Lipid and liver abnormalities in haemoglobin A1c-defined prediabetes and type 2 diabetes

Background and aimsWe aimed to investigate lipid abnormalities and liver steatosis in patients with HbA1c-defined prediabetes and type 2 diabetes compared to individuals with HbA1c-defined normoglycaemia.Methods and resultsNinety-one subjects with prediabetes according to HbA1c, i.e. from 5.7 to 6.4% (39–46 mmol/mol), 50 newly diagnosed patients with HbA1c-defined type 2 diabetes (HbA1c ≥6.5% [≥48 mmol/mol]), and 67 controls with HbA1c lower than 5.7% (<39 mmol/mol), were studied. Fasting blood samples for lipid profiles, fatty liver index (FLI), bioimpedance analysis, ultrasound scan of the liver, and BARD (body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes) score for evaluation of liver fibrosis, were performed in all subjects. In comparison to controls, subjects with prediabetes were characterised by: lower apolipoprotein AI and HDL cholesterol levels, higher blood pressure, triglycerides levels and apolipoprotein B/apolipoprotein AI ratio, higher FLI, increased prevalence of and more severe hepatic steatosis, similar BARD score, and higher total body fat mass. In comparison to subjects with diabetes, subjects with prediabetes exhibited: similar blood pressure and apolipoprotein B/apolipoprotein AI ratio, similar FLI, reduced prevalence of and less severe hepatic steatosis, lower BARD score, increased percent fat and lower total body muscle mass. In comparison to controls, subjects with diabetes showed: lower apolipoprotein AI and HDL cholesterol levels, higher blood pressure and triglycerides levels, higher FLI, increased prevalence of and more severe hepatic steatosis, higher BARD score, and higher total body muscle mass. Moreover, HbA1c was correlated with BMI, HOMA-IR, triglycerides, HDL cholesterol, AST, and ALT.ConclusionsSubjects with HbA1c-defined prediabetes and type 2 diabetes, respectively, are characterised by abnormalities in lipid profile and liver steatosis, thus exhibiting a severe risk profile for cardiovascular and liver diseases.     

Alanine aminotransferase levels and fatty liver in childhood obesity: associations with insulin resistance, adiponectin, and visceral fat

BACKGROUND: Concurrent with the rise in obesity, nonalcoholic fatty liver disease is recognized as the leading cause of serum aminotransferase elevations in obese youth. Nevertheless, the complete metabolic phenotype associated with abnormalities in biomarkers of liver injury and intrahepatic fat accumulation remains to be established. METHODS: In a multiethnic cohort of 392 obese adolescents, alanine aminotransferase (ALT) levels were related with parameters of insulin sensitivity, glucose, and lipid metabolism as well as adipocytokines and biomarkers of inflammation. A subset of 72 adolescents had determination of abdominal fat partitioning and intrahepatic fat accumulation using magnetic resonance imaging. FINDINGS: Elevated ALT (> 35 U/liter) was found in 14% of adolescents, with a predominance of male gender and white/Hispanic race/ethnicity. After adjusting for potential confounders, rising ALT was associated with reduced insulin sensitivity and glucose tolerance as well as rising free fatty acids and triglycerides. Worsening of glucose and lipid metabolism was already evident as ALT levels rose into the upper half of the normal range (18-35 U/liter). When hepatic fat fraction was assessed using fast magnetic resonance imaging, 32% of subjects had an increased hepatic fat fraction, which was associated with decreased insulin sensitivity and adiponectin, and increased triglycerides, visceral fat, and deep to superficial sc fat ratio. The prevalence of the metabolic syndrome was significantly greater in those with fatty liver. INTERPRETATION: Deterioration in glucose and lipid metabolism is associated even with modest ALT elevations. Hepatic fat accumulation in childhood obesity is strongly associated with the triad of insulin resistance, increased visceral fat, and hypoadiponectinemia. Hence, hepatic steatosis may be a core feature of the metabolic syndrome.     

Liver steatosis in juvenile obesity: correlations with lipid profile, hepatic biochemical parameters and glycemic and insulinemic responses to an oral glucose tolerance test

OBJECTIVE: The aim of this study was to evaluate liver steatosis in prepubertal and pubertal obese and the correlations with the lipid profile, the serum levels of hepatic parameters and the glycemic and insulinemic responses to an oral glucose tolerance test. SUBJECTS: 375 obese, 205 males and 170 females, Tanner pubertal stage I (n=82), stages II-III (n=80) and stages IV-V (n=213). MEASUREMENTS: Body mass index (BMI), waist-hip ratio (WHR), total cholesterol and high density lipoprotein (HDL), cholesterol/HDL ratio, low density lipoprotein (LDL), very low density lipoprotein (VLDL), triglycerides (TGL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gGT, glycemia (G), insulinemia (IRI), fasting IRI/G ratio (FIGR), glycemic (mean blood glucose, MBG) and insulinemic (mean serum insulin, MSI) responses during a 120 min oral glucose tolerance test (OGTT), expressed as area under the curve (AUC)/120 min, pancreatic insulinemic response to glucose (IRG), and liver ultrasound scanning for assessing the degree of steatosis (moderate, severe). RESULTS: Liver steatosis was found in 33% of subjects in Tanner pubertal stage I, 36% in stage II-III and 47% in stages IV-V. BMI and transaminases were correlated with the degree of steatosis in all pubertal stages. AST, ALT and gGT were higher in the presence of steatosis, while elevated TGL was present in late puberty only; however the increase of ALT is specific for steatosis. CONCLUSION: Juvenile obesity involves a high risk of liver steatosis associated with alterations of transaminases and lipid but not glucose metabolism. These changes are apparent even to the prepubertal stage.     

Addition of rosiglitazone to glimepirid and metformin combination therapy in type 2 diabetes

The study was planned to determine the efficacy and safety of adding rosiglitazone to a combination of glimepiride and metformin therapy with insufficiently controlled type 2 diabetes. This was an open-label study with a follow-up period of 26 weeks. Thirty patients were taking 3 mg glimepiride two times and 850 mg metformin two times per day. Patients were told to take one rosiglitazone 4 mg tablet before breakfast additionally. The primary efficacy measure was the mean change in HbA1c from baseline to the end of the study. Secondary efficacy parameters included the mean changes from baseline to the end of the study in fasting plasma glucose (FPG) and insulin levels, as well as total cholesterol, HDL-C, LDL-C, triglycerides, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Mean HbA1c levels decreased significantly from 7.54 +/- 0.9% to 6.57 +/- 0.7% (p < 0.001) at 26th week. FPG levels fell from 169.39 +/- 37.8 mg/dl to 135.69 +/- 28.0 mg/dl (p < 0.001), respectively. Insulin levels decreased from 19.60 +/- 9.8 U/L to 14.66 +/- 11.6 U/L (p = 0.026) at 26th week. No one experienced elevations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels greater than 2.5 times the upper limit of the reference range. This study confirms that the addition of rosiglitazone (4 mg/day) to sulphonylurea and metformin treatment for patients with type 2 diabetes improves glycemic control, is safe, and generally well tolerated.     

Glucose intolerance and serum aminotransferase activities in Japanese men

BACKGROUND/AIMS: Elevated activities of serum aminotransferase are commonly observed in patients with diabetes mellitus. Few studies have addressed the relation between glucose intolerance and serum activities of aminotransferase in free-living populations. METHODS: Using a 75 g oral glucose tolerance test, we examined the association of impaired fasting glycemia (IFG), impaired glucose tolerance (IGT), and type 2 diabetes mellitus with serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT) among 4621 men aged 49-59 years of the Japan Self-Defense Forces. Statistical adjustment was made for body mass index, waist-hip ratio, and other possible confounding factors. RESULTS: Proportions of an elevated ALT (>50 IU/l) in men with normal glucose tolerance, IFG, IGT, and newly diagnosed diabetes mellitus were 3.5%, 9.5%, 7.7%, and 18.0%, respectively. Adjusted odds ratios of an elevated ALT for IFG, IGT, and newly diagnosed diabetes mellitus were 2.2 (95% confidence interval 1.1-4.3), 1.7 (1.2-2.4), and 4.4 (3.0-6.6), respectively. IGT and diabetes mellitus were also significantly positively associated with elevated AST (>40 IU/l) and GGT (>50 IU/l). CONCLUSIONS: Glucose intolerance is associated with elevated serum aminotransferase independent of obesity, but even a mildly elevated ALT is relatively uncommon in free-living men with glucose intolerance.     

A comparison of associations of alanine aminotransferase and gamma-glutamyltransferase with fasting glucose, fasting insulin, and glycated hemoglobin in women with and without diabetes

Associations between biomarkers of nonalcoholic fatty liver disease (NAFLD) alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT), with 3 separate measures of glucose homeostasis: fasting glucose, fasting insulin and glycated hemoglobin (HbA1c) were studied and compared between women with and without diabetes in order to gain insight into the documented associations between NAFLD, insulin resistance and diabetes. Data from the British Women's Health and Heart Study, a random sample of British women aged 60-79 years (N = 3394; 3086 without diabetes and 308 with diabetes) was used. Associations of ALT and GGT with fasting glucose and HbA1c and of ALT with fasting insulin (and homeostasis model assessment of insulin resistance [HOMA]) are stronger in women with diabetes compared to women without diabetes (P for interaction < 0.001). GGT is associated with fasting insulin (and HOMA) to the same extent in all women, irrespective of diabetes status. Results excluding hyperinsulinemic women, i.e., in the highest fourth of the fasting insulin distribution, were similar to those obtained for all non-diabetic women as were results excluding women in the highest quartile of the alcohol consumption distribution and for women with ALT and GGT levels within the normal range. Associations did not differ substantially between obese and non-obese non-diabetic women. CONCLUSION: elevation of liver enzymes and hepatic insulin resistance as reflected by fasting insulin occur in the early stages of insulin resistance and highlight the central role of the liver in insulin resistance in the general population.     

Efficacy and safety in sitagliptin therapy for diabetes complicated by chronic liver disease caused by hepatitis C virus

Aim: Diabetes is present in patients with chronic liver disease caused by hepatitis C virus (HCV). The aim of this case–control study is to assess the efficacy and safety of dipeptidyl peptidase‐4 inhibitor (sitagliptin) for type 2 diabetes mellitus (T2DM) with chronic liver disease caused by HCV. Methods: Sixteen HCV positive patients with T2DM treated by sitagliptin were retrospectively enrolled. These patients were given sitagliptin between December 2009 and January 2010. Another 16 HCV patients with T2DM treated only with diet and excise for 48 weeks were selected as the control group. Serum levels of fasting plasma glucose (FPG), hemoglobin A1C (HbA1C), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured before and 12, 24, 36 and 48 weeks after the initiation of treatment. Results: In the sitagliptin group, the average HbA1C level decreased approximately 0.8% at 48 weeks after the initiation of sitagliptin. Next, the average FPG level decreased approximately 20 mg/dL during follow up after the initiation of sitagliptin. All the patients were able to take sitagliptin of 50 mg/day without reduction because of sitagliptin‐related side‐effects. On the other hand, in the control group, the average HbA1C and FPG level did not change with statistical significance during follow up of 48 weeks. Regarding aminotransferase, there were no significant changes of average AST and ALT level during follow up of 48 weeks in both the sitagliptin group and control group. Conclusion: Our results indicate that sitagliptin is effective and safe for the treatment of T2DM complicated with HCV positive chronic liver disease.     

Prevalence of non-alcoholic fatty liver disease and its association with impaired glucose metabolism in Japanese adults.

AIMS: To assess the prevalence of non-alcoholic fatty liver disease (NAFLD) and its association with impaired glucose metabolism in Japanese subjects. METHODS: One thousand, nine hundred and fifty subjects enrolled in a general health examination programme from September 2002 to February 2003 were recruited. NAFLD was diagnosed if a person showed 'fatty liver' on ultrasonography, and his/her alcohol consumption, estimated by questionnaire, was < 40 gram/week. A general linear model was used for the comparison of estimated means of metabolic variables adjusted for age and body mass index (BMI) between subjects with NAFLD and those without fatty liver. Multivariate regression with fasting plasma glucose (FPG) as the dependent variable was performed in 1547 non-diabetic individuals after adjusting for age, gender, BMI and NAFLD. RESULTS: NAFLD was found in 566 of the 1950 health-check examinees (29%). Its prevalence increased with increasing FPG levels: 27% in the subgroup with normal fasting glucose, 43% in impaired fasting glucose and 62% in newly diagnosed diabetes. Adjusted means of FPG, HbA1c, triglyceride, total protein, albumin, AST and ALT were all significantly higher, while adjusted means of HDL cholesterol and AST/ALT ratio were significantly lower in subjects with NAFLD than those without fatty liver. Multivariate regression analysis showed that NAFLD was independently associated with increasing FPG in non-diabetic individuals. CONCLUSIONS: The prevalence of NAFLD was 29% in apparently healthy middle-aged Japanese adults and NAFLD was independently associated with impaired glucose metabolism.     

Ezetimibe decreases SREBP-1c expression in liver and reverses hepatic insulin resistance in mice fed a high-fat diet

Ezetimibe inhibits intestinal cholesterol absorption, thereby reducing serum cholesterol. Recent studies suggest that ezetimibe affects liver steatosis and insulin resistance. We investigated the impact of ezetimibe on insulin sensitivity and glucose metabolism in C57BL/6 mice. We analyzed 4 mouse groups fed the following diets: normal chow (4% fat) for 12 weeks, normal chow for 10 weeks followed by normal chow plus ezetimibe for 2 weeks, high-fat chow (32% fat) for 12 weeks, and high-fat chow for 10 weeks followed by high-fat chow plus ezetimibe for 2 weeks. In the normal chow + ezetimibe group, ezetimibe had no impact on body weight, fat mass, lipid metabolism, liver steatosis, glucose tolerance, or insulin sensitivity. In the high-fat chow + ezetimibe group, ezetimibe had no impact on body weight or fat mass but significantly decreased serum low-density lipoprotein cholesterol, triglyceride, and glutamate pyruvate transaminase levels; liver weight; hepatic triglyceride content; and hepatic cholesterol content and increased the hepatic total bile acid content. In association with increases in IRS-2 and Akt phosphorylation, ezetimibe ameliorated hepatic insulin resistance in the high-fat chow + ezetimibe group, but had no effect on insulin sensitivity in primary cultured hepatocytes. A DNA microarray and Taqman polymerase chain reaction revealed that ezetimibe up-regulated hepatic SREBP2 and SHP expression and down-regulated hepatic SREBP-1c expression. SHP silencing mainly in the liver worsened insulin resistance, and ezetimibe protected against insulin resistance induced by down-regulation of SHP. Ezetimibe down-regulated SREBP-1c in the liver and reversed hepatic insulin resistance in mice fed a high-fat diet.     

The role of the plasma glycosylated hemoglobin A1c/Apolipoprotein A-l ratio in predicting cardiovascular outcomes in acute coronary syndrome

Background and aimsGlucose and lipid metabolism are major prognostic indicators of coronary heart disease. The ratio of plasma glycosylated hemoglobin A1c (HbA1c) to apolipoprotein A-l (ApoA-l) is an indirect measure of insulin resistance. The study aimed to evaluate whether the HbA1c/ApoA-1 ratio can predict the prognosis in patients with the acute coronary syndrome (ACS).Methods and resultsA total of 476 ACS patients diagnosed by coronary angiography were enrolled in this longitudinal, observational, retrospective study. Plasma HbA1c, fasting blood glucose and lipid profile were measured. Patients were stratified according to the tertiles of HbA1c/ApoA-l levels. Cox proportional hazard model was used to examine the predictive value of HbA1c/ApoA-l for study endpoints. The association between the Log HbA1c/ApoA-l ratio and major adverse cardiovascular events (MACEs) was estimated using multiple logistic regression. Baseline characteristics showed a mean age of 66 ± 8 years, and 52.5% were hypertensive, 26.8% diabetic, and 54.5% current or prior smokers. During a mean follow-up period of 22.3 ± 1.7 months, 59 deaths occurred. After adjusting for age, gender, smoking, hypertension, diabetes, and coronary artery disease severity, patients in the highest HbA1c/ApoA-l ratio tertile had a 4.36-fold increased risk of mortality compared with those in the lowest tertile. The multivariate logistic regression showed that the Log HbA1c/ApoA-l ratio was associated with MACEs (Odds ratio 2.95, p = 0.013).ConclusionAfter adjusting for traditional cardiovascular risk factors and ACS severity scores, the HbA1c/ApoA-1 ratio remained an independent predictor of all-cause mortality and MACEs in the ACS patients undergoing angiography.     

Clinical presentation of chronic hepatitis C in patients with end-stage renal disease and on hemodialysis versus those with normal renal function

BACKGROUND: The natural history of chronic hepatitis C (CHC) remains to be defined in patients with end-stage renal disease (ESRD). AIMS: To determine the clinical presentation of CHC and the factors associated with stage III-IV fibrosis in patients with CHC and ESRD. METHODS: The study included patients with CHC and ESRD (n = 91) or normal renal function (NRF, n = 159). Both groups were matched for mean age, gender, history of alcohol use, and estimated duration of hepatitis C virus (HCV) infection. RESULTS: Presentation of CHC and ESRD was independently associated with non-Caucasian ethnicity (OR = 3.24, p= 0.0003), a history of diabetes mellitus (DM, OR = 7.911, p < 0.0001), and lower frequencies of being obese (OR = 0.457, p= 0.035), of having hepatic steatosis (OR = 0.372, p= 0.003), and stage III-IV fibrosis (OR = 0.403, p= 0.016). After adjusting for serum levels of alpha-fetoprotein (AFP) and HCV RNA, CHC, and ESRD were independently associated with lower frequencies of elevated alanine aminotransferase (ALT, OR = 0.175, p= 0.02) and aspartate aminotransferase (AST, OR = 0.169, p= 0.04), but higher frequencies of AST/ALT ratio >1 (OR = 7.173, p= 0.002) and hypoalbuminemia (OR = 9.567, p= 0.0007). Compared to patients with NRF and stage III-IV fibrosis, those with ESRD and stage III-IV fibrosis had a significantly higher frequency of a history of DM (OR = 8.014, p= 0.0031) and lower frequency of elevated AST (OR = 0.054, p= 0.004), which were independent of the frequencies of lower levels of ALT and albumin, and AST/ALT ratio >1. In patients with CHC and ESRD, the presence of stage III-IV fibrosis was significantly associated with hepatic steatosis (OR = 4.523, p= 0.012) and thrombocytopenia (OR = 4.884, p= 0.044), which were independent of the frequencies of a history of DM, splenomegaly, and a higher level of AST. CONCLUSIONS: CHC and ESRD are independently associated with a higher frequency of a history of DM, but lower frequencies of being obese, and having hepatic steatosis, stage III-IV fibrosis, and elevated transaminases. In patients with CHC and ESRD, stage III-IV fibrosis is not associated with a history of DM, but is independently associated with hepatic steatosis and thrombocytopenia.     

The association between AST/ALT ratio and all-cause and cardiovascular mortality in patients with hypertension

Previous studies had shown that an increased aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT ratio) was associated with cardiovascular disease. This study aimed to assess the relationship between AST/ALT ratio and all-cause and cardiovascular mortality in patients with hypertension.By March 31, 2020, a cohort of 14,220 Chinese hypertensive patients was followed up. The end point was all-cause and cardiovascular death. Hazard ratios (HRs) and 95% CIs were calculated for mortality associated with AST/ALT ratio, using Cox proportional hazards models and competing risk model.In an average of 1.7 years of follow-up, 1.39% (n = 198) of patients died, 55.5% (n = 110) of whom from cardiovascular disease. AST/ALT ratio was associated with increased risk of all-cause death (HR:1.37, 95% CI:1.15–1.63) and cardiovascular death (HR:1.32, 95% CI:1.03–1.68) after adjustment for other potential confounders. Compared with low AST/ALT ratio (Tertile 1), high AST/ALT ratio was associated with high cause mortality (Tertile 2: HR:1.35, 95% CI:0.86–2.10; Tertile 3: HR:2.10, 95% CI:1.37–3.21; P for trend <.001). Compared with low AST/ALT ratio (Tertile 1), a statistically significant increased risk of cardiovascular mortality was also observed (Tertile 2: HR:1.27, 95% CI:0.70–2.29; Tertile 3: HR:1.92, 95% CI:1.09–3.37; P for trend <.001). High AST/ALT ratio was also associated with high cardiovascular mortality (Tertile 2: HR:1.27, 95% CI:0.70–2.29; Tertile 3: HR:1.92, 95% CI:1.09–3.37; P for trend <.001).Present study indicated that increased AST/ALT ratio levels were predictive of all-cause and cardiovascular mortality among Chinese hypertensive patients.Trial registration: CHICTR, CHiCTR1800017274. Registered 20 July 2018.     

Luseogliflozin improves liver fat deposition compared to metformin in type 2 diabetes patients with non‐alcoholic fatty liver disease: A prospective randomized controlled pilot study

This study aimed to assess the effect of luseogliflozin on liver fat deposition and compare luseogliflozin to metformin in type 2 diabetes (T2D) patients with non‐alcoholic fatty liver disease (NAFLD). Thirty‐two T2D patients with NAFLD diagnosed by computed tomography or abdominal sonography were recruited. Participants were randomly assigned to receive either luseogliflozin (2.5 mg, newly administered) or metformin (1500 mg, newly or additionally administrated). Data on the liver‐to‐spleen attenuation ratio (L/S), visceral fat area, body mass index, glycated hemoglobin (HbA1c), alanine aminotransferase (ALT), fasting plasma glucose, C‐peptide immunoreactivity (CPR), and CPR index were collected at baseline and after 6 months. The change in L/S was significantly greater in the luseogliflozin group than in the metformin group. Similarly, the changes in the visceral fat area, HbA1c, and body mass index were significantly greater in the luseogliflozin group than in the metformin group. The changes in ALT, fasting glucose, CPR, and CPR index were not significant in both groups. In conclusion, luseogliflozin significantly reduced liver fat deposition as compared to metformin, which may indicate clinical relevant benefits for NAFLD.     

Increased liver markers are associated with higher risk of type 2 diabetes

AIM: To investigate the association between liver markers and the risk of type 2 diabetes (T2DM) and impaired fasting glucose (IFG).METHODS: A total of 8863 participants (3408 men and 5455 women) over 30 years of age were analyzed from the fifth Korean National Health and Nutrition Examination Survey (2010-2011). The associations of serum liver markers such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), AST/ALT, and gamma-glutamyltransferase (GGT) with T2DM and IFG were analyzed using logistic regression models. Participants were divided into sex-specific quartiles on the basis of liver markers.RESULTS: The prevalence of T2DM and IFG were 11.3% and 18.3%. Increasing quartiles of ALT and GGT were positively and AST/ALT were negatively correlated with T2DM and IFG. Analysis of the liver marker combinations showed that if any two or more markers were in the highest risk quartile, the risks of both T2DM and IFG increased significantly. The risk was greatest when the highest ALT and GGT and lowest AST/ALT quartile were combined, with the risk of T2DM at 3.21 (95%CI: 1.829-5.622, P < 0.001) in men and 4.60 (95%CI: 3.217-6.582, P < 0.001) in women. Men and women with the highest AST and ALT and lowest AST/ALT quartile had a 1.99 and 2.40 times increased risk of IFG.CONCLUSION: Higher levels of GGT and ALT and lower AST/ALT within the physiological range are independent, additive risk factors of T2DM and IFG.     

Silymarin in non alcoholic fatty liver disease

AIM: This study was undertaken to evaluate the hepatic effects of silybum marianum on non alcoholic fatty liver disease (NAFLD).METHODS: In 72 patients affected by NAFLD, main metabolic, hepatic and anti-inflammatory parameters were assayed after 3 mo of a restricted diet and before silymarin treatment (twice a day orally). The brightness of liver echography texture (hepatorenal ratio brightness) was also defined at same time. These evaluations were repeated after 6 mo of treatment.RESULTS: Serum levels of some metabolic and anti-inflammatory data nonsignificantly lowered after 6 mo of silymarin. On the contrary, Steato test, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase were significantly (P < 0.001) reduced. Instead, the AST/ALT ratio unchanged. Finally, the hepatorenal brightness ratio, as an index of hepatic steatosis, significantly (P < 0.05) dropped.CONCLUSION: The obtained results indicate that silymarin appears to be effective to reduce the biochemical, inflammatory and ultrasonic indices of hepatic steatosis. Some parameters indicative of early stage of atherosclerosis were also lowered.     

AST/ALT比值在慢性肝病患者中的特点和判断预后价值

目的 分析不同病因、不同病情的慢性肝病患者天冬氨酸氨基转移酶和丙氨酸氨基转移酶比值(AST/ALT)的特点,评价AST/ALT比值判断慢性肝病患者预后方面的价值.方法 对534例不同病因的肝硬化、原发性肝癌患者的住院资料进行分析,比较各类患者AST/ALT比值的特点.运用接受者运行曲线(ROC)及曲线下面积,比较AST/ALT比值与终末期肝病模型(MELD)、Child-Turcotte-Pugh(CTP)分级(CC)和评分(CS)在判断慢性肝病患者中短期预后方面的准确性;运用非参数相关分析,计算Spearman相关系数,分析三者之间的相关性.结果 在原发性肝癌患者,AST/ALT比值明显高于肝硬化患者(P＜0.05);病毒性肝病患者和非病毒性肝病患者的AST/ALT比值无明显差异(P=0.852).死亡患者的AST/ALT比值明显高于生存患者的平均值(P=0.000);随着CTP分级的升高,AST/ALT比值也逐渐升高,A、B、C三级之间的AST/ALT比值具有显著差异(P＜0.05).AST/ALT比值和MELD、CS及CC在判断慢性肝病患者生存3个月的ROC曲线下面积分别是0.88、0.92、0.69和0.59,判断生存1年时间的ROC曲线下面积分别为0.64、0.77、0.65和0.63;AST/ALT比值与MELD、CS和CC三者之间的相关系数分别是0.185、0.291和0.297(P=0.000).结论 AST/ALT比值随着肝脏病变的加重而逐渐升高.AST/ALT比值和MELD在判断慢性肝病患者短期预后方面是较好的指标.AST/ALT比值和MELD、CS、CC三者之间具有显著相关性.     

2型糖尿病患者血清肝酶谱与甲状腺激素和中国人内脏脂肪指数的关系

目的探讨2型糖尿病患者血清肝酶谱与甲状腺激素和中国人内脏脂肪指数(Chinese visceral adipose index,CVAI)的关系,分析影响肝酶的因素。方法选取700例于本院内分泌科住院的2型糖尿病患者,根据肝酶是否升高分为肝酶升高组和肝酶正常组,再将丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、谷氨酰胺转肽酶(GGT)分别进行三等分分组。比较2组间及ALT、AST、GGT三等分分组间甲状腺激素和CVAI的差异,分析ALT、AST、GGT与甲状腺激素和CVAI的相关性。结果肝酶升高组较肝酶正常组T4、CVAI升高(P<0.05)。随着ALT、AST的升高,FT3、T3、T4逐渐升高(P<0.05);随着ALT、GGT的升高,CVAI也逐渐升高(P<0.05)。相关性分析显示,ALT、AST与FT3、T3、T4呈正相关;ALT、GGT与CVAI呈正相关;CVAI与FT3、T3呈正相关;HbA1C与FT3、T3和T4呈负相关。回归分析显示,FT3、CVAI和HbA1C是ALT的影响因素,T4是AST的影响因素,T3和HbA1C是GGT的影响因素。结论2型糖尿病患者中甲状腺激素和CVAI与肝酶水平均有一定相关性。     

Ursodeoxycholic acid ameliorates hepatic lipid metabolism in LO2 cells by regulating the AKT/mTOR/SREBP-1 signaling pathway

BACKGROUND Nonalcoholic fatty liver disease(NAFLD), the most common chronic liver disease, can progress into nonalcoholic steatohepatitis(NASH), cirrhosis, and even hepatocellular carcinoma. Bile acids such as ursodeoxycholic acid(UDCA)play an essential role in the pathogenesis of NAFLD by regulating the level of sterol regulatory element-binding protein(SREBP) 1 c, but the underlying regulatory mechanism remains elusive. Increased evidence indicates that the AKT/mTOR/SREBP-1 signaling pathway is a key pathway to regulate hepatic cellular lipid metabolism. UDCA may regulate the AKT/mTOR/SREBP-1 signaling pathway to ameliorate hepatic lipid metabolism.AIM To investigate the functional mechanism of UDCA in an oleic acid(OA)-induced cellular model of NAFLD.METHODS The cellular model of NAFLD was established using OA and treated with UDCA.First, the best concentration of UDCA was selected. For the best time-dependent assay, cells were stimulated with OA only or co-treated with OA and 2 mmol/L UDCA for 24 h, 48 h, and 72 h. Oil red O staining was used to observe the accumulation of intracellular lipids, while the intracellular contents of triglyceride, alanine aminotransferase(ALT), gamma-glutamyl transpeptidase(GGT), and aspartate aminotransferase(AST) were detected by enzymatic methods. Meanwhile, the expression levels of AKT/mTOR/SREBP-1 signaling pathway-related proteins were detected by real-time PCR and Western blot.RESULTS In the NAFLD cell model established with LO2 cells induced using OA, lipid accumulation was obvious. UDCA significantly inhibited lipid accumulation at different concentrations(especially 2 mmol/L) and decreased cell growth ability at different time points. The biochemical parameters like ALT, AST, and GGT were significant improved by UDCA. UDCA treatment vividly repressed the activation of AKT, mTOR, and CRTC2 and the expression of nSREBP-1 in LO2 cells induced with OA.CONCLUSION Our findings demonstrate the effect of UDCA in improving NAFLD. UDCA attenuates OA-induced hepatic steatosis mainly by regulation of AKT/mTOR/SREBP-1 signal transduction.     

Meal-stimulated glucagon release is associated with postprandial blood glucose level and does not interfere with glycemic control in children and adolescents with new-onset type 1 diabetes

CONTEXT: The role of glucagon in hyperglycemia in type 1 diabetes is unresolved, and in vitro studies suggest that increasing blood glucose might stimulate glucagon secretion. OBJECTIVE: Our objective was to investigate the relationship between postprandial glucose and glucagon level during the first 12 months after diagnosis of childhood type 1 diabetes. DESIGN: We conducted a prospective, noninterventional, 12-month follow-up study conducted in 22 centers in 18 countries. PATIENTS: Patients included 257 children and adolescents less than 16 yr old with newly diagnosed type 1 diabetes; 204 completed the 12-month follow-up. SETTING: The study was conducted at pediatric outpatient clinics. MAIN OUTCOME MEASURES: We assessed residual beta-cell function (C-peptide), glycosylated hemoglobin (HbA(1c)), blood glucose, glucagon, and glucagon-like peptide-1 (GLP-1) release in response to a 90-min meal stimulation (Boost) at 1, 6, and 12 months after diagnosis. RESULTS: Compound symmetric repeated-measurements models including all three visits showed that postprandial glucagon increased by 17% during follow-up (P = 0.001). Glucagon levels were highly associated with postprandial blood glucose levels because a 10 mmol/liter increase in blood glucose corresponded to a 20% increase in glucagon release (P = 0.0003). Glucagon levels were also associated with GLP-1 release because a 10% increase in GLP-1 corresponded to a 2% increase in glucagon release (P = 0.0003). Glucagon levels were not associated (coefficient -0.21, P = 0.07) with HbA(1c), adjusted for insulin dose. Immunohistochemical staining confirmed the presence of Kir6.2/SUR1 in human alpha-cells. CONCLUSION: Our study supports the recent in vitro data showing a stimulation of glucagon secretion by high glucose levels. Postprandial glucagon levels were not associated with HbA(1c), adjusted for insulin dose, during the first year after onset of childhood type 1 diabetes.     

Pulsatile insulin secretion in elderly patients with diabetes

Insulin pulsation is impaired in type 2 diabetes. GLP-1 increases pulsatile insulin secretion in these patients. We conducted these studies with the hypothesis that GLP-1 would enhance pulsatile insulin secretion and alter glucose metabolism in elderly patients with type 2 diabetes. Experiments were conducted in nine patients (age: 72+/-5 years; BMI: 27+/-3kg/m(2); diabetes duration: 7+/-3 years; HbA(1c): 6.6+/-0.9%). Subjects underwent three glucose clamp studies. The first was a euglycemic clamp to determine individual insulin clearance. In the second, GLP-1 was infused from 0-240min (0.75pM/kg/min) and glucose was maintained at fasting levels. The third was similar except that octreotide (30ng/kg/min) was infused with GLP-1 to suppress pulsatile insulin. Insulin and glucose were given to match levels during the second study. 3-(3)H-glucose was infused to allow calculation of hepatic glucose production and glucose disposal rates. There was no significant difference in measurements of pulsatile insulin secretion or hepatic glucose production and glucose disposal rates between the studies. Because there was no difference in pulsatile insulin between experiments, we could not test the effect of pulsatile insulin on glucose metabolism. Further studies are required to determine the impact of insulin pulses on glucose metabolism.