Effects of tibolone or continuous combined oestradiol/norethisterone acetate on glucose and insulin metabolism.

Objective: To determine the effects of tibolone or oestradiol (E(2) )/norethisterone acetate (NETA) hormone replacement therapy on glucose and insulin metabolism in postmenopausal women.

Design: Single-centre double-blind placebo-controlled randomized clinical trial.

Subjects/methods: We randomized 105 healthy postmenopausal women to tibolone 2·5 mg daily, continuous combined oral E(2) 2 mg/NETA 1 mg daily or placebo over a 2-year study.

Growth differentiation factor-15 predicts mortality and morbidity after cardiac resynchronization therapy.

Aims: The aim of this study was to determine whether growth differentiation factor-15 (GDF-15) predicts mortality and morbidity after cardiac resynchronization therapy (CRT). Growth differentiation factor-15, a transforming growth factor-beta-related cytokine which is up-regulated in cardiomyocytes via multiple stress pathways, predicts mortality in patients with heart failure treated pharmacologically.

Methods And Results: Growth differentiation factor-15 was measured before and 360 days (median) after implantation in 158 patients with heart failure [age 68 +/- 11 years (mean +/- SD), left ventricular ejection fraction (LVEF) 23.

Randomized trial of effects of continuous combined HRT on markers of lipids and coagulation in women with acute coronary syndromes: WHISP Pilot Study.

Aims: Randomized trials have not demonstrated coronary heart disease benefit from hormone replacement therapy (HRT). We hypothesized that low-dose HRT may avoid harm.

Methods And Results: We studied the effects of HRT on lipids and coagulation in women with acute coronary syndromes.

Impaired insulin sensitivity as an independent risk factor for mortality in patients with stable chronic heart failure.

Objectives: The aim of this study was to determine the significance of insulin resistance as an independent risk factor for impaired prognosis in patients with chronic heart failure (CHF).

Background: In CHF, impaired insulin sensitivity (S(I)) indicates abnormal energy metabolism and is related to decreased exercise capacity and muscle fatigue. The relationship between insulin resistance (i.

Randomized trial of effects of estradiol in combination with either norethisterone acetate or trimegestone on lipids and lipoproteins in postmenopausal women.

Objective: This double-blind, randomized, multicenter study was designed to compare the blood lipid profiles in postmenopausal women after treatment with either a combined formulation containing estradiol (2 mg) and trimegestone (TMG 0.25 or 0.5 mg) or a standard hormone therapy (HT) containing estradiol and norethisterone acetate.

Hemostatic risk factors and insulin sensitivity, regional body fat distribution, and the metabolic syndrome.

Disturbances in the thrombotic and fibrinolytic systems are a feature of insulin resistance, obesity, and the metabolic syndrome. However, there are few studies in which these relationships have been explored in mainly asymptomatic individuals using sophisticated measures of insulin sensitivity and regional adiposity. Variables of the hemostatic system were measured in 106 men (aged 32-68 yr; body mass index, 20-34 kg/m(2)).

Effects of low and high dose oestradiol and dydrogesterone therapy on insulin and lipoprotein metabolism in healthy postmenopausal women.

Objective: Menopause diminishes insulin secretion and elimination, increases risk of diabetes and adversely affects lipoprotein metabolism. This study was undertaken to establish whether oral oestradiol plus dydrogesterone postmenopausal hormone therapy can modify these changes.

Design: Randomized prospective trial of postmenopausal women taking low dose therapy (1 mg/day oestradiol-17 beta with 5 or 10 mg/day dydrogesterone for days 17-28 of each cycle, n = 15) or high dose therapy (2 mg/day oestradiol-17 beta with 10 or 20 mg/day orally administered dydrogesterone, n = 9).

Randomized trial of effect of transdermal continuous combined hormone replacement therapy on cardiovascular risk markers.

Whether hormone replacement therapy (HRT) is beneficial for coronary heart disease (CHD) is controversial. We hypothesized that continuous combined transdermal HRT may have benefits on CHD risk markers without the potential adverse effects seen with certain other HRT regimens. Sixty apparently healthy postmenopausal women, aged 40-65 years, entered a prospective, double-blind, randomized, placebo-controlled clinical trial; 55 women completed the 6-month study.

Effects of short- and long-term growth hormone replacement on lipoprotein composition and on very-low-density lipoprotein and low-density lipoprotein apolipoprotein B100 kinetics in growth hormone-deficient hypopituitary subjects.

In this study, we concurrently examined the effects of 8 and 40 weeks of growth hormone replacement (GHR) on lipids, lipoprotein composition, low-density lipoprotein (LDL) size, very-low-density lipoprotein (VLDL) apolipoprotein (apo)B kinetics and LDL apoB kinetics. Eight weeks of GHR did not alter lipid profiles. Forty weeks of GHR increased high-density lipoprotein-cholesterol (HDL-C) concentration (P =.

Effects of oestrogen-only and oestrogen-progestogen replacement therapy upon circulating angiotensin I-converting enzyme activity in postmenopausal women.

Objective: Levels of angiotensin I-converting enzyme (ACE) in blood are associated with variation in cardiovascular disease risk. Serum ACE activity in women may be reduced by combined oestrogen-progestogen hormone replacement therapy (HRT). However, the relative contribution of each hormonal component to this observation is uncertain.

Effect of postmenopausal oestradiol and dydrogesterone therapy on lipoproteins and insulin sensitivity, secretion and elimination in hysterectomised women.

Objectives: To investigate in depth the metabolic effects of oestradiol-17 beta both alone and in combination with the progestagen dydrogesterone.

Methods: Fifteen hysterectomised postmenopausal women were studied before treatment and after 24 weeks taking oestradiol-17 beta alone (2 mg per day), then following a further 6 (oestrogen-alone phase) and 12 (oestrogen plus progestagen phase) weeks with inclusion of dydrogesterone (10 mg per day for days 17-28 of each 28 day cycle). Measurements at each visit included fasting serum lipid and lipoprotein concentrations, insulin sensitivity, secretion and elimination by modelling analysis of intravenous glucose tolerance test glucose, insulin and C-peptide concentrations, body fat distribution by dual-energy X-ray absorptiometry (DXA) and arterial function by carotid artery ultrasound.

Plasma total homocysteine concentrations are unrelated to insulin sensitivity and components of the metabolic syndrome in healthy men.

Plasma homocysteine levels are lowered by insulin and can be elevated in insulin-resistant states. However, it is uncertain whether homocysteine and insulin resistance or components of the metabolic (insulin resistance) syndrome are related in healthy individuals. Total homocysteine concentrations were measured by gas chromatography-mass spectrometry in samples from 100 male participants in the second follow-up cohort of the Heart Disease and Diabetes Risk Indicators in a Screened Cohort Study.

Non-invasive assessment of vascular function; paradoxical vascular response to intravenous glucose in coronary heart disease.

Background: In healthy individuals, insulin administration causes an increase in forearm blood flow which is dependent on the effects of insulin on the vascular endothelium. Glucose, administered as an intravenous bolus, produces a transient hyperinsulinaemic response. We hypothesized that the insulin response to an intravenous glucose challenge during the intravenous glucose tolerance test might lead to increases in forearm blood flow in healthy individuals, and that such a response might be altered in patients with coronary heart disease.

Hyperleptinemia as a component of a metabolic syndrome of cardiovascular risk.

In humans, production of the adipocyte-derived peptide leptin has been linked to adiposity, insulin, and insulin sensitivity. We therefore considered that alterations in plasma leptin concentrations could constitute an additional component of a metabolic syndrome of cardiovascular risk. To explore this hypothesis, we employed factor analysis, a multivariate statistical technique that allows reduction of large numbers of highly intercorrelated variables to composite, biologically meaningful factors.

Evidence for a role of tumor necrosis factor alpha in disturbances of triglyceride and glucose metabolism predisposing to coronary heart disease.

Elevated plasma levels of triglyceride-rich lipoproteins, a decreased high-density lipoprotein (HDL) cholesterol concentration, hyperinsulinemia, and impaired fibrinolytic function frequently aggregate in patients with premature coronary heart disease (CHD). Experimental studies suggest that the cytokine tumor necrosis factor alpha (TNFalpha) produced by adipocytes plays a part in the regulation of triglyceride and glucose metabolism. The present study examined whether TNFalpha is implicated in these metabolic and fibrinolytic disturbances in young postinfarction patients.

Third trimester fetal growth and measures of carbohydrate and lipid metabolism in umbilical venous blood at term.

Aim: To compare measures of carbohydrate and lipid metabolism in umbilical venous blood after birth at term in pregnancies with normal and retarded fetal growth during the third trimester.

Methods: Three groups of pregnancies reaching term, in which fetal growth had been prospectively monitored by repeated ultrasound measurements during the third trimester, were studied. Sequential fetal abdominal circumference measurements remained above the 10th centile in 42 (normal size, normal growth group), below the 10th centile but did not depart further than 1.

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 parameters showed significant univariate relations with HDL cholesterol 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.

Lipid and carbohydrate metabolic risk markers for coronary heart disease and blood pressure in healthy non-obese premenopausal women of different racial origins in the United Kingdom.

Metabolic risk markers for coronary heart disease (CHD) were determined in apparently healthy females of differing racial origins residing in the United Kingdom. The females were of black (n=122), Oriental (n=144), South Asian (n=128), and white (n=271) origin, premenopausal, non-obese, and aged 16-45 years. In comparison to whites, South Asians had lower serum high-density lipoprotein (HDL) cholesterol and HDL2 cholesterol and higher fasting and oral glucose tolerance test plasma insulin responses.

Association of insulin and insulin propeptides with an atherogenic lipoprotein phenotype.

A characteristic lipoprotein phenotype, including hypertriglyceridemia, a low high-density lipoprotein (HDL) cholesterol concentration, and a predominance of small, dense low-density lipoprotein (LDL) particles, is linked to insulin resistance and hyperinsulinemia. Individuals with these characteristics are supposed to be at increased risk of developing coronary heart disease (CHD). To address this issue further, relations between basal and postload glucose, insulin and insulin propeptide concentrations and subfractions of apolipoprotein (apo) B-containing lipoproteins were examined in 62 consecutive Swedish nondiabetic men who had experienced a first myocardial infarction before the age of 45.

Insulin, intact and split proinsulin, and coronary artery disease in young men.

Background: Glucose intolerance and hyperinsulinemia are common disturbances in nondiabetic men with premature coronary artery disease (CAD). To investigate the relation between insulin-like molecules and severity of coronary atherosclerosis, 62 consecutive nondiabetic men presenting with a first myocardial infarction before the age of 45 were studied along with 41 healthy, age-matched, male, population-based control subjects.

Methods And Results: Specific two-site immunoradiometric assays were used to distinguish intact proinsulin, (des 31,32) proinsulin, and "true" insulin in fasting plasma and during an oral glucose tolerance test (OGTT).

Hormone replacement therapy and serum angiotensin-converting-enzyme activity in postmenopausal women.

The mechanisms by which hormone replacement therapy (HRT) reduces the risk of coronary heart disease (CHD) are incompletely understood, but may include direct arterial effects. We examined the effect of oestrogen/progestagen HRT on serum angiotensin-converting-enzyme (ACE) activity in postmenopausal women. After 6 months, ACE activity was reduced by 20% (p < 0.

Relationships of insulin and intact and split proinsulin to haemostatic function in young men with and without coronary artery disease.

Glucose intolerance, hyperinsulinaemia, dyslipoproteinaemia and multiple disturbances of haemostatic function are characteristics of young men with premature coronary artery disease. The relations between glucose, insulin and insulin propeptides, in the fasting state, and after an oral glucose load, and haemostatic function were examined in 62 consecutive non-diabetic men with myocardial infarction before the age of 45 and in 41 age-matched healthy men. "True" hyperinsulinaemia, raised plasma concentrations of insulin propeptides, dyslipoproteinaemia, elevated plasma levels of fibrinogen, factor VII antigen (VIIag) and plasminogen activator inhibitor-1 (PAI-1) activity, and lower antithrombin activity (p < 0.

Serum angiotensin-I-converting enzyme activity in women with cardiological syndrome X: relation to blood pressure and lipid and carbohydrate metabolic risk markers for coronary heart disease.

Polymorphism of the angiotensin-I-converting enzyme (ACE) gene is associated with variations in serum ACE activity and the incidence of cardiovascular disease. Whether a similar association exists with cardiological syndrome X (chest pain, positive ECG exercise test, and normal angiography) is unclear. As ACE activity affects vascular tone, it could be involved in the pathogenesis of this syndrome.

Aldosterone concentration in normal, growth-retarded, anemic, and hydropic fetuses.

Objective: To establish a gestational age reference range for fetal plasma aldosterone concentration and to determine whether anemia, growth retardation, or hydrops are associated with abnormal levels.

Methods: Aldosterone concentration was measured in umbilical venous blood obtained by funipuncture from pregnancies complicated by red blood cell isoimmunization (n = 17), fetal growth retardation (n = 8), and nonimmune hydrops fetalis (n = 17). Values were compared to reference ranges constructed from the study of samples obtained by funipuncture or at elective cesarean delivery from 40 essentially normal fetuses and maternal blood from 33 uncomplicated pregnancies.

Atrial natriuretic factor concentration in normal, growth-retarded, anemic, and hydropic fetuses.

Objective: Our purpose was to establish a reference range with gestation for plasma concentrations of atrial natriuretic factor in fetal blood and to examine whether the concentration is altered in fetal anemia, acidemia, or hydrops.

Study Design: Atrial natriuretic factor was measured in umbilical venous blood taken by cordocentesis from pregnancies complicated by red blood cell isoimmunization (n = 17), intrauterine growth retardation (n = 12), and hydrops fetalis (n = 20) and from controls (n = 66). Additionally, maternal blood atrial natriuretic factor concentration was measured in 40 uncomplicated pregnancies.