Pharmacological suppression of NLRP3 inflammasome attenuated the development of autoimmune thyroiditis.

Autoimmune thyroiditis (AIT), characterized by an endless inflammatory process of self-destruction, ultimately leads to chronic swelling of the thyroid gland and its dysfunction. Here, we investigated the involvement of the NLR pyrin domain-containing 3 (NLRP3) inflammasome in AIT development. We found that NLRP3 is significantly upregulated in the thyroid of AIT patients and mice with experimental autoimmune thyroiditis (EAT). Pharmacological suppression of NLRP3 using its inhibitor MCC950 suppressed the progression of EAT in vivo. Furthermore, MCC950 treatment significantly reduced the numbers of infiltrating CD4+ and CD8+ T cells in the thyroid. Moreover, MCC950 significantly lowered the amounts of T helper 1 cells, T helper 17 cells, interferon gamma, and interleukin-17A; however, it significantly increased regulatory-T-cell numbers and interleukin-10 levels. These results suggest that suppression of NLRP3 inflammasome activation reverses AIT by inhibiting Th1- and Th17-cell responses and promoting Treg cell responses. Hence, the NLRP3 inflammasome is a promising therapeutic and theragnostic target in AIT. inhibits Th1- and Th17-cell responses and promotes Treg cell responses.

IgM-associated gut bacteria in obesity and type 2 diabetes in C57BL/6 mice and humans.

AIMS/HYPOTHESIS: IgM is the primary antibody produced by B cells and we hypothesise that IgM antibodies to gut microbiota may play a role in immunometabolism in obesity and type 2 diabetes. To test our hypothesis, we used B6 mice deficient in activation-induced cytidine deaminase (Aid-/- [also known as Aicda-/-]) which secrete only IgM antibodies, and human faecal samples. METHODS: We studied the immunometabolic effects and gut microbial changes in high-fat-diet-induced obesity (HFDIO) in Aid-/- B6 mice compared with wild-type mice. To determine similarities between mice and humans, human stool samples were collected from children and adolescents who were obese with normal glucose tolerance (NGT), obese with glucose intolerance (IGT), or obese and newly diagnosed with type 2 diabetes, for faecal microbiota transplant (FMT) into germ-free (GF) B6 mice and we assessed IgM-bound bacteria and immune responses. RESULTS: Compared with wild-type mice, Aid-/- B6 mice developed exacerbated HFDIO due to abundant levels of IgM. FMT from Aid-/- B6 to GF B6 mice promoted greater weight gain in recipient mice compared with FMT using wild-type mouse faecal microbiota. Obese youth with type 2 diabetes had more IgM-bound gut bacteria. Using the stools from the obese youth with type 2 diabetes for FMT to GF B6 mice, we observed that the gut microbiota promoted body weight gain and impaired glucose tolerance in the recipient GF B6 mice. Importantly, some clinical features of these obese young individuals were mirrored in the GF B6 mice following FMT. CONCLUSIONS/INTERPRETATION: Our results suggest that IgM-bound gut microbiota may play an important role in the immuno-pathogenesis of obesity and type 2 diabetes, and provide a novel link between IgM in obesity and type 2 diabetes in both mice and humans. DATA AVAILABILITY: The 16s rRNA sequencing datasets supporting the current study have been deposited in the NCBI SRA public repository ( https://www.ncbi.nlm.nih.gov/sra ; accession no. SAMN18796639).

Alteration of the Intestinal Microbial Flora and the Serum IL-17 Level in Patients with Graves' Disease Complicated with Vitamin D Deficiency.

BACKGROUND: Intestinal flora is associated with Graves' disease (GD). This study explored the association of serum 25(OH)D with the diversity of the intestinal flora and serum IL-17 in GD patients. METHODS: Patients newly diagnosed with GD at 2 centers between 2018 and 2021 were consecutively included. According to their 25(OH)D levels, they were divided into the deficiency group, the insufficiency group, and the sufficiency group. Some patients with vitamin D deficiency or insufficiency were randomly selected and were matched with healthy volunteers (normal control [NC]) in terms of sex, age, and case number. The diversity and differential species of the intestinal flora and serum IL-17 levels were compared. RESULTS: Serum 25(OH)D negatively correlated with serum IL-17, the platelet/lymphocyte ratio, and TSH receptor antibody. The diversity of the intestinal flora decreased in the GD group, with noticeable differences in the composition of the intestinal flora when compared with the NC group. At the phylum level, the GD group exhibited a significantly lower abundance of Firmicutes but a higher abundance of Actinobacteria. At the genus level, the GD group exhibited higher relative abundances of Bifidobacterium, Collinsella, and Pediococcus but lower abundances of Roseburia and Dialister. CONCLUSIONS: The changes in the vitamin D level and the composition of the intestinal flora may partially contribute to the development of GD.

Monocyte to high-density lipoprotein cholesterol ratio as an independent risk factor for papillary thyroid carcinoma.

BACKGROUND: Papillary thyroid carcinoma (PTC) is considered to be an inflammatory disease. This study aimed to investigate the association of monocyte to high-density lipoprotein cholesterol ratio (MHR) with PTC. METHODS: Clinical parameters from 300 patients with PTC and 552 patients with benign thyroid nodule were compared. Serum renal function and liver enzymes, fasting plasma glucose, lipid profile, and blood cell count were measured. RESULTS: Patients with PTC had a higher MONO (p < 0.001) and MHR (p < 0.001). There was a step-wise increase in the prevalence of PTC (p = 0.003) with the tertile of MHR. Logistic regression analysis revealed that MHR could be considered an independent risk factor (p < 0.001) in the case-control study and the cohort study. Pearson correlation analysis and simple linear regression analysis indicated that MHR was positively associated with neutrophil (NEU) and lymphocyte (LYM) count as well as neutrophil-to-lymphocyte ratio (NLR). Area under the curve (AUC) was 0.711. The optimal cutoff of MHR was 0.33 × 109 /mmol. CONCLUSION: This study identifies novel evidence that patients with PTC have a higher MHR. MHR is an independent risk factor for PTC. These findings support the application of MHR to predict, diagnose, and evaluate the occurrence of PTC.

GESTATIONAL WEIGHT GAIN AS AN INDEPENDENT RISK FACTOR FOR MACROSOMIA IN WOMEN WITH INTERMEDIATE STATE GESTATIONAL BLOOD GLUCOSE.

Objective: Macrosomia is closely associated with gestational diabetes mellitus (GDM) but its relationship with maternal intermediate state gestational blood glucose (ISGBG; normal fasting blood glucose and 7.8 mmol/L <1 hour blood glucose [BG] <10 mmol/L or 6.7 mmol/L <2 hour BG <8.5 mmol/L) is unclear. Here, we analyzed the clinical characteristics and pregnancy outcomes and explored risk factors for macrosomia in women with ISGBG. Methods: A total of 847 women with normal glucose tolerance gestation, 330 with ISGBG, and 99 with GDM were included. Maternal and fetal clinical data were collected and 3-point BG following oral glucose tolerance test, fasting insulin, glycated hemoglobin, and blood lipids profile were measured. Results: The incidence rate of macrosomia among the neonates of women with ISGBG was as high as 10.9%. In the ISGBG group, prepregnancy body mass index (BMI), gestational weight gain (GWG) and the proportion of women with excessive GWG (eGWG) were significantly higher in women with macrosomia compared with those who delivered a normal weight neonate. In women with ISGBG, neonate weight was positively correlated with maternal prepregnancy weight (r = 0.183, P<.01), prepregnancy BMI (r = 0.135, P<.01), and GWG (r = 0.255, P<.01), and negatively correlated with high-density lipoprotein cholesterol (r = -0.172, P<.01). Nonetheless, only eGWG was an independent risk factor (odds ratio = 3.18, 95% confidence interval = 1.26 to 7.88, P<.05) for macrosomia. The risk of macrosomia in pregnant women with prepregnancy BMI <25 kg/m2 or BMI ≥25 kg/m2 and eGWG was 3.39 and 3.27 times, respectively. Conclusion: The incidence rate of macrosomia is increased in women with ISGBG and eGWG is the strongest independent risk factor. In order to reduce the risk for macrosomia, timely lifestyle intervention to promote appropriate weight gain during pregnancy deserves evaluation. Abbreviations: AUC = area under the curve; BG = blood glucose; 1 hour BG = 1 hour blood glucose after OGTT; 2 hour BG = 2 hour blood glucose after OGTT; BMI = body mass index; CI = confidence interval; eGWG = excessive gestational weight gain; FBG = fasting blood glucose; FINS = fasting insulin; GDM = gestational diabetes mellitus; HbA1c = glycated hemoglobin; HDL-C = high-density lipoprotein cholesterol; HOMA-IR = homeostasis model assessment of insulin resistance index; ISGBG = intermediate state gestation blood glucose; LDL-C = low-density lipoprotein cholesterol; Ln = natural logarithm; MLBW = mature low birth weight; NGTG = normal glucose tolerance gestation; OGTT = oral glucose tolerance test; OR = odds ratio; SD = standard deviation.

Evaluation of serum ferritin and thyroid function in the second trimester of pregnancy.

Ferritin is a universal intracellular protein that acts as an iron carrier. Several studies have indicated that iron deficiency affects thyroid function in non-pregnant women. Our objective was to assess the relationship between serum ferritin levels and thyroid function in pregnant women during the second trimester. Pregnant women with sufficient iodine intake and normal antithyroid antibodies during the second trimester were recruited from the obstetric outpatient department of the Fifth People's Hospital of Fudan University. Serum ferritin (SF) levels, thyroid function, anti-thyroid antibodies and vitamin B12 were determined by electrochemiluminescence immunoassay kit. Maternal serum iron (Fe), unsaturated iron binding capacity (UIBC), hemoglobin (Hb), creatinine (Cr), fasting blood glucose (FBG), and alanine aminotransferase (ALT) were also evaluated. Stepwise regressions performed to evaluate the associations between SF and other maternal parameters. In the second trimester, 11.4% pregnant women had a SF concentration less than 12 µg/L, and 7.6% pregnant women were anemic. SF levels were negatively correlated with serum TSH levels (r = -0.219, p < 0.05), and positively correlated with FT4 levels (r = 0.203, p < 0.05). Linear regression analysis showed only SF, age, week of gestation were significant predictors of regression with TSH as the dependent variable (ß: -0.007, -0.059, and 0.118 respectively; all p < 0.05). However consistent relation between the SF levels and FT4 was not observed in stepwise linear regression. Maternal iron status is a determinant of TSH concentrations during pregnancy in pregnant women during the second trimester.

NLRP3 deficiency protects from type 1 diabetes through the regulation of chemotaxis into the pancreatic islets.

Studies in animal models and human subjects have shown that both innate and adaptive immunity contribute to the pathogenesis of type 1 diabetes (T1D). Whereas the role of TLR signaling pathways in T1D has been extensively studied, the contribution of the nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing protein (NLRP) 3 inflammasome pathway remains to be explored. In this study, we report that NLRP3 plays an important role in the development of T1D in the nonobese diabetic (NOD) mouse model. NLRP3 deficiency not only affected T-cell activation and Th1 differentiation, but also modulated pathogenic T-cell migration to the pancreatic islet. The presence of NLRP3 is critical for the expression of the chemokine receptors CCR5 and CXCR3 on T cells. More importantly, NLRP3 ablation reduced the expression of chemokine genes CCL5 and CXCL10 on pancreatic islet cells in an IRF-1-dependent manner. Our results suggest that molecules involved in chemotaxis, accompanied by the activation of the NLRP3 inflammasome, may be effective targets for the treatment of T1D.

MicroRNA-181c inhibits cigarette smoke-induced chronic obstructive pulmonary disease by regulating CCN1 expression.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an obstinate pulmonary disease, causing irreversible alveoli collapse and increasing the risk for cardiovascular disease. Accumulating evidence has shown that the dysregulation of miRNAs is crucially involved in the pathogenesis and development of COPD. However, the effects and role of microRNA-181c (miR-181c) have not been investigated in a murine model of COPD. METHODS: miR-181c expression was detected in human lung tissue samples of 34 patients, an in vivo murine model of CS exposure, and primary human bronchial epithelial cells (HBECs) by qRT-PCR. Degeneration of lung tissue, necrosis, infiltration and neutrophil cells were assessed with H&E and flow cytometry. Interleukin (IL)-6 and IL-8 levels were determined by an enzyme-linked immunosorbent assay and qRT-PCR. Luciferase reporter assay and correlation analyses were used to confirm and measure the levels between miR-181c and its target CCN1. RESULTS: We showed that miR-181c was significantly down-regulated in lung tissues from patients with COPD compared to individuals who had never smoked (p < 0.01). We also observed a down-regulation of miR-181c in HBECs and a mouse model after cigarette smoke (CS) exposure. Functional assays demonstrated that miR-181c over-expression decreased the inflammatory response, neutrophil infiltration, reactive oxygen species (ROS) generation, and inflammatory cytokines induced by CS, while its down-regulation produced the opposite effects. Subsequent investigation found that CCN1 was a direct target of miR-181c. CCN1 expression was increased in lung tissues of COPD patients, and was negatively correlated with miR-181c expression in human COPD samples (p < 0.01). CONCLUSIONS: Taken together, our data suggest the critical roles of miR-181c and its target CCN1 in COPD development, and provide potential therapeutic targets for COPD treatment.

Ablation of Wntless in endosteal niches impairs lymphopoiesis rather than HSCs maintenance.

Osteoblasts and perivascular stromal cells constitute essential niches for HSC self-renewal and maintenance in the bone marrow. Wnt signaling is important to maintain HSC integrity. However, the paracrine role of Wnt proteins in osteoblasts-supported HSC maintenance and differentiation remains unclear. Here, we investigated hematopoiesis in mice with Wntless (Wls) deficiency in osteoblasts or Nestin-positive mesenchymal progenitor cells, which presumptively block Wnt secretion in osteoblasts. We detected defective B-cell lymphopoiesis and abnormal T-cell infiltration in the bone marrow of Wls mutant mice. Notably, no impact on HSC frequency and repopulation in the bone marrow was observed with the loss of osteoblastic Wls. Our findings revealed a supportive role of Wnts in osteoblasts-regulated B-cell lymphopoiesis. They also suggest a preferential niche role of osteoblastic Wnts for lymphoid cells rather than HSCs, providing new clues for the molecular nature of distinct niches occupied by different hematopoietic cells.

Dexamethasone-induced apoptosis of osteocytic and osteoblastic cells is mediated by TAK1 activation.

Increased apoptosis of osteoblasts and osteocytes is the main mechanism of glucocorticoid (GC)-induced osteonecrosis. In the current study, we investigated whether dexamethasone (Dex)-induced osteoblastic and osteocytic cell apoptosis is mediated through activation of transforming growth factor-ß (TGF-ß)-activated kinase 1 (TAK1), and whether TAK1 inhibition could promote survival opposing the deleterious effects of Dex. We found that TAK1 was activated by Dex in both osteocytic MLO-Y4 and osteoblastic OB-6 cells, which was prevented by two known anti-oxidants N-acetylcysteine (NAC) and ebselen. TAK1 inhibitors, including LYTAK1 and 5Z-7-oxozeaenol (57-OZ), inhibited Dex-induced apoptosis of MLO-Y4 and OB-6 cells. Meanwhile shRNA-mediated knockdown of TAK1 also suppressed Dex-induced damages to MLO-Y4 and OB-6 cells. On the other hand, exogenously over-expressing TAK1 enhanced Dex-induced MLO-Y4 and OB-6 cell apoptosis. At the molecular level, we found that TAK1 mediated Dex-induced pro-apoptotic Pyk2-JNK activation. Inhibition or silencing of TAK1 almost abolished Pyk2-JNK phosphorylations by Dex in MLO-Y4 and OB-6 cells. TAK1 over-expression, on the other hand, increased Dex's activity on Pyk2-JNK phosphorylations in above cells. We conclude that part of the pro-apoptotic actions of Dex on osteoblastic and osteocytic cells are mediated through TAK1 activation, and that inhibition of TAK1 might protect from GC-induced damages to osteoblasts and osteocytes.

Elevated plasma myoglobin level is closely associated with type 2 diabetic kidney disease.

BACKGROUND: Diabetic kidney disease (DKD) is the most frequent complication in patients with type 2 diabetes mellitus (T2DM). It causes a chronic and progressive decline in kidney function, and ultimately patients require renal replacement therapy. To date, an increasing number of clinical studies have been conducted to explore the potential and novel biomarkers, which can advance the diagnosis, estimate the prognosis, and optimize the therapeutic strategies at the early stage of DKD. In the current study, we sought to investigate the association of plasma myoglobin with DKD. METHODS: A total of 355 T2DM patients with DKD and 710 T2DM patients without DKD were enrolled in this study. Laboratory parameters including blood cell count, hemoglobin A1c, biochemical parameters, and plasma myoglobin were recorded. Patients were classified on admission according to the tertile of myoglobin and clinical parameters were compared between the groups. Pearson correlation analysis, linear regression, logistic regression, receiver operating characteristics (ROC) analysis, and spline regression were performed. RESULTS: Plasma myoglobin significantly increased in patients with DKD and was associated with renal function and inflammatory parameters. Plasma myoglobin was an independent risk factor for the development of DKD. The area under ROC curve of myoglobin was 0.831. Spline regression showed that there was a significant linear association between DKD incidence and a high level of plasma myoglobin when it exceeded 36.4 mg/mL. CONCLUSIONS: This study shows that elevated plasma myoglobin level is closely associated with the development of kidney injury in patients with T2DM.

Increased Circulating IL-32 Is Associated With Placenta Macrophage-derived IL-32 and Gestational Diabetes Mellitus.

OBJECTIVE: Placenta-derived inflammation plays a vital role in the pathophysiology of gestational diabetes mellitus (GDM). IL-32 is a novel pro-inflammatory cytokine and metabolic regulator involved in the development of metabolic disease. We investigated the effect of IL-32 in GDM. MATERIALS AND METHODS: First-trimester C-reactive protein (CRP) level was monitored in a case-control study of 186 women with GDM and 186 women without. Placental tissue was lysed and analyzed by high-resolution liquid chromatography-tandem mass spectrometry. Circulating level of inflammatory cytokines IL-32, IL-6, and TNF-α were measured by ELISA kits. The expression of placenta-derived macrophages, inflammatory cytokines, and related pathway proteins were assessed by reverse transcriptase-quantitative PCR, western blot, immunohistochemistry, or immunofluorescence. RESULTS: First-trimester CRP level in peripheral blood was closely associated with glucose and insulin resistance index and was an independent correlation with the development of GDM. High-resolution liquid chromatography-tandem mass spectrometry revealed that placenta-derived CRP expression was dramatically elevated in women with GDM. Interestingly, the expression of placenta-derived IL-32 was also increased and located in the macrophages of placental tissue. Meanwhile, the expression of IL-6, TNF-α, and p-p38 were up-regulated in the placental tissues with GDM. Either IL-6 or TNF-α was colocated with IL-32 in the placental tissue. Importantly, circulating IL-32 throughout pregnancy was increased in GDM and was related to placental-derived IL-32 expression, circulating IL-6, and TNF-α, glucose and insulin resistance index. CONCLUSION: Increased circulating IL-32 throughout pregnancy was closely associated with placenta macrophage-derived IL-32 expression and GDM. First trimester IL-32 level in peripheral blood may serve to predict the development of GDM.

Meta-analysis of the effect of KCNQ1 gene polymorphism on the risk of type 2 diabetes.

The potassium voltage-gated channel, KQT-like subfamily member 1 (KCNQ1) is a member of 11 mammalian Kv channel families that plays a key role for the repolarization of the cardiac action potential as well as water and salt transport. Genome-wide association studies have identified KCNQ1 as a type 2 diabetes (T2D) susceptibility gene in populations of Asian descent. After that, a number of studies reported that the rs2237892, rs2237895, rs2237897, rs2283228, and rs231362 polymorphism in KCNQ1 has been implicated in T2D risk. However, studies on the association between these polymorphism and T2D remain conflicting. To derive a more precise estimation of the relationship, a meta-analysis of 114,140 patients and 167,322 controls from 30 published case-control studies was performed. Overall, significantly elevated T2D risk was associated with rs2237892, rs2237895, rs2237897, rs2283228, and rs231362 risk allele when all studies were pooled into the meta-analysis. In the subgroup analysis by ethnicity, sample size, and Hardy-Weinberg equilibrium status of controls, significantly increased risks were found for these polymorphisms. In conclusion, this meta-analysis suggests that rs2237892, rs2237895, rs2237897, rs2283228, and rs231362 polymorphisms in KCNQ1 are associated with elevated T2D risk.

Comparison of newly diagnosed COPD patients and the non-COPD residents in Shanghai Minhang District.

Background: To compare whether the general population, especially those without characteristic symptoms, need spirometry screening for chronic obstructive pulmonary disease (COPD). Methods: Residents aged > 40 years old in Minhang, Shanghai, China, filled out screening questionnaires and underwent spirometry. The structured questionnaire integrating COPD population screening and COPD screening questionnaire was designed to obtain data on demographic characteristics, risk factors of COPD, respiratory symptoms, lifestyle habits, and comorbidities. We assessed the correlations between variables and COPD and the impact factors of FEV1% predicted. Results: A total of 1,147 residents were included with a newly diagnosed mild to moderate COPD prevalence of 9.4% (108/1,147); half of the patients (54/108) were asymptomatic. Multivariate analysis did not reveal any significant differences in symptoms or lifestyle factors between newly diagnosed COPD patients and non-COPD participants. However, according to the generalized linear model, older age (ß = -0.062, p < 0.001), male sex (ß = -0.031, p = 0.047), and respiratory symptoms (ß = -0.025, p = 0.013) were associated with more severe airflow limitation. Conclusion: Newly diagnosed COPD patients had few differences compared with the general population, which suggests that a targeted case finding strategy other than general screening was currently preferred. More attention should be paid to respiratory symptoms when making a diagnosis and exploring new therapies and interventions for COPD in the early stage.

Decreased Monocyte Count Is Associated With Gestational Diabetes Mellitus Development, Macrosomia, and Inflammation.

CONTEXT: The immune system plays a central role in the pathophysiology of gestational diabetes mellitus (GDM). Monocytes, the main innate immune cells, are especially important in the maintenance of a normal pregnancy. OBJECTIVE: Here, we investigated the potential effect of monocytes in GDM. METHODS: Monocyte count was monitored throughout pregnancy in 214 women with GDM and 926 women without in a case-control and cohort study. Circulating levels of inflammatory cytokines, placenta-derived macrophages, and their products were measured. RESULTS: Throughout pregnancy, monocyte count was significantly decreased in women with GDM, and was closely associated with glucose level, insulin resistance, and newborn weight. First-trimester monocyte count outperformed that of the second and third trimester as a risk factor and diagnostic predictor of GDM and macrosomia both in the case-control and cohort study. In addition, our cohort study showed that as first-trimester monocyte count decreased, GDM and macrosomia incidence, glucose level, and newborn weight increased in a stepwise manner. Risk of GDM started to decrease rapidly when first-trimester monocyte count exceeded 0.48 × 109/L. Notably, CD206 and interleukin 10 (IL-10) were significantly lower, whereas CD80, CD86, tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) were higher both in GDM placental tissue and peripheral blood. First-trimester monocyte count was positively related to IL-10 and CD206, but negatively related to CD80, CD86, TNF-α, and IL-6. CONCLUSION: Decreased monocyte count throughout pregnancy was closely associated with the development of GDM, macrosomia, and the chronic inflammatory state of GDM. First-trimester monocyte count has great potential as an early diagnostic marker of GDM.

Fibrinogen to Albumin Ratio as an Independent Risk Factor for Type 2 Diabetic Kidney Disease.

PURPOSE: Diabetic kidney disease (DKD) is an inflammatory disease. This study aimed to investigate the association of fibrinogen to albumin ratio (FAR) with DKD. PATIENTS AND METHODS: A total of 1022 type 2 diabetes mellitus (T2DM) patients with DKD and 1203 T2DM patients without DKD were enrolled in this study. Laboratory values including blood cell count, hemoglobin A1c, biochemical parameters, and fibrinogen and albumin creatinine ratio were recorded. Patients were classified according to tertile of admission FAR. Clinical parameters were compared between groups. Logistic regression, linear regression, ROC analysis and spline regression were carried out. RESULTS: FAR in the DKD group was significantly higher than that in the non-DKD group. FAR had the highest odds ratio as an independent risk factor for the development of DKD and the highest area under ROC curve for predicting DKD compared with albumin (ALB) or fibrinogen (FIB) alone. Simple linear regression analyses revealed a significant and linear correlation of FAR with neutrophil and neutrophil-to-lymphocyte ratio. FAR was an independent risk factor for development of DKD. Spline regression showed that there was a significant linear association between DKD incidence and continuous FAR value when it exceeded 67.3mg/g. CONCLUSION: FAR is a stronger independent predictor of DKD than FIB and ALB. FAR is an independent risk factor for DKD development when it exceeded 67.3mg/g. FAR might be one of novel diagnostic biomarkers to predict and prevent DKD progression. However, a prospective study to validate the prognostic model is still needed.

Serum ferritin as a risk factor for type 2 diabetes mellitus, regulated by liver transferrin receptor 2.

OBJECTIVE: The aim of this study was to evaluate the effect of TFR2 on iron storage in type 2 diabetes. METHODS: A cross-sectional study was conducted among 1938 participants from the Jiangchuan Community of Shanghai. A total of 784 participants with T2DM and 1154 normal participants (non-T2DM) were enrolled in this study. Serum ferritin, fasting blood glucose, postprandial blood glucose, and HbA1C (glycated hemoglobin A1c) levels were determined. Eighteen Wistar male rats were randomly assigned into three groups (n = 6/group): rats in a high-fat diet streptozotocin (HFD+STZ) group were fed with HFD for 4 weeks and intraperitoneally injected with streptozotocin (STZ); rats in a control group were fed with a standard diet for 4 weeks and intraperitoneally injected with buffer; rats in an STZ group were fed with a standard diet for 4 weeks and intraperitoneally injected with streptozotocin. Glucose tolerance test was performed at the end of the study. Blood samples and liver tissues were assessed for liver TFR2, blood glucose, serum ferritin, and iron levels. RESULTS: The mean serum ferritin level of T2DM participants was significantly higher than that of the control group (227 (140-352) vs 203.5 (130.5-312) ng/mL, P < 0.05). Serum ferritin level was an independent risk factor for T2DM (high ferritin group vs low ferritin group, 1.304 (1.03-1.651), P < 0.05). Diabetic rats showed reduced liver TFR2 levels, with increased serum ferritin levels. CONCLUSION: T2DM participants exhibited iron disorder with elevated serum ferritin levels. Elevated serum ferritin levels in diabetic rats were accompanied by reduced liver TFR2 levels.

Serum cystatin C is closely associated with euthyroid Hashimoto's thyroiditis in adult female Chinese patients.

OBJECTIVE: The aim of our study was to explore the association between serum cystatin C (CysC) and euthyroid Hashimoto's thyroiditis. METHODS: There were 119 female euthyroid Hashimoto's thyroiditis patients and 225 healthy controls who were recruited. Serum CysC, thyroid function, thyroid autoantibodies, fasting glucose, liver enzymes, and lipid profile were determined. Clinical parameters were compared between two groups. RESULTS: Serum CysC levels were significantly higher in euthyroid Hashimoto's thyroiditis patients compared with controls. In the lowest, middle, and highest tertile groups of CysC, the percentage of Hashimoto's thyroiditis was 15.9%, 34.2%, and 53.5%, respectively. The percentage of Hashimoto's thyroiditis was significantly higher in the highest tertile than in the lowest and middle tertiles. Spearman's correlation analysis showed that serum CysC levels were negatively correlated with free triiodothyronine (FT3), and positively correlated with serum thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb). Logistic regression analysis showed that serum CysC was independently related to the status of euthyroid Hashimoto's thyroiditis. CONCLUSIONS: The present study shows the first evidence suggesting that serum CysC levels are positively correlated with TPOAb and TGAb. Serum CysC might underlie the pathophysiologic features of euthyroid Hashimoto's thyroiditis.

Prealbumin to fibrinogen ratio is closely associated with diabetic peripheral neuropathy.

The aim of our study was to explore the diagnostic value of prealbumin to fibrinogen ratio (PFR) for predicting prognosis with the optimal cut-off value in diabetic peripheral neuropathy (DPN) patients. A total of 568 type 2 diabetes mellitus (T2DM) patients were enrolled in this study. The values including Toronto clinical neuropathy score (TCNS), nerve conduction velocity (NCV), vibration perception threshold (VPT), blood cells count, biochemical parameters, fibrinogen and PFR were recorded. The patients were divided into tertiles based on admission PFR value. First, clinical parameters were compared among the groups. Secondly, a logistic regression and ROC analysis were performed as the statistical model. The percentage of DPN, TCNS and VPT were significantly higher in the lowest PFR tertile than in the middle PFR tertile and the highest PFR tertile (P < 0.01-0.001). NCV was significantly lower in lowest PFR tertile than in the middle PFR tertile and the highest PFR tertile (P < 0.01-0.001). The Spearman correlation analysis showed that PFR was negatively correlated with TCNS and VPT (P < 0.001), while PFR was positively correlated with median motor NCV (P < 0.001), peroneal motor NCV (P < 0.001), median sensory NCV (P < 0.001), and peroneal sensory NCV (P < 0.001). After adjusting these potentially related factors, PFR was independently related to DPN (P = 0.007). The area under ROC curve was 0.627. This study finds the first evidence to suggest PFR may be the key component associated with DPN in T2DM, while PFR might underlie the pathophysiologic features of DPN.

Elevated First-Trimester Neutrophil Count Is Closely Associated With the Development of Maternal Gestational Diabetes Mellitus and Adverse Pregnancy Outcomes.

Chronic low-grade inflammation plays a central role in the pathophysiology of gestational diabetes mellitus (GDM). To investigate the ability of different inflammatory blood cell parameters in predicting the development of GDM and pregnancy outcomes, 258 women with GDM and 1,154 women without were included in this retrospective study. First-trimester neutrophil count outperformed white blood cell count and the neutrophil-to-lymphocyte ratio in the predictability for GDM. Subjects were grouped based on tertiles of neutrophil count during their first-trimester pregnancy. The results showed that as the neutrophil count increased, there was a stepwise increase in GDM incidence as well as in glucose and glycosylated hemoglobin levels, HOMA for insulin resistance (HOMA-IR), macrosomia incidence, and newborn weight. Neutrophil count was positively associated with prepregnancy BMI, HOMA-IR, and newborn weight. Additionally, neutrophil count was an independent risk factor for the development of GDM, regardless of the history of GDM. Spline regression showed that there was a significant linear association between GDM incidence and the continuous neutrophil count when it was >5.0 × 109/L. This work suggested that the first-trimester neutrophil count is closely associated with the development of GDM and adverse pregnancy outcomes.