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.

The key role of a glucagon-like peptide-1 receptor agonist in body fat redistribution.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are an ideal therapy for type 2 diabetes and, as of recently, for obesity. In contrast to visceral fat, subcutaneous fat appears to be protective against metabolic diseases. Here, we aimed to explore whether liraglutide, a GLP-1RA, could redistribute body fat via regulating lipid metabolism in different fat depots. After being fed a high-fat diet for 8 weeks, 50 male Wistar and Goto-Kakizaki rats were randomly divided into a normal control group, a diabetic control group, low- and high-dose liraglutide-treated groups and a diet-control group. Different doses of liraglutide (400 µg/kg/day or 1200 µg/kg/day) or an equal volume of normal saline were administered to the rats subcutaneously once a day for 12 weeks. Body composition and body fat deposition were measured by dual-energy X-ray absorptiometry and MRI. Isotope tracers were infused to explore lipid metabolism in different fat depots. Quantitative real-time PCR and Western blot analyses were conducted to evaluate the expression of adipose-related genes. The results showed that liraglutide decreased visceral fat and relatively increased subcutaneous fat. Lipogenesis was reduced in visceral white adipose tissue (WAT) but was elevated in subcutaneous WAT. Lipolysis was also attenuated, and fatty acid oxidation was enhanced. The mRNA expression levels of adipose-related genes in different tissues displayed similar trends after liraglutide treatment. In addition, the expression of browning-related genes was upregulated in subcutaneous WAT. Taken together, the results suggested that liraglutide potentially redistributes body fat and promotes browning remodeling in subcutaneous WAT to improve metabolic disorders.

Changes of immunoglobulins and CD series in patients with Graves' orbitopathy treated with high-dose methylprednisolone / 中华内分泌代谢杂志

Objective To study the effect of high-dose methylprednisolone intravenous pulse therapy on immunoglobulins and CD series in patients with active moderate-to-severe Graves' orbitopathy. Methods Twenty-seven patients with active moderate-to-severe Graves' orbitopathy were enrolled in this study. All the patients received iv methylprednisolone pulse therapy for 12 weeks according to the 2016 European Thyroid Association/European Group on Graves'Orbitopathy(EUGOGO) Guidelines. Serum thyroidal autoantibodies, such as thyroid-stimulating hormone receptor antibody ( TRAb) , anti-thyroperoxidase antibody ( TPOAb) , and serum immunoglobulins, such as IgG, IgE, IgA, IgM were evaluated at the baseline, at the end of 4th and 12th week. Percentages of CD3+ T cells, CD4+ T cells, CD8+T cells and CD19+ B cells, CD16+ or CD56+ NK cells were also evaluated at each time point. Results TRAb, TPOA and IgE, IgG, IgA were significantly decreased both after 4th week and after 12th week (all P<0.05). Percentages of CD3+ T cells, CD4+ T cells and CD4+/CD8+ ratio were gradually decreased after treatment. However, change of CD8+T cells was not significant (P>0.05). Conclusion High-dose methylprednisolone may exert an immunosuppressive effect not only by modifying humoral and cellular immune functions, but also by decreasing serum immunoglobulins.

The use of antidiabetic medications in community-dwelling diabetic patients in Shanghai in 2018 / 中华内分泌代谢杂志

Objective@#To investigate the use of diabetes medications and their effects on the community diabetic patients in Shanghai, China, and provide the evidence for the use of antidiabetic drugs in diabetic patients in the region.@*Methods@#The data were from a database of a 2018 Survey on Community Diabetes Mellitus in Shanghai, China. There were 4 612 subjects included in this cross-sectional study in 2018. According to the use of antidiabetic drugs, the population was divided into untreated group, single drug group, double drugs combination group and multi-drugs combination group, to compare the fasting blood glucose, glycosylated hemoglobin, BMI and prevalence of diabetic complications in different groups.@*Results@#About 70.9% of the 4 612 patients used hypoglycemic agents, 34.8% used metformin, 35.1% used sulfonylureas, 22.9% used alpha glycosidase inhibitors, and 13.8% used insulin. The prevalence of diabetic nephropathy, retinopathy, neuropathy, stroke, and diabetic foot was higher in the combination than in the untreated and single-drug users (P<0.01). Only 41.3% subjects had HbA1C<7%. The fasting blood glucose and HbA1C values were lower in the untreated group than in other three medication groups, and the rate of the HbA1C reaching target in the untreated group was higher than the other medication groups (P<0.01). As the types of drug increased, HbA1C was less likely to reach the target (P<0.01). There were 42.2% of patients with BMI<24 kg/m2, and there was no significant difference in the proportion of BMI reaching target among the four groups (P>0.05).@*Conclusion@#The most common used antidiabetic drugs in diabetic patients in Shanghai are metformin, sulfonylureas, α-glycosides inbibitor, and insulin. The blood glucose control in diabetic patients in Shanghai community is not good enough. Patients with a longer duration of diabetes, a lower rate of HbA1C at goal, and a higher prevalence of diabetic complications may be more prone to use multiple hypoglycemic drugs.

Changes of immunoglobulins and CD series in patients with Graves′ orbitopathy treated with high-dose methylprednisolone / 中华内分泌代谢杂志

Objective@#To study the effect of high-dose methylprednisolone intravenous pulse therapy on immunoglobulins and CD series in patients with active moderate-to-severe Graves′ orbitopathy.@*Methods@#Twenty-seven patients with active moderate-to-severe Graves′ orbitopathy were enrolled in this study. All the patients received iv methylprednisolone pulse therapy for 12 weeks according to the 2016 European Thyroid Association/European Group on Graves′Orbitopathy(EUGOGO) Guidelines. Serum thyroidal autoantibodies, such as thyroid-stimulating hormone receptor antibody (TRAb), anti-thyroperoxidase antibody (TPOAb), and serum immunoglobulins, such as IgG, IgE, IgA, IgM were evaluated at the baseline, at the end of 4th and 12th week. Percentages of CD3+ T cells, CD4+ T cells, CD8+ T cells and CD19+ B cells, CD16+ or CD56+ NK cells were also evaluated at each time point.@*Results@#TRAb, TPOA and IgE, IgG, IgA were significantly decreased both after 4th week and after 12th week (all P<0.05). Percentages of CD3+ T cells, CD4+ T cells and CD4+ /CD8+ ratio were gradually decreased after treatment. However, change of CD8+ T cells was not significant (P>0.05).@*Conclusion@#High-dose methylprednisolone may exert an immunosuppressive effect not only by modifying humoral and cellular immune functions, but also by decreasing serum immunoglobulins.

A Glucagon-Like Peptide-1 Receptor Agonist Lowers Weight by Modulating the Structure of Gut Microbiota.

In addition to improving glucose metabolism, liraglutide, a glucagon-like peptide-1 receptor agonist, has weight-loss effects. The underlying mechanisms are not completely understood. This study was performed to explore whether liraglutide could lower weight by modulating the composition of the gut microbiota in simple obese and diabetic obese rats. In our study, Wistar and Goto-Kakizaki (GK) rats were randomly treated with liraglutide or normal saline for 12 weeks. The biochemical parameters and metabolic hormones were measured. Hepatic glucose production and lipid metabolism were also assessed with isotope tracers. Changes in gut microbiota were analyzed by 16S rRNA gene sequencing. Both glucose and lipid metabolism were significantly improved by liraglutide. Liraglutide lowered body weight independent of glycemia status. The abundance and diversity of gut microbiota were considerably decreased by liraglutide. Liraglutide also decreased obesity-related microbial phenotypes and increased lean-related phenotypes. In conclusion, liraglutide can prevent weight gain by modulating the gut microbiota composition in both simple obese and diabetic obese subjects.