Effect of macrophage migration inhibitory factor on insulin resistance and islet β-cell function in gestational diabetes mellitus

To study the level of macrophage migration inhibitory factor (MIF) in serum and the expression of MIF mRNA in abdominal subcutaneous adipose tissue,and to investigate its impact on insulin resistance and islet β-cell dysfunction in gestational diabetes mellitus (GDM).120 pregnancy women from the Affiliated Hospital of Qingdao University Medical College and Taian Central Hospital were enrolled,including 60 GDM women and 60 women with normal glucose tolerance (NGT).The serum MIF in GDM group was higher than that of NGT group [(3.58±1.02 vs 1.23±0.62) ng/ml,P<0.01].Multiple stepwise regression analysis showed that body mass index was an independent affective factor of the serum levels of MIF (r2 =0.516).The serum levels of MIF and the expressions of MIF mRNA in abdominal subcutaneous adipose tissue were significantly higher in GDM group than NGT group.MIF may contribute to insulin resistance and β-cell dysfunction in GDM.Body mass index seems to be an independent factor in affecting the serum levels of MIF.     

血清视黄醇结合蛋白4在妊娠糖尿病患者中显著升高

To investigate the relationship between serum retinol-binding protein 4(RBP4) and gestational diabetes mellitus (GDM) in Chinese Han pregnant women.195 (23-42 years) pregnant women were recruited (July 2005 to December 2007) from the Department of Gynecology and Obstetric in Ruijin Hospital during their visiting for routine prenatal examination.99 subjects belonged to GDM group,and 96 belonged to the group with normal glucose tolerance (NGT).65 non-pregnant healthy women served as control.Serum RBP4 was measured using sandwich enzyme linked immunosorbent assay (ELISA).Pregnant women had higher level of serum RBP4 than that of non-pregnant control.The concentration of serum RBP4 was significantly increased in GDM group as compared with NGT group[(43.04±1.85 vs 33.84±2.17) rag/L,P<0.01].Multiple stepwise regression analysis showed that triglycerides and homeostasis assessment for insulin resistance (HOMA-IR) were independent variables of RBP4 (r2 =0.165) in pregnant women.The results suggest that serum RBP4 level is significantly increased in pregnant women.Women with GDM had even higher RBP4 level than that of normal pregnant women,and RBP4 levele was positively correlated with triglycerides and HOMA-IR.     

血清视黄醇结合蛋白4在妊娠糖尿病患者中显著升高

To investigate the relationship between serum retinol-binding protein 4(RBP4) and gestational diabetes mellitus (GDM) in Chinese Han pregnant women.195 (23-42 years) pregnant women were recruited (July 2005 to December 2007) from the Department of Gynecology and Obstetric in Ruijin Hospital during their visiting for routine prenatal examination.99 subjects belonged to GDM group,and 96 belonged to the group with normal glucose tolerance (NGT).65 non-pregnant healthy women served as control.Serum RBP4 was measured using sandwich enzyme linked immunosorbent assay (ELISA).Pregnant women had higher level of serum RBP4 than that of non-pregnant control.The concentration of serum RBP4 was significantly increased in GDM group as compared with NGT group[(43.04±1.85 vs 33.84±2.17) rag/L,P<0.01].Multiple stepwise regression analysis showed that triglycerides and homeostasis assessment for insulin resistance (HOMA-IR) were independent variables of RBP4 (r2 =0.165) in pregnant women.The results suggest that serum RBP4 level is significantly increased in pregnant women.Women with GDM had even higher RBP4 level than that of normal pregnant women,and RBP4 levele was positively correlated with triglycerides and HOMA-IR.     

Serum insulin, insulin resistance, p-cell dysfunction, and gallstone disease among type 2 diabetics in Chinese population: A community-based study in Kinmen, Taiwan

AIM: To explore the association of serum insulin, insulin resistance, and β-cell dysfunction with gallstone disease (GSD) in type 2 diabetics. METHODS: We used a community-based study conducted between 1991 and 1993 in Kinmen, Taiwan to identify type 2 diabetics. A screening program for GSD was performed in 2001 by a panel of specialists who employed real-time ultrasound sonography to examine the abdominal region after the patient had fasted for at least 8 h. Screening was conducted in 2001 on 848 patients diagnosed with type 2 diabetes. The HOMA method was used to compare the profile differences for insulin resistance (HOMA IR) and β-cell dysfunction (HOMA β-cell). RESULTS: We studied 440 type 2 diabetics who attended sonography check-ups. After excluding eight insulin-treated diabetics, the prevalence of GSD among the remaining 432 was 13.9% (26/187) among males and 14.7% (36/245) among females. After adjustment for other GSD-associated risk factors in addition to age and obesity, GSD risk increased among females with levels of serum insulin [4th vs 1st quartile odds ratios (OR) = 4.46 (95%CI: 1.71-11.66)] and HOMA IR [4th vs 1st quartile OR = 4.46 (95%CI: 1.71-11.66)]. Better HOMA β-cell function was significantly related to decreased risk of GSD [4th vs 1st quartile OR = 0.16 (95%CI: 0.03-1.70)]. Among males, age and central obesity were the most significant risk factors for GSD. No association of GSD with serum insulin, HOMA IR, and HOMA β-cell was observed among males. CONCLUSION: Serum insulin, insulin resistance, and β-cell dysfunction are risk factors for GSD in females, but not males with type 2 diabetes.     

Expression of PI3-K,PKB and GSK-3β in the skeletal muscle tissue of gestational diabetes mellitus

Objective:To analyze the expression of phosphatidylinositol 3 kinase(PI3-K),protein kinase B(PKB)and glycogen synthase kinase 3 beta(GSK-3β)in skeletal muscle tissue of gestational diabetes mellitus(GDM).Methods:A total of 90 cases of pregnant women were divided into observation group and control group according to the occurrence of GDM with 45 cases in either,and the expression of PI3-K,PKB,GSK-3βmRNA expression in skeletal muscle tissue was compared between two groups.Results:The total PI3-K p85 protein was significantly higher in the observation group compared with the control group,the activity of PI3-K was lower than that of the latter;The total PKB,GSK-3βprotein in skeletal tissue had no significant difference between two groups,while the serine phosphorylation levels of PKB and GSK-3βwere significantly lower in observation group compared with the control group.Conclusions:The downregulation of PI3-K,PKB and GSK-3βin skeletal tissue of GDM caused by phosphorylation dysfunction of signaling molecules is the reason for insulin resistance and transporter function decline which lead to GDM.     

Correlation of iron metabolism with some stress hormones and insulin resistance in patients with gestational diabetes mellitus

正Objective To investigate the association of iron with stress hormones and insulin resistance in patients with gestational diabetes mellitus (GDM).Methods Seventyfive pregnant women diagnosed as GDM during 24-28weeks were collected from January to November 2015 in Yantai Yuhuangding Hospital, and 75 normal pregnant women were used as control group. Blood glucose, insulin, stress hormones and iron metabolism related indexes     

Serum leptin and soluble leptin receptor in non-alcoholic fatty liver disease

AIM： To determine the role of leptin system in non-alcoholic fatty liver disease （NAFLD） development by delineating the changes in serum levels of leptin and soluble leptin receptor （sOB-R）.
METHODS： Blood samples were collected from 30 consecutive patients with liver-biopsy-proven NAFLD and 30 patients with cholecystolithiasis （stationary phase） as controls. Serum leptin levels were determined by radioimmunoassay and concentration of sOB-R was measured by ELISA. Body mass index （BMI） was calculated for all subjects, and serum insulin, C-peptide, and lipoprotein levels were also detected.
RESULTS： Mean serum leptin level and BMI in the NAFLD group were significantly higher than in the controls （both P 〈 0.001）, but mean sOB-R level was lower in the NAFLD group when compared to the controls. Both men and women in the NAFLD group had higher mean serum leptin levels and lower sOB-R levels than did the men and women in the control group （all P 〈 0.001）. There was a significant negative correlation between serum leptin and sOB-R levels （r = -0.725, P 〈 0.001）. Multivariate analysis showed that the percentage of hepatocyte steatosis, sex, BMI, and homeostasis model assessment of insulin resistance （HOMA IR） were independently related to serum leptin levels.
CONCLUSION： Elevated serum leptin seems to be afeature of steatosis, and serum leptin seems to increase as hepatocyte steatosis develops. An enhanced release of leptin is accompanied by an decrease in sOB-R concentration, which suggests higher resistance of peripheral tissues towards the action of leptin.     

Association of insulin resistance and β-cell function with macrosomia among pregnant women with gestational diabetes mellitus

正Objective To investigate the associations of insulin resistance andβ-cell function with macrosomia among pregnant women with gestational diabetes mellitus(GDM).Methods Totally 165 women with GDM were enrolled from January 2017 to June 2017 in the Nutrition Clinic of Beijing Obstetrics and Gynecology Hospitals of Capital Medical University,and they were followed-up     

Biochemical characterization of ketosis-resistant young diabetics of northern India.In vivo effects of i.v. glucose,s.c. epinephrine and i.v. glucagon andin vitro effects of anti-insulin serum on adipose tissue lipolysis

Summary Epinephrine (10 μg/kg body weight) s.c., glucagon (1 μg/kg body weight) i.v. and glucose (0.5 g/kg body weight) i.v. were injected in groups of ketosis-prone young diabetics, ketosis-resistant young diabetics, maturity-onset diabetics, young and mature controls, each group comprising 8 subjects. Samples were drawn at timed intervals and analyzed for glucose, FFA, acetone, citrate and plasma free insulin. FFA and glycerol release by the adipose tissuein vitro was studied in 6 of each of the following groups: young diabetics and young controls in the presence of norepinephrine, anti-insulin serum or both. Failure of the adipose tissue of ketosis-resistant young diabetics to respond to lipolytic and ketogenic hormones has been suggested by others as the basis for the clinically observed resistance to ketoacidosis. The present data do not confirm any failure of the liver or adipose tissue to respond to glucagon, epinephrine or norepinephrine in these diabetics. The ketosis-resistant young diabetics have some endogenous insulin secretory capacity still preserved as evident from their basal and post-glucose free insulin levels and effects of anti-insulin serum onin vitro lipolysis by their adipose tissues. The available endogenous insulin though adequate in preventing excessive lipolysis and ketogenesis, appears insufficient to check hyperglycemia.     

Metabolic dysfunction and cardiovascular disease:molecular mechanisms

Obesity is a common risk factor for the development of cardiovascular disease.It is estimated that 71%of men,61%of women and 33%of children are overweight in the United States,and this trend toward increasing body mass is found world-wide as more cultures acquire a Western lifestyle.In the United States,life expectancy declines by 3 years for those with a body mass index over 30 and by 10 years for those with a body mass index over 40 due,in large part,to the increased prevalence of cardiovascular disease.Over the past decade we have come to appreciate that adipose tissue functions as an endocrine organ,and that obesity contributes to cardiovascular and metabolic disorders through cytokine imbalances that promote the development of a chronic,low grade inflammatory state.Bioactive proteins secreted from fat are generally referred to as adipokines.Under conditions of obesity,adipose tissue expresses higher levels of pro-inflammatory adipokines,such as TNF- and IL- 6,and lower levels of anti-inflammatory cytokines. Adiponectin in the prototypical anti-inflammatory adipokine,and its expression is down-regulated in obese individuals.Low adiponectin levels have shown to be an independent risk factor for developing type 2 diabetes,myocardial infarction and hypertension. Studies with genetically manipulated mice have shown that adiponectin protects against the development of a number of diseases that are prevalent in obese individuals including insulin re- sistance,atherosclerosis,LV hypertrophy,and a peripheral artery disease.However,no adiponectin-based therapies have been successfully launched in the clinic due,in large part,to difficulties associated with the high natural abundance of adiponectin (0.01%of the serum protein) and its complex structure.My laboratory performs genetic screens to identify novel adiponectin-like factors involved in metabolic and cardiovascular regulation.One of these newly discovered factors,referred to as Sfrp5, is a secreted protein that is largely produced by adipocytes.Sfrp5 functions     

Association of visceral obesity and early colorectal neoplasia

AIM:To examine whether visceral adipose tissue(VAT)serves as a risk factor for colorectal adenoma-early colorectal cancer(CRC)sequence.METHODS:A retrospective case-control study was conducted with 153 patients with stageⅠCRC,age/sex-matched 554 patients with colorectal adenoma and557 normal controls.All subjects underwent various laboratory tests,abdominal fat computed tomography(CT),and colonoscopy.VAT was defined as an intraabdominal adipose tissue area measured by CT scan.Adipose tissue area was measured at the level of the umbilicus from CT scan.We used the lowest quartile of VAT and subcutaneous adipose tissue area as a reference group.RESULTS:The body mass index(BMI),total cholesterol,fasting glucose and VAT areas were significantly different among normal,adenoma and CRC groups.The VAT area was 120.6±49.0 cm2in normal controls,130.6±58.4 cm2in adenoma group and 117.6±51.6cm2in CRC group(P=0.002).In univariate analysis,increased BMI was a risk factor for CRC compared to control(P=0.025).However,VAT area was not a risk factor for CRC compared to control.In multivariate analysis that adjusted for smoking,alcohol consumption and subcutaneous adipose tissue area,VAT area was inversely related to CRC,compared to the adenoma(OR=0.53,95%CI:0.31-0.92,highest quartile vs lowest quartile).CONCLUSION:Our study shows that visceral obesity is not a risk factor for early CRC.Visceral obesity might influence the normal-adenoma sequence but not the adenoma-early carcinoma sequence.     

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 β-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 eff...     

Excision of a large abdominal wall lipoma improved bowel passage in a Proteus syndrome patient

Proteus syndrome is an extremely rare congenital disorder that produces multifocal overgrowth of tissue. This report presents a surgical case of a large lipoma in the abdominal wall of a patient with Proteus syndrome. She was diagnosed with Proteus syndrome based on certain diagnostic criteria. The neoplasm increased in size gradually, producing hemihypertrophy of her left lower extremity and trunk, and spread to her retroperitoneum and her left abdominal wall. She experienced gradually progressive constipation, nausea, vomiting, and abdominal pain. Computed tomography （CT） of the abdomen demonstrated a large mass in the subcutaneous adipose tissue of the left lower abdominal wall which measured 12 cm×8 cm×6 cm in diameter and encased the left colon. This mass in the abdominal wall was excised. The weight of the excised mass was 1550 g. The histopathological diagnosis of this mass was lipoma. After surgery, the encasement of the left colon was improved, and the patient was able to move her bowels twice per day. The excision of the large lipoma in the abdominal wall contributed to the improved bowel passage in this patient with Proteus syndrome.     

A paradox： Insulin inhibits expression and secretion of resistin which induces insulin resistance

AIM： To confirm whether insulin regulates resistin expression and secretion during differentiation of 3T3-L1 preadipocytes and the relationship of resistin with insulin resistance both in vivo and in vitro. METHODS： Supernatant resistin was measured during differentiation of 3T3-L1 preadipocytes. L6 rat myoblasts and hepatoma cell line H4IIE were used to confirm the cellular function of resistin. Diet-induced obese rats were used as an insulin resistance model to study the relationship of resistin with insulin resistance. RESULTS： Resistin expression and secretion were enhanced during differentiation 3T3-L1 preadipocytes. This cellular differentiation stimulated resistin expression and secretion, but was suppressed by insulin. Resistin also induced insulin resistance in H4IIE hepatocytes and L6 myoblasts. In diet-induced obese rats, serum resistin levels were negatively correlated with insulin sensitivity, but not with serum insulin. CONCLUSION： Insulin can inhibit resistin expression and secretion in vitro, but insulin is not a major regulator of resistin in vivo. Fat tissue mass affects insulin sensitivity by altering the expression and secretion of resistin.     

Endocrinology and Metabolism

2011306 Association of serum ferritin with β-cell function and insulin resistance in elderly patients with type 2 diabetes and impaired glucose tolerance. ZHA Ying(查英),et al.Dept Endocrinol,Shanghai 5th People's Hosp,Fudan Univ,Shanghai 200240.Abstract:Objective To investigate the relationship between serum ferritin and β-cell function,insulin resistance in elderly patients(age>60 years) with type 2 diabetes and impaired glucose tolerance. Methods Total 1 143 patients with type 2 diabetes,448 patients     

Hepatitis C virus induced insulin resistance impairs response to anti viral therapy

Hepatitis C virus (HCV) infection is an important risk factor for insulin resistance (IR). The latter is the pathogenic foundation underlying metabolic syndrome, steatosis and cirrhosis, and possibly hepatocellular carcinoma (HCC). The interplay between genetic and environmental risk factors ultimately leads to the development of IR. Obesity is considered a major risk factor, with dysregulation of levels of secreted adipokines from distended adipose tissue playing a major role in IR. HCV-induced IR may be due to the HCV core protein inducing proteasomal degradation of insulin receptor substrates 1 and 2, blocking intracellular insulin signaling. The latter is mediated by increased levels of both tumour necrosis factor-α (TNF-α) and suppressor of cytokine signaling 3 (SOC-3). IR, through different mechanisms, plays a role in the development of steatosis and its progression to steatohepatitis, cirrhosis and even HCC. In addition, IR has a role in impairing TNF signaling cascade, which in turn blocks STAT-1 translocation and interferon stimulated genes production avoiding the antiviral effect of interferon.     

Type 2 diabetes mellitus and CA 19-9 levels

AIM： To prospectively investigate serum CA 19-9 levels in type 2 diabetic patients in comparison with age and gender-matched control subjects.
METHODS： We recorded duration of diabetes and examined fasting glucose levels, HbAlc levels and serum CA 19-9 levels in 76 type 2 diabetic patients and 76 controls. Abdominal CT was performed in order to eliminate abdominal malignancy in the diabetic and control groups.
RESULTS： The average CA 19-9 level was 46.0 ± 22.4 U/mL for diabetic patients whereas it was 9.97± 7.1 U/mL for the control group （P 〈 0.001 ）. Regression analysis showed a positive correlation between diabetes and CA 19-9 independent from age, gender, glucose level and HbAlc level （t = 8.8, P 〈 001 ）. Two of the diabetic patients were excluded from the study because of abdominal malignancy shown by CT at the initial evaluation. For all patients, abdominal CT showed no pancreatic abnormalities.
CONCLUSION： CA 19-9 is a tumor-associated antigen, which is elevated in pancreatic, upper gastrointestinal tract, ovarian hepatocellular, and colorectal cancers, as well as in inflammatory conditions of the hepatobiliary system, biliary obstruction and in thyroid diseases. Diabetes has been claimed to be a risk factor for pancreatic cancer, which is increasing its incidence and has one of the lowest survival rates of all cancers. CA 19-9 is used in the diagnosis of pancreatic cancer but is also a marker of pancreatic tissue damage that might be caused by diabetes. We propose that a higher cutoff value of CA 19-9 should be used in diabetics to differentiate benign and malignant pancreatic disease, and subtle elevations of CA 19-9 in diabetics should be considered as the indication of exocrine pancreatic dysfunction.     

Effect of insulin and metformin on methylation and glycolipid metabolism of peroxisome proliferator-activated receptor γcoactivator-1A of rat offspring with gestational diabetes mellitus

Objective:To discuss the effect of insulin and metformin on amethylation and glycolipid metabolism of peroxisome proliferator-activated receptor γ coactivator-1A(PPARGC1A) of rat offspring with gestational diabetes mellitus(GDM).Methods:A total of 45 pregnant rats received the intraperitoneal injection of streptozotocin to establish the pregnant rat model of GDM.A total of 21 pregnant rats with GDM were randomly divided into three groups,with 7ruts in each group,namely the insulin group,metformin group and control group.Rats in the insulin group received the abdominal subcutaneous injection of 1 mL/kg recombinant insulin glargine at 18:00 every day.Rats in the metformin group received the intragastric infusion of metformin hydrochloride at 18:00 every day,with the first dose of 300 mg/kg.The doses of two groups were adjusted every 3 d to maintain the blood glucose level at 2.65-7.62 mmol/L.Rats in the control group received the intragastric infusion of 1 mL normal saline at 18:00 every day.After the natural delivery of pregnant rats.10 offspring rats were randomly selected from each group.At birth,4 wk and 8 wk after the birth of offspring rats,the weight of offspring rats was measured.The blood glucose level of offspring rats was measured at 4wk and 8 wk,while the level of serum insulin,triglyceride and leptin was measured at 8 wk.Results:The weight of offspring rats at birth in the insulin group and metformin group was significantly lower than the one in the control group(P0.05),and there was no significant difference at 4 wk and 8 wk among three groups(P0.05).The fasting blood glucose and random blood glucose in the insulin group and metformin group at 4 wk and 8 wk were all significantly lower than ones in the control group(P0.05);there was no significant difference between the insulin group and metformin group(P0.05).The expression of PPARGC1 A mRNA in the insulin group and metformin group was significantly higher and the methylation level of PPARGC1 A was significantly lower than the one in the control group(P0.05),but there was no significant difference between the insulin group and metformin group(P0.05).Insulin and leptin at 8 wk in the insulin group and metformin group were significantly higher,while triglyceride was significantly lower than the one in the control group(P0.05);triglyceride level of rats in the insulin group was significantly higher than the one in the metformin group(P0.05).There was no significant difference in insulin and leptin level of offspring rats between the insulin group and metformin group(P0.05).Conclusions:GDM can induce the methylation of PPARGC1 A of offspring rats to reduce the expression of PPARGC1 A mRNA and then cause the disorder of glycolipid metabolism when the offspring rats grow up;the insulin or metformin in the treatment of pregnant rats with GDM can reduce the methylation level of PPARGC1 A and thus improve the abnormal glycolipid metabolism of offspring rats.     

The Study on the Correlation Between Plasma Adiponectin Level and Coronary Heart Disease

Objectives To investigate the relationship between plasma adiponectin level and coronary heart disease （CHD）, and some established cardiovascular risk factors and to probe its probable pathogenesis which adiponectin results in CHD. Methods The levels of plasma adiponectin, fasting plasma insulin （FINS）, C-reactive protein （CRP） and P-selectin were measured by ELISA, plasma ET-1 was measured by radioimmunoassay （RIA） in 75 male patients with CHD and 30 healthy male people. Body mass index （BMI）, waist / hip ratio （WHR） and insulin resistance index （Homa-IR） were calculated respectively. Results （1）The plasma adiponectin levels in CHD group were lower compared with control group[（5.18±2.57）mg / L vs（8.94±2.59）mg / L, P〈 0.001 ], there was no significant difference of plasma adiponectin levels in CHD sub-groups （P 〉 0.05）.（2） Based on multinominal stepwise logistic regression analysis, adiponectin was one of significant and independent risk factors for CHD. （3） Multivariate liner stepwise regression analysis showed that adiponectin had significant correlation with BMI and TG, BMI and TG were independent factors influencing on plasma adiponectin levels. （4） Pearson correlation analysis indicated plasma adiponectin levels were inversely related to FINS levels , Homa-IR, CRP, P-selectin and ET-1. Conclusions （ 1 ）Plasma adiponectin levels are lower in CHD patients compared the control　subjects, there are no significant difference of plasma adiponectin levels in patients with SAP, UAP and AMI. （2） Plasma adiponectin levels are relative with CHD. Hypoadiponectinemia is an independent risk factor for CHD. （3）Established cardiovascular risk factors such as BMI and TG have an obvious influence on adiponectin. （4）The probable pathogenesis by which adiponectin involves in CHD is suggested that adiponectin relates to insulin resistance, inflammatory reaction and dysfunction of vessel endothelium.     

Relationship of Omentin-1 and insulin resistant in gestational diabetes mellitus

正Objective To explore the relationship between Omentin-1 and insulin resistant in women with gestational diabetes mellitus (GDM).Methods 26 GDM and 24healthy control subjects were enrolled in this study. Serum Omentin-1 was measured with ELISA method. The expression of Omenitn-1 and IRS-1, IRS-2 in visceral Omental adipose tissue were detected by quantitative re-