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.     

不同糖耐量人群胰岛素抵抗和胰岛β细胞功能的比较研究

目的观察不同糖耐量人群胰岛素抵抗(Insulin Resistance,IR)和胰岛β细胞功能改变的特点,为临床正确选择干预病变的靶点和治疗措施提供依据。方法对9922例初诊或疑诊为2型糖尿病(T2DM)患者的口服75 g葡萄糖耐量试验(Oral Glucose Tolerance Test,OGTT)及胰岛素释放结果进行分析。根据空腹血糖(FBG)6.1 mmol/L和7.0 mmol/L及餐后2 h血糖(2 hPG)7.8 mmol/L和11.1 mmol/L四个切点将人群分为正常糖耐量组1362例(NGT组)、单纯空腹血糖受损组982例(I-IFG组)、单纯糖耐量减低组778例(I-IGT组)、联合糖耐量减低组1300例(C-IGT组)、空腹正常型糖尿病组250例(NFD组)、空腹受损型糖尿病组1186例(IFD组)、餐后正常型糖尿病组14例(NPD组)、餐后受损型糖尿病组332例(IPD组)、空腹合并餐后型糖尿病组3708例(CFPD组)。结果①稳态模型胰岛素抵抗指数(HOMA-IR)由小到大依次为NGT组、I-IGT组、NFD组、I-IFG组、C-IGT组、IFD组、IPD组、CFPD组,组间比较差异有统计学意义(P<0.05);NPD组与NGT组、I-IGT组、C-IGT组比较差异有统计学意义(P<0.05),与其他组差异无统计学意义。②胰岛素分泌指数(ΔI30/ΔG30)由小到大依次为CFPD组、IFD组、NFD组、IPD组、C-IGT组、NPD组、I-IGT组、I-IFG组、NGT组,各组间比较差异有统计学意义(P<0.05)。③校正IR影响后,胰岛β细胞分泌功能由弱到强依次为CFPD组、IPD组、IFD组、NPD组、NFD组、C-IGT组、I-IFG组、I-IGT组、NGT组,各组间比较差异有统计学意义(P<0.05)。结论不同糖耐量人群IR和胰岛β细胞功能具有FBG越高基础胰岛素抵抗越严重,单纯以餐后增高为特征的糖尿病患者并未表现出基础胰岛素抵抗,主要是早晚相胰岛素分泌缺陷,空腹相当时餐后血糖越高胰岛分泌功能越弱,即随着空腹、餐后糖代谢紊乱的不断进展,IR逐渐加重,胰岛β细胞分泌功能进行性减退。针对此特点进行个体化干预及治疗尤为重要。     

某市东部沿海地区糖调节受损人群生化指标变化及危险因素分析

目的 观察分析某市东部沿海地区糖调节受损(IGR)人群血液生化指标和体格特征的变化,探讨影响IGR发生的危险因素.方法 按世界卫生组织糖尿病专家委员会1999年诊断标准,将IGR人群分为I-IFG、I-IGT和IGT/IFG三个类型组,并与正常糖耐量组(NGT)进行比较,然后运用单因素和多因素非条件Logistic回归分析影响IGR发生的危险因素.结果 ① IGR三个类型组与NGT组比较,其年龄、血压、BMI、WHR、FPG、2 hPG、TC、TG、LDL-C、UA、FINS、HOMA-IR水平均较高,HDL-C水平较低,差异具有统计学意义(P<0.05或P<0.01).IFG/IGT组与I-IFG、I-IGT两组比较,其FPG、2 hPG、HbA1c、TC、TG、LDL-C、UA、FINS、HOMA-IR水平均较高,HDL-C水平较低,差异具有统计学意义(P<0.05).②进入多因素非条件Logistic回归模型的因素有年龄、血压、BMI、WHR、TC、TG、LDL-C、低HDL-C、UA及糖尿病家族史(P<0.05或P<0.01).结论 ①IGR人群不同程度存在着血糖、血脂代谢异常和胰岛素抵抗,检测血糖、血脂及胰岛素等生化指标,对于评价IGR有一定的作用.②年龄增长、中心性肥胖、高血压、血脂紊乱、高尿酸血症及糖尿病家族史为IRG的主要危险因素.     

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.     

Fasting glucose, obesity, and coronary artery calcification in community-based people without diabetes

OBJECTIVE Our objective was to assess whether impaired fasting glucose (IFG) and obesity are independently related to coronary artery calcification (CAC) in a community-based population. RESEARCH DESIGN AND METHODS We assessed CAC using multidetector computed tomography in 3,054 Framingham Heart Study participants (mean [SD] age was 50 [10] years, 49% were women, 29% had IFG, and 25% were obese) free from known vascular disease or diabetes. We tested the hypothesis that IFG (5.6-6.9 mmol/L) and obesity (BMI ≥30 kg/m(2)) were independently associated with high CAC (>90th percentile for age and sex) after adjusting for hypertension, lipids, smoking, and medication. RESULTS High CAC was significantly related to IFG in an age- and sex-adjusted model (odds ratio 1.4 [95% CI 1.1-1.7], P = 0.002; referent: normal fasting glucose) and after further adjustment for obesity (1.3 [1.0-1.6], P = 0.045). However, IFG was not associated with high CAC in multivariable-adjusted models before (1.2 [0.9-1.4], P = 0.20) or after adjustment for obesity. Obesity was associated with high CAC in age- and sex-adjusted models (1.6 [1.3-2.0], P < 0.001) and in multivariable models that included IFG (1.4 [1.1-1.7], P = 0.005). Multivariable-adjusted spline regression models suggested nonlinear relationships linking high CAC with BMI (J-shaped), waist circumference (J-shaped), and fasting glucose. CONCLUSIONS In this community-based cohort, CAC was associated with obesity, but not IFG, after adjusting for important confounders. With the increasing worldwide prevalence of obesity and nondiabetic hyperglycemia, these data underscore the importance of obesity in the pathogenesis of CAC.     

Estimated number of adults with prediabetes in the US in 2000: opportunities for prevention

OBJECTIVE: To estimate the percent and number of overweight adults in the U.S. with prediabetes who would be potential candidates for diabetes prevention as per the American Diabetes Association Position Statement (12). RESEARCH DESIGN AND METHODS: We analyzed data from the Third National Health and Nutrition Examination Survey (NHANES III; 1988-1994) and projected our estimates to the year 2000. We defined impaired glucose tolerance (IGT; 2-h glucose 140-199 mg/dl), impaired fasting glucose (IFG; fasting glucose 110-125 mg/dl), and prediabetes (IGT or IFG) per American Diabetes Association (ADA) criteria. The ADA recently recommended that all overweight people (BMI >or=25 kg/m(2)) who are >or=45 years of age with prediabetes could be potential candidates for diabetes prevention, as could prediabetic people aged >25 years with risk factors. In NHANES III, 2-h postload glucose concentrations were done only among subjects aged 40-74 years. Because we were interested in overweight people who had both the 2-h glucose and fasting glucose tests, we limited our estimates of IGT, IFG, and prediabetes to those aged 45-74 years. RESULTS-Overall, 17.1% of overweight adults aged 45-74 years had IGT, 11.9% had IFG, 22.6% had prediabetes, and 5.6% had both IGT and IFG. Based on those data, we estimated that in the year 2000, 9.1 million overweight adults aged 45-74 had IGT, 5.8 million had IFG, 11.9 million had prediabetes, and 3.0 million had IGT and IFG. CONCLUSIONS: Almost 12 million overweight individuals aged 45-74 years in the U.S. may benefit from diabetes prevention interventions. The number will be substantially higher if estimation is extended to individuals aged >75 and 25-44 years.     

Cardiovascular risk profile in individuals with borderline glycemia: the effect of the 1997 American Diabetes Association diagnostic criteria and the 1998 World Health Organization Provisional Report

OBJECTIVE: In 1997, the American Diabetes Association (ADA) recommended a new diagnostic category, impaired fasting glucose (IFG), to describe individuals with borderline glucose tolerance. On the other hand, the World Health Organization (WHO) suggested retaining the category of impaired glucose tolerance (IGT). We studied the prevalence of IFG and IGT in a multiethnic society and compared the cardiovascular risk profiles of subjects with IFG, IGT, or both IFG and IGT. RESEARCH DESIGN AND METHODS: A total of 3,568 subjects were examined from the 1992 National Health Survey of Singapore, which involved a combination of disproportionately stratified sampling and systematic sampling. Anthropometric, blood pressure, insulin, lipid profile, and uric acid measurements were taken, and a standard 75-g oral glucose tolerance test was performed after a 10-h overnight fast. RESULTS: The prevalence rates of IFG only, IGT only, and both IFT and IGT were 3.45, 10.2, and 3.4%, respectively. The degree of agreement (kappa) between the two diagnostic criteria (the ADA IFG and the WHO IGT) was only 0.25. A fasting glucose level of 5.5 mmol/l was the optimal cutoff for predicting a 2-h postload glucose level of > or =7.8 mmol/l. The following cardiovascular risk factors were higher in subjects with both IFG and IGT compared with those with either IFG or IGT alone: systolic blood pressure (131 +/- 20 vs. 125 +/- 21 and 125 +/- 19 mmHg, respectively; P < 0.05 and P < 0.001, respectively); diastolic blood pressure (77 +/- 12 vs. 73 +/- 12 and 74 +/- 12 mmHg, respectively; P < 0.05); BMI (26.2 +/- 4.2 vs. 24.4 +/- 4.0 and 24.6 +/- 4.4 kg/m2, respectively; P < 0.01 and P < 0.001, respectively); waist circumference (84.1 +/- 10.3 vs. 79.3 +/- 10.7 and 79.3 +/- 10.6 cm, respectively; P < 0.001); waist-to-hip ratio (0.84 +/- 0.08 vs. 0.82 +/- 0.09 and 0.81 +/- 0.08, respectively; P < 0.05 and P < 0.001, respectively); fasting insulin (12.1 +/- 9.7 vs. 9.2 +/- 5.3 and 9.9 +/- 7.7 mU/l; P < 0.01); insulin resistance (by homeostasis model assessment [HOMA]) (3.41 +/- 2.77 vs. 2.58 +/- 1.50 and 2.43 +/- 1.83, respectively; P < 0.01 and P < 0.001, respectively); total cholesterol (5.81 +/- 1.1 vs. 5.51 +/- 1.1 and 5.53 +/- 1.1 mmol/l, respectively; P < 0.05) and apolipoprotein(B) [apo(B)] (1.5 +/- 0.38 vs. 1.40 +/- 0.34 and 1.39 +/- 0.35 mmol/l, respectively; P < 0.01). The pattern of difference remained significant only for fasting insulin, insulin resistance (HOMA), and apo(B) (borderline) after adjustment for age, sex, and ethnic differences. CONCLUSIONS: Obvious discordance was evident in the classification of glycemic status when applying the criteria proposed by the ADA (IFG) or WHO (IGT) in a multiethnic society like Singapore. However, subjects with either IFG or IGT had similar cardiovascular risk profiles. Therefore, both criteria identified individuals at high risk for cardiovascular disease. Individuals with both IFG and IGT had a greater incidence of the cardiovascular dysmetabolic syndrome.     

Basal-State Hyperinsulinemia in Healthy Normoglycemic Adults Is Predictive of Type 2 Diabetes Over a 24-Year Follow-Up: A preliminary report

OBJECTIVE

We examined the predictive value of hyperinsulinemia in the basal state on the 24-year progression from normoglycemia to dysglycemia.

RESEARCH DESIGN AND METHODS

A sample of 515 normoglycemic men and women were studied again after 24 years for glycemic status.

RESULTS

Half of the participants developed dysglycemia: 11.1% progressed to impaired fasting glucose (IFG), 9.9% to impaired glucose tolerance (IGT), 4.5% to both IFG and IGT, and another 24.3% to type 2 diabetes. Elevated levels of overnight fasting (basal) insulin, triglycerides, BMI ≥27 kg/m², fasting blood glucose, blood pressure, North African or Yemenite background, and male sex each favored conversion to dysglycemia after 24 years. In multiple ordered logistic regression analysis, the most significant predictor of progression to dysglycemia was hyperinsulinemia (upper quintile), after adjusting for BMI, ethnic origin, sex, age, smoking, physical activity, blood pressure, and triglycerides.

CONCLUSIONS

Basal hyperinsulinemia in normoglycemic adults constitutes an independent risk factor for developing dysglycemia over 24 years.This study examined hyperinsulinemia in the basal state as an independent factor associated with the 24-year progression to dysglycemia (impaired fasting glucose [IFG]/impaired glucose tolerance [IGT] or type 2 diabetes) in normoglycemic ethnically diverse adult men and women.In the 1980s, Modan et al. (1,2), following the analysis of baseline information of the present cohort, proposed that hyperinsulinemia, reflecting peripheral insulin resistance, is linked to hypertension, obesity, dyslipidemia, and glucose intolerance, a cluster termed “metabolic syndrome” by Reaven (3). Insulin resistance has since been assigned a central place in the metabolic disturbances associated with obesity and type 2 diabetes. We previously reviewed the evidence for the possible role of hyperinsulinemia, especially in the basal state, in sustaining, expanding, or initiating insulin resistance (4).     

Different mechanisms for impaired fasting glucose and impaired postprandial glucose tolerance in humans

OBJECTIVE: To compare the pathophysiology of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) in a more comprehensive and standardized fashion than has hitherto been done. RESEARCH DESIGN AND METHODS: We studied 21 individuals with isolated IFG (IFG/normal glucose tolerance [NGT]), 61 individuals with isolated IGT (normal fasting glucose [NFG]/IGT), and 240 healthy control subjects (NFG/NGT) by hyperglycemic clamps to determine first- and second-phase insulin release and insulin sensitivity. Homeostasis model assessment (HOMA) indexes of beta-cell function (HOMA-%B) and insulin resistance (HOMA-IR) were calculated from fasting plasma insulin and glucose concentrations. RESULTS: Compared with NFG/NGT, IFG/NGT had similar fasting insulin concentrations despite hyperglycemia; therefore, HOMA-IR was increased approximately 30% (P < 0.05), but clamp-determined insulin sensitivity was normal (P > 0.8). HOMA-%B and first-phase insulin responses were reduced approximately 35% (P < 0.002) and approximately 30% (P < 0.02), respectively, but second-phase insulin responses were normal (P > 0.5). NFG/IGT had normal HOMA-IR but approximately 15% decreased clamp-determined insulin sensitivity (P < 0.03). Furthermore, HOMA-%B was normal but both first-phase (P < 0.0003) and second-phase (P < 0.0001) insulin responses were reduced approximately 30%. IFG/NGT differed from NFG/IGT by having approximately 40% lower HOMA-%B (P < 0.012) and approximately 50% greater second-phase insulin responses (P < 0.005). CONCLUSIONS: Since first-phase insulin responses were similarly reduced in IFG/NGT and NFG/IGT, we conclude that IFG is due to impaired basal insulin secretion and preferential resistance of glucose production to suppression by insulin, as reflected by fasting hyperglycemia despite normal plasma insulin concentrations and increased HOMA-IR, whereas IGT mainly results from reduced second-phase insulin release and peripheral insulin resistance, as reflected by reduced clamp-determined insulin sensitivity.     

Definition of prediabetes

Diabetes evolves through prediabetes, defined as impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). Subjects with IFG/IGT have an increased risk of developing diabetes and a higher prevalence of cardiovascular disease than normoglycemic individuals. However, there is considerable evidence that glucose levels lower than those meeting the current definition of prediabetes may also be associated with similar concerns, particularly in high-risk individuals in accordance with a continuous glycemic risk perspective. Therefore, an absolute definition of prediabetes may underestimate the implications and vastness of this disorder. Research should focus on these aspects to minimize the risk of developing a preventable condition.     

Using metabolic syndrome traits for efficient detection of impaired glucose tolerance

OBJECTIVE: Efficient detection of impaired glucose tolerance (IGT) is needed to implement type 2 diabetes prevention interventions. RESEARCH DESIGN AND METHODS: We assessed the capacity of the metabolic syndrome (MetS) to identify IGT in a cross-sectional analysis of 3,326 Caucasian Framingham Offspring Study (FOS), 1,168 Caucasian and 1,812 Mexican-American San Antonio Heart Study (SAHS), 1,983 Mexico City Diabetes Study (MCDS), and 452 Caucasian, 407 Mexican-American, and 290 African-American Insulin Resistance Atherosclerosis Study (IRAS) men and women aged 30-79 years who had a clinical examination and an oral glucose tolerance test (OGTT) during 1987-1996. Those with diabetes treatment or fasting plasma glucose > or =7.0 mmol/l were excluded (MetS was defined by Third Report of the National Cholesterol Education Program's Adult Treatment Panel criteria and IGT as 2-h postchallenge glucose [2hPG] > or =7.8 mmol/l). We calculated positive (PPV) and negative predictive values (NPV), population attributable risk percentages (PAR%), age- and sex-adjusted odds ratios (ORs), and areas under the receiver operating characteristic curve (AROCs) associated with MetS traits. RESULTS: Among FOS, SAHS, and MCDS subjects, 24-43% had MetS and 15-23% had IGT (including 2-5% with 2hPG > or =11.1 mmol/l). Among those with MetS, OR for IGT were 3-4, PPV were 0.24-0.41, NPV were 0.84-0.91, and PAR% were 30-40%. Among subjects with MetS defined by impaired fasting glucose (IFG) and any two other traits, OR for IGT were 9-24, PPV were 0.62-0.89, NPV were 0.78-0.87, and PAR% were 3-12%. Among IRAS subjects, 24-34% had MetS and 37-41% had IGT. Among those with MetS, ORs for IGT were 3-6, PPVs were 0.57-0.73, and NPVs were 0.67-0.72. In logistic regression models, IFG, large waist, and high triglycerides were independently associated with IGT (AROC 0.71-0.83) in all study populations. CONCLUSIONS: The MetS, especially defined by IFG, large waist, and high triglycerides, efficiently identifies subjects likely to have IGT on OGTT and thus be eligible for diabetes prevention interventions.     

Metabolic characteristics in individuals with impaired glucose homeostasis

We sought to clarify whether impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or both (IFG/IGT) represent the most severe impairment in insulin resistance (IR) and insulin secretion. Among the 159 Chinese subjects, 21 were diagnosed as having IFG, 103 as having IGT and 35 as having both. IR and beta-cell function were assessed using homeostatic model assessment (HOMA) and an insulin-suppression test (IST). No differences were evident between the groups in blood pressure, body mass index, plasma insulin fasting levels and lipid profiles. However, plasma 2-h insulin levels were higher in the IGT and IFG/IGT groups. Beta-cell functions were not different between these groups. But, the result of glucose tolerance was different, in which the IFG/IGT and IFG groups displayed higher insulin sensitivity than IGT via HOMA instead of no difference via IST in the three patient groups.     

Impaired glucose tolerance and impaired fasting glucose share similar underlying pathophysiologies

Both impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) are pre-diabetic states. IGT was defined as having normal fasting plasma glucose (< 6.1 mmol/l) and abnormal 2-hr post-challenge plasma glucose. IFG was defined as having abnormal fasting plasma and normal 2-hr post-challenge plasma glucose (< 7.8 mmol/l). To explore whether these two abnormalities share similar underlying pathophysiologies, we evaluated risk factors of IGT and IFT using the models of factor analysis. The present study included 107 subjects with IGT and 52 with IFG. An oral glucose tolerance test and insulin suppression test, which could quantify insulin resistance, were performed on separate days. The risk factors include waist-to-hip ratio (WHR), triglycerides, high-density lipoprotein (HDL)-cholesterol, blood pressure, and fasting plasma glucose, which are associated with metabolic syndrome and insulin resistance. Factor analysis is a commonly used statistical method that could reduce a large number of risk factors into smaller numbers of groups, also called dimension. Accordingly, the complicated data could be interpreted more easily, since the related risk factors are grouped in one dimension. The results showed that the risk factors of IGT and IFG have similar grouping patterns. Triglyceride, insulin resistance, and HDL-cholesterol were grouped in one dimension (the lipid dimension), while WHR, mean blood pressure and fasting plasma glucose were grouped in another dimension (the metabolic dimension). In conclusion, except for WHR, the grouping patterns of the components in both IGT and IFG were nearly identical. These results suggest that IGT and IFG may share similar pathophysiologies.     

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.     

Postload hyperglycemia is associated with increased subclinical inflammation in patients with prediabetes

Abstract

Background/aims. In this present study, we aimed: (i) To clarify if prediabetes is associated with subclinical inflammation independent of underlying obesity, and (ii) to evaluate the effect of postload glucose concentration on subclinical inflammation markers in a group of patients with elevated fasting glucose. Material and methods. In a cohort of 165 patients with newly detected fasting hyperglycemia, according to 75 g oral glucose tolerance test (OGTT), subjects were classified either as newly diagnosed type 2 diabetes (diabetes group, n = 40), impaired fasting glucose (IFG) plus impaired glucose tolerance (IGT) (IFG/IGT group, n = 42) or IFG only (IFG group, n = 83). A control group (n = 47) consisted of age- and body mass index (BMI)-matched healthy subjects with a normal OGTT. Circulating concentrations of lipids, insulin, interleukin-6 (IL-6), interleukin-8 (IL-8) and high sensitive C-reactive protein (hsCRP) were measured. HOMA index was calculated. Results. Subclinical inflammation markers were elevated in patients with diabetes and IFG/IGT compared to healthy controls and also IFG patients (diabetes vs. control: p < 0.05 for hsCRP, IL-8, and IL-6; IFG/IGT vs. control: p < 0.05 for hsCRP, and IL-6; diabetes vs. IFG: p < 0.05 for hsCRP, and IL-6; IFG/IGT vs. IFG: p < 0.05 for hsCRP, and IL-6). In multiple regression analysis, postload glucose concentration was independently associated with circulating hsCRP and IL-6 concentrations when the data was controlled for age, gender, BMI and lipid concentrations (p < 0.05 for hsCRP, and IL-6). Conclusion. Our results suggest that patients with prediabetes, independent of underlying obesity, have increased concentrations of subclinical inflammation which is mostly driven by postload glucose concentrations.     

Higher medical care costs accompany impaired fasting glucose

OBJECTIVE: The purpose of this study was to estimate medical costs associated with elevated fasting plasma glucose (FPG) and to determine whether costs differed for patients who met the 2003 (> or = 100 mg/dl) versus the 1997 (> or = 110 mg/dl) American Diabetes Association (ADA) cut point for impaired fasting glucose. RESEARCH DESIGN AND METHODS: We identified 28,335 patients with two or more FPG test results of at least 100 mg/dl between 1 January 1994 and 31 December 2003. Those with evidence of diabetes before the second test were excluded. We categorized patients into two stages of abnormal glucose (100-109 mg/dl and 110-125 mg/dl) and matched each of these subjects to a patient with a normal FPG test (<100 mg/dl) on age, sex, and year of FPG test. All subjects were followed until an FPG test qualified them for a higher stage, dispensing of an anti-hyperglycemic drug, health plan termination, or 31 December 2003. RESULTS: Adjusted annual costs were dollar 4,357 among patients with normal FPG, dollar 4,580 among stage 1 patients, and dollar 4,960 among stage 2 patients (P < 0.001, all comparisons). After removing patients with normal FPG tests whose condition progressed to a higher stage or diabetes, costs in the normal FPG stage were dollar 3,799. Patients in both stages 1 and 2 had more cardiovascular comorbidities than patients with normal FPG. CONCLUSIONS: Our results demonstrate that abnormal glucose metabolism is associated with higher medical care costs. Much of the excess cost was attributable to concurrent cardiovascular disease. The 2003 ADA cut point identifies a group of patients with greater costs and comorbidity than normoglycemic patients but with lower costs and less comorbidity than patients with FPG above the 1997 cut point.     

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.     

急性脑梗死患者糖调节受损的分布及其临床价值分析

目的：探讨急性脑梗死糖调节受损（IGR）的分布情况,并就FG、HbA1c、餐后2h血糖及胰岛素对急性脑血管患者血糖评估的价值进行重新评价。方法：测定2007年1月-2008年12月急性脑梗死患者的空腹血糖及胰岛素、餐后2h血糖及胰岛素、HbA1c等,按世界卫生组织的正常血糖、IGR、糖尿病诊断标准进行评定,了解IGR在急性脑血管病的分布情况,并对以上各指标的临床价值进行重新评估。结果：263例急性脑梗死患者既往已确诊有2型糖尿病史者103例,经连续2次空腹血糖测定≥7．0mmol·L^-1而新确诊为2型糖尿病者17例,IGR5例;经口服糖耐量试验（OGTT）试验后新诊糖尿病患者36例,即入院后的急性脑梗死患者中新诊糖尿病患者为53倒,占总病例数的20．15％,在263例患者,最终确诊糖尿患者数为156例,即合并糖尿患者比例由入院时的39．16％增加至59．32％;另新诊断IGR患者27例,其中IFG10例,I-IGT12例,IFG＋IGT5例,糖代谢异常率由入院时的47．53％上升至OGTT试验后的69．58％。NGT组、IGR组、DM组的HbAIc异常率分别为5／80（6．25％）,13／27（48．15％）,132／156（84．62％）,空腹胰岛素值分别为：10．06±9．28,9．55±5．42,9．98±5．26mU·L^-1,餐后2h胰岛素分别为28．18±18．06,50．77±32．37,35．6±27．2mu·L^-1.NIHSS评分分别为4．21±2．27,4．80±2．81,5．83±2．88。结论：急性脑梗死患者中存在广泛的糖代谢畀常,仅据空腹血糖和既往糖尿病史将使81．48％IGR、20．15％糖尿病病人漏诊,对急性脑血管病人进行餐后2h血糖及胰岛素、HbA1c测定有利于对患者血糖的正确评估及治疗。     

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.     

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.