2型糖尿病胰岛素抵抗的可能发生机理

胰岛素抵抗是2型糖尿病发病的重要因素，关于胰岛素抵抗发生机制尚不完全清楚，各种实验研究结果显示，下列因素可能导致胰岛素抵抗状态的出现：1）炎症假说；2）信号转导假说，包括PKC-ζ、SH3GL2、PTPN1等；3）其它可能因素，包括β3-AR基因突变、CETP—Taq1B基因、胰岛素受体底物（IRS）-2分子等。这些都是可能导致胰岛素抵抗状态发生的相关因素，胰岛素抵抗贯穿于糖尿病的全过程中，导致一系列的重要病理生理变化，明确2型糖尿病胰岛素抵抗的发生机理对于治疗糖尿病有着十分积极的意义，这就有待于我们医务工作者进一步深入探讨。     

2型糖尿病肾病大鼠胰岛素抵抗与足细胞减少的相关性分析

目的探讨2型糖尿病肾病大鼠胰岛素抵抗与足细胞减少的关系。方法选取40只Wistar大鼠随机分为2组（对照组和糖尿病肾病组），观察各组大鼠血糖、血胰岛素、24h尿微量白蛋白及足细胞的动态变化。结果2型糖尿病肾病大鼠胰岛素抵抗与足细胞减少呈正相关。结论胰岛素抵抗在2型糖尿病’肾病发病及足细胞减少过程中起一定的作用。     

OGTT实验中的1小时血糖升高值临床意义探究

目的：探讨OGTT实验中的1h血糖（1hPG）与胰岛素抵抗的相关性。方法：总结近期的相关论文,以综合评价1hPG与糖尿病发生风险及胰岛素抵抗的关系。结果：同餐后2h血糖及空腹血糖值相比,1hPG与胰岛素分泌及胰岛素抵抗的相关性更好。结论：1hPG能够更好地反映胰岛素抵抗,更好地预测糖尿病发生。     

番石榴叶对2型糖尿病大鼠胰岛素抵抗的治疗作用

目的：研究番石榴叶水煎剂对2型糖尿病大鼠胰岛素抵抗的影响。方法：建立2型糖尿病大鼠模型，随机分为模型对照组、番石榴叶大、中、小剂量组，每组10只，用番石榴叶水煎剂治疗8周，测定空腹血糖、血清胰岛素，计算出胰岛素抵抗指数。结果：治疗组胰岛素抵抗指数高于模型组，并且与正常对照组比较差异无显著性意义。结论：番石榴叶能降低2型糖尿病大鼠的胰岛素抵抗。     

老年2型糖尿病患者高甘油三酯血症对血管内皮功能的影响

2型糖尿病患者中有40%～50%合并脂代谢异常,高甘油三酯 (TG)血症和高血糖症是心脑血管病的独立危险因素[1].胰岛素抵抗可能是它们的共同发病基础,内皮功能减退是它们共同作用的结果.为此,我们分析60例血压正常的老年2型糖尿病患者,探讨血脂水平与老年2型糖尿病患者血管内皮功能、胰岛素抵抗(IR)及血糖代谢之间的关系,并追踪观察高TG血症控制后的血管内皮功能变化.     

抵抗素与肥胖、胰岛素抵抗的研究进展

抵抗素(resistin)是新近发现的脂肪细胞分泌的一种富含半胱氨酸的蛋白质，被认为是小鼠肥胖与胰岛素抵抗之间的重要中间环节。resistin的发现为肥胖与胰岛素抵抗提供了一个新的研究方向，它可能是肥胖与胰岛素抵抗、糖尿病的一个联系纽带，但其生物学功能及与肥胖、胰岛素抵抗、2型糖尿病的关系尚有待进一步研究。本介绍了resitin的结构特点及其与肥胖、胰岛素抵抗、糖尿病的关系等。     

老年糖尿病胰岛素抵抗与脂代谢紊乱

目的：探讨老年糖尿病患胰岛素抵抗与脂代谢紊乱之间的关系。方法P：测定118例老年糖尿病患空腹血糖，血脂，载脂蛋白，胰岛素并与90例非糖尿病人作对照，糖尿病患被分为胰岛素抵抗组与非胰岛素抵抗组。结果：（1）胰岛素抵抗组的TG，CH，LDL，VLDL水平与非糖尿病人组及非胰岛素抵抗组相比显升高（P＜0．01）。（2）非胰岛素抵抗组与非糖尿病组相比CH明显升高（P＜0．05），结论：老年糖尿病胰岛素抵抗与脂代谢紊乱密切相关。     

2型糖尿病家系胰岛素抵抗及危险因素分析

目的 研究2型糖尿病（T2DM）家系人群的胰岛素抵抗与心血管疾病危险因素聚集的关系。方法 选取2型糖尿病家系115个。共计570人，其中268例糖尿病患者为病例组，非糖尿病一级血缘亲属302人为内对照组，健康者161人为外对照组，应用x^2检验以及二项分类Logistic回归方法。结果 3组的心血管危险因素聚集程度与胰岛素抵抗程度有关（均P〈0．05）。随着胰岛素抵抗指数（HOMA-IR）的增高，3组人群的心血管疾病危险因素聚集的风险均增加。内对照组的胰岛初期分泌功能指数的平均水平高于T2DM人群和外对照人群（P=0．018，0．000）。结论 健康人群在未发生糖尿病之前均有胰岛素抵抗，因胰岛β细胞代偿性分泌增加，故不发病；当其失代偿时．则导致糖尿病发生。胰岛素抵抗为心血管疾病危险因素聚集的基础，心血管疾病危险因素聚集则是导致家系2型糖尿病高发的原因之一。     

2型糖尿病患者正常糖耐量一级亲属红细胞膜胰岛素受体变化及与胰岛素抵抗的相关性

目的探讨2型糖尿病患者正常糖耐量一级亲属(NFDR)红细胞膜胰岛素受体变化及与胰岛素抵抗的相关性。方法102例2型糖尿病患者正常糖耐量一级亲属作观察组,60例无糖尿病家族史的非糖尿病患者作对照组,测定空腹血糖(FPG)、胰岛素(FINS)、血脂、餐后2 h血糖(2 h PG)、2 h胰岛素(2 h INS),并检测高、低亲和力红细胞膜胰岛素受体数目(R1、R2)和高、低亲和力常数(K1、K2),同时计算胰岛素抵抗指数(IRI)。结果2型糖尿病患者正常糖耐量一级亲属R1、R2明显低于对照组;2 h PG、三酰甘油、低密度脂胆白胆固醇水平高于对照组,差别有统计学意义(P<0.05,P<0.01);FINSI、RI高于对照组,差别有统计学意义(P<0.05)。多元线性逐步回归分析结果显示,体质指数、三酰甘油、R1、R2是影响2型糖尿病患者正常糖耐量一级亲属胰岛素抵抗独立的危险因素。结论2型糖尿病患者正常糖耐量一级亲属存在明显胰岛素抵抗,且与红细胞膜胰岛素受体数目的减少有一定关系。     

罗格列酮对初诊2型糖尿病患者胰岛素抵抗指数C-反应蛋白影响

目前研究认为糖尿病是一种免疫反应和炎症性疾病，胰岛素抵抗是2型糖尿病的发生、发展过程中的重要发病机制，同时也是心脑血管疾病的参与因素。罗格列酮是噻唑烷二酮类药物，具有抗炎、增加胰岛素敏感性、改善胰岛素抵抗的作用，作者单用罗格列酮对50例初诊2型糖尿病进行治疗，现报告如下。     

Cigarette smoking and risk of type 2 diabetes mellitus among middle-aged and elderly Japanese men and women

For examination of sex- and age-specific relations between smoking and risk of type 2 diabetes mellitus, 39,528 nondiabetic men and 88,613 nondiabetic women aged 40-79 years who underwent health checkups in Ibaraki-ken, Japan, in 1993 were followed through 2002. Risk ratios for diabetes according to smoking habits were calculated using a Cox proportional hazards model. Compared with never smokers, the risk ratio for diabetes among current smokers, after adjustment for age, systolic blood pressure, antihypertensive mediation use, alcohol intake, parental history of diabetes, body mass index, fasting status, blood glucose concentration, total and high density lipoprotein cholesterol levels, and log-transformed triglyceride level, was 1.27 (95% confidence interval (CI): 1.16, 1.38) in men and 1.39 (95% CI: 1.20, 1.61) in women. The excess risk was more pronounced among men with a parental history of diabetes than among men without one. The excess risk among current smokers was observed in both age subgroups (40-59 and 60-79 years). Respective multivariate risk ratios for the age subgroups were 1.37 (95% CI: 1.18, 1.60) and 1.20 (95% CI: 1.08, 1.34) in men and 1.45 (95% CI: 1.18, 1.79) and 1.34 (95% CI: 1.09, 1.66) in women. Smoking was independently associated with increased risk of type 2 diabetes among both middle-aged and elderly men and women.     

Does breastfeeding influence risk of type 2 diabetes in later life? A quantitative analysis of published evidence

BACKGROUND: Observational evidence suggests that having been breastfed in infancy may reduce the prevalence of type 2 diabetes in later life. OBJECTIVE: The objective was to examine the influence of initial breastfeeding on type 2 diabetes and blood glucose and insulin concentrations. DESIGN: A systematic review of published studies identified 1010 reports; 23 examined the relation between infant feeding and type 2 diabetes in later life or risk factors for diabetes. Risk factors in infants were examined separately from those in children and adults. All estimates were pooled by using fixed-effect models; differences <0 and ratios <1 imply a beneficial effect of breastfeeding. RESULTS: Subjects who were breastfed had a lower risk of type 2 diabetes in later life than did those who were formula fed (7 studies; 76 744 subjects; odds ratio: 0.61; 95% CI: 0.44, 0.85; P = 0.003). Children and adults without diabetes who had been breastfed had marginally lower fasting insulin concentrations than did those who were formula fed (6 studies; 4800 subjects; percentage difference: -3%; 95% CI: -8%, 1%; P = 0.13); no significant difference in fasting glucose concentrations was observed. Breastfed infants had lower mean preprandial blood glucose (12 studies; 560 subjects; mean difference: -0.17 mmol/L; 95% CI: -0.28, -0.05 mmol/L; P = 0.005) and insulin (7 studies; 291 subjects; mean difference: -2.86 pmol/L; 95% CI: -5.76, 0.04 pmol/L; P = 0.054) concentrations than did those who were formula fed. CONCLUSION: Breastfeeding in infancy is associated with a reduced risk of type 2 diabetes, with marginally lower insulin concentrations in later life, and with lower blood glucose and serum insulin concentrations in infancy.     

Weight excess and abdominal fat in the metabolic syndrome among Japanese-Brazilians

OBJECTIVE: Obesity, especially abdominal, has been associated with cardiovascular risk factors such as dyslipidemia, hypertension and diabetes mellitus (DM). The importance of these risk factors among Japanese-Brazilians was previously shown, although obesity is not a typical characteristic of Japanese migrants. In this study the prevalence of weight excess and central adiposity (CA) among Japanese-Brazilians and their association with metabolic disorders was evaluated. METHODS: A sample of 530 1st and 2nd generation Japanese-Brazilians (aged 40 - 79 years) went through anthropometric and blood pressure measurements, lipid profile and oral glucose tolerance tests. The prevalence rate (point and confidence interval) of overweight was calculated using a cut-off value of >26.4 kg/m2. CA diagnosis was based on waist-to-hip circumference ratio (WHR): greater-than-or-equal 0.85 and 0.95 in women and men, respectively. RESULTS: The prevalence of weight excess was 22.4% (CI 95% 20.6 - 28.1), and CA was 67.0% (95% CI 63.1 - 70.9). In addition to higher prevalence of DM, hypertension and dyslipidemia, stratifying by BMI and WHR, people with weight excess and CA revealed a poorer metabolic profile: blood pressure levels were significantly higher among those with weight excess with or without CA; CA individuals had higher glucose, triglycerides, total and LDL cholesterol, and lower HDL than those without weight excess or CA; fasting insulinemia was significantly higher among subjects with weight excess (with or without CA) than among those without weight excess or CA. CONCLUSION: Comparing subgroups with and without CA supports the hypothesis that abdominal fat accumulation represents a risk factor for insulin resistance-related diseases, even among Japanese descendants. The increased prevalence of metabolic syndrome among Japanese migrants could be attributed to visceral fat deposition, which has been implicated in the genesis of insulin resistance.     

Variation by body mass index and age in waist-to-hip ratio associations with glycemic status in an aboriginal population at risk for type 2 diabetes in British Columbia, Canada

BACKGROUND: It is unclear whether obesity and age modify or confound relations between abdominal adiposity and metabolic risk factors for type 2 diabetes. OBJECTIVE: Our objective was assess the consistency of relations between abdominal adiposity and glycemic variables across discrete categories of obesity and age. DESIGN: We performed a stratified analysis of prevalence data from a rural screening initiative in British Columbia, Canada. Subjects were Salishan Indians, all healthy relatives of individuals with type 2 diabetes [n = 151; age: 18-80 y; body mass index (BMI, in kg/m2): 17.0-48.2]. We measured waist-to-hip ratio (WHR) (2 categories); insulin, glycated hemoglobin (Hb A1c), and 2-h glucose concentrations (2 categories); and BMI (4 categories). BMI and age-specific odds ratios (ORs) and 95% CIs were calculated. RESULTS: WHR-glycemic variable relations were not consistent across BMI and age strata. Risks associated with high WHR were: for persons with BMIs from 25 to 29, elevated insulin (OR: 6.71; 95% CI: 1.41, 34.11) and Hb A1c (OR: 16.23; 95% CI: 2.04, 101.73) concentrations; for persons aged 18-34 y, elevated insulin concentrations [OR: indeterminate (+infinity); 95% CI: 1.89, +infinity]; and, for persons aged 35-49 y, elevated Hb A1c (OR: +infinity; 95% CI: 3.17, +infinity) and 2-h glucose (OR: 9.15; 95% CI: 1.74, 59.91) concentrations. CONCLUSIONS: WHR discriminates risk of type 2 diabetes in overweight but not obese individuals. Abdominal adiposity is associated with elevated insulin concentrations in younger age groups and with impaired glucose control in middle-aged groups, suggesting metabolic staging by age on a continuum from insulin resistance to impaired glucose tolerance.     

Blood viscosity and hematocrit as risk factors for type 2 diabetes mellitus: the atherosclerosis risk in communities (ARIC) study

Several lines of evidence support the notion that elevated blood viscosity may predispose to insulin resistance and type 2 diabetes mellitus by limiting delivery of glucose, insulin, and oxygen to metabolically active tissues. To test this hypothesis, the authors analyzed longitudinal data on 12,881 initially nondiabetic adults, aged 45-64 years, who were participants in the Atherosclerosis Risk in Communities (ARIC) Study (1987-1998). Whole blood viscosity was estimated by using a validated formula based on hematocrit and total plasma proteins at baseline. At baseline, estimated blood viscosity was independently associated with several features of the metabolic syndrome. In models adjusted simultaneously for known predictors of diabetes, estimated whole blood viscosity and hematocrit predicted incident type 2 diabetes mellitus in a graded fashion (P(trend (linear)) < 0.001): Compared with their counterparts in the lowest quartiles, adults in the highest quartile of blood viscosity (hazard ratio = 1.68, 95% confidence interval: 1.53, 1.84) and hematocrit (hazard ratio = 1.63, 95% confidence interval: 1.49, 1.79) were over 60% more likely to develop diabetes. Therefore, elevated blood viscosity and hematocrit deserve attention as emerging risk factors for insulin resistance and type 2 diabetes mellitus.     

上海市长宁区糖尿病高危人群筛查结果分析

目的 利用长宁区糖尿病高危人群的血糖筛查结果数据,分析长宁区糖尿病高危人群中糖尿病和糖调节受损的检出率,分析影响高危人群中糖尿病和糖调节受损的危险因素,为加强社区糖尿病防治力度提供参考依据。方法 收集糖尿病高危人群的基本信息、糖尿病危险因素及相关症状、体格检查数据及血糖数据进行统计分析。结果 2016 - 2017年,12 567名糖尿病高危人群中共检出糖尿病1 171人,糖调节受损者1 547人,检出率分别为9.3%、12.3%。多因素logistic回归分析发现,高龄（OR:1.032,95%CI:1.026～1.038）、男性（OR:1.161,95%CI:1.036～1.301）、低学历（P＜0.05）、糖调节受损史（OR: 6.257,95% CI:4.756～8.232）、亲属患2型糖尿病（OR: 1.388,95% CI:1.169～1.649）、高血压（OR: 1.463,95% CI:1.268～1.688）和体型超重/肥胖（OR: 2.228,95% CI: 1.940～2.559）是血糖代谢障碍的独立预测因素;高龄（OR:1.040,95% CI:1.035～1.045）、男性（OR:1.361,95% CI:1.224～1.581）、低学历（P＜0.05）、糖调节受损史（OR: 2.644,95% CI:1.949 ～3.586）、亲属患2型糖尿病（OR: 1.417,95% CI:1.217～1.650）、高血压（OR: 1.360,95% CI:1.199 ～1.543）、血脂异常（OR = 1.208,95% CI:1.019～1.432）、一过性类固醇糖尿病史（OR = 2.397, 95% CI:1.195～4.807)、长期静坐生活方式（OR = 2.542,95% CI:1.376～4.699）以及体型超重/肥胖（OR: 1.975,95% CI:1.754～2.224）是检出糖尿病的独立预测因素。结论 长宁区糖尿病高危人群的糖尿病和糖调节受损检出率较高。在高危人群中筛查,能使超过五分之一的血糖异常者得到早期诊断,应持续开展此项工作。     

Glucose, insulin, and incident hypertension in the multi-ethnic study of atherosclerosis

Diabetes mellitus and hypertension commonly coexist, but the nature of this link is not well understood. The authors tested whether diabetes and higher concentrations of fasting serum glucose and insulin are associated with increased risk of developing incident hypertension in the community-based Multi-Ethnic Study of Atherosclerosis. At baseline, 3,513 participants were free of hypertension, defined as systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or use of antihypertensive medications to treat high blood pressure. Of these, 965 participants (27%) developed incident hypertension over 4.7 years' median follow-up between 2002 and 2007. Compared with participants with normal baseline fasting glucose, those with impaired fasting glucose and diabetes had adjusted relative risks of hypertension of 1.16 (95% confidence interval (CI): 0.96, 1.40) and 1.41 (95% CI: 1.17, 1.71), respectively (P = 0.0015). The adjusted relative risk of incident hypertension was 1.08 (95% CI: 1.04, 1.13) for each mmol/L higher glucose (P < 0.0001) and 1.15 (95% CI: 1.05, 1.25) for each doubling of insulin (P = 0.0016). Further adjustment for serum cystatin C, urinary albumin/creatinine ratio, and arterial elasticity measured by tonometry substantially reduced the magnitudes of these associations. In conclusion, diabetes and higher concentrations of glucose and insulin may contribute to the development of hypertension, in part through kidney disease and arterial stiffness.     

血浆抗素水平与胰岛素抵抗的关系研究

目的:探讨血浆抗素(resistin)与肥胖、胰岛素抵抗及糖尿病之间的关系。方法:对型糖尿病(DM)组122例、糖耐量低减组(IGT)56例、糖耐量正常对照组(NGT)122例,采用争性酶联免疫分析法检测空腹血浆抗素浓度;同时测定血脂水平、空腹血浆葡萄糖浓度(FPG)和浆胰岛素浓度(FINS);测量身高、体重、腰围、血压(SBP、DBP),计算体质指数(BMI)、体脂百比(%Fat)、稳态模型胰岛素抵抗指数(HOMA-IR)。结果:与糖耐量正常组比较,糖尿病组体脂百分比甘油三酯(TG)、总胆固醇(TC)、血浆抗素水平、胰岛素抵抗指数较高(P<0.05)。相关分析显示浆Resistin水平与体质指数、体脂百分比、腰围、总胆固醇、胰岛素、血糖、胰岛素抵抗指数呈正关,调整BMI、年龄后,血浆抗素水平仍与胰岛素、血糖、胰岛素抵抗指数呈正相关。结论:Ⅱ型尿病患者血浆抗素水平较高,血浆抗素水平与胰岛素、空腹血糖水平及胰岛素抵抗指数相关,提示素是胰岛素抵抗发生的一个重要危险因素,在胰岛素抵抗与糖尿病之间建立联系。     

Longitudinal study of prepregnancy cardiometabolic risk factors and subsequent risk of gestational diabetes mellitus: The CARDIA study

This study examined prepregnancy cardiometabolic risk factors and gestational diabetes mellitus (GDM) in subsequent pregnancies. The authors selected 1,164 women without diabetes before pregnancy who delivered 1,809 livebirths between 5 consecutive examinations from 1985 to 2006 in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. The authors measured prepregnancy cardiometabolic risk factors and performed multivariate repeated-measures logistic regression to compute the odds of GDM adjusted for race, age, parity, birth order, and other covariates. Impaired fasting glucose (100-125 vs. <90 mg/dL), elevated fasting insulin (>15-20 and >20 vs. <10 μU/mL), and low levels of high-density lipoprotein cholesterol (<40 vs. >50 mg/dL) before pregnancy were directly associated with GDM: The odds ratios = 4.74 (95% confidence interval (CI): 2.14, 10.51) for fasting glucose, 2.19 (95% CI: 1.15, 4.17) for middle insulin levels and 2.36 (95% CI: 1.20, 4.63) for highest insulin levels, and 3.07 (95% CI: 1.62, 5.84) for low levels of high-density lipoprotein cholesterol among women with a negative family history of diabetes; all P < 0.01. Among overweight women, 26.7% with 1 or more cardiometabolic risk factors developed GDM versus 7.4% with none. Metabolic impairment exists before GDM pregnancy in nondiabetic women. Interconceptual metabolic screening could be included in routine health assessments to identify high-risk women for GDM in a subsequent pregnancy and to potentially minimize fetal exposure to metabolic abnormalities that program future disease.     

Hyperuricemia in young adults and risk of insulin resistance, prediabetes, and diabetes: a 15-year follow-up study

The objective of this study was to assess the utility of hyperuricemia as a marker for diabetes and prediabetes (impaired fasting glucose) and insulin resistance in young adults. Using Cox proportional hazards regression models, the authors analyzed 15-year follow-up data on 5,012 persons in 4 US cities who were aged 18-30 years and diabetes-free at the time of enrollment. At baseline (1986), 88% of participants had a body mass index (weight (kg)/height (m)(2)) less than 30. During the follow-up period (through 2001), the incidence rates of diabetes and prediabetes (insulin resistance and impaired fasting glucose) were higher among persons with greater serum urate concentrations. In multivariable Cox regression analyses that adjusted for age, gender, race, body mass index, family history of diabetes, diastolic blood pressure, total cholesterol, smoking, and alcohol use, the hazard ratios for diabetes, insulin resistance, and prediabetes among persons with hyperuricemia (serum urate level >7 mg/dL vs. ≤7.0 mg/dL) were 1.87 (95% confidence interval (CI): 1.33, 2.62), 1.36 (95% CI: 1.23, 1.51), and 1.25 (95% CI: 1.04, 1.52), respectively. This observation was generally consistent across subgroups. The authors conclude that hyperuricemia in the midtwenties is an independent marker for predicting diabetes and prediabetes among young adults in the subsequent 15 years.