Comparison of the Efficacy of Rosuvastatin Monotherapy 20 mg with Rosuvastatin 5 mg and Ezetimibe 10 mg Combination Therapy on Lipid Parameters in Patients with Type 2 Diabetes Mellitus

BACKGROUND: The apolipoprotein B/A1 (apoB/A1) ratio is a stronger predictor of future cardiovascular disease than is the level of conventional lipids. Statin and ezetimibe combination therapy have shown additional cardioprotective effects over statin monotherapy. METHODS: This was a single-center, randomized, open-label, active-controlled study in Korea. A total of 36 patients with type 2 diabetes mellitus were randomized to either rosuvastatin monotherapy (20 mg/day, n=20) or rosuvastatin/ezetimibe (5 mg/10 mg/day, n=16) combination therapy for 6 weeks. RESULTS: After the 6-week treatment, low density lipoprotein cholesterol (LDL-C) and apoB reduction were comparable between the two groups (−94.3±15.4 and −62.0±20.9 mg/dL in the rosuvastatin group, −89.9±22.7 and −66.8±21.6 mg/dL in the rosuvastatin/ezetimibe group, P=0.54 and P=0.86, respectively). In addition, change in apoB/A1 ratio (−0.44±0.16 in the rosuvastatin group and −0.47±0.25 in the rosuvastatin/ezetimibe group, P=0.58) did not differ between the two groups. On the other hand, triglyceride and free fatty acid (FFA) reductions were greater in the rosuvastatin/ezetimibe group than in the rosuvastatin group (−10.5 mg/dL [interquartile range (IQR), −37.5 to 29.5] and 0.0 µEq/L [IQR, −136.8 to 146.0] in the rosuvastatin group, −49.5 mg/dL [IQR, −108.5 to −27.5] and −170.5 µEq/L [IQR, −353.0 to 0.8] in the rosuvastatin/ezetimibe group, P=0.010 and P=0.049, respectively). Both treatments were generally well tolerated, and there were no differences in muscle or liver enzyme elevation. CONCLUSION: A 6-week combination therapy of low-dose rosuvastatin and ezetimibe showed LDL-C, apoB, and apoB/A1 ratio reduction comparable to that of high-dose rosuvastatin monotherapy in patients with type 2 diabetes mellitus. Triglyceride and FFA reductions were greater with the combination therapy than with rosuvastatin monotherapy.

Ultrasonographic ovarian dynamic, plasma progesterone, and non-esterified fatty acids in lame postpartum dairy cows

The objective of this study was to compare ovulation rate, number of large ovarian follicles, and concentrations of plasma progesterone (P4) and non-esterified fatty acids (NEFA) between lame (n = 10) and non-lame (n = 10) lactating Holstein cows. The study was conducted in an organic dairy farm, and cows were evaluated by undertaking ultrasonography and blood sampling every 3 days from 30 days postpartum for a period of 34 days. Cows which became lame during the first 30 days postpartum experienced a lower ovulation rate determined by the presence of a corpus luteum (50% presence for lame cows and 100% for non-lame cows, p ≤ 0.05). The number of large ovarian follicles in the ovaries was 5 for lame cows and 7 for non-lame cows (p = 0.09). Compared to non-lame cows, lame cows had significantly lower (p ≤ 0.05) concentrations of plasma P4. Furthermore, NEFA concentrations were lower (p ≤ 0.05) in lame cows than in non-lame cows. It is concluded that lameness in postpartum dairy cows is associated with ovulation failure and lower concentrations of P4 and NEFA.

Clinical diagnosis value of NEFA,ALB,BMG and CREA in patient with type 2 diabetic nephropathy / 国际检验医学杂志

Objective To investigate the clinical application value of serum non-esterified fatty acid(NE-FA),albumin(ALB),creatinine(CREA)and β2-microglobulin(BMG)levels in type 2 diabetic nephropathy (T2DN).Methods 140 cases of type 2 diabetes mellitus(T2DM)in this hospital from October 2016 to Febru-ary 2017 were selected and divided into the T2DM non-nephropathy group(47 cases)and T2DN group(93 ca-ses)according to urinary albumin and urinary microalbumin.The T2DN group was further divided into the ALB high value subgroup(ALB>30 g/L,47 cases)and ALB low value subgroup(ALB≤30 g/L,46 cases)ac-cording to serum ALB detection results.Meanwhile 51 persons undergoing healthy physical examination were selected as the healthy control group.The levels of NEFA,ALB,CREA and BMG were measured in each group.Then the correlation among groups was analyzed.Results The levels of serum NEFA and NEFA/ALB in the T2DM non-nephropathy group were significantly higher than those in the healthy control group,the difference was statistically significant(P<0.05).The serum NEFA level in the T2DN group was significantly higher than that in the healthy control group,and the levels of NEFA/ALB,BMG and CREA were higher than those in the healthy control group and T2DM non nephrotic group,while the ALB level was significantly lower than that in the healthy control group and T 2DM non nephropathy group,the difference was statistical-ly significant(P<0.05).The levels of BMG and CREA in the ALB high value subgroup and ALB low value subgroup were significantly higher than those in the T 2DM non-nephropathy group ,the difference was statisticallysignificant( P < 0 .05) ;the levels of NEFA and ALB in the ALB low value subgroup were significantlylower than those in the T2DM non-nephropathy group and ALB high value subgroup ,while the NEFA/ALBlevels were significantly higher than those in the T2DM non-nephropathy group ,the difference was statisticallysignificant(P < 0 .05) .The ALB was positively correlated with NEFA level (r = 0 .252 ,P < 0 .01) ,and wasnegatively correlated with BMG and CREA levels (r = - 0 .424 ,r = - 0 .281 ,P < 0 .01) ;serum BMG level waspositively correlated with serum CREA level (r = 0 .920 ,P < 0 .01 ) .Conclusion Serum BMG ,CREA ,NEFAand ALB play an important role in progress of T2DN ,and can serve as the monitoring indicators of renal injury degree in T2DM .

Predictive value of Hcy, CRP and NEFA levels for prognosis of aged patients with ischemic stroke / 心血管康复医学杂志

Objective: To explore predictive value of homocysteine (Hcy), C reactive protein (CRP) and non-esterified fatty acid (NEFA) levels for prognosis of aged patients with ischemic stroke. Methods: Clinical data of 188 aged patients with ischemic stroke from our hospital were retrospectively analyzed. After three-month follow-up, patients were divided into good prognosis group (n=136) and poor prognosis group (n=52) according to their prognosis. Baseline data of two groups received single-factor and multi-factor Logistic regression analysis. ROC curve was drawn to evaluate the predictive value of Hcy, CRP and NEFA levels for prognosis of acute ischemic stroke. Results: Compared with good prognosis group, there were significant rise in percentages of hypertension, diabetes mellitus (DM) history, levels of fasting blood glucose (FBG), glycosylated hemoglobin A1c (HbA1c), Hcy, CRP and NEFA in poor prognosis group, P＜0. 01 all. Multi-factor Logistic regression analysis indicated that DM history, Hcy, CRP and NEFA were independent risk factors for prognosis of acute ischemic stroke (OR=3. 501～5. 270, P=0. 001 all). Area under the ROC curve (AUC) of Hcy predicting prognosis was 0. 830, the optimal cutoff value was 17. 950 with sensitivity=0. 615 and specificity=0. 882. AUC of CRP predicting prognosis was 0. 805, the optimal cutoff value was 1. 395 with sensitivity=0. 731 and specificity=0. 735. AUC of NEFA predicting prognosis was 0. 723, the optimal cutoff value was 0. 485 with sensitivity=0. 615 and specificity=0. 706. Conclusion: Homocysteine, C reactive protein and non-esterified fatty acid are independent risk factors for prognosis of acute ischemic stroke, which possess certain predictive value for prognosis of acute ischemic stroke.

Effect of ghrelin O-acyltransferase inhibition by small interfering RNA on hepatocyte fatty degeneration and related mechanism of action / 临床肝胆病杂志

Objective To investigate the effect of inhibition of ghrelin O-acyltransferase (GOAT) by small interfering RNA (siRNA) on hepatocyte fatty degeneration and related mechanism of action.Methods Human LO2 hepatocytes were treated with free fatty acid (FFA)to induce hepatocyte fatty degeneration.LO2 hepatocytes were treated with FFA and siRNA-GOAT alone or in combination and then divided into normal control (NC) group (treated with phosphate buffered saline alone),siRNA-GOAT group (treated with siRNA-GOAT at a final concentration of 10 nm),FFA group (treated with FFA at a final concentration of 1 mm),and FFA + siRNA-GOAT group (treated with FFA at a final concentration of 1 mm and siRNA-GOAT at a final concentration of 10 nm).Oil red O staining was performed for hepatocytes to identify lipid droplets;the triglyceride (TG) test kit was used to measure the lipid level in LO2 hepatocytes;Western blot,qRT-PCR,immunofluorescent staining,and electron microscopy were used to measure autophagy;ELISA and RT-PCR were used to measure the levels of tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6);ELISA was used to measure the changes in the levels of mammalian target of rapamycin (mTOR),phosphorylated mTOR (p-mTOR),AMP-activated protein kinase (AMPK),and phosphorylated AMPK.A one-way analysis of variance was used for comparison between multiple groups,and the least significant difference t-test was used for further comparison between any two groups.Results Compared with the FFA group,the FFA + siRNA-GOAT group had a significant reduction in the formation of lipid droplets and a significantly lower TG level (P ＜0.001).Compared with the FFA group,the FFA + siRNA-GOAT group had significant reductions in the protein and mRNA expression of TNFα and IL-6 (all P ＜ 0.005).The siRNA + GOAT group had significantly higher mRNA expression of LC3-Ⅱ and Beclin-1 than the NC group (all P ＜0.001).The FFA + siRNA-GOAT group had significantly higher mRNA expression of LC3-Ⅱ and Beclin-1 than the FFA group (all P ＜0.001).The siRNA + GOAT group had significantly higher protein expression of LC3-Ⅱ and Beclin-1 than the NC group (all P ＜ 0.05).The FFA + siRNA-GOAT group had significantly higher protein expression of LC3-Ⅱ and Beclin-1 than the FFA group (all P ＜ 0.05).Immunofluorescent staining showed that compared with the FFA group and the siRNA-GOAT group,the FFA + siRNA-GOAT group had a significant increase in the expression of endogenous LC3-Ⅱ in LO2 hepatocytes.Electron microscopy showed that compared with the FFA group,the FFA + siRNA-GOAT group had a significant increase in the expression of autophagosome.After the LO2 hepatocytes were treated by autophagy inhibitors siRNA-ATG5 and 3-MA or an autophagy stimulant,rapamycin,there was a significant difference in TG level between the FFA + siRNA-ATG5 group and the FFA + siRNA-GOAT group (P ＜ 0.001),as well as between the FFA + 3-MA group and the FFA + rapamycin group (P ＜ 0.001).The FFA + siRNA-GOAT group had a significantly higher level of LC3-Ⅰ/Ⅱ than the FFA + siRNA-ATG5 group (P ＜0.05),and the FFA + rapamycin group had a significantly higher level of LC3-Ⅰ/Ⅱ than the FFA + 3-MA group (P ＜ 0.05).Compared with the FFA group,the FFA + siRNA-GOAT group had significantly higher protein expression of p-AMPK (P ＜ 0.05) and significantly lower protein expression of p-rmTOR (P ＜ 0.05).Conclusion GOAT inhibition by siRNA can upregnlate autophagy and alleviate hepatocyte fatty degeneration,possibly by regulating the AMPK/mTOR pathway.

In Vitro Effect of Fatty Acids Identified in the Plasma of Obese Adolescents on the Function of Pancreatic β-Cells

BACKGROUND: The increase in circulating free fatty acid (FFA) levels is a major factor that induces malfunction in pancreatic β-cells. We evaluated the effect of FFAs reconstituted according to the profile of circulating fatty acids found in obese adolescents on the viability and function of the murine insulinoma cell line (mouse insulinoma [MIN6]). METHODS: From fatty acids obtained commercially, plasma-FFA profiles of three different youth populations were reconstituted: obese with metabolic syndrome; obese without metabolic syndrome; and normal weight without metabolic syndrome. MIN6 cells were treated for 24 or 48 hours with the three FFA profiles, and glucose-stimulated insulin secretion, cell viability, mitochondrial function and antioxidant activity were evaluated. RESULTS: The high FFA content and high polyunsaturated ω6/ω3 ratio, present in plasma of obese adolescents with metabolic syndrome had a toxic effect on MIN6 cell viability and function, increasing oxidative stress and decreasing glucose-dependent insulin secretion. CONCLUSION: These results could help to guide nutritional management of obese young individuals, encouraging the increase of ω-3-rich food consumption in order to reduce the likelihood of deterioration of β-cells and the possible development of type 2 diabetes mellitus.

Study on changes of ratio of serum NEFA/ALB in children with primary ne-phrotic syndrome / 中国免疫学杂志

Objective:To study on the changes of the ratio of serum NEFA/ALB in children with primary nephrotic syndrome , and to provide new indicators for the diagnosis and severity assessment of clinical PNS .Methods:The levels of serum albumin ( ALB) , free fatty acid (NEFA),urea nitrogen(BUN),uric acid(UA),creatinine(Scr),total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol ( LDL-C) ,high density lipoprotein cholesterol ( HDL-C) were quantitatively measured in 52 patients with PNS in acute stage ( acute stage group ) and 34 patients with PNS in complete remission ( remission stage group ) and 50 healthy children ( con-trol group).The lipid/lipoprotein and renal function parameters were also analyzed .Results: Compared with controls group ,the levels of serum ALB,HDL-C in acute group and remission group decreased significantly ( P<0.05 ) ,but the levels of serum NEFA/ALB,TC, TG,LDL-C,UA,BUN,Scr in acute group increased significantly ( P<0.05 ) ,the levels of serum TG ,LDL-C in acute group increased significantly (P<0.05).Compared with remission group,the levels of serum ALB in acute group decreased significantly (P<0.05), but the levels of serum NEFA/ALB,TC,TG,LDL-C,UA,BUN,Scr increased significantly (P<0.05).In PNS children,the ratio of NEFA to ALB was positively correlated with the levels of TC ,TG,LDL-C,UA,BUN (P<0.05),while negatively correlated with ALB (P<0.05).Multiple linear regression analysis showed that the ratio of NEFA to ALB had an independent association with BUN levels (β=0.045,t=1.602,P=0.003).Conclusion:In the development process of PNS disease ,serum ratio of NEFA to ALB increased in-dicates impaired kidney function or reduced kidney function ,and it can help doctor assess and judge the clinical condition .

Molecular mechanism of free fatty acids-induced insulin resistance / 解放军医学杂志

Insulin resistance (IR) is a complex metabolic disorder related to several diseases including type 2 diabetes (T2DM), hypertension and dyslipidemia. These diseases are all independent risk factors for cardiovascular disease. Lipid metabolism disorder has toxic effects on cells and may cause or aggravate IR in performance of elevated plasma levels of triglyceride (TG) and free fatty acids (FFA), the last one is an independent risk factor for IR. It has been clear that FFA may induce IR by endoplasmic reticulum (ER) stress, oxidative stress, apoptosis and inflammation, although the specific mechanisms remained unknown. The present paper summarizes the related molecules involved in the pathogenic process of IR and its mechanism, might provide a theoretical basis for the molecular mechanism of IR caused by FFA, and therapeutic reference for clinical treatment of IR and prevention of T2DM.

Investigation on reference interval of serum non-esterified fatty acid among population in Wuhan area / 国际检验医学杂志

Objective To preliminarily establish the reference interval of serum non‐esterified fatty acids(NEFA)among popula‐tion in Wuhan area by enzymatic assay .Methods NEFA level of serum samples from A total of 1 250 individuals undergoing healthy physical examination in our hospital were selected as the research subjects .The Olympus AU5400 biochemistry analyzer and SEKISUI reagents were adopted to detect serum NEFA level .The regression analysis was adopted to analyze the NEFA influencing factors .The NEFA 95% reference interval was estimated by using the normal distribution method and the reference interval was verified .Results The regression analysis showed that the body mass index (BMI)and age had significant effect on NEFA (P<0 .01) .NEFA was highest in the group aged ≥60 years old ,followed by the group of 18- <45 years old ,and lowest in the group of 45-60 years old ;NEFA was highest in the group of BMI<18 .5 kg/m2 .The 95% reference interval of NEFA for healthy popula‐tion in Wuhan area was estimated as 204 .6 -975 .2 μmol/L .The detected NEFA level for clinical verifiers was 242 .0 -831 .2μmol/L ,which conformed to the above reference interval .Conclusion The serum NEFA reference interval among healthy popula‐tion in Wuhan area is primarily established .

The influence of cholecystokinin-octopeptide on oxidative stess in islet beta cells injured by free fat acids / 重庆医学

Objective To observe the effect of cholecystokinin-octopeptide(CCK-8) on oxidative stress and cell proliferation in mice islet β cells (NIT-1 cells) injured by high concentration free fat acids .Methods In vitro cultured NIT-1 cells were divided into 3 groups ,they were control group ,FFAs group (add 0 .25 mmol/mL of oleinic acid + 0 .25 mmol/mL of palmic acid) and CCK-8 group (add FFAs and 1 × 10 - 8 mmol/L of CCK-8 simultaneously) .Cell morphologies were observed ;NIT-1 cells proliferations were detected by M TT method ,and apoptosis rates were measured by flow cytometry ;The levels of T-AOC ,GSH-Px ,CAT ,SOD and MDA in supernatant were also measured .Results There were less cell debris in CCK-8 group than FFAs group(all P< 0 .01) ;the OD570 value of CCK-8 group was significant higher than FFAs group(P< 0 .01) ,and the 72 h CCK-8 group was higher than 48 h CCK-8 group(P< 0 .01) .Compared with FFAs group ,the levels of CAT ,T-AOC ,SOD and GSH-Px in CCK-8 group were in-creased and the concentration of MDA was decreased obviously(P< 0 .05) ,the levels of CAT ,SOD in 72 h CCK-8 group were high-er than 48 h CCK-8 group ,MDA was lower than 48 h CCK-8 group(P< 0 .05) .Conclusion CCK-8 could protect islet β cells injury from FFAs through anti-oxidative stress mechanism and promote NIT-1 cells proliferation .

The levels and clinical value of serum free fatty acid in patients with ankylosin g spondylitis / 中华风湿病学杂志

Objective To study the association between serum free fatty acid (FFA) and ankylosing spondylitis (AS).Methods According to the classification criteria,a total of 90 newly diagnosed AS patients,223 healthy individuals and 82 patients with non-inflammatory diseases were divided into three groups,and biochemistry and immunology biomarks were measured in all individuals.One-Way analysis of variance (ANOVA) test was used to compare the difference between the three groups in the serum indexes,and Logistic regression analysis was used to identify AS risk factors associated with AS.Results There were no significant differences in gender,age,body mass index (BMI),white blood cells (WBC),high-level data link control (HDL-C),low-density lipoprotein control (LDL-C),lipoproteins [Lp (a)],alkaline phosphatase (ALP) and TG in the three groups,and our results showed that serum FFA was statistical different between the three groups (F=24.191,P＜0.01),the serum level of FFA in patients with AS was higher compared with patients with noninflammatory diseases and healthy controls [(0.48 ±0.18) mmol/L,(0.28 ±0.09) mmol/L,(0.29±0.16) mmol/L;t=-5.969,P＜0.01;t=5.106,P＜0.01].Seral IgA,IgG,IgM levels,ESR and CRP were statistically different between the three groups (F=14.870,P＜0.01;F=16.464,P＜0.01;F=4.124,P=0.018;F=97.002,P＜0.01;F=22.069,P＜0.01).Gender,age,BMI,serum IgA,IgM,ALP,HDL-C,LDL-C,Lp(a) and TG levels were not associated with AS by logistic regression analysis.However,serum IgG level,ESR and CRP were associated with AS [OR05％CI):1.659(1.032,2.660),P=0.037;OR05％CI):1.340(1.005,1.787),P=0.046;OR05％CI):1.820 (1.025,3.232),P=0.041],and there is an association between FFA and AS was observed in logistic regression analysis (OR=1.132,95％CI:1.014-1.421,P=0.033).Conclusion We suggest that incre-ased FFA is closely associated with AS,and may be an underlying risk factor for AS.

The effect of therapeutic life style on serum FFA and constitution index in patients with coronary heart disease complicated metabolic syndrome / 重庆医学

Objective To investigate the level of serum free fatty acid (FFA )after improving the life style in patients with coronary heart disease complicated metabolic syndrome and the effect of therapeutic life style on traditional risk factors of coronary artery disease.Methods A total of 395 patients with coronary heart disease complicated metabolic syndrome were recruited.Pa-tients were divided into intervention group (group A,conventional drug therapy+ intensive life style intervention,n=97)and non-intervention group (group B,conventional drug therapy,n=38)according to the scores of life style.Serum free fatty acid (FFA) was determined by ELASA.The scores of life style was obtained bylife style questionnaire.Results (1)The serum FFA of pa-tients with coronary heart disease complicated metabolic syndrome were positively related to waist circumference and waist-high-ra-tio.(2)Waist circumference,BMI and FFA of group A were significantly lower than those in group B after therapeutic life style in-tervention(P <0.05).(3)Compared with the baseline,the constitution index and FFA in group A were significantly lower after 6-months therapeutic life style intervention(P <0.05).Conclusion Therapeutic life style can reduce the level of FFA and constitution index of the patients with coronary heart disease complicated metabolic syndrome.

The changes of LCHAD in preeclampsia with different clinical features and the correlation with NADPH P47-phox, p38MAPK- α, COX-2 and serum FFA and TG / 中华妇产科杂志

Objective To investigate the changes of fatty acid oxidase in the placenta of preeclampsia cases with different clinical features, and the relationship with oxidative stress and inflammatory response. To study the correlation of serum free fatty acid (FFA) and triglycerides (TG) level in early second trimester with the molecular changes of the long-chain fatty acid oxidase in the third trimester. Methods This was prospective cohort study, in which cases with singleton pregnancies who archived in Haidian Maternal and Children′s Hospital, Beijing, from January 1st 2012 to May 31st, with regular prenatal care were included. Doppler ultrasound was used for screening for the presence of early diastolic notch of uterine artery at 22-24 weeks of gestation. All the 101 cases with the early diastolic notch of uterine artery were included as the notch group, and 377 cases without the early diastolic notch of uterine artery were included as the non-notch group. The perinatal outcomes and the incidence of hypertensive disorders in pregnancy of the two groups were observed. The serum level of FFA and TG was tested, and the mRNA and protein expression of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD), P47-phox subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, p38 mitogen-activated protein kinase α (p38MAPK-α) and cyclooxygenase-2 (COX-2) were detected using real-time quantitative PCR and western blot. The relationship between serum level of FFA and TG and the mRNA and protein expression of LCHAD, NADPH P47-phox,p38MAPK-α and COX-2 of the placental tissue specimens were analyzed. Results (1) In the notch group, there were 9 cases of early-onset preeclampsia,15 cases of late-onset preeclampsia and 10 cases of gestational hypertension;and there were 8 cases of late-onset preeclampsia and 18 cases of gestational hypertension in the non-notch group. 15 cases with normal blood pressure in each group were randomly selected as the control group.(2)The serum level of TG of cases of early-onset preeclampsia, late-onset preeclampsia and gestational hypertension in the notch group were(2.0±0.8),(1.8±0.6)and (1.9±0.7)mmol/L, and that of FFA were(0.68±0.26),(0.52±0.10)and(0.52±0.17)mmol/L, respectively. The serum level of TG of cases of late-onset preeclampsia and gestational hypertension in the non-notch group were(1.6±0.6)and(1.4±0.4)mmol/L, and that of FFA were(0.49±0.11)and(0.48±0.05)mmol/L, respectively. The serum level of TG and FFA in the control group were(1.4±0.5)and(0.52±0.06)mmol/L, respectively. The TG level of the notch group was higher than that of the control group, and the difference was statistically significant (P 0.05).(6)The mRNA expression of placental LCHAD in the early-onset preeclampsia in the notch group was significantly negatively correlated with the mRNA expression of placental NADPH P47-phox and COX-2 (r=- 0.877,-0.762, P<0.05). The mRNA expression of placental LCHAD in the control group was significantly negatively correlated with the mRNA expression of placental COX-2 (r=- 0.565, P<0.01). The protein expression of placental LCHAD in the early-onset preeclampsia in the notch group was significantly negatively correlated with the protein expression of NADPH P47-phox (r=- 0.818, P<0.01). The protein expression of placental LCHAD in the control group was significantly negatively correlated with the protein expression of COX-2 (r=- 0.502,P<0.01). Conclusions The placental mRNA and protein expression of long-chain fatty acid oxidation enzymes were different in different clinical features of preeclampsia, which were reduced more obviously in the early-onset preeclampsia in the notch group than that of the late-onset preeclampsia in the notch group, and were negatively correlated with the elevated serum FFA level, significantly enhanced oxidative stress and inflammatory response, but with no correlation with serum TG level.

Effects of supplementation with omega-3 on insulin sensitivity and non-esterified free fatty acid (NEFA) in type 2 diabetic patients / Efeito da suplementação com ômega-3 sobre a sensibilidade à insulina e aos ácidos graxos livres não esterificados (AGNE) em pacientes com diabetes tipo 2

Objective: The aim of this study was to determine the role of omega-3 supplementation on NEFA concentration, insulin sensitivity and resistance, and glucose and lipid metabolism in type 2 diabetic patients. Subjects and methods: Forty-four type 2 diabetic patients were randomly recruited into two groups. Group A received 4 g/day omega-3 soft gels, and group B received a placebo for 10 wks. Blood samples were collected after 12-h fast. Physical activity records, three-day food records, and anthropometric measurements were obtained from all participants at the beginning and end of the study. Results: Omega-3 supplementation caused a significant reduction in NEFA in the intervention group compared with the placebo group (P = 0.009). Additionally, the administration of omega-3 resulted in significantly greater changes (Diff) for the intervention group in various parameters, such as insulin and Quicki indices compared with the placebo group (P < 0.05). Conclusions: Omega-3 fatty acid supplementation in type 2 diabetic patients improved insulin sensitivity, probably due to the decrease in NEFA concentrations. Arq Bras Endocrinol Metab. 2014;58(4):335-40 .

Objetivo: O objetivo deste estudo foi analisar o papel da suplementação com ácidos graxos ômega-3 sobre a concentração de ácidos graxos não esterificados (AGNE), resistência e sensibilidade à insulina e metabolismo de lipídios em pacientes com diabetes melito tipo 2. Sujeitos e métodos: Quarenta e quatro pacientes com diabetes tipo 2 foram recrutados aleatoriamente e alocados em um de dois grupos. O Grupo A recebeu 4 g/dia de ômega-3 na forma de cápsulas gelatinosas e o grupo B recebeu placebo durante 10 semanas. Amostras de sangue foram coletadas após 12 horas de jejum. Registros da atividade física, da dieta de três dias e medidas antropométricas foram obtidos de todos os participantes no início e no final do estudo. Resultados: A suplementação com ômega-3 causou uma redução significativa na AGNE em comparação com grupo placebo (P = 0,008). Além disso, a administração de ômega-3 resultou em alterações significativamente maiores (Dif) em vários parâmetros, tais como a insulina, HOMA-IR e QUICKI, comparando com placebo (P < 0,05). Conclusões: A suplementação com ácidos graxos ômega-3 em pacientes diabéticos tipo 2 melhorou a sensibilidade à insulina, provavelmente devido à diminuição da concentração de AGNE. Arq Bras Endocrinol Metab. 2014;58(4):335-40 .

The tryptophan utilization concept in pregnancy

The decrease in maternal plasma total (free + albumin-bound) tryptophan (Trp) during the third pregnancy trimester is attributed to induction of indoleamine 2,3-dioxygenase (IDO). When measured, free [Trp] is increased because of albumin depletion and non-esterified fatty acid elevation. The Trp depletion concept in pregnancy is therefore not supported because of incorrect interpretation of changes in Trp disposition and also for not addressing mouse strain differences in Trp-related responses and potential inhibition of Trp transport by the IDO inhibitor 1-methyl tryptophan. Application of the Trp utilization concept in pregnancy offers several physiological advantages favoring fetal development and successful outcome, namely provision of Trp for fetal protein synthesis and growth, serotonin for signaling pathways, kynurenic acid for neuroprotection, quinolinic acid for NAD+ synthesis, and other kynurenines for suppression of T cell responses. An excessive increase in Trp availability could compromise pregnancy by undermining T cell suppression, e.g., in pre-eclampsia.

Plasma free fatty acids composition and its association with nonalcoholic fatty liver disease / 重庆医学

Objective To study the relationship between plasma free fatty acids composition and the incidence of nonalcoholic fatty liver disease(NAFLD) .Methods By the design of case‐control study ,105 patients with NAFLD as cases and 110 healthy peo‐ple as controls were enrolled into the study .Plasma free fatty acid levels were determined by gas chromatography .Results High level of plasma palmitic acid(C16 :0)(OR=1 .769) was the risk factors of NAFLD ,while plasma levels of linoleic acid(C18 :2 n‐6) (OR=0 .855) and arachidonic acid(C20 :4 n‐6)(OR=0 .181)were negatively associated with the incidence of NAFLD .Conclusion These findings suggest that a proper ratio of diet fatty acids intake may reduce the risk of NAFLD .

Establishment and Application of Hyperinsulinemic-Euglycemic Clamp Technique in Conscious Rats / 天津医药

Objective To establish the hyperinsulinemic-euglycemic clamp(HEC) technique in conscious rats, and to explore the effect of acute infusion of lipid on glucose infusion rate (GIR) in rats. Methods Ten SD rats were random-ly divided into two groups, 5 rats for each group. The right jugular vein and left carotid artery were catheterized and under-went a HEC with infusion of lipid (intralipid group) for 6 hours, and with continuing infusion of 5%glucose (control group). The plasma levels of free fatty acid(FFA) and GIR were measured by HEC method. Results The level of FFA concentration increased by 17.6-fold, and GIR was reduced by 27%in the intralipid group compared to those of control group (P＜0.001). Conclusion The rat model of HEC has been successfully established by intravenous intralipid infusion, which can be con-firmed by HEC technique.

The Correlation Analysis of CHGA and ATGL in Patients of Type 2 Diabetes Mellitus with Nonalcoholic Fatty Liver Disease / 天津医药

Objective To investigate the relationship between plasma levels of chromogranin A (CHGA) and adi-pose triglyceride lipase (ATGL) in patients with type 2 diabetes (T2DM) combined non-alcoholic fatty liver disease (NAFLD). Methods The plasma levels of CHGA and ATGL were assayed by enzyme-linked immunosorbent assay (ELISA) in T2DM patients with NAFLD (group A, n=74), T2DM without NAFLD (group B, n=76), and normal group (group NC, n=75). The correlation between CHGA, ATGL and other metabolic index was analyzed. Results The plasma level of CHGA was significantly higher in group A (83.15±9.46) and group B (70.90±2.75) than that of group NC (46.74±8.15, P<0.01), and the level of CHGA was significantly higher in group A than that of group B (P<0.01). The plasma level of ATGL was sig-nificantly lower in group A (21.36±13.42) and group B (40.29±22.83) than that of group NC (72.30±26.41, P<0.01), and the level was lower in group A than that of group B (P<0.01). There was a negative correlation between the plasma CHGA, AT-GL and carbohydrate oxidation rate in group A. There was a positive correlation between fasting insulin (FINS), insulin resis-tance index (HOMA-IR), free fatty acid (FFA) and fat oxidation rate in group A. There was a negative correlation between plasma level ATGL and body mass index (BMI), FINS, cholesterol (TC), triglyceride (TG) and HOMA-IR, meanwhile, it was positively correlated with FFA. The multiple stepwise regression analysis showed that FINS, ATGL and FFA were indepen-dent variables for CHGA. The Logistic regression analysis showed that plasma levels of CHGA, ATGL and FFA were the in-dependent predictors of T2DM with NAFLD. Conclusion The plasma levels of CHGA and ATGL are closely correlated with substance and energy metabolism, and the interaction between them may play an important role in the pathogenesis of T2DM with NAFLD .

Correlation of free fatty acid and blood lipids in early second trimester and uterine artery notch in pre-eclampsia / 中华围产医学杂志

Objective To analyze the heterogeneous variation of serum free fatty acid (FFA) and lipids during early second trimester in women with or without uterine artery notch in pre-eclampsia (PE).Methods This is a prospective cohort study of 4 000 women with singleton pregnancies registered in early pregnancy and in whom regular check-ups were performed in Haidian Maternal & Child Health Hospital.Blood specimens were collected at gestational age 14-18 weeks at the same time of screening for Down's syndrome.One hundred and one cases with early diastolic notch of the uterine artery were included in the N+ group,and 172 cases without notch but at high risk of PE were included in the N-group at 22-24 weeks.In addition,205 women who were selected randomly at a ratio of 1 ∶ 5,without notch or PE high-risk factors,were also included in the N group.Both groups were subgrouped according to the outcomes of pregnancy complications:early-onset PE group EPE,late-onset PE (LPE),gestational hypertension (GH) group,gestational diabetes mellitus (GDM) group with normal blood pressure,and no complications (NC) group.The variation in FFA and other lipid metabolism indicators in the PE subgroups were compared and analyzed by two independent-sample t-test,one-factor analysis of variance,Chi-square test (or Fisher's exact) and Logistic regression.Results History of PE and pre-hypertension at first visit differed significantly between the N+ and N-groups [3.9％ (4/101) vs.0.8％ (3/377),x2=5.52,P＜0.05; pre-hypertension at first visit,42.2％ (43/101) vs.25.7％ (97/377),x2=10.91,P＜0.05].In the N+ group,23.8％ (n=24) of women had PE,of which 37.5％ (n=8) were early onset.In the N group,2.1％ (n=8) had PE,and all were late onset.The incidence of PE differed significantly between the N+ and N-groups (x2=59.72,P＜0.05).In the N+ group,FFA gradually decreased among the ePE,IPE,GH and NC groups [(0.68±0.27),(0.58±0.21),(0.57±0.21) and (0.49±0.19) mmol/L,F=2.78,P＜0.05]; Multivariate regression analysis showed that FFA (OR=135.68,95％CI:3.78-4 873.00) and PE history (OR=123.25,95％CI:9.27-i 638.00) were risk factors of ePE.Pre-hypertension at registration (OR=4.69,95％CI:2.08-10.58) and pre-pregnancy body mass index (BMI) 24-28 (OR=3.69,95％CI:1.26-10.83) were risk factors ofGH.FFA (OR=9.08,95％CI:2.49-33.01) and pre-pregnancy BMI ≥ 28 (OR=5.08,95％CI:2.16-11.92) were risk factors for GDM.Conclusions Serum FFA and TG levels in early second trimester are correlated with PE,especially the early-onset PE.The onset of PE is heterogeneous and affected by many factors,and occurs in patients with or without early diastolic notch of the uterine artery in the second trimester.Patients with notch are more likely to have early-onset PE,which is correlated with blood FFA and TG levels.

Effects of Puerarin on Glucose, Lipid Metabolism and Gastric Motility in Early Period Type 2 Diabetic Rats / 中国中医药信息杂志

Objective To investigate the effects of Puerarin on glucose and lipid metabolism and gastric motility in early period type 2 diabetic (T2DM) rats.Methods Rat model of T2DM was established by high fat-sugar diet fed and low-dose streptozotocin-treated. SD rats were divided randomly into normal control group (NC), normal+Puerarin group (NP), diabetes control group (DC) and diabetes+Puerarin group (DP). NP and DP rats were given Puerarin 400 mg/(kg?d) once per day for 5 weeks, NC and DC rats were given PBS. Half time of gastric emptying and emptying rate were evaluated by SPECT. The serum level of FBG, GSP, FFA, TC, TG and INS were measured by kit.Results Compared with NC group, DC rats had higher FBG, FFA, TC, GSP, TG and emptying rate, but INS and half time of gastric emptying decreased significantly (P<0.05,P<0.01). Compared with DC group, TG, GSP, FFA and emptying rate of DP rats were reduced (P<0.05), but had more half time of gastric emptying (P<0.05). The results of multivariate stepwise regression analysis showed that FBG related to half time of gastric emptying.Conclusion Type 2 diabetic rats have faster gastric motility, higher blood glucose and lipid. Puerarin might improve the disorders of GSP, TG, FFA and gastric emptying in diabetic rats.