Reduction of postchallenge hyperglycaemia prevents acute endothelial dysfunction in subjects with impaired glucose tolerance

OBJECTIVES: To investigate whether selective reduction of postchallenge hyperglycaemia influences acute endothelial dysfunction, a very early manifestation of vascular disease, in patients with impaired glucose tolerance. METHODS: In a randomized, double-blind, placebo-controlled, cross-over study the acute effect of 200-mg acarbose was investigated in 28 subjects with diagnosed impaired glucose tolerance. Flow-mediated dilation (FMD) of the brachial artery was determined as a measure of endothelial function before and 2 and 3 h after ingestion of 100-g saccharose. Asymmetrical dimethylarginine (ADMA) was measured by high-performance liquid chromatography. RESULTS: A negative correlation was observed between the changes of glucose and FMD (r = 0.416, P = 0.0018) 2 h after ingestion of saccharose. At 3 h, neither blood glucose nor FMD were different from baseline. Changes of both blood glucose (P = 0.0007) and FMD (P = 0.046) were significantly lower after administration of acarbose. Subgroup analysis revealed that the effect of acarbose was restricted to those subjects with an increase of blood glucose above the median increase of glycaemia. No changes of plasma ADMA were observed. CONCLUSIONS: Our data clearly demonstrate that the postchallenge alteration of vascular function in patients with impaired glucose tolerance is caused by the acute elevation of glycaemia but not mediated by ADMA.     

Risk factors for development of pre-diabetic state from normal glucose regulation

As a strategy to prevent the progression of diabetes mellitus, it is important to screen out the subjects who will develop a pre-diabetic state (PDS) in the future. To find out the potential risk factors for PDS, we employed the values of fasting plasma glucose and hemoglobin A1c (HbA1c), which are routinely measured in our health checkup. We selected 3,879 individuals who had normal glucose regulation at both fasting plasma glucose < 6.1 mmol/l and HbA1c < 5.5% in 1997 and investigated whether they would develop PDS in the next 5 years. PDS is defined at fasting plasma glucose >or= 6.1 mmol/l and HbA1c >or= 5.5%. Among 3,879 individuals, 21 developed PDS and 2,128 maintained normal glucose regulation in 2001. The remaining 1,730 subjects fit one of the two criteria for PDS. The parameters measured in 1997, including fasting plasma glucose, HbA1c, triglyceride, alanine aminotransferase, gamma-glutamyltranspeptidas, cholinesterase, uric acid, red blood cells, hemoglobin, percent body fat and diastolic blood pressure, were significantly higher in the individuals who developed PDS than in those who maintained normal glucose regulation. On the other hand, hematocrit was significantly lower in PDS than in normal glucose regulation. Logistic regression analysis identified alanine aminotransferase >or= 40 U/l, triglyceride >or= 1.69 mmol/l, low-density lipoprotein cholesterol >or= 3.62 mmol/l and hematocrit < 38% as valuable factors for predicting the development of PDS. The present study demonstrates that the subjects with high risks for PDS could be identified from several clinical parameters and that they should be encouraged to improve their living habits not to develop diabetes mellitus.     

Abnormal glucose tolerance and increased risk for cardiovascular disease in Japanese-Americans with normal fasting glucose

OBJECTIVE: To compare the American Diabetes Association (ADA) fasting glucose and the World Health Organization (WHO) oral glucose tolerance test (OGTT) criteria for diagnosing diabetes and detecting people at increased risk for cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS: Study subjects were 596 Japanese-Americans. Fasting insulin, lipids, and C-peptide levels; systolic and diastolic blood pressures (BPs); BMI (kg/m2); and total and intra-abdominal body fat distribution by computed tomography (CT) were measured. Study subjects were categorized by ADA criteria as having normal fasting glucose (NFG), impaired fasting glucose (IFG), and diabetic fasting glucose and by WHO criteria for a 75-g OGTT as having normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and diabetic glucose tolerance (DGT). RESULTS: Of 503 patients with NFG, 176 had IGT and 20 had DGT These patients had worse CVD risk factors than those with NGT . The mean values for NGT, IGT, and DGT, respectively, and analysis of covariance P values, adjusted for age and sex, are as follows; intra-abdominal fat area by CT 69.7, 95.0, and 101.1 cm2 (P < 0.0001); total CT fat area 437.7, 523.3, and 489.8 cm2 (P < 0.0001); fasting triglycerides 1.40, 1.77, and 1.74 mmol/l (P = 0.002); fasting HDL cholesterol 1.56, 1.50, and 1.49 mmol/l (P = 0.02); C-peptide 0.80, 0.90, 0.95 nmol/l (P = 0.002); systolic BP 124.9, 132.4, and 136.9 mmHg (P = 0.0035); diastolic BP 74.8, 77.7, and 78.2 mmHg (P = 0.01). CONCLUSIONS: NFG patients who had IGT or DGT had more intra-abdominal fat and total adiposity; higher insulin, C-peptide, and triglyceride levels; lower HDL cholesterol levels; and higher BPs than those with NGT. Classification by fasting glucose misses many Japanese-Americans with abnormal glucose tolerance and less favorable cardiovascular risk profiles.     

Diabetic nephropathy and proliferative retinopathy with normal glucose tolerance

A 61-yr-old man presented with the nephrotic syndrome and normal oral glucose tolerance. Renal biopsy showed the nodular (Kimmelstiel-Wilson) and diffuse glomerulosclerosis lesions characteristic of diabetes. Direct ophthalmoscopy and fluorescein angiography demonstrated a picture of advanced proliferative diabetic retinopathy. The patient had no history of diabetes mellitus and upon testing had normal glucose values in response to an oral glucose tolerance test. Insulin response to an intravenous glucose tolerance test was abnormally low. It is concluded that the nodular glomerulosclerosis lesions and proliferative retinopathy, thought to be specific for diabetes mellitus, may present in the absence of either overt clinical diabetes or impaired glucose tolerance.     

Determinants for the progression from impaired glucose tolerance to non-insulin-dependent diabetes mellitus

The World Health Organization distinguishes among non-diabetic persons a form of glucose intolerance defined as impaired glucose tolerance (IGT). The main reason for considering IGT as a diagnostic entity is its prognostic value for the development of non-insulin-dependent diabetes mellitus (NIDDM). However, the use of one or two oral glucose tolerance tests (OGTT) for the definition of IGT and the large variability of the 2-h glucose level may explain the wide range of the incidence rates reported for NIDDM in subjects with IGT. It is evident that the pathogenesis of diabetes is still poorly understood. Both insulin resistance and impaired function of the β-cell are thought to be important contributing factors in the development of diabetes. The 2-h post-load glucose level from the OGTT is most powerful for the prediction of the development of NIDDM. In addition, a fasting hyperinsulinaemia and a low glucose removal rate, both reflecting insulin resistance, were found to be associated with a higher risk for the progression of NIDDM. In the San Antonio Study and in the Hoorn Study high fasting proinsulin levels, reflecting β-cell dysfunction, were associated with progression to NIDDM. Lipid levels did not predict progression to NIDDM in most studies. A two-step model for the development of NIDDM is hypothesized. The first step, the transition from normal to impaired glucose tolerance, is assumed to depend mainly on the presence of insulin resistance. The second step, progressing from IGT to diabetes, although accompanied by some further worsening of insulin resistance, is thought to be primarily dependent on the development of β-cell dysfunction.     

580例正常糖耐量人群糖化血红蛋白的检测与分析

目的 确定我院生物化学实验室糖化血红蛋白（glycatedhemoglobin,GHb）的参考范围,研究正常糖耐量人群糖化血红蛋白水平与年龄和性别的关系。方法根据要求从2012年1月3日-2012年月9月30日,前来我院就诊或体检者中筛选出符合条件的正常糖耐量人群580人的HbAlc检测值,并记录受捡者的年龄,性别等基本信息。采用正态分布法双侧95％可信区间确定参考范围,并分析糖化血红蛋白与性别、年龄的关系。结果580例正常糖耐量者测得HbAlc参考范围3．93％～5。97％。其中男性糖化血红蛋白平均值为4．92％,女性为4,98％,两者差异没有统计学意义（t=-1．49,P〉0．05）。不同年龄组糖化血红蛋白平均值分别为：儿童组4．42％,少年组4．65％,青年组5．11％,中年组5．07％,老年组5．12％。老年组与中年组、青年组,中年组和青年组的差异没有统计学意义,其他各组之间的差异均有显著统计学意义（P〈0．01）。结论我院生物化学实验室糖化血红蛋白参考范围3．93％～5．97％。糖化血红蛋白水平与性别无关,但随年龄有一定增加,建议实验室设置不同年龄组的参考范围。     

Effect of guar on second-meal glucose tolerance in normal man

Whole body glucose turnover and absorption of a 50 g glucose drink was studied in six healthy volunteers on two occasions, 4 h after a 'breakfast' of 50 g of glucose, mixed on one occasion with 20 g of guar gum. Plasma glucose concentrations were significantly reduced with guar gum compared with those obtained without guar gum (P less than 0.0001). Whole body glucose turnover studied by an intravenous primed dose constant infusion technique using D-[3-3H]glucose showed no significant difference between the two groups: 353 +/- 15 mmol with guar and 350 +/- 9 mmol without guar. Total oral glucose absorption, followed with a D-[1-14C]glucose tracer, was significantly decreased by guar treatment, being 219 +/- 3 mmol with guar and 239 +/- 5 mmol without guar (P less than 0.05). Serum insulin levels were lowered by guar treatment (P less than 0.05) while those of C-peptide, gastric inhibitory polypeptide, glucagon, cortisol and pancreatic polypeptide did not differ significantly. Blood lactate concentrations were raised in the guar treated group (P less than 0.05) whereas pyruvate, alanine, glycerol and 3-hydroxybutyrate concentrations did not differ significantly. These results support the suggestion that guar improves second-meal tolerance to glucose by decreasing absorption.     

Significance of high HbA1 levels in normal glucose tolerance

The significance of high hemoglobin A1 (HbA1) levels (greater than or equal to 8.0%) found in 12.1% of 648 individuals with normal glucose tolerance constituting a part of a representative population sample was examined. Measurement error in HbA1 and/or glucose-tolerance levels was precluded by HbA1 remaining in the same range over 3.5 yr in 89.7% of 29 individuals with initially high and 68.1% of 22 individuals with initially low (less than 6.5%) HbA1. Rate of deterioration to glucose intolerance (6.9%) in the high group during that period resembled the rate (11.8%) in a control group (n = 279). Fasting plasma glucose significantly accounted for only 2.4% of total HbA1-population variance. No correlation of HbA1 was found with other correlates of glucose tolerance or with daily caloric intake and physical activity. A small but significant increment in HbA1 was associated with smoking (7.1 vs. 6.8%, P less than .01) and with clinically overt atherosclerosis (7.3 vs. 6.9%, P less than .01). We conclude that factors unrelated to glucose metabolism are the main determinants of HbA1 level in normal glucose tolerance and play an important role in diabetes as well. These factors have bearing on evaluation of diabetic control by HbA1 and possibly on risk for diabetic complications.     

Lifestyle intervention in individuals with normal versus impaired glucose tolerance

BACKGROUND: Lifestyle intervention is effective in the prevention of type 2 diabetes in individuals with impaired glucose tolerance (IGT). It is currently unknown whether it has beneficial effects on metabolism to a similar extent, in individuals with normal glucose tolerance (NGT) compared to individuals with IGT. MATERIALS AND METHODS: Data from 181 subjects (133 with NGT and at risk for type 2 diabetes and 48 with IGT) who participated in the Tuebingen Lifestyle Intervention Program with increase in physical activity and decrease in caloric intake were included into this study. Body fat distribution was quantified by whole-body magnetic resonance (MR) tomography and liver fat and intramyocellular fat by (1)H-MR spectroscopy. Insulin sensitivity was estimated from an oral glucose tolerance test (OGTT). RESULTS: After 9 +/- 2 months of follow-up, the diagnosis of IGT was reversed in 24 out of 48 individuals. Only 14 out of 133 participants with NGT developed IGT. Body weight decreased in both groups by 3% (both P < 0.0001). Two-hour glucose concentrations during an OGTT decreased in individuals with IGT (-14%, P < 0.0001) but not with NGT (+2%, P = 0.66). Insulin sensitivity increased both in individuals with IGT (+9%, P = 0.04) and NGT (+17%, P < 0.0001). Visceral fat (-8%, P = 0.006), liver fat (-28%, P < 0.0001) and intramyocellular fat (-15%, P = 0.006) decreased in participants with IGT. In participants with NGT these changes were significant for visceral fat (-16%, P < 0.0001) and liver fat (-35%, P < 0.0001). CONCLUSIONS: Moderate weight loss under a lifestyle intervention with reduction in total, visceral and ectopic fat and increase in insulin sensitivity improves glucose tolerance in individuals with IGT but not with NGT. In individuals with NGT, the beneficial effects of a lifestyle intervention on fat distribution and insulin sensitivity possibly prevent future deterioration in glucose tolerance.     

Visual impairment and retinopathy in people with normal glucose tolerance, impaired glucose tolerance, and newly diagnosed NIDDM.

OBJECTIVE: Prevalence rates of visual impairment and retinopathy were compared in 1992 people with normal glucose tolerance, impaired glucose tolerance (IGT), or newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: Glucose tolerance status was based on an oral glucose tolerance test after exclusion of those with a history of diabetes and/or diabetes medication use in an upper middle-class community of older white adults in southern California between 1984 and 1987. RESULTS: Although many sex-specific comparisons were made between glucose tolerance groups, only a few emerged as statistically significant. Among those, women with IGT had significantly higher age-adjusted rates of visual impairment (10.8%) than women with normal glucose tolerance (4.4%). Among men, those with IGT had significantly higher age-adjusted rates of visual impairment (7.9%) than men with newly diagnosed NIDDM (4.0%). CONCLUSIONS: Low frequencies of retinopathy were found in all three glucose tolerance groups.     

Plasma glucose within the normal range is not associated with carotid atherosclerosis: prospective results in subjects with normal glucose tolerance from the Bruneck Study.

OBJECTIVE: There is substantial evidence that glucose intolerance is associated with an increased risk of cardiovascular disease. However, it is not well established whether plasma glucose is independently related to atherosclerosis when glucose tolerance is normal and, if so, to which stage of the complex atherosclerotic process. RESEARCH DESIGN AND METHODS: We prospectively examined the status of carotid arteries in 625 subjects aged 40-79 years who were randomly selected from the general population and had normal glucose tolerance (according to World Health Organization criteria) both at baseline and at 5 years of follow-up. All subjects had high-resolution echo-duplex evaluation of the common and internal carotid arteries (eight regions of interest on both sides) in 1990 and 1995 to detect the change in carotid status over time. The occurrence of new plaques in previously normal segments was termed "incident nonstenotic" or "early atherosclerosis," and the occurrence of stenosis in >40% of previously normal segments was termed "incident stenotic" or "advanced atherosclerosis." In addition, we evaluated the changes in the atherosclerosis score (the sum of all plaques) during the follow-up, and we measured intimal-medial thickening (IMT) in the common carotid artery in 1995. In all subjects, several candidate risk factors were assessed: sex, age, BMI, waist-to-hip ratio, glucose, HbA1c, insulin, urate, lipids, apolipoproteins A1 and B, blood pressure, lipoprotein(a), fibrinogen, antithrombin III, factor V Leiden mutation, ferritin, leukocyte count, smoking, alcohol intake, physical activity, and socioeconomic status. Fasting plasma glucose (FPG), plasma glucose 2 hr after the glucose load (2-h PG), and HbA1c concentrations in 1990 and 1995 were averaged in each subject to obtain an estimate of long-term glucose exposure of the arterial wall. RESULTS: Linear or logistical regression analyses indicated that neither baseline glucose and HbA1c levels nor mean FPG, mean 2-h PG, or mean HbA1c in 1990 and 1995 were independently related to IMT, a 5-year change in the atherosclerotic score, incident nonstenotic (early) atherosclerosis, or incident stenotic (advanced) atherosclerosis. Likewise, subjects with FPG levels above the median and subjects in the new category of "impaired fasting glucose" did not have an increased occurrence or progression of atherosclerosis. All results were consistent before and after adjustment for other vascular risk factors and possible confounders. CONCLUSIONS: These results suggest that plasma glucose levels within the normal range (<7.8 mg/dl both at FPG and 2-h PG) are not independently related to any stage of atherosclerosis.     

不同年龄段的正常糖耐量人群血糖值及其相关因素分析

目的 分析不同年龄段正常糖耐量(NGT)者血糖水平及相互关系.方法 选择上海市杨浦区部分街道流行病学调研2098例30岁以上居民,根据糖耐量(OGTT)检测中空腹血糖值(FPG)和2 h血糖值(2 hPG),诊断为NGT、糖耐量低减(IGT)、空腹血糖受损(IFG)、IGT合并IFG(IGT/IFG)、糖尿病(DM),将NGT者按年龄分成5组,观察各年龄组的血糖水平,用稳态模式分析胰岛β细胞功能指数(HBCI),并对其进行统计学分析.结果 在NGT中60～69年龄组FPG值(5.17±0.48)mmol/L、糖化血红蛋白(HbA1c)(6.01±0.62)%较50～59年龄组FPG值(5.09±0.44)mmol/L、HbA1c值(5.95±0.66)%高(t值分别为2.06、2.48,P均<0.05).60～69年龄组FIG值较40～49年龄组FPG值(5.01±0.47)mmol/L高(t=2.26,P<0.01),50～59年龄组FPG值较40～49年龄组高(t=2.48,P<0.01),5组按年龄从小至大比较,空腹胰岛素(FINS)值变化无明显规律;60岁以上HBCI较60岁以下的HBCI值下降,差异有统计学意义(F值为33.75,P<0.01).结论 NGT人群随着年龄的增长,FPG、HbAlc可能增高.

Abstract：

Objective To compare the glucose levels and associated factors among the normal glucose tolerance subjects with different age.Methods Totally a community-based population of 2098 residences aged above 30 years Were tested with OGTT,and classified into normal glucose tolerance group(NGT),impaired glucose tolerance group(IGT),impaired fasting glucose group(IFG),both IGT and IFG group(ICT/IFC),anddiabetes group(DM) according to fasting and 2 hours glucose level(2 hPG).The subjects in NGT group were further divided into 5 groups according to different ages.The levels of blood glucose and HBCI in different groups and subgroups were measured and analyzed statistically. Results For patients in NGT,the FPG([5.17.±0.48]mmol/L vs.[5.09±0.44]mmol/L,P<0.05)and HbA1c([6.01±0.62]%vs.[5.95±0.66]%.P<0.05)in group aged 60-69 Were higher than that in group aged 50-59.The FPG in group aged 60-69 was also higher than those in group aged 40-49([5.17±0.48]mmol/L vs.[5.00±0.47]mmol/L,P<0.01),and the FPG in group aged 50-59 Was also higher than those in group aged 40-49([5.09±0.44]mmol/L vs..[5.00±0.47]mmol/L,P<0.01).There was no correlation between age and FINS,while a tendency of decreasing HBCI could be observed along with increasing of age(F=33.75,P<0.05).Conclusion In NGT subjects,the FPG and HbA1 C inereased along with age.     

The relationship between homeostasis model assessment and cardiovascular risk factors in Iranian subjects with normal fasting glucose and normal glucose tolerance

BACKGROUND: Insulin resistance is a complex problem which may not always correlate with all its cardiovascular risk factors in various populations. We investigated the relationship between homeostasis model assessment of insulin resistance (HOMA-IR) with cardiovascular risk factors in Iranian subjects with normal fasting glucose (NFG) and normal glucose tolerance (NGT). METHODS: Of the 605 subjects aged 25-79 y enrolled in this study, after the oral glucose tolerance test, 366 subjects aged 25-50 y and 135 aged >50 y were classified as NFG and NGT. Insulin resistance was estimated by the HOMA-IR. RESULTS: Women had higher values of body mass index (BMI), insulin and HOMA-IR than men in both age groups. The prevalence of insulin resistance, general and abdominal obesity, low HDL-C and physical inactivity was higher in women than men in the 2 age groups. Men had a higher prevalence of hypertension and hypertriglyceridemia in the group with age 25-50 y. The Pearson correlation controlled for age, BMI, waist circumference and physical activity showed that HOMA-IR had significant correlation with triglyceride and inversely associated with HDL-C in both sexes. In addition, the results of HOMA-IR quartiles demonstrated that the prevalence of hypertension, obesity, and low HDL-C was particular high in women with HOMA-IR >2.39. Multiple regression indicated that log HOMA-IR was independently predicted by BMI, triglyceride and HDL-C in men and BMI, HDL-C and waist-to-hip (WHR) ratio in women. CONCLUSIONS: HOMA-IR is associated with the features of metabolic syndrome with a sex difference in the degree and predictors of HOMA-IR and the frequency of cardiovascular risk factors.     

糖耐量正常人群HbA1c分布特点及相关因素分析

目的分析糖化血红蛋白(Hb A1c)在糖耐量正常(NGT)人群中的分布特点及相关因素。方法选择北京市首钢四个社区糖尿病普查人群的资料,所有参加者进行人体学测量、75 g葡萄糖耐量试验(OGTT),同时检测Hb A1c、空腹血糖(FPG)、OGTT后2 h血糖值(2 h PG)及血生化。将9 711名符合入选标准的NGT人群的结果纳入分析,比较Hb A1c在不同性别及年龄组间(青年组、中年组、老年组及老老年组)的差异;根据Hb A1c水平分为≤5.6%、5.7%~6.4%和≥6.5%三组,比较三组的临床特点;采用Logistic回归方法分析与Hb A1c相关的因素。结果 (1)Hb A1c在NGT人群呈正态分布,平均(5.69±0.44)%,95%CI为4.83%~6.55%;男性与女性之间Hb A1c的水平有差异(P<0.05),尤其在老年组(60~79岁)差异显著(P<0.01)。(2)Hb A1c随着年龄的增加逐渐升高,Hb A1c、FPG及2 h PG在青年组(16~44岁)与中年组(45~59岁)间均有统计学差异(P<0.01);Hb A1c、FPG在青年组、中年组都与老年组(60~79岁)和老老年组(≥80岁)间有统计学差异(P<0.01),而2 h PG与老老年组无统计学差异;老年组和老老年组无统计学差异。(3)Hb A1c≤5.6%与Hb A1c 5.7%~6.4%和≥6.5%组之间在年龄、体质量指数(BMI)、腰臀比(WHR)、收缩压(SBP)、血胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)水平、FPG和2 h PG均有统计学差异(P<0.01或P<0.05);而Hb A1c 5.7%~6.4%与≥6.5%组之间比较差异均无统计学意义。(4)Logistic回归分析显示Hb A1c与性别、年龄、BMI、WHR、SBP、TC、FPG呈正相关,与DBP、HDL-C呈负相关。结论 NGT人群的Hb A1c随年龄的增长而升高,并与FPG呈正相关;处于高危Hb A1c范围的非糖尿病人群应加强对FPG、2 h PG和心血管危险因素的监测。