Differences in cardiovascular risk factors, insulin resistance, and insulin secretion in individuals with normal glucose tolerance and in subjects with impaired glucose regulation: the Telde Study

OBJECTIVE: To assess the cardiovascular risk profile, the degree of insulin resistance, and beta-cell secretion in a cohort of subjects with different categories of impaired glucose regulation (IGR): impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and combined IFG/IGT. RESEARCH DESIGN AND METHODS: We studied 902 nondiabetic subjects between 30 and 80 years of age, recruited from a cross-sectional population-based study in Telde, Gran Canaria Island, Spain. Categories of glucose tolerance were defined according to 2003 modified American Diabetes Association criteria. Risk factors for cardiovascular disease, the presence of the metabolic syndrome, and indirect measures of both insulin resistance and beta-cell function were analyzed. RESULTS: A total of 132 (14.6%) participants had isolated IFG, 59 (6.5%) isolated IGT, and 48 (5.3%) combined IFG/IGT. Groups with normal glucose tolerance (NGT) and combined IFG/IGT had, respectively, the most favorable and unfavorable levels of cardiovascular risk factors, metabolic syndrome rates, and measures of insulin resistance. Subjects with IFG and IGT showed an intermediate profile between NGT and IFG/IGT categories. We found no significant differences between IFG and IGT in cardiovascular risk factors, metabolic syndrome prevalence, or insulin resistance. The IFG group exhibited a more impaired insulin secretion than those with IGT or IFG/IGT. CONCLUSIONS: Individuals with IGR, especially those with IFG/IGT, have increased values of cardiovascular risk factors and higher indexes of insulin resistance. Groups with isolated IFG and isolated IGT present similar cardiovascular risk profiles. Subjects with IFG are characterized by more defective beta-cell function than other forms of IGR.     

Impaired glucose tolerance is a risk factor for cardiovascular disease, but not impaired fasting glucose. The Funagata Diabetes Study.

OBJECTIVE: To determine whether the new category of impaired fasting glucose (IFG) recently proposed by the Expert Committee of the American Diabetes Association is a risk factor for cardiovascular disease. RESEARCH DESIGN AND METHODS: Death certificates and residence transfer documents from the cohort population consisting of participants of the diabetes prevalence study in Funagata, Yamagata prefecture, Japan, 1990-1992, were analyzed up through the end of 1996. First, the cohort population was classified into three groups: normal glucose tolerance (NGT) (n = 2,016), impaired glucose tolerance (IGT) (n = 382), and diabetic (n = 253). Then the same population was reclassified into normal fasting glucose (NFG), IFG, and diabetic. The cumulative survival rates among the groups were compared using the classical life-table method, and age-adjusted analyses, the person-year method, and Cox's proportional hazard model were adopted. RESULTS: At the end of seven observed years, the cumulative survival rates from cardiovascular disease of IGT and diabetes were 0.962 and 0.954, respectively, both significantly lower than that of NGT (0.988). The Cox's proportional hazard model analysis showed that the hazard ratio of IGT to NGT on death from cardiovascular disease was 2.219 (95% CI 1.076-4.577). However, the cumulative survival rate of IFG from cardiovascular disease was 0.977, not significantly lower than that of NFG (0.985). The Cox's hazard ratio of IFG to NFG on death from cardiovascular disease was 1.136 (0.345-3.734), which was not significant either. CONCLUSIONS: IGT was a risk factor for cardiovascular disease, but IFG was not.     

Elevated white blood cell count in subjects with impaired glucose tolerance

OBJECTIVE: Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) differ in their risk of all-cause and cardiovascular mortality, but previous cross-sectional studies have suggested little difference in their levels of lipids or blood pressure. We compared the white blood cell (WBC) count between subjects with IFG and IGT. RESEARCH DESIGN AND METHODS: The subjects were 4,720 nondiabetic Japanese men aged 24-84 years. Based on the 75-g oral glucose tolerance test, the subjects were classified into the following four groups: normal fasting glucose/normal glucose tolerance (n = 3,753), isolated IFG (n = 290), isolated IGT (n = 476), and IFG/IGT (n = 201). We compared the WBC count among the four groups and investigated variables that showed a significant association with the WBC count. RESULTS: The isolated IGT group had a significantly higher WBC count than the isolated IFG group (6,530 vs. 6,210/mm(3), P < 0.05). By stepwise analyses, age, triglycerides, HDL cholesterol, fasting insulin, and 2-h postchallenge plasma glucose (PG) showed an independent association with the WBC count (adjusted R(2) = 0.057). In the analysis stratified by smoking status, the WBC count was independently associated with 2-h PG and triglycerides, irrespective of smoking status. CONCLUSIONS: Individuals with isolated IGT had a significantly higher WBC count than those with isolated IFG. The WBC count was associated with 2-h PG and various components of the metabolic syndrome.     

综合干预对老年人糖代谢异常进程的影响

目的分析在综合干预状态下,老年糖耐量正常者(NGT)进展为糖调节异常者(IGR),以及IGR进展为糖尿病(DM)的情况。方法于2002年对军队老年离退休干部心血管疾病危险因素进行了4年综合干预,对其中549例NGT、110例IGR定期随访4年。结果综合干预结束时,研究人群的血压、血脂、体质量指数(BMI)均有显著性下降(P<0.01)。NGT进展为IGR的比率为30.97%,其中6.74%进展为空腹血糖受损(IFG),16.39%进展为糖耐量异常(IGT),7.83%进展为空腹血糖受损合并糖耐量异常(IFG/IGT),由NGT进展为IGT的比率明显高于IFG(P<0.01);IFG检出率增加了1.11倍,进展为IFG1的比率(4.55%)明显高于IFG2(2.19%)(P<0.05)。110例IGR人群中,19.61%的IGT进展为DM,16.28%的IFG进展为DM,IGT与IFG进展为糖尿病的比例差异无统计学意义(P>0.05)。8.70%的IFG1进展为DM,25.00%的IFG2进展为DM(P>0.05);43.75%的IFG/IGT进展为DM,进展率明显高于IFG、IGT(P<0.05)。基线时IGR累计进展为DM的比率是21.82%。结论老年人进展为IGT的比率明显高于IFG,IFG/IGT进展为DM的比率明显高于单独的IFG或IGT。     

Coronary artery calcification in type 2 diabetes and insulin resistance: the framingham offspring study

OBJECTIVE: To assess risk for subclinical coronary atherosclerosis using electron beam- computed tomography in subjects with or without insulin resistance and with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT/impaired fasting glucose [IFG]) or type 2 diabetes. RESEARCH DESIGN AND METHODS: We categorized glucose tolerance by type 2 diabetes therapy (diagnosed diabetes) or with an oral glucose tolerance test (OGTT) (IFG, IGT, and OGTT-detected diabetes) and insulin resistance as an elevated fasting insulin level, in subjects attending the fifth examination (1991-1995) of the Framingham Offspring Study. A representative subset of subjects without clinical atherosclerosis was selected for electron beam computed tomography in 1998-1999 from age- and sex-stratified quintiles of the Framingham risk score. The presence of subclinical atherosclerosis was defined as the upper quartile of the Agatston score distribution (score > 170). We assessed risk for subclinical atherosclerosis using multivariable logistic regression. RESULTS: Of 325 subjects aged 31-73 years, 51% were men, 11.2% had IFG/IGT, and 9.9% had diabetes (2.8% with diagnosed diabetes); 14.5% had insulin resistance. Compared with NGT, subjects with IFG/IGT tended to be more likely (adjusted odds ratio 1.5, 95% CI 0.7-3.4) and those with diabetes were significantly more likely (2.7, 1.2-6.1) to have subclinical coronary atherosclerosis. In age- and sex-adjusted models, subjects with insulin resistance were more likely to have subclinical atherosclerosis than those without insulin resistance (2.1, 1.01-4.2), but further risk factor adjustment weakened this association. In adjusted models including insulin resistance, diabetes remained associated with risk for subclinical atherosclerosis (2.8, 1.2-6.7); diagnosed diabetes (6.0, 1.4-25.2) had a larger effect than OGTT-detected diabetes (2.1, 0.8-5.5). CONCLUSIONS: Individuals with diabetes have an elevated burden of subclinical coronary atherosclerosis. Aggressive clinical atherosclerosis prevention is warranted, especially in diagnosed diabetes.     

老年人不同糖耐量状态胰岛素抵抗和胰岛β细胞功能的研究

目的观察老年人群中空腹血糖受损(IFG)、糖耐量受损(IGT)和糖调节受损(IFG/IGT)三种不同糖耐量状态下的胰岛素抵抗(IR)和胰岛β细胞功能的变化,了解其发病机制。方法筛选60~75岁的IFG40例,IGT60例,IGT/IFG40例,正常糖耐量(NGT)70例。HOMA-IR评价胰岛素抵抗,HBC I和I30/G30分别评价基础及糖负荷后早期胰岛β细胞功能。结果(1)HOMA-IR:IFG、IFG/IGT和IGT组明显高于NGT组,P<0.01,IFG/IGT组高于IFG和IGT组,P<0.01;(2)HBC I:IFG组和IFG/IGT组明显低于NGT和IGT组,P<0.01;(3)I30/G30:IGT组和IFG/IGT组明显低于NGT组及IFG组,P<0.01。结论老年人群IFG主要表现基础状态下β细胞功能受损伴有胰岛素抵抗,IGT主要表现为早期胰岛素分泌缺陷,IFG/IGT胰岛β细胞早期胰岛素分泌功能受损更明显,胰岛素抵抗更严重。     

Prevalence and risk factors of neuropathic pain in survivors of myocardial infarction with pre‐diabetes and diabetes. The KORA Myocardial Infarction Registry

The lowest glycemic threshold for and the risk factors associated with neuropathic pain have not been established. The aim of this study was to determine the prevalence and risk factors of neuropathic pain in survivors of myocardial infarction with diabetes, impaired glucose tolerance (IGT), impaired fasting glucose (IFG), normal glucose tolerance (NGT). Subjects aged 25–74 years with diabetes (n=214) and controls matched for age and sex (n=212) from the population‐based KORA (Cooperative Health Research in the Region of Augsburg) Myocardial Infarction Registry were assessed for neuropathic pain by the Michigan Neuropathy Screening Instrument using its pain‐relevant questions and an examination score cutpoint >2. An oral glucose tolerance test was performed in the controls. Among the controls, 61 (28.8%) had IGT (either isolated or combined with IFG), 70 (33.0%) had isolated IFG, and 81 had NGT. The prevalence of neuropathic pain was 21.0% in the diabetic subjects, 14.8% in those with IGT, 5.7% in those with IFG, and 3.7% in those with NGT (overall p<0.001). In the entire population studied (n=426), age, waist circumference, peripheral arterial disease (PAD), and diabetes were independent factors significantly associated with neuropathic pain, while in the diabetic group it was waist circumference, physical activity, and PAD (all p<0.05). In conclusion, the prevalence of neuropathic pain is relatively high among survivors of myocardial infarction with diabetes and IGT compared to those with isolated IFG and NGT. Associated cardiovascular risk factors including abdominal obesity and low physical activity may constitute targets to prevent neuropathic pain in this population.     

C-reactive protein predicts the deterioration of glycemia in chinese subjects with impaired glucose tolerance

OBJECTIVE: Recent studies have shown that C-reactive protein (CRP) predicts future risk of diabetes in healthy Caucasians. We determined whether plasma CRP level was elevated in Chinese subjects with impaired glucose tolerance (IGT) and whether CRP level could be used to predict progression to type 2 diabetes or reversion to normal glucose tolerance (NGT) in these high-risk individuals. RESEARCH DESIGN AND METHODS: A total of 228 subjects with IGT at baseline from the Hong Kong Cardiovascular Risk Factors Prevalence Study underwent repeat oral glucose tolerance testing after 2 years. Plasma high-sensitivity CRP was measured from their stored baseline samples and from 228 subjects with NGT matched for age and BMI by an immunoturbidimetric assay. RESULTS: Subjects with IGT at baseline had higher plasma CRP levels than subjects with NGT: 1.18 mg/l (0.52-2.52) vs. 0.87 mg/l (0.37-1.84), median (interquartile range), P = 0.01. At 2 years, 117 subjects with IGT reverted to NGT, 84 remained in IGT, and 21 progressed to diabetes. Individuals who progressed to diabetes had the highest plasma CRP levels at baseline (P < 0.0001). Those with baseline CRP levels in the third and top quartile had a relative risk of remaining in IGT or progressing to diabetes of 2.87 (95% CI 1.06-7.82) and 2.76 (1.06-7.31), respectively, after adjusting for anthropometric measure and lifestyle factors. CONCLUSIONS: CRP independently predicts the risk of remaining in IGT or progressing to diabetes in Chinese subjects with IGT. CRP might provide an adjunctive measure for identifying subjects with the highest risk of progression to diabetes who would derive the greatest benefits from preventive interventions.     

上海社区代谢综合征患者膳食及糖尿病知信行调查

目的:调查上海社区代谢综合征患者的膳食状况以及其对糖尿病营养治疗相关的知识、态度和行为(knowledge,atti-tude and practice,KAP)状况。方法:2007年9～12月采用分层随机抽样法,抽取上海市曹杨社区所辖的20岁以上居民3 000人进行代谢综合征筛查,将筛查出的368例代谢综合征患者作为调查对象,由接受过专门培训的调查员以面对面访谈方式进行糖尿病营养治疗KAP问卷调查,同时采用连续3 d膳食回顾法进行膳食调查。结果:368例代谢综合征患者中,糖尿病患者109例(29.6%,糖尿病组)、糖耐量异常或糖调节受损者154例(41.8%,糖尿病前期组)、糖耐量正常者105例(28.5%,糖耐量正常组)。与糖耐量正常组比较,糖尿病组和糖尿病前期组碳水化合物摄入比例较高(P<0.05),蛋白质摄入比例较低(P<0.05);3组患者维生素和矿物质摄入均未达到推荐摄入量(recommended nutrient intakes,RNI)。糖尿病营养治疗KAP调查显示,糖尿病组KAP总分显著高于糖尿病前期组与糖耐量正常组(P<0.05)。结论:应该采取有效措施以提高社区人群对糖尿病饮食及营养治疗知识的知晓率。     

Cardiometabolic risk in impaired fasting glucose and impaired glucose tolerance: the Atherosclerosis Risk in Communities Study

OBJECTIVE: We compared and contrasted cardiovascular disease (CVD) risk factors, subclinical manifestations of CVD, incident coronary heart disease (CHD), and all-cause mortality by categories of impaired glucose regulation in nondiabetic individuals. RESEARCH DESIGN AND METHODS: The study included 6,888 participants aged 52-75 years who had no history of diabetes or CVD. All-cause mortality and incident CHD were ascertained over a median of 6.3 years of follow-up. RESULTS: Agreement between fasting and postchallenge glucose impairment was poor: 3,048 subjects (44%) had neither impaired fasting glucose (IFG) nor impaired glucose tolerance (IGT), 1,690 (25%) had isolated IFG, 1,000 (14%) had isolated IGT, and 1,149 (17%) had both IFG and IGT. After adjustment for age, sex, race, and center, subjects with isolated IFG were more likely to smoke, consume alcohol, and had higher mean BMI, waist circumference, LDL cholesterol, and fasting insulin and lower HDL cholesterol than those with isolated IGT, while subjects with isolated IGT had higher mean triglycerides, systolic blood pressure, and white cell counts. Measures of subclinical CVD and rates of all-cause mortality and incident CHD were similar in isolated IFG and isolated IGT. CONCLUSIONS: Neither isolated IFG nor isolated IGT was associated with a more adverse CVD risk profile.     

From Pre-Diabetes to Type 2 Diabetes in Obese Youth: Pathophysiological characteristics along the spectrum of glucose dysregulation

OBJECTIVE

Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) are considered pre-diabetes states. There are limited data in pediatrics in regard to their pathophysiology. We investigated differences in insulin sensitivity and secretion among youth with IFG, IGT, and coexistent IFG/IGT compared with those with normal glucose tolerance (NGT) and type 2 diabetes.

RESEARCH DESIGN AND METHODS

A total of 24 obese adolescents with NGT, 13 with IFG, 29 with IGT, 11 with combined IFG/IGT, and 30 with type 2 diabetes underwent evaluation of hepatic glucose production ([6,6-²H₂]glucose), insulin-stimulated glucose disposal (R_d, euglycemic clamp), first- and second-phase insulin secretion (hyperglycemic clamp), body composition (dual-energy X-ray absorptiometry), abdominal adiposity (computed tomography), and substrate oxidation (indirect calorimetry).

RESULTS

Adolescents with NGT, pre-diabetes, and type 2 diabetes had similar body composition and abdominal fat distribution. R_d was lower (P = 0.009) in adolescents with type 2 diabetes than in those with NGT. Compared with adolescents with NGT, first-phase insulin was lower in those with IFG, IGT, and IFG/IGT with further deterioration in those with type 2 diabetes (P < 0.001), and β-cell function relative to insulin sensitivity (glucose disposition index [GDI]) was also lower in those with IFG, IGT, and IFG/IGT (40, 47, and 47%, respectively), with a further decrease (80%) in those with type 2 diabetes (P < 0.001). GDI was the major determinant of fasting and 2-h glucose levels.

CONCLUSIONS

Obese adolescents who show signs of glucose dysregulation, including abnormal fasting glucose, glucose intolerance or both, are more likely to have impaired insulin secretion rather than reduced insulin sensitivity. Given the impairment in insulin secretion, they are at high risk for progression to type 2 diabetes. Further deterioration in insulin sensitivity or secretion may enhance the risk for this progression.Pre-diabetes, defined as the presence of elevated fasting glucose, abnormal glucose tolerance, or both, is associated with an enhanced risk for development of type 2 diabetes in adults (1), but there are limited data to define the significance in children. A recent change in the definition of the abnormal fasting glucose to a lower level (100–125 mg/dl) has increased the prevalence of pre-diabetes in both adults and youth (2–4). It is unclear from the literature what role a defect in insulin secretion or an abnormality of insulin sensitivity might play in the impairment of glucose regulation, leading to glucose intolerance or elevated fasting plasma glucose.Epidemiological studies suggest that subjects with impaired fasting glucose (IFG) have lower insulin sensitivity and higher insulin secretion (5,6) based largely on fasting indexes of insulin sensitivity and an oral glucose tolerance (OGTT)–derived single index of insulin secretion (5). Adult studies reveal similar or lower insulin sensitivity in subjects with impaired glucose tolerance (IGT) compared with those with IFG who have lower insulin secretion (7,8). These studies are contrasted with clamp studies in Pima Indians showing similar insulin sensitivity in subjects with IFG and IGT but lower insulin secretion in those with fasting dysglycemia (9).Pediatric data are limited. In overweight Latino children with a family history of type 2 diabetes (10), children with impaired versus normal fasting glucose had no significant differences in insulin sensitivity or acute insulin response. However, the glucose disposition index (GDI), or insulin secretion relative to insulin sensitivity, was significantly reduced (15% lower) in children with IFG. A more recent study in obese adolescents revealed that subjects with IFG had decreased glucose sensitivity of first-phase insulin secretion and liver insulin sensitivity, whereas those with IGT had more severe degrees of peripheral insulin resistance compared with subjects with normal glucose tolerance (NGT) (11). We recently demonstrated that insulin secretion relative to insulin sensitivity shows a significantly declining pattern: highest in youth with NGT, intermediate in youth with IGT, and lowest in youth with type 2 diabetes (12).In an attempt to clarify the controversy concerning the metabolic derangements in the different categories of the pre-diabetes state, the aims of the present study were to 1) to investigate the metabolic characteristics of insulin sensitivity and secretion in obese youth, with IFG versus IGT, of similar body composition and abdominal adiposity and 2) to compare them not only with those with NGT but also with children with type 2 diabetes.     

The Singapore impaired glucose tolerance follow-up study: does the ticking clock go backward as well as forward?

OBJECTIVE: To 1). document the change in glucose tolerance for subjects with normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) over time, 2). identify baseline factors associated with worsening of glucose tolerance, and 3). determine whether cardiovascular disease (CVD) risk factors associated with IGT improved in tandem with glucose tolerance. RESEARCH DESIGN: Subjects with IGT and NGT (matched for age, sex, and ethnic group) were identified from a cross-sectional survey conducted in 1992. Subjects with IGT (297) and NGT (298) (65.0%) were reexamined in 2000. Glucose tolerance (assessed by 75-g oral glucose tolerance test), anthropometric data, serum lipids, blood pressure, and insulin resistance were determined at baseline and at the follow-up examination. RESULTS: For NGT subjects, 14.0% progressed to IGT and 4.3% to diabetes over 8 years. For IGT subjects, 41.4% reverted to NGT, 23.0% remained impaired glucose tolerant, and 35.1% developed diabetes. Obesity, hypertriglyceridemia, higher blood pressure, increased insulin resistance, and lower HDL cholesterol at baseline were associated with worsening of glucose tolerance in both IGT and NGT subjects. Those with IGT who reverted to NGT remained more obese and had higher blood pressure than those with NGT in both 1992 and 2000. However, serum triglyceride, HDL cholesterol, and insulin resistance values in 2000 became indistinguishable from those of subjects who maintained NGT throughout the study period. CONCLUSIONS: Some, but not all, CVD risk factors associated with IGT and with the risk of future diabetes normalize when glucose tolerance normalizes. Continued surveillance and treatment in subjects with IGT, even after they revert to NGT, may be important in the prevention of CVD.     

Immunoglobulin E and mast cell proteases are potential risk factors of impaired fasting glucose and impaired glucose tolerance in humans

Aim. Mast cells are important in experimental diabetes. Plasma levels of immunoglobulin E (IgE), tryptases, and chymases are inflammatory markers of human diabetes. Whether they also correlate with the risk of pre-diabetes, however, remains unknown.

Methods and results. A total of 260 subjects 55–75 years of age were grouped as normal glucose tolerance (NGT), isolated impaired fasting glucose (I-IFG), isolated impaired glucose tolerance (I-IGT), and mixed IFG/IGT. There were significant differences in plasma levels of high-sensitivity C-reactive protein (hsCRP) (P < 0.001) and IgE (P = 0.003) among all subgroups of pre-diabetes, and chymase in I-IGT (P = 0.043) and mixed IFG/IGT (P = 0.037) subgroups compared with NGT group. High-sensitivity CRP was a risk factor in all subgroups of pre-diabetes; IgE was a risk factor of mixed IFG/IGT; and chymase was a risk factor of I-IGT and mixed IFG/IGT. Interactions between hsCRP and high waist circumference (WC), waist-to-hip ratio (WHR), or HOMA-β index, and interactions between IgE and high WC or tryptase levels all increased further the risk of developing I-IFG, I-IGT, or mixed IFG/IGT.

Conclusion. Plasma hsCRP, IgE, and chymase levels associate with pre-diabetes status. While hsCRP, IgE, and chymase are individual risk factors of pre-diabetes, interactions with metabolic parameters increased further the risk of pre-diabetes.     

The relationship between endothelial dysfunction and oxidative stress in diabetes and prediabetes

Objective: Diabetes mellitus is associated with endothelial dysfunction and oxidative stress (OS). The aim of the present study was to determine whether increased OS and impaired endothelial function, are present in early states of diabetes, such as impaired glucose tolerance (IGT) and impaired fasting glucose (IFG). Methods: Brachial artery flow‐mediated dilatation (FMD) and nitrate‐induced dilatation were measured in 133 subjects with carbohydrate abnormalities (45 IGT, 44 IFG and 44 Type 2 diabetes mellitus) and in 46 subjects with normal glucose tolerance (NGT). Waist circumference, body mass index, blood pressure and fasting lipid profiles were obtained, and glucose and insulin values in response to a 75‐g oral glucose load were also measured. Plasma malondialdehyde (MDA) and superoxide dismutase (SOD) activity were determined. Results: Patients with diabetes and prediabetes had a higher plasma MDA concentration, but a lower plasma SOD activity than the NGT group (p = 0.006) and SOD activity was positively associated with FMD (p = 0.039). FMD were significantly reduced in the groups of subjects with abnormal carbohydrate metabolism compared with the NGT group (p = 0.035). Among the subjects with diabetes and prediabetes, FMD showed a negative correlation with fasting glucose and/or plasma glucose level at 120 min after oral glucose tolerance test (p = 0.028). Conclusions: The results showed that endothelial dysfunction and increased OS were present in subjects with IGT and IFG, indicating endothelial damage in these stages.     

探讨糖尿病前期患者血浆IL-18、PAI-1水平变化与胰岛素抵抗的相关性

目的探讨血浆白细胞介素-18(IL-18)、纤溶酶原激活物抑制物-1(PAI-1)水平变化与Ⅱ型糖尿病发病危险因素的关系.方法 设立健康人对照(NGT)组、糖耐量减低( IGT )组、空腹血糖受损合并糖耐量减低(IFG/IGT)组,每组各100例.测定各受试者血浆 IL-18、PAI-1、血清空腹胰岛素、空腹血糖、餐后2 h血糖,应用稳态模型评估法评价胰岛素抵抗(HOMA-IR).结果 IGT组、IFG/IGT组血浆 IL-18、PAI-1 水平均高于NGT组(P<0.01).IFG/IGT组血浆 IL-18、PAI-1 水平均高于IGT组(P<0.05).相关分析显示IL-18、PAI-1 水平与空腹血糖、餐后2 h血糖、HOMA-IR呈正相关(P<0.01).结论血浆 IL-18、PAI-1 水平升高可能是加重糖尿病前期患者胰岛素抵抗的危险因素;在糖尿病前期,IL-18、PAI-1可能参与了Ⅱ型糖尿病的发生、发展.     

Insulin secretion and insulin sensitivity pattern is different in isolated impaired glucose tolerance and impaired fasting glucose: the risk factor in Impaired Glucose Tolerance for Atherosclerosis and Diabetes study

OBJECTIVE: Isolated impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) are two risk categories for type 2 diabetes. This study compared both categories with respect to the degree of insulin secretion abnormalities and insulin resistance. RESEARCH DESIGN AND METHODS: This is a crossover comparison of a population at high risk for type 2 diabetes. The subjects were recruited from the Risk Factor in Impaired Glucose Tolerance for Atherosclerosis and Diabetes (RIAD) study. They underwent a 75-g oral glucose tolerance test, with measurement of specific insulin, C-peptide, proinsulin, and free fatty acids at baseline and every 30 min after load for 2 h. Factor analysis was performed to evaluate the importance of insulin resistance and secretion abnormalities in both categories. RESULTS: All categories of prediabetic hyperglycemia had a higher cardiovascular risk factor level when adjusted for sex, age, and BMI compared to control subjects with normal glucose tolerance. Subjects with isolated IFG were more insulin resistant than those with IGT. By contrast, subjects with isolated IGT exhibited a more severe deficit in early- and late-phase insulin secretion versus IFG subjects. As shown with factor analysis, in IFG the insulin resistance factor explained 28.4% of the variance, whereas in IGT the insulin secretion factor was dominant, explaining 31.1% of the total variance. CONCLUSIONS: Our cross-sectional data from the RIAD study demonstrate that isolated IFG and isolated IGT are different with respect to the degree of insulin resistance and anomalies in insulin secretion, and that subjects with IGT exhibit a deficit in the early and late phases of insulin secretion. This finding may be important for a differential approach in primary prevention of type 2 diabetes.     

Contributions of beta-cell dysfunction and insulin resistance to the pathogenesis of impaired glucose tolerance and impaired fasting glucose

Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) are intermediate states in glucose metabolism that exist between normal glucose tolerance and overt diabetes. Epidemiological studies demonstrate that the two categories describe distinct populations with only partial overlap, suggesting that different metabolic abnormalities characterize IGT and IFG. Insulin resistance and impaired beta-cell function, the primary defects observed in type 2 diabetes, both can be detected in subjects with IGT and IFG. However, clinical studies suggest that the site of insulin resistance varies between the two disorders. While subjects with IGT have marked muscle insulin resistance with only mild hepatic insulin resistance, subjects with IFG have severe hepatic insulin resistance with normal or near-normal muscle insulin sensitivity. Both IFG and IGT are characterized by a reduction in early-phase insulin secretion, while subjects with IGT also have impaired late-phase insulin secretion. The distinct metabolic features present in subjects with IFG and IGT may require different therapeutic interventions to prevent their progression to type 2 diabetes.     

Changing the definition of impaired fasting glucose: impact on the classification of individuals and risk definition

OBJECTIVE: This study evaluates the impact of lowering the diagnostic threshold for impaired fasting glucose (IFG) from 6.1 to 5.6 mmol/l as proposed by the American Diabetes Association (ADA) on the prevalence of the condition, classification of individuals, and risk definition. RESEARCH DESIGN AND METHODS: A total of 1,285 employees of the Italian Telephone Company aged 35-59 years without known diabetes underwent an oral glucose tolerance test (OGTT). BMI, serum cholesterol, triglycerides, and blood pressure were measured. Medication use was recorded. RESULTS: With the new ADA criterion, the proportion of people diagnosed with IFG increased from 3.2 to 9.7%. The newly proposed IFG category identified 41% of all subjects with impaired glucose tolerance (IGT) compared with 16.2% identified with the use of the World Health Organization criterion for IFG; the improvement in accuracy has been achieved at the cost of classifying more previously "normal" subjects as having IFG (from 2.3 to 7.3%). Both IFG and IGT were associated with an unfavorable risk profile for diabetes and cardiovascular disease, with a higher estimated risk for IGT than IFG. CONCLUSIONS: Even with the revised diagnostic criterion, IFG and IGT identify distinct groups that have a different background risk. The cost/benefit of preventive measures tested in people with IGT may not apply to the new IFG category.     

血糖调节异常者胰岛素抵抗及胰岛β细胞功能研究

目的研究胰岛素抵抗和胰岛β细胞功能与中国人血糖调节异常(IGR)的关系。方法根据口服葡萄糖耐量试验(OGTT)将209例受试者分为正常糖耐量(NGT)组、空腹血糖受损(IFG)组、糖耐量减退(IGT)组、IFG/IGT组和糖尿病(DM)患者组,用胰岛素敏感指数(ISI-COM)评价胰岛素抵抗(IR),用调整β细胞功能指数(modifiedβcell function index,MBCI)评价β细胞功能,并用早期胰岛分泌指数(△I30/△G30)评价急性期胰岛分泌功能,OGTT胰岛素曲线下面积评价二相期胰岛素分泌功能。结果IGR各组与DM组ISI-COM较NGT组有显著降低,差异有统计学意义(P0.01),而IGR各组间差异无统计学意义(P0.05)。IFG组和IGT组β细胞功能较NGT组显著降低,差异有统计学意义(P0.01),而IFG/IGT组与DM组间差异无统计学意义(P0.05)。各病例组早期胰岛分泌功能亦较NGT组有显著性降低,差异有统计学意义(P0.01),IGT组与IFG组间差异也有统计学意义(P0.01)。结论IGR各阶段均存在不同程度的IR和β细胞功能异常,其中IFG和IGT有不同的发病机制和过程,提示对于不同糖代谢异常的患者需要不同的治疗方式,以延缓血糖代谢异常的进展。     

Glycemic status and development of kidney disease: the Framingham Heart Study

OBJECTIVE: Diabetes is a major risk factor for the development of kidney disease and is the leading cause of end-stage renal disease in the U.S. Whether pre-diabetes is associated with the development of kidney disease is unclear. RESEARCH DESIGN AND METHODS: Subjects free of chronic kidney disease (CKD) were drawn from the Framingham Heart Study offspring cohort (1991-1995), given an oral glucose tolerance test, and followed for an average of 7 years for development of CKD (glomerular filtration rate [GFR] of <59 ml/min per 1.73 m2 in women and <64 ml/min per 1.73 m2 in men). Multivariable logistic regression models, adjusted for cardiovascular disease risk factors including age, sex, hypertension, smoking, BMI, total and HDL cholesterol levels, and prevalent myocardial infarction or congestive heart failure, were used to estimate the odds of patients developing kidney disease among glycemic categories. RESULTS: Of 2,398 subjects (53% women; mean age 54 years), 63% were normoglycemic, 29% had impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), 3.4% were newly diabetic, and 4.6% had known diabetes. By glycemic category, mean GFR at follow-up was 87, 85, 82, and 78 ml/min per 1.73 m2, respectively. The fully adjusted odds of developing CKD were 0.98 (95% CI 0.67-1.45), 1.71 (95% CI 0.83-3.55), and 1.93 (95% CI 1.06-3.49) among those with IFG or IGT, newly diagnosed diabetes, or known diabetes, respectively, compared with those who were normoglycemic at baseline. Among participants without diabetes, metabolic syndrome was not associated with kidney disease at follow-up (odds ratio 1.46, P = 0.06). CONCLUSIONS: Cardiovascular disease risk factors explain much of the relationship between prediabetes and the development of chronic kidney disease. Clinical trials are warranted to determine whether vascular risk factor modification can slow the decline of kidney function among those with pre-diabetes.