高血压合并糖耐量减低患者血清脂联素水平的研究

非高血压(HT)者43例,其中糖耐量正常者(NGT)30例,糖耐量减低者(IGT)13例。HT者45例,其中17例伴NGT,28例伴IGT,研究显示:脂联素水平(mg/L)HT伴NGT组低于非HT的NGT组(4.3±1.7vs7.1±3.6),HT伴IGT组低于非HT的IGT组(4.0±2.1vs6.6±1.4)(P均<0.05);NGT与IGT组脂联素水平的差异无统计学意义;IGT组脂联素与DBP、TG、C肽负相关;NGT组脂联素水平与BMI、SBP负相关。     

内脂素基因启动子多态性与中国人2型糖尿病脂代谢紊乱的相关性

目的探讨内脂素基因启动子-1535C/T多态性的分布及其与中国人2型糖尿病(T2DM)脂代谢紊乱的关系。方法采用聚合酶链反应-限制性片段长度多态性技术,检测208例初诊T2DM患者和162例糖耐量正常(NGT)者的内脂素基因启动子-1535C/T多态性,分析该基因多态性与腰围、BMI、血浆内脂素及血脂代谢指标的相关性。结果 两组内脂素基因型分布及等位基因频率比较无统计学差异(P0.05);但与TC、CC基因型患者比较,T2DM组TT基因型患者甘油三酯升高、HDL-C降低(P0.05)。荧光素酶活性比较,pGL3-1535T的相对荧光素酶表达活性较pGL3-1535C下降了约28%(P0.01)。结论内脂素基因启动子-1535C/T多态性与中国人T2DM脂代谢紊乱有相关性。     

脂联素在糖调节受损患者冠状动脉病变风险中的意义

目的 探讨脂联素在不同糖调节受损者冠脉病变发生及严重程度中的临床意义.方法 疑似冠心病行冠脉造影者210例,分为正常血糖组(NGT) 42例,空腹血糖调节受损组(IFG) 36例,糖耐量受损组(IGT)92例(其中IGT1组44例2 h 血糖＜10 mmol/L;IGT2组48例2h血糖≥10mmol/L),IFG+IGT组40例.检测体重指数、血压、血脂、胰岛素、脂联素、C反应蛋白,并进行Gensini评分.结果 IGT、IFG+IGT组冠心病患病率及Gensini评分显著高于IFG及NGT(P＜0.05);脂联素在IGT、IFG+IGT两组中显著低于IFG、NGT组(P＜0.05),C反应蛋白在IGT、IFG+IGT两组显著升高(P＜0.05);IGT2组较IGT1组Gensini显著升高、脂联素显著下降(P＜0.05);Gensini与脂联素负相关,与C反应蛋白、HOMA-IR正相关(p＜0.05);多因素逐步回归分析显示脂联素和HOMA-IR是冠脉病变严重程度独立影响因素.结论 低脂联素血症可更敏感地预测IGR患者的冠脉病变程度,尤其在IGT组中,如餐后血糖控制在10 mmol/L以下可能会带来更大的心血管获益.     

2型糖尿病患者非糖尿病后代心率变异性与血清脂联素水平的相关性研究

目的旨在探讨血清脂联素浓度降低是否与2型糖尿病(T2DM)患者非糖尿病后代心率变异性(heart rate variability,HRV)改变有关.方法31例(男16例,女15例)T2DM患者,所有子女(91例)排除已进行药物治疗的T2DM患者14例,其余空腹静脉取血测定血浆葡萄糖,排除≥7.0 mmol/L者3例,排除5.6~7.0 mmol/L之间者7例.选择其空腹血糖≤5.6 mmol/L后代行口服葡萄糖耐量试验,均未达到T2DM诊断标准,分为正常葡萄糖耐量组(NGT,n=32),葡萄糖耐量异常组(IGT,n=35),对照组(n=32)为无糖尿病家族史的健康查体者.行24 h动态心电图检查测定HRV,指标包括:全部正常窦性R-R间期值的标准差(SDNN);全程按5 min分成连续的时间段,先计算每5 min正常R-R间期的平均值,再计算所有平均值的标准差(SDANN);全部相邻R-R间期差的均方根(rMSSD);总功率(TP);低频功率(LF);高频功率(HF).ELISA法测定血清脂联素.结果T2DM非糖尿病后代血清脂联素水平与其体重指数(BMI)、空腹胰岛素负相关,与高密度脂蛋白胆固醇(HDL-c)、SDNN、SDANN、rMSSD、TP、LF、HF正相关.对照组、NGT组、IGT组之间血清脂联素逐渐降低、空腹胰岛素、SDNN、SDANN、rMSSD、TP、LF、HF逐渐升高.IGT组BMI、血清三酰甘油高于HDL-c,低于对照组和NGT组.结论自主神经平衡的改变与胰岛素抵抗和血清脂联素水平改变具有相关性.     

不稳定型心绞痛合并糖耐量减低患者血清脂联素的测定及其意义

目的:通过测定血清脂联素,探讨不稳定型心绞痛(UAP)合并糖耐量减低(IGT)患者血清脂联素的含量变化及其意义。方法:UAP患者被分为糖耐量正常组(单纯UAP组)和糖耐量减低组UAP/IGT,测血清胰岛素,血脂,血清脂联素含量。结果:UAP/IGT组患者较单纯UAP组血清脂联素降低(P<0.05)。结论:血清脂联素在冠状动脉粥样硬化的发生中发挥保护作用。     

老年男性人群高血压合并糖耐量减低与全因死亡风险的相关性

目的 探讨高血压合并糖耐量减低(IGT)对老年男性人群全因死亡风险的影响.方法 纳入2005年5月至2007年5月在解放军总医院第二医学中心行口服葡萄糖耐量试验检出的老年男性IGT患者和正常糖耐量(NGT)人群,根据基线时是否存在高血压病史和IGT分为4组:非高血压(NH)+正常糖耐量(NGT)组、高血压(H)+NGT...     

糖耐量受损和2型糖尿病患者血清C反应蛋白与脂联素的水平及相关性

目的 探讨血清C反应蛋白(CRP)与脂联素在糖耐量受损(IGT)和2型糖尿病(T2DM)患者中的水平及其相关性.方法 选取56例IGT患者、55例T2DM患者及50例健康对照组人群作为研究对象,分别测定血清CRP、脂联素、总胆固醇、甘油三酯、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇、血糖、胰岛素,血压、身高、体重、腰围、臀围,计算体重指数,采用MINIMOD计算机软件包计算胰岛素敏感指数(SI)及急性胰岛素反应(AIR),并进行分析比较.结果 T2DM组、IGT组血清CRP分别为(2.46±0.25 )mg/L、(3.12±0.46 )mg/L,对照组为(0.46±0.21 )mg/L,前者显著高于后者;T2DM组、IGT组血清脂联素分别为(3.49±1.21) mg/L、(4.13±1.54) mg/L,对照组为(7.81±2.65) mg/L,前者显著低于后者.T2DM组和IGT组SI及AIR显著低于对照组,甘油三酯及低密度脂蛋白胆固醇显著高于对照组,差异均有统计学意义(P＜0.05);CRP与脂联素、AIR和SI呈负相关,脂联素与AIR和SI呈正相关(P＜0.05).结论 血清CRP与脂联素在IGT和T2DM患者血清中表达发生异常改变,且与患者胰岛素抵抗密切相关,检测其血清水平对预测疾病预后及指导早期干预意义重大.     

2型糖尿病一级亲属血清脂联素、瘦素及其比值与胰岛素抵抗的相关性研究

目的 研究血清瘦素、脂联素与2型糖尿病(T2DM)一级亲属胰岛素抵抗(IR)相关性,探讨二者在T2DM发病中作用.方法 收集既往无糖耐量异常史的T2DM一级亲属, 分为糖耐量正常(NGT)组174例、空腹血糖受损(IFG)或糖耐量低减(IGT)组55例,及新发T2DM组71例;以其无糖尿病家族史的配偶或亲友中OGTT正常者114例作为正常对照组(NC).酶联免疫法测定上述人群的血清真胰岛素(TI)、瘦素和脂联素水平.用HOMA-IR评价胰岛素抵抗(IR)状态.结果 从NC至NGT、IGT/IFG到DM组,IR进行性加重(HOMA-IR分别为1.3±0.7、1.7±1.5、 2.2±1.4 和3.2±2.8,P＜0.01);血清瘦素水平进行性增高(P＜0.01),瘦素水平与HOMA-IR正相关(r=0.35, P＜0.01);血清脂联素水平进行性降低(分别为20±12、17±11、13±8和10±6mg/L,P＜0.01),与HOMA-IR负相关(r=-0.41,P＜0.01);脂联素/瘦素比值进性行降低,与HOMA-IR负相关(r=-0.53, P＜0.01). 结论 T2DM一级亲属在NGT时即存在瘦素水平升高和脂联素水平明显下降.脂联素/瘦素比值下降趋势与IR和糖调节受损的严重程度密切相关,推测该比值的变化可能是糖尿病一级亲属存在的固有遗传缺陷的一种表现,可能在IR和T2DM的发生发展中起重要作用,因而渴望作为预测T2DM发病的早期观察指标.     

阿卡波糖对冠心病伴糖耐量受损患者血清脂联素和瘦素水平的影响

目的:探讨冠心病(CHD)合并糖耐量受损患者的血清脂联素和瘦素水平及阿卡波糖的干预效果。方法:将46例CHD患者按照口服葡萄糖耐量(OGTT)试验分为单纯CHD组(27例)和CHD伴糖耐量受损(IGT)组(19例),33例体检者也根据OGTT试验分为正常对照组(18例)和单纯IGT组(15例)。测定受试者血清脂联素和瘦素水平,记录OGTT试验结果,检测血脂、超敏C反应蛋白(hs-CRP)、空腹胰岛素,并测量身高、体重、腰围等。对CHD并IGT组和单纯IGT组均给予阿卡波糖干预3个月后复测上述指标。结果:血清脂联素水平在CHD患者中降低,合并IGT时更加显著,其水平与HDL-C、HOMA-IR、SBP及性别相关。血清瘦素水平在IGT患者中升高,其水平与腰围、BMI相关,女性显著高于男性。经阿卡波糖干预后,血清脂联素水平显著升高,TC的变化与其升高的水平相关;血清瘦素水平降低,女性降低更甚。结论:阿卡波糖可改变CHD合并IGT患者血清脂联素和瘦素水平,并可能通过其变化来改善餐后高血糖、血脂紊乱、肥胖及胰岛素抵抗等,从而发挥其心血管保护作用。     

不同血糖水平老年人脂联素、瘦素水平及其比值与胰岛素抵抗的相关性

目的研究不同血糖水平老年人脂联素、瘦素水平的变化,脂联素瘦素比值与胰岛素抵抗的相关性。方法选取不同血糖水平老年人146例,包括对照组:糖耐量正常的健康人群52例,研究组:糖耐量异常(IGT)患者39例,新近诊断糖尿病(T2DM)患者55例。研究脂联素、瘦素水平以及其比值和胰岛素抵抗指数、体重指数、腰臀比、血脂等指标的相关性。结果 IGT组和T2DM组的腰臀比、体重指数、甘油三酯、瘦素、胰岛素抵抗指数较正常对照组显著增加,脂联素水平较正常组明显下降;脂联素/瘦素与腰围、腰臀比、体重指数、空腹胰岛素、甘油三酯、低密度脂蛋白、HO-MA-IR负相关,与高密度脂蛋白正相关。Logistic回归结果显示脂联素/瘦素是胰岛素抵抗指数的独立危险因素。结论不同血糖水平老年人中,脂联素/瘦素比值与胰岛素抵抗密切相关。     

Glucose tolerance and free fatty acid metabolism in adults with variations in TCF7L2 rs7903146

ObjectiveTCF7L2 variant rs7903146 is associated with increased risk for type 2 diabetes. We investigated the effect of TCF7L2 variant rs7903146 and glucose tolerance on free fatty acid (FFA) metabolism.Research Design and MethodsWe recruited 120 individuals, half homozygous for the major CC allele and half homozygous for the minor TT allele at rs7903146; each underwent a 2-h, 75 g oral glucose tolerance test (OGTT). Plasma glucose, insulin and free fatty acid concentrations were measured on blood collected before and during the OGTT.ResultsTotal FFA concentrations and percent FA species during OGTT were not different in CC and TT carriers when males and females were considered together. However, monounsaturated fatty acid (MUFA) concentrations and percentages were greater in TT than CC females during the OGTT. TT carriers with high HOMA-IR had significantly greater fasting FFA concentrations, lower disposition index (DI) and greater AUC of glucose than high HOMA-IR CC carriers, whereas no such differences were observed in the low HOMA-IR group. We found that fasting (826 ± 25 vs. 634 ± 22 μmol/L, P < 0.0001) and OGTT plasma FFA concentrations were greater in IGT than NGT subjects, and the difference remained after adjusting for sex, age, BMI, and genotype. Finally, IGT subjects had greater MUFA concentrations and percentages than NGT subjects during OGTT.ConclusionsDespite similar fasting insulin and glucose, fasting plasma FFA are greater in IGT than NGT adults. Insulin resistance and sex influence plasma FFA responses amongst carriers of the minor T allele of TCF7L2 rs7903146.     

Effects of rosglitazone on plasma adiponectin, insulin sensitivity, and insulin secretion in high-risk African Americans with impaired glucose tolerance test and type 2 diabetes

We examined the metabolic effects of rosiglitazone therapy on glucose control, insulin sensitivity, insulin secretion, and adiponectin in first-degree relatives of African Americans with type 2 diabetes (DM) with impaired glucose tolerance (IGT) and DM for 3 months. The study was comprised of 12 first-degree relatives with IGT, 17 newly diagnosed DM, and 19 healthy relatives with normal glucose tolerance (NGT). Oral glucose tolerance test (OGTT) was performed before and after 3 months of rosiglitazone therapy (4 to 8 mg/d) in patients with IGT and DM. Serum glucose, insulin, C-peptide, and adiponectin levels were measured before and 2 hours during OGTT in the NGT and patients with IGT and DM. Insulin resistance index (HOMA-IR) and beta-cell function (HOMA-%B) were calculated in each subject using homeostasis model assessment (HOMA). Rosglitazone improved the overall glycemic control in the IGT and DM groups. Following rosiglitazone, the beta-cell secretion remained unchanged, while HOMR-IR was reduced in DM by 30% (4.12 +/- 1.95 v 6.33 +/- 3.54, P < .05) and the IGT group (3.78 +/- 2.45 v 4.81 +/- 3.49, P = not significant [NS]). Mean plasma adiponectin levels were significantly (P < .05) lower in the DM (6.74 +/- 1.95 microg/mL) when compared with the NGT group(9.61 +/- 5.09). Rosiglitazone significantly (P < .001) increased adiponectin levels by 2-fold in patients with IGT (22.2 +/- 10.97 microg/mL) and 2.5-fold greater in DM (15.68 +/- 8.23 microg/mL) at 3 months when compared with the 0 month. We conclude that adiponectin could play a significant role (1) in the pathogenesis of IGT and DM and (2) the beneficial metabolic effects of thiazolidinediones (TZDs) in high-risk African American patients.     

血管紧张素转化酶基因插入／缺失多态性与老年糖耐量低减合并冠心病相关性研究

目的：探讨血管紧张素转化酶基因（ACE）多态性与中国汉族老年人糖耐量低减（IGR）及合并冠心病（CAD）的关系。方法：使用多聚合酶链反应方法检测79例糖耐量低减老年人和49例糖耐量正常（NGF）老年对照者的ACE第16内含子中长度为287bp碱基片段的插入／缺失（I／D）情况,结果：IGT组（n=79)和NGT组（n=40)相比,D型等位基因和DD基因型频率升高（P＜0．05,P＜0．005）;IGT合并冠心病组（n=31)和IG非冠心病组（n=48）相比,DD基因型频率升高（P＜均0．005）,结论：ACE多态性和与老年人糖耐量减冠心病相关,IGT和DD基因型是老年冠心病的重要危险因子。     

The influence of genetic variations in HHEX gene on insulin metabolism in the German MESYBEPO cohort

Background In the present study, we aimed to validate the type 2 diabetes (T2DM) susceptibility alleles identified in the first genome‐wide association study in the hematopoietically expressed homeobox protein (HHEX) gene region (rs1111875 and rs7923837). Furthermore, we investigated quantitative metabolic risk phenotypes of these two variants for association with three key components of the insulin metabolism: insulin secretion, insulin sensitivity and insulin degradation. Methods Two HHEX polymorphisms were genotyped in 1026 subjects from the German MESYBEPO cohort. Complete OGTT data were available for a subset of 420 with normal glucose tolerance (NGT), 282 with impaired glucose tolerance/impaired fasting glucose (IGT/IFG) and 146 diabetic subjects. Results We validated association of both HHEX polymorphisms with T2DM. In the non‐diabetic subcohort including NGT and IFG/IGT subjects, the risk alleles of rs7923837 and rs1111875 were significantly associated with decreased first and second phases of insulin secretion and lower insulinogenic index after oral glucose loading. In healthy, normal glucose‐tolerant subjects, the same association of HHEX SNP rs1111875 with OGTT‐derived phases of insulin secretion were detectable, however, rs7923837 was only weakly associated with reduced insulinogenic index. For both polymorphisms, no significant correlations with insulin sensitivity were obtained. Reduced insulin clearance was also observed in heterozygous carriers of rs1111875. Conclusions We validated the association of polymorphisms of the HHEX gene with T2DM in the MESYBEPO cohort. Importantly, variations within the HHEX gene conferred the impaired insulin secretion and changes of insulin degradation but no alteration in insulin sensitivity in carriers of risk alleles. Copyright © 2008 John Wiley & Sons, Ltd.     

Characteristics of Japanese subjects who progress from normal to impaired glucose tolerance. Longitudinal study excluding changes in body weight

In this retrospective longitudinal study, we focused on the clinical characteristics of Japanese individuals with recent onset impaired glucose tolerance (IGT) who have been followed up for insulin secretory function and 75-gram oral glucose tolerance test (OGTT) for more than 3 years annually before they progressed from normal glucose tolerance (NGT) to IGT. Subjects whose body weight did not show significant change for the period were selected and labeled as either NGT (no change in OGTT over 3 years) or IGT (progressors from NGT to IGT) groups (n = 24, each). We compared the basal biochemical data and response of plasma glucose and serum insulin after OGTT of the two groups. In the IGT progressors, significant increase of plasma glucose at 30 to 120 minutes during OGTT and significant decrease of HDL-cholesterol were observed since 3 years before onset of IGT. In addition to increase of serum glucose and decrease of HDL-cholesterol, serum insulin at 120 minutes during OGTT were significantly and remarkably high at onset and 3 years before onset of IGT. Plasma glucose at 30-120 minutes and serum insulin level at 120 minutes after glucose load are potentially significant predictors of progression from NGT to IGT even in subjects who do not show increase of body weight.     

Contribution of nonesterified fatty acids to insulin resistance in the elderly with normal fasting but diabetic 2-hour postchallenge plasma glucose levels: the Baltimore Longitudinal Study of Aging

Isolated postchallenge hyperglycemia (IPH) with normal fasting plasma glucose <100 mg/dL and plasma glucose with diabetic 2-hour plasma glucose >or=200 mg/dL after an oral glucose tolerance test (OGTT) is a common occurrence in the elderly. We sought to understand what unique characteristics this population might have that puts it at risk for this particular metabolic finding. We therefore conducted a longitudinal study of volunteers in the Baltimore Longitudinal Study of Aging (BLSA). All volunteers had an OGTT performed (75 g) on 2 or more occasions. We measured plasma levels of glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), ghrelin, leptin, adiponectin, resistin, C-reactive protein, cytokines, and their soluble receptors, as well as nonesterified free fatty acids (NEFAs). We determined that 22 subjects in BLSA had IPH, accounting for 2.1% of the BLSA population. All 22 were older than 65 years. They were then matched by age, sex, and body mass index to 12 subjects who had isolated impaired glucose tolerance (IGT) and 15 subjects with normal glucose tolerance (NGT). All subjects had normal fasting glucose levels <100 mg/dL in accordance with the American Diabetes Association Expert Committee on the Classification and Diagnosis of Diabetes Mellitus criteria (2003). We found that subjects with IPH had similar plasma insulin levels to the other 2 groups, except at the 2-hour time when their insulin levels were higher than NGT (P < .05). Although there was a clear trend for differences in the insulinogenic index, the areas under the curves for insulin, systolic blood pressure, adiponectin, and C-reactive protein across the glucose tolerance categories revealed no statistical significance. Cytokines and their soluble receptors, gut hormones, and adipokines were similar in all 3 groups. The NEFA levels were significantly elevated in the fasting state (P < .05) in the IPH compared with NGT, with IGT intermediate between the other 2 groups. The rate of clearance of NEFAs after the OGTT decreased progressively from the NGT to the IPH group (in micromoles per liter per minute: NGT, 11.9 vs IGT, 7.6 vs IPH, 3.0). We conclude that the rate of suppression of lipolysis in the elderly determines the sensitivity of glucose uptake to insulin after OGTT.     

不同糖耐量人群血浆脂肪酸谱与胰岛素抵抗

目的　研究不同糖耐量人群血浆脂肪酸谱与胰岛素抵抗 (IR)之间的关系。方法　将受试者根据口服葡萄糖耐量试验 (OGTT)结果分为正常糖耐量组 (NGT) ,糖耐量受损组 (IGT )及 2型糖尿病组(DM )。采用毛细血管气相色谱法测定血浆脂肪酸谱 ,用胰岛素敏感指数 (IAI)评估IR。结果　DM组及IGT组血浆软脂酸 (C16:0 )、硬脂酸 (C18:0 )、二十二烷酸 (C2 2 :0 )、二十四烷酸 (C2 4:0 )和饱和脂肪酸浓度较NGT组明显升高 (P <0 .0 5～P <0 .0 1) ;花生四烯酸 (C2 0 :4)分别从NGT、IGT和DM组依次升高 ,差异有显著性 (P <0 .0 5～P <0 .0 1) ;血浆饱和脂肪酸 (SFA)从NGT、IGT、DM亚组依次升高 (P <0 .0 5～P <0 .0 1) ;NGT组的多不饱和脂肪酸 (PUFA)与饱和脂肪酸 (SFA)的比率高于IGT组和DM组 (均P <0 .0 5 ) ;血浆C16:0、C2 0 :4、C2 2 :0、SFA与IAI呈负相关 (P均 <0 .0 1)、PUFA/SFA与IAI呈正相关 (P <0 .0 1)。结论　不同糖耐量者血浆脂肪酸谱不同 ,糖耐量减低与 2型糖尿病患者SFA浓度升高 ,PUFA/SFA下降 ,且与胰岛素抵抗密切相关     

1193例住院高血压病患者胰岛素分泌和敏感性情况

目的用口服葡萄糖耐量试验中各点血糖和胰岛素的值来计算反映胰岛素敏感性及β细胞功能的参数,回顾性研究住院高血压病人糖代谢情况。方法根据WHO和美国糖尿病协会标准计算血糖分布情况,去除新诊断的糖尿病病人后,分成正常血糖(NGT)、单纯性空腹血糖升高(IFG)、单纯性餐后血糖升高(IGT)和空腹、餐后血糖均升高(IFG,／IGT)组进行比较。再分别以口服75g葡萄糖后30min或60min血糖正常值为标准对NGT组和IGT组进行分组。用HOMA-IR和Composite胰岛素敏感性指数(ISI)计算胰岛素敏感性,HOMA-B和△I／AG计算β细胞功能。结果1193例住院的原发性高血压病人中,新诊断的糖尿病病人为11．1％,其中57．9％仅有餐后血糖升高。IGT、和IFG／ICT组的HOMA-IR高于NGT组,Composite ISI和AI／AG低于NGT组。无论是否30min或60min血糖升高,IGT组的Composite ISI均低于30min和60min血糖正常的NGT组。30min和(或)60min血糖升高的NGT组△I／AG低于30min和60min血糖正常的NGT组。结论IGT或IFG／IGT的高血压患者同时存在空腹和总体胰岛素敏感性的下降和糖负荷后早期β细胞分泌功能的受损。30min和(或)60min血糖升高的NGT高血压病人存在糖负荷后早期β细胞分泌功能的受损。     

Novel polymorphisms in the GCKR gene and their influence on glucose and insulin levels in a Danish twin population.

AIM: The glucokinase regulatory protein gene is a candidate gene for Type 2 diabetes. This study reveals three new polymorphisms and examines the impact of one new and one known polymorphism on insulin secretion and parameters associated with the insulin resistance syndrome in Danish twins with different degrees of glucose tolerance. METHODS: Single nucleotide polymorphism detection was performed in 20 healthy subjects and in 20 subjects with Type 2 diabetes. The effect of the polymorphisms on lipid, glucose and insulin measures was studied in 566 same-sex twins aged 55-74 years. RESULTS: The new nucleotide (nt) 363 polymorphism was found only in subjects with impaired glucose tolerance and Type 2 diabetes. The nt 11216 polymorphism influenced insulin measured at 120 min during an oral glucose tolerance test (OGTT). Subjects with genotype C11216C/T11216C had 21% higher insulin values (P<0.05) than subjects with genotype T11216T. In twins discordant for this genotype, the C-allele was associated with significantly higher plasma insulin levels at all time points during the OGTT, higher beta-cell function and lower plasma glucose levels during the OGTT. CONCLUSION: The C-allele of nt 11216 polymorphism was associated with increased insulin secretion, and may therefore exert a potentially protective effect against Type 2 diabetes. This remains to be shown in a larger study population.