Endocrine Abstracts

Objective:This study was designed to estimate the prevalence of nonalcoholic fatty liver in Saudi type-2 diabetics attending medical outpatient clinic in a Saudi teaching hospital and to study some of their characteristics.Research Design and Method:The study was conducted at King Abdulaziz University Hospital, Jeddah, Saudi Arabia from September 2001 to September 2002. A sample of 116 patients was randomly s...

The renin-angiotensin system (RAS) is a key factor in the regulation of blood pressure and therefore its' blockade may reduce the vascular complications which arise with polycystic ovary syndrome (PCOS). Adipose tissue expresses all the components of the RAS system that includes the pre-prohormone angiotensinogen (AGT) and its' active metabolite angiotensin II (ANG II), which mediates vasoconstriction and electrolyte balance and as such may contribute to obesity associated hyp...

IntroductionWe aimed to establish whether Body Mass Index (BMI) affected outcomes including duration of intensive care stay and in-hospital mortality following cardiac surgery in an Irish cardiac surgery centre.MethodsA retrospective analysis of a consecutive series of 1055 cardiac surgery patients from June 2001 to June 2003 was carried out.ResultsBMI (kg/m2) dat...

Low testosterone levels in men are associated with increased atherosclerosis, and testosterone replacement therapy has been shown to reduce myocardial ischemia in men with coronary artery disease. Vascular smooth muscle cell (VSMC) apoptosis is proposed to reduce plaque stability, but the role of testosterone in this process is unknown. Testosterone causes vasodilatation via calcium channel antagonism and the calcium channel antagonist nifedipine induces VSMC apoptosis. We hav...

Atherosclerotic plaque smooth muscle cells (SMCs) are sensitive to apoptotic stimuli, increasing plaque instability. Testosterone replacement therapy is beneficial in men with coronary artery disease, although its effect upon plaque stability is unknown. We have utilised the rat A7r5 vascular SMC line to investigate the effects of testosterone on apoptosis induced by serum deprivation or the calcium channel antagonist nifedipine.Cells were plated at 1500...

Objective: To investigate pancreatic beta cell morphology and function in rat adult offspring of dams fed a high fat diet in pregnancy.Methods: Female Sprague Dawley rats were fed either a control breeding diet (4% fat) or a high fat diet (20% animal fat) balanced for vitamins and nutrients. Experimental diets were fed for 10 days prior to mating, throughout pregnancy and weaning. Weaned pups were fed standard low fat chow throughout adult life. The time...

Objective: To evaluate the impact of laser treatment on the severity of facial hirsutism as well as psychological morbidity in women with polycystic ovary syndrome (PCOS).Methods: Randomised controlled trial of 5 high fluence treatments (intervention) or 5 low fluence treatments (control) over 6 months. 88 women with facial hirsutism due to PCOS were recruited from hospital outpatient clinics and a patient support group in 2002. Main outcomes were self r...

Mechanisms underlying the association of low birth weight with the metabolic syndrome in adults remain poorly understood. Epidemiological studies suggest that obesity is not programmed by early life events, but amplifies the risks of intra-uterine growth retardation. We have explored the effects of dietary obesity in rats in which features of the metabolic syndrome have been programmed by prenatal dexamethasone.16 pregnant Wistar rats were treated with d...

Some people with obesity have hormonal, metabolic and circulatory changes that constitute the metabolic syndrome that resemble characteristics of patients with Cushing's syndrome. A link between the two conditions, possibly genetic, has therefore been suspected, and the glucocorticoid receptor gene (GRL, 5q31-q32) has been one of the candidate genes.The single nucleotide polymorphism N363S is an ATT to GTT missense alteration within exon 2 of G...

Background: The gut hormone PYY3-36 (PYY) is released into the circulation after eating and physiologically inhibits food intake. Obese and lean subjects are equally sensitive to this effect, however fasting levels of PYY are reduced in obese subjects.Methods: We investigated the postprandial PYY response and satiety response using a visual analogue scale (VAS) to 6 test meals of increasing calorie content in 20 lean and 20 obese subjects. We also infuse...

Aim: Acute bouts of exercise are known to have a beneficial effect on glucose homeostasis immediately following exercise in people with Type 2 Diabetes. Evidence suggests that this effect is independent of the effects of insulin. In this study we compare recently developed indices of insulin sensitivity derived from the oral glucose tolerance test to determine whether the improvements in glucose homeostasis following physical activity are independent of the effects of insulin....

Abnormal foetal growth is associated with an increased predisposition to impaired glucose metabolism (Hales and Barker. Diabetologia 1992; 35: 595-601). The aim of the study was to examine whether size at birth influenced glucose tolerance in pigs at 5 months of age.The litters from 4 multiparous sows were weighed at birth. A low (L: <10th percentile) and normal (N: 40th-60th percentile) piglet was selected from each l...

The nuclear receptor PPARgamma is important for biological processes including adipogenesis and glucose homeostasis. In subjects with severe insulin resistance, we have previously reported two types of human PPARgamma gene defect: heterozygous, missense mutations (P467L, V290M) in the ligand binding domain (LBD) which inhibit wild type (WT) receptor action in a dominant negative manner by recruitment of transcriptional corepressors; or double heterozygosity for a frameshift/pr...

Background and Hypothesis:- A common NOS3 Single nucleotide polymorphisms (SNP) (894 G/T) which encodes a Glu298Asp amino acid substitution in endothelial NO synthase has been associated with cardiovascular disorders in which NO bioactivity is impaired. The gene coding for p22phox, a critical component of the NADH/NAD(P)H oxidase enzyme system, a major source of vascular SO, is CYBA. Among the allelic polymorphisms reported in CYBA is C242T, associated wit...

Chronic exposure to elevated circulating glucocorticoids can lead to metabolic changes, which resemble those observed in Metabolic Syndrome. Features of the Metabolic Syndrome can be reversed by lowering systemic glucocorticoid levels or by treatment with a glucocorticoid receptor antagonist. At the intracellular level, exposure to glucocorticoids is regulated by two distinct 11beta-hydroxysteroid dehydrogenases, 11beta-HSD type 1 and type 2. 11beta-HSD1 predominantly acts as ...

Background: Transient Receptor Potential (TRP) channels are expressed in many epithelial cells and respond to mechanical or osmotic stress by initiating a number of calcium-dependent mechanisms. The human serum and glucocorticoid regulated kinase (hSGK) is one such calcium-dependent protein found in the kidney. Stimulated by cell shrinkage, this volume-regulated kinase stimulates sodium transport. Aberrant absorption of sodium has been implicated in the development of hyperten...

Central obesity is strongly associated with insulin resistance and chronic sub-clinical inflammation, which is implicated in the development of type 2 diabetes (T2DM). However, the mechanisms underlying this link remain unclear. Recently JNK, a mitogen activated protein kinase (MAPK), has been implicated in obesity and insulin resistance by interfering with insulin action. Studies in rodent models show that phosphorylated JNK-1 is elevated in obesity, whilst the absence of JNK...

Chronic sub-clinical inflammation is associated with increased risk of diabetes and cardiovascular disease and is particularly observed in patients that have undergone CABG. Resistin, a novel adipocyte derived protein, has been linked with central adiposity, insulin resistance and sub-clinical inflammation and may mediate both systemic and local paracrine pro-inflammatory responses in vivo. As such we investigated serum resistin from CABG patients and examined whether e...

Both hyperhomocysteinemia and increased inflammatory activity are shown to be associated with atherosclerosis. But, the relation of inflammatory activity to homocysteine levels is not well established. In the present study, we aimed to evaluate the relation of plasma homocysteine (tHcy) levels to atherosclerotic vascular disease and inflammatory activity in type 2 diabetic patients.Ninty type 2 diabetic patients were included in the study. Forty one of t...

IntroductionThe metabolic syndrome is associated with an increased risk of cardiovascular disease and diabetes. The insulin-like growth factor (IGF) system has been implicated in the pathogenesis of cardiovascular disease and glucose intolerance. We have previously shown that a low IGFBP-1 concentration coupled with a low circulating IGF-I predicts worsening glucose tolerance. In this study we further investigated relationships between the IGF-system and...

Hyponatraemia is a common biochemical abnormality associated with significant mortality. However, adequate investigation and accurate diagnosis are frequently lacking. We have evaluated the assessment and management of severe hyponatraemia in a large teaching hospital. Inpatients with a plasma sodium (pNa) <125mmol/L were identified prospectively by laboratory database, over a 6 month period. Notes were examined and data extracted. Data was also retrospectively reviewed by ...

Type 2 diabetes (T2DM) is associated with insulin resistance and chronic sub-clinical inflammation. Pro-inflammatory cytokines produced from adipose tissue are secreted as part of the innate immune response and also associated with insulin resistance. In contrast, adipocyte derived adiponectin is associated with insulin sensitivity and also has anti-inflammatory properties. Hence fat may represent a site for mediating the innate immune response. We therefore investigated a mec...

The role of 11beta-HSD2 is to provide selective access of aldosterone to the mineralocorticoid receptor (MR) by inactivating cortisol. Evidence suggests impaired 11beta-HSD2 activity in some patients with hypertension but also in patients with renal disease where it may contribute to sodium retention, oedema and hypertension. To date these studies have relied upon urinary cortisol metabolite analyses as markers of renal 11beta-HSD2 activity. We have directly analysed renal 11b...

Studies in rats suggest that androgens are involved in sex-specific differences in blood pressure. In human studies there is no difference in blood pressure between boys and girls, but following puberty, men present with a higher blood pressure than women. Modulation of sodium reabsorption through the ENaC is an important component in the control of sodium balance. This is clearly demonstrated by rare genetic disorders of sodium-channel activity (Liddle's syndrome and pseudohy...

Background Phytoestrogens are a group of biologically active plant substances with chemical structures similar to that of endogenous estrogen. Their beneficial effects on cardiovascular protection have been indicated by the relatively lower incidence of cardiovascular diseases in people with higher phytoestrogen consumption. Recent studies show that they have anti-oxidative properties, which have not been studied in human endothelial cells under different glucose conditions.</...

The PPARgamma is a ligand activated transcription factor that plays an important role in various biological processes including adipocyte differentiation and glucose homeostasis. Alternate promoter usage generates two receptor isoforms: PPARgamma2, containing 28 additional aminoterminal residues, is selectively expressed in adipose tissue whereas PPARgamma1 is more ubiquitously distributed. PPARgamma2 is strongly up regulated during adipogenesis, suggesting a specific role for...

Peripheral metabolic signals such as leptin, glucose and insulin are integrated by neurons in the hypothalamus to regulate both short and long term energy balance. However, the signal transduction mechanisms by which neurons sense glucose and insulin levels are unclear and specific parts of the pathways may be distinct from those in the pancreas. The aim of this study was to quantitatively analyse hypothalamic expression of genes known to be involved in pancreatic glucose/insu...

Intra-adipose steroid metabolism may be a key determinant of accumulation and distribution of body fat. Adverse 'central' fat can be driven by glucocorticoid excess or decreased oestrogen/androgen ratio. We previously demonstrated increased regeneration of cortisol by 11beta-HSD1 in adipose in human obesity. Here, we measured mRNAs for enzymes dictating local activation of oestrogens (aromatase) and androgens (5alpha-reductase type 1) in subcutaneous human adipose and related ...

The peptide hormone ACTH can stimulate lipolysis and suppress leptin expression in murine adipocytes. These effects are mediated via the Melanocortin 2 Receptor (MC2-R), which is expressed when 3T3-L1 cells are induced to differentiate into adipocytes. In this study we have investigated the transcriptional activation of the MC2-R gene during adipogenesis.5' deletion analysis of the murine MC2-R promoter revealed the presence of a transcriptional enhancer...

Testosterone therapy has been shown to be beneficial in men with coronary artery disease (CAD) and chronic heart failure (CHF), effects which are proposed to be due to a direct vasodilatory action. We utilised fluorescence measurements to investigate whether testosterone inhibits extracellular calcium entry induced by 50mM high potassium (K+) buffer, in A7r5 vascular smooth muscle cells.A7r5 cells were grown on coverslips in 12-well plates in ...

Testosterone reduces myocardial ischaemia in men with coronary artery disease (CAD) and improves symptoms and exercise capacity in men with congestive heart failure (CHF), effects proposed to be due to testosterone-induced vasodilatation. Isolated vessel studies suggest this occurs via a calcium antagonistic action upon voltage-gated Ca2+ channels but this has yet to be investigated directly.We therefore employed patch clamp methodology to stu...

Low serum testosterone levels in men predict the future development of insulin resistance and Type 2 diabetes. Furthermore, men with Type 2 diabetes have lower testosterone levels than nondiabetic men. Testosterone is known to be positively correlated with insulin sensitivity. It has also been demonstrated that low levels of circulating androgens are associated with coronary artery disease, dyslipidaemia, hypertension and visceral obesity. The purpose of this study was to dete...

Leptin hormone is mainly secreted from adipose tissue and has an important role in energy metabolism. There have been very few studies examining effects of leptin on oxidant stress. The aim of the present study was to investigate whether leptin affects lipid peroxidation and antioxidant status in the brain of mice. Adult male Bulb-c mice were divided into two groups. Leptin was intraperitoneally administered to the first group at a dose of 40ug/animal for 5 days. Controls rece...

Testosterone reduces myocardial ischaemia in men with coronary artery disease, and improves symptoms and exercise capacity in men with heart failure, effects proposed to be due to testosterone-induced coronary, systemic and pulmonary vasodilatation. Endothelial-independent calcium channel antagonism is proposed as the effector mechanism from in vitro animal studies, but this has yet to be confirmed in humans.In the present study we have investigated the ...

Background: PYY is a gut hormone that physiologically inhibits appetite. Currently only radioimmunoassay (RIA) techniques are available for its estimation. The aim of the study was to evaluate our in-house assay for precision, detection limit, interference of haemolysis, suitability of serum versus plasma and biological variation within one subject.Method: All samples were obtained from one subject on two occasions following an over night fast and the co...

Sixty-six patients with type 2 diabetes, obesity and no known history of cardiovascular disease were recruited to a lifestyle-intervention study. The aims of this study were to quantify the presence of silent and symptomatic ischaemia using a Bruce protocol treadmill-test, and to identify factors associated with a positive stress-test in these patients. Ethical approval was obtained from the local ethics committee.54/66 patients had blood pressure (BP) g...

IntroductionWomen with Turner Syndrome (TS) have an increased risk of diabetes mellitus (DM), both types 1 and 2, and obesity is a common problem. This study aimed to characterise the relationship between markers of obesity and metabolic factors which might predispose to DM.MethodAnthropometric and fasting metabolic assessments were performed in 56 non-diabetic women with TS and 24 control women (mean±...

Studies in the general population have shown a prevalence of the metabolic syndrome of 17-25%. We have studied the prevalence of the metabolic syndrome in patients with diabetes mellitus (DM). A total of 150 consecutive patients with type 1 (21%) or type 2 DM (79%), mean age 59.1y (28-85), attending for annual review were studied to determine if they satisfy (ATP III) diagnostic criteria for the metabolic syndrome. Fasting plasma glucose, triglycerides, HDL cholesterol, blood ...

All adolescent and young adult T1DM attending our clinic, based in a university teaching hospital are reviewed three monthly and receive individual advice from dietician, nurse educator and consultant diabetologist at each visit. We aimed to identify deficits in diabetes related knowledge and assess diabetic control in this population.Subjects were asked to complete ADKnowl(Audit of Diabetes Knowledge) Questionnaire. Demographic data and measures of glyc...

The binding characteristics of maternal serum human chorionic gonadotrophin (hCG) to immobilised lectins, specifically Concanavalin A (Con A), Lens culinaris agglutinin (LCA) and Wheat germ agglutinin (WGA), have been shown be compatible with the proposed glycosyl structures of hCG as inferred from other analytical methods. We have shown that serum hCG from groups of pregnant women with or without type 1 diabetes show identical affinity for Con A and LCA, but serum hCG from th...

Background: Hyperinsulinaemia and insulin resistance is observed in both lean and obese women with Polycystic Ovary Syndrome (PCOS). This condition affects 52% of Asian Indian compared to 22% of Caucasian women. Lifestyle changes, particularly diet and exercise can significantly impact the future prevention of type 2 diabetes, dyslipidaemia and hypertension in these patients.Objectives: We hypothesised that regular intensive exercise would be effective i...

High levels of physical inactivity contribute to the development of obesity. We aimed to evaluate the benefits of exercise instruction in obese patients with type 2 diabetes who have demonstrated difficulty with weight management since diagnosis. Ethical approval was obtained from the local committee.Sixty-six patients were recruited from the diabetes out-patient clinics. All patients underwent treadmill-testing prior to randomisation. Patients were matc...

Hyponatraemia is one of the commonest biochemical abnormalities in hospitalised patients, and is generally associated with a poor outcome. Large controlled studies of severely hyponatraemic patients are however unusual. From our biochemistry laboratory database we prospectively collected all patients with a sodium (Na) <125 mmol/L over a 6 month period (n=104).For each hyponatraemic case, a normotraemic control was chosen as the next sequential patient in time on the labora...