葡萄糖激酶基因启动子G/A变异与空腹高血糖相关

目的　研究葡萄糖激酶 (GCK)基因启动子 - 30G/A变异在中国南方地区汉族人群中的分布并比较其在正常糖耐量 (NGT)者及糖耐量低减 (IGT)者中的差别及其与糖代谢相关指标之间的关系。方法　研究对象为 4 4 4例无糖尿病及亲缘关系的中国南方地区汉族人 ,其中 2 2 2例为NGT ,2 2 2例为IGT。通过PCR RFLP检测GCK启动子 - 30位置的G→A变异所导致BsiHKAⅠ酶切位点的缺失。结果　在IGT及NGT的人群中含有A等位基因的频率分别为 18.2 %及 19.8%。与GG基因型的人群相比 ,带有A等位基因的人群空腹血糖显著增高〔(5 .35± 0 .5 9vs 5 .19± 0 .5 3)mmol/L ,P =0 .0 0 6〕 ,在IGT的人群中 ,带有A等位基因的人群空腹血糖仍显著增高〔(5 .5 4± 0 .5 8vs 5 .35± 0 .5 2 )mmol/L ,P =0 .0 2〕 ,而在NGT的人群中 ,不同GCK基因型者的空腹血糖差异无显著性。结论GCK基因启动子 - 30G/A变异与空腹高血糖水平相关 ,可能对中国人的IGT有一定的影响。     

Angiographic coronary artery disease is associated with progressively higher levels of fasting plasma glucose

This study evaluated the association between progressively higher levels of fasting glycemia (G) and insulin resistance parameters with coronary artery disease (CAD) in patients referred for coronary angiography. All 145 patients (age 58.4+/-0.9 years, 51.7% men) underwent clinical and laboratory evaluation before coronary angiography and subjects were divided into four groups: normal (N, <88 mg/dl), high-normal (H-N, 89-99 mg/dl), impaired fasting glucose (IFG, 100-125 mg/dl) and diabetes (DM, >126 mg/dl or known diabetics). Arteriographic evidence of CAD was determined by two criteria: (1) a 30% or greater diameter stenosis in at least one major coronary artery; (2) a 70% or greater diameter stenosis in at least one major coronary artery. HOMA-IR increased progressively according to each group: N=1.74+/-0.2, H-N=3.14+/-0.3, IFG=4.67+/-0.6 and DM=8.00+/-2.9; p=0.001. The proportion of patients with CAD according to both criteria increased with each G level: CAD criteria 1: N=39.4%, H-N=50%, IFG=60% and DM=69.6%, p=0.006; CAD criteria 2: N=27.3%, H-N=30%, IFG=36% and DM=50%, p=0.03. We demonstrated a significant association between subtle disturbances of the glucose metabolism, assessed by subnormal levels of fasting glucose and insulin resistance parameters, and angiographically documented coronary artery disease.     

Significant association of the interleukin-6 gene polymorphisms C-174G and A-598G with type 2 diabetes

Elevated blood concentrations of IL-6 have been shown to predict type 2 diabetes. Because the impact of IL-6 gene polymorphisms on diabetes status, parameters of the metabolic syndrome, and low-grade systemic inflammation has not been analyzed in a population-based study, we investigated the association of the IL-6 single nucleotide polymorphisms C-174G and A-598G on these parameters in 704 elderly participants of the Kooperative Gesundheitsforschung im Raum Augsburg/Cooperative Research in the Region of Augsburg (KORA) Survey 2000. Both -174G and -598G alleles were significantly associated with type 2 diabetes (-174G: odds ratio = 1.51, 95% confidence interval = 1.11-2.07, P = 0.0096; -598G: odds ratio = 1.56, 95% confidence interval = 1.13-2.15, P = 0.0069) but not with impaired glucose tolerance. In subgroup analyses, the association reached statistical significance in men and in leaner subjects (body mass index 相似文献   

Classical cardiovascular risk factors according to fasting plasma glucose levels

BACKGROUND: To compare the prevalence of classical cardiovascular risk factors (CVRF) and metabolic syndrome (MetS) in our population according to fasting plasma glucose levels (FPG). METHODS: We have studied 344 subjects between 20-70 years of age, recruited in a Primary Care Clinic. Subjects were divided into four groups according to their fasting plasma glucose (FPG) values: normal plasma glucose (NG) when FPG < 5.6 mmol/L; FPG between 5.6 and 6.0 mmol/L (FPG1); FPG between 6.1-6.9 mmol/L (FPG2); and diabetes (DM) FPG > or = 7 mmol/L or previous diagnosis of diabetes. Cardiovascular risk factors (hypertension, TC/HDL-C index and Apo B values), presence of the MetS and indirect measure of insulin resistance (HOMA) were analyzed. RESULTS: Subjects with FPG2 have a prevalence of classic CVRF and MetS similar to that observed in subjects with type 2 diabetes mellitus (T2DM). The TC:HDL-C index > or = 5 in 56% and 57%, Apo B > or = 1.2 g/L in 59% and 57%, hypertension in 60% and 54% of FPG2 and T2DM subjects, respectively. MetS was diagnosed in 79% of FPG2 and 80% of T2DM. We found significant differences with FPG1 group who presented low CVRF and MetS proportion. CONCLUSION: In our population FPG2 and T2DM subjects show a similar cardiovascular risk profile. On the other hand, such risk is significantly lower in subjects with FPG between 5.6-6.0 mmol/L. These results might have practical implications.     

Seasonal variation in fasting plasma glucose levels in man

Summary A Southern California community study of 4,541 men and women (aged 20–79 years) showed significant seasonal variation in fasting plasma glucose. There was a mean 0.6 mmol/l difference between highest levels in winter and lowest levels in spring. This difference was consistent over a two-year period, similar at all ages and seen in both men and women. Fasting plasma glucose levels correlated directly with percentage possible sunshine (p= 0.03) and inversely with temperature (p= 0.04). Adjustment for the level of measured obesity did not alter the observed association, but a history of recent weight gain corresponded to the season of maximum fasting plasma glucose level.     

A variant in the G6PC2/ABCB11 locus is associated with increased fasting plasma glucose, increased basal hepatic glucose production and increased insulin release after oral and intravenous glucose loads

Aims/hypothesis

An association between elevated fasting plasma glucose and the common rs560887 G allele in the G6PC2/ABCB11 locus has been reported. In Danes we aimed to examine rs560887 in relation to plasma glucose and serum insulin responses following oral and i.v. glucose loads and in relation to hepatic glucose production during a hyperinsulinaemic–euglycaemic clamp. Furthermore, we examined rs560887 for association with impaired fasting glycaemia (IFG), impaired glucose tolerance (IGT), type 2 diabetes and components of the metabolic syndrome.

Methods

rs560887 was genotyped in the Inter99 cohort (n?=?5,899), in 366 young, healthy Danes, in non-diabetic relatives of type 2 diabetic patients (n?=?196), and in young and elderly twins (n?=?159). Participants underwent an OGTT, an IVGTT or a 2 h hyperinsulinaemic–euglycaemic clamp.

Results

The rs560887 G allele associated with elevated fasting plasma glucose (p?=?2?×?10^?14) but not with plasma glucose levels at 30 min (p?=?0.9) or 120 min (p?=?0.9) during an OGTT. G allele carriers had elevated levels of serum insulin at 30 min during an OGTT (p?=?1?×?10^?4) and relatives of type 2 diabetes patients carrying the G allele had an increased acute insulin response (p?=?4?×?10^?4) during an IVGTT. Among elderly twins, G allele carriers had higher basal hepatic glucose production (p?=?0.04). Finally, the G allele associated with the risk of having IFG (OR 1.26, 95% CI 1.08–1.47, p?=?0.002), but not with IGT (OR 0.94, 95% CI 0.82–1.08, p?=?0.4) or type 2 diabetes (OR 0.93, 95% CI 0.84–1.04, p?=?0.2).

Conclusions/interpretation

The common rs560887 G allele in the G6PC2/ABCB11 locus is associated with increased fasting glycaemia and increased risk of IFG, associations that may be partly related to an increased basal hepatic glucose production rate.     

血糖正常人群不同空腹及口服葡萄糖耐量试验2h血糖水平与代谢综合征的关系

目的在血糖正常的中国人群样本中比较不同血糖表型人群代谢综合征患病率及其各组分水平。方法来自2002年青岛湛山社区糖尿病流行病学调查。共有2438名20-74岁常住居民参加调查,其中2109人进行了人体测量学指标测定、口服75g葡萄糖耐量试验（OGTT）并检测总胆固醇、甘油三酯、高密度脂蛋白胆固醇（HDL-C）、空腹血胰岛素等。本研究选取其中1341名血糖正常者作为研究对象,根据OGTr2h血糖是否大于空腹血糖水平分为表型A组（2h血糖≤空腹血糖）和表型B组（2h血糖〉空腹血糖）。组间比较采用t检验、协方差分析或卡方检验。多因素logistic回归分析评价血糖表型与代谢综合征的相关性。结果研究对象中表型A、B的比例分别为42．3％（564／1341）和57．9％（777／1341）。校正年龄、性别的影响后,表型B组平均体质指数、腰围、收缩压、舒张压、空腹血胰岛素、甘油三酯、非HDL-C均高于表型A组,而且表型B组代谢综合征患病率[19．1％（149／777）]亦高于表型A组[14．7％（83／564）],差异有统计学意义（X^2=3．91,P〈0．05）。多因素logistic回归分析发现,具有血糖表型B是代谢综合征的危险因素,相应的OR值为1．32（95％CI1．02-1．74）。结论在血糖正常的人群中,OGTT2h血糖不能回落到空腹血糖水平的人群合并代谢综合征的风险较高,提示可能对心血管疾病的早期筛查和预防提供依据。     

A genetic variant of G6PC2 is associated with type 2 diabetes and fasting plasma glucose level in the Chinese population

Aims/hypothesis  Single nucleotide polymorphisms (SNPs) in G6PC2 have been reported to be associated with fasting plasma glucose level in several populations of European descent. However, whether G6PC2 variants have a similar effect in other ethnic groups is unknown. The aim of this study was to investigate the effect of common variants of G6PC2 on type 2 diabetes and related clinical features in a Chinese population. Methods  We selected four SNPs, rs13387347, rs2232316, rs492594 and rs16856187, tagging all the common variants spanning the G6PC2 gene (r ² ≥ 0.8) based on HapMap Chinese data, and genotyped them in a group of 3,676 Shanghai Chinese individuals, comprising 1,876 cases and 1,800 controls. Results  Three SNPs were nominally associated with type 2 diabetes, with rs16856187 showing the strongest evidence for association (p = 0.0009, empirical p = 0.0047). Further conditional analysis revealed that the association signal arose from an individual SNP, rs16856187. This SNP was also associated with fasting plasma glucose level in participants with normal glucose regulation (p = 0.0002), with the fasting plasma glucose level observed to increase by 0.067 mmol/l with each copy of the rare C allele. Conclusions/interpretation  In this study we identified a novel risk-conferring G6PC2 SNP for type 2 diabetes in a Chinese population and confirmed the previous finding that G6PC2 variants are associated with fasting plasma glucose concentration. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorised users. An erratum to this article can be found at     

Interaction of the G182C polymorphism in the APOA5 gene and fasting plasma glucose on plasma triglycerides in Type 2 diabetic subjects.

AIM: Apolipoprotein AV (APOA5) is an important determinant of plasma triglyceride concentration. This study aimed to investigate the relationship of an amino acid substitution at position 182 (G182C) of the apolipoprotein AV (APOA5) gene with triglyceride concentration in a Taiwanese population. METHODS: This study enrolled two cohorts: non-diabetic subjects (112 males and 89 females) aged 50.3+/-11.0 years (mean+/-sd) and diabetic subjects (106 males and 96 females) aged 62.1+/-10.3 years. The relationship between the G182C polymorphism (rs 2075291) and plasma triglycerides was examined. Demographic and metabolic parameters including age, sex, body mass index, fasting plasma glucose and total cholesterol were also obtained. RESULTS: The G182C polymorphism was a determinant of plasma triglycerides in both non-diabetic (P=0.022) and diabetic (P=0.003) groups, independent of age, gender, fasting plasma glucose, body mass index and total cholesterol. In the diabetic group, this genetic polymorphism interacts significantly (P=0.032) with fasting plasma glucose concentration on plasma triglycerides after adjustment for age, sex, body mass index and total cholesterol. CONCLUSIONS: In conclusion, the G182C polymorphism of the APOA5 gene affects plasma triglycerides in both non-diabetic and diabetic populations. The observed interaction of gene and glycaemic control further indicates a multifactorial nature of clinical phenotypes in subjects with Type 2 diabetes.     

Correlation among fasting plasma glucose, two-hour plasma glucose levels in OGTT and HbA1c

A study was made on the association among 2-h plasma glucose (PG) in oral glucose tolerance test (OGTT), fasting plasma glucose (FPG) using correlation and regression equation. Subjects were 13 174 OGTT examinees tested between 1980 and 1998. Blood glucose was determined by the glucose oxidase method and glycated hemoglobin (HbA1c) by the HPLC method. As for correlation between 2-h PG and FPG, regression equation of the <60 year group was y=57.1+0.336x (r=0.866, P<0.0001) and that of the 60 year group was y=61.5+0.286x (r=0.814, P<0.0001). FPG was calculated at 124.3 in the <60 year group and 118.7 mg/dl in the 60 year group for 2-h PG of 200 mg/dl, 2-h PG were calculated at 199.5 and 210.7 mg/dl for FPG of 126 mg/dl, respectively. In the <60 year group, FPG were calculated at 121.7 and 124.4 mg/dl and 2-h PG at 193.2 and 199.3 mg/dl for HbA1c of 6.0 and 6.1%, respectively. As for associations between HbA1c and FPG or 2-h PG being high correlation, it is possible to estimate a prevalence of DM in a group using HbA1c6.1%. High correlations were demonstrated among all the three measures; FPG, 2-h PG, HbA1c. If 2-h PG is used in diagnosing diabetes mellitus, an FPG of 126 mg/dl proposed by ADA and World Health Organization (WHO) as a diagnostic level of FPG is an acceptable value for the Japanese.     

Association of aortic pressures with fasting plasma glucose in patients with and without impaired fasting glucose

BACKGROUND: Diabetes mellitus and impaired fasting glucose (IFG) are associated with future cardiovascular disorders. Aortic pulse pressure (PP) and fractional pulse pressures (FPPs) are strong and independent indicators of the risk of coronary heart disease. These conditions have been reported to be associated with endothelial dysfunction. In the present study, aortic PP and FPPs of patients with and without impaired fasting glucose were evaluated. METHODS: Fifty patients with IFG with a mean age of 56.8+/-12.2 years and 47 patients with normal fasting glucose (NFG) with a mean age of 53.1+/-11.2 years were included in the study. All subjects had angiographically proven normal coronary arteries without coronary slow flow. Aortic systolic and diastolic blood pressures were measured invasively. Mean pressure, PP and FPPs (aortic PP/mean pressure) were calculated. RESULTS: All parameters measured were significantly higher in the IFG group than in the control (NFG) group (133+/-21 mmHg and 117+/-12 mmHg, p<0.001 for aortic systolic pressure; 79+/-12 mmHg and 74+/-8 mmHg, p = 0.035 for aortic diastolic pressure; 97+/-14 mmHg and 88+/-9 mmHg, p = 0.001 for aortic mean pressure; 54+/-13 mmHg and 43+/-8 mmHg, p<0.001 for aortic PP; 0.56+/-0.10 and 0.48+/-0.08, p<0.001 for aortic FPP). In addition, in linear regression analysis, a positive correlation was found between fasting plasma glucose and the aortic FPP (p = 0.001, R2 = 0.12). CONCLUSION: Ascending aorta PP and FPPs are significantly associated with the presence of IFG. These findings suggest that IFG is associated with endothelial dysfunction and so aortic stiffness.     

Differences in the risk of fatty liver for onset of impaired fasting glucose according to baseline plasma glucose levels

Journal of Gastroenterology - It remains unclear whether fatty liver is a risk factor for the onset of abnormal glucose tolerance in any patient. The objective of this study was to clarify the...     

Relationship between response of gamma-glutamyltransferase to alcohol consumption and levels of fasting plasma glucose

To examine whether the response of fasting plasma glucose (FPG) to alcohol consumption differs among individuals, a cross-sectional study was conducted in 6100 men with a body-mass index below 24 who did not take medication for diabetes. Information regarding current medication and lifestyle habits was obtained by a self-reported questionnaire. The subjects were divided into four groups according to their level of alcohol consumption: non-drinkers, light drinkers (1–188 ml/week), intermediate drinkers (189–377 ml/week), and heavy drinkers (378 ml/week). The frequency of subjects with an FPG of 110 mg/dl or more rose significantly as alcohol consumption increased, from 6.7% in non-drinkers to 10.1% in intermediate drinkers and 12.1% in heavy drinkers. In contrast, when only the subjects with a γ-glutamyltransferase level of less than 40 IU/L were analyzed, no difference was observed in the frequency of subjects with an FPG level of 110 mg/dl or more among the four groups. Multiple logistic regression analysis also revealed similar results. The findings suggested individual variability in the response of FPG to drinking. Appropriate levels of drinking could be different among individuals.     

Postprandial plasma glucose: a good index of glycemic control in type 2 diabetic patients having near-normal fasting glucose levels

To investigate the effect of postprandial plasma glucose (PG) concentrations on HbA1c levels in type 2 diabetic patients, we evaluated the relationship between HbA1c levels and postprandial PG concentrations after a meal tolerance test in 35 type 2 diabetic patients who had fasting PG concentrations persistently < 7.8 mmol/l and stable HbA1c levels. Two-hour postprandial PG concentrations were found to be more strongly correlated (r = 0.51) with HbA1c levels than 1-h postprandial PG (r = 0.35) and fasting PG (r = 0.46) concentrations. Patients whose HbA1c levels were high (HbA1c > or = 7%) had significantly higher 2-h postprandial PG concentrations and areas under the glucose curve than those whose HbA1c levels were lower (8.12+/-1.10 (SD) vs 6.70+/-2.22 mmol l(-1), P = 0.004 and 17.43+/-1.92 vs 15.58+/-3.26 mmol h(-1) l(-1), P = 0.02, respectively). Although fasting PG concentrations of patients with higher HbA1c levels were slightly higher, they did not differ significantly from those with lower HbA1c levels (6.21+/-0.89 vs 5.73+/-0.68 mmol l(-1)). Age, duration of diabetes, body mass index, serum C-peptide, both fasting and postprandial, did not differ between these two groups. This study suggests that postprandial hyperglycemia, particularly 2-h postprandial PG concentrations, is associated with high HbA1c levels in type 2 diabetic patients whose fasting PG levels were within normal or near-normal levels.     

ADIPOR2 variant is associated with higher fasting glucose level in non-diabetic Chinese Han population

A high but normal fasting plasma glucose level in adults is a marker for insulin resistance and future development of type 2 diabetes mellitus. We aimed to investigate whether ADIPOR2 variants are associated with increased fasting plasma glucose (FPG) in non-diabetic Chinese Han subjects who had normal FPG levels. This study included 2038 subjects among the non-diabetic Chinese Han population. The ADIPOR2 polymorphisms were genotyped by the TaqMan method. For the analysis, participants were divided into low-normal FPG group (FPG?<?4.88 mmol/L) and high-normal FPG group (6.1 mmol/L?>?FPG?≥?4.88 mmol/L). We identified five single nucleotide polymorphisms (SNPs) of ADIPOR2 gene: rs10773989, rs2370055, rs9300298, rs10773983, and rs13611594. There was no significant difference in FPG levels between different genotypes of rs10773989, rs2370055, rs9300298, and rs13611594. Our data showed a significant association of rs10773983 with higher FPG levels, fasting insulin levels, and homeostatic model assessment of insulin resistance (HOMA-IR) in A-allele carriers (p =?0.006, p <?0.001, and p <?0.001, respectively). The subjects in high FPG group had higher median fasting insulin level (9.25 vs 8.16 μIU/mL, p =?0.003) and higher HOMA-IR (2.21 vs 1.58, p <?0.001) than those in normal FPG group. Subjects with the A-allele of rs10773983 compared to subjects with G-allele had 1.222-fold higher risk for high-normal FPG (OR?=?1.222, 95%CI?=?1.010–1.478, p =?0.039). Our findings suggest that ADIPOR2 rs10773983 polymorphism may be associated with an increased risk of high-normal FPG among non-diabetic Chinese Han subjects who have normal FPG levels.