Insulin sensitivity, proinsulin and insulin as predictors of coronary heart disease. A population-based 10-year, follow-up study in 70-year old men using the euglycaemic insulin clamp

Aims/hypothesis The association between CHD and insulin sensitivity (Si) measured by the euglycaemic insulin clamp has not been examined previously. Earlier studies found a relationship between CHD and elevated plasma insulin, an analysis that may have been confounded by co-determination of proinsulin, which has evolved as a stronger predictor of CHD. The aim was to determine the longitudinal relationships between Si, intact proinsulin, 32–33 split proinsulin, specific insulin and subsequent CHD.Methods This was a population-based cohort study of 815 men in Uppsala, Sweden, aged 70 years at baseline with a follow-up of up to 10 years. Baseline insulin sensitivity was determined by euglycaemic insulin clamp. Fasting proinsulin, 32–33 split proinsulin and specific insulin concentrations were analysed using specific two-site immunometric assays. CHD was taken as diagnosed, if stated (in the event of death) on the Cause of Death Registry, or for subjects hospitalised for the first time with CHD, if CHD was recorded in the Hospital-Discharge Registry. The associations were analysed using Coxs proportional hazards, presented as hazard ratios (HRs) with their 95% CIs for a one-SD increase in the predictor.Results In multivariate analysis, Si (HR:0.80, CI:0.65–0.97) adjusted for serum cholesterol, systolic blood pressure, fasting plasma glucose, BMI and smoking predicted CHD. Intact proinsulin (HR:1.18, CI:1.01–1.38), adjusted as the model above, predicted CHD, whereas 32–33 split proinsulin (HR:1.13, CI:0.95–1.35) or specific insulin (HR:1.07, CI:0.89–1.30) did not.Conclusions/interpretation Insulin resistance measured by the euglycaemic insulin clamp predicts subsequent CHD in elderly men. Proinsulin provides a better prediction of CHD than insulin.     

血清瘦素水平与胰岛素原、真胰岛素及胰岛素敏感性的关系

目的　研究中国人群空腹瘦素水平与真胰岛素 (TI)、胰岛素原 (PI)、PI/TI比值及胰岛素敏感性之间的关系。方法　 90 2例非糖尿病者均系 2 0 0 0年接受糖尿病流行病学调查者。测定空腹瘦素、TI和PI浓度以及空腹及餐后 2h血糖。瘦素、TI及PI检测采用本室建立的特异的酶联免疫分析法 (ELISA)。胰岛素敏感性以HOMA胰岛素抵抗指数 (HOMA IR)评价。结果　血清瘦素水平女性高于男性。相关分析显示血清瘦素水平与空腹TI、PI及HOMA IR显著正相关 (男性 792例 ,r分别为0 345、0 2 36和 0 364 ;女性 1 1 0例 ,r分别为 0 574、0 375和 0 576 ,P <0 0 0 1 ) ,但与空腹血糖仅在男性呈弱相关 (r=0 1 5 ,P =0 0 1 5) ,与空腹PI/TI比值不相关。在调整年龄、体重指数 (BMI)和腰臀围比(WHR)后 ,尽管相关性减弱 ,瘦素水平仍然与TI、PI以及HOMA IR显著相关。结论　本组的血清瘦素浓度与TI、PI以及胰岛素抵抗显著正相关 ,且在一定程度上独立于肥胖和脂肪分布。瘦素水平高或瘦素抵抗的个体可能存在高胰岛素血症和胰岛素抵抗 ,提示其瘦素 胰岛素轴的调节异常。本研究未发现瘦素水平与空腹PI/TI比值的相关 ,提示瘦素可能与这一反映胰岛 β细胞的功能异常的标志无关。本研究揭示的高瘦素 高胰岛素血症或胰岛素抵抗之间的     

高血压病患者的真胰岛素、胰岛素原水平及其与血压的关系

目的 探讨高血压病患的真胰岛素（TI）,胰岛素原（PI）水平及其与血压的关系,方法 测定非糖尿病的66例高血压病患及73例血压正常的收缩压（SBP）,舒张压（DBP）,血脂及口服葡萄糖耐量试验（OGTT）各点的血糖,血清TI和PI水平,TI及PI测定采用特异的单克隆抗体放大酶联免疫分析法（BA－ELISA）。结果 高血压病组在调整年龄,体重指数（BMI）和腰臂比（WHR）,其糖负荷后2h的PI及PI／TI水平显高于对照组（P＜0．05）,两而组间TI差异无统计学意义,单相关分析显SBP与空腹PI,2h PI及2h PI/TI 显相关,而BP仅与2h PI/TI显相关（P＜0．05）,仅在非肥胖组发现SBP与2hTI呈正相关（P＜0．05）,多因素回归分析显示2h PI独立于年龄,BMI,血糖和血脂等影响血压的混杂因素与SBP及高血压显相关。结论 本人群中高血压病患存在糖负荷后高PI血症,血清PI而非TI水平与高血压显正相关。     

Insulin,proinsulin, proinsulin:insulin ratio,and the risk of developing type 2 diabetes mellitus in women

PURPOSE: To assess the associations among baseline levels of fasting insulin and proinsulin, proinsulin:insulin ratio, and the development of type 2 diabetes mellitus in apparently healthy middle-aged women. METHODS: In a nested case-control study involving a nationwide cohort of 27,628 participants from the Women's Health Study, 126 women with diabetes diagnosed during a 4-year follow-up period were compared with 225 age-matched controls. Fasting insulin level and proinsulin:insulin ratio were assessed in quartiles, and proinsulin level was assessed in categories (< or =4.0 pmol/L, 4.01 to 6.99 pmol/L, > or =7.0 pmol/L). The risk of developing type 2 diabetes was determined using conditional logistic regression analysis that adjusted for body mass index and other diabetes risk factors. RESULTS: Baseline insulin and proinsulin levels and proinsulin:insulin ratios were significantly higher among cases than among controls. Women with elevated insulin levels in the highest as compared with the lowest quartile were more likely to develop diabetes (odds ratio [OR] = 5.6; 95% confidence interval [CI]: 1.8 to 17.6), as were women with elevated (> or =7.0 pmol/L vs. < or =4.0 pmol/L) proinsulin levels (OR = 16.4; 95% CI: 5.8 to 46.8) and women with proinsulin:insulin ratios in the highest quartile (OR = 9.6; 95% CI: 3.1 to 30.8). Similar results were observed among women with a baseline hemoglobin A(1c) level < or =6.0%. In time-trend analyses, fasting insulin was a consistent predictor of long-term risk. Proinsulin and proinsulin:insulin ratio, although predictive throughout the study, were especially strong predictors of rapid progression to type 2 diabetes. CONCLUSION: Elevated fasting insulin and proinsulin levels and proinsulin:insulin ratio are associated with an increased risk of developing type 2 diabetes in apparently healthy middle-aged women.     

Heritability and genetic correlations of insulin sensitivity measured by the euglycaemic clamp.

AIMS: Studies investigating genetic factors influencing insulin sensitivity/insulin resistance have measured this phenotype using a variety of methods. In this study, genetic correlations and heritability of insulin sensitivity measured using the euglycaemic hyperinsulinaemic clamp and related phenotypes were examined. METHODS: The study population included 818 non-diabetic individuals from 297 nuclear families. Genetic correlations and heritability estimates were calculated using variance components methods. RESULTS: Homeostasis model of insulin resistance (HOMA-IR) and fasting insulin were very highly phenotypically and genetically correlated (r = 0.99 and r = 0.99). HOMA-IR and insulin sensitivity measured with the euglycaemic clamp were only moderately genetically correlated (r = -0.53), suggesting that the two traits may be influenced, at least in part, by different genes. Heritabilities for fasting insulin (h2 = 0.36) and HOMA-IR (h2 = 0.38) were consistent with the published literature, but heritability for insulin sensitivity measured by the euglycaemic clamp was slightly lower than other published estimates (h(2) = 0.24). CONCLUSIONS: Because HOMA-IR (or fasting insulin) and insulin sensitivity measured with the euglycaemic clamp are not highly genetically correlated, they should not be used interchangeably in genetic studies. Given the very high correlations between fasting insulin and HOMA-IR, HOMA-IR does not offer any advantage over fasting insulin in analyses of insulin sensitivity in this population.     

胰岛素原、真胰岛素与冠心病危险因素的关系

目的 探讨胰岛素原（PI）,真胰岛素（TI）是否与冠心病危险因素相关。方法 采用BAELISA法测定119例入选口服葡萄糖耐量试验（OGTT）各时相的PI,TI水平,并与冠心病危险因素及其数目作相关分析。结果 空腹及糖负荷2h PI,TI与冠心病危险因素数目（r=0.19-0.33), 体重指数（BMI）(r=0.23-0.41)及WHR（r=0.32-0.51)呈正相冯,而与HDL－C（r=0.22-0.30),负相关;空腹PI及2h糖同PI,TI高血压（r=0.18-0.20),葡萄糖耐量减低（IGT）（r=0.13-0.34),TG(r=0./32-0.33)和尿酸（r=0.27-0.36)呈正相关,空腹及2h PI与apoB(r=0.26)呈正相关,2h PI与TC（r=0.21)及家庭史（r=0.21)呈正相关;经校正年龄,性别,BMI,WHR（腰臂比值）,空腹及2h血糖后,TI与血脂的关系消失,PI与血脂的关系减弱;空腹PI与TG（r=0.32),apoB(r=0.19)及尿酸（r=0.22)呈正相关,2h PI与apoB(r=0.27)及尿酸（r=0.20)正相关,与HDL－C（r=-0.21)呈负相关,多元逐步回归分析法亦显示PI与血脂的关系比TI更密切,结论 PI,TI与冠心病危险因素有明显关系,而且PI比TI与冠心病危险因素的关系更密切。     

肥胖青少年血清瘦素、胰岛素和胰岛素原水平的变化

目的　检测肥胖青少年血清瘦素、胰岛素、胰岛素原水平的变化 ,探讨青少年肥胖与代谢综合征的关系。方法　从年龄 14～ 16岁的 2 2 17例学生中筛选出体重指数 (BMI)≥ 2 5kg/m2 的肥胖学生 (肥胖组 ) 198例 ,BMI在 18 5～ 2 3 0kg/m2 之间的体重正常学生 (正常组 ) 78例 ,用放射免疫方法测定血清瘦素、胰岛素和胰岛素原水平 ,同时测定血糖及血脂水平 ,比较两组间差异。结果　血清瘦素水平女生明显高于同龄男生 [(18 5 3± 1 4 1) μg/L比 (6 33± 1 79) μg/L]。肥胖组血清瘦素、胰岛素和胰岛素原水平均高于同龄体重正常者 [分别为 (19 94± 1 91) μg/L比 (11 2 7± 2 0 4 ) μg/L ,(15 34± 1 6 6 ) μIU/L比 (13 17± 1 4 3) μIU/L ,(16 19± 1 6 4 )pmol/L比 (11 79± 1 70 )pmol/L ],血糖、甘油三酯 (TG)和高密度脂蛋白胆固醇 (HDL C)水平虽然在正常范围内 ,但肥胖者血糖和TG水平高于同龄体重正常者 [分别为 (4 6 3± 0 5 0 )mmol/L比 (4 13± 0 33)mmol/L ,(1 2 0± 0 5 6 )mmol/L比 (0 90±0 32 )mmol/L],HDL C水平低于同龄体重正常者 [(1 14± 0 2 4 )mmol/L比 (1 38± 0 2 6 )mmol/L]。结论　肥胖青少年可能存在瘦素抵抗、胰岛素抵抗及潜在的糖代谢和脂代谢异常等代谢综合征改变 ,     

不同糖耐量个体血清瘦素水平与特异胰岛素、胰岛素原及胰岛素敏感性的关系探讨

目的　研究不同糖耐量人群空腹瘦素水平与特异胰岛素、胰岛素原及胰岛素敏感性之间的关系。方法　用放射免疫法测量 5 4例正常糖耐量 (NGT)、33例糖耐量低减 (IGT)、4 7例新发 2型糖尿病 (DM )的空腹瘦素水平、口服葡萄糖耐量试验 (OGTT) 0、1/2、1、2h的特异胰岛素 (SI)和胰岛素原 (PI)。结果　 (1)多元逐步回归分析显示 ,性别、体重指数 (BMI)、胰岛素敏感性指数是影响空腹瘦素水平最重要的因素 (校正的R2 分别为 0 .2 5 1、0 .4 19、0 .4 38,P值分别为 <0 .0 0 1、<0 .0 0 1、<0 .0 5 ) ;空腹血清瘦素水平与OGTT各时间点PI、SI、PI/SI值无相关性。 (2 )在校正性别、BMI等影响因素后 ,空腹血清瘦素水平在不同糖耐量组差异无显著性 ;DM组OGTT各时间点PI/SI值明显高于IGT组和NGT组 (P <0 .0 1) ;胰岛素敏感性 (ISI)为NGT组 >IGT组 >DM组 (P <0 .0 0 1)。结论　在测定特异胰岛素、胰岛素原时 ,血清瘦素水平除了与性别、BMI相关外 ,尚与胰岛素敏感性 (按SI水平计算 )相关 ;不同糖耐量状态对血清瘦素水平无明显影响 ;DM组存在胰岛素不敏感、PI/SI失调     

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     

The relation of proinsulin and insulin to insulin sensitivity and acute insulin response in subjects with newly diagnosed Type II diabetes: the Insulin Resistance Atherosclerosis Study

Abstract Aims/hypothesis. Proinsulin concentrations are increased relative to insulin concentrations in subjects with Type II (non-insulin-dependent) diabetes mellitus. This could be secondary to hyperglycaemia or insulin resistance or due to a defect in insulin secretion. Methods. We investigated the association between fasting insulin, intact proinsulin and the intact proinsulin: insulin ratio with insulin sensitivity, estimated by a frequently sampled intravenous glucose tolerance test and the minimal model and with acute insulin response (AIR) in 182 newly diagnosed Type II diabetic subjects aged 40 to 69 years. None of the subjects was receiving hypoglycaemic medication. Results. Insulin sensitivity correlated inversely with fasting insulin (r _s = –0.42) and intact proinsulin (r _s = –0.32) (p < 0.001). The intact proinsulin:insulin ratio was not correlated with insulin sensitivity. AIR correlated positively with intact proinsulin (r _s = 0.23) and inversely with the intact proinsulin:insulin ratio (r _s = –0.29, p < 0.001). Fasting glucose correlated positively with intact proinsulin (r _s = 0.34) and the intact proinsulin:insulin ratio (r _s = 0.24, p < 0.001). The intact proinsulin:insulin ratio increased by decreasing AIR (quartiles of AIR from high to low: 7.8, 8.2, 9.7 and 12.1 %, p < 0.001). This association was independent of age, sex, ethnicity, body mass index, fasting glucose, and insulin sensitivity. Conclusion/interpretation. Insulin resistance (low insulin sensitivity) was not related to the intact proinsulin:insulin ratio in subjects with Type II diabetes. In contrast, both low AIR and high fasting glucose concentrations were associated with a disproportionate increase in proinsulin concentration. These results suggest that increased intact proinsulin:insulin ratio is a marker of a defect in insulin secretion in Type II diabetic subjects. [Diabetologia (1999) 42: 1060–1066] Received: 25 February 1999 and in revised form: 12 April 1999     

Reduction of platelet aggregation induced by euglycaemic insulin clamp

Summary To examine the effect of serum insulin independent of the level of blood glucose in vivo on platelet aggregation in healthy individuals, a euglycaemic insulin clamp was applied up to 4 h. During the clamp, blood glucose at 5.0 mmol/l and insulin levels at 100 U/ml were maintained. Blood samples were drawn before, 2 and 4 h after the start of the insulin clamp. The platelet aggregation induced by 1 mol/l and 2 mol/l ADP, 1 g/ml collagen and 2.7 mol/l epinephrine was measured in the blood samples. Platelet aggregation induced by adenosine diphosphate, collagen and epinephrine in the 4 h sample was significantly reduced from the pre-clamp value of 8.4% to 3.9% (p<0.05), 26.2% to 7.0% (p<0.01) and 31.8% to 9.1% (p<0.01), respectively. On the other hand, when the same individuals were infused with physiological saline and blood glucose (4.4 mmol/l) and insulin level (10 mIU/l) were kept within normal values, there was no difference between the values of induced platelet aggregation in samples drawn before and during the insulin infusion. It was concluded that hyperinsulinaemia reduces platelet aggregation in vivo when euglycaemia was maintained.     

胰岛素抵抗与老年男性高血压和卒中的关系

目的探讨胰岛素抵抗与老年男性高血压和卒中的关系。方法采用前瞻性设计,收集70例脑梗死（脑梗死组）、62例脑出血（脑出血组）、58例非卒中（对照组）老年男性患者的临床资料。每组再根据有无高血压病史进一步分层,3组依次有高血压病史分别为40、42、32例,无高血压病史分别为30、20、26例。清晨空腹取血,分别测定血脂、空腹血糖、空腹胰岛素,计算胰岛素敏感指数。在控制高血压、脂质异常后,应用多元Logistic回归分析卒中与胰岛素抵抗的关系。结果①与对照组比较,脑梗死组和脑出血组组三酰甘油、胆固醇、低密度脂蛋白胆固醇、空腹胰岛素水平升高,差异有统计学意义（P〈0.05）;高密度脂蛋白胆固醇、胰岛素敏感指数水平降低,差异有统计学意义（P〈0.05）。②按有无高血压病史进行分层后比较胰岛素抵抗,3组中无论有无高血压病史,脑梗死和脑出血患者的空腹胰岛素及胰岛素敏感指数与对照组比较,差异均有统计学意义（均P〈0.05）。高血压合并卒中患者的空腹胰岛素、胰岛素敏感指数与血压正常卒中患者比较,差异有统计学意义（P〈0.05）。而3组空腹血糖比较,差异无统计学意义（P〉0.05）。③控制了高血压、脂质异常等因素之后,多元Logistic回归分析显示,胰岛素抵抗是卒中的独立危险因素（P=0.010,OR=1.495,95％ CI：1.102-2.028）。结论高血压可能通过增加胰岛素抵抗而增加卒中发生的风险。胰岛素抵抗可能是老年男性卒中发生的独立危险因素。     

The short insulin tolerance test for determination of insulin sensitivity: a comparison with the euglycaemic clamp.

The glucose clamp technique is currently regarded as the standard test for measuring insulin sensitivity against which other methods are compared but is unsuitable for routine screening of patients outside a hospital base. There is thus a need for a simpler test to measure insulin sensitivity. We have therefore compared the glucose disappearance rate KITT in the first 15 min of the insulin tolerance test (ITT) with the M and M/I values derived from the standard euglycaemic clamp in nine normal subjects and eight subjects with Type 2 (non-insulin dependent) diabetes mellitus and coexisting obesity. All subjects underwent the ITT and euglycaemic clamp in random order. Nine subjects later had a repeat ITT to determine the reproducibility of the test. In the ITT, 0.1 U kg-1 body weight, human Actrapid insulin was given as an IV bolus and simultaneous arterialized and venous blood samples were obtained every minute for 15 min. The first order rate constant for the disappearance of glucose KITT over the period 3-15 min was taken as a measure of insulin sensitivity. The euglycaemic clamp was performed with an insulin infusion of 50 mU kg-1 h-1 for 120 min and a variable rate glucose infusion to maintain blood glucose concentration at 0.5 mmol l-1 below fasting level to minimize the effect of endogenous insulin secretion. The ratio of the mean rate of glucose infused (M, mumol kg-1 min-1) to the plasma insulin over the last 30 min of the clamp was taken as a measure of tissue sensitivity to insulin (M/I) assuming endogenous glucose output was suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)     

老年人真胰岛素、胰岛素原水平及β细胞功能的变化

目的：探讨增龄对血清真胰岛素（TI）、胰岛素原（PI）水平及胰岛β细胞功能的影响。方法：筛选糖耐量正常的健康老年人7例（60－78岁）和中青年对照组60例（30－49岁）。测量血压，身高，体重，腰臂围，计算体重指数（BMI）和腰臂比（WHR）。测定空腹血脂及口服葡萄糖耐量试验各点的血糖、TI及PI浓度。结果：两组性别、BMI和空腹血糖相匹配（P＞0．05），老年组的WHR及血压高于对照组（P＜0．05）。老年组的空腹PI水平和PI／TI比值的几何均值分别为5．0pmol/L和0．21，明显高于对照组（分别为3．1pmol/L和0．13，均为P＜0．01），糖负荷后2h的PI和PI／TI值老年组也高于对照组（34．1pmol/L与20．5pmol/L，0．30与0．22，均为P＜0．05），但在调整WHR和血糖后统计学差别消失（P＞0．05）。两组间空腹和服糖后2h的TI水平，差异均无统计学意义（P＞0．05）。结论：老年人存在空腹高PI血症及PI不成比例的分泌增加，提示其β细胞功能异常，这一变化趋势可能与老年人易发2型糖尿病有关。     

Association of fasting glucagon and proinsulin concentrations with insulin resistance

Aims/hypothesis Hyperproinsulinaemia and relative hyperglucagonaemia are features of type 2 diabetes. We hypothesised that raised fasting glucagon and proinsulin concentrations may be associated with insulin resistance (IR) in non-diabetic individuals. Methods We measured IR [by a euglycaemic–hyperinsulinaemic (240 pmol min⁻¹ m⁻²) clamp technique] in 1,296 non-diabetic (on a 75 g OGTT) individuals [716 women and 579 men, mean age 44 years, BMI 26 kg/m² (range 18–44 kg/m²)] recruited at 19 centres in 14 European countries. IR was related to fasting proinsulin or pancreatic glucagon concentrations in univariate and multivariate analyses. Given its known relationship to IR, serum adiponectin was used as a positive control. Results In either sex, both glucagon and proinsulin were directly related to IR, while adiponectin was negatively associated with it (all p < 0.0001). In multivariate models, controlling for known determinants of insulin sensitivity (i.e. sex, age, BMI and glucose tolerance) as well as factors potentially affecting glucagon and proinsulin (i.e. fasting plasma glucose and C-peptide concentrations), glucagon and proinsulin were still positively associated, and adiponectin was negatively associated, with IR. Finally, when these associations were tested as the probability that individuals in the top IR quartile would have hormone levels in the top quartile of their distribution independently of covariates, the odds ratio was ∼2 for both glucagon (p = 0.05) and proinsulin (p = 0.02) and 0.36 for adiponectin (p < 0.0001). Conclusions/interpretation Whole-body IR is independently associated with raised fasting plasma glucagon and proinsulin concentrations, possibly as a result of IR at the level of alpha cells and beta cells in pancreatic islets. Electronic supplementary material The online version of this article (doi:) contains a list of the European Group for the Study of Insulin Resistance RISC investigators, which is available to authorised users.     

胰岛素瘤及正常胰腺组织中胰岛素原、胰岛素的表达

目的 检测胰岛素瘤及瘤旁正常胰腺组织中胰岛素、胰岛素原、C肽的表达水平,探讨它们的作用.方法 选取2006年9月至2009年12月确诊的38例胰岛素瘤及20例相应瘤旁正常胰腺组织标本,采用免疫组化染色的方法检测组织中胰岛素原、胰岛素、C肽的表达.结果 胰岛细胞瘤和瘤旁正常胰腺组织均表达胰岛素、C肽、胰岛素原.100%的胰岛素瘤组织胰岛素原和C肽强表达,而55%～60%正常胰腺组织为弱表达;79%的胰岛素瘤组织胰岛素表达为+++,而85%的正常胰腺组织胰岛素的表达为++++.38例胰岛素瘤的胰岛素原、C肽阳性表达细胞数占80%～100%,胰岛素阳性表达细胞数占50%～70%,胰岛素原/胰岛素＞1占78.9%,正常胰腺组织分别为20%～80%、60%～90%、10.0%,两者差异均非常显著(P值均＜0.05).结论 胰岛素瘤组织的胰岛素原/胰岛素＞1者占78.9%,测定血浆胰岛素原可能有助于其诊断.     

血清真胰岛素、胰岛素原与冠心病关系初探

目的：探讨冠心病（CHD）患者血清真胰岛素（TI）,胰岛素原（PI）水平,并分析这二者与其他CHD危险因子的关系。方法：对30例确诊CHD患者和30例正常人采用高度特异性的ELISA法分别检测空腹血清TI,PI和以RIA法检测空腹血清免疫活性胰岛素（IRI）水平,同时检测这二组对象的空腹和餐后2小时血糖,血脂以及血压水平,结果：CHD组IRI,TI,PI水平均高于对照组（P＜0．05）,而胰岛素敏感指数（ISI）则低于对照组（P＜0．05）,CHD组中TI,PI与年龄,BMI,血糖和血脂均有独立的相关关系,结论：CHD患者有高胰岛素血症和胰岛素抵抗状态,TI,PI分别与血糖,血脂等CHD危险因子呈群聚关系。     

In vitro conversion of proinsulin to insulin by cathepsin B and role of C-peptide

Summary Cathepsin B, purified from isolated islets of Langerhans, when incubated with proinsulin underin vitro conditions could convert proinsulin to insulin and C-peptide, releasing free arginine and lysine. When C-peptide, prepared from rat pancreas, was added to the incubation system consisting of proinsulin and cathepsin B, it completely inhibited the conversion of proinsulin to insulin. Communication no. 2295 from the Central Drug Research Institute, Lucknow, India.     

Antibodies to proinsulin and insulin as predictive markers of type 1 diabetes

The aim of the present study was to test whether proinsulin autoantibodies (IgG-PAA), insulin autoantibodies (IgG-IAA), and islet cell antibodies (ICA) may be used to identify subjects at risk for Type 1 diabetes. Pre-diabetic sera from 18 individuals who later developed diabetes were tested. Results were compared with 18 age-, sex-, and HLA-DR-matched non-diabetic control subjects from families with Type 1 diabetes. At a mean of 2.4 yr before the onset of diabetes, ICA were found in 13 patients (vs 0 control subjects, p less than 0.001), ELISA-determined IgG-IAA in 8 patients (vs 1 control subject, p less than 0.05) and ELISA-determined IgG-PAA in 4 patients (vs 2 control subjects, NS). ELISA-determined IgG-PAA do not appear to be useful predictors of the future development of Type 1 diabetes.