The G-250A substitution in the promoter region of the hepatic lipase gene is associated with the conversion from impaired glucose tolerance to type 2 diabetes: the STOP-NIDDM trial

OBJECTIVES: Dyslipidaemia that includes high levels of triglycerides and low high-density lipoprotein cholesterol is a risk factor for type 2 diabetes. Hepatic lipase gene encoding a lipolytic enzyme participating in remodelling of plasma lipoproteins and formation of serum lipid profile is a promising candidate gene for type 2 diabetes. The purpose of the study was to investigate whether the G-250A promoter polymorphism of the LIPC gene predicts the conversion from impaired glucose tolerance (IGT) to type 2 diabetes. SUBJECTS AND DESIGN: Study population comprised of subjects who participated in the STOP-NIDDM trial aiming to investigate the effect of acarbose compared with placebo on the prevention of type 2 diabetes in subjects with IGT. RESULTS: Compared with subjects carrying the G-250G genotype, subjects with the A-250A genotype of the LIPC gene had a 2.35-fold [95% confidence interval (CI) 1.27-4.33, P = 0.006] higher risk of developing type 2 diabetes. Subjects in the placebo group and all women carrying the A-250A genotype had an especially high risk for the conversion to type 2 diabetes [odds ratio (OR) 2.74, 95% CI 1.14-6.61, P = 0.024 and OR 3.70, 95% CI 1.35-10.1, P = 0.011 respectively]. CONCLUSION: The G-250A promoter polymorphism of the LIPC gene is associated with an increased risk of development of type 2 diabetes in high-risk subjects with IGT. Therefore, genes regulating atherogenic dyslipidaemia are promising candidate genes for type 2 diabetes.     

Interaction of single nucleotide polymorphisms in ADRB2, ADRB3, TNF, IL6, IGF1R, LIPC, LEPR, and GHRL with physical activity on the risk of type 2 diabetes mellitus and changes in characteristics of the metabolic syndrome: The Finnish Diabetes Prevention Study

Single nucleotide polymorphisms (SNPs) in the ADRB2, ADRB3, TNF, IL6, IGF1R, LIPC, LEPR, and GHRL genes were associated with the conversion from impaired glucose tolerance (IGT) to type 2 diabetes mellitus (T2D) in the Finnish Diabetes Prevention Study (DPS). In this study, we determined whether polymorphisms in these genes modified the effect of changes in physical activity (PA) on the risk of T2D in the DPS. Moreover, we assessed whether the polymorphisms modified the effect of changes in PA on changes in measures of body fat, serum lipids, and blood pressure during the first year of the follow-up of the DPS. Overweight subjects with IGT (n = 487) were followed for an average of 4.1 years, and PA was assessed annually with a questionnaire. The interactions of the polymorphisms with changes in total and moderate-to-vigorous PA on the conversion to T2D during the 4.1-year follow-up were assessed using Cox regression with adjustments for the other components of the intervention (dietary changes, weight reduction). Univariate analysis of variance was used to assess interactions on changes in continuous variables during the first year of the follow-up. No interaction between the polymorphisms and PA on the conversion to T2D was found. The Leu72Met (rs696217) polymorphism in GHRL modified the effect of moderate-to-vigorous PA on changes in weight and waist circumference, the -501A/C (rs26802) polymorphism in GHRL modified the effect of total and moderate-to-vigorous PA on change in high-density lipoprotein cholesterol, and the Lys109Arg (rs1137100) polymorphism in LEPR modified the effect of total PA on change in blood pressure. In conclusion, genetic variation may modify the magnitude of the beneficial effects of PA on characteristics of the metabolic syndrome in persons with IGT.     

Genetic variation in leptin receptor gene is associated with type 2 diabetes and body weight: The Finnish Diabetes Prevention Study

OBJECTIVE: Genetic variation in leptin receptor (LEPR) gene has been reported to associate with insulin and glucose metabolism and adiposity in different study settings and various populations. We wanted to evaluate the association between LEPR polymorphisms, diabetes risk and body weight in Finnish subjects with impaired glucose tolerance (IGT). METHODS: We investigated the associations of the three LEPR polymorphisms (Lys109Arg, Gln223Arg, 3'UTR Del/Ins) with the conversion to type 2 diabetes and the changes in body weight in 507 individuals with IGT participating in the Finnish Diabetes Prevention Study. Participants were randomized to either an intensive diet and exercise intervention group or a control group. RESULTS: After 3 years, the odds ratio for the development of type 2 diabetes in individuals in the control group with the Lys109Lys genotype was 2.38-fold higher than in individuals with other genotype combinations (P=0.016). Irrespective of group individuals with the Gln223Gln genotype had higher conversion to type 2 diabetes (OR 2.01 (95% CI 1.03-3.93)) than the Arg223 allele carriers (P=0.042). The risk was more pronounced in the control group than in the intervention group. Individuals having the 3'UTR Del/Del genotype had a slightly higher body weight throughout the study than those with the insertion allele (P=0.020), although no difference in weight change was observed. CONCLUSION: Two polymorphisms (Lys109Arg, Gln223Arg) in the extracellular domain of the leptin receptor predicted the conversion to type 2 diabetes in high-risk individuals with IGT. The Del/Ins polymorphism in the 3'UTR of LEPR was associated with body weight.     

空腹血糖受损、糖耐量受损人群3年自然转归及其影响因素的研究

目的 探讨空腹血糖受损(IFG)、糖耐量受损(IGT)人群发生糖尿病的危险性及其影响因素. 方法对2003年4～6月朝阳市市区居民1 062人糖尿病普查中IFG、IGT患者79人于2006年4～6月进行随访调查.测量身高、体重、腰围、血压,做过夜空腹75g葡萄糖耐量试验,同时测定血总胆固醇(TC),甘油三酯(TG),高密度脂蛋白胆固醇(HDL-C).结果 随访的65人中22人发生糖尿病.其中孤立性IFG(I-IFG)糖尿病转变率为10.8%,孤立性IGT(I-IGT)为9.2%, IFG/IGT为10.4%.在不同的年龄组,随着年龄增长糖代谢异常、高血压、肥胖、脂代谢异常有增加趋势,在40岁以上人群糖代谢异常的患病率有明显增加趋势.进行单因素相关分析结果发现血糖升高可能与增龄、糖尿病(DM)家族史、劳动强度、腰围指数(WC)增加、收缩压(SBP)增加、血脂异常等相关.进行Logistic回归分析,高龄、血压升高、中心性肥胖、体力活动强度减弱均为糖尿病危险因素.结论 I-IGT、IGT/IFG人群糖尿病累计发病率明显高于I-IFG人群.增龄、向心性肥胖、高血压、体力活动减少是糖代谢异常的重要危险因素,因此控制血压、体重,增加体力活动,对糖尿病预防具有重要意义.     

Involvement of polymorphisms in the chemokine system in the susceptibility for coronary artery disease (CAD). Coincidence of elevated Lp(a) and MCP-1 -2518 G/G genotype in CAD patients

Genetic variation in the hepatic lipase (HL) gene (LIPC) promoter is an important determinant of HL activity in Caucasians. As HL activity is increased in patients with type 2 diabetes mellitus, we have investigated whether the -514 C-to-T polymorphism acted independently of type 2 diabetes to regulate HL activity. The frequency of this polymorphism and its effect on plasma HL activity and lipids were examined in 203 Chinese patients with type 2 diabetes and 205 controls. The frequency of the T allele was 0.343 and 0.376 in male and female diabetic patients, respectively, compared with 0.371 and 0.372 in male and female controls. The effect of LIPC genotype on HL activity was similar between men and women, and between diabetic patients and non-diabetic controls, with the lowest HL activity being found in those subjects with the TT genotype. On multivariate analysis, gender, LIPC genotype, the presence of type 2 diabetes and body mass index were independent predictors of HL activity, accounting for 22, 9, 5 and 3%, respectively, of the variance in HL activity (whole model adjusted R(2)=0.39, P<0.0001). The T allele was associated with higher high-density lipoprotein in the controls but not in the diabetic patients, and no associations were found between LIPC genotype and low-density lipoprotein subfractions in either groups. In conclusion, despite the higher frequency of the T allele in Chinese than in Caucasians, gender was the best predictor for HL activity, with LIPC gene polymorphism and type 2 diabetes making relatively smaller contributions to the variation in HL activity.     

Association of lipoprotein lipase gene polymorphisms with obesity and type 2 diabetes in an Asian Indian population

AIMS: Lipoprotein lipase (LPL), a pivotal enzyme in lipoprotein metabolism, catalyzes the hydrolysis of triglycerides of very low-density lipoproteins and chylomicrons. Assuming that the variants in the promoter of the LPL gene may be associated with changes in lipid metabolism leading to obesity and type 2 diabetes, we examined the role of promoter variants (-T93G and -G53C) in the LPL gene in an urban South Indian population. METHODS: The study subjects (619 type 2 diabetic and 731 normal glucose-tolerant (NGT) subjects) were chosen from the Chennai Urban Rural Epidemiology Study, an ongoing population-based study in southern India. The polymorphisms were genotyped using polymerase chain reaction-restriction-fragment length polymorphism (PCR-RFLP). Linkage disequilibrium (LD) was estimated from the estimates of haplotypic frequencies. RESULTS: The two polymorphisms studied were not in LD. The -T93G was not associated with type 2 diabetes but was associated with obesity. 11.5% of the obese subjects (62/541) had the XG(TG+GG) genotype compared with 6.4% of the nonobese subjects (52/809; P=0.001). The odds ratio for obesity for the XG genotype was 1.766 (95% CI: 1.19-2.63, P=0.005). Subjects with XG genotype also had higher body mass index and waist circumference compared with those with TT genotype. With respect to G53C, subjects with the XC(GC+CC) genotype had 0.527 and 0.531 times lower risk for developing type 2 diabetes and obesity, respectively. CONCLUSIONS: Among Asian Indians, the -T93G SNP of the LPL gene is associated with obesity but not type 2 diabetes, whereas the -G53C SNP appears to be protective against both obesity and type 2 diabetes.     

Association of the Leu72Met polymorphism of the ghrelin gene with the risk of Type 2 diabetes in subjects with impaired glucose tolerance in the Finnish Diabetes Prevention Study.

AIMS: Ghrelin is a gut-brain regulatory peptide stimulating appetite and controlling energy balance. In previous studies, the Leu72Met polymorphism of the ghrelin gene has been associated with obesity and impaired insulin secretion. We investigated whether the Leu72Met polymorphism is associated with the incidence of Type 2 diabetes in subjects with impaired glucose tolerance (IGT) participating in the Finnish Diabetes Prevention Study (DPS). METHODS: DPS was a longitudinal intervention study carried out in five participating centres in Finland. A total of 522 subjects with IGT were randomized into either an intervention or a control group and DNA was available from 507 subjects. The Leu72Met polymorphism was screened by the restriction fragment length polymorphism method. RESULTS: There were no differences in clinical and anthropometric characteristics among the genotypes at baseline. IGT subjects with the Met72 allele were at higher risk of developing Type 2 diabetes than subjects with the Leu72Leu genotype (P = 0.046). Our data also demonstrated that IGT subjects with the common Leu72Leu genotype developed Type 2 diabetes less frequently under intervention circumstances than subjects with the Met72 allele (OR = 0.28, 95% CI 0.10-0.79; P = 0.016). CONCLUSIONS: Subjects with the Leu72Leu genotype had a lower risk for the development of Type 2 diabetes. This was observed particularly in the study subjects who underwent an intensive diet and exercise intervention. Defective first-phase insulin secretion related to the Met72 allele might be one factor contributing to the conversion to Type 2 diabetes.     

二甲双胍和食物纤维在糖耐量低减人群向2型糖尿病发展中的干预作用

目的　观察二甲双胍和食物纤维预防糖耐量低减 (IGT)人群进展为 2型糖尿病 (DM)的作用。　方法　以口服 75 g葡萄糖耐量试验 (OGTT)确诊 (WHO标准 )的 IGT2 93例中男 2 16例 ,女 77例。入选者年龄 35岁以上 ,体重指数 (BMI)在 19kg/ m2以上。随机分为对照组 72例 ,教育组 5 7例 ,食物纤维组 84例 ,二甲双胍组 80例。对照组进行一般的健康教育 ;教育组进行饮食指导 ,每半年1次 ;食物纤维组除健康教育外 ,每日口服食物纤维 12 g;二甲双胍组每日口服二甲双胍 0 .75 g,分 3次餐后口服。对四组参试者每半年作 1次 OGTT,同时测身高、体重、BMI、12 h尿白蛋白 ,复查日当天不服干预药物或食物纤维。共观察 3年。若 2次 OGTT或最后 1次复查结果为 DM,则判断为已发展为 DM。　结果　 2 93例 IGT在观察中有 2 3例 (7.8% )退出。空腹血糖 (FBS)和服糖后 1h血糖 (1hPBS)在对照组、教育组和食物纤维组均较治疗前略有升高 ,但在二甲双胍治疗组均有下降。四组间FBS比较 F=8.118,P<0 .0 1,四组间 1h PBS比较 F=3.6 97,P=0 .0 12。观察期末对照组 16例 (2 5 .0 % )、教育组 11例 (2 1.6 % )、食物纤维组 13例 (16 .3% )、二甲双胍组 7例 (9.3% )转化为 DM,二甲双胍组在治疗后 DM转化率明显低于对照组 (χ2 =6 .318,P<0 .0     

Cross-sectional and prospective associations between abdominal adiposity and proinsulin concentration.

The objective of this study was to investigate the associations of total and abdominal obesity with variation in proinsulin concentration in a Native Canadian population experiencing an epidemic of type 2 diabetes mellitus (DM). Between 1993 and 1995, 728 members of a Native Canadian community participated in a population-based survey to determine the prevalence and risk factors for type 2 DM. Samples for glucose, C-peptide, and proinsulin were drawn after an overnight fast, and a 75-g oral glucose tolerance test was administered. Type 2 DM and impaired glucose tolerance (IGT) were diagnosed using World Health Organization criteria. Height, weight, waist circumference, and percent body fat were measured. In 1998, 95 individuals who, at baseline, had IGT or normal glucose tolerance with an elevated 2-h glucose level (> or = 7.0 mM) participated in a follow-up evaluation using the same protocol. After adjustment for age, sex, C-peptide concentration, per cent body fat, and waist circumference, proinsulin was found to be significantly elevated in diabetic subjects, relative to subjects with both impaired and normal glucose tolerance (both P < 0.0001); and the concentration in those with IGT was higher, compared with normals (P < 0.0001). Among nondiabetic subjects, proinsulin showed significant univariate associations with percent body fat, body mass index, and waist circumference (r = 0.34, 0.45, 0.41, respectively, all P < 0.0001). After adjustment for body fat and other covariates, waist circumference remained significantly associated with proinsulin concentration in nondiabetic subjects (r = 0.20, P < 0.0001). In prospective analysis, adjusted for covariates (including baseline IGT and follow-up glucose tolerance status), baseline waist circumference was positively associated with both follow-up and change in proinsulin concentration (r = 0.27, P = 0.01; r = 0.24, P = 0.03, respectively). These data highlight the detrimental effects of abdominal obesity on beta-cell function, and support the hypothesis that beta-cell dysfunction occurs early in the natural history of glucose intolerance.     

Common polymorphisms in the genes regulating the early insulin signalling pathway: effects on weight change and the conversion from impaired glucose tolerance to Type 2 diabetes.

Aims/hypothesis Type 2 diabetes is a complex disorder with strong heritability. The aim of our study was to investigate whether common polymorphisms in the genes regulating the early insulin signalling pathway (insulin; A-23T, insulin-like growth factor 1 receptor [IGF-1R]; GAG1013GAA, plasma cell membrane glycoprotein 1 [PC-1]; K121Q, insulin receptor substrate [IRS-1]; G972R, insulin receptor substrate 2 [IRS-2]; G1057D and phosphatidylinositol 3-kinase p85 [PI3K]; M326I) affect the weight change and development of Type 2 diabetes in the Finnish Diabetes Prevention Study.Methods We screened for the polymorphisms in 490 overweight subjects with impaired glucose tolerance whose DNA was available from the Finnish Diabetes Prevention Study. These subjects were randomly allocated into a control group and an intervention group characterised by intensive, individualised diet and exercise.Results In carriers of the GAA1013GAA genotype of IGF-1R, the R972 allele of IRS-1 and the D1057D genotype of IRS-2, lifestyle intervention did not lead to significant differences in weight loss between the intervention and control groups, implying a role of these risk genotypes in the regulation of body weight. We observed a statistically significant difference in the conversion rate from IGT to diabetes between the genotypes of the IGF-1R gene (GAG1013GAG: 18.6%, GAG1013GAA: 10.4%, GAA1013GAA: 19.5%, p=0.033). Common polymorporphisms in the insulin, PC-1 and PI3K genes did not regulate weight change or conversion to diabetes.Conclusions/interpretation The common polymorphisms of the IGF-1R, IRS-1 and IRS-2 genes may modify the weight change response to a lifestyle intervention but not the conversion from IGT to Type 2 diabetes, whereas IGF-1R may also regulate the risk of developing Type 2 diabetes.Abbreviations DPS Finnish Diabetes Prevention Study - IGF-1R insulin-like growth factor 1 receptor - PC-1 plasma cell membrane glycoprotein-1 - PI3K phosphatidylinositol 3-kinase - PI3K p85 phosphatidylinositol 3-kinase regulatory subunit p85 - PPAR peroxisome proliferator-activated receptor - VNTR variable number of tandem repeat     

Prevention of type 2 diabetes by lifestyle intervention: a Japanese trial in IGT males

Prevention of type 2 diabetes by intensive lifestyle intervention designed to achieve and maintain ideal body weight was assessed in subjects with impaired glucose tolerance (IGT). Male subjects with IGT recruited from health-screening examinees were randomly assigned in a 4:1 ratio to a standard intervention group (control group) and intensive intervention group (intervention group). The final numbers of subjects were 356 and 102, respectively. The subjects in the control group and in the intervention group were advised to maintain body mass index (BMI) of <24.0 kg/m2 and of <22.0 kg/m2, respectively, by diet and exercise. In the intervention group, detailed instructions on lifestyle were repeated every 3-4 months during hospital visits. Diabetes was judged to have developed when two or more consecutive fasting plasma glucose (FPG) values exceeded 140 mg/dl. A 100g oral glucose tolerance test was performed every 6 months to detect improvement of glucose tolerance. The subjects were seen in an ordinary outpatient clinic. The cumulative 4-year incidence of diabetes was 9.3% in the control group, versus 3.0% in the intervention group, and the reduction in risk of diabetes was 67.4% (P < 0.001). Body weight decreased by 0.39 kg in the control group and by 2.18 kg in the intervention group (P < 0.001). The control group was subclassified according to increase and decrease in body weight. The incidence of diabetes was positively correlated with the changes in body weight, and the improvement in glucose tolerance was negatively correlated. Subjects with higher FPG at baseline developed diabetes at a higher rate than those with lower FPG. Higher 2h plasma glucose values and higher BMI values at baseline were also associated with a higher incidence of diabetes, but the differences were not significant. Subjects with a low insulinogenic index (DeltaIRI/DeltaPG 30 min after an oral glucose load) developed diabetes at a significantly higher rate than those with a normal insulinogenic index. Comparison of the BMI data and incidence of diabetes in five diabetes prevention studies by lifestyle intervention revealed a linear correlation between the incidence of diabetes and the BMI values, with the exception of the DaQing Study. However, the slope of the reduction in incidence of diabetes in the intensive intervention groups was steeper than expected simply on the basis of the reduction of BMI, suggesting that the effect of lifestyle intervention cannot be solely ascribed to the body weight reduction. We conclude that lifestyle intervention aimed at achieving ideal body weight in men with IGT is effective and can be conducted in an outpatient clinic setting.     

Central obesity predicts the worsening of glycemia in southern Chinese.

AIMS: The association between obesity and type 2 diabetes has been found to be consistent across different ethnic populations. Our aim was to study the contribution of obesity to the development of type 2 diabetes in a non-obese Chinese population with a high prevalence of diabetes (9.8% in 1995-1996). METHODS: Six-hundred and forty-four non-diabetic subjects were recruited from the Hong Kong Cardiovascular Risk Factor Prevalence Study (1995-1996). This was a community-based population study which involved the use of a 75 g oral glucose tolerance test and 1985 World Health Organization diagnostic criteria. Their glycemic status was reassessed at 2 y. RESULTS: In subjects with impaired glucose tolerance (n=322), the annual progression rate to diabetes (4.8%; 95% CI 2.5-7.1%), was 8-fold that in control subjects (0.6%; 95% CI 0.0-1.4%; P<0.001). Baseline waist-hip ratio (WHR; OR per unit increase=1.05; 95% CI 1.02-1.07, P=0.0003) and post-load 2 h plasma glucose (OR per unit increase=2.02; 95% CI 1.76-2.34, P<0.0001) were significantly associated with glycemic status at 2 y in stepwise polytomous logistic regression analysis. Subjects with high baseline waist circumference or WHR (> or =median) were more likely to have worsening of glucose tolerance at 2 y than those with low waist circumference (相似文献   

Relative role of insulin resistance and beta-cell dysfunction in the progression to type 2 diabetes--The Kinmen Study

This study compared the relative role of insulin resistance and beta-cell dysfunction (both assessed using the HOMA method) with glucose intolerance conditions in the progression to type 2 diabetes among a high risk group of subjects with fasting plasma glucose (FPG) 5.6-7.0 mmol/l in Kinmen, Taiwan. Data were collected during a continuing prospective study (1998-99) of a group of Taiwanese subjects at high-risk of developing type 2 diabetes who had fasting hyperglycemia (5.6-7.0 mmol/l) and exhibited 2-h postload glucose concentrations <11.1 mmol/l from 1992-94 to 1995-96. Among 644 non-diabetic subjects at baseline, 79.8% (514/644) had at least one follow-up examination. There were 107 new cases of diabetes diagnosed by 1999 WHO criteria in 2918.7 person-years of follow-up. The incidence rate was 3.67%/year (107/2918.7). After adjustment for other possible associative variables, including gender, age, BMI, waist circumference, insulin resistance, and beta-cell dysfunction, Cox's hazard model showed that those individuals with isolated IFG (impaired fasting glucose) and those individuals with isolated IGT (2-h glucose impairment) exhibited similar risk of developing diabetes. Those individuals with isolated IFG and isolated IGT showed a comparable impairment of basal or hepatic insulin sensitivity, but those individuals with isolated IFG had a greater beta-cell dysfunction by the HOMA method.     

Effects of race and family history of type 2 diabetes on metabolic status of women with polycystic ovary syndrome

Racial origin and family history of type 2 diabetes impact upon the risk of developing impaired glucose tolerance (IGT) and type 2 diabetes, both of which are common in women with polycystic ovary syndrome (PCOS). We examined the effects of race and family history of type 2 diabetes on the risk of IGT and type 2 diabetes in a large cohort of women with PCOS. Data obtained at baseline were analyzed from 408 premenopausal women with PCOS. Multivariate linear regression models were used to assess the impact of race (white, black, and other) and family history of type 2 diabetes on body mass index, waist circumference, and waist to hip ratio; glycemic measures (glucose and insulin levels obtained during a standard 75-g oral glucose tolerance test, fasting glucose to insulin ratio, and homeostasis model assessment model of insulin resistance derived from fasting levels of glucose and insulin), hemoglobin A(1c), and SHBG, and dehydroepiandrosterone sulfate levels. Sixteen (4%) of the 408 patients had type 2 diabetes, 94 (23%) had IGT, and the remaining 298 (73%) had normal glucose tolerance. A history of type 2 diabetes in either parent (FHxPOS) was present in seven (44%) of the 16 diabetic women with PCOS, 37 (39%) of the 94 women with IGT, and 62 (21%) of those with normal glucose tolerance (P < 0.01, by chi(2) test). The prevalences of IGT and type 2 diabetes were significantly higher in FHxPOS PCOS women compared with FHxNEG PCOS women, IGT evident in 37 (35%) FHxPOS compared with 57 (19%) FHxNEG women, and type 2 diabetes evident in seven (7%) FHxPOS compared with nine (3%) FHxNEG women. Among the 392 nondiabetic subjects, after adjustment for the effects of race, FHxPOS differed significantly from FHxNEG patients in having a higher mean waist to hip ratio, hemoglobin A(1c) level, 2-h glucose level, fasting glucose and insulin levels, glucose to insulin ratio, homeostasis model assessment model of insulin resistance, and areas under the glucose and insulin curves during the oral glucose tolerance test. A family history of type 2 diabetes was present with a significantly greater frequency among women with PCOS who had IGT or type 2 diabetes compared with those with normal glucose tolerance. Conversely, a family history of type 2 diabetes in a first-degree relative was associated with a significantly higher risk for IGT or type 2 diabetes in women with PCOS. Even among nondiabetic women with PCOS, a positive family history of type 2 diabetes was strongly associated with metabolic characteristics associated with an increased risk for type 2 diabetes. Finally, the fasting glucose concentration was poorly associated with 2-h glucose concentrations among PCOS women with IGT, suggesting that the fasting glucose concentration is inadequate to predict the presence of IGT in PCOS.     

高血压病伴代谢综合征患者463例的干预治疗研究

目的　分析高血压病伴代谢综合征人群新发糖尿病的预测因素,同时评价较理想的降压药物以降低危险因素,防止糖尿病发生。方法　用随机平行对照临床试验,选轻、中度高血压病患者符合下列 3项中 2项者进入研究: (1)腰围及(或)体质脂数(BMI)异常; (2)甘油三酯(TG)及(或 )低高密度脂蛋白胆固酯(HDL C)升高; (3)糖耐量异常 (IGT)。将患者分成三个干预治疗组: (1)吲哒帕胺+福辛普利组 (第 1组,n=151); (2)阿替洛尔 +尼群地平组 (第 2组,n=160); (3)阿替洛尔+尼群地平+二甲双胍组(第 3组,n=152)。每月随访 1次,按血压水平调整剂量。每 6个月测定空腹血糖及服 75g葡萄糖 2h后血糖,发现异常者定为新发糖尿病而终止试验。在最后随访时重复测定糖耐量试验(OGTT)、胰岛素释放试验(InRT)、血脂、体重及腰围。结果　(1)在三组降压幅度相似(P>0 05)的基础上,新发糖尿病共 23例,三组分别为 10例, 8例, 5例。虽然加服二甲双胍组比不加组新发人数较少但差异未达统计学意义; (2)从三组危险因素构成比看, 第 2、3组,TG升高者在治疗后,分别下降 14 7%及 9 3% (P<0 05),向心性肥胖分别减少 16 7%及 15 9% (P<0 05 ),IGT分别减少 6 6%及 29 6% (P<0 05),而第 1组服药后均无明显变化; (3)平均随访 1年 5个月后基础状态危险因素 (     

Calpain 1 O基因多态性与中国人2型糖尿病遗传易感性的相关性研究

目的 了解Calpain 10基因对中国汉族人2型糖尿病遗传易感性的影响。方法 采用病例对照研究方法：以聚合酶链式反应－限制性内切酶长度多态性（PCR－RFLP）技术，对211例2型糖尿病患者及127例正常对照Calpain 10基因SNP43及SNP19多态性进行基因分型。结果 同对照组相比，SNP43的G等位基因频率在2型糖尿病人群中显著升高（91．9％ vs 85.8%,P=0.01)。但SNP19位点等位基因频率在上述两组中的频率分布无显著差异。此外，本研究还观察到在正常对照组中，SNP43GG基因型与体重指数和腰－臂围比值增加相关。结论 Calpain 10基因SNP43位点G等位基因可直接或与其他糖尿病基因相互作用决定汉族人2型糖尿病的遗传易感性。     

Subscapular skinfold thickness distinguishes between transient and persistent impaired glucose tolerance: Study on Lifestyle-Intervention and Impaired Glucose Tolerance Maastricht (SLIM).

AIMS: To assess whether adding anthropometric measurements to an oral glucose tolerance test (OGTT) can help to distinguish between transient and persistent impaired glucose tolerance (IGT). METHODS: From the SLIM project (Study on Lifestyle-Intervention and IGT Maastricht), a study designed to evaluate whether diet and physical activity intervention can improve glucose tolerance in subjects at risk for diabetes, 108 subjects with IGT underwent a repeated OGTT 2-4 months after the initial OGTT. Following the second test, subjects were classified as transient IGT, or persistent IGT. Anthropometric measurements, including body mass index, waist and hip circumference, sagittal and transverse abdominal diameters and skinfold thickness measurements, were done during the second OGTT. RESULTS: Persistent IGT was diagnosed in 47 subjects (44%), transient IGT in 40 (37%), impaired fasting glucose in eight subjects (7%), and diabetes in 13 cases (12%). Two-hour blood glucose levels at the initial OGTT and subscapular skinfold thickness were significantly higher in subjects with persistent IGT (2-h blood glucose 9.8+/-0.1 mmol/l vs. 10.2+/-0.1 mmol/l for transient IGT and persistent IGT, respectively; subscapular skinfold thickness 25.4+/-1.4 mm vs. 29.8+/-1.2 mm for transient IGT and persistent IGT, respectively). After adjustment for age, sex and family history of diabetes mellitus, logistic regression indicated that 2-h blood glucose level during the initial OGTT represented the strongest predictor of persistent IGT (P<0.02), followed by subscapular skinfold thickness (P<0.05). After adjustment for 2-h blood glucose levels during the first OGTT, subscapular skinfold thickness remained significantly associated with persistent IGT (odds ratio 1.84; P<0.05). CONCLUSIONS: In addition to the 2-h blood glucose level, subscapular skinfold thickness was the best predictor of persistent IGT, suggesting that adding simple anthropometric measures to oral glucose tolerance testing may improve the distinction between persistent and transient glucose intolerance.     

The -250G>A promoter variant in hepatic lipase associates with elevated fasting serum high-density lipoprotein cholesterol modulated by interaction with physical activity in a study of 16,156 Danish subjects

CONTEXT: Hepatic lipase plays a pivotal role in the metabolism of high-density lipoprotein (HDL) and low-density lipoprotein by involvement in reverse cholesterol transport and the formation of atherogenic small dense low-density lipoprotein. OBJECTIVES: The objective was to investigate the impact of variants in LIPC on metabolic traits and type 2 diabetes in a large sample of Danes. Because behavioral factors influence hepatic lipase activity, we furthermore examined possible gene-environment interactions in the population-based Inter99 study. DESIGN: The LIPC -250G>A (rs2070895) variant was genotyped in the Inter99 study (n = 6070), the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care Denmark screening cohort of individuals with risk factors for undiagnosed type 2 diabetes (n = 8662), and in additional type 2 diabetic patients (n = 1,064) and glucose-tolerant control subjects (n = 360). RESULTS: In the Inter99 study, the A allele of rs2070895 associated with a 0.057 mmol/liter [95% confidence interval (CI) 0.039-0.075] increase in fasting serum HDL-cholesterol (HDL-c) (P = 8 x 10(-10)) supported by association in the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care study [0.038 mmol/liter per allele (95% CI 0.024-0.053); P = 2 x 10(-7)). The allelic effect on HDL-c was modulated by interaction with self-reported physical activity (P(interaction) = 0.002) because vigorous physically active homozygous A-allele carriers had a 0.30 mmol/liter (95% CI 0.22-0.37) increase in HDL-c compared with homozygous G-allele carriers. CONCLUSIONS: We validate the association of LIPC promoter variation with fasting serum HDL-c and present data supporting an interaction with physical activity implying an increased effect on HDL-c in vigorous physically active subjects carrying the -250 A allele. This interaction may have potential implications for public health and disease prevention.     

Glucose tolerance in a rural population of Bangladesh

CONTEXT:

The prevalence of type 2 diabetes is increasing in the Bangladeshi population. However, there is little information available on the prevalence of glucose intolerance, ie, type 2 diabetes, impaired glucose tolerance, and impaired fasting glucose.

AIMS:

The main aim of this study is to determine the prevalence of different categories of glucose intolerance and their relationship with different anthropometric and demographic characteristics.

SETTINGS AND DESIGN:

This cross-sectional study was performed in a rural area of Bangladesh.

MATERIALS AND METHODS:

A random sample of 5000 persons aged ≥ 20 years was included in this study. Fasting blood glucose was measured in 3981 individuals and 2-h post-glucose blood glucose was measured in 3954 subjects after the known cases of diabetes (n = 27) were excluded. Height, weight, waist and hip circumference, and blood pressure were measured.

STATISTICAL ANALYSIS:

Pearson Chi-squared test and correlation test were used for analysis as appropriate.

RESULTS:

The prevalence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and diabetes (DM) were 1.3, 2.0, and 7.0%, respectively. IFG, IGT, and IFG + IGT were more prevalent in females. Age showed a significant positive relationship with increasing levels of glucose intolerance. Body mass index, waist circumference, and waist-to-hip ratio were higher in the glucose-intolerant group than in the normal glucose tolerance (NGT) group. There was a positive correlation between FBG and 2-h BG in NGT and DM subjects.

CONCLUSION:

The FBG value identified more people with glucose intolerance than the 2-h BG. These findings will help developing diabetes preventive strategy in rural populations.