin in patients with type 1 diabetes was shown for the first time by Ginsberg in the 1970s [20].…”

Section: Prace Oryginalnesupporting

confidence: 88%

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Markery ryzyka rozwoju cukrzycy typu 1 u krewnych I stopnia osób chorych na cukrzycę typu 1

Siewko¹,

Popławska-Kita²,

Telejko³

et al. 2014

Endokrynologia Polska

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Introduction: The aim of this study was to evaluate beta-cell function and insulin resistance in relation to the occurrence of anti-islet antibodies in first degree relatives of patients with type 1 diabetes (T1D). Material and methods:The group studied consisted of 90 relatives and 60 healthy individuals without a family history of diabetes. An intravenous glucose tolerance test (IVGTT) was performed in all participants and the first phase insulin response index (FPIR) was calculated. Serum concentrations of GADA, IAA and IA-2A were measured by RIA. HOMA-IR and HOMA%B indices were calculated using a computer calculator from website. Results: At least one positive antibody was found in 28 relatives (31.1%) but in none of the controls. The most frequently detected antibodies were IAA (22.2%). The relatives of diabetic patients had significantly higher fasting insulin level (p), significantly lower FPIR index (p), as well as higher HOMA-IR (p) and lower HOMA%B (p) compared to the controls. A positive correlation between IAA concentration and HOMA-IR (r = 0.287, p < 0.005) and a negative correlation between IAA level and HOMA%B (r = -0.226, p < 0.05) were also shown. Conclusions: Our results confirmed that more than 30% of the first-degree relatives of diabetic patients have positive markers of autoimmune beta-cell destruction. The study showed also that these individuals, in spite of normal glucose tolerance, have markedly decreased beta-cell secretory reserve and decreased sensitivity to insulin action, strongly suggesting an increased risk for developing diabetes later in life.

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Section: Prace Oryginalnesupporting

confidence: 88%

“…To date, it is not well understood when this autoimmune destruction begins in relation to the clinical presentation of the disease and what screening tests can accurately select the subjects who are at risk for developing the disease [1]. Moreover, it has been suggested that not…”

Section: Introductionmentioning

confidence: 99%

Markery ryzyka rozwoju cukrzycy typu 1 u krewnych I stopnia osób chorych na cukrzycę typu 1

Siewko¹,

Popławska-Kita²,

Telejko³

et al. 2014

Endokrynologia Polska

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“…Clear signs of ␤-cell damage often appear months or years before the manifestation of clinical diabetes (10), suggesting that prospective studies starting before the appearance of autoantibodies may be helpful in studying the etiology of the disease. In addition, early recognition of the individuals with ongoing ␤-cell damage may make it possibile to delay or halt ␤-cell destruction.…”

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confidence: 99%

Enterovirus infection as a risk factor for beta-cell autoimmunity in a prospectively observed birth cohort: the Finnish Diabetes Prediction and Prevention Study.

et al. 2000

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Previous studies suggest that enterovirus infections may initiate and accelerate ␤-cell damage years before the clinical manifestation of type 1 diabetes. We have now analyzed the role of enterovirus infections in the initiation of autoimmunity in children who have tested positive for diabetes-associated autoantibodies in a prospective study starting at birth (the Finnish Diabetes Prediction and Prevention Study). The frequency of enterovirus infections was studied using both serology and testing for the presence of enterovirus RNA in the sera of 21 children who developed and retained autoantibodies and in 104 control subjects chosen from the same study cohort and matched for the time of birth, sex, and HLA alleles determining genetic diabetes susceptibility. Sample intervals were taken as basic units of follow-up, to which the observed number of infections was adjusted. Enterovirus infections were detected in 26% of sample intervals in the case subjects and in 18% of the sample intervals in the control children (P = 0.03). A temporal relationship between enterovirus infections and the induction of autoimmunity was found; enterovirus infections were detected in 57% of the case subjects during a 6-month follow-up period preceding the first appearance of autoantibodies compared with 31% of the matched control children in the same agegroup (odds ratio 3.7, 95% CI 1.2-11.4). The frequency of adenovirus infections did not differ between the patient and control groups. Our data imply that enterovirus infections are associated with the development of ␤-cell autoimmunity and provide evidence for the role of enteroviruses in the initiation of ␤-cell destruction. Diabetes 49:1314-1318, 2000 T he etiology of type 1 diabetes comprises both genetic and environmental components. Enterovirus infections have long been suspected as potential environmental factors playing a role in the pathogenesis of type 1 diabetes (1,2). Recent prospective studies, based on enterovirus serology (3-5) and detection of enterovirus RNA in sera of prediabetic children (6), suggest that enterovirus infections may initiate and accelerate the ␤-cell-damaging process years before the clinical manifestation of type 1 diabetes. Enterovirus RNA has also been detected more frequently in patients with newly diagnosed type 1 diabetes than in healthy control subjects (7-9).Clear signs of ␤-cell damage often appear months or years before the manifestation of clinical diabetes (10), suggesting that prospective studies starting before the appearance of autoantibodies may be helpful in studying the etiology of the disease. In addition, early recognition of the individuals with ongoing ␤-cell damage may make it possibile to delay or halt ␤-cell destruction. The Finnish Diabetes Prediction and Prevention (DIPP) Study is a prospective population-based birth-cohort study in which Finnish children with increased genetic risk for type 1 diabetes are studied for the appearance of diabetes-associated autoantibodies at 3-to 12-month intervals from birth. We have now stud...

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“…Positivity of pancreatic autoantibodies in T1DM patients in Japan are 60-70% for GADA, 45-50% for IAA, and 60-65% for IA-2 antibodies at the time of diagnosis. 15 Our results indicated that GADA, IAA and ICA were positive in 80.6%, 35.5% and 6.5% of Korean patients with T1DM.Many studies have shown that siblings of patients with T1DM are at an increased risk of diabetes-related autoimmunity.11,12 Knip et al 16 reported that pancreas autoantibodies were positive in 24.1% of siblings of T1DM subjects. Onengut-Gumuscu et al 17 revealed that the pancreas autoantibodies were showed in 9% of first-degree relatives of T1DM patients in European countries.…”

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confidence: 59%

Frequency of diabetes and thyroid autoantibodies in patients with type 1 diabetes and their siblings

Kim¹,

Oh²,

Kim³

et al. 2016

EJEA

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The aim of this study was to better understand the frequency of autoimmune thyroid and diabetes antibodies in patients with type 1 diabetes mellitus (T1DM) compared with their siblings. Glutamic acid decarboxylase antibodies (GADA), islet cell antibodies (ICA), insulin autoantibodies (IAA), and thyroid autoantibodies were studied in all subjects. The rates of positive GADA and IAA were significantly higher in probands compared to in siblings (p＜0.001) or controls (p＜0.001). All pancreatic autoantibodies were not significantly different between the siblings and the healthy controls. Thyroid antiperoxidase antibody (TPOAb) and antithyroglobulin antibody (TGAb) were significantly different between the probands and the control subjects (p=0.002 and p=0.018, respectively). The rates of TPOAb and TGAb positivity in siblings were higher than in those of the controls, but there was no significant difference between the two groups. However, thyroid autoimmunity (TA) was significantly different among the groups (p=0.004). Siblings of the TA-positive probands were shown to have a greater prevalence of thyroid antibodies than did the controls (p=0.022), but siblings of the TA-negative probands did not have such a prevalence compared with the control subjects. The prevalence of pancreatic and thyroid antibodies positivity in probands was statistically significant compared with the siblings and the controls. Siblings of TA-positive probands revealed a greater prevalence of thyroid antibodies than did the controls. Therefore, the screening for TA in siblings, particularly siblings of TA-positive probands, is as important as it is in probands. INTRODUCTIONType 1 diabetes mellitus (T1DM) results from lack of insulin secretion caused by the destruction of pancreatic  cells.1 Most patients with T1DM have the diabetes autoantibodies such as insulin autoantibodies (IAA), glutamic acid decarboxylase (GADA), and islet cell antibody (ICA). 2T1DM patients are at an increased risk for additional autoimmune diseases like that Graves' disease, Hashimoto's thyroiditis, and Addison's disease. 3 The most common autoimmune disorder related with T1DM is autoimmune thyroid disease (AIT). [4][5][6][7] The frequency of thyroid autoantibody positivity in children with T1DM has been reported in about 50% in different ethnicity.8 Thyroid disorders occurred within 3 to 4 years in fifty percent of the thyroid autoantibody positive subjects. 5,9 It has been suggested that T1DM and AIT have common genetic sources since they often co-occur in patients and families. 10 The risk for this autoimmune disorder is known to increase in first-degree relatives of T1DM subjects, and 8% of first-degree families have AIT. 11,12 To our best knowledge, the frequency of autoantibodies for diabetes and thyroid in Korean children with T1DM and their siblings have not been investigated. So, in this study, we aim to investigate the frequency of autoimmune thyroid and diabetes antibodies in patients of T1DM, their siblings, and healthy controls. MATERIALS AND METHODS Su...

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Natural history of preclinical IDDM in high risk siblings

Cited by 47 publications

References 23 publications

Markery ryzyka rozwoju cukrzycy typu 1 u krewnych I stopnia osób chorych na cukrzycę typu 1

Markery ryzyka rozwoju cukrzycy typu 1 u krewnych I stopnia osób chorych na cukrzycę typu 1

Enterovirus infection as a risk factor for beta-cell autoimmunity in a prospectively observed birth cohort: the Finnish Diabetes Prediction and Prevention Study.

Frequency of diabetes and thyroid autoantibodies in patients with type 1 diabetes and their siblings

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