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.

C-peptide is associated with NAFLD inflammatory and fibrotic progression in type 2 diabetes.

BACKGROUND: A higher prevalence of nonalcoholic steatohepatitis (NASH) and advanced stages of fibrosis was observed in type 2 diabetes. We aim to investigate whether C-peptide is associated with nonalcoholic fatty liver disease (NAFLD) progression in type 2 diabetic adults. METHODS: A total of 4937 diabetic participants were enrolled from China in 2018. Liver steatosis was detected by ultrasound. Subjects with NAFLD were categorized into simple NAFLD and probable NASH by the concurrent presence of metabolic syndrome. NAFLD fibrosis score was used to identify patients with probable advanced fibrosis. RESULTS: Individuals with a longer history of type 2 diabetes had a lower C-peptide level and a lower prevalence of probable NASH but a higher prevalence of advanced fibrosis. C-peptide was positively associated with simple NAFLD and probable NASH, with odds ratios (ORs) of 4.55 [95% confidence interval (CI) 3.16, 6.55] and 5.28 (95% CI 3.94, 7.09), respectively, comparing quartile 4 with quartile 1 (both p for trend <0.001). However, C-peptide quartiles were negatively associated with the probable presence of advanced fibrosis (Q4 vs. Q1, OR 0.59, 95% CI 0.36, 0.97, p for trend <0.05). A 1-SD increment of ln(C-peptide) was also significantly associated with inflammatory and fibrotic progression (OR 1.34, 95% CI 1.27, 1.41; OR 0.88, 95% CI 0.79, 0.98, respectively). CONCLUSIONS: Significant but opposite associations between C-peptide and inflammatory and fibrotic progression of NAFLD were observed. Understanding islet hormone changes during type 2 diabetes and differentiating the stage of NAFLD may help to personalize treatment strategies for NAFLD patients with type 2 diabetes.

Age and gender-specific distribution of metabolic syndrome components in East China: role of hypertriglyceridemia in the SPECT-China study.

BACKGROUND: Chinese population are experiencing remarkably changes of economic and cultural environments. The present study was to examine the prevalence of metabolic syndrome (MetS) by age between genders and to investigate the current characteristics of MetS and its components in China. METHODS: SPECT-China is a population-based cross-sectional survey on Chinese adults aged ≥18 years in East China. A total of 10,441 Chinese residents participated in anthropometric and laboratory measurements. Of these, 9969 subjects (females, 5868) were eligible for the data analysis reported here. Estimates of the prevalence of MetS and its components were calculated. Presence of MetS was defined based on the IDF/AHA harmonized criteria. MetS z-score was calculated to evaluate the degree of total metabolic disorder. RESULTS: The age-standardized prevalence of the metabolic syndrome was 22.0% (21.9% in men and 22.0% in women). Unlike the continuous MetS rise with age in females, the MetS prevalence in males remained stable among 46-55, 56-65 and > 65 yrs. age groups (31.2%, 31.4%, 32.5%, p = 0.538). In the five components of MetS, contrary to the elevated BP and BG disorders, the frequency of TG disorders decreased with age in males (46.6%(46-55 yrs), 37.2% (56-65 yrs), 27.7%(> 65 yrs), p < 0.001). Multivariable logistic regression showed that in males, more TG disorders were associated with higher BMI, higher educational level and current nonsmoker. In the MetS subjects, the 3-factor combinations which included TG disorders decreased with age in both genders. The whole metabolic profile became better in older male MetS subjects, which was opposite to the female. CONCLUSION: Our results showed a distinct age-related prevalence of MetS between genders in dramatically changed China, in which the TG disorders played an important role. More targeted measures need to be taken to meet the serious challenges of metabolic diseases. TRIAL REGISTRATION: ChiCTR-ECS- 14005052 , Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China).

Exposure to severe famine in the prenatal or postnatal period and the development of diabetes in adulthood: an observational study.

AIMS/HYPOTHESIS: Limited studies have compared the effect of prenatal or postnatal exposure to different severities of famine on the risk of developing diabetes. We aimed to measure the association between diabetes in adulthood and the exposure to different degrees of famine early in life (during the prenatal or postnatal period) during China's Great Famine (1959-1962). METHODS: Data from 3967 individuals were included (a total of 2115 individuals from areas severely affected by famine, 1858 from moderately affected areas, 6 excluded due to missing data). A total of 2335 famine-exposed individuals were further divided into those exposed during the fetal stage, childhood or adolescence/young adulthood. We constructed a difference-in-differences model to compare HbA1c and fasting plasma glucose among the participants exposed to different degrees of famine intensity at different life stages. Logistic analyses were used as measures of the association between diabetes and the different levels of famine severity at different life stages. RESULTS: Individuals who had been exposed to famine during the fetal period, childhood, and adolescence/adulthood and who had lived in a severely affected area had a 0.31%, 0.20% and 0.27% higher HbA1c, respectively, (all p < 0.01) compared with unexposed individuals. After adjusting for age, sex, smoking status, education level and waist circumference, participants exposed to severe famine during the fetal stage (OR 1.90, 95% CI 1.12, 3.21) and childhood (OR 1.44, 95% CI 1.06, 1.97) had significantly higher odds estimates. Unexposed participants living in severely and moderately affected areas had a comparable prevalence of diabetes (OR 1.22, 95% CI 0.80, 1.87). A significant interaction between famine exposure during the fetal and childhood periods and the level of severity in the area of exposure was found (p < 0.05). CONCLUSIONS/INTERPRETATION: Exposure to severe famine in the fetal or childhood period may predict a higher HbA1c and an increased diabetes risk in adulthood. These results from China indicate that both the prenatal and postnatal period may offer critical time windows for the determination of the risk of diabetes.

The nine-year changes of the incidence and characteristics of metabolic syndrome in China: longitudinal comparisons of the two cross-sectional surveys in a newly formed urban community.

BACKGROUND: To assess the 9-year changes of the incidence and characteristics of metabolic syndrome (MetS) in Chinese community under the background of dramatically changed environment. METHODS: Two cross-sectional surveys of the general population were carried out in 2005 and 2014 in Dengmin and Hongnan villages of Fengcheng community, a newly formed urban community from rural area 10 years ago. All permanent adult residents aged 18-80 without active malignant tumors and pregnancy were invited to attend the study. They participated in clinical examinations for anthropometric and blood pressure measurements. Fasting blood samples were drawn for analysis of lipids and glucose. Presence of MetS was defined based on the IDF/AHA harmonized criteria. MetS z-score was calculated to evaluate the degree of total metabolic disorder. RESULTS: A total of 1042 subjects in 2005 and 1053 subjects in 2014 were included in the final analysis. The participants were stratified by gender. The incidence of MetS was higher in 2014 than 2005 in both genders (female, 48.28 vs 31.61 %; male, 41.12 vs 26.30 %; p value, both <0.001). Of the five MetS components, the FBG and TG levels were higher in 2014 than 2005 in both gender, however, the SBP and DBP values were even lower in 2014 than 2005. The differences of FBG, blood pressure and lipid levels between 2005 and 2014 still exist after ruling out recognized diabetic, hypertensive and dyslipidemic subjects, individually. In MetS subjects, MetS z-score showed the whole metabolic profile get worse in 2014 than 2005 in both sex (female, 1.97 ± 2.53 vs 1.74 ± 2.29; male, 2.51 ± 2.79 vs 1.01 ± 2.38. both P < 0.001). Using 3 abnormal components as a combination, we found the frequency of different kinds of combination also changed in MetS subjects. In female, the combination of WC + BP + HDL disorder decreased from 29.7 % (2005) to 11.0 % (2014) and WC + FBG + BP disorder became the most popular phenotype (18.8 %) in 2014. CONCLUSIONS: The dramatically changed environments have extensive influence on metabolic parameters of local residents. More targeted measures need to be taken to meet the serious challenges of metabolic diseases. Trial registration ChiCTR-ECS-14005052, http://www.chictr.org, Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China).

New insight into ectopic thyroid glands between the neck and maxillofacial region from a 42-case study.

BACKGROUND: Ectopic thyroid is a rare disease. In the present study at the 9th People's Hospital in Shanghai, China, 42 patients' ectopic thyroid glands between the neck and maxillofacial region were subjected to a retrospective and transverse study based on data from 1978 to 2012 to explore the natural characteristics of ectopic thyroid. METHODS: The patients' clinical data were collected. In addition, scintigraphy (Tc-99 m, Iodine-131), CT scan, histology and pathology were performed. The protein expression of thyroid transcription factor-1 (TTF-1), thyroglobulin (TG), calcitonin (CT), Ki-67 and parathyroid hormone (PTH) were analyzed from paraffin wax-stored specimens of ectopic thyroid tissue compared with those of orthotopic thyroid tissue. RESULTS: There were 42 total ectopic thyroid patients, approximately 1.24 patients per year on average at our hospital. These patients were aged from 6 to 85 years old, and there were 35 females (83.3 %), seven males (16.7 %). In total, 27 of the patients had lingual thyroid (64 %); seven, sublingual thyroid (17 %); five, dual areas occupied by ectopic thyroid (12 %) and three, other types (7 %). The following conditions were also presented: nodular goiter (13 %), adenoma (8.7 %) and Hashimoto's thyroiditis (4.3 %), no malignancy and no accompanying ectopic parathyroid. TTF-1 expression was significantly higher in ectopic samples than that in orthotopic samples (P = 0.007), but CT and Ki-67 levels displayed no difference. PTH was negative in ectopic tissue. CONCLUSION: Ectopic thyroid is a rare disease and females were more prone to the disease. The most frequent location was lingual thyroid. Nodular goiter, adenoma and Hashimoto's thyroiditis was observed as orthotopic thyroid without accompanying ectopic parathyroid. TTF-1 was highly expressed in ectopic tissue, which may be related to abnormal embryogenesis leading to the thyroid gland being in an abnormal position. The expression of calcitonin (CT) and Ki-67 was not increased, and there were no malignant cells in any sample, which could indicate that it is not easy for ectopic thyroids to become malignant between the neck and maxillofacial region.

Vitamin D Status, Vitamin D Receptor Polymorphisms, and Risk of Type 2 Diabetes: A Prospective Cohort Study.

CONTEXT: Vitamin D status has been associated with risk of type 2 diabetes (T2D), but evidence is scarce regarding whether such relation differs by glycemic status. OBJECTIVE: To prospectively investigate the association between serum 25-hydroxyvitamin D (25(OH)D) and risk of incident T2D across the glycemic spectrum and the modification effect of genetic variants in the vitamin D receptor (VDR). METHODS: This prospective study included 379 699 participants without T2D at baseline from the UK Biobank. Analyses were performed according to glycemic status and HbA1c levels. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs. RESULTS: During a median of 14.1 years of follow-up, 6315 participants with normoglycemia and 9085 patients with prediabetes developed T2D. Compared with individuals with 25(OH)D < 25 nmol/L, the multivariable-adjusted HRs (95% CIs) of incident T2D for those with 25(OH)D ≥ 75 nmol/L was 0.62 (0.56, 0.70) among the normoglycemia group and 0.64 (0.58, 0.70) among the prediabetes group. A significant interaction was observed between 25(OH)D and VDR polymorphisms among participants with prediabetes (P interaction = .017), whereby the reduced HR of T2D associated with higher 25(OH)D was more prominent in those carrying the T allele of rs1544410. Triglyceride levels mediated 26% and 34% of the association between serum 25(OH)D and incident T2D among participants with normoglycemia and prediabetes, respectively. CONCLUSION: Higher serum 25(OH)D concentrations were associated with lower T2D risk across the glycemic spectrum below the threshold for diabetes, and the relations in prediabetes were modified by VDR polymorphisms. Improving the lipid profile, mainly triglycerides, accounted for part of the favorable associations.

Inhibitory effect of paeoniflorin on the inflammatory vicious cycle between adipocytes and macrophages.

Obesity is associated with a state of chronic, low-grade inflammation. It is considered that the paracrine loop involving free fatty acid (FFA) and tumor necrosis factor (TNF)α between adipocytes and macrophages establishes an inflammatory vicious cycle that augments the inflammatory changes and insulin resistance in obese adipose tissue. Paeoniflorin (PF), one of the major components of Paeony root, has been shown to have anti-inflammatory effects in vivo. We investigated the effect of PF on the production of FFA and TNFα in the interaction between adipocytes and macrophages. Coculture of 3T3-L1 adipocytes and RAW 264.7 macrophages markedly enhanced the production of TNFα and FFA compared with the control cultures, however, treatment with PF dose-dependently inhibited the production. We further examined the effects of PF on TNFα-stimulated adipocyte lipolysis and on FFA-induced macrophage TNFα expression. PF inhibited TNFα-stimulated adipocyte lipolysis in a dose-dependent manner, which was compatible with suppressed phosphorylation of TNFα-activated ERK1/2 and preserved downregulation of perilipin. Palmitate, one of the most important saturated FFAs, induced macrophage TNFα upexpression, but PF partially attenuated the effect. These results indicate that PF exhibits anti-inflammatory properties by inhibiting the vicious cycle between adipocytes and macrophages. PF may be useful for ameliorating the inflammatory changes in obese adipose tissue.

Association of Insulin Resistance and ß-cell Function With Bone Turnover Biomarkers in Dysglycemia Patients.

Background: The interrelation between glucose and bone metabolism is complex and has not been fully revealed. This study aimed to investigate the association between insulin resistance, ß-cell function and bone turnover biomarker levels among participants with abnormal glycometabolism. Methods: A total of 5277 subjects were involved through a cross-sectional study (METAL study, http://www.chictr.org.cn, ChiCTR1800017573) in Shanghai, China. Homeostasis model assessment of insulin resistance (HOMA-IR) and ß-cell dysfunction (HOMA-%ß) were applied to elucidate the nexus between ß-C-terminal telopeptide (ß-CTX), intact N-terminal propeptide of type I collagen (P1NP) and osteocalcin (OC). ß-CTX, OC and P1NP were detected by chemiluminescence. Results: HOMA-IR was negatively associated with ß-CTX, P1NP and OC (regression coefficient (ß) -0.044 (-0.053, -0.035), Q4vsQ1; ß -7.340 (-9.130, -5.550), Q4vsQ1 and ß -2.885 (-3.357, -2.412), Q4vsQ1, respectively, all P for trend <0.001). HOMA-%ß was positively associated with ß-CTX, P1NP and OC (ß 0.022 (0.014, 0.031), Q4vsQ1; ß 6.951 (5.300, 8.602), Q4vsQ1 and ß 1.361 (0.921, 1.800), Q4vsQ1, respectively, all P for trend <0.001). Conclusions: Our results support that lower bone turnover biomarker (ß-CTX, P1NP and OC) levels were associated with a combination of higher prevalence of insulin resistance and worse ß-cell function among dysglycemia patients. It is feasible to detect bone turnover in diabetes or hyperglycemia patients to predict the risk of osteoporosis and fracture, relieve patients' pain and reduce the expenses of long-term cure.

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.

Relationship between Free Thyroxine and Islet Beta-cell Function in Euthyroid Subjects.

Thyroid hormones have a specific effect on glucose-induced insulin secretion from the pancreas. We aimed to investigate the association between euthyroid hormones and islet beta-cell function in general population and non-treated type 2 diabetes mellitus (T2DM) patients. A total of 5089 euthyroid participants (including 4601 general population and 488 non-treated T2DM patients) were identified from a cross-sectional survey on the prevalence of metabolic diseases and risk factors in East China from February 2014 to June 2016. Anthropometric indices, biochemical parameters, and thyroid hormones were measured. Compared with general population, non-treated T2DM patients exhibited higher total thyroxine (TT4) and free thyroxine (FT4) levels but lower ratio of free triiodothyronine (T3):T4 (P<0.01). HOMA-ß had prominently negative correlation with FT4 and positive relationship with free T3:T4 in both groups even after adjusting for age, body mass index (BMI) and smoking. When analyzed by quartiles of FT4 or free T3:T4, there were significantly decreased trend of HOMA-ß going with the higher FT4 and lower free T3:T4 in both groups. Linear regression analysis showed that FT4 but not FT3 and free T3:T4 was negatively associated with HOMA-ß no matter in general population or T2DM patients, which was independent of age, BMI, smoking, hypertension and lipid profiles. FT4 is independently and negatively associated with islet beta-cell function in euthyroid subjects. Thyroid hormone even in reference range could play an important role in the function of pancreatic islets.

A Cross-Sectional Study of Oral Lichen Planus Associated With Thyroid Diseases in East China.

Objective: To investigate the prevalence of thyroid diseases in patients with oral lichen planus (OLP) and to explore the correlation between the two diseases. Methods: A cross-sectional study was conducted to investigate the history of thyroid disease in 585 patients with oral lichen planus diagnosed in the Department of Oral Mucosal Diseases of the Ninth People's Hospital, Shanghai Jiaotong University, School of Medicine from June 2017 to April 2018 and in 10,441 normal people in an epidemiological survey conducted by endocrinology department of Ninth People's Hospitalin eastern China from 2014 to 2015. Personal medical history of thyroid disease was obtained through questionnaire and thyroid function was also tested. Results: Of the 585 patients with OLP, 190 (32.48%) had thyroid disease (excluding coexistence of multiple thyroid diseases), 62 (32.6%) had thyroid nodules, and 71 (37.4%) had Hashimoto's thyroiditis. Hyperthyroidism was diagnosed in six patients (3.2%), hypothyroidism in seven patients (3.7%), and thyroid cancer in 11 patients (5.8%). The prevalence of Hashimoto's thyroiditis was significantly higher in patients with oral lichen planus than in the general population. The probability of thyroid disease was significantly higher in women with OLP than in men with OLP (P < 0.001). Conclusion: OLP is associated with a high probability of developing thyroid disease, especially Hashimoto's thyroiditis. In the management of OLP patients, especially in female patients, thyroid disease must be screened.

Comparison of Abdominal Obesity and Fatty Liver and Their Association with Insulin Resistance and Metabolic Syndrome in Chinese Adults.

OBJECTIVE: The purpose of this study was to explore the similarities and differences between nonalcoholic fatty liver (FL) disease (NAFLD) and abdominal obesity in their association with insulin resistance and metabolic syndrome (MetS). METHODS: The Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China) is a population-based survey of Chinese adults. A total of 9,685 participants (median age, 53 years; interquartile range, 44-63) were grouped into four categories by waist circumference (WC) and NAFLD status: NWC/FL(-), NWC/FL(+), HWC/FL(-), and HWC/FL(+) [FL(-), without NAFLD; FL(+), with NAFLD; HWC, higher WC; NWC, normal WC]. Logistic regression models were used to obtain the odds ratios as estimates of the associations between different categories and MetS. RESULTS: Male participants with HWC/FL(-) had higher homeostatic model assessment for insulin resistance scores than subjects with NWC/FL(+), but female subjects showed the opposite results. Compared with NWC/FL(+), HWC was associated with an increased likelihood of blood pressure disorder and a decreased likelihood of triglyceride and blood glucose disorders in men, but in women, HWC was associated with only a lower likelihood of triglyceride disorder. Despite these differences, patients with NWC/FL(+) and HWC/FL(-) had almost equally serious degrees of metabolic disorders (MetS z score). CONCLUSIONS: There are significant differences between sexes regarding the association between NAFLD and abdominal obesity status and MetS components.

Bone Turnover Markers and Probable Advanced Nonalcoholic Fatty Liver Disease in Middle-Aged and Elderly Men and Postmenopausal Women With Type 2 Diabetes.

Objective: Type 2 diabetic patients have a higher incidence of nonalcoholic steatohepatitis (NASH) and advanced stages of fibrosis, and nonalcoholic fatty liver disease (NAFLD) is associated with impaired bone health. We aimed to investigate whether bone turnover is associated with the probable presence of NASH and fibrosis. Methods: In total, 4,937 diabetic participants from Shanghai, China were enrolled in 2018. Subjects with NAFLD were categorized into simple NAFLD and probable NASH groups based on the presence of a metabolic syndrome. The NAFLD fibrosis score was used to identify patients with a higher likelihood of advanced fibrosis. Results: In postmenopausal women, large N-mid fragment of osteocalcin (N-MID osteocalcin) was negatively associated with probable NASH (P for trend < 0.001). ß-C-terminal cross-linked telopeptides of type I collagen (ß-CTX) and procollagen type I N-terminal propeptide (P1NP) were positively associated with the probable presence of significant fibrosis in postmenopausal women (P for trend 0.015 and <0.001). However, in men, N-MID osteocalcin and ß-CTX were negatively associated with the probable presence of significant fibrosis (P for trend 0.029 and 0.027). Conclusions: Significant associations among N-MID osteocalcin, ß-CTX and P1NP, and probable advanced NAFLD were observed. Further prospective and animal studies are warranted to understand the causal relationship and underlying mechanism.

Berberine acutely inhibits insulin secretion from beta-cells through 3',5'-cyclic adenosine 5'-monophosphate signaling pathway.

Berberine, a hypoglycemic agent, has recently been shown to activate AMP-activated protein kinase (AMPK) contributing to its beneficial metabolic effects in peripheral tissues. However, whether berberine exerts a regulatory effect on beta-cells via AMPK or other signaling pathways and counteracts glucolipotoxicity remains uncertain. In the present study, the impact of berberine on beta-cell function was investigated in vivo and in vitro. In high-fat-fed rats, berberine treatment for 6 wk significantly decreased plasma glucose and insulin levels before and after an oral glucose challenge along with the reduction of body weight and improvement of blood lipid profile. In accordance with the in vivo results, berberine acutely decreased glucose-stimulated insulin secretion (GSIS) and palmitate-potentiated insulin secretion in MIN6 cells and rat islets. However, pretreated with berberine for 24 h augmented the response of MIN6 cells and rat islets to glucose and attenuated the glucolipotoxicity. Berberine acutely increased AMPK activity in MIN6 cells. However, compound C, an AMPK inhibitor, completely reversed troglitazone-suppressed GSIS, not berberine-suppressed GSIS. Otherwise, berberine decreased cAMP-raising agent-potentiated insulin secretion in MIN6 cells and rat islets. These results suggest that the activation of AMPK is required for troglitazone-suppressed GSIS, whereas cAMP signaling pathway contributes, at least in part, to the regulatory effect of berberine on insulin secretion.

Astragaloside IV attenuates lipolysis and improves insulin resistance induced by TNFalpha in 3T3-L1 adipocytes.

Increased circulating free fatty acid (FFA) concentrations have been demonstrated to potentially link obesity, insulin resistance and cardiovascular diseases. Astragaloside IV (AS-IV) is a saponin which is widely used in traditional Chinese medicine to treat type 2 diabetes and cardiovascular diseases. The purpose of the present study was to examine the effects of AS-IV on the lipolysis and insulin resistance induced by tumor necrosis factor-alpha (TNFalpha) in cultured 3T3-L1 adipocytes. TNFalpha promotes lipolysis in mammal adipocytes via the mitogen activated protein kinase (MAPK) family resulting in reduced expression/function of perilipin. Application of AS-IV inhibited TNFalpha-induced accelerated lipolysis in a dose-dependent manner, which was compatible with suppressed phosphorylation of ERK1/2 and reversed the downregulation of perilipin. Moreover, TNFalpha induced downregulation of key enzymes in lipogenesis, including LPL, FAS and GPAT, were also attenuated by AS-IV. Further studies showed that AS-IV improved TNFalpha-induced insulin resistance in 3T3-L1 adipocytes. This study provides the first direct evidence of the antilipolytic action of AS-IV in adipocytes, which may allow this agent to decrease the circulating FFA levels, thus increase insulin sensitivity and treat cardiovascular diseases.

Fatty Liver as a Potential Surrogate for Waist Circumference in the Diagnosis of Metabolic Syndrome: A Population-Based Study among Chinese Adults.

Increased waist circumference (WC) is an essential component of metabolic syndrome (MetS). Asians have been found to have more intra-abdominal adipose tissue than Caucasians, in spite of having smaller WC. The purpose of this study was to explore whether NAFLD could be used as a surrogate for MetS diagnosis in the normal WC population. A total of 9694 Chinese residents were selected from SPECT-China, a population-based survey of Chinese adults aged ≥ 18 years in East China. Insulin resistance was calculated by the homeostatic model assessment for insulin resistance (HOMA-IR). MetS z-score was used to evaluate the degree of total metabolic disorder. Logistic regression models were used to obtain the associations between different categories and metabolic syndrome (MetS) components. The prevalence of NAFLD was 27.6%, in which 35.2% were without abnormal WC. Subjects with only NAFLD had similarly severe insulin resistance and OR for clustering of MetS components compared with those with only abnormal WC. A considerable number of NAFLD cases, although had severe metabolic disorder, would not be detected by the current MetS definition. NAFLD could be used as a potential surrogate marker for the diagnosis of MetS in normal WC population.

Ectopic thyroids have lower computed tomography attenuation values than orthotopic thyroids.

PURPOSE: To determine whether ectopic thyroid had the same computed tomography (CT) value as orthotopic thyroid. METHODS: Twenty-one patients with 23 ectopic thyroids and 23 controls with orthotopic thyroids underwent CT scans and were included in this retrospective study. The CT images were reviewed in a blinded fashion by two radiologists. Independent-Samples T-test was used for comparison of CT attenuation values between two groups. RESULTS: Ectopic thyroids had significantly lower non-enhanced attenuation (91.04 ± 5.97 Hounsfield Units vs. 106.56 ± 4.06 Hounsfield Units, P = 0.038) and contrast-enhanced attenuation (141.32 ± 6.42 Hounsfield Units vs. 169.82 ± 4.30 Hounsfield Units, P = 0.001) values than orthotopic thyroids. CONCLUSIONS: Ectopic thyroids have lower CT attenuation values than orthotopic thyroids probably due to the structural or functional abnormalities. The dysgenesis and pathological changes of the ectopic thyroids may contribute to functional deficiency which finally leads to decrease of the CT attenuation values.

Ginsenoside Rb1 promotes adipogenesis in 3T3-L1 cells by enhancing PPARgamma2 and C/EBPalpha gene expression.

Evidence has accumulated that ginseng and its main active constituents, ginsenosides, possess anti-diabetic and insulin-sensitizing properties which may be partly realized by regulating adipocyte development and functions. In the present study, we explored the effect of ginsenoside Rb(1), the most abundant ginsenoside in ginseng root, on adipogenesis of 3T3-L1 cells. We found that with standard differentiation inducers, ginsenoside Rb(1) facilitated adipogenesis of 3T3-L1 preadipocytes in a dose-dependent manner; 10 microM Rb(1) increased lipid accumulation by about 56%. Treatment of differentiating adipocytes with 10 microM Rb(1) increased the expression of mRNA and protein of PPARgamma(2) and C/EBPalpha, as well as mRNA of ap2, one of their target genes. After the treatment of differentiating adipocytes with Rb(1), basal and insulin-mediated glucose uptake was significantly augmented, accompanied by the up-regulation of mRNA and protein level of GLUT4, but not of GLUT1. In addition, ginsenoside Rb(1) also inhibited the proliferation of preconfluent 3T3-L1 preadipocytes. Our data indicate that anti-diabetic and insulin-sensitizing activities of ginsenosides, at least in part, are involved in the enhancing effect on PPARgamma2 and C/EBPalpha expression, hence promoting adipogenesis.