非酒精性脂肪肝与胰岛素抵抗

鉴于在一般人群特别是肥胖人群和2型糖尿病人群中合并非酒精性脂肪肝（NAFL）者增加，NAFL的重要性已引起临床重视。本期胰岛素抵抗及其相关疾病专栏刊出了颜红梅、路影和姚定国等作者撰写的有关NAFL的文章，分别对无糖尿病、糖耐量减低（IGT）和2型糖尿病三种人群伴发NAFL和胰岛素抵抗的相关性等进行了临床观察比较。为此，特请本刊编委高鑫教授就NAFL与胰岛素抵抗的相关机制及其对2型糖尿病的防治意义发表评论，期望引起读、作者和临床同道的关注，进一步开展对NAFL的临床和相关机制的研究。[编者按]     

非肥胖T2DM患者IR与NAFL的相关性

对46例非肥胖T2DM伴有和40例不伴有NAFL的患者进行胰岛素抵抗指数（HOMA-IR）等测定。结果伴有NAFL组TG、FPG、FINS、HOMA—OR均显著高于不伴有NAFL组。logistic回归分析显示：NAFL与HOMA—IR呈独立相关（OR3．197，P=0．003）。结论即使是非肥胖的T2DM如伴有NAFL也有更显著的IR，且IR是NAFL的独立危险因素。     

非肥胖T2DM患者IR与NAFL的相关性

对46例非肥胖T2DM伴有和40例不伴有NAFL的患者进行胰岛素抵抗指数(HOMA-IR)等测定.结果 伴有NAFL组TG、FPG、FINS、HOMA-OR均显著高于不伴有NAFL组.logistic回归分析显示NAFL与HOMA-IR呈独立相关(OR3.197,P=0.003).结论 即使是非肥胖的T2DM如伴有NAFL也有更显著的IR,且IR是NAFL的独立危险因素.     

非酒精性脂肪肝:代谢综合征的另一个特征

目的　分析非酒精性脂肪肝 (NAFL)临床及生化特征 ,以探讨NAFL可否成为代谢综合征的一个组成部分。方法　对 85例NAFL患者测体重指数、腰臀比、空腹血糖、血脂、胰岛素、餐后 2h血糖和胰岛素抵抗指数。以 43例非脂肪肝的体检者为对照组。结果　 1.在NAFL患者中 ,中心性肥胖占 70 .5 9% ,高血压病占 3 1.77% ,高TG血症占 62 .3 5 % ,低HDL C占 3 6.47% ,均明显高于对照组 (P <0 .0 0 5～ 0 .0 1) ,而DM/IGT/IPG的患病率 ,两组相比无明显差异 ;2 .血清FINS水平和IR脂肪肝组也较对照组明显增加 (P <0 .0 1) ;3 .在 12 8例研究对象中 ,有 2 1例患者患有代谢综合征 ,其中脂肪肝者占 85 .71% ,中心性肥胖者占 90 .48% ,高血压者占 76.19% ,血脂紊乱者占 10 0 % ,DM/IGT/IPG者占 3 8.10 %。结论　NAFL患者存在明显的胰岛素抵抗 ,可作为代谢综合征的一个组成部分。     

非酒精性脂肪肝患者瘦素抵抗和胰岛素抵抗研究

为了研究非酒精性脂肪肝(NAFL)患者的瘦素(Leptin)抵抗和胰岛素抵抗的状况，对40例NAFL患者和30例正常对照组的血清瘦素、胰岛素等水平进行了分析研究，现将结果报道如下。     

丹栀逍遥散加味对肥胖伴非酒精性脂肪性肝病及胰岛素抵抗的影响

目的：观察丹栀逍遥散加味对湿热内蕴型肥胖伴非酒精性脂肪性肝病的作用及胰岛素抵抗的影响。方法：将60例肥胖者（BMI≥28）辨证为湿热内蕴型肥胖伴非酒精性脂肪性肝病患者给予丹栀逍遥散加味口服，疗程24周，并与同期60例健康体检者比较。治疗结束后观察所有患者体重指数（BMI）、腰臀比（WHR）、丙氨酸氨基转移酶（ALT）、门冬氨酸氨基转移酶（AST）、空腹血糖（FPG）、空腹胰岛素（FINS）、胰岛素敏感性指数（ISI）、血清总胆固醇（TC）、甘油三酯（TG）及血压变化。结果：治疗前湿热内蕴型肥胖伴非酒精性脂肪性肝病患者与健康组比较ISI显著下降（P〈0．01），治疗后患者BIM、WHR、ALT、AST、TC、TG明显下降（P〈0．05），ISI明显上升（P〈0．05）。结论：丹栀逍遥散加味不仅能显著降低湿热内蕴型肥胖伴非酒精性脂肪性肝病患者BMI、WHR、血脂，保肝降酶，同时也能改善胰岛素抵抗，预防高血压病、糖尿病等相关疾病。     

肥胖和非肥胖糖耐量受损患者胰岛素敏感性和1相胰岛素分泌研究

目的研究肥胖和非肥胖糖耐量受损(IGT)患者的胰岛素敏感性和β细胞1相胰岛素分泌功能,以探讨在IGT患者中肥胖对胰岛素抵抗和1相胰岛素分泌的影响。方法共有99位受试者(包括正常对照者32名,肥胖IGT44例,非肥胖IGT23例)接受了口服75 g葡萄糖耐量试验(OGTT)和胰岛素改良的减少样本数(采血样12次)的Bergman微小模型技术结合静脉葡萄糖耐量试验(FSIGTT)。胰岛素抵抗由FSIGTT中胰岛素敏感性指数(SI)加以评估,而OGTT中糖负荷后30 min胰岛素增值与血糖增值之比值[ΔI30/ΔG30=(I30 min-I0 min) /(G30 min-G0 min)]和FSIGTT中急性胰岛素分泌反应(AIRg)则用以评价胰岛β细胞分泌功能。处理指数(DI =AIRg×SI)用于评价AIRg是否代偿机体的胰岛素抵抗。结果与正常对照组[(7.52±10.89)×10-4]相比,二组IGT患者之SI明显降低,而肥胖IGT组的SI[(1.72±1.11)×10-4]较非肥胖组[(3.15±1.49)×10-4]更低(均P<0.01); AIRg和ΔI30/ΔG30在正常组(412±191,14.45±8.47)和肥胖IGT组(378±235,17.02±11.30)之间差异无统计学意义,但均大于非肥胖组(196±160,8.93±6.69,均P<0.01);与正常组(2 851±1 180)相比,DI指数在二组IGT显著降低(595±485,584±517),但后二组间此值差异无统计学意义。SI与2 h胰岛素、体重指数、尿酸和胆固醇呈显著的负相关性(校正r2=0.603,P<0.01);而AIRg与ΔI30/ΔG30显著正相关,与空腹血糖负相关(校正r2=0.479,P<0.01)。结论IGT患者存在胰岛素抵抗和β细胞功能异常。与非肥胖IGT患者相比,肥胖IGT患者胰岛素抵抗程度更为严重,但胰岛β细胞胰岛素1相分泌相对充分。     

脂肪肝合并2DM及IGT的临床特点及其相关危险因素

探讨51例体检健康者及143例脂肪肝者，结果：（1）脂肪肝组血脂、血糖、胰岛素、C肽、BMI、HOMA-IR均高于正常对照组（P〈0.05）；（2）合并2DM及IGT者存在着更明显的胰岛素抵抗（P〈0.01）；（3）脂肪肝组中ALT高于正常组（P〈0.05）。结论：脂肪肝者存在着明显的糖脂代谢紊乱，肝功异常和胰岛素抵抗，合并2DM及IGT者胰岛素抵抗更重。     

非酒精性脂肪肝患病率及其相关因素探讨

目的探讨某油田职工非酒精性脂肪肝（NAFL）患病率及其与肥胖、血脂异常、糖尿病的相关性。方法对743名某油田职工,测量身高、体重,行血脂、血糖、肝肾功能及腹部B超等检查,进行NAFL组和非NAFL组的对比分析。结果（1）743名职工中检出NAFL221名,检出率29．7％;其中BMI≥28者检出率为64．3％,BMI-Q24者检出率为13．4％,24≤BMI％28者检出率为48．6％;肥胖患者NAFL榆出率明显高于非肥胖者（P〈0．01）。（2）NAFL组的BMI、TG、HDL—C、FBG与非NAFL组比较,差异有统计学意义（P〈0．01）。（3）NAFL组中肥胖症、高脂血症、糖尿病的患病率显著高于非NAFL组（P〈0．01）。结论肥胖、血脂异常、糖尿病和高血压发生率NAFL组高于非NAFL组。     

中心性肥胖的糖耐量低减患者的临床特点分析

目的探讨中心性肥胖的糖耐量低减（IGT）患者的临床特点及防治策略。方法将IGT患者69例分为中心性肥胖组（试验组）31例，非中心性肥胖组（对照组）38例，比较其体重指数、收缩压和脉压、血脂异常和心血管病发病率、饮食和运动习惯等的差异。结果合并中心性肥胖的IGT患者超重和肥胖率、非HDL-C性高脂血症的发生率、饮食和运动习惯的良好率与对照组相比差异有显著性。收缩压和脉压、心血管病的发生率与对照组相比差异无显著性。结论合并中心性肥胖的IGT患者肥胖、高脂血症的发病率更高，胰岛素抵抗更严重，应从饮食和运动习惯人手积极干预，预防糖尿病及其血管病变的发生。     

Pathophysiologic heterogeneity in the development of type 2 diabetes mellitus in Korean subjects

OBJECTIVE: To investigate the clinical characteristics and predisposing metabolic abnormalities in the development of glucose intolerance and diabetes mellitus in obese and non-obese Korean subjects. METHODS: Four hundred Korean subjects were classified into five groups according to degree of glucose tolerance by OGTT: NGT, IGT alone, IFG alone, IFG+IGT, and DM. The groups were also subdivided into obese and non-obese group according to body mass index. Insulin resistance was assessed by using homeostasis model assessment of insulin resistance (HOMA-R), and insulinogenic index was used as an index of early-phase insulin secretion. RESULTS: Impaired early-phase insulin secretion was seen in non-obese IGT alone, IFG alone, and IFG+IGT, though more profound secretory defects were noted in IFG+IGT and DM. No significant difference were found in HOMA-R among non-obese IGT alone, IFG alone, or IFG+IGT, or in terms of early-phase insulin secretion in obese IGT alone, IFG alone, or IFG+IGT. However, the magnitude of insulin resistance differed in the obese group, IFG+IGT and DM being more insulin resistant than IGT alone or IFG alone. CONCLUSIONS: These results suggest that the predisposing metabolic abnormality in non-obese subjects with IGT alone or IFG alone and in progression to IFG+IGT might be deterioration of early phase insulin secretion, whereas insulin resistance might be the major contributory factor in obese subjects. The predisposing metabolic abnormality leading to diabetes in both obese and non-obese groups was deterioration of early-phase insulin secretion.     

Plasma islet amyloid polypeptide levels in obesity, impaired glucose tolerance and non-insulin-dependent diabetes mellitus.

We examined the response of plasma islet amyloid polypeptide (IAPP) to an oral glucose load in non-obese and obese subjects with normal glucose tolerance or impaired glucose tolerance (IGT), and in non-obese patients with non-insulin-dependent diabetes mellitus (NIDDM). Plasma IAPP response to intravenous glucagon injection in NIDDM patients was also studied. Plasma IAPP concentration was determined by a sensitive and specific radioimmunoassay. Basal levels of plasma IAPP in non-obese subjects with normal glucose tolerance, IGT and NIDDM were not significantly different from each other. Non-obese subjects with IGT showed delayed and higher plasma IAPP response to oral glucose load compared to normal non-obese subjects. In NIDDM patients, IAPP response to glucose was delayed and lower when compared to normal non-obese subjects. Basal levels of plasma IAPP in normal obese subjects and obese subjects with IGT were significantly higher than those in normal non-obese subjects. Plasma IAPP response to glucose load in these obese subjects was higher than that in normal non-obese subjects. Plasma IAPP response was decreased in diabetic patients treated with diet, oral hypoglycemic agents and insulin in that order. We conclude that the secretion of IAPP is reduced with progression of NIDDM, although it appears to be rather augmented in IGT compared to normal non-obese subjects.     

Insulin secretion and sensitivity in non-obese and obese Japanese patients with coronary artery disease

In a cross-sectional study of 240 patients with angiographically documented coronary artery disease (CAD), we investigated whether obese and non-obese subjects differed as to the influence of insulin deficiency and insulin resistance on glucose intolerance and cardiovascular risk. Patients were classified according to a 75-g oral glucose tolerance test as having normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or diabetes mellitus (DM). We defined obesity as a body mass index (BMI) exceeding 25 kg/m(2). Early phase insulin secretion (insulinogenic index) declined with worsening glucose intolerance in non-obese (tau = -.216, P <.001; Kendall's correlation coefficient) and obese subjects (tau = -.392, P <.001). Total insulin secretion was higher in obese subjects with NGT or IGT than in controls and decreased in association with worsening glucose intolerance in obese subjects (tau = -.239, P <.001). Insulin sensitivity was calculated by 3 proposed indices. The first of these decreased in association with worsening in glucose tolerance in non-obese subjects (tau = -.137, P <.01). The second showed such a pattern in both groups (non-obese, tau = -.407, P <.001; obese, tau = -.311, P <.001), as did the third (non-obese, tau = -.512, P <.001; obese, tau = -.488, P < 0.001). Because even prediabetic Japanese subjects with CAD showed a latent insulin secretion defect in response to a glucose load, as well as impaired insulin sensitivity, compensatory hyperinsulinemia is not a sensitive indicator of coronary risk.     

Association of beta3-adrenergic receptor gene polymorphism with insulin resistance in Japanese-American men

The Trp64Arg variant of the beta3-adrenergic receptor (beta3-AR) gene is relatively common in Japanese people. We hypothesized that this variant may be associated with obesity and insulin resistance when combined with a westernized lifestyle. To test this hypothesis, we investigated the relationships between the beta3-AR gene variant and obesity and insulin resistance in Japanese-American men, who are known to have a higher prevalence of type 2 diabetes mellitus (DM). The subjects were 152 Japanese-American men living in Hawaii, 83 with normal glucose tolerance (NGT), 40 with impaired glucose tolerance (IGT), and 29 with DM. The frequency of the Trp64Arg allele of the beta3-AR gene was 0.18, almost identical to that of the mainland Japanese. The prevalence of the Trp64Arg allele was 30.1% in NGT, 35.0% in IGT, and 41.4% in DM subjects (nonsignificant). The Trp64Arg variant of the beta3-AR gene showed no significant relationship with obesity or insulin resistance in NGT subjects. However, fasting and 2-hour insulin levels and insulin resistance as determined by homeostasis model assessment (HOMA) were significantly higher in IGT subjects with the Trp64Arg variant. Although indices of obesity were the same in IGT subjects with and without the Trp64Arg variant, differences in the body mass index (BMI) and percent body fat between NGT and IGT subjects were greater for individuals with the Trp64Arg variant. Thus, there is an association between the Trp64Arg variant of the beta3-AR gene and insulin resistance in Japanese-Americans with IGT.     

不同糖耐量水平人群血清真胰岛素和胰岛素原水平的临床意义

目的 探讨不同糖耐量者血清真胰岛素（ＴＩ）及胰岛素原（ＰＩ）水平的变化及临床意义。方法 用特异的单克隆抗体夹心放大酶联免疫分析法（ＢＡ－ＥＬＩＳＡ）检测１３５例正常糖耐量（ＮＧＴ）、８６例糖耐量低减（ＩＧＴ）及１０１例Ⅱ型糖尿病（ＤＭ）者口服葡萄糖耐量试验（ＯＧＴＴ）各点血清ＴＩ及ＰＩ水平。结果 ３组血清空腹ＴＩ差异无显著性（Ｐ〉０．０５）,免疫反应胰岛素（ＩＲＩ）Ⅱ型ＤＭ组明显升高（Ｐ〈０．０１     

不同状态的糖调节受损患者胰岛素分泌和胰岛素敏感性的差异

目的评估初发的单纯空腹血糖受损（IFG）和单纯糖耐量受损（IGT）患者的胰岛素分泌以及胰岛素敏感性（IS）特征。方法北京市东城区既往无糖尿病史的2388名受试者行葡萄糖耐量试验,同时行胰岛素释放试验,本文纳入2244例,其中糖耐量正常（NGT）1608例,IFG240例,IGT243例,IFG＋IGT 153例。比较各组胰岛素抵抗指数（HOMA-IR）、IS指数（Matsudaindex）、B细胞功能指数（1相Stumvoll index、△I30／△G30）。结果与NGT组比较,其余三组HOMA-IR显著升高,Matsuda指数及B细胞功能指数均显著降低（P均〈0．01）;IFG组HOMA-IR及Matsuda指数均高于IGT组;IFG组△I30／△G30高于IGT组,而Stumvoll指数低于IGT组（P〈0．01）;与IFG组、IGT组比较,IFG＋IGT组HOMA-IR显著升高,Matsuda指数、1相Stumvoll指数显著降低（P均〈0．01）。结论糖尿病前期人群存在不同程度的胰岛素分泌缺陷和IR,IFG组肝IR较重,而IGT组肌肉IR较重。     

Differences in insulin sensitivity, pancreatic beta cell function and circulating adiponectin across glucose tolerance status in Thai obese and non-obese women

Although adiponectin levels are associated with obesity and insulin insensitivity, the role of adiponectin in the progression to diabetes in non-obese subjects is unclear. Therefore, 289 women aged 50–80 years without previous history of diabetes or impaired glucose tolerance (IGT) were studied. They were classified as normal glucose tolerance (NGT), IGT or diabetes based on WHO criteria. Insulin sensitivity (S) and beta cell function (B) indices were calculated using homeostasis model assessment (HOMA). In obese women with BMI ≥ 25 kg/m² (n = 161), there were declines in HOMA-%S (P < 0.001), HOMA-%B (P < 0.05) and circulating adiponectin (P < 0.001) across glucose tolerance status. In non-obese women with BMI < 25 kg/m² (n = 128), there was no significant change in HOMA-%S in women with IGT and diabetes as compared to women with NGT. However, HOMA-%B (P < 0.05) and serum adiponectin levels (P < 0.001) were significantly decreased across glucose tolerance. Serum adiponectin levels were correlated to HOMA-%S in both obese and non-obese women while negative correlations between circulating adiponectin and HOMA-%B were demonstrated only in obese women. We have demonstrated in the present study the predominant role of beta cell dysfunction as compared to that of insulin resistance in the deterioration of glucose tolerance in non-obese women. Circulating adiponectin appears to be inversely related to beta cell dysfunction in addition to insulin resistance only in obese women.     

The effect of long-term glibenclamide treatment on glucose tolerance, insulin secretion and serum lipids in subjects with impaired glucose tolerance

The effects of glibenclamide plus diet (n = 27) or diet alone (n = 18) on glucose tolerance, insulin secretion and serum lipids in non-obese subjects with normal or low insulin responses and impaired glucose tolerance (IGT) has been followed up for two years. Glucose tolerance and insulin secretion were characterized by means of a glucose infusion test consisting of an initial injection of 0.33 g glucose/kg body weight followed by 12 mg/kg body weight/min for 2 h. Dietary treatment did not improve glucose tolerance in normal and low insulin-responders. Glibenclamide plus diet succeeded in improving glucose tolerance only in low insulin responders whereas glucose tolerance remained unchanged in normal insulin responders. There was a significant decrease in fasting and glucose-stimulated insulin levels after two years of glibenclamide treatment in both the normal and low insulin-responders. The body weight was not altered. Triglyceride and cholesterol levels both decreased. In summary, the present study failed to demonstrate an increase in insulin secretion under chronic administration of glibenclamide in subjects with IGT independent of the type of insulin response. From the practical point of view, glibenclamide is of benefit in the treatment of non-obese subjects with IGT and relative insulin deficiency.     

肥胖症患者和新诊断的2型糖尿病患者真胰岛素和前胰岛素的改变

目的 了解真胰岛素（ｔｒｕｅ ｉｎｓｕｌｉｎ，ＴＩ）和前胰岛素（ｐｒｏｉｎｓｕｌｉｎ，ＰＩ）在肥胖症和２型糖尿病患者中的改变，了解免疫活性胰岛素（ｉｍｍｕｎｏｒｅａｃｔｉｖｅ ｉｎｓｕｌｉｎ，ＩＲＩ）能否准确反映ＴＩ。方法 ３３例糖耐量正常（ＮＧＴ），２４例糖耐量减低（ＩＧＴ）和５３例新诊断的２型糖尿病患者行口服葡萄糖耐量实验，并根据体重指数（ＢＭＩ）分为肥胖和非肥胖组；采用ＥＬＩＳＡ方法（其单克