No abstract

The proinflammatory cytokine interleukin (IL)-1β is implicated in the development of insulin resistance and β-cell dysfunction, whereas higher circulating levels of IL-1 receptor antagonist (IL-1RA), an endogenous inhibitor of IL-1β, has been suggested to improve glycemia and β-cell function in patients with type 2 diabetes. To elucidate the protective role of IL-1RA, this study aimed to identify genetic determinants of circulating IL-1RA concentration and to investigate their associations with immunological and metabolic variables related to cardiometabolic risk. In the analysis of seven discovery and four replication cohort studies, two single nucleotide polymorphisms (SNPs) were independently associated with circulating IL-1RA concentration (rs4251961 at the IL1RN locus [n = 13,955, P = 2.76 × 10−21] and rs6759676, closest gene locus IL1F10 [n = 13,994, P = 1.73 × 10−17]). The proportion of the variance in IL-1RA explained by both SNPs combined was 2.0%. IL-1RA–raising alleles of both SNPs were associated with lower circulating C-reactive protein concentration. The IL-1RA–raising allele of rs6759676 was also associated with lower fasting insulin levels and lower HOMA insulin resistance. In conclusion, we show that circulating IL-1RA levels are predicted by two independent SNPs at the IL1RN and IL1F10 loci and that genetically raised IL-1RA may be protective against the development of insulin resistance.

These results suggest that genetic variation in the IL-1 gene family is associated with measures of glucose homeostasis and prevalent diabetes.

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Low-grade inflammation is a major player in obesity and the metabolic syndrome predicting development of type 2 diabetes (T2DM). The interleukin-1 receptor antagonist (IL-1Ra) is a vital and natural anti-inflammatory factor and mediator in glucose homeostasis disturbances. The predictive role is independent of multiple confounders, and elevated levels appear few years before T2DM. The role of IL-1Ra is important for accumulated risk factors, dysregulated metabolism and glucose homeostasis, and dietary interventions. Longitudinal and cross-sectional population study cohorts have enabled the approximation of IL-1Ra limit values for metabolic dysregulation and guide further analysis as a potential biomarker. The limit value of IL-1Ra is reaching 400 pg/mL with prediabetes and before T2DM. However, subjects with metabolic syndrome are suggested to have lower limit values, especially among men. Future research may evaluate the role of IL-1Ra in actual glucose homeostasis together with routine fasted laboratory tests, such as glucose and C-reactive protein (CRP) instead of the oral glucose tolerance test. The significance of intermediate low IL-1Ra levels in metabolic abnormalities should be further analyzed. It is possible to specify the impact of multiple lifestyle and metabolic parameters together with age and sex. IL-1Ra could be studied in multiple approaches including interventional studies of metabolic diseases.

Our aim was to investigate the occurrence of clinical and subclinical autoimmune thyroid disease in 79 patients with celiac disease as reflected in thyroid function, antibodies, and ultrasound. Since subclinical thyroid diseases are common in the population, 184 nonceliac controls were also studied. Normal thyroid function combined with positive antibodies and marked hypoechogenicity was considered subclinical disease. Autoimmune thyroid disease was observed in 13.9% of celiac patients and in 2.1% of controls (P = 0.0005); and subclinical disease in 10.1% and 3.3%, respectively (P = 0.048). The mean thyroid gland volume was 8.3 ml in celiac patients and 10.4 ml in controls (P = 0.007). Hypoechogenicity was found in 73% of celiac patients and in 42% of controls (P < 0.0001). Positive thyroid antibodies were associated with hypoechogenicity in celiac patients but not in controls. In conclusion, the occurrence of both clinical and subclinical autoimmune thyroid disease was increased in celiac disease; subclinical thyroid disease indicates regular surveillance.

Moderately elevated testosterone concentrations together with obesity-related inflammatory factors modify glucose homeostasis by increasing insulin resistance and early insulin secretion.

Evaluation of infectious etiology in subacute thyroiditis lack of association with Coxsackievirus infection. APMIS 106: 500 -504, 1998. The etiology of subacute granulomatous thyroiditis (SAT) is obscure. although it is postulated to be associated with viral infections and genetic factors. In the present study. the possibility of an infectious etiology was prospectively studied in 27 consecutive patients with SAT. Special emphasis was put on the role of enteroviruses. Coupled sera (interval one month) were taken from all patients and single sera from 29 control subjects for virus antibody determinations. Stool samples were collected for virus isolation and fine-needle aspiration samples from thyroid gland for the detection of enterovirus RNA using RT-PCR were taken from SAT patients. Enteroviral antibodies were tested using three different methods: indirect EIA, heavy chain capture RIA, and standard complement fixation (CF) test. Antibodies against other common viral pathogens, including enteroviruses, were screened using the CF test and those against Mycoplamu pneumoniue and Chlurnydiu pncwrnoniar using EIA and microimmunofluorescence techniques, respectively. Common respiratory viruses were also screened from nasopharyngeal suction samples by antigen detection EIA. Based o n serological findings, one patient had acute Cytomegalovirus infection. All other patients were negative in antibody tests, virus isolation, RT-PCR, and antigen detection. Enterovirus RNA was not detected by PCR in the thyroid tissue in any of the fine-needle aspiration samples. There was no evidence of recent cnteroviral infections in SAT patients. The results suggest that SAT is not usually associated with acute infections. No evidence was obtained to support the proposed role of enteroviruses as an important etiologic agent of SAT.The etiology of subacute granulomatous thyroiditis (SAT) is still incompletely understood, although an association with viral infections such as Coxsackievirus and other enterovirus infections has been reported ( 3 , 4,9,20,23). Enterovirus infections are considered possible triggering events also in certain other immune-