T Cell Subsets are Associated with Clinical Activity and Efficacy of 4.5g Intravenous Glucocorticoid for Moderate-To-Severe Thyroid-Associated Ophthalmopathy.

BACKGROUND: Intravenous glucocorticoid (IVGC) remains the main treatment for moderate-to-severe and active thyroid-associated ophthalmopathy (TAO). However, a substantial number (20-30%) of active moderate-to-severe TAO patients may not respond to IVGC. Some patients may have disease progression despite IVGC treatment or relapse after steroid withdrawal. OBJECTIVES: To analyze risk factors for clinical activity and predictive factors for clinical outcomes of 4.5 g IVGC therapy in patients with moderate-to-severe TAO. DESIGN AND METHODS: Our study was performed in two steps: step 1 involved 110 moderate-to-severe TAO patients and analyzed risk factors for TAO activity; step 2 involved 53 active moderate-to-severe TAO patients from step 1 who were treated with 4.5 g IVGC therapy and analyzed predictive factors for clinical outcomes of IVGC therapy. Multivariate logistic regression analysis was used to identify the independent predictors and establish the predictive model. RESULTS: Abnormal TRAb (OR = 4.717; P = 0.019) and the percentage of CD3+CD4+ T cell (OR = 1.092; P = 0.028) were independently associated with the activity of moderate-to-severe TAO patients. The pretreatment CAS-max in both eyes (OR = 7.221; P = 0.013) and the percentage of pretreatment CD3+T cell (OR = 0.718; P = 0.037) were independently associated with therapeutic efficacy. The pretreatment CAS-max in both eyes (OR = 156.53; P = 0.028) and the percentage of post-treatment CD3+T cell (OR = 0.554; P = 0.043) were independently associated with therapeutic efficacy. Besides, multivariable prediction models were established, which were better in the forecasting aspect than single-variable prediction models. CONCLUSIONS: Based on the findings of this study, we should monitor the peripheral blood T cell subsets for TAO, which could be helpful to timely judge the condition of clinical manifestation and effect of treatment for TAO patients. Multivariable prediction models have been established, which have great significance for clinical work.

Positive association of glucagon with bone turnover markers in type 2 diabetes: A cross-sectional study.

AIMS: The osteo-metabolic changes in type 2 diabetes (T2D) patients are intricate and have not been fully revealed. It is not clear whether glucagon is entirely harmful in the pathogenesis of diabetes or a possible endocrine counter-regulation mechanism to reverse some abnormal bone metabolism. This study aimed to investigate the association between glucagon and bone turnover markers (BTMs) in T2D patients. METHODS: A total of 3984 T2D participants were involved in a cross-sectional study in Shanghai, China. Serum glucagon was measured to elucidate its associations with intact N-terminal propeptide of type I collagen (P1NP), osteocalcin (OC), and ß-C-terminal telopeptide (ß-CTX). Glucagon was detected with a radioimmunoassay. Propeptide of type I collagen, OC, and ß-CTX were detected using chemiluminescence. The diagnosis of T2D was based on American Diabetes Association criteria. RESULTS: The concentration of glucagon was positively correlated with two BTMs [OC-ß: 0.034, 95% CI: 0.004, 0.051, p = 0.024; CTX-ß: 0.035, 95% CI: 0.004, 0.062, p = 0.024]. The result of P1NP was [P1NP-regression coefficient (ß): 0.027, 95% CI: -0.003, 0.049, p = 0.083]. In the glucagon tertiles, P for trend of the BTMs is [P1NP: 0.031; OC: 0.038; CTX: 0.020], respectively. CONCLUSIONS: Glucagon had a positive effect on bone metabolism. The concentrations of the three BTMs increased as glucagon concentrations rose. This implied that glucagon might speed up skeletal remodelling, accelerate osteogenesis, and promote the formation of mature bone tissue. At the same time, the osteoclastic process was also accelerated, providing raw materials for osteogenesis to preserve the dynamic balance. In view of the successful use of single-molecule as well as dual/triple agonists, it would be feasible to develop a preparation that would reduce osteoporosis in diabetic patients.

Follicle-stimulating hormone is associated with non-alcoholic fatty liver disease in Chinese women over 55 years old.

BACKGROUND AND AIM: Obesity and diabetes are related to non-alcoholic fatty liver disease (NAFLD). A reduction in follicle-stimulating hormone (FSH) is associated with obesity and diabetes in postmenopausal women. Thus, we aim to investigate whether FSH is associated with NAFLD in women over 55 who were postmenopausal with a high probability. METHODS: Our data were obtained from the 2014 Survey on Prevalence in East China for Metabolic Diseases and Risk Factors. A total of 1635 women at the age of 55-89 years were selected. The degrees of fatty liver were categorized into mild and moderate-severe hepatic steatosis groups by ultrasonography. FSH and other sex hormones were measured by chemiluminescence. RESULTS: A total of 366 (22.4%) and 417 (25.5%) women had mild and moderate-severe hepatic steatosis, respectively. FSH was negatively correlated with waist circumference, homeostasis model assessment of insulin resistance (HOMA-IR), and other metabolic factors (all P < 0.05). After adjusting for age, estradiol, and total testosterone, increased quartiles of FSH were associated with significantly decreased odds ratios of mild and moderate-severe groups (both P for trends <0.05). After further adjustment for waist circumference and HOMA-IR, FSH was no longer associated with mild hepatic steatosis. The association of FSH with moderate-severe hepatic steatosis was attenuated by waist circumference and HOMA-IR but persisted in the fully adjusted model (P for trend <0.01). CONCLUSION: Follicle-stimulating hormone was negatively associated with NAFLD in women over 55 years old. Adiposity and insulin resistance explained most of the association of mild hepatic steatosis and partially explained the association of moderate-severe hepatic steatosis with FSH.

Effects of exenatide therapy on insulin resistance in the skeletal muscles of high-fat diet and low-dose streptozotocin-induced diabetic rats.

PURPOSE: The glucagon-like peptide (GLP)-1 agonist exenatide shows the same multiple effects on glucose homeostasis as native GLP-1, which can reduce blood glucose levels in individuals with type-2 diabetes mellitus (T2DM). However, its underlying action mechanism on glucose metabolism in the skeletal muscle of T2DM cases is unknown. We investigated the effects and action mechanisms of exenatide on insulin resistance (IR) in the skeletal muscle of high-fat diet and low-dose streptozotocin-induced T2DM rats. METHODS: Four groups of Sprague-Dawley rats were studied: non-T2DM (control, C); non-T2DM + exenatide (C + E); T2DM (D); and T2DM + exenatide (D + E). After eight weeks, isotope-tracer methodology was applied to measure the total rate of appearance (Ra) of glucose and glucose infusion rate (GIR) using a hyperinsulinemic-euglycemic clamp with 3-(3)H-glucose infusion. Glucose uptake in gastrocnemius muscles was determined by measuring 2-deoxy-D-(14)C-glucose radioactivity. Simultaneously, ultrastructural changes in the cells of gastrocnemius muscles were studied. RESULTS: In the D + E group, body weight and levels of fasting plasma glucose, triglyceride, total cholesterol, low-density lipoprotein and insulin were decreased significantly (p < 0.01) compared with the D group. The Ra of glucose (94.70 ± 13.46 versus 121.07 ± 16.55 µmol/kg/min) was decreased (p < 0.01), whereas the exogenous GIR (144.68 ± 11.03 versus 114.50 ± 9.40 µmol/kg/min) and glucose uptake in muscle (0.24 ± 0.02 versus 0.17 ± 0.02 µmol/g/min) were increased markedly (p < 0.01). Ultrastructural observations revealed that exenatide attenuated the effect of swollen mitochondrial and endoplasmic reticulum within the cells of the skeletal muscle of T2DM rats. CONCLUSIONS: These data suggest that exenatide can significantly improve insulin sensitivity in skeletal muscle by increasing glucose uptake in T2DM rats.

Obesity Patterns, Metabolic Abnormality, and Diabetic Kidney Disease in Patients with Type 2 Diabetes.

Objective: Obesity has been identified as a risk factor for chronic kidney disease. However, the impact of obesity, with or without a metabolically healthy condition, on diabetic kidney disease (DKD) remains unclear. We aimed to examine the associations of obesity patterns and metabolic abnormalities with the prevalence of DKD. Methods: This cross-sectional study included 4079 patients with type 2 diabetes from eleven communities in Shanghai, China. General obesity was assessed by body mass index (BMI) and abdominal obesity assessed by waist-to-hip ratio. Metabolic abnormalities were determined according to the Adult Treatment Panel III criteria. DKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m2 or urinary albumin-creatinine ratio ≥30 mg/g. Poisson regression model with inverse probability of treatment weighting was used to estimate prevalence ratios (PRs) and 95% CIs. Results: Higher BMI and WHR were each associated with a greater prevalence of DKD after mutual adjustment. When considered jointly, patients with both general obesity and abdominal obesity had the highest odds of DKD (PR 1.51, 95% CI 1.29-1.76). The associations of BMI and WHR with prevalent DKD were mainly observed in patients with use of antidiabetic drugs but not in those without drug use. Compared with normal-weight patients with 0-1 metabolic abnormality, patients who were overweight or obese with 0-1 metabolic abnormality showed increased odds of DKD. The PRs (95% CI) of DKD for patients with both overweight/obesity and abdominal obesity who had 0-1, 2, and 3 metabolic abnormalities were 1.59 (1.20-2.10), 1.68 (1.29-2.18), and 2.16 (1.67-2.78), respectively, relative to those with normal BMI and no abdominal obesity who had 0-1 metabolic abnormality. Conclusion: BMI and WHR were positively associated with DKD prevalence. Obesity composite and metabolic abnormalities had an additive effect on the odds of DKD. Further longitudinal studies are warranted to elucidate the role of obesity and metabolic abnormalities in the development of DKD.

Influence of 4-week or 12-week glucocorticoid treatment on metabolic changes in patients with active moderate-to-severe thyroid-associated ophthalmopathy.

Thyroid-associated ophthalmopathy (TAO) is a serious, progressive, vision-threatening and difficult-to-treat organ-specific autoimmune disease. The course, therapeutic effects and prognosis of moderate to severe TAO vary greatly. High-dose intravenous glucocorticoid (IVGC) therapy is considered a first-line treatment for active moderate-to-severe TAO, but there is still insufficient evidence regarding the treatment duration. Long-term IVGC therapy can influence the metabolism of glucose, lipids, and bone. This study was designed to compare changes in metabolic and immunological indexes as well as the magnetic resonance imaging apparent diffusion coefficient (ADC) of the extraocular muscles after 4 and 12 weeks of IVGC therapy. Forty-eight patients with active moderate-to-severe TAO were included in this retrospective cohort study. Metabolism and immunological indexes were measured before and after therapy. The ADC and clinical activity score (CAS) were used to evaluate the efficacy of treatment in these patients. We found that the patients in the 12-week group had increased fasting plasma glucose (p = 0.004), glycated hemoglobin (p = 0.028), total cholesterol (p < 0.001), and low-density lipoprotein (p < 0.001) after therapy. The patients in both groups had reduced bone metabolism markers after therapy. Thyroid peroxidase antibody and thyrotropin receptor antibody levels decreased after treatment in both groups (p < 0.001). A significant decrease in thyroglobulin antibody levels was found in the 4-week group (p = 0.006). The change in the ADC was higher in the 4-week group than in the 12-week group (p = 0.014). However, there were no significant differences in CAS values between the two groups. Therefore, 4-week IVGC therapy was recommended for patients with TAO with glucose and lipid disorders.

Comparison between acute kidney injury (AKI) and non-AKI patients secondary to severe hypothyroidism.

Hypothyroidism was a rare cause of rhabdomyolysis, which finally progressed to acute kidney injury (AKI). We compared nine patients with AKI secondary to hypothyroidism and six patients with severe hypothyroidism. Besides creatine kinase, globulin could be an alternative biomarker of rhabdomyolysis related to hypothyroidism.

The GLP-1 analogue exenatide improves hepatic and muscle insulin sensitivity in diabetic rats: tracer studies in the basal state and during hyperinsulinemic-euglycemic clamp.

OBJECTIVE: Glucagon-like peptide-1 (GLP-1) analogues (e.g., exenatide) increase insulin secretion in diabetes but less is known about their effects on glucose production or insulin-stimulated glucose uptake in peripheral tissues. METHODS: Four groups of Sprague-Dawley rats were studied: nondiabetic (control, C); nondiabetic + exenatide (C + E); diabetic (D); diabetic + exenatide (D + E) with diabetes induced by streptozotocin and high fat diet. Infusion of 3-(3)H-glucose and U-(13)C-glycerol was used to measure basal rates of appearance (Ra) of glucose and glycerol and gluconeogenesis from glycerol (GNG). During hyperinsulinemic-euglycemic clamp, glucose uptake into gastrocnemius muscles was measured with 2-deoxy-D-(14)C-glucose. RESULTS: In the diabetic rats, exenatide reduced the basal Ra of glucose (P < 0.01) and glycerol (P < 0.01) and GNG (P < 0.001). During the clamp, Ra of glucose was also reduced, whereas the rate of disappearance of glucose increased and there was increased glucose uptake into muscle (P < 0.01) during the clamp. In the nondiabetic rats, exenatide had no effect. CONCLUSION: In addition to its known effects on insulin secretion, administration of the GLP-1 analogue, exenatide, is associated with increased inhibition of gluconeogenesis and improved glucose uptake into muscle in diabetic rats, implying improved hepatic and peripheral insulin sensitivity.

[Integrative study of Guangdong ecological-economic system based on emergy analysis].

Based on the theories and methodologies of emergy, a quantitative analysis on the development sustainability of Guangdong Province in 1990-2003 was made from the aspects of environment, society, and economy at system and subsystem levels. The results showed that Guangdong Province was of developed provinces in China, and highly depended on the input of feedback emergy. Though the pollution control was fruitful, the increasing environmental loading was still not relieved on the whole, and the development sustainability was relatively low. This Province was increasingly relied on international market, and actually, under the status to the bad in exporting primary products and importing high-tech products. To improve the development sustainability of this Province, more concerns should be paid on improving the added values of products, making full use of the natural and labor resources in its underdeveloped area, and further bringing the economic superiority of its developed area into play.