Increased plasminogen activator inhibitor-1 activity in offspring of type 2 diabetic patients: lack of association with plasma insulin levels

OBJECTIVE: To determine whether a dysregulation of the fibrinolytic system exists in normal glucose tolerant offspring of type 2 diabetic patients. RESEARCH DESIGN AND METHODS: In this cross-sectional study, 32 offspring of type 2 diabetic patients and 26 subjects with no family history of diabetes were studied. With respect to the metabolic parameters, plasma fasting and 2-h postload (75 g glucose) glucose and insulin levels, total cholesterol, triglycerides, and HDL cholesterol concentrations were determined. To evaluate the status of hemostatic factors, fibrinogen, tissue plasminogen activator (tPA) antigen level, plasminogen activator inhibitor-1 (PAI-1) antigen level, and PAI-1 activity were assessed. The statistical analyses included the Mann-Whitney U test to check the significance of differences between variables in the two groups and Spearman's rank correlation tests to check the interrelationships between the hemostatic and metabolic parameters in the offspring group. RESULTS: All subjects had normal glucose tolerance according to the American Diabetes Association criteria. Plasma fasting and postload insulin concentrations were significantly higher in offspring compared with control group (P<0.00001 and P<0.01, respectively). Plasma fasting and postload glucose, fibrinogen, tPA antigen, total cholesterol, and BMI were comparable between the groups. The offspring had significantly higher waist-to-hip ratio (WHR) (P = 0.03), higher triglycerides (P = 0.01), and lower HDL cholesterol (P<0.01) compared with the control group. PAI-1 antigen level and PAI-1 activity were higher in the offspring (P = 0.05 and P = 0.04, respectively). In the offspring group, PAI-1 activity was correlated with plasma PAI-1 antigen level (r = 0.40, P = 0.02), fibrinogen (r = 0.45, P = 0.01), and HDL cholesterol (r = -0.36, P = 0.04). However, tPA antigen level, fasting and postload plasma glucose and insulin, total cholesterol, triglycerides, WHR, and BMI did not correlate with PAI-1 activity. CONCLUSIONS: These data suggest that normal glucose tolerant offspring of type 2 diabetic subjects have elevated PAI-1 activity indicating to hypofibrinolysis in this group. The elevated PAI-1 activity has no association with plasma insulin concentration.     

Relationship between fasting insulin and cardiovascular risk factors is already present in young men: the Verona Young Men Atherosclerosis Risk Factors Study

The associations between fasting plasma insulin concentration and risk factors for cardiovascular diseases were examined in 979 18-year-old men participating in the Verona Young Men Atherosclerosis Risk Factors Study, a cross-sectional population-based study. Body mass index (BMI), waist-to-hip ratio (WHR), plasma triglycerides and uric acid concentrations, and blood pressure values significantly increased, and the high-density lipoprotein (HDL)–total cholesterol ratio decreased, across quartiles of fasting insulin. Total and low-density lipoprotein cholesterol concentrations did not change significantly with the increase in fasting insulin levels. After adjustment for BMI, WHR, smoking, alcohol intake and physical activity, only plasma triglycerides significantly increased across insulin quartiles ( F  =7.1; P  <0.001). However, systolic blood pressure and uric acid were close to statistical significance ( P  =0.06–0.07). Multiple linear regression analysis confirmed that plasma insulin was independently correlated with plasma triglycerides and, to a lesser extent, with blood pressure and uric acid concentration. This analysis pointed out that BMI was a stronger independent predictor of all cardiovascular disease risk factors than fasting insulin. When subjects were categorized according to the number of metabolic and haemodynamic disorders occurring within the same individual, subjects with multiple disorders (i.e. three or four) had higher plasma insulin levels than those with none or few disorders, even after adjusting for BMI, WHR and behavioural variables ( F  =4.0; P  <0.01). These results indicate that hyperinsulinaemia is already associated with a cluster of cardiovascular disease risk factors in young adulthood, the strongest independent association being with plasma triglycerides.     

Relationship between fasting insulin and cardiovascular risk factors is already present in young men: the Verona Young Men Atherosclerosis Risk Factors Study

The associations between fasting plasma insulin concentration and risk factors for cardiovascular diseases were examined in 979 18-year-old men participating in the Verona Young Men Atherosclerosis Risk Factors Study, a cross-sectional population-based study. Body mass index (BMI), waist-to-hip ratio (WHR), plasma triglycerides and uric acid concentrations, and blood pressure values significantly increased, and the high-density lipoprotein (HDL)–total cholesterol ratio decreased, across quartiles of fasting insulin. Total and low-density lipoprotein cholesterol concentrations did not change significantly with the increase in fasting insulin levels. After adjustment for BMI, WHR, smoking, alcohol intake and physical activity, only plasma triglycerides significantly increased across insulin quartiles (F =7.1; P <0.001). However, systolic blood pressure and uric acid were close to statistical significance (P =0.06–0.07). Multiple linear regression analysis confirmed that plasma insulin was independently correlated with plasma triglycerides and, to a lesser extent, with blood pressure and uric acid concentration. This analysis pointed out that BMI was a stronger independent predictor of all cardiovascular disease risk factors than fasting insulin. When subjects were categorized according to the number of metabolic and haemodynamic disorders occurring within the same individual, subjects with multiple disorders (i.e. three or four) had higher plasma insulin levels than those with none or few disorders, even after adjusting for BMI, WHR and behavioural variables (F =4.0; P <0.01). These results indicate that hyperinsulinaemia is already associated with a cluster of cardiovascular disease risk factors in young adulthood, the strongest independent association being with plasma triglycerides.     

Plasma concentration of IGF-I is independently associated with insulin sensitivity in subjects with different degrees of glucose tolerance

OBJECTIVE: We studied the relationships between plasma IGF-I concentrations and insulin sensitivity in subjects with various degrees of glucose tolerance. RESEARCH DESIGN AND METHODS: A total of 357 nondiabetic subjects, 54 subjects with impaired glucose tolerance and 98 newly diagnosed type 2 diabetic subjects, were consecutively recruited, and anthropometric and biochemical characteristics were collected. RESULTS: IGF-I concentrations were negatively correlated with age, BMI, waist-to-hip ratio, triglyceride levels, and systolic and diastolic blood pressure. IGF-I concentrations were positively correlated with HDL cholesterol and homeostasis model assessment of insulin sensitivity (HOMA-S). The correlations remained significant after adjusting for sex, age, and BMI. Correlations for HOMA-S with these metabolic and anthropometric variables were of a similar degree and direction to those for IGF-I concentrations. Stepwise linear regression analysis in a model, which included well-known modulators of insulin sensitivity such as sex, age, BMI, glucose tolerance status, family history of diabetes, waist-to-hip ratio, systolic and diastolic blood pressure, HDL cholesterol, and triglyceride levels, revealed that IGF-I concentrations were independently associated with insulin sensitivity accounting for 10.8% of its variation (P < 0.0001). IGF-I concentrations were significantly lower in subjects with World Health Organization (WHO)-defined metabolic syndrome compared with subjects without metabolic syndrome (P < 0.0001). Logistic regression analysis showed that each unit increase in log-transformed IGF-I concentrations was associated with a 90.5% reduction in the risk of WHO-defined metabolic syndrome. CONCLUSIONS: These data indicate that IGF-I has the characteristics to be a marker for the insulin resistance syndrome. This suggests that low IGF-I levels may be a useful marker for identifying subjects at risk for cardiovascular disease.     

Familial clustering for features of the metabolic syndrome: the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study

OBJECTIVE: Metabolic syndrome-related traits (obesity, glucose intolerance/insulin resistance, dyslipidemia, and hypertension) have been shown to be genetically correlated. It is less clear, however, if the genetic correlation extends to novel risk factors associated with inflammation, impaired fibrinolytic activity, and hyperuricemia. We present a bivariate genetic analysis of MetS-related traits including both traditional and novel risk factors. RESEARCH DESIGN AND METHODS: Genetic correlations were estimated using a variance components procedure in 1,940 nondiabetic white individuals from 445 families in the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study. Twelve MetS-related traits, including BMI, waist circumference, blood pressure, white blood cell count, fasting serum triglycerides, HDL cholesterol, insulin, glucose, plasminogen activator inhibitor-1 antigen, uric acid, and C-reactive protein, were measured and adjusted for covariates, including lifestyle variables. RESULTS: Significant genetic correlations were detected among BMI, waist circumference, HDL cholesterol, triglycerides, insulin, and plasminogen activator inhibitor-1 antigen and between uric acid and all of the above variables except insulin. C-reactive protein and white blood cell count were genetically correlated with each other, and both showed significant genetic correlations with waist circumference and insulin. Fasting glucose was not significantly genetically correlated with any of the other traits. CONCLUSIONS: These results suggest that pleiotropic effects of genes or shared family environment contribute to the familial clustering of MetS-related traits.     

Sagittal abdominal diameter is a strong anthropometric marker of insulin resistance and hyperproinsulinemia in obese men

OBJECTIVE: It is clinically important to find noninvasive markers of insulin resistance and hyperproinsulinemia because they both predict cardiovascular and diabetes risk. Sagittal abdominal diameter (SAD) or "supine abdominal height" is a simple anthropometric measure previously shown to predict mortality in men, but its association with insulin resistance and hyperproinsulinemia is unknown. RESEARCH DESIGN AND METHODS: In a common high-risk group of 59 moderately obese men (aged 35-65 years, BMI 32.6 +/- 2.3 kg/m(2)), we determined anthropometry (SAD, BMI, waist girth, and waist-to-hip ratio [WHR]); insulin sensitivity (euglycemic-hyperinsulinemic clamp); and plasma concentrations of intact proinsulin, specific insulin, C-peptide, glucose, and serum IGF binding protein-1 (IGFBP-1). To compare SAD with other anthropometric measures, univariate and multiple regression analyses were used to determine correlations between anthropometric and metabolic variables. RESULTS: SAD showed stronger correlations to all measured metabolic variables, including insulin sensitivity, than BMI, waist girth, and WHR. SAD explained the largest degree of variation in insulin sensitivity (R(2) = 0.38, P < 0.0001) compared with other anthropometric measures. In multiple regression analyses, including all anthropometric measures, SAD was the only independent anthropometric predictor of insulin resistance (P < 0.001) and hyperproinsulinemia (P < 0.001). CONCLUSIONS: In obese men, SAD seems to be a better correlate of insulin resistance and hyperproinsulinemia (i.e., cardiovascular risk) than other anthropometric measures. In overweight and obese individuals, SAD could represent a simple, cheap, and noninvasive tool that could identify the most insulin resistant in both the clinic and clinical trials evaluating insulin sensitizers. These results need confirmation in larger studies that also include women and lean subjects.     

Salt sensitivity correlates positively with insulin sensitivity in healthy volunteers

BACKGROUND: The aim of the study was to assess the relationship between insulin sensitivity and salt sensitivity in healthy subjects who display a wide range of insulin sensitivity. As a secondary objective, we assessed the relationship between salt sensitivity and the other characteristics of the insulin resistance syndrome. STUDY DESIGN: Forty-seven normotensive volunteers (age 34 +/- 15 years) with a normal glucose tolerance test were selected. We measured insulin sensitivity using the hyperinsulinaemic euglycaemic clamp (50 mU kg-1 h-1), blood pressure, waist-to-hip ratio, fasting insulin levels, serum lipids and uric acid levels. In a subset of 21, representing a wide range of insulin sensitivity, salt sensitivity was determined as the difference in mean arterial blood pressure (MAP) at the end of a high-salt diet (10 g of NaCl per day for 1 week) vs. a low-salt diet (2 g of NaCl per day for 1 week). RESULTS: Insulin sensitivity (M/I value, range 0.49-4.41 mg kg-1 min-1 per pmol L-1 x 100) was negatively correlated with MAP (r = -0.54, P < 0. 001) and waist-to-hip ratio (r = - 0.59, P < 0.001) but positively correlated with salt sensitivity (r = 0.47, P = 0.03). Salt sensitivity also correlated with high-density lipoprotein (HDL)-cholesterol (r = 0.46, P = 0.038) but not with waist-to-hip ratio, fasting insulin levels, low-density lipoprotein cholesterol, serum triglycerides or serum uric acid. CONCLUSIONS: In healthy normotensive subjects who display a wide range of insulin sensitivity, as measured with the euglycaemic clamp technique, salt sensitivity correlates positively with insulin sensitivity and HDL-cholesterol, but not with the other characteristics of the insulin resistance syndrome.     

葛根素对急性冠状动脉综合征患者胰岛素抵抗及纤溶活性的影响

目的:探讨葛根素对急性冠状动脉综合征(ACS)患者胰岛素抵抗(IR)及纤溶活性异常的影响.方法:63例ACS患者分为常规治疗组(30例)和葛根素治疗组(33例).葛根素治疗组于常规治疗基础上加用葛根素500 mg静脉滴注,每日1次,3周为1个疗程.均于治疗前及治疗结束时检测空腹血糖(FBG)、空腹胰岛素(FINS)、纤溶指标,计算胰岛素敏感性指数(ISI);并行静脉闭塞试验(VOT).选择30例健康人作为正常对照组.结果:与正常对照组比较,ACS患者FINS浓度增高,ISI降低,VOT前后组织型纤溶酶原激活物(t-PA)活性降低,纤溶酶原激活物抑制物-1(PAI1)活性升高,P均<0.01.葛根素组治疗后,FINS浓度降低,ISI增高,VOT前后t-PA活性增高,PAI-1活性下降(P<0.05或P<0.01).常规组治疗前及葛根素组治疗后FINS、ISI与PAI-1及VOT后t-PA活性之间呈线性相关(P<0.05或P<0.01).结论:葛根素可改善ACS患者的IR及与IR密切相关的纤溶活性异常.     

血清铁蛋白与2型糖尿病关系的研究

目的探讨血清铁蛋白与2型糖尿病的关系。方法对80例2型糖尿病患者以及69例健康体检者分别测定身高、体重、腰围、臀围、血压;空腹血糖、口服75 g葡萄糖粉测量2小时血糖、空腹胰岛素、血清铁蛋白、总胆固醇、甘油三酯、高密度脂蛋白、低密度脂蛋白及C反应蛋白浓度。计算体重指数、腰臀围比及胰岛素抵抗指数。结果与对照组相比,初诊的2型糖尿病患者具有较高的BMI、WHR、FINS、TG、C-RP以及SBP水平(P<0.05);HOMA-IR明显升高(P<0.05);较低的HDL-C水平(P<0.05);而TC、LDL-C水平及DBP无明显差异(P>0.05);糖尿病组不论男性与女性SF浓度明显高于对照组(P<0.05)。通过直线相关分析可知,经对数转换后的2型糖尿病患者SF与TC、TG、LDL-C、C-RP呈正相关(P<0.05);与FBG、PBG、HOMR-IR及DBP显著正相关(P<0.01);与HDL-C呈负相关(P<0.05);与SBP、BMI、WHRF、INS非线性关系。经多因素逐步回归分析发现血清铁蛋白是参与HOMR-IR的独立变量。结论本研究证实2型糖尿病患者体内铁超负荷;而铁超负荷可能是导致胰岛素抵抗,促进糖尿病发生的许多重要的危险因素之一;并且血清铁蛋白可以预测糖尿病代谢控制程度。     

Liver fat content measured by magnetic resonance spectroscopy at 3.0 tesla independently correlates with plasminogen activator inhibitor-1 and body mass index in type 2 diabetic subjects

We measured liver fat content by 3-Tesla magnetic resonance spectroscopy (MRS) in 34 non- to mild obese Japanese subjects with type 2 diabetes, who were not complicated with any liver diseases including clinical fatty liver (liver/spleen ratio of computed tomography [CT] < 0.9) and were not being treated with oral hypoglycemic agents, insulin, or lipid-lowering agents, and analyzed the relationship between liver fat content and body composition and plasma metabolite. The liver fat content is significantly correlated with variables relating to obesity (body mass index [BMI], body weight, fat mass, waist to hip ratio, visceral fat area, subcutaneous fat area, and serum triglyceride), insulin resistance (fasting plasma insulin and homeostasis model assessment of insulin resistance [HOMA-IR]), adipocytokines (serum plasminogen activator inhibitor-1 [PAI-1] and leptin), and serum cholinesterase, but not CT liver/spleen ratio, which is correlated only with fasting plasma glucose, BMI, and HOMA-IR. Multiple regression analysis revealed that the liver fat content is independently associated with serum PAI-1 level (p < 0.001) and BMI (p < 0.05), but not visceral fat area. MRS is a more sensitive method for quantifying liver fat content than CT in type 2 diabetic subjects with non- to mild obesity and without clinical fatty liver.     

罗格列酮对2型糖尿病患者血浆tPA和PAI1活性的影响

目的:运用胰岛素增敏剂罗格列酮治疗2型糖尿病患者,观察罗格列酮对2型糖尿病患者血浆tPA和PAI1活性水平的影响。方法:48例2型糖尿病患者,口服罗格列酮(文迪雅)4mg/d,共12周,观察治疗前后的血浆tPA和PAI1活性、血糖和胰岛素等,计算胰岛素敏感指数和胰岛素抵抗指数,并将各指标进行分析比较。结果:罗格列酮治疗后2型糖尿病患者血浆tPA活性升高(P<0.05),PAI1活性及PAI1/tPA活性比值降低(P<0.05,P<0.01)。血糖、胰岛素水平降低(均P<0.05);胰岛素敏感指数明显升高(P<0.05);胰岛素抵抗指数降低(P<0.05)。结论:罗格列酮在降低血糖、改善胰岛素抵抗、提高胰岛素敏感指数的同时,能增强糖尿病患者纤溶系统的活性,对心血管起到保护作用。     

肾病综合征患者血浆脂蛋白(a)水平与部分纤溶指标活性的关系

目的研究肾病综合征患者血浆脂蛋白(a)与部分纤溶指标活性的关系。方法应用酶联免疫吸附试验(ELISA)分别测定60例肾病综合征患者及51名健康对照者的血浆脂蛋白(a)浓度,并以底物显色法测定其组织型纤溶酶原激活剂(tPA)及其抑制物(PAI)活性。结果肾病综合征患者血浆脂蛋白(a)浓度和PAI活性明显升高,tPA活性明显降低;脂蛋白(a)浓度与血浆尿素氮水平、PAI活性均呈正相关;脂蛋白(a)浓度与tPA活性呈负相关。结论肾功能对血浆脂蛋白(a)浓度起一定的调节作用,脂蛋白(a)水平的升高与纤溶活性低下有关。     

Increased intimal-medial thickness in newly detected type 2 diabetes: risk factors.

OBJECTIVE: To examine carotid intimal-medial thickness (IMT) and its determinants in newly detected type 2 diabetic subjects, classified according to the new criteria of the American Diabetes Association, in comparison with age- and sex-matched control subjects with normal glucose tolerance. RESEARCH DESIGN AND METHODS: This study was case-controlled, with matched pairs for 71 newly diagnosed type 2 diabetic individuals. Subjects aged 40-70 years were recruited from a risk population for diabetes seen in the Risk Factors in IGT for Atherosclerosis and Diabetes (RIAD) Study. Standard risk factors, 75-g oral glucose tolerance test with real insulin, proinsulin, and C-peptide, and ultrasound measurement of the IMT of the common carotid artery were performed. RESULTS: The diabetic subjects, both men and women, displayed carotid intimal-medial thickening, even in the subgroup with fasting plasma glucose between 7.0 and 7.8 mmol/l. HbA1c was significantly increased in the diabetic patients (6.33 vs. 5.48%). Insulin, proinsulin, and C-peptide were also significantly higher. Among the coronary risk factors, triglycerides and plasminogen activator inhibitor were significantly increased. After age and sex adjustment. IMT in the diabetic group was correlated to triglycerides and the total-to-HDL cholesterol ratio. In the total group, IMT was significantly correlated to blood pressure, 2-h glucose in oral glucose tolerance testing, triglycerides, albuminuria, and the total-to-HDL cholesterol ratio, and inversely correlated to HDL cholesterol. No independent determinant of IMT was found in the diabetic group by multivariate analysis. CONCLUSIONS: Newly detected type 2 diabetic patients exhibit a higher degree of early atherosclerosis than normal glucose-tolerant subjects matched for age and sex. Our data suggest that hyperglycemia, together with a clustering of risk factors, and in particular dyslipidemia, may cause intimal-medial thickening in the early phases of diabetes.     

The metabolic syndrome defined by factor analysis and incident type 2 diabetes in a chinese population with high postprandial glucose

OBJECTIVE: The aim of this study was to examine how the major components of the metabolic syndrome relate to each other and to the development of diabetes using factor analysis. RESEARCH DESIGN AND METHODS: The screening survey for type 2 diabetes was conducted in 1994, and a follow-up study of nondiabetic individuals at baseline was carried out in 1999 in the Beijing area. Among 934 nondiabetic and 305 diabetic subjects at baseline, factor analysis was performed using the principle components analysis with varimax orthogonal rotation of continuously distributed variables considered to represent the components of the metabolic syndrome. Fasting insulin was used as a marker for insulin resistance. Of the 559 subjects without diabetes at baseline, 129 developed diabetes during the 5-year follow-up. Factors identified at baseline were used as independent variables in univariate and multivariate logistic regression models to determine risk factor clusters predicting the development of diabetes. RESULTS: Four factors were identified in nondiabetic and diabetic subjects. Fasting insulin levels, BMI, and waist-to-hip ratio were associated with one factor. Systolic and diastolic blood pressures were associated with the second factor. Two-hour postload plasma glucose (2-h PG) and serum insulin and fasting plasma glucose were associated with the third factor. Serum total cholesterol and triglycerides were associated with the fourth factor. The first and the third factors predicted the development of diabetes. In diabetic patients at baseline, the combination of systolic and diastolic blood pressure was the most important factor, and urinary albumin excretion rate clustered with fasting and 2-h PG levels. CONCLUSIONS: Insulin resistance alone does not underlie all features of the metabolic syndrome. Different physiological processes associated with various components of the metabolic syndrome contain unique information about diabetes risk. Microalbunuria is more likely to be a complication of type 2 diabetes or hypertension than a marker for the metabolic syndrome.     

Plasminogen activator inhibitor-1 4G/5G polymorphism is associated with metabolic syndrome parameters in Malaysian subjects

The plasminogen activator inhibitor-1 4G/5G and tissue plasminogen activator Alu-repeat insertion/deletion polymorphisms might be genetic determinations of increased or decreased of their plasma activities. The aim of this study was to investigate the association of plasminogen activator inhibitor-1 4G/5G and tissue plasminogen activator Alu-repeat I/D polymorphisms with metabolic syndrome parameters in normal Malaysian subjects and to assess the impact of these polymorphisms on their plasma activities and antigens. The genetic polymorphisms were genotyped in 130 normal subjects. In addition, the plasma activities and antigens of plasminogen activator inhibitor-1 and tissue plasminogen activator as well as levels of insulin, glucose, and lipid profile at fasting state were investigated. The subjects with homozygous 4G/4G showed association with an increased triglyceride (p = 0.007), body mass index (p = 0.01) and diastolic blood pressure (p = 0.03). In addition, the plasminogen activator inhibitor-1 4G/5G polymorphism modulates plasma plasminogen activator inhibitor-1 activity and antigen and tissue plasminogen activator activity (p = 0.002, 0.014, 0.003) respectively. These results showed that, the plasminogen activator inhibitor-1 4G/5G polymorphism is associated with metabolic syndrome parameters, plasminogen activator inhibitor-1 and tissue plasminogen activator activities in Malaysian subjects, and may serve to increase the risk of type 2 diabetes and cardiovascular disease in Malaysian subjects.     

Diabetes and impaired fasting glycemia in a rural population of Bangladesh

OBJECTIVE: To determine the prevalence of type 2 diabetes and impaired fasting glycemia (IFG) in a rural population of Bangladesh. RESEARCH DESIGN AND METHODS: A cluster sampling of 4,923 subjects >/=20 years old in a rural community were investigated. Fasting plasma glucose, blood pressure, height, weight, and girth of waist and hip were measured. BMI and waist-to-hip ratio (WHR) were calculated. Total cholesterol, triglycerides, and HDL cholesterol were also estimated. We used the 1997 American Diabetes Association diagnostic criteria. RESULTS: The crude prevalence of type 2 diabetes was 4.3% and IFG was 12.4%. The age-standardized prevalence of type 2 diabetes (95% CI) was 3.8% (3.12-4.49) and IFG was 13.0% (11.76-14.16). The subjects with higher family income had significantly higher prevalence of type 2 diabetes (5.9 vs. 3.5%, P < 0.001) and IFG (15.6 vs. 10.8%, P < 0.001) than those with lower income. Employing logistic regression in different models, we found that wealthy class, family history of diabetes, reduced physical exercise, and increased age, BMI, and WHR were the important predictors of diabetes. Total cholesterol, triglycerides, and HDL cholesterol showed no association with diabetes and IFG. CONCLUSIONS: The prevalence of diabetes and IFG in the rural population was found to be on the increase compared with the previous reports of Bangladesh and other Asian studies. Older age, higher obesity, higher income, family history of diabetes, and reduced physical activity were proved significant risk factors for diabetes and IFG, whereas plasma lipids showed no association with diabetes and IFG. Further study may address whether diabetes is causally associated with insulin deficiency or insulin resistance.     

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.     

Association of serum proinsulin with hormone replacement therapy in nondiabetic older women: the Rancho Bernardo Study

OBJECTIVE: One putative benefit of hormone replacement therapy (HRT) is a reduced risk of diabetes or reduced fasting glucose level. We report here the association of HRT with proinsulin, insulin, and fasting and postchallenge glucose levels in older adults. RESEARCH DESIGN AND METHODS: Current HRT use was validated and cross-sectionally compared with diabetes-related variables in 785 women without diabetes by history or glucose tolerance test. RESULTS: Median age was 72 years (range 50-97); median value of fasting plasma glucose, postchallenge plasma glucose, and proinsulin was 5.08 mmol/l, 6.93 mmol/l, and 9.3 pmol/l, respectively. In age-adjusted comparisons, current HRT use was associated with significantly lower fasting plasma glucose and higher postchallenge plasma glucose compared with never/previous HRT use, as well as with lower LDL and higher HDL cholesterol and higher triglycerides. Fasting and postchallenge intact insulin did not differ by HRT group, but proinsulin was significantly lower in current HRT users than in previous and never HRT users. The significant association between proinsulin and HRT status persisted after adjustment for age, waist-to-hip ratio, pulse pressure, LDL-to-HDL cholesterol ratio, triglycerides, fasting and postchallenge glucose, and intact insulin. CONCLUSIONS: Reduced fasting and increased 2-h glucose replicate findings in a randomized clinical trial. The proinsulin effect has not been previously reported. Decreased fasting glucose and proinsulin levels in current HRT use suggest a potential antidiabetes effect of HRT. Increased postchallenge glucose in HRT, however, suggests insulin resistance and would be expected to increase the risk of heart disease.     

Insulin resistance, lipid and fatty acid concentrations in 867 healthy Europeans. European Group for the Study of Insulin Resistance (EGIR)

BACKGROUND: Insulin resistance, dyslipidaemia and abnormal nonesterified fatty acid (NEFA) metabolism are features of the 'metabolic syndrome', but the mechanisms of these relationships are uncertain. MATERIALS AND METHODS: We studied associations between insulin resistance and lipoprotein concentrations by retrospective analysis of euglycaemic hyperinsulinaemic clamp data from 867 normoglycaemic subjects in 21 European centres. Data on NEFA concentrations were available in a subgroup of 541 subjects from 9 clinical centres. These subjects' characteristics do not vary significantly from those of the whole cohort. RESULTS: After adjustment for the effects of age, sex, obesity and intercentre variability, regression analysis showed relationships between triglycerides and markers of insulin sensitivity. There were significant correlations between triglycerides and fasting plasma glucose (P < 0.0001), fasting plasma insulin (P < 0.0001) and mean glucose infusion rate at steady state (M-value, P < 0.0001). Indices of insulin resistance were related to NEFA concentrations. Fasting NEFA were negatively correlated with the M-value (P < 0.0001). Non-esterified fatty acids at steady state were positively correlated with fasting markers of insulin resistance: fasting plasma glucose (P < 0.05), fasting plasma insulin (P < 0.005) and negatively correlated with the M-value (P < 0.0005). There were relationships between fasting concentrations of plasma lipids and of NEFAs. Non-esterified fatty acids at steady state correlated with fasting triglycerides (P < 0.0001), but not with any of the other plasma lipoprotein concentrations. The associations of fasting triglycerides with the M-value and with NEFAs at steady state were independent of each other. All these associations were independent of obesity and geographical location CONCLUSION: The results in this large cohort of healthy European subjects suggest that triglyceride concentrations depend upon both insulin's gluco-regulation (estimated by glucose uptake) and antilipolytic insulin action (measured by NEFA levels) during an euglycaemic clamp.     

Relationship between fibrinolytic and metabolic variables: a study in patients attending a lipid clinic

We investigated the relationship between plasma levels of metabolic and fibrinolytic variables in 163 fasted patients attending a lipid clinic. Of these patients, 118 had hypertriglyceridaemia (HTG) and 45 had normotriglyceridaemia (NTG). In HTG, basal fibrinolytic activity, ie tissue plasminogen activator (t-PA) activity, was impaired as a result of high plasminogen activator inhibitor type 1 (PAI-1) antigen and activity. Multiple stepwise regression analysis identified insulin and triglyceride levels as independent determinants of plasma PAI-1 levels (R2 = 0.18; P = 0.0001). When the patients were stratified into tertiles according to their levels of triglyceride and insulin, PAI-1 antigen levels were found to increase with rising levels of triglyceride in each insulin tertile. In contrast, the increase of PAI-1 with rising insulin levels was evident in the highest triglyceride tertile. In addition, subjects in the lowest tertile of both triglyceride and insulin had the lowest PAI-1 antigen levels, and subjects in the highest tertile of both triglyceride and insulin had the highest levels of PAI-1. Both basal and stimulated levels of t-PA antigen were significantly higher in HTG than in NTG. Multiple stepwise regression analysis identified triglyceride level as the sole major determinant of t-PA antigen levels (R2 = 0.13; P = 0.00003). The observation that both insulin and triglycerides correlate with PAI-1, whereas triglycerides were involved only in the increased secretion of t-PA, suggests that these two proteins are regulated by different mechanisms.