Metabolic syndrome and non-alcoholic fatty liver disease:Asian definitions and Asian studies

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), as conventionally recognized, is a metabolic disorder largely confined to residents of affluent industrialized Western countries. However, obesity and insulin resistance are not restricted to the West, as witnessed by their increasingly universal distribution. In particular, there has been an upsurge in metabolic syndrome in the Asia-Pacific region, although there are critical differences in the extent of adiposity between Eastern and Western populations. DATA SOURCES: An English-language literature search using PubMed (1999-2007) on obesity, metabolic syndrome and NAFLD, focusing on Asian definitions and Asian studies. RESULTS: NAFLD appears to be of long-standing insulin resistance and likely represents the hepatic manifestation of the metabolic syndrome. With insulin resistance as a common factor, the disease is associated with atherosclerosis and cardiovascular risk. All features of the metabolic syndrome and related events are assessed for practical management of NAFLD, although the criteria for the diagnosis of obesity and central obesity differ across racial groups. CONCLUSIONS: The increasing prevalence of obesity, coupled with diabetes, dyslipidemia, hypertension and ultimately metabolic syndrome, puts a very large population at risk of developing NAFLD in the coming decades. The simultaneous identification and appropriate treatment of the components of metabolic syndrome are crucial to reduce hepatic as well as cardiovascular morbidity and mortality.

Effects of different free fatty acids on insulin resistance in rats

BACKGROUND: Much evidence demonstrates that elevated free fatty acids (FFAs) are associated with insulin resistance. However, it is not clear whether different FFAs can cause different degrees of peripheral insulin resistance. This study aimed to investigate the effects of short-term elevation of FFAs on hepatic and peripheral insulin action, and determine whether FFAs with different degrees of saturation have differential effects on hepatic insulin resistance. METHODS: Intralipid+heparin (IH, polyunsaturated fatty acids), oleate (OLE), lard oil+heparin (LOH), and saline (SAL) were separately infused intravenously for 7 hours in normal Wistar rats. During the last 2 hours of the fat/saline infusion, a hyperinsulinemic-euglycemic clamping was performed with [6-H-3] glucose tracer. Plasma glucose was measured using the glucose oxygenase method. Plasma insulin and C-peptide were determined by radioimmunoassays. Plasma FFAs were measured using a colorimetric method. RESULTS: Compared with infusion of SAL, plasma FFA levels were significantly elevated by infusions of IH, OLE, and LOH (P<0.001). All three fat infusions caused remarkably higher hepatic glucose production (HGP) than SAL (P<0.001). OLE and LOH infusions induced much higher HGP than IH (P<0.01). Glucose utilization (GU) was decreased with all three fat infusions relative to SAL (P<0.001), but GU did not differ among the three types of fat infusions. CONCLUSIONS: Short-term elevation of FFAs can induce hepatic and peripheral insulin resistance. Polyunsaturated fatty acids induced less hepatic insulin resistance than monounsaturated or saturated fatty acids. However, IH, OLE, and LOH infusions induced similar peripheral insulin resistance.

Effect of sodium salicylate on oxidative stress and insulin resistance induced by free fatty acids

BACKGROUND: It has been reported that high-dose salicylates improve free fatty acids (FFAs)-induced insulin resistance and beta-cell dysfunction in vitro, but the mechanism remains uncertain. In insulin-resistant rats, we found that the supplementation of sodium salicylate is associated with a reduction of plasma malondialdehyde (MDA), a marker of oxidative stress. Few studies have investigated the effects of salicylates on oxidative stress levels in insulin-resistant animal models. This study aimed to assess the effect of sodium salicylate on insulin sensitivity and to explore the potential mechanism by which it improves hepatic and peripheral insulin resistance. METHODS: Intralipid+heparin (IH), saline (SAL), or intralipid+heparin+sodium salicylate (IHS) were separately infused for 7 hours in normal Wistar rats. During the last 2 hours of the infusion, hyperinsulinemic-euglycemic clamping was 3 performed with [6-(3)H] glucose tracer. Plasma glucose was measured using the glucose oxygenase method. Plasma insulin and C-peptide were determined by radioimmunoassay. MDA levels and glutathione peroxidase (GSH-PX) activity in the liver and skeletal muscle were measured with colorimetric kits. RESULTS: Compared with infusion of SAL, IH infusion increased hepatic glucose production (HGP), and decreased glucose utilization (GU) (P<0.05). The elevation of plasma free fatty acids increased the MDA levels and decreased the GSH-PX activity in the liver and muscle (P<0.01). Sodium salicylate treatment decreased HGP, elevated GU (P<0.05), reduced MDA content by 60% (P<0.01), and increased the GSH-PX activity by 35% (P<0.05). CONCLUSIONS: Short-term elevation of fatty acids induces insulin resistance by enhancing oxidative stress levels in the liver and muscle. The administration of the anti-inflammatory drug sodium salicylate reduces the degree of oxidative stress, therefore improving hepatic and peripheral insulin resistance. IKK-beta and NF-kappa B provide potential pathogenic links to oxidative stress.

Forkhead box O1 / pancreatic and duodenal homeobox 1 intracellular translocation is regulated by c-Jun N-terminal kinase and involved in prostaglandin E-2-induced pancreatic beta-cell dysfunction

Prostaglandin E-2(PGE(2)) is a well-known mediator of beta-cell dysfunction in both type 1 and type 2 diabetes.We recently reported that down-regulation of the Akt pathway activity is implicated in PGE(2)-induced pancreatic beta-cell dysfunction.The aim of this study was to further dissect the signaling pathway of this process in pancreatic beta-cell line HIT-T15 cells and primary mouse islets.We found that PGE(2) time-dependently increased the c-Jun N-terminal kinase(JNK) pathway activity.JNK inhibition by the JNK-specific inhibitor SP600125 reversed PGE(2)-inhibited glucose-stimulated insulin secretion(GSIS).PGE(2) induced dephosphorylation of Akt and FOXO1, leading to nuclear localization and transactivation of FOXO1.Activation of FOXO1 induced nuclear exclusion but had no obvious effect on the whole-cell protein level of pancreatic and duodenal homeobox 1(PDX1).However, these effects were all attenuated by JNK inhibition.Furthermore, adenovirus-mediated overexpression of dominant-negative(DN)FOXO1 abolished whereas constitutively active(CA)-FOXO1 mimicked the effects of PGE(2) on GSIS in isolated mouse islets.In addition, we demonstrated that DN-JNK1 but not DN-JNK2 or CA-Akt abolished the PGE(2)-induced AP-1 luciferase reporter activity, whereas DN-JNK1 and CA-Akt but not DN-JNK2 reversed the effect of PGE(2) on FOXO1 transcriptional activity, and overexpression of DN-JNK1 rescued PGE(2)-impaired GSIS in mouse islets.Our results revealed that activation of the JNK is involved in PGE(2)induced beta-cell dysfunction.PGE(2)-mediated JNK1 activation, through dephosphorylation of Akt and FOXO1, leads to nuclear accumulation of FOXO1 and nucleocytoplasmic shuttling of PDX1, finally resulting in defective GSIS in pancreatic beta-cells.

Prevention of relapse of graves' disease by treatment with an intrathyroid injection of dexamethasone

Introduction:Antithyroid drugs are widely used in the treatment of Graves' disease(GD), but the relapse rate is very high after therapy withdrawal.We evaluated the reduction effects of intrathyroid injection of dexamethasone(IID) on the relapse rate of hyperthyroidism in patients with newly diagnosed GD.Patients and Methods:A total of 191 patients with GD completed the study.After 6 months of treatment with methimazole(MMI), the patients were randomly assigned to receive either MMI(96 patients) alone or MMI combined with IID(MMI + IID;95 patients) treatment for 3 months, followed by continuing a dose of MMI that would maintain euthyroidism for the next 9 months in all of the patients.After withdrawal of the medical therapy, patients were followed for 24 months, and the relapse rate of hyperthyroidism was evaluated.Results:No statistical difference was observed in the levels of serum FT4, TSH, or TSH receptor antibodies(TR-Ab), the thyroid volume, or the TR-Ab positive rate between the two groups at month 6.After the next 3 months of treatment with MMI + IID or MMI alone, the levels of TSH increased significantly, and the levels of serum TR-Ab, the TR-Ab positive rate, and thyroid volume decreased significantly in the MMI + IID group compared with the MMI group.Seven patients(7.4%) experienced a relapse of overt hyperthyroidism in the MMI + IID group and 49 patients(51%) in MMI group during the 2-yr follow-up period(P < 0.001).Conclusions:MMI + IID treatment is helpful to prevent relapse of hyperthyroidism in GD after medical therapy withdrawal.

Inappropriate secretion of antidiuretic hormone:a rare complication after common bile duct exploration

BACKGROUND: The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) as a dilutional hyponatremia is due to a pathological increase of antidiuretic hormone (ADH). It is characterized by hyponatremia and decreased serum osmolarity as well as an increase in urinary osmolarity. The most common etiological factors of this syndrome include diseases or trauma of the central nervous system and malignant tumor or inflammation of the lung. SIADH following abdominal surgery is rare. METHODS: We report the case of a 68-year-old woman who developed, 24 hours after common bile duct exploration and stone removal, continuous hyponatremia for 20 days and clinical manifestations of nausea, vomiting, and lethargy without focal neurological signs. RESULT: Laboratory examinations supported the diagnosis of SIADH. After therapy with fluid restriction, the patient recovered. CONCLUSION: There are diverse causes for SIADH. It is important to have kept this clinical possibility in mind in the differential diagnosis of refractory hyponatremia under any circumstances.

Relationship between serum iron metabolism and glucose and lipid metabolism in patients with type 2 diabetes mellitus

Objective To explore the relationship between serum iron (SI) metabolism and glucose and lipid metabolism in patients with type 2 diabetes mellitus(T2 DM).Methods A total of 170 T2 DM patients hospitalized in the Department of Endocrinology,Lanzhou University First Hospital from 2019 to 2021 were included.During the same period.

Correlation between serum uric acid/high density lipoprotein cholesterol ratio and type 2 diabetic peripheral neuropathy

Objective To explore the correlation between blood uric acid/HDL-C ratio(UHR) and peripheral neuropathy(DPN) in T2DM.Methods A total of 127 T2DM patients admitted to the Endocrinology Department of Wujin Traditional Chinese Medicine Hospital in Changzhou City from August 2022 to August 2023 were selected.They were divided into a simple T2DM group(n=62) and a combined DPN group (DPN,n=65)based on whether or not they had DPN.

Risk factors analysis and risk prediction model construction of 30-day unplanned readmission in type 2 diabetes mellitus

Objective To investigate the risk factors of unplanned readmission in patients with diabetes and to develop the risk prediction model.Methods 240 type 2diabetes mellitus (T2DM) patients hospitalized in the Department of Endocrinology,Hainan Hospital Affiliated to Hainan Medical College from December 2016 to December 2020 were selected.Patients were divided into re-admission group (RG,n=55) and non-readmission group (NRG,n=185) according to whether they were readmitted within 30 days.

Vaspin improves insulin sensitivity in type 2 diabetes rats by regulating the polarization of adipose tissue macrophages

Objective To explore the effect of Vaspin on adipose tissue macrophage polarization and its underlying mechanism.Methods Fifty male SD rats,aged 8 weeks,were chosen and randomly allocated into three groups:the normal control(NC),the type 2 diabetes(T2DM),and various concentrations of Vaspin intervention(V1:480 ng/kg,V2:960 ng/kg,V3:1440 ng/kg).Vaspin was administered via intraperitoneal injection for 8 weeks.Glucose tolerance and insulin sensitivity were evaluated via intraperitoneal glucose tolerance test(IPGTT),intraperitoneal insulintolerance test(IPITT)and hyperinsulinemic-euglycemcicclamp.Adipose tissue inflammation and macrophage polarization were assessed using immunofluorescence,RT-PCR and western bloting.Results After 8 weeks of intervention,there were no statistically significant differences in body weight and blood lipid levels among groups.IPGTT,IPITT,and hyperinsulinemic-euglycemic clamp experiments demonstrated that Vaspin intervention improved blood glucose and insulin sensitivity.

Pathological types and clinical features of unilateral primary aldosteronism.

Objective Toinvestigate the distribution of pathological types of unilateral primary aldosteronism,and to explore the clinical characteristics and prognosis of patients with different pathological types.Methods A total of 241 patients with unilateral primary aldosteronism who underwent adrenal surgery were included in this study.The clinical and postoperative follow-up data were collected,and the postoperative tissue sections were stained with HE and aldosterone synthase.According to the staining results,pathological types of 241 patients were classified,and the clinical characteristics and surgical prognosis of patients with unilateral primary aldosteronism were compared.Results According to the international histopathology consensus forunilateral primary aldosteronism,among 241 patients with unilateral primary aldosteronism,223 were classical(92.5%),17 were non-classical(7.1%),and 1 was aldosterone producing carcinoma(0.4%).Among classical cases,189 were aldosterone producing adenoma and 34 were aldosterone producing nodule.In the non-classical cases,8 cases were mnultiple aldosterone producing nodule and 9 cases were multiple aldosterone producing nodule.

Surgical prognosis and influencing factors in 406 patients with primary aldosteronism

Objective To evaluate postoperative biochemical and clinical remission rates in patients with unilateral primary aldosteronism and analyze related influencing factors.Methods A total of 406 patients of primary aldosteronism with confirmed subtyping,who underwent adrenalectomy and completed follow-up inthe Department of Endocrinology of the First Affiliated Hospital of Chongqing Medical University from November 2013to March 2022 were retrospectively enrolled.

Rapamycin restores CD4^(+)T cell subsets imbalance in Graves' ophthalmopathy mice model

Objective To study the effect of rapamycin on the disorder of CD4^(+)T cell subsets in Graves’ophthalmopathy (GO) mice,as well as the ophthalmopathy and hyperthyroidism phenotype,and to provide new possibilities for the treatment of GO.Methods 6-8weeks old female Balb/c mice were injected intramuscularly with adenovirus expressing the A-subunit of TSHR(A-sub-Ad) 9 times.Rapamycin was given by embedding in the feed (14 ppm).

Association between different obesity indicators and carotid intima-media thickness in patients with type 2 diabetes mellitus

Objective To explore the relationship between different obesity indicators and carotid intima-media thickness (CIMT) in patients with type 2 diabetes mellitus (T2DM).Methods A total of 1 762 T2DM patients who visited the Endocrinology Department of Changzhou Second People’s Hospital Affiliated to Nanjing Medical University and the Integrated Traditional Chinese and Western Medicine Hospital Affiliated to Nanjing University of Traditional Chinese Medicine from January2019 to February 2022 were enrolled in this study.

Association of time in range with metabolic associated fatty liver disease and liver fibrosis in patients with type 2 diabetes

Objective To investigate the association of time in rangewith metabolic associated fatty liver disease(MAFLD)and advanced liver fibrosis in patients with type 2 diabetes.Methods This study was a retrospective study.A total of 494 type 2 diabetic patients were recruited in the Department of Endocrinololgy of Henan Provincial People's Hospital from November 2019 to April 2022.Timein range(TIR)was calculatedwith continuous glucose monitoring data.Abdominal ultrasound scan was used to diagnose fatty liver.Liver stiffness measurement(LSM)by transient elastography was used to evaluateliver fibrosis.Pearson and multivariate linearregression analysis was used to evaluate the associationbetween TIR and LSM.Multivariate logistic regression analysis was usedto analyze the association of TIR with risk of MAFLD and advanced liver fibrosis.

Effect of Dapagliflozin on cell proliferation, apoptosis and inflammation of podocytes induced by high glucose via regulating p38 MAPK pathway

Objective To investigate the effect of Dapagliflozin on high glucose-induced podocyte proliferation and apoptosis through p38 mitogen-activated protein kinase(p38 MAPK)pathway.Methods Human glomerular podocytes(HGPC)were divided into control(Con)group,low/medium/high D-glucose(Glu 10,Glu 20,Glu 30)group,high glucose(HG)group,low/medium/high concentration Dapagliflozin(HG+Dap 12.5,HG+Dap 25,HG+Dap 50)group,Dapagliflozin(HG+Dap)group,inhibitor(HG+SB 203580)group,Dapagliflozin+inhibitor(HG+Dap+SB 203580)group and Dapagliflozin+activator(HG+Dap+C16-PAF)group.After 24 hours of intervention,the cell viability,proliferation rate,apoptosis rate and levels of related factors were tested.Results Compared with Con group,IL-1β,TNF-α,apoptosis rate,Caspase-3 mRNA and protein expression,p53,P-p38 MAPK protein expression were increased(P<0.05),while cell proliferation rate,Cyclin D1 mRNA and protein expression were decreased in HG group(P<0.05).Compared with HG group,the proliferation rate,Cyclin D1 mRNA and protein expression were increased(P<0.05),while IL-1β,TNF-α,apoptosis rate,Caspase-3 mRNA and protein expression,p53,P-p38 MAPK protein expression were decreased in the HG+Dap and HG+SB 203580 groups(P<0.05).Compared with HG+Dap group,cell proliferationn rate.

Correlation of serum and follicular fluid SREBP1c and LRG1 levels with insulin resistance in PCOS patients

Objective To investigate the serum and follicular fluid levels of sterol regulatory element-binding protein 1 c(SREBP-lc),leucine-rich α-2-glycoprotein 1 (LRG1)and the correlation with insulin resistance (IR) in nonovarian etiology infertility patients and polycystic ovary syndrome (PCOS) patients with or without IR.

Serum TSH levels in women aged 40 and above:association with lifespan and 10-year mortality

Objective To investigate the relationship between thyroid-stimulating hormone(TSH)levels and 10-year mortality in women aged 40 years and older.Methods Residents aged 40 and over in urban areas of Guiyang City who participated in the“Epidemiological Study of Cancer Risk in Patients with Type 2 Diabetes in China(REACTION)”were followed up in 2011.Finally,5614 people were enrolled,and the baseline general information,physical examination and TSH detection were carried out.The average follow-up was(9.77±1.55)years,and the treatment and death of thyroidrelated diseases were recorded.The Cox proportional hazards model was used to analyze the relationship between TSH level and 10-year mortality in middle-aged and elderly women,and plotting survival time curves(Kaplan-Meier curves)to study the association between elevated TSH levels and lifespan in subjects under 65 years old.Results The multivariate Cox proportional hazards model showed that compared with the normal group,after multivariate adjustment,the risk of death in the TSH increased group was decreased(HR=0.644,95%CI0.478-0.868,P<0.05).