Postload Plasma Insulin Research Articles

Adiponectin and leptin in Afro-Caribbean men and women with HIV infection: Association with insulin resistance and type 2 diabetes

Aim Insulin resistance and type 2 diabetes (T2D) are commonly seen in human immunodeficiency virus (HIV) infection and are related to antiretroviral therapy. Adiponectin and leptin secreted by adipocytes are both linked to body-fat distribution and insulin sensitivity. The present study aimed to assess the prevalence of insulin resistance and T2D, and their association with adiponectin and leptin, in Afro-Caribbean men and women with HIV infection. Methods This cross-sectional study was conducted in an unselected sample of 237 HIV-1-infected patients. Clinical and metabolic parameters were measured, including fasting and postload plasma insulin, and circulating adiponectin and leptin levels. Insulin resistance was estimated by homoeostasis model assessment (HOMA-IR). Adjusted multiple logistic regressions were used to estimate the association of insulin resistance with adipokine levels and patients’ characteristics. Results A total of 132 men (mean age: 49 years) and 105 women (mean age: 48 years) were included in the study. Prevalences of T2D and insulin resistance were higher in women than in men [16.2% vs 8.3% ( P = 0.06) and 24% vs 9.9% ( P < 10 −3), respectively]. Abdominal obesity was found in 47% of women and in 7% of men ( P < 10 −4). Insulin resistance was independently associated with adiponectin in women and with leptin in men. Conclusion Insulin resistance is frequent in Afro-Caribbean women with HIV infection. Overweight and obesity are major risk factors in such a population. Systematic screening for insulin resistance should be carried out in this population, which has a high prevalence of T2D.

The Effect of Water-Based Exercise on Glucose and Insulin Response in Overweight Women: A Pilot Study

The aim of this study was to investigate the effectiveness of a 12-week moderate intensity, water-based circuit-type training intervention on glucose and insulin responses in overweight women with normal or impaired glucose tolerance. Fifteen overweight women (body mass index [BMI] > 25 kg/m(2)) with normal glucose tolerance (NGT; n = 7) or impaired glucose tolerance (IGT; n = 8) were recruited for this study. All women completed a 12-week training intervention utilizing a combination of aerobic and resistance exercises in an aquatic environment, 3 days per week and 60 min per session at 70-75% mode-specific maximum heart rate. A standard 75-g oral glucose tolerance test (OGTT) was administered pre- and post-intervention, from which fasting and post-load plasma insulin and glucose levels were assessed. Following the 12-week period, fasting insulin levels had decreased by 44% and 2-h glucose by 30.4% in the group with IGT. Waist circumference (WC) had decreased by 5.3% in this group at the end of the intervention. Only WC and waist-to-hip ratio (WHR) decreased (6.0% and 5.5%, respectively) following the intervention in the NGT group. Moderate intensity, water-based circuit-type exercises appear to be an effective exercise modality to improve glucose and insulin response to a glucose challenge in overweight women with IGT.

Insulin sensitivity: Gender-related differences in subjects with normal glucose tolerance

Background and aims To verify whether age and the perimenopausal state may herald the onset of the metabolic syndrome (MS) in females as compared to age-matched males, we studied subjects with normal glucose tolerance, according to ADA definition. Methods and results In 368 eligible subjects subdivided into three age groups we measured insulin sensitivity by ISI-glycaemia, resistance by HOMA-IR, computed, during OGTT, from fasting and 2-h post-load plasma insulin and glucose concentrations. The significance of differences was tested between different age groups and between males and females within corresponding age groups. Insulin sensitivity fell slightly and insulin resistance rose significantly in the perimenopausal group as compared to younger and older female patients, and compared to men of the same age. This pattern remains after excluding patients with high blood pressure, and after adjusting for WHR and BMI by multivariate analysis. HOMA-IR averaged 2.9±1.8 in females, 2.2±1.2 in men aged 45–54 years ( p<0.02), while in the other age groups insulin resistance was higher in men. Conclusion The onset of MS during the menopause is associated with a physiological shift in insulin resistance occurring even in normal glucose tolerant subjects, suggesting that it may depend upon critical metabolic changes occurring specifically in that age period.

Lipoprotein candidate genes for multivariate factors of the insulin resistance syndrome: a sib-pair linkage analysis in women twins.

The insulin resistance syndrome (IRS) is characterized by a combination of interrelated coronary heart disease risk factors, including low high-density lipoprotein cholesterol (HDLC) levels, obesity and increases in triglyceride (TG), systolic and diastolic blood pressure (BP), small low-density lipoprotein particles (LDL-size), and fasting and postload plasma insulin and glucose. Using factor analysis, we previously identified multivariate factors based on data from women participating in the Kaiser Permanente Women Twins Study: 1) Weight/Fat, 2) Insulin/Glucose, 3) Lipids, and 4) BP. The purpose of this study is to evaluate evidence for genetic linkage between the multivariate factors and candidate genes. Quantitative sib-pair analysis based on the factor scores with markers for 9 candidate genes was carried out based on data from 126 pairs of dizygotic (DZ) women twins from the second exam of the Kaiser Permanente Women Twins study. Suggestive evidence for linkage was found for the Weight/fat factor and the Apo E gene (p = 0.01), and stronger evidence for linkage with the Lipid factor and the cholesterol ester transfer protein (p = 0.002) gene. Therefore, the CETP gene appears to influence covariation in LDL size, TG, and HDL, and may account for a portion of the well-established statistical and metabolic associations observed between these risk factors.

Lipoprotein Candidate Genes for Multivariate Factors of the Insulin Resistance Syndrome: A Sib-pair Linkage Analysis in Women Twins

AbstractThe insulin resistance syndrome (IRS) is characterized by a combination of interrelated coronary heart disease risk factors, including low high-density lipoprotein cholesterol (HDLC) levels, obesity and increases in triglyceride (TG), systolic and diastolic blood pressure (BP), small low-density lipoprotein particles (LDL-size), and fasting and postload plasma insulin and glucose. Using factor analysis, we previously identified multivariate factors based on data from women participating in the Kaiser Permanente Women Twins Study: 1) Weight/Fat, 2) Insulin/Glucose, 3) Lipids, and 4) BP. The purpose of this study is to evaluate evidence for genetic linkage between the multivariate factors and candidate genes. Quantitative sib-pair analysis based on the factor scores with markers for 9 candidate genes was carried out based on data from 126 pairs of dizygotic (DZ) women twins from the second exam of the Kaiser Permanente Women Twins study. Suggestive evidence for linkage was found for the Weight/fat factor and the Apo E gene (p= 0.01), and stronger evidence for linkage with the Lipid factor and the cholesterol ester transfer protein (p= 0.002) gene. Therefore, the CETP gene appears to influence covariation in LDL size, TG, and HDL, and may account for a portion of the well-established statistical and metabolic associations observed between these risk factors.

Serum insulin-like growth factor-I level is independently associated with coronary artery disease progression in young male survivors of myocardial infarction: beneficial effects of bezafibrate treatment

OBJECTIVESWe investigated whether the effect of bezafibrate on progression of coronary atherosclerosis in the BEzafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) was related to insulin-like growth factor (IGF)-I and glucose-insulin homeostasis.BACKGROUNDBECAIT, the first double-blind, placebo-controlled, randomized, serial angiographic trial of a fibrate compound, demonstrated that progression of focal coronary atherosclerosis in young patients after infarction could be retarded by bezafibrate treatment.METHODSThe treatment effects on serum concentrations of IGF-I and insulin-like growth factor binding protein (IGFBP)-1, as well as on basal and postload glucose and insulin levels, were examined, and on-trial determinations were related to the angiographic outcome measurements.RESULTSBezafibrate treatment resulted in a significant reduction of serum IGF-I levels, both at two and five years, and on-trial serum IGF-I levels were directly related to changes in both minimal lumen diameter (r = 0.25, p < 0.05) and mean segment diameter (r = 0.29, p < 0.05). In contrast, none of the available indexes of insulin resistance (homeostasis model assessment estimate, basal and postload plasma insulin concentrations and serum IGFBP-1 levels) were related to the angiographic changes, nor were they significantly affected by bezafibrate treatment. Multiple stepwise regression analysis showed that the relation between on-trial serum IGF-I level and coronary artery disease (CAD) progression was independent of baseline angiographic score, age, body mass index, serum lipoprotein and plasma fibrinogen concentrations and measures of glucose–insulin homeostasis.CONCLUSIONSIGF-I could be implicated in the progression of premature CAD, and a reduction of serum IGF-I concentration could account partly for the effect of bezafibrate on progression of focal coronary atherosclerosis.

Heritability of factors of the insulin resistance syndrome in women twins.

The insulin resistance syndrome (IRS) is characterized by a combination of interrelated coronary heart disease (CHD) risk factors, including low high-density lipoprotein cholesterol (HDL-C) levels, obesity and increases in triglyceride (TG), blood pressure, small low-density lipoprotein particles (LDL), and both fasting and postload plasma insulin and glucose. Using factor analysis, we previously identified 3 uncorrelated factors that explained 66% of the variance among these variables, based on data from women participating in examination 2 of the Kaiser Permanente Women Twins Study in Oakland, CA during 1989-1990. The factors were interpreted as: 1) body mass/fat distribution, 2) insulin/glucose, and 3) lipids: TG, HDL-C, LDL peak particle diameter. In this analysis, heritability of each of the factors was estimated based on data from 140 monozygotic and 96 dizygotic pairs of non-diabetic women twins. Heritability estimates were calculated using the classical approach, the analysis of variance (ANOVA) approach, and the maximum likelihood approach. For the body mass/fat distribution factor heritability estimates suggest moderate genetic influences; 0.61 (P < 0.001), 0.14 (P > 0.05), and 0.71 (P < 0.001), respectively. The insulin/glucose factor appeared to be highly heritable, with estimates of 0.87, 0.92, and 0.57 (all P < 0.001), respectively. The heritability estimates for the lipid factor were moderate and consistent across methods: 0.25 (P < 0.10), 0.32 (P < 0.05), and 0.30 (P < 0.05), respectively. These results are consistent with genetic influences on each of the 3 "factors," and suggest that both genetic and environmental effects are involved in the clustering of IRS risk factors.

High-density lipoprotein: Relations to metabolic parameters and severity of coronary artery disease

The regulation of plasma high-density lipoprotein (HDL) cholesterol level by the joint influence of plasma lipoprotein lipids, lipoprotein lipase (LPL), hepatic lipase (HL), cholesteryl ester transfer protein (CETP), oral glucose tolerance, and postload plasma insulin and proinsulin levels was investigated in young postinfarction patients and healthy population—based control subjects. In addition, the association between HDL cholesterol and the number and severity of coronary stenoses previously reported in this cohort of young postinfarction patients was further investigated by analyzing the determinants and angiographic relations of HDL subclasses measured by gradient gel electrophoresis. The following parametres showed significant univariate relations with HDL choleterol level in the patient group: very—low-density lipoprotein (VLDL) cholesterol and triglyceride, low-density lipoprotein (LDL) triglyceride, and postload plasma insulin concentrations, preheparin plasma LPL mass, and postheparin plasma HL activity. In the control group, significant correlations with HDL cholesterol concentration in addition to those noted among the patients were found for body mass index (BMI), LDL cholesterol level postload plasma intact proinsulin concentration, and LPL activity in postheparin plasma. In contrast to the patients, no significant relations were noted for postload plasma insulin level and preheparin plasma LPL mass. Multiple stepwise regression analysis showed that 42% of the variability of HDL cholesterol in the patients could be accounted for by VLDL cholesterol concentration (29%), LDL triglyceride level (7%), and postheparin plasma HL activity (6%), whereas the corresponding figure in controls was 35% (VLDL cholesterol concentration [9%] and postheparin plasma HL activity [26%]). The strength of the relationships of HDL cholesterol and HDL subclasses to the coronary stenosis score was similar and statistically significant ( r = .25 to .36). When the metabolic parameters that correlated with HDl cholesterol and HDL subclass concentrations in univariate analysis were used as covariates, all relations to the coronary stenosis score disappeared. This clearly indicates that the influence of triglyceride-rich lipoproteins and lipolytic enzymes needs to be considered when assessing the association between HDL cholesterol and coronary artery disease (CAD).

Insulin and Cardiovascular Disease: Paris Prospective Study

The Paris Prospective Study is a long-term investigation of coronary heart disease (CHD) risk factors in a large population of working men. The baseline cohort included 7028 men, 6093 who had a 75-g oral glucose tolerance test with measurement of plasma insulin and glucose levels (0 and 2 h) and 125 who were known non-insulin-treated diabetic patients. After a mean follow-up of 11 yr, 126 deaths ascribed to CHD were reported. Major independent predictors of CHD death were blood pressure, smoking, plasma cholesterol level, and fasting and 2-h postload plasma insulin level. Impairment of glucose tolerance, including overt diabetes, did not rank as an independent predictor when other baseline variables were accounted for. In the subset of the baseline cohort who presented with impaired glucose tolerance or diabetes (n = 943), 26 died from CHD during the follow-up. The strongest independent predictor of subsequent CHD death in this subsample with abnormal glucose tolerance was plasma triglyceride level. In view of the accumulating evidence that hyperinsulinemia and hypertriglyceridemia generally occur in the same type of subjects, in relation to insulin resistance and central obesity, the epidemiological findings of the Paris Prospective Study and of other investigations support the hypothesis that a constellation of mild metabolic abnormalities may play a deleterious role with regard to cardiovascular disease risk.

Hyperinsulinaemia as a predictor of coronary heart disease mortality in a healthy population: the Paris Prospective Study, 15-year follow-up

The Paris Prospective Study is a long-term, large-scale study of the factors predicting coronary heart disease. The first follow-up examination included, for subjects not known as having diabetes mellitus, a 75 g oral glucose tolerance test with measurement of plasma insulin and glucose levels, fasting and 2 h post-load. Between 1968 and 1973, 6903 men aged 43-54 years were thus examined. Causes of death were ascertained within this group after 15 years of mean follow-up. The baseline variables were tested as predictors of death from coronary heart disease by a Cox regression analysis. Significant independent predictors of coronary heart disease death were: systolic blood pressure, number of cigarettes per day, plasma cholesterol level, and 2 h post-load plasma insulin level when entered as a categorical variable (below or above 452 pmol/l. i.e. the lower limit of the fifth quintile of the distribution). This dichotomization was performed to account for the non-linear univariate distribution of deaths with increasing post-load insulin values. Fasting plasma insulin level was not an independent predictor of death by coronary heart disease over this long-term follow-up. Levels of blood glucose were not significant independent predictors of death by coronary heart disease when plasma insulin levels were included in the model. The same applied to abnormalities of glucose tolerance when the 125 men with known non-insulin-treated diabetes at baseline were added to the group. Under the assumption that hyperinsulinaemia is a marker of insulin resistance, the results are consistent with the hypothesis that insulin resistance is associated with a higher risk of coronary heart disease mortality. However, it is doubtful that circulating insulin per se is a direct cause of arterial complications.

Relationship of glucose tolerance and plasma insulin to the incidence of coronary heart disease: results from two population studies in Finland.

The relationship of glucose tolerance to the incidence of coronary heart disease (CHD) has been investigated in two cohorts of Finnish men: 3267 men ages 40--59 yr from the Social Insurance Institution's (SII) Coronary Heart Disease Study and 1059 men ages 30--59 yr from the Helsinki Policemen Study. The relationship of plasma insulin level to the incidence of CHD was also investigated in the Helsinki Policemen Study. An oral glucose lead of 60, 75, or 90 g according to body surface area was used in both studies. In the SII Study, plasma glucose was determined from venous blood samples taken 1 h after glucose load. In the Helsinki Policemen Study, blood glucose was determined from venous blood samples taken at 0, 1, and 2 h, and at a 5-yr reexamination, plasma insulin was measured during OGTT at 0, 1, 2 h. In the SII Study cohort, the 4-yr mortality from CHD and the 4-yr incidence of nonfatal myocardial infarction (MI) did not show a definite relationship to 1-h postload plasma glucose. In the Helsinki Policemen Study cohort, the 5-yr incidence of "hard criteria" CHD (CHD death and nonfatal MI) was significantly related to high 1-h postload blood glucose level but not to fasting or 2-h postload blood glucose levels. 10-yr mortality from CHD was significantly higher in the top quintile of fasting and 1- and 2-h postload blood glucose levels, as was the incidence of "hard criteria" CHD. However, in multivariate analyses including age, systolic blood pressure, plasma cholesterol, and smoking, the blood glucose variables showed no statistically significant independent contribution in predicted risk of CHD. Univariate analyses by quintiles of plasma insulin levels measured at the 5-yr reexamination showed that the incidence of "hard criteria" CHD during the subsequent 5 yr was significantly higher in the top quintiles of fasting and 1-h and 2-h postload plasma insulin than in the combined lower quintiles. Multivariate analyses showed that the value of high 1-h or 2-h postload plasma insulin level for predicting CHD risk was independent of other risk factors, including blood glucose levels during OGTT.