Serum IL-17A concentration and a IL17RA single nucleotide polymorphism contribute to the risk of autoimmune type 1 diabetes.

AIMS: Interleukin (IL)-17 is associated with autoimmunity. This study aimed to affirm the role of IL-17A, IL-17F and single nucleotide polymorphisms (SNPs) in genes related to them and their receptors in autoimmune type 1 diabetes (T1D) for Chinese population. METHODS: In this study, 130 patients with autoimmune T1D and 140 non-T1D controls were included for analysis. Clinical and biochemical data were collected, and serum levels of IL-17A, IL-17F, IL-6, and high-sensitivity C reactive protein were measured using ELISA. The SNPs rs2275913, rs8193036, rs3819025, rs763780, rs879577, rs4819554, and rs708567 were genotyped using the SNaPshot assay. RESULTS: IL-17A levels were higher in patients with autoimmune T1D than in controls (median [IQR] 28.83[37.38] vs. 16.68[8.10], p < 0.001) and high IL-17A was a risk factor for autoimmune T1D (odds ratio (OR), 1.013; 95% CI, 1.003-1.023; p = 0.013) after adjusting for confounding factors. Linear regression analysis revealed that log10 IL-17A levels were independently associated with fasting C-peptide, IL-6, body mass index, and IL-17F. However, no independent association was found between IL-17F and autoimmune T1D. The GG genotype of SNP rs4819554 in the interleukin 17 receptor A (IL17RA) gene was associated with a decreased risk of autoimmune T1D (OR, 0.458; 95% CI, 0.246-0.852; p = 0.014) after adjusting for other confounders. The IL17RA rs4819554 GG genotype was negatively correlated with serum glutamic acid decarboxylase antibody appearance (p < 0.05). CONCLUSIONS: Increased serum IL-17A, but not IL-17F, is a risk factor for autoimmune T1D. The GG genotype of IL17RA rs4819554 might decrease the risk for autoimmune T1D.

A total weight loss of 25% shows better predictivity in evaluating the efficiency of bariatric surgery.

OBJECTIVES: The need for a unified definition of weight loss (WL) after bariatric surgery has recently been highlighted. We aimed to evaluate the reliability of two clinically common WL indications including percentage of total WL (%TWL) and percentage of excess WL (%EWL) through comparing their performances in predicting metabolic syndrome (MetS) remission 1 year after bariatric surgery. METHODS: A total of 430 individuals with obesity who underwent bariatric surgery were enrolled. Participants were evaluated for changes in anthropometric parameters, metabolic indexes, MetS components and medications before and 1 year after surgery. MetS was defined using the criteria of the National Cholesterol Education Program Adult Treatment Panel III criteria for Asian-Americans. RESULTS: The prevalence of MetS is 92.3% (397) at baseline. One year after bariatric surgery, 337 individuals (84.9%) were in MetS remission. The multivariate adjusted ORs were 1.16 (95% confidence interval [CI] 1.10-1.22) for each 1% increase in %TWL for MetS remission and 1.18 (95% CI 1.11-1.25) for each 5% increase in %EWL. This association with MetS remission remained statistically significant for %TWL after additional adjustment for %EWL (P for trend 0.029), and disappeared for %EWL. Receiver operating curve (ROC) analyses showed that the %TWL was more predictive than the %EWL (AUC%TWL vs. AUC%EWL, 0.749 vs. 0.700, p = 0.023). The Youden index indicated that the optimal %TWL cutoff point to identify MetS remission was 25%. CONCLUSIONS: We recommend that good responders to bariatric surgery should be defined as those exhibiting %TWL ≥ 25%.

Comparison of Four Risk Prediction Models for Diabetes Remission after Roux-en-Y Gastric Bypass Surgery in Obese Chinese Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) is a major type of bariatric surgery. Various models have been established for facilitating clinical decision-making and predicting outcomes after RYGB; the ABCD, DiaRem, advanced-DiaRem (Ad-DiaRem), and DiaBetter scores are among the most commonly used risk prediction models. However, these models were primarily developed based on retrospective analyses of patients from Western countries at 1 year after RYGB. The present study was to assess the performance of these models and identify the optimal model, for predicting postoperative diabetes remission in diabetic Chinese patients. METHODS: The present study included a total of 253 RYGB patients; 214 completed a 1-year follow-up and 131 completed a 3-year follow-up. The assessments and comparisons of the predictive performance of the four models were based on both discrimination and calibration measures. Discrimination was assessed according to the area under the receiver operating characteristic curve (AUC), and calibration was evaluated by Hosmer-Lemeshow goodness-of-fit tests and predicted-to-observed ratios. RESULTS: One hundred thirteen (52.8%) in the 1-year follow-up group and 59 (45.0%) in the 3-year follow-up group achieved complete diabetes remission. Although all models showed similar discriminatory capacity and good calibration, the DiaBetter model exhibited the best predictive performance (1-year follow-up, AUC 0.760, 95% confidence interval [CI] 0.697-0.815, predicted-to-observed ratio 1.04; 3-year follow-up, AUC 0.804, 95% CI 0.726-0.868, predicted-to-observed ratio 0.95). CONCLUSIONS: The present results indicated that the DiaBetter model is the optimal model for predicting postoperative diabetes remission in diabetic Chinese individuals, due to its excellent predictive accuracy and ready availability for use in clinical practice.

Decreased Leptin Is Associated with Alterations in Thyroid-Stimulating Hormone Levels after Roux-en-Y Gastric Bypass Surgery in Obese Euthyroid Patients with Type 2 Diabetes.

BACKGROUND: Leptin has been shown to stimulate the hypothalamus-pituitary-thyroid (HPT) axis in vivo and vitro. Its role in thyroid axis regulation after weight loss induced by bariatric surgery is still unknown. The aim of this study was to evaluate the influence of leptin on weight loss and thyroid function variation induced by Roux-en-Y gastric bypass (RYGB) surgery in euthyroid individuals with obesity and type 2 diabetes mellitus (T2DM). METHODS: 65 Chinese individuals with obesity and T2DM who underwent RYGB, and 27 healthy volunteers were enrolled in this retrospective study. Participants were evaluated for changes in anthropometric parameters, metabolic indexes, thyroid function, and leptin levels before and 12 months after surgery. RESULTS: After RYGB, all of these patients experienced significant weight reduction and improved glucose control. Metabolic parameters were significantly ameliorated after surgery compared with baseline. Thyroid hormones including free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) declined in parallel. Median (IQR) plasma leptin levels decreased from 33.7 ng/mL (17.9-63.1) to 10.3 ng/mL (4.0-18.5). Pearson correlation analysis showed that TSH was significantly positively correlated with body mass index, C-reactive protein (CRP), and leptin. Multiple stepwise linear regression indicated that leptin and CRP were independent factors affecting TSH. The ß coefficients were 0.38 (p = 0.001) and 0.32 (p = 0.004), respectively. There was a significant positive correlation between ΔTSH and Δleptin (r = 0.33, p = 0.01). CONCLUSION: Decreased or normalized TSH levels after weight loss induced by RYGB might be mediated by the decline in leptin. There could be cross talk between adipose tissue and the HPT axis.

Development of Multimarker Diagnostic Models from Metabolomics Analysis for Gestational Diabetes Mellitus (GDM).

Although metabolomics are desirable to understand the pathophysiology of gestational diabetes mellitus (GDM), comprehensive metabolomic studies of GDM are rare. We aimed to offer a holistic view of metabolites alteration in GDM patients and investigate the possible multimarker models for GDM diagnosis. Biochemical parameters and perinatal data of 131 GDM cases and 138 controls were collected. Fasting serum samples at 75 g oral glucose tolerance test were used for metabolites by ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry, ultra performance liquid chromatography-triple triple-quadrupole-mass spectrometry and gas chromatography- time-of- flight mass spectrometry platforms. Significant changes were observed in free fatty acids, bile acids, branched chain amino acids, organic acids, lipids and organooxygen compounds between two groups. In receiver operating characteristic (ROC) analysis, different combinations of candidate biomarkers and metabolites in multimarker models achieved satisfactory discriminative abilities for GDM, with the values of area under the curve (AUC) ranging from 0.721 to 0.751. Model consisting of body mass index (BMI), retinol binding protein 4 (RBP4), n-acetylaspartic acid and C16:1 (cis-7) manifested the best discrimination [AUC 0.751 (95% CI: 0.693-0.809), p < 0.001], followed by model consisting of BMI, Cystatin C, acetylaspartic acid and 6,7-diketoLCA [AUC 0.749 (95% CI: 0.691-0.808), p < 0.001]. Metabolites alteration reflected disorders of glucose metabolism, lipid metabolism, amino acid metabolism, bile acid metabolism as well as intestinal flora metabolism in GDM state. Multivariate models combining clinical markers and metabolites have the potential to differentiate GDM subjects from healthy controls.

5-ALA ameliorates hepatic steatosis through AMPK signaling pathway.

5-Aminolevulinic acid (5-ALA), the first compound in the porphyrin synthesis pathway, has been reported to ameliorate the diabetic state in Otsuka Long-Evans Tokushima Fatty rats by reducing fat pad weight in the retroperitoneal region. Dietary supplementation with 5-ALA has additionally demonstrated the capacity to lower blood glucose and HbA1c levels among subjects with diabetes. The etiology of nonalcoholic fatty liver disease (NAFLD) is complex and its typical characteristics include obesity and insulin resistance. As 5-ALA supplementation has previously normalized glucose and insulin resistance, we sought to investigate whether 5-ALA had potential therapeutic effects on NAFLD and elucidate the signal pathway mediating these effects. To explore these questions, we fed C57BL/6J mice a high-fat diet (HFD) to induce a fatty liver disease and supplemented the diet-induced obese (DIO) mice with 5-ALA. The mice in the presence of 5-ALA demonstrated a decrease in body weight and hepatic lipid content and moderate improvement in glucose homeostasis compared to untreated controls. Further, we found that 5-ALA activated AMPK signaling pathway, which was correlated with enhanced lipolysis and fatty acid ß-oxidation. Human hepatocarcinoma cells (HepG2 cells) treated with 5-ALA were additionally used to investigate the mechanics of 5-ALA. Treated cells had a higher expression of lipolysis-related genes, including PGC-1α. Our data indicated that 5-ALA might represent a novel compound that could be useful for the treatment of nonalcoholic fatty liver disease (NAFLD), likely through the restoration of phosphorylation levels of AMPK (Thr172) and acetyl-CoA (ACC) (Ser79), further enhanced PGC1α and CPT1α expression.

Relationship between High Serum Cystatin C Levels and the Risk of Gestational Diabetes Mellitus.

AIMS: Serum cystatin C (CysC) has recently been shown to be associated with the incidence of type 2 diabetes mellitus (T2DM) and progression to the pre-diabetic state. The aim of this study was to explore the relationship between serum CysC and the risk of gestational diabetes mellitus (GDM) in Chinese pregnant women. METHODS: This cross-sectional study consisted of 400 pregnant women including 111 with GDM and 289 with normal glucose tolerance at 24-28 weeks of gestation. The subjects were further divided into four groups according to the CysC quartiles, and their clinical characteristics were compared. The serum CysC concentration was measured using immunoturbidimetry and the degree of insulin resistance was assessed by the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Serum CysC levels were significantly higher in pregnant women with GDM than in the healthy pregnant women[1.0(0.8-1.8) vs 0.7(0.6-1.0), P<0.01). The Spearman's correlation analysis showed that serum CysC was positively associated with HOMA-IR(r = 0.118, P<0.05) and the occurrence of GDM(r = 0.348, P<0.01). The pregnant women were divided into quartiles according to their serum CysC concentrations. Compared to the first quartile, pregnant women in Q2 (OR, 2.441; P = 0.025), Q3 (OR, 3.383; P = 0.001) and Q4 (OR, 5.516; P<0.001) had higher risk of GDM after adjusted for age, BMI, HbA1c and HOMA-IR. Further, with a rise in the serum CysC, there was an increasing trend in the HOMA-IR levels (P<0.05). A binary logistic regression analysis after adjusting for other confounding variables revealed a significant and independent association between serum CysC and GDM [OR = 14.269; 95% confidence interval, 4.977-40.908, P<0.01].The receiver operating characteristic curve analysis revealed that the optimal cutoff point for serum CysC to indicate GDM was 0.95 mg/L. CONCLUSIONS: Serum CysC is significantly and independently associated with insulin resistance and GDM. It may be a helpful biomarker to identify the risk of GDM in Chinese pregnant women.

The key role of 99mTc-MIBI SPECT/CT in the diagnosis of parathyroid adenoma: a case report.

The concomitant occurrence of primary hyperparathyroidism (PHPT) due to parathyroid adenoma and papillary thyroid carcinoma (PTC) is not common. The co-occurrence of parathyroid tumors and thyroid diseases can lead to misdiagnosis owing to mutual interference of imaging in the early period of disease. The most commonly used imaging techniques for the preoperative localization of parathyroid and thyroid adenomas are technetium-99m sestamibi (99mTc-MIBI) scintigraphy and ultrasonography of the neck. Recently, 99mTc-MIBI single-photon emission computed tomography associated with computed tomography scintigraphy (SPECT/CT) has been used to detect PHPT, and its diagnostic value is being evaluated. Herein, we report a patient with an unusual co-occurrence of parathyroid adenoma and multiple thyroid diseases, including papillary thyroid carcinoma, thyroid adenoma and lymphocytic thyroiditis, which were localized with 99mTc-MIBI SPECT/CT and confirmed surgically. We suggest that 99mTc-MIBI SPECT/CT can play an important role in the diagnosis of parathyroid and thyroid lesions.

The key role of 99mTc-MIBI SPECT/CT in the diagnosis of parathyroid adenoma: a case report

The concomitant occurrence of primary hyperparathyroidism (PHPT) due to parathyroid adenoma and papillary thyroid carcinoma (PTC) is not common. The co-occurrence of parathyroid tumors and thyroid diseases can lead to misdiagnosis owing to mutual interference of imaging in the early period of disease. The most commonly used imaging techniques for the preoperative localization of parathyroid and thyroid adenomas are technetium-99m sestamibi (99mTc-MIBI) scintigraphy and ultrasonography of the neck. Recently, 99mTc-MIBI single-photon emission computed tomography associated with computed tomography scintigraphy (SPECT/CT) has been used to detect PHPT, and its diagnostic value is being evaluated. Herein, we report a patient with an unusual co-occurrence of parathyroid adenoma and multiple thyroid diseases, including papillary thyroid carcinoma, thyroid adenoma and lymphocytic thyroiditis, which were localized with 99mTc-MIBI SPECT/CT and confirmed surgically. We suggest that 99mTc-MIBI SPECT/CT can play an important role in the diagnosis of parathyroid and thyroid lesions. Arch Endocrinol Metab. 2015;59(3):265-9.

Hashimoto's thyroiditis concomitant with sequential autoimmune hepatitis, chorea and polyserositis: a new entity of autoimmune polyendocrine syndrome?

We herein report a case of Hashimoto's thyroiditis (HT) with sequential autoimmune hepatitis (AIH), chorea and polyserositis. The patient was a 24-year-old man who underwent subtotal thyroidectomy due to compression symptoms caused by goiter and was diagnosed with HT postoperatively based on pathological examinations two years previously. He had exhibited liver dysfunction and intermittent chorea since 2008. His liver function and polyserositis improved remarkably following the administration of ursodeoxycholic acid (UDCA) and methylprednisolone. This is a very rare case that can be classified as autoimmune polyglandular syndrome (APS) type 3. Early and adequate UDCA and glucocorticoid treatment may lead to a favorable prognosis.

Use of glycated albumin to distinguish occult diabetes mellitus from stress-induced hyperglycemia in Chinese orthopedic trauma patients.

BACKGROUND: Some nondiabetic trauma patients with hyperglycemia have been found to have occult diabetes mellitus (ODM). We studied whether glycated albumin (GA) was an effective tool for detecting ODM in orthopedic trauma patients with elevated glucose levels. METHODS: A cross-sectional, sequential case series study of adult patients presenting to the Orthopedic Trauma Center between September 2009 and March 2010 with new limb fractures was performed. Hemoglobin A1c (HbA1c) and GA levels were measured in hyperglycemic patients with no prior diabetes mellitus. A receiver operating characteristic curve was plotted to examine the sensitivity, specificity, and positive and negative predictive values of GA in identifying occult diabetes in hospitalized patients with acute hyperglycemia. RESULTS: A total of 2,058 trauma patients were screened and 399 patients (19.4%) with no known diabetes mellitus were noted to be hyperglycemic. Of these 399 patients, 38.3% (n = 153) had ODM according to the HbA1c diagnosis cutoff point. GA level was strongly correlated with HbA1c using Pearson's correlation analysis (r = 0.887, p < 0.01). Using logistic regression analysis, GA (odds ratio [OR] = 1.60, p < 0.001) and fasting plasma glucose (OR = 1.974, p < 0.001) were identified as significant risk factors for the diagnosis of ODM. Receiver operating characteristic curve analysis showed that a GA value of 17.5% gave an optimal sensitivity of 73.20% and specificity of 99.12% for distinguishing ODM from stress-induced hyperglycemia. CONCLUSION: Almost 40% of nondiabetic orthopedic trauma patients presenting with hyperglycemia were found to have ODM. A GA value of 17.5%, the optimal cutoff point, could distinguish between ODM and stress-induced hyperglycemia in Chinese orthopedic trauma subjects. LEVEL OF EVIDENCE: II, diagnostic study.

[Relation between the level of serum CA19-9 and glucose control in inpatients with diabetes].

OBJECTIVE: To investigate the effect of hemoglobin A1c (HbA1c) and glycated albumin (GA) on serum CA199 in diabetic patients. METHODS: 29 NGT matched control subjects and 371 hospitalized diabetic patients were enrolled. Diabetic patients were divided into satisfactory group (< 6.5%), general group (6.5%-7.5%) and dissatisfactory group (> 7.5%) by the level of HbA1c. The levels of serum CA199 among three groups were compared. The relationship between HbA1c and CA199, GA and CA199 was analysed. Multiple stepwise regression analysis was performed to compare the effect of different variables on CA199 as the independent variables were sex, age, duration, TC, TG, HDL, LDL, FBG, PBG, HbA1c and GA. RESULTS: (1) CA199 level of the group of HbA1c above 7.5% was significantly higher than the group of HbA1c between 6.5% and 7.5% and the group of HbA1c less than 6.5%. (2) The coefficient of correlation between HbA1c and CA199 was 0.394 (P = 0.000), and that was 0.381 between GA and CA199 (P = 0.000). (3) Multiple stepwise regression analysis show standard regression coefficient of HbA1c is 0.364 (P = 0.000). CONCLUSION: (1) CA199 level of diabetic patient in poor glucose control was significantly higher than the patient in good control. (2) CA199 was positively correlated with FBG, PBG, HbA1c and GA. (3) HbA1c is the independent risk factor of CA199. The elevated CA199 in diabetic patient has close relationship with poor glucose control in a long period.

The metabolic syndrome increased risk of cardiovascular events in Chinese--a community based study.

BACKGROUND: Whether metabolic syndrome (MetS) could serve as a valid indicator for cardiovascular disease (CVD) is in controversy. The aim of the study was to prospectively evaluate the predictive value of the MetS for CVD events in Chinese population by different MetS definitions. METHODS: This was a community-based cohort study. MetS was defined according to the World Health Organization (WHO), the International Diabetes Federation (IDF), the National Cholesterol Education Program Adult Treatment Panel III (NCEPIII) and Joint Committee for Developing Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults (JCDCG), respectively. 2788 subjects were included. The incidence of CVD events was monitored during a 5.5-year period. RESULTS: The proportion of MetS defined by the WHO, IDF, NCEPIII and JCDCG criteria was 25.9%, 15.4%, 22.0% and 26.1%, respectively in men, and 24.5%, 28.0%, 31.1% and 23.0%, respectively in women. After adjusting for age, all four definitions were associated with increased risk of CVD events in women, but not in men. The corresponding hazard ratios (HRs) [95% confidence intervals (CIs)] in women were 2.13 (1.44-3.16), 1.49 (1.01-2.19), 1.50 (1.02-2.21) and 2.10 (1.41-3.11). The HRs remained significant with WHO and JCDCG definitions, not with the IDF and NCEPIII definitions, when factors of LDL cholesterol, and smoking were adjusted. CONCLUSION: The MetS by the WHO and JCDCG definition was associated with increased risk of CVD events in Chinese women after adjustment for age, total cholesterol, LDL cholesterol, and smoking.

Serum C-reactive protein and risk of cardiovascular events in middle-aged and older chinese population.

The purpose of the present study was to investigate the effect of high-sensitivity C-reactive protein (hs-CRP) on the risk of cardiovascular disease (CVD) in a Chinese population. A total of 2,656 participants (aged 30 to 95 years) with baseline hs-CRP levels available were monitored for the incidence of a composite of CVD events (stroke and coronary heart disease) during a 5.5-year period. With increasing quartiles of hs-CRP (<0.47, 0.47 to 0.97, 0.97 to 2.09, and >or=2.09 mg/L), the incidence of CVD increased progressively (11.7, 16.4, 24.7, and 36.5 per 1,000 person-years, respectively). In a Cox model adjusted for other traditional risk factors (e.g., age, blood pressure, diabetes mellitus, lipids, body mass index, smoking status), elevated hs-CRP (>or=2.0 mg/L) independently predicted the risk of CVD (hazard ratio 1.39; 95% confidence interval 1.04 to 1.87). The effect was especially significant for stroke (hazard ratio 1.58; confidence interval 1.08 to 2.31). In conclusion, the results of our study suggest that elevated hs-CRP (>or=2.0 mg/L) is an effective predictor of CVD in a Chinese population.