Evaluation of interleukin-29 in autoimmune and inflammatory thyroid diseases.

OBJECTIVE: Interleukins play an important role in the development of autoimmune disorders. The aim of this study was to compare the concentration of interleukin-29 (IL-29) between healthy controls (CS) and patients with selected thyroid disorders: Graves' disease (GD), Hashimoto's thyroiditis (HT) and subacute thyroiditis (SAT). DESIGN AND METHODS: The following parameters were examined in the group of 95 individuals (45 with GD, 22 with HT, 28 with SAT) and 72 CS: thyroid hormones and autoantibodies, inflammatory markers and the concentration of IL-29 in serum. RESULTS: The concentration of IL-29 in the GD subgroup was higher than that in the CS subgroup [264.0 (62.5-1018.0) vs. 62.5 (62.5-217.0) pg/mL, P = .001]. We found no differences in IL-29 concentrations between the CS and HT or SAT subgroups. Multivariable linear regression analysis indicated that IL-29 was a statistically significant independent predictor of GD presence (r = 0.24; P = .003) after adjustment for TRAb (R2  = 0.45; P < .001). The ROC analysis of IL-29 at GD diagnosis revealed an IL-29 cut-off of 123 pg/mL (sensitivity: 0.689 and specificity: 0.625) as the best value, which significantly indicated the presence of GD [area under the ROC curve (AUC): 0.676; 95% confidence interval (CI): 0.574-0.778, P < .001]. CONCLUSION: This is the first study to demonstrate elevated IL-29 serum levels in patients with GD. Our results suggest that IL-29 might be engaged in one of the pathogenetic pathways of GD, but no HT and SAT. Future studies are required to evaluate the potential of the protein as a therapeutic target in GD.

Evaluation of IL-29 in Euthyroid Patients with Graves' Orbitopathy: A Preliminary Study.

BACKGROUND: The most frequent cause of hyperthyroidism is Graves' disease (GD). Orbitopathy is the most prevalent and recognizable extrathyroidal manifestation of Graves' disease with unrevealed pathogenesis. Interleukin 29 (IL-29) is a relatively newly discovered inflammatory cytokine. Thus, the aim of this study was to evaluate the relationship between IL-29 and Graves' orbitopathy (GO) in euthyroid patients. METHODS: Thirty-one euthyroid patients with Graves' disease and with active GO [clinical activity score (CAS) ≥ 3/7], seventeen euthyroid patients with GD but without GO, and seventy-two healthy control subjects (CS) matched for age and gender were enrolled in the study. The following parameters were evaluated in every participant: thyroid-related hormones and autoantibodies and inflammatory markers (white blood cells, hsCRP). ELISA assay was applied to measure the concentration of IL-29. RESULTS: We found higher level of IL-29 in GO group in comparison with CS [165 (133-747) vs. 62 (62-217) pg/mL, p < 0.001]. Furthermore, participants in the subgroup with GD with GO as compared with GD without GO had higher concentration of IL-29 [165 (133-747) vs. 62 (62-558) pg/mL, p = 0.031]. The ROC analysis for IL-29 revealed IL-29 cut-off of 105 pg/mL (sensitivity 1.000 and specificity 0.597) as the best value significantly indicating the presence of GO in GD [area under the ROC curve (AUC): 0.739, 95% confidence interval (CI): 0.646-0.833, p < 0.001]. CONCLUSIONS: The present study revealed for the first time an elevated level of IL-29 in the serum of patients with GD and GO that might suggest its involvement in the pathogenesis of GD ocular complications.

Insulin resistance is associated with impaired olfactory function in adult patients with type 1 diabetes: A cross-sectional study.

AIM: To investigate whether insulin resistance is a predictor for decreased olfactory function in adult type 1 diabetes patients (T1DM). MATERIALS AND METHODS: The following parameters were examined in the group of 113 T1DM participants: body mass index (BMI), waist-hip ratio (WHR), TG/HDL ratio, glycated hemoglobin (HbA1c ), visceral fat (VF) in body bioimpedance, specific calculators (eGDR, VAI). Bilateral olfactory test score (BOTS) was performed using 12-odour-tests from Sniffin' Sticks. Then participants were allocated to one of two groups: normosmia (10-12 odours identified) or hyposmia/anosmia (0-9 odours). The association between BOTS and insulin resistance indicators was analyzed using: Spearman's rank correlation, multivariate linear regression analysis, and receiver operating characteristic (ROC) curve. RESULTS: 49.6% participants were diagnosed with hyposmia/anosmia, median BOTS was 10. BOTS correlated significantly with: WHR, TG, VF index, TG/HDL ratio, VAI, and eGDR. In multivariate linear regression analysis higher WHR turned out to be statistically significant independent predictor of lower BOTS (ß = -0.36; P = .005) after adjustment for age, sex, TG and peripheral neuropathy (R2 = 0.19; P = .0005). The ROC analysis indicated a WHR cut-off of 0.92 [area under the ROC curve (AUC): 0.737; 95% confidence interval (CI): 0.647-0.828, P < .0001] as the best among evaluated factors significantly affecting hyposmia/anosmia occurrence (sensitivity of this cut-off 0.50 and specificity 0.86). CONCLUSIONS: We have provided evidence of an association between lowered insulin sensitivity expressed in bioelectrical impedance analysis, anthropometrical (WHR), laboratory (TG/HDL ratio) measurements, specific calculators (eGDR, VAI) and deteriorated olfactory function.

Novel Biochemical Markers of Neurovascular Complications in Type 1 Diabetes Patients.

Type 1 diabetes mellitus (T1DM) is associated with chronic complications, which are the result of neurovascular changes. There is still a lack of universal biochemical markers of microvascular damage. The present study aimed to investigate whether selected inflammatory proteins are related to the prevalence of microvascular complications in adult T1DM patients. The following markers were determined in a group of 100 T1DM participants: epidermal growth factor (EGF), metalloproteinase 2 (MMP-2), growth/differentiation factor 15 (GDF-15), and interleukin 29 (IL-29). Screening for microvascular complications, such as autonomic and peripheral neuropathy, diabetic kidney disease, and retinopathy, was conducted. The group was divided according to the occurrence of microvascular complications. At least one complication was required for the patient to be included in the microangiopathy group. The median EGF concentration in the microangiopathy group was higher than in the group without microangiopathy (p = 0.03). Increasing EGF concentration was a statistically significant predictor of the presence of microangiopathy in multivariate logistic regression analysis (p < 0.0001). Additionally, a higher GDF-15 level was associated with diabetic kidney disease, peripheral neuropathy, and proliferative retinopathy vs. nonproliferative retinopathy. GDF-15 concentration correlated negatively with estimated glomerular filtration rate (eGFR) (r = -0.28; p = 0.02). To conclude, higher EGF concentration is an independent predictor of the presence of microvascular complications in T1DM patients. Besides the relation between GDF-15 and diabetic kidney disease, it may be also associated with peripheral neuropathy and retinopathy.

Nonadherence to potassium replacement protocol leads to prolonged management of diabetic ketoacidosis.

Introduction Diabetic ketoacidosis is a life-threatening condition that requires prompt management. Objectives We aimed to assess the impact of adherence to potassium replacement protocol according to the guidelines of Diabetes Poland on the duration of diabetic ketoacidosis (DKA) treatment. Patients and methods This retrospective analysis included 242 adults (median age, 27 years; range, 21-38 years). Nonadherence to potassium replacement protocol was assessed, along with the relationship between nonadherence and duration of DKA management. Nonadherence to the protocol was defined as too low or too high doses of potassium compared with the recommended potassium replacement protocol. Results The median duration of DKA treatment was longer in the nonadherent group than in the adherent group: 37 hours (interquartile range [IQR], 27-48) and 30 hours (IQR, 17-43), respectively (P = 0.005). Treatment duration correlated positively with nonadherence to potassium replacement protocol (r = 0.18; P = 0.005) and severity of DKA (r = 0.52; P <0.0001). Stepwise multivariate linear regression analysis indicated nonadherence to the protocol (ß = 0.14; P = 0.02) and severity of DKA (ß = 0.43; P <0.0001) as predictors of treatment duration, after adjustment for body mass index and age (R2 = 0.28; P <0.0001). Conclusions Nonadherence to potassium replacement protocol leads to prolongation of DKA management. Medical staff should be educated about the benefits of potassium replacement and precision in potassium administration and dosing in patients with DKA.

Higher free triiodothyronine concentration is associated with lower prevalence of microangiopathic complications and better metabolic control in adult euthyroid people with type 1 diabetes.

PURPOSE: Type 1 diabetes mellitus (T1DM) is a disorder of insulin deficiency but with a wide range of hormones simultaneously disturbed. The study was performed to explore relation of free triiodothyronine (FT3) with metabolic control and occurrence of microangiopathic complications. METHODS: A total of 266 adult T1DM participants [56% men; 32 (interquartile range, IQR: 25-39) years and disease duration 13 (IQR: 8-19) years] in euthyroid state with negative history for hypothyroidism were included to the study. Participants were screened for thyroid-stimulating hormone (TSH), free thyroxine (FT4) and FT3. Moreover, microangiopathic complications (retinopathy, diabetic kidney disease, peripheral and autonomic neuropathy), markers of metabolic control such as glycated hemoglobin (HbA1c) were evaluated. RESULTS: A total of 114 (42.9%) people had diagnosed at least one microangiopathic complication. In multivariable linear regression higher HbA1c was statistically significant independent predictor of lower FT3 (ß = -0.25; p < 0.0001) after adjustment for sex, T1DM duration, HbA1c, waist-to-hip ratio (WHR) (R2 = 0.15, p < 0.0001). Higher FT3 was simultaneously a predictor of lower prevalence of microangiopathy in multivariate logistic regression analysis (odds ratio, 0.51; 95% confidence interval, 0.27-0.98; p = 0.04) after an adjustment for: age, hypertension, HbA1c, WHR and total cholesterol (TC). CONCLUSIONS: FT3 as tissue active hormone plays a clinically important role in T1DM people. The higher FT3 concentration is related to the lower prevalence of microangiopathy and better metabolic control of the disease in adult euthyroid people with T1DM.

Association Between Self-reported Physical Activity and Skin Autofluorescence, a Marker of Tissue Accumulation of Advanced Glycation End Products in Adults With Type 1 Diabetes: A Cross-sectional Study.

PURPOSE: The accumulation of advanced glycation end products (AGEs) in local tissue is an important cause of low-grade inflammation and oxidative stress and is linked to late diabetic complications. Physical activity has various beneficial cardiometabolic effects in type 1 diabetes (T1D) and is associated with lower frequency of chronic complications of diabetes, although the specific mechanisms still remain unclear. The present study determines the association between self-reported physical activity and skin autofluorescence (AF), a marker of tissue accumulation of AGEs in adults with T1D. METHODS: We enrolled 119 patients (63 women), aged 34 years (interquartile range [IQR], 26-41 years), with T1D duration of 17 years (IQR, 12-25 years), glycosylated hemoglobin (HbA1c) of 7.9% (IQR, 7.1%-8.9%) referred to an outpatient diabetes clinic. Patients with diabetes duration of <5 years, age >65 years, concomitant diabetic ketoacidosis, and severe complications that restrict physical activity (eg, diabetic foot, diabetic proliferative retinopathy, blindness) were excluded. Physical activity was measured with the short version of the International Physical Activity Questionnaire (IPAQ-SF), and raw scores were then log-transformed because of non-normality. The accumulation of AGEs in the skin was assessed on the basis of skin AF. Correlations between AF and various laboratory and clinical findings were assessed, and multivariate linear regression analysis was used to examine factors that influenced AGEs. FINDINGS: Skin AF correlated positively with age (Spearman's coefficient [Rs] = 0.47; P < 0.0001), HbA1c (Rs = 0.30; P = 0.001), waist-to-hip ratio (WHR; Rs = 0.23; P = 0.02), and negatively with logIPAQ-SF (Rs = -0.28; P = 0.002). A stepwise multivariable linear regression analysis indicated age (ß = 0.46; P < 0.0001), HbA1c (ß = 0.21; P = 0.01), and logIPAQ-SF score (ß = -0.17; P = 0.04) as predictors of the skin AF after adjustment for sex and WHR (R2 = 0.36; P < 0.0001). IMPLICATIONS: Higher physical activity is related to lower accumulation of AGEs in patients with T1D. Our study provides new insight into the beneficial effects of physical activity in T1D according to tissue accumulation of AGEs.

Association of olfactory function with the intensity of self-reported physical activity in adults with type 1 diabetes.

INTRODUCTION    Olfactory function is impaired in patients with type 1 diabetes and can be recognized as a form of diabetic neuropathy. Physical activity has various beneficial effects on type 1 diabetes. OBJECTIVES    The aim of this study was to assess a relation between physical activity and olfactory function in patients with type 1 diabetes. PATIENTS AND METHODS    We enrolled 120 patients with type 1 diabetes referred to an outpatient diabetes clinic. Patients with diabetes duration of less than 5 years, age above 65 years, concomitant diabetic ketoacidosis, and those using drugs affecting nasal mucosa were excluded. The final study sample included 90 patients. A control group comprised 22 healthy participants. Olfactory function was assessed using 12 odor­emitting apens called Sniffin' Sticks. Physical activity was measured using the short version of the International Physical Activity Questionnaire (IPAQ­SF). RESULTS    There was a significant difference in the occurrence of hyposmia between diabetic patients and healthy controls (70.0% vs 45.5%, respectively; P = 0.03). There were no significant differences in IPAQ­SF results between the groups. Moreover, IPAQ­SF results correlated positively with olfactory test scores (r = 0.25; P = 0.02) and negatively with age. Additionally, patients with retinopathy and autonomic neuropathy obtained lower IPAQ­SF scores than patients without those complications. A stepwise multivariable linear regression analysis indicated IPAQ scores, body mass index, and peripheral neuropathy as predictors of the olfactory test score (R = 0.2).  CONCLUSIONS    Our study confirms the beneficial role of physical activity in type 1 diabetes within the structures of the central nervous system.