2型糖尿病患者非酒精性脂肪肝与微血管病变关系的研究

目的探讨2型糖尿病(T2DM)患者中非酒精性脂肪肝(NAFLD)与慢性肾脏疾病(CKD)及糖尿病视网膜病变(DR)的关系。方法收集2008年5月至2009年7月上海交通大学附属第一人民医院内分泌代谢科448例T2DM患者的临床资料,按是否合并NAFLD分组,比较两组间CKD和DR的发生率及其与NAFLD的联系。结果(1)448例T2DM患者中NAFLD合并率为59.4%。(2)与无NAFLD组相比,NAFLD组尿白蛋白/肌酐比值(UACR)及CKD和DR的发病率明显升高(P0.01)。(3)Logistic回归分析显示,NAFLD是T2DM患者发生CKD和DR的独立危险因素(OR=1.9,P0.05;OR=2.8,P0.01)。结论T2DM患者中NAFLD与CKD和DR密切相关,提示通过早期诊断和干预NAFLD可预防微血管并发症。     

Arterial wall thickness is associated with insulin resistance in type 2 diabetic patients

The aim of the present study was to investigate the independent association of the intimal-medial thickness of carotid and femoral arteries (CA-IMT and FA-IMT), a marker of atheroscelosis, with insulin resistance in type 2 diabetic patients. We evaluated CA-IMT and FA-IMT by high-resolution ultrasonography and insulin resistance determined by euglycemic hyperinsulinemic clamp in 119 type 2 diabetic subjects, 71 males and 48 females (age, 54 +/- 12 (SD) years). In simple regression analyses, CA-IMT and FA-IMT were significantly inversely correlated with insulin sensitivity index (CA-IMT, r = -0.225, p = 0.010; FA-IMT, r = -0.186, p = 0.043, respectively). Multiple regression analysis was performed with the logarithm of CA-IMT or FA-IMT as a dependent variable and insulin sensitivity index as an independent variable along with known clinical risk factors. Insulin sensitivity index exhibited a significant independent contribution to log (CA-IMT) (beta = -0.204, p = 0.033) and to log (FA-IMT) (beta = -0.237, p = 0.010) in these models (CA-IMT, R(2) = 0.347, p < 0.0001; FA-IMT, R(2) = 0.398, p < 0.0001, respectively). In conclusion, insulin resistance is associated with both CA-IMT and FA-IMT in type 2 diabetic patients, suggesting that it is an independent risk factor for the development of atherosclerosis in type 2 diabetes.     

Non-alcoholic fatty liver disease is independently associated with an increased prevalence of chronic kidney disease and retinopathy in type 1 diabetic patients

Aims/hypothesis  

Non-alcoholic fatty liver disease (NAFLD) is associated with an increased prevalence of chronic kidney disease (CKD) and retinopathy in patients with type 2 diabetes. Information on this issue is lacking for type 1 diabetes. We evaluated whether NAFLD is associated with increased prevalence of retinopathy and CKD in type 1 diabetic patients.     

Non-alcoholic fatty liver disease is independently associated with an increased prevalence of chronic kidney disease and proliferative/laser-treated retinopathy in type 2 diabetic patients

Aims/hypothesis Non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiovascular disease in type 2 diabetes. Currently, there is a lack of information on associations between NAFLD and microvascular complications of diabetes. We assessed the associations between NAFLD and both chronic kidney disease (CKD) and retinopathy in a large cohort of type 2 diabetic individuals using a cross-sectional design. Methods Prevalence rates of retinopathy (by ophthalmoscopy) and CKD (defined as overt proteinuria and/or estimated GFR ≤60 ml min⁻¹ 1.73 m⁻²) were assessed in 2,103 type 2 diabetic individuals who were free of diagnosed cardiovascular disease and viral hepatitis. NAFLD was ascertained by patient history, blood sampling and liver ultrasound. Results NAFLD patients had higher (p < 0.001) age- and sex-adjusted prevalence rates of both non-proliferative (39 vs 34%) and proliferative/laser-treated retinopathy (11 vs 5%), and CKD (15 vs 9%) than counterparts without NAFLD. In logistic regression analysis, NAFLD was associated with increased rates of CKD (odds ratio 1.87; 95% CI 1.3–4.1, p = 0.020) and proliferative/laser-treated retinopathy (odds ratio 1.75; 1.1–3.7, p = 0.031) independently of age, sex, BMI, waist circumference, hypertension, diabetes duration, HbA_1c, lipids, smoking status and medications use. Conclusions/interpretation Our findings suggest that NAFLD is associated with an increased prevalence of CKD and proliferative/laser-treated retinopathy in type 2 diabetic individuals independently of numerous baseline confounding factors. Further studies are required to confirm the reproducibility of these results and to evaluate whether NAFLD contributes to the development or progression of CKD and retinopathy.     

Non-alcoholic fatty liver disease is associated with cardiovascular disease risk markers

Recognition of the link between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) has boosted research in this area. The main objective of this paper is to review the literature on NAFLD in the context of CVD, focussing on underlying mechanisms and treatment. Besides excessive fatty acid influx, etiologic factors may include components of the metabolic syndrome, cytokines and mitochondrial dysfunction. NAFLD is associated with both hepatic and systemic insulin resistance. In the case of NAFLD, the liver overproduces several atherogenic factors, notably inflammatory cytokines, glucose, lipoproteins and coagulation factors, and factors increasing blood pressure. Intervention studies on diet and laparoscopic surgery revealed improvements of hepatic fat content and CVD risk profile. Pharmacological approaches with potential benefit have been developed as well, but effects are often confounded by weight change. NAFLD is associated with an increased CVD risk profile (and hepatic risk). In order to improve CVD risk profile, prevention and treatment of NAFLD seem advisable. However, well-designed intervention studies, randomized clinical trials and long-term follow-up studies are scarce.     

非酒精性脂肪肝、非酒精性脂肪肝合并代谢综合征患者血清脂联素水平及其与胰岛素抵抗程度的相关性分析

目的 研究非酒精性脂肪肝、非酒精性脂肪肝合并代谢综合征患者血清脂联素水平及其与胰岛素抵抗程度的相关性.方法 选取非酒精性脂肪肝106例,非酒精性脂肪肝合并代谢综合征58例,单纯肥胖32例,健康体检42例作为对照组.测定体重指数（BMI）和腰臀比（WHR）,检测空腹血糖（FBS）、丙氨酸氨基转移酶（ALT）、胆固醇（TC）、甘油三脂（TG）和高密度脂蛋自（HDL）等生化指标并行肝脏B超检查.放射免疫法测定空腹胰岛素（FINS）水平,计算胰岛素抵抗指数（HOMA）.同时酶联免疫法测定血清脂联素水平,并用相关及多元回归分析脂联素与各参数的相关性.结果 非酒精性脂肪肝组BMI、ALT、TC、TG、FBS、FINS和HOMA均较正常对照组高,HDL和脂联素水平较正常对照组低;非酒精性脂肪肝合并代谢综合征组胰岛素抵抗程度较非酒精性脂肪肝组更严重,脂联素水平更低.单纯肥胖组ALT、TC高于对照组,脂联素水平有下降趋势.非酒精性脂肪肝ALT异常组与ALT正常组比较,脂联素水平下降.结论 非酒精性脂肪肝存在不同程度胰岛素抵抗,脂联素水平降低;合并代谢综合征者胰岛素抵抗更为严重,脂联素水平更低;合并ALT异常时脂联素水平下降     

Non-alcoholic fatty liver disease is not associated with a lower health perception

AIM: To examine the association between nonalcoholic fatty liver disease(NAFLD) and general health perception.METHODS: This cross sectional and prospective follow-up study was performed on a cohort of a subsample of the first Israeli national health and nutrition examination survey, with no secondary liver disease or history of alcohol abuse. On the first survey, in 2003-2004, 349 participants were included. In 2009-2010 participants from the baseline survey were invited to participate in a follow-up survey. On both baseline and follow-up surveys the data collected included: self-reported general health perception, physical activity habits, frequency of physician's visits, fatigue impact scale and abdominal ultrasound. Fatty liver was diagnosed by abdominal ultrasonography using standardized criteria and the ratio between the median brightness level of the liver and the right kidney was calculated to determine the Hepato-Renal Index.RESULTS: Out of 349 eligible participants in the first survey, 213 volunteers participated in the follow-up cohort and were included in the current analysis, NAFLD was diagnosed in 70/213(32.9%). The prevalence of "very good" self-reported health perception was lower among participants diagnosed with NAFLD compared to those without NAFLD. However, adjustment for BMI attenuated the association(OR = 0.73, 95%CI: 0.36-1.50, P = 0.392). Similar results were observed for the hepato-renal index; it was inversely associated with "very good" health perception but adjustment for BMI attenuated the association. In a full model of multivariate analysis, that included all potential predictors for health perception, NAFLD was not associated with the self-reported general health perception(OR = 0.86, 95%CI: 0.40-1.86, P = 0.704). The odds for "very good" self-reported general health perception(compared to "else") increased among men(OR = 2.42, 95%CI: 1.26-4.66, P = 0.008) and those with higher performance of leisure time physical activity(OR = 1.01, 95%CI: 1.00-1.01, P 0.001, per every minute/week) and decreased with increasing level of BMI(OR = 0.91, 95%CI: 0.84-0.99, P = 0.028, per every kg/m~2) and older age(OR = 0.96, 95%CI: 0.93-0.99, P = 0.033, per one year). Current smoking was not associated with health perception(OR = 1.31, 95%CI: 0.54-3.16, P = 0.552). Newly diagnosed(naive) and previously diagnosed(at the first survey, not naive) NAFLD patients did not differ in their self-health perception. The presence of NAFLD at the first survey as compared to normal liver did not predict health perception deterioration at the 7 years follow-up. In terms of health-services utilization, subjects diagnosed with NAFLD had a similar number of physician's visits(general physicians and specialty consultants) as in the normal liver group. Parameters in the fatigue impact scale were equivalent between the NAFLD and the normal liver groups.CONCLUSION: Fatty liver without clinically significant liver disease does not have independent impact on selfhealth perception.     

Polymorphism of human leptin receptor gene is associated with type 2 diabetic patients complicated with non-alcoholic fatty liver disease in China

Background and Aim:  To investigate the relationship between human leptin receptor ( LEPR ) gene G3057A polymorphism and type 2 diabetes mellitus (T2DM) patients complicated with or without non-alcoholic fatty liver disease (NAFLD).
Methods:  Two hundred and sixteen cases of newly diagnosed T2DM patients (104 cases complicated with NAFLD) and 108 cases of normal glucose tolerances (NGT) were recruited. Hemi-nested polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and PCR-direct sequence analysis were conducted to detect the polymorphism of LEPR G3057A variation. Plasma leptin levels were measured by enzyme-linked immunosorbent assay kit. Plasma lipid and glucose metabolic parameters were measured routinely. Liver ultrasound was carried out for all subjects.
Results:  T2DM patients complicated with NAFLD had higher plasma insulin, leptin, triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) levels than those without NAFLD and NGT subjects. The variant frequency at nucleotide 3057 G→A transversion was 76.0% in type 2 diabetic patients complicated with NAFLD, which was also significantly higher than those without NAFLD (62.1%) and NGT cases (53.2%). There was also significant difference in genotype distribution between the three groups (χ² = 14.63, P  < 0.01).
Conclusion:  The polymorphism of LEPR gene 3057 probably contributes to the onset of NAFLD by regulating lipid metabolism and affecting insulin sensitivity.     

Non-alcoholic fatty liver disease is associated with high prevalence of gastro-oesophageal reflux symptoms

Background

Gastro-oesophageal reflux symptoms are usually reported by patients with obesity and metabolic syndrome. Aim of this study was to assess the prevalence and clinical characteristics of gastro-oesophageal reflux symptoms in subjects with non-alcoholic fatty liver disease.

Methods

Cross-sectional, case–control study of 185 consecutive patients with non-alcoholic fatty liver disease and an age- and sex-matched control group of 112 healthy volunteers. Participants were interviewed with the aid of a previously validated questionnaire to assess lifestyle and reflux symptoms in the 3 months preceding enrolment. Odds ratios were determined before and after adjustment for body mass index, increased waist circumference, physical activity, metabolic syndrome and proton pump inhibitors and/or antiacid medication.

Results

The prevalence of heartburn and/or regurgitation and of at least one of gastro-oesophageal reflux symptoms was significantly higher in the non-alcoholic fatty liver disease group. Non-alcoholic fatty liver disease subjects were associated to higher prevalence of heartburn (adjusted odds ratios: 2.17, 95% confidence intervals: 1.16–4.04), regurgitation (adjusted odds ratios: 2.61, 95% confidence intervals: 1.24–5.48) and belching (adjusted odds ratios: 2.01, 95% confidence intervals: 1.12–3.59) and had higher prevalence of at least one GER symptom (adjusted odds ratios: 3.34, 95% confidence intervals: 1.76–6.36).

Conclusion

Non-alcoholic fatty liver disease is associated with a higher prevalence of gastro-oesophageal reflux symptoms.     

Non-alcoholic fatty liver disease is associated with left ventricular diastolic dysfunction in essential hypertension

Background and aimInsulin resistance is recognized as the pathophysiological hallmark of non-alcoholic fatty liver disease (NAFLD). A relation between insulin sensitivity and left ventricular morphology and function has been reported in essential hypertension, where a high prevalence of NAFLD has been recently found. We investigated the inter-relationship between left ventricular morphology/function, metabolic parameters and NAFLD in 86 never-treated essential hypertensive patients subdivided in two subgroups according to the presence (n = 48) or absence (n = 38) of NAFLD at ultrasonography.Methods and resultsThe two groups were similar as to sex, age and blood pressure levels. No patient had diabetes mellitus, obesity, hyperlipidemia, or other risk factors for liver disease. Body mass index, waist circumference, triglycerides, glucose, insulin, homeostasis model of assessment index for insulin resistance (HOMA-IR), aspartate aminotransferase and alanine aminotransferase were higher and adiponectin levels were lower in patients with NAFLD than in patients without NAFLD, and were associated with NAFLD at univariate analysis. Patients with NAFLD had similar prevalence of left ventricular hypertrophy compared to patients without NAFLD, but a higher prevalence of diastolic dysfunction (62.5 vs 21.1%, P < 0.001), as defined by E/A ratio <1 and E-wave deceleration time >220 ms. Diastolic dysfunction (P = 0.040) and HOMA-IR (P = 0.012) remained independently associated with NAFLD at backward multivariate analysis.ConclusionsNon-alcoholic fatty liver disease was associated with insulin resistance and abnormalities of left ventricular diastolic function in a cohort of patients with essential hypertension, suggesting a concomitant increase of metabolic and cardiac risk in this condition.     

2型糖尿病非增生型视网膜病变与颈动脉内膜中层厚度的关系

目的探讨2型糖尿病（T2DM）患者非增生型视网膜病变（NPDR）与颈动脉内膜中层厚度（IMT）之间的关系。方法选择NPDR组97例,糖尿病正常眼底（NDR）对组照100例。B超检测IMT。结果（1）NPDR组IMT明显高于NDR组（P〈0．01）。（2）NPDR与年龄、病程、收缩压、舒张压、糖化血红蛋白、IMT、尿白蛋白呈正相关（P〈0.05）,与HDL-C、餐后2hC肽呈负相关（P〈0．05）。Logistic回归显示IMT是NPDR的主要危险因素（P〈0.01）。（3）IMT增厚组（60．7G）NPDR发病率明显高于正常组（44．1％）（P〈0.05）。结论T2DM合并颈动脉IMT增厚者NPDR发病率显著增高,推测动脉粥样硬化可能是NPDR的一个重要的相关因素。     

SOX13抗体与2型糖尿病患者颈动脉内中膜厚度的关系

目的 探讨SOX13抗体(SOX13-Ab)与2型糖尿病(T2DM)患者颈动脉内中膜厚度(IMT)的关系. 方法 选取248例谷氨酸脱羧酶抗体(GAD-Ab)阴性的T2DM患者,检测SOX13-Ab指数等,彩色B超测量受试者颈动脉IMT及可视斑块范围.探讨SOX13-Ab指数与IMT增厚、斑块发生的相互关系. 结果 (1)IMT与发病年龄呈显著正相关,与SOX13-Ab指数呈显著负相关(P均<0.05).(2)随SOX13-Ab指数升高,IMT、内膜增厚(IMT>0.9mm)风险性及斑块阳性率渐降;SOX13-Ab最低五分位组IMT显著高于其他各分位;内膜增厚风险性显著高于4th1/5、5th1/5分位组,斑块阳性率显著高于4th1/5分位组(P均<0.05).(3)随斑块严重程度的增加,SOX13-Ab指数递减;0级组患者SOX13-Ab指数显著高于2级组(P<0.05). 结论 SOX13-Ab指数与T2DM患者IMT具有良好负相关性,可望成为判断T2DM患者发生IMT增厚及动脉粥样硬化危险性的新指标.