糖耐量受损者胰岛素敏感性及胰岛β细胞功能的研究

目的 研究糖耐量受损(IGT)者的胰岛素抵抗(IR)及胰岛β细胞功能变化。方法 选取正常糖耐量(NGT)、IGT、2型糖尿病(T2DM)者共34例，以高胰岛素正血糖钳夹技术测定IR，行静脉葡萄糖耐量试验评估胰岛β细胞分泌功能。结果 与NGT组相比，IGT组、T2DM组的IR显著升高；IGT组胰岛素第一时相分泌明显下降，空腹胰岛素(FIns)水平及第二时相分泌水平升高；T2DM组IR与IGT组处于同一水平，FIns较NGT组显著减少。结论 由NGT向IGT的演变过程中，IR和胰岛素分泌缺陷共同起作用。     

沈阳地区糖耐量受损者胰岛β细胞功能和胰岛素抵抗

2003年美国糖尿病学会（ADA）糖尿病诊断和分型专家委员会提出将空腹血糖受损（IFG）的空腹血糖（FPG）切点由6．1mmol／L下调至5．6mmol／L。按新标准划分的中国的糖代谢异常者是否存在着糖尿病前期阶段的代谢特征？本研究运用能精确测定胰岛素抵抗程度的正血糖高胰岛素钳夹技术和能反映胰岛素早期分泌缺陷的静脉葡萄糖耐量试验（IVGTT），来研究比较新旧切点下不同糖耐量的胰岛素抵抗程度和β细胞分泌功能的异同。     

胰岛细胞与胰岛素抵抗

临床曾观察到,2型糖尿病和糖耐量受损(IGT)时均伴有血胰高血糖素(Glc)的升高,而且在20世纪80年代Unger等就提出了糖尿病发病的“双激素异常”学说,认为糖尿病的临床表现是由于α细胞及β细胞功能共同异常所致[1,2]。这些现象提示α细胞Glc分泌增多,可能系胰岛素的抑制作用减弱所致,间接暗示α细胞Glc对胰岛素存在抵抗的可能。胰岛α细胞产生神经肽Y(NPY)和Glc[3]。本组在以往的研究中发现,糖尿病大鼠下丘脑弓状核和胰岛的NPYmRNA表达和蛋白含量均升高,予以胰岛素治疗24周后下丘脑NPY含量显著降低,而胰岛NPY却无明显变化,提示胰岛…     

经典1型糖尿病患者胰岛素抵抗的高胰岛素正葡萄糖钳夹研究

目的 应用高胰岛素正葡萄糖钳夹技术评价1 型糖尿病(T1DM)患者胰岛素抵抗程度.方法 选择新诊断T1DM患者8例,初诊未治2型糖尿病(T2DM)患者8例,均经2周胰岛素强化治疗后进行高胰岛素正葡萄糖钳夹检测胰岛素敏感性指数(ISI),并与正常糖耐量志愿者10例进行比较.结果 T1DM组的年龄、BMI、空腹胰岛素(FIns)及空腹C-肽等各项参数显著低于正常对照组(P＜0.05),而腰臀比(WHR)、收缩压(SBP)、舒张压(DBP)、TC、TG、LDI-C、HDL-C均与正常对照组差异无统计学意义.T1DM组与T2DM组比较,年龄、BMI、WHR、FIns、空腹C-肽、SBP、TC、TG均显著低于T2DM组(P＜0.05).正常对照组、T1DM组、T2DM组ISI分别为12.83±1.09、9.95±0.50、3.80±0.20,3组间ISI差异有统计学意义(P＜0.05).结论 高胰岛素正葡萄糖钳夹检测结果显示,TIDM患者的ISI显著低于正常人,但高于T2DM患者.     

胰岛素抵抗和胰岛β细胞分泌功能对妊娠糖尿病的影响

目的探讨胰岛素抵抗(IR)和β细胞分泌功能对妊娠糖尿病(GDM)的影响。方法观察妊娠中晚期孕妇糖耐量正常(NGT)者35例、糖耐量减低(IGT)者33例和GDM者38例在不同糖耐量状态下的IR和β细胞分泌功能,采用HOMA-IR和HOMA-β分别评价IR和β细胞分泌功能。结果IGT组的HOMA-IR明显高于NGT组(P<0·05),两组的HOMA-β的差异无统计学意义;GDM组的HOMA-IR明显高于NGT和IGT组(P<0·05),HOMA-β明显低于NGT和IGT组,差异均有统计学意义。结论妊娠中晚期孕妇IGT阶段胰岛素早期分泌功能受损,到GDM阶段兼有严重的IR和β细胞缺陷。从NGT、IGT到GDM,随着糖代谢紊乱的不断进展,IR逐渐加重,胰岛β细胞功能进行性减退。     

原发性高血压患者胰岛β细胞功能和胰岛素抵抗研究

目的:探讨不同糖代谢状态下原发性高血压(EH)患者空腹胰岛β细胞功能(FBCI)和胰岛素抵抗(IR)状况。方法:选取符合入选标准的150例EH患者,分为伴糖尿病组与不伴糖尿病组,以健康者50例作为对照组,分别进行OGTT试验和同步胰岛素释放试验,计算胰岛素抵抗指数(HOMA-IR)和FBCI。结果:不伴糖尿病的EH患者FBCI和HOMA-IR高于对照组;伴糖尿病的EH患者FBCI和HOMA-IR显著升高,与不伴糖尿病的EH者比较,差异有统计学意义(P<0.01)。结论:不同糖代谢状态下EH患者均存在糖代谢紊乱和IR,简单的FBCI计算公式不能够反映真实EH患者的胰岛β细胞功能。     

胰岛素抵抗、胰岛β细胞分泌功能对妊娠糖尿病发生的影响

妊娠糖尿病 (ＧＤＭ)往往是妊娠中晚期伴随胰岛素抵抗(ＩＲ)的发展而发生的 ,故经典的观点认为ＧＤＭ主要与ＩＲ有关。ＩＲ是指胰岛素靶组织 (如骨胳肌、脂肪组织、肝脏等 )对胰岛素敏感性降低 ,对葡萄糖的利用降低及抑制肝葡萄糖输出的作用减弱。妊娠期的ＩＲ与胎盘分泌具有拮抗胰岛素作用的激素有关。不过 ,单一的ＩＲ尚不能引起ＧＤＭ。因为妊娠中晚期ＩＲ均增加 ,但仅约 5 %发展为ＧＤＭ。提示ＧＤＭ妇女除了有ＩＲ ,胰岛素分泌可能也存在缺陷〔1〕。本研究通过观察不同糖耐量状态〔ＧＤＭ、糖耐量低减(ＩＧＴ)、糖耐量正常 (ＮＧＴ)〕…     

空腹C肽质量浓度与胰岛素抵抗相关性研究

目的比较C肽和胰岛素在评估胰岛素抵抗性(IR)的差异。方法依口服糖耐量试验将2003年3月至2004年3月中国医科大学附属第二医院门诊及周围社区的44例汉族人分为正常糖耐量(NGT)组、孤立空腹血糖受损(I-IFG)组、孤立糖耐量受损(I-IGT)组,联合糖耐量受损(C-IGT)组。观察葡萄糖钳夹试验测定的IR指标(葡萄糖输注速率,GIR)和其空腹胰岛素、C肽的关系。结果I-IFG、I-IGT、C-IGT组的GIR明显低于NGT(P<0.01),但各组的空腹C肽浓度差异无显著性。各组的胰岛素作用指数(IAI)、稳态模式评估法指数(HOMA-IR)、空腹胰岛素衍生的IR指标定量胰岛素敏感性检测指数(QUICKI)与GIR均呈良好相关(P<0.05),相关系数在0.766~0.498之间,但空腹C肽替代胰岛素后的IR指标与GIR无明显相关,相关系数在0.394~0.042之间(P>0.05)。结论空腹C肽质量浓度和胰岛素抵抗程度没有相关性。     

2型糖尿病患者血浆抵抗与胰岛素抵抗胰岛B细胞功能的研究

目的了解2型糖尿病(T2DM)患者血浆抵抗素(Resistin)质量浓度的改变,并探讨与胰岛素抵抗、胰岛B细胞功能的关系。方法2004-01~2004-10选取苏北医院测定了64例2型糖尿病和30名正常对照组的血浆Resistin、空腹血糖(FPG)、糖化血红蛋白(HbA1c)、空腹血浆胰岛素(FINS)、血脂、体重指数(BMI),计算胰岛素抵抗指数(HOMA-IR)及B细胞功能指数(HOMA-B)。比较Resistin质量浓度的改变及与其它因素的相关性。结果肥胖的糖尿病组与正常对照组比较Resistin明显升高,差异有统计学意义。而在肥胖的糖尿病组对非肥胖糖尿病组,以及非肥胖的糖尿病组对正常对照组的比较中,Resistin数值差异无统计学意义。在糖尿病患者中,血浆Resistin与BMI、HOMA-IR呈正相关,与FBG、FINS、HbA1c、HDL-c、LDL-c、TG、TC及HOMA-B相关性不明显。结论糖尿病患者血浆Resistin质量浓度与体内脂肪容积、胰岛素抵抗有一定的关系,在胰岛素抵抗和2型糖尿病的产生中可能起一定的作用。     

应用高胰岛素正葡萄糖钳夹技术评价我国LADA患者的胰岛素抵抗

目的应用高胰岛素正葡萄糖钳夹技术评估我国成人隐匿性自身免疫性糖尿病（LADA）患者的胰岛素抵抗。方法研究对象分为LADA组、2型糖尿病（T2DM）组、正常对照（NC）组。糖尿病患者均为初诊未治,经2周胰岛素强化治疗血糖控制达标后进行研究。对全部研究对象空腹测定临床参数及生化指标,应用高胰岛素正葡萄糖钳夹技术测定胰岛素敏感性指数（ISI）。结果LADA组FC-P及Fins显著低于NC组（P〈0．05）,年龄、BMI、wHR、SBP、DBP、TC、TG、LDL—C、HDL-C与NC组比较,均无统计学差异。LADA组BMI、WHR、SBP、Fins、FC-P、TC、TG、LDL-C均显著低于T2DM组（P均〈0．05）。NC组、LADA组、T2DM组ISI分别为12．83±1．09、6．70±0．71、3．80±0．20,三组间比较有统计学差异（P〈0．05）。结论与NC组相比,LADA患者存在胰岛素抵抗,其程度较T2DM组轻。     

Post-partum reclassification of glucose tolerance in women previously diagnosed with gestational diabetes mellitus.

AIMS: To re-evaluate post-partum screening; fasting plasma glucose (FPG) vs. oral glucose tolerance test (OGTT) in Caucasian women with previous gestational diabetes mellitus (GDM). METHODS: Once breast-feeding had finished, an OGTT was performed in 120 women with previous GDM. They were classified according to World Health Organization (WHO) 1985 and American Diabetes Association (ADA) 1997 criteria. The kappa-statistic measure of agreement was used to compared both diagnostic categories. A receiver-operating characteristic (ROC) curve studied the FPG as a test to detect abnormal glucose tolerance. RESULTS: Identical diabetes prevalence (2%) but quite different intermediate categories (12% impaired glucose tolerance vs. 3% impaired fasting glucose) were observed with both criteria. The kappa-statistic (scaled from 0 to 1) was 0.38 (fair agreement), P = 0.000. The ROC curve area of the FPG was 0.65. CONCLUSIONS: FPG is an unsatisfactory method of evaluating the glucose tolerance of Caucasian women with previous GDM. OGTT may be a better test for such a purpose.     

Prevalence of diabetes mellitus and impaired glucose tolerance in parents of women with gestational diabetes

Summary Nuclear families of non-insulin-dependent diabetic (NIDDM) patients are uncommon, as usually one or both parents have died. In order to aid identification of complete nuclear families, we have ascertained the disease process at a younger age by studying subjects with previous gestational diabetes. One hundred women who had had gestational diabetes, age (±SD) 38 (6) years, were screened by fasting plasma glucose (fpg). Sixty-one were found to have either fasting hyperglycaemia (5.5fpg<7.8 mmol/l) or diabetes. Of these women 35 had both parents alive and the parents of 14 of these women agreed to the assessment of their metabolism by a continuous infusion of glucose with model assessment (CIGMA). Seven probands had impaired glucose tolerance (IGT) and seven were diabetic. They were age 35 (4) years and had body mass index (BMI) 26 (5) kg/m². The parents were aged 62 (6) years and had BMI 29 (6) kg/m² and their affection status was defined as presence of glucose intolerance (fpg or post-infusion achieved plasma glucose level >2 SD of an age and obesity matched population). In the 14 families, five probands (36%) had neither parent affected, six (43%) had one parent affected and three (21%) had both parents affected. Only three probands had a parent with diabetes as defined by World Health Organisation criteria. We concludes that the study of women who have had gestational diabetes allows detection of probands with diabetes or impaired glucose tolerance, who have both parents available for study. A substantial proportion had neither parent affected with impaired glucose tolerance or diabetes, similar to the nuclear families of NIDDM patients. The results are in accord with studies of nuclear families of NIDDM patients in suggesting polygenic inheritance or environmental influences rather than autosomal dominant inheritance with high penetrance.Abbreviations IGT Impaired glucose tolerance - GTT glucose tolerance test - NIDDM non-insulin-dependent diabetes mellitus - fpg fasting plasma glucose - apg achieved plasma glucose - CIGMA continuous infusion of glucose test - BMI body mass index     

Epidemiology of gestational diabetes mellitus and its association with Type 2 diabetes.

Gestational diabetes (GDM) is defined as carbohydrate intolerance that begins or is first recognized during pregnancy. Although it is a well-known cause of pregnancy complications, its epidemiology has not been studied systematically. Our aim was to review the recent data on the epidemiology of GDM, and to describe the close relationship of GDM to prediabetic states, in addition to the risk of future deterioration in insulin resistance and development of overt Type 2 diabetes. We found that differences in screening programmes and diagnostic criteria make it difficult to compare frequencies of GDM among various populations. Nevertheless, ethnicity has been proven to be an independent risk factor for GDM, which varies in prevalence in direct proportion to the prevalence of Type 2 diabetes in a given population or ethnic group. There are several identifiable predisposing factors for GDM, and in the absence of risk factors, the incidence of GDM is low. Therefore, some authors suggest that selective screening may be cost-effective. Importantly, women with an early diagnosis of GDM, in the first half of pregnancy, represent a high-risk subgroup, with an increased incidence of obstetric complications, recurrent GDM in subsequent pregnancies, and future development of Type 2 diabetes. Other factors that place women with GDM at increased risk of Type 2 diabetes are obesity and need for insulin for glycaemic control. Furthermore, hypertensive disorders in pregnancy and afterwards may be more prevalent in women with GDM. We conclude that the epidemiological data suggest an association between several high-risk prediabetic states, GDM, and Type 2 diabetes. Insulin resistance is suggested as a pathogenic linkage. It is possible that improving insulin sensitivity with diet, exercise and drugs such as metformin may reduce the risk of diabetes in individuals at high risk, such as women with polycystic ovary syndrome, impaired glucose tolerance, and a history of GDM. Large controlled studies are needed to clarify this issue and to develop appropriate diabetic prevention strategies that address the potentially modifiable risk factors.     

Diabetes screening after gestational diabetes mellitus: poor performance of fasting plasma glucose

Abstract. Gestational diabetes mellitus (GDM) is an established risk factor for the development of overt diabetes. Since the change in diagnostic criteria for diabetes in 1997, it is unclear whether there should be any preference for fasting or post-glucose challenge blood glucose in diagnosing diabetes after GDM. The study aimed at assessing the usefulness of both diagnostic methods in women after GDM. The study enrolled 193 women with previous GDM. Women who did not have a current diagnosis of diabetes were screened for impaired fasting glucose (IFG) and for glucose intolerance with an oral 75-g glucose tolerance test. A total of 45 (23.3%) subjects declared to be already diabetic. Of the 148 non-diabetic subjects, 141 (95.3%) had normal fasting plasma glucose, whereas four (2.8%) had IFG (i.e. FPG6.1 and <7.0 mmol/l) and 3 (2.5%) had FPG7.0 mmol/l. Upon OGTT, among the 141 subjects with normal FPG, 6 (4.3%) were diagnosed with diabetes and 23 (16.3%) with impaired glucose tolerance (IGT); the remaining 112 (79.5%) had normal glucose tolerance. Three out of four subjects with IFG had IGT. The sensitivities of fasting criteria for diagnosis of diabetes and IFG/IGT were 14.3% (95% CI, 8.0%–37.2%) and 17.1% (95% CI, 8.6%–19.8%), respectively. The specificities were 98.6% (95% CI, 97.9%–99.7%) and 99.1% (95% CI, 96.5%–100%), respectively. The kappa for diabetes diagnosis was 0.177 (95% CI, 0.018–0.507). For women with previous GDM, the sensitivity of the new criteria based upon fasting plasma glucose is unacceptably low. In addition, the two sets of criteria are not interchangeable. Therefore, we suggest full glucose tolerance diagnostic procedures in women after GDM, including assessment of post-glucose challenge values.     

������������Ҫ��

妊娠糖尿病(GDM)的妇女产后发生2型糖尿病、高血压的危险增高。妊娠糖尿病易导致巨大儿,其次还会导致流产、早产、死胎的发生率增高等。高风险的妇女应在怀孕后即进行糖耐量试验,若未发现血糖的异常,则应在妊娠24～28周复查。经饮食控制后空腹血糖大于5.8 mmol/L或餐后2 h血糖大于6.7 mmol/L的患者需用药物治疗,治疗首选人胰岛素,其剂量和剂型应个体化。ADA指南推荐空腹时低于5.3 mmol/L,餐后1 h低于7.8 mmol/L,2 h低于6.7 mmol/L。     

Screening for gestational diabetes; past, present and future.

Gestational diabetes is carbohydrate intolerance, with onset or first recognition of hyperglycaemia during pregnancy. Several studies have suggested that gestational hyperglycaemia is associated with adverse maternal and fetal outcomes, promoting the case for screening. Conversely, others argue that screening for gestational diabetes may colour the clinical judgement, influencing further management, e.g. more 'unjustified' caesarean sections. Additionally, the lack of definitive data either on a clear-cut glycaemic threshold for the development of adverse outcomes or on the impact of intervention is emphasized by opponents of screening. This review attempts to evaluate the available data on screening for gestational diabetes. Oral glucose tolerance test is promoted on the basis that the diabetogenic stress of pregnancy is encountered during late gestation and is best recognized in the fed state. There are different tests, including the 1 h/50-g, 2 h/75-g and 3 h/100-g tests, with practical limitations, including the time and cost involved and the unpleasant supra-physiological glucose load that is unrelated to body weight, and issues of reproducibility and sensitivity/specificity profiles. Despite its convenience, the poor sensitivity of random glucose has precluded its routine use for screening. Fasting glucose appears to be promising but further testing is required to ensure satisfactory sensitivity/specificity in different populations. Despite its limitations, the oral glucose tolerance test has become established as the 'most acceptable' diagnostic test for gestational diabetes. More convenient methods, e.g. fasting or random or post-load glucose, have to be validated therefore against the oral glucose tolerance test to gain acceptance for routine screening.     

Elevated concentrations of asymmetric dimethylarginine are associated with deterioration of glucose tolerance in women with previous gestational diabetes mellitus

OBJECTIVE: Women with previous gestational diabetes mellitus (GDM) have a high risk for development of type 2 diabetes mellitus. The endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) could be related to disorders of the glucose metabolism. To evaluate if ADMA predicts deterioration of glucose tolerance in women with previous GDM and to assess concentration changes we analysed ADMA in women with previous GDM after delivery and after a median follow-up of 2.75 years (interquartile range: 1.47-4.60). DESIGN: Prospective cohort study. Subjects and methods. ADMA, symmetric dimethylarginine (SDMA) and L-arginine were determined in 77 women with previous GDM who underwent a 75-g oral glucose tolerance test 4 months after delivery and at follow-up. RESULTS: Deterioration in glucose tolerance was observed in 36% of the women with ADMA above and 11% of those with ADMA below the median (0.56 micromol L(-1); P = 0.008, log-rank test). ADMA correlated significantly with mean arterial blood pressure and nonsignificantly with body mass index (P = 0.050) but not with insulin resistance, fasting glucose, lipids or glomerular filtration rate. The fully adjusted hazard ratio for a decline of glucose tolerance during follow-up was 3.94 (95% CI: 1.16-13.37; P = 0.028) for subjects with ADMA above the median. SDMA and L-arginine were not associated with changes in the glucose tolerance status. ADMA and L-arginine decreased significantly during follow-up. CONCLUSIONS: High serum ADMA after delivery is associated with deterioration in glucose tolerance in women with previous GDM and declines in the following years.     

The association of gestational diabetes mellitus with fetal birth weight

Aims

Gestational diabetes mellitus (GDM) and different time-point glucose levels might have different effects on fetal birth weight. The aim of this study was to further evaluate the associations of GDM and different time-point blood glucose levels with fetal birth weight in a prospective cohort study.

Roles of insulin resistance and beta cell dysfunction in macrosomia among Chinese women with gestational diabetes mellitus

Aims

The aim was to examine associations of insulin resistance and beta cell dysfunction with macrosomia in Chinese women with gestational diabetes mellitus (GDM).