Endocrine Abstracts

Introduction: Non-Alcoholic Fatty Liver Disease (NAFLD) is reported to be common in patients undergoing bariatric surgery, but the diagnostic accuracy of non-invasive NAFLD biomarkers to stage disease and track progress longitudinally has not been assessed.Methods: 274 patients undergoing bariatric surgery were included in the study. Intra-operative liver biopsies were taken from 163 patients and histologically graded using t...

Background: Low vitamin B12 (B12) during pregnancy is associated with higher maternal obesity, insulin resistance (IR) and gestational diabetes (GDM). However, it is not clear whether these are causally related.Objective: B12 is a key co-factor of the DNA methylation cycle (1-carbon metabolism). We hypothesize that B12 plays a role in epigenetic regulation by altering circulating miRNAs (miRs) during adipocyte differentiation...

Intestinal nutrient sensing and transport are gaining increasing attention in the field of obesity research. To date, in vitro studies in this area have largely used two dimensional (2D) cell culture models. However, 2D cell cultures are limited by a lack of cellular heterogeneity, behaviour, and communication observed in vivo. There has consequently been growing interest for the application of three-dimensional (3D) cell culture ...

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic disease. Steroid hormones and bile acids are established regulators of metabolic phenotype. 5β-reductase (AKR1D1) is highly expressed in human liver where it inactivates steroid hormones and catalyzes a fundamental step in bile acid synthesis. We hypothesized that AKR1D1 plays a key role in hepatic metabolic homeostasis. Genetic manipulation of AKR1D1 ...

Glucocorticoid (GC) excess drives obesity, insulin resistance and type 2 diabetes. Obstructive sleep apnoea (OSA) is a prevalent condition associated with both activation of the hypothalamic-pituitary-adrenal (HPA) axis and an adverse metabolic phenotype. However, a causal link between these two features has not been established. We designed a novel human model of intermittent hypoxia (IH) aimed at replicating the systemic insulin resistance associ...

Idiopathic intracranial hypertension (IIH) is a condition of unknown aetiology characterised by raised intracranial pressure, chronic headaches and blindness. Akin to polycystic ovary syndrome (PCOS), IIH patients are almost exclusively obese females of reproductive age. A distinct androgen excess profile has been noted in PCOS. Here, we aimed to delineate androgen metabolism in IIH compared to PCOS and simple obesity.Women w...

High protein diets are highly satiating but hard to maintain. By understanding the mechanisms underlying these effects we may be able to identify new anti-obesity therapies. Protein is broken-down into amino acids in the gut which are detected by a series of nutrient sensors. The calcium sensing receptor (CaSR) is primarily activated by calcium ions, but is positively allosterically modulated by aromatic amino acids, especially L-phenylalanine. Sti...

Introduction: Intrahepatic cholestasis of pregnancy (ICP) is characterised by maternal pruritus and raised serum bile acids, and is associated with adverse fetal outcomes (e.g. preterm birth, neonatal unit admission and stillbirth). Maternal metabolic impacts include higher rates of gestational diabetes mellitus, hypertriglyceridaemia and hypercholesterolaemia. Glucose and lipid metabolism are influenced by gut incretin release, and bile acids are ...

Context: Polycystic ovary syndrome (PCOS) has been linked to non-alcoholic fatty liver disease (NAFLD) that carries an increased risk of liver cirrhosis. The Enhanced Liver Fibrosis (ELF) score comprises serum hyaluronic acid (HA), procollagen III N-terminal peptide (PIIINP) and tissue inhibitor of metalloproteinase-1 (TIMP1) that correlate with hepatic fibrosis staging.Objective: To determine the effect of vitamin D suppleme...

Babies born to mothers with diabetes during pregnancy are exposed to high circulating leptin before birth and, in turn, are at increased risk of developing diabetes in later life. In pancreatic islets isolated from fetal sheep, leptin influences β-cell proliferation in a bimodal manner. This study examined the effect of exogenous leptin infusion and leptin receptor antagonism on pancreatic β-cell mass in the sheep fetus in vivo.<...

Idiopathic intracranial hypertension (IIH) is a condition characterised by raised intracranial pressure (ICP) that primarily affects obese women of reproductive age. The aetiology is poorly understood but involves imbalance of cerebrospinal fluid (CSF) secretion and absorption. IIH patients share similar phenotypic characteristics to PCOS patients, a condition with a distinct androgen signature. We hypothesise that obesity and androgen excess maybe...

Background: Vitamin B12 (B12) deficiency results in disturbance of 1-carbon metabolites [methylmalonyl coenzyme A (MMA), homocysteine and S-adenosyl homocysteine (SAH), S-adenosyl methionine (SAM) and methionine] that collectively affect lipogenesis leading to risk of cardiovascular diseases. In clinical studies, B12 deficiency is associated with higher BMI and dyslipidaemia (high triglycerides and low HDL). The role of B12 in hepatic metabolism of...

Background: Male sexual dysfunction is common in obesity with complex underlying mechanisms. Testosterone replacement has often been initiated in clinical practice in the presence of sexual dysfunction and male obesity-associated secondary hypogonadism. The benefits to sexual functioning, however, are not well documented. The aims of the study were to investigate the relationship between sexual function and hypogonadism in severe obesity and to understand the impact of bariatr...

Obesity in pregnancy is associated with an increased risk of complications for mother and child. Epigenetic modifications have been proposed as an important underlying mechanism. As the placenta plays a key role in fetal nutrition and metabolism we hypothesized there would be placental DNA methylation differences between lean and obese placenta. DNA methylation array (Human Methylation 450K) was performed on placentas from n=31 obese (BMI&...

Background: Vitamin B12 (B12) is an essential micronutrient required for optimal hematopoietic, neurologic and other several metabolic reactions. Longitudinal studies and animal models showed that low maternal vitamin B12 deficiency is associated with the maternal obesity, development of insulin resistance and metabolic syndrome phenotype. Although the mechanisms underpinning metabolic disorders remain poorly defined, it has become increasingly cle...

Chronically exposure to stress promotes in individuals high intake of foods with high content of carbohydrates and fat and may develop obesity. Stress-induced sustained elevation of glucocorticoid serum levels may be due to impaired functioning of the hypothalamic glucocorticoid receptor GR, altering the hypothalamic-pituitary-adrenal axis regulation. As a result, chronically stressed individuals are unable to respond with higher cortisol levels wh...

Introduction: Obesity is associated with increased cardiovascular disease (CVD) risk but the underlying pathways are unclear. Extracellular vesicles (EVs) are circulating submicron particles containing proteins, enzymes and mRNA of their donor cells. They could mediate some of these risks by paracrine actions in target cells.Aims: To compare the concentration and characteristics of circulating EVs from healthy volunteers (HV)...

Background: Emerging evidence suggests that impaired high density lipoprotein (HDL) function is associated with cardiovascular disease (CVD). HDL is essential for removing excess circulating cholesterol by reverse cholesterol transport (RCT). Additionally HDL reduces inflammation and oxidative stress, especially through paraoxonase-1. Whereas HDL’s capacity to accept cholesterol from peripheral cells is key (i.e. cholesterol efflux capacity (CEC)), successful RCT depends ...

Introduction: Zinc homeostasis is involved in numerous physiological and pathological conditions, ranging from type 1 and type 2 diabetes to memory impairment and cancer, and is determined by at least 28 genes, including 24 SLC (Solute Carrier) family members and 4 MTs (Metallothioneins). To explore the potential role of zinc homeostasis in MetS (metabolic syndrome) and IR (insulin resistance), we investigated 28...

Introduction: Obesity is a major risk factor for mortality from a range of causes. We investigated whether skinfold measurements predict mortality independently of variation in body mass index (BMI).Methods: A prospective analysis of mortality in 870 apparently healthy adult Caucasian men participating in an occupational health cohort was undertaken. At baseline, skinfold measurements were taken at biceps, triceps, iliac and ...

Introduction: Obesity results in an imbalance of systemic adipokines as well as pro and anti-inflammatory biomarkers. The attenuation of anti-inflammatory proteins, including Annexin A1 (AnxA1) in human obesity, may be a contributing factor to the chronic inflammatory phenotype which results. However, increased AnxA1 mRNA and protein levels in mature adipocytes suggest an additional role for AnxA1 in adipose tissue biology.Ai...

Aim: To explore the metabolic phenotype of Male Obesity-associated Secondary Hypogonadism (MOSH) and following treatment with long-acting intramuscular (IM) testosterone undecanoate.Methods: A prospective observational pilot study on metabolic effects of IM testosterone undecanoate in MOSH (Hypogonadal [HG] group, n=13), including baseline comparisons with controls (Eugonadal [EG] group, n=15). Half the subj...

Background: Obesity is a major modifiable risk factor for cardiovascular disease. Bariatric surgery is considered to be the most effective treatment option for weight reduction in obese patients with and without type 2 diabetes.Aims: To evaluate changes in lipoproteins, insulin resistance, mediators of systemic and vascular inflammation and endothelial dysfunction following Roux-en-Y bariatric surgery in obese patients with a...

Background: Increased adiposity is associated with increased cardiovascular disease (CVD) risk but among overweight individuals clarification is needed of relationships between insulin sensitivity, fat distribution and metabolic health that might contribute to this risk.Methods: During the Heart Disease and Diabetes Research Indicators in a Screened Cohort (HDDRISC) study, 560 employment cohort normoglycaemic (FPG less than 7...

Background: Obesity is a common risk factor for obstructive sleep apnoea (OSA) and polycystic ovary syndrome (PCOS).Objective: To examine the prevalence of OSA in women with PCOS.Search sources: Electronic databases [Medline, Embase, Cinahl, PsycInfo, Scopus, Web of Science, Opengrey, and Cochrane Central Register of Controlled Trials], conference abstracts, and reference lists of relevant articles. The...

Background: Bariatric surgery for severe obesity can lead to micronutrient/vitamin deficiencies.Aim: To study baseline and post-surgical prevalence of vitamin D deficiency in patients undergoing bariatric surgery.Setting: University teaching hospital in North-West England.Methods: We performed an observational cohort analysis of longitudinal data on vitamin D and related parameters in patients who underwent b...

Case: A 34 years old lady presented to the antenatal clinic at 7 weeks gestation with unplanned pregnancy. She had background history of HTN, poorly controlled T2DM and hypercholesterolemia . She continued taking metformin, gliclazide, sitagliptin and simvastatin which were stopped at the booking appointment . Metformin continued and started on insulin. Blood tests at booking showed HbA1c 126, Cholesterol 5.2 , Triglycerides 2.7. She was started on...

Background: Human immunodeficiency virus (HIV) infection and the Acquired Immune Deficiency Syndrome (AIDS) are health problems with infected individuals frequently manifesting some abnormalities including significant weight loss. This has been associated withtumor necrosis factor alpha and interleukin 1β production by circulating mononuclear white blood cells in patients with HIV infection andaltered metabolism due to cytokine dysregulation and metabolic demands of antir...

One of the major risk factors for type 2 diabetes is Obesity (accounts for 80-85% of overall risk of developing type 2 diabetes). The UK is currently amid an obesity epidemic and it is recommended that the UK population reduce their daily calorie intake. As people are surrounded by food, it was acknowledged that this can be challenging to achieve on a long-term basis. This pilot study aimed to identify common social cues that encourage people to in...

Introduction: The number of people with type 2 diabetes is increasing worldwide. Currently, 415 million adults have diabetes worldwide and It has been projected that this will increase to 642 million people by 2040. Several important risk factors have been linked to the development of type 2 diabetes, the most important of which is excess body weight.This study set out to determine the blood glucose levels of people in a semi...

Glycogen storage disease, which is a metabolic disorderof glycogen storage, affecting 1 in 20000-40000 ive births. This is a case of yound adolescent female with glycogen storage disease type1b, presented with lactic acidosis and managed in ITU.18 years old femae from Honk kong, student in a college, admitted to a dgh hospital with fever, vomiting and abdominal pain for a week. examination showed severe features of dehydratio...