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Fleiner, H. F., Bjoro, T., Midthjell, K., Grill, V., & Asvold, B. O. (2016). Prevalence of Thyroid Dysfunction in Autoimmune and Type 2 Diabetes: The Population-Based HUNT Study in Norway. The Journal of clinical endocrinology and metabolism, 101(2), 669–677.
Abstract: CONTEXT: Associations between autoimmune diabetes and autoimmune thyroid disease are known but insufficiently characterized. Some evidence suggests that type 2 diabetes may also be associated with hypothyroidism. OBJECTIVE: The objective of the study was to investigate associations of autoimmune and type 2 diabetes with the prevalence of hypo- and hyperthyroidism. DESIGN AND SETTING: This was a cross-sectional, population-based study of adults in two surveys of the Nord-Trondelag Health (HUNT) Study. PARTICIPANTS: A total of 34 235 participants of HUNT2 (1995-1997) and 48 809 participants of HUNT3 (2006-2008) participated in the study. MAIN OUTCOME MEASURES: Prevalence of hypo- and hyperthyroidism was estimated, assessed by self-report, serum measurements, and linkage with the Norwegian Prescription Database. RESULTS: In HUNT2, autoimmune diabetes was associated with a higher age-adjusted prevalence of hypothyroidism among both women (prevalence ratio 1.79, 95% confidence interval [CI] 1.30-2.47) and men (prevalence ratio 2.71, 95% CI 1.76-4.19), compared with having no diabetes. For hyperthyroidism, the corresponding cumulative prevalence ratios were 2.12 (95% CI 1.36-3.32) in women and 2.54 (95% CI 1.24-5.18) in men with autoimmune diabetes. The age-adjusted excess prevalence of hypothyroidism ( approximately 6 percentage points) and the presence of thyroid peroxidase antibodies (8-10 percentage points) associated with autoimmune diabetes was similar in women and men. Type 2 diabetes was not associated with the prevalence of hypothyroidism. In HUNT3, associations were broadly similar to those in HUNT2. CONCLUSIONS: Autoimmune diabetes, but not type 2 diabetes, was strongly and gender neutrally associated with an increased prevalence of hypo- and hyperthyroidism and the presence of thyroid peroxidase antibodies. Increased surveillance for hypothyroidism appears not necessary in patients with type 2 diabetes.
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Sorgjerd, E. P., Skorpen, F., Kvaloy, K., Midthjell, K., & Grill, V. (2013). Prevalence of ZnT8 antibody in relation to phenotype and SLC30A8 polymorphism in adult autoimmune diabetes: results from the HUNT study, Norway. Autoimmunity, 46(1), 74–79.
Abstract: Zinc transporter 8 (ZnT8), a product of the SLC30A8 gene, is a target-antigen in autoimmune diabetes. Associations between ZnT8 antibody (ZnT8A), phenotype and the genetic variant rs13266634 in the SLC30A8 gene have primarily been studied in patients with young-onset diabetes. We explored such associations in adult-onset autoimmune diabetes identified from the all-population based Nord-Trondelag health Study (HUNT) ZnT8A (assayed by a fusion probe of C-terminal Arg325 and Trp325), and antibodies against glutamic decarboxylase (GADA) and tyrosine phosphatase-like protein insulinoma antigen-2 (IA-2A) were analysed in 266 subjects classified as having adult-onset autoimmune diabetes ( >/= 25 years of age at diagnosis). Of these, 161 subjects fulfilled the criteria of latent autoimmune diabetes in adults (LADA), whereas 105 subjects were termed “classical” type 1 diabetes. Ten out of 161 LADA (6.2%) and 23 out of 105 adult-onset “classical” type 1 diabetic patients (22%) were ZnT8A positive. Adult-onset diabetic subjects positive both for GADA and IA-2A (n = 17), had lower waist circumference (p = 0.024) and higher fasting glucose levels (p = 0.023) than those positive both for GADA and ZnT8A (n = 13). Genotyping results of rs13266634 (available in 178 adult-onset diabetic subjects), showed a tendency for association between ZnT8A positivity and the TT- and CC genotypes of SNP rs13266634 (p = 0.101) using the standard cut-off level of 0.06ai, and a significant association at a lower cut-off level of 0.01ai (p = 0.005). We conclude that ZnT8A positivity in a population of adult-onset autoimmune diabetes is a less strong marker of autoimmunity than IA-2A. Further, positivity could be influenced by polymorphism of the SLC30A8 gene.
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