修正的最小模型在分析胰岛素敏感性和分泌功能中的应用

胰岛素抵抗(即胰岛素敏感性降低)和胰岛β细胞功能衰减在糖尿病发生发展过程中起着重要作用,因此,正确地评价人群的胰岛素敏感性和胰岛β细胞功能在临床工作中越来越受到关注。胰岛素敏感性包括外周胰岛素敏感性(在胰岛素作用下,机体在外周组织摄取和清除葡萄糖的能力)和肝胰岛     

减少样本数的最小模式对Ⅱ型糖尿病患者胰岛素抵抗的临床应用研究

用减少样本数的ＦＳＩＧＴＴ，通过最小模式研究轻型ＮＩＤＤＭ者胰岛素抵抗指标ＳＩ和ＳＧ。结果显示，减少样本数的ＦＳＩＧＴＴ所得ＳＩ较标准的ＦＳＩＧＴＴ所得ＳＩ虽有所增高，平均ＣＶ增加了６．２％，但无显著性差异（Ｐ＞０．０５）；而ＳＧ、ＡＵＣ１、ＡＵＣ２及ＡＵＣ的ＣＶ虽有增加，然增幅很小，不足２％（Ｐ＞０．０５）。提示减少样本数的ＦＳＩＧＴＴ仍不失为大规模调查研究ＮＩＤＤＭ及易感人群者胰岛素抵抗状况的可行方法。     

减少样本数的最小模型测定单纯性肥胖和糖耐量受损者的胰岛素敏感性

Bergman提出的最小模型(MMM)计算公式是一较为公认的胰岛素敏感性测定方法，由于取血次数多，影响临床上的应用，故人们进行了多种尝试，用减少样本数的多样本静脉注射葡萄糖耐量试验(FSIGTT)，通过MMM来研究胰岛素抵抗(IR)。我们以减少样本数(14次)的MMM检测了正常人(NC)、单纯性肥胖(Ob)、糖耐量受损(IGT)者的胰岛素敏感指数(ISI)，旨在探讨减少样本数的MMM在IR中的应用。     

Bergman最小模型法及其研究新进展

Bergman等提出的最小模型法是一种较为公认的胰岛素敏感性测定方法,为了简化并将其广泛地应用于临床,近年来国内外专家学者从3个途径对它进行了深入的研究：静脉葡萄糖耐量试验和数学模型基本不变,努力提高减少样本数后计算结果的精确性;静脉葡萄糖耐量试验和数学模型基本不变,但通过应用口服药纠正胰岛素缺乏对胰岛素敏感性测定的影响;改进数学模型,使之与口服葡萄糖耐量试验或膳食糖耐量试验相结合,同时评估胰岛素敏感性和胰岛素分泌功能.     

线性最小模型在分析胰岛素敏感性和分泌功能中的应用--660例天津地区中国人口服葡萄糖耐量试验资料的分析研究

目的 探讨利用口服葡萄糖耐量试验（OGTT）中5个时点的血糖值和胰岛素值，借助线性最小模型（LMM）计算胰岛素敏感指数（ISI）和分泌功能指数（BCI）的可行性。方法 对660例天津地区的中国人正常糖耐量组150例、糖调节受损组220例、糖尿病组290例的OGTT资料进行研究，分析比较4种ISI：李氏IAI、DeFronzo-ISI、HOMA-IR、LMM-ISI，和5种BCI：李氏MBCI、HOMA-β、△I30／△G30、△I60／△G60、LMM-BCI。结果 （1）用HOMA-β调整后，在4种ISI中，LMM-ISI与G梯形的相关性相对最好（r=-0．6083，P〈0．001）。（2）用DeFronzo-ISI调整后，在5种BCI中，LMM-BCI与G梯形的相关性相对最好（r=-0．9092，P〈0．001）。（3）LMM-ISI与LMM-BCI相配合可以较好的解释G梯形的变化（决定系数R^2=0．836，P〈0．001）。结论 利用OGTT资料所计算的LMM-ISI和LMM-BCI是一对相对较好的反映胰岛素敏感性和胰岛素分泌功能的指数。     

Bergman最小模型法及其研究新进展

Bergman等提出的最小模型法是一种较为公认的胰岛素敏感性测定方法,为了简化并将其广泛地应用于临床,近年来国内外专家学者从3个途径对它进行了深入的研究:静脉葡萄糖耐量试验和数学模型基本不变,努力提高减少样本数后计算结果的精确性;静脉葡萄糖耐量试验和数学模型基本不变,但通过应用口服药纠正胰岛素缺乏对胰岛素敏感性测定的影响;改进数学模型,使之与口服葡萄糖耐量试验或膳食糖耐量试验相结合,同时评估胰岛素敏感性和胰岛素分泌功能。     

减少样本数的Bergman最小模型技术在胰岛素抵抗综合征中？…

目的 研究单纯性肥胖、糖耐量减退（ＩＧＴ）和２型糖尿病（ＤＭ）患者胰岛素抵抗的发病机制。方法 用减少样本数的Ｂｅｒｇｍａｎ最小模型技术结合多样本静脉葡萄糖耐量试验分别测定正常人、单纯性肥胖、ＩＧＴ和２型ＤＭ患者胰岛素敏感性指数（ＳＩ）、葡萄糖自身代谢效能（ＳＧ）及胰岛β细胞分泌功能,同时测定体重指数（ＢＭＩ）和腰臀比（ＷＨＲ）。结果 正常组的ＳＩ和ＳＧ均明显高于ＩＧＴ和２型ＤＭ组,但与肥胖组相比,     

葡萄糖钳夹技术在糖尿病研究中的应用

本文介绍葡萄糖钳夹技术在糖尿病研究中的应用。通过葡萄糖钳夹技术可研究在正常或高血糖情况下机体的胰岛素敏感性，胰岛素分泌和葡萄糖，脂类和蛋白质代谢等变化。     

Prader—Willi综合征患者一例胰岛素敏感性分析及文献复习

目的评价1例Prader-Willi综合征患者的胰岛素敏感性。方法1例18岁男性患者因体重进行性增加15年就诊,临床确诊为Prader—Willi综合征。对患者进行系统的内分泌检查并行高胰岛素正葡萄糖钳夹试验,评价患者的胰岛素敏感性。结果患者身高156em,体重115kg,体质指数（BMI）47．3kg／m2;糖化血红蛋白6．8％,2次口服葡萄糖耐量试验（OGTr）均达到糖尿病的诊断标准,同步胰岛B细胞功能评价提示晚时相胰岛素分泌高峰延迟。胰岛素：0min43．7mU／L,1h247．6mU／L,2h230．9mU／L。甲状腺功能、肾上腺皮质功能均正常。钳夹试验时基础血浆葡萄糖为4．5mmol／L,钳夹开始20-120min内葡萄糖输注率（GIR）为6．6mg／（kg·min）,稳态期GIR为6．2mg／（kg·min）。结论Prader—Willi综合征患者存在胰岛素抵抗。     

Effects of Heparin-induced Non-esterified Free Fatty Acid on Minimal Model-derived Insulin Sensitivity in Individuals with Varying Degrees of Glucose Intolerance

The effects of heparin-induced non-esterified free fatty acid (NEFA) release on insulin sensitivity index were studied in individuals with varying degrees of glucose intolerance and beta cell dysfunction during the frequently sampled intravenous glucose tolerance test (IVGTT). The groups comprised: Group 1 (n = 5): newly diagnosed Type 2 diabetic patients, Group 2 (n = 11): impaired glucose tolerance patients (IGT), and Group 3 (n = 16): healthy normal glucose tolerance subjects. The serum insulin and c-peptide levels were severely blunted in the diabetic patients when compared to both non-diabetic groups. Mean fasting and post-heparin plasma NEFA levels were approximately 1.8 fold greater (p < 0.05) in the diabetic patients when compared to the other two groups. The mean insulin sensitivity index was lowest in the diabetic patients, intermediate in the IGT patients, and highest in the healthy controls. A significant negative relationship was found between the insulin sensitivity index and stimulated NEFA (r = ?0.537, p < 0.008) but not with the fasting NEFA levels in our subjects. In summary, the frequently sampled IVGTT protocol that employs heparin flushes results in marked elevations in NEFA in Type 2 diabetic patients with poor beta cell dysfunction but not in subjects with intermediate or normal glucose tolerance. The higher plasma NEFA levels during heparin injections could worsen the model-derived, insulin sensitivity index and could impair the ability to achieve an acceptable modelling in Type 2 diabetic patients. We therefore suggest heparin should be avoided in such patients when using this protocol.     

Genome-wide linkage scans for prediabetes phenotypes in response to 20 weeks of endurance exercise training in non-diabetic whites and blacks: the HERITAGE Family Study

Aims/hypothesis Impaired insulin secretion, insulin action, insulin-independent glucose effectiveness, glucose tolerance and the associated abnormalities in insulin and glucose metabolism phenotypes are precursors of type 2 diabetes. Genome-wide multipoint variance component linkage scans were carried out using 654 markers to identify quantitative trait loci for insulin sensitivity, acute insulin response to glucose, disposition index and glucose effectiveness training responses in whites and blacks in the HERITAGE Family Study.Methods These phenotypes were obtained from an IVGTT with the minimal model. The distributions of insulin sensitivity, acute insulin response to glucose and disposition index training responses (post-training minus baseline) were approximately normalised using a square-root transformation. All phenotypes were adjusted for the effects of age, BMI and their respective baseline values within sex and generation by race prior to linkage scans.Results In blacks, a promising linkage with a maximum lod score of 3.1 on 19q (54–62 Mb) for glucose effectiveness training response was found. Six interesting linkages with lod scores of at least 1.0 were found for disposition index training response in whites. They included 1p (30 Mb), 3q (152 Mb), 6p (23–42 Mb), 7q (95–96 Mb), 10p (15 Mb) and 12q (119–126 Mb).Conclusions/interpretation Quantitative trait loci for 20 weeks of endurance exercise training responses in insulin action and glucose metabolism phenotypes were found on chromosome 19q as well as 6p and 7q, with nominal (6p, 7q) but consistent (6p) linkages across the races.     

Relationships between fibrinogen and insulin resistance

A relationship between plasma fibrinogen levels and insulinemia, as well as the different parameters of the insulin resistance syndrome has been described. The aim of the present paper was to investigate whether plasma fibrinogen concentrations were linked to plasma insulin levels or to the degree of insulin resistance. For this purpose, 62 nondiabetic, nonhypertensive patients, 30 men and 32 women, with body mass indexes (BMIs) and ages ranging from 18.6 to 50.2 kg/m² and from 19 to 60 years, respectively, were studied. Insulin sensitivity was quantified by the minimal model procedure over a 180-min intravenous glucose tolerance test with iterative sampling. Plasma insulin was determined by radioimmunoassay without cross-reactivity to human proinsulin, and fibrinogen by the method of Clauss. Insulin sensitivity ranged from 0.009 to 23.2 min⁻¹/(μU/ml)×10⁻⁴, covering the whole range of insulin sensitivities. Fibrinogen ranged from 1.70 to 5.07 g/l. There was a significant negative correlation between fibrinogen and insulin sensitivity (r=−0.76, P<0.0001) and a positive correlation between fibrinogen and basal insulin (r=0.56, P<0.0001). After adjustment for BMI, body fat mass and waist-to-hip ratio, these two relationships remained significant. In addition, a multiple regression analysis was performed to assess the independent effect of the following related variables: fibrinogen, insulin sensitivity, insulinemia and BMI. Only insulin sensitivity appeared to account for the ability to predict fibrinogen values. Thus, we hypothesized it was likely that the state of insulin resistance rather than hyperinsulinemia per se was related to hyperfibrinogenemia. We proposed an interpretation of these data in connection with some factors like free fatty acids or tumor necrosis factor-, which have been implicated in the pathogenesis of insulin resistance. Nevertheless, prospective and intervention studies are needed to assess whether there is a simple association or a causal relationship between insulin resistance and hyperfibrinogenemia.     

薏苡仁多糖对实验性2型糖尿病大鼠胰岛素抵抗的影响

目的 观察薏苡仁多糖对实验性2型糖尿病大鼠胰岛素抵抗的影响。方法 用小剂量链脲佐菌素（25mg/kg,iv)加高热量饲料（热卡：20.083J/g)建立实验性2型糖尿病大鼠模型，然后用薏苡仁多糖分三个剂量组（25、50、100mg/kg，ip)给药治疗2周，并测定葡萄糖耐量，血浆胰岛素以及肝糖原、肌糖原、肝细胞膜胰岛素受体结合率和肝葡萄糖激酶活性。结果 薏苡仁多糖能改善实验性2型糖尿病大鼠糖耐量异常，增加肝糖原量和肝葡萄糖激酶活性，且呈现一定的量效关系。但对血浆胰岛素水平及胰岛素受体最大结合率和受体最大结合容量均无影响。结论 薏苡仁多糖能够改善实验性2型糖尿病大鼠胰岛素抵抗，这可能与其调节糖代谢酶的活性有关。     

新HOMA稳态模型在临床中的应用

目的研究利用新HOMA稳态模型HOMA2计算的胰岛素敏感性指数（ISI）和分泌功能指数在临床的应用价值。方法选取80名志愿者，其中正常糖耐量（NGT）31人、糖调节异常（IGR）26人，2型糖尿病（T2DM）23人；抽取空腹血测定血糖、胰岛素（Ins）、真胰岛素（TI）和C肽水平，利用HOMA2计算器分别计算三种ISI（HOMA2-％S-Ins、HOMA2-％S-TI和HOMA2-％S-C）和三种胰岛素分泌功能指数（HOMA2-％B-Ins、HOMA2-％B-TI和HOMA2-％B-C），比较上述指数区分不同糖耐量组的胰岛素敏感性和分泌功能变化的能力。结果在三种ISI中，利用空腹TI计算的HOMA2-％S-TI区分三组的胰岛素敏感性的能力相对最强（F=4．888，P〈0．01），利用空腹Ins计算的HOMA2-％S-Ins次之（F=3．397，P〈0．05），利用空腹C肽计算的HOMA2-％S-C不能区分三组的胰岛素敏感性（F=1．042，P〉0．05）。利用HOMA2-％S-TI调整后，三种胰岛素分泌功能指数区分三组胰岛素分泌功能的能力非常接近（F值分别为60．323、58．203和58．179，P〈0．01），且均可很好区分IGR组和DM组的胰岛素分泌功能，其中只有HOMA2-％B-C可较好区分NGT组和IGR组的胰岛素分泌功能（t=2．2709，P〈0．05）。结论利用新HOMA稳态模型计算的HOMA2-％S-TI是一个相对较好的计算ISI的公式，HOMA2-％B-C是一个相对较好的计算胰岛素分泌功能指数的公式。