Searchable abstracts of presentations at key conferences in endocrinology
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Society for Endocrinology BES 2010

Poster Presentations

Diabetes and metabolism

ea0021p129 | Diabetes and metabolism | SFEBES2009

Profile of elderly patients with diabetes admitted into Obafemi Awolowo University Teaching Hospital

Ikem Rosemary , Soyoye David , Adebayo Joseph , Ojo Busola , Ugwu Ejiofor , Kolawole Babatope

Introduction: The average life expectancy and the prevalence of diabetes are increasing. Among the elderly population, type 2 diabetes is a growing problem, with a large proportion of newly diagnosed diabetics. Treating elderly diabetes can present unique challenges. Impaired cognitive and physical functioning among some elderly patients can make adjusting to a diabetes care routine more difficult and thus, contribute to the complexity of managing diabetes.<p class="abstex...

ea0021p130 | Diabetes and metabolism | SFEBES2009

Factitious hypoglycaemia in a patient without diabetes

Reddy Monika , Leaper Craig , Drubra Upkar , Abbara Ali , Baoku Yetunde , Darko Daniel , Mehta Sanjeev

A 53-year-old Asian supermarket produce supervisor was noted at work to have slurred speech, sweating, and to feel lightheaded. Paramedics were called and on arrival his capillary blood glucose (CBG) was 1.7 mmol/l. This rose to 2.7 mmol/l after he was given glucose gel followed by complex carbohydrate. He remained lightheaded so was taken to hospital. CBG on admission was 2.0 mmol/l, so samples were taken for plasma glucose, insulin, C-peptide and sulphonylurea screen. Plasma...

ea0021p131 | Diabetes and metabolism | SFEBES2009

Gender and the metabolic syndrome in type 2 DM

Ogbera Anthonia

Background: The prevalence of diabetes mellitus (DM) is on the increase and with this scenario, a possible increase in burden of DM which may be largely attributed to cardiovascular complications is expected. The objective of this report is to determine the prevalence and compare gender characteristics in subjects with type 2 DM.Methods: Subjects with type 2 DM were recruited from an urban hospital for the study and clinical data obtained. The anthropome...

ea0021p132 | Diabetes and metabolism | SFEBES2009

Positive correlation between serum omentin and thrombospondin-1 in gestational diabetes despite lack of correlation with insulin resistance indices

Lewandowski Krzysztof , Cypryk Katarzyna , Nadel Iwona , Lewinski Andrzej , Bienkiewicz Malgorzata , Tan Bee , Randeva Harpal

Background: Gestational diabetes (GDM) is characterized by insulin resistance and a pro-inflammatory state, both factors possible related to adipokine expression. In our study we have endeavoured to assess serum levels of insulin-sensitising omentin and pro-inflammatory thrombospondin-1 (TSP-1) in GDM.Subjects and methods: The study included 20 women with GDM, diagnosed according to the WHO criteria, age 29.7±5.5 (mean±S.D.), BMI...

ea0021p133 | Diabetes and metabolism | SFEBES2009

Pancreatic polypeptide: a novel substrate for the endopeptidase neprilysin

Baxter Jordan , Minnion James , Shilto-Cuenco Joy , Tan Tricia , Murphy Kevin , Ghatei Mohammad , Bloom Stephen

Pancreatic polypeptide (PP) is a 36 amino acid peptide, secreted from the endocrine pancreas. Previous work has shown that peripheral administration of PP inhibits food intake in rodents and humans. However, PP has a short circulating half-life that limits its use as an anti-obesity agent. Determining the mechanisms involved in the physiological breakdown of PP will allow the rational design of long-acting analogues with greater clinical utility in the treatment of obesity. PP...

ea0021p134 | Diabetes and metabolism | SFEBES2009

Bariatric surgery in renal transplant recipients

Kamaledeen Salma S , Bueter Marco , Ahmed Ahmed , Le Roux Carel W

Objectives: The long-term outcome of bariatric surgery on renal function in the morbidly obese renal transplant recipient is still unknown. We describe three cases of morbidly obese renal transplant recipients who have subsequently undergone bariatric surgery.Patient 1: A 44-year-old man (BMI 42.2 kg/m2) had received a renal transplant for chronic renal disease secondary to childhood reflux nephropathy. Laparoscopic Roux-en-Y gastric bypass re...

ea0021p135 | Diabetes and metabolism | SFEBES2009

Testosterone replacement therapy has no effect on ultrasound assessed carotid artery stiffness and intima-media thickness in men with insulin treated type 2 diabetes

Stanworth Roger , Jones T Hugh

Context: Testosterone replacement therapy (TRT) has shown benefit on insulin resistance, glycaemic control and cardiovascular risk markers in hypogonadal men with diabetes. Arterial stiffness and intima-media thickness (IMT) are vessel wall properties associated with future cardovascular risk which allow the progress of atherosclerosis to be assessed non-invasively. Low testosterone has been associated with the presence and progression of carotid atherosclerosis as assessed by...

ea0021p136 | Diabetes and metabolism | SFEBES2009

A novel role for neuropeptide Y in the regulation of energy homeostasis

Leavy Emma , Gardiner James , Buckley Niki , Richardson Errol , Martin Niamh , Bloom Stephen , Smith Kirsty

The hypothalamus regulates multiple homeostatic systems, and is essential for the regulation of appetite and energy balance. Neuropeptide Y, a 36 amino acid peptide and member of the PP-fold family, is a key hypothalamic neuropeptide involved in the regulation of energy balance, potently stimulating food intake following central administration. NPY is expressed in the arcuate nucleus (ARC) and NPYergic neurones project to multiple hypothalamic nuclei and extra-hypothalamic sit...

ea0021p137 | Diabetes and metabolism | SFEBES2009

Salicylate induces insulin sensitivity by alleviating endoplasmic reticulum (ER) stress in cultured primary human adipocytes

Tripathi Gyanendra , Alhusaini Saif , McGee Kirsty , Lois Kostantinos , Harte Alison , McTernan Philip , Kumar Sudhesh

Background: Adipose tissue (AT) may have a significant role in obesity associated inflammation but, the mechanisms underlying the pathogenesis of obesity induced inflammation remains unclear. Recent murine studies indicate that ER stress is critical to the initiation and integration of inflammation and insulin signalling pathways. The ER stress occurs primarily due to accumulation of unfolded proteins and results in activation of the unfolded protein response to restore ER hom...

ea0021p138 | Diabetes and metabolism | SFEBES2009

Herbal remedies as a cause of recurrent hypoglycaemia

Whitfield Thompson , Rana Subhash , Bangar Vijay , Mousa Abdusalam

Objective: Factitious hypoglycaemia presents diagnostic difficulties. We report a case presenting with hypoglycaemia, due to use of herbal remedies for enhancement of sexual performance.Case: A 73-year-old male known to have peptic ulcer admitted with feeling dizzy and unwell, with blood glucose of 1.6 needed 10% dextrose infusion in the first 48 h of admission. Medications folic acid, adcal d3, omeprazole 20 mg, herbal medicine for improving sexual func...

ea0021p139 | Diabetes and metabolism | SFEBES2009

The effects of chloroquine on blood glucose and plasma insulin concentrations in male Sprague--Dawley rats

Musabayane Cephas , Murambiwa Pretty , Joosab Naseera , Masola Bubuya , Mukaratirwa Samson

Chloroquine, the commonly used in the treatment of malaria has been reported to elicit adverse effects such as hypoglycaemia through unknown mechanisms. In particular, literature to date has revealed that the effects of the drug on insulin concentrations remain obscure. Our investigation therefore focuses on establishing a possible mechanism of CHQ-induced hypoglycaemia with regards to its effects on plasma insulin concentrations. The purpose of this study was to investigate t...

ea0021p140 | Diabetes and metabolism | SFEBES2009

The impact of thiazolidinediones on microalbuminuria in adults with type 2 diabetes mellitus: a systematic review

Patel Mayur , Fowkes Robert , Sampson Mike , Holland Richard

Background: Microalbuminuria is an early marker of diabetic nephropathy in type 2 diabetes mellitus (T2DM) which predicts the development of later stages of nephropathy. Thiazolidinediones are a class of oral hypoglycaemic drugs used in diabetes glycaemic management that act through PPARγ receptors. Studies have suggested they significantly reduce urinary albumin excretion; however, most trials were small. We therefore performed a systematic review to clarify the effectiv...

ea0021p141 | Diabetes and metabolism | SFEBES2009

Diabetic keto-acidosis in patients with Type 2 diabetes mellitus: a relatively common occurrence, the severity of which correlates with HbA1c

Begbie Helen , Barber Thomas , Reddy Narendra , Simpson Hugh

Aims: Our aim was to explore factors related to the acute presentation of diabetic keto-acidosis (DKA) in patients with Type 2 diabetes mellitus (T2D), and to identify any predictors for severity of DKA in T2D.Methods: This was a retrospective study based on acute medical admissions presenting to the Royal Berkshire Hospital during 2008. Criteria for inclusion included a confirmed diagnosis of DKA (defined by a plasma glucose level >11.1 mmol/l, keto...

ea0021p142 | Diabetes and metabolism | SFEBES2009

Healthcare professionals frequently fail to recognise severe obesity

Ahern Tomas , McGowan Anne , Davis Maeve , Billfalk-Kelly Astrid , O'Shea Donal

Severe obesity continues to dramatically increase in prevalence and is associated with significant mortality and morbidity. The American Society of Metabolic and Bariatric Surgery recommends that bariatric surgery only be performed on those with severe obesity. Gastric bypass surgery decreases mortality by 40% at 7.5 years.Using photographs of volunteers from a hospital based weight management clinic, we performed a survey of endocrinologists, general pr...

ea0021p143 | Diabetes and metabolism | SFEBES2009

Starvation ketoacidosis in pregnancy

Frise Charlotte , Mackillop Lucy

Introduction: Starvation ketosis outside pregnancy is a rare phenomenon and is unlikely to cause a severe acidosis. Pregnancy is an insulin resistant state due to placental production of hormones including glucagon and human placental lactogen. Insulin resistance increases with advancing gestation and this confers a susceptibility to ketosis, particularly in the third trimester. Starvation ketoacidosis in pregnancy has been reported and is usually precipitated by a period of s...

ea0021p144 | Diabetes and metabolism | SFEBES2009

Protective effects of annexin A1 in experimental endotoxaemia are mediated by an FPR-dependent mechanism

Hughes Ellen L , Buckingham Julia C , Gavins Felicity N E

Sepsis is a major clinical problem, caused by a hyperactive immune response following infection. Worldwide prevalence is estimated at 1.8 m/year and mortality at around 40%1. Protective effects of the endogenous anti-inflammatory protein annexin A1 have previously been shown in many models, including sepsis2. We therefore chose to investigate the role of the annexin A1 peptide mimetic, Ac2–26, in murine experimental endotoxaemia, and to ascertain whe...

ea0021p145 | Diabetes and metabolism | SFEBES2009

Toll-like receptor 2 (TLR2) as a biomarker for cardiovascular diseases in type 2 diabetes mellitus patients

Mohamed Kamal Gihan , Sayed Abd ElBaki Rania , Saleh ElHagrasi Rehab , Yousif Shaheen Rasha , Mohamed Samir Dina

Content: Type 2 diabetes mellitus (T2DM) may be associated with disorders in innate immune system. Toll-like receptor 2 (TLR2) is an important mediator of the innate immunity with subsequent proinflammatory reactions that thought to be involved in the cardiovascular complications in T2DM.Objective: We evaluate the role of TLR2 in T2DM patients with cardiovascular complications.Patients and methods: The study was conducted on 60 pat...

ea0021p146 | Diabetes and metabolism | SFEBES2009

Regulation of the melanocortin receptor accessory protein (MRAP) in Y1 adrenal cells

Siddiq Imran , Chung Teng-Teng , Clark Adrian

Melanocortin receptor accessory protein (MRAP) is a single transmembrane domain protein, which has been identified as essential for the cell surface trafficking and signalling of the ACTH receptor (melanocortin 2 receptor (MC2R)). MRAP is essential for the function of MC2R, but regulation of its expression remains unclear. This study aims to identify factors regulating MRAP gene expression and whether these factors would affect the signalling of MC2R.The...

ea0021p147 | Diabetes and metabolism | SFEBES2009

Annexin 1 affords cerebroprotection in sepsis

Gavins Felicity , Hughes Ellen , Patel Honeysha , Buckingham Julia

Sepsis continues to be a leading clinical problem, with ~1.8 million people worldwide affected. This continual increase in sepsis and related deaths is in part due to age, increased frequency of invasive procedures and widespread bacterial antibiotic resistance, with mortality often related to underlying disorders that often accompany sepsis. Sepsis affects the brain, and the impairment of brain function is often associated with severe infectious disease1. The endog...

ea0021p148 | Diabetes and metabolism | SFEBES2009

The lipoprotein lipase HindIII polymorphism and susceptibility to hypertension

Hemimi Neveen , Abd-Elsalam Mona , Abd-Elwahab Mahmoud

Background: Lipoprotein lipase (LPL) enzyme plays a central role in lipid metabolism. The primary function of LPL enzyme is the hydrolysis of the core triglycerides of circulating chylomicrons and very low-density lipoprotein (VLDL). It releases monoglycerides and free fatty acids, which are taken up by skeletal muscle or adipose tissue.Aim: The present work aimed to study the association of the common variant of LPL HindIII (H+) and hypertens...

ea0021p149 | Diabetes and metabolism | SFEBES2009

Intravitréal bevacizumab injection for proliferative diabetic retinopathy

Jaouad Laayoun , Yassine Mouzari , Abderrahman Douhal

Introduction: To report the efficacy and safety of intravitreal bevacizumab (avastin) as an adjunctive treatment for proliferative diabetic retinopathy (PDR).Objectives and methods: Thirteen patients (13 eyes) with PDR underwent an intravitreal injection of 1.25 mg of bevacizumab. All patients underwent a complete ophthalmic examination, anterior segment or fundus photographs at baseline and after bevacizumab injection.Results: Ele...

ea0021p150 | Diabetes and metabolism | SFEBES2009

Diabetic ketoacidosis: a 5-year retrospective analysis

O'Shea Triona , Healy Marie Louise , Nolan John , McQuaid Siobhan

Introduction and methods: Despite advances in diabetes treatment, diabetic ketoacidosis (DKA) remains a significant cause of morbidity. We performed a 5-year retrospective analysis of DKA episodes (2004–2008). Results were compared with an earlier study (1997–2001).Results: Ninety-four episodes of DKA (defined as hyperglycaemia, ketosis and acidosis) were identified through Hospital Inpatient Enquiry (HIPE). Patients with Type 1 diabetes mellit...

ea0021p151 | Diabetes and metabolism | SFEBES2009

Effect of rimonabant and metformin on oxidative stress in obese patients with polycystic ovary syndrome (PCOS)

Aye Myint M , Shepherd John , Cho Liwei , Ng J M , Marie Coady Anne , Kilpatrick Eric S , Atkin Stephen L , Sathyapalan Thozhukat

Background: Insulin resistance and obesity are characteristic features of PCOS. Oxidative stress leads to the formation of lipid peroxidation products in the skeletal muscles and has the potential to interfere with insulin signaling and thereby contribute to insulin resistance. Malondialdehyde (MDA) is a lipid peroxidation end product and is widely used as a marker of oxidative stress.Rimonabant has been shown to reduce weight and insulin resistance in o...

ea0021p152 | Diabetes and metabolism | SFEBES2009

At high dietary fat levels, dietary fish–oil may enhance metabolic efficiency but may favour a reduction in the deposition of adipose tissue

Sleeth Michelle , Thompson Emily , Anastasovska Jelena , Bell Jimmy , Frost Gary

Background: Obesity is the excessive accumulation of adipose tissue to the extent that health may be impaired. Determination of the mechanisms governing adipose deposition and body weight regulation are now a scientific priority. High dietary fat intake is generally considered to be a factor in obesity’s multi-factorial aetiology and the metabolic syndrome. Yet not all dietary fats appear to be obese genic to the same degree.Objective: To study the ...

ea0021p153 | Diabetes and metabolism | SFEBES2009

A role for aquaglyceroporins in adipogenesis

Brown James , Conner Matthew , Bill Roslyn , Ramanjaneya Manjunath , Bailey Clifford , Randeva Harpal , Conner Alex

Aims/objectives: Glycerol cycling plays an essential regulatory role in metabolism in both health and disease. Aquaporins (AQPs) are a recently described family of water transporting membrane proteins, which contain a subset of members that also have the ability to transport glycerol across the cell membrane. This study sought to investigate the adipose tissue expression profile of AQPs in humans, and to assess the role of AQPs in adipocyte differentiation.<p class="abstex...

ea0021p154 | Diabetes and metabolism | SFEBES2009

Infidelity of ectopic transcription using a pseudo splice site: lessons from HNF-1β mutation causing familial juvenile hyperuricaemic nephropathy

Piret Sian , Reed Anita , Reilly Jennifer , Turner Neil , Thakker Rajesh

Ectopic (or ‘illegitimate’) transcripts, which have been widely used to study disease-causing mutations when samples from the appropriate tissue cannot be obtained, are generally faithful representations of the normal tissue-specific counterparts. Here, we report the occurrence of ectopic transcripts of the hepatocyte nuclear factor-1 beta (HNF-1β) gene, mutations of which may result in maturity onset diabetes of the young type 5 (MODY5), the renal cysts ...

ea0021p155 | Diabetes and metabolism | SFEBES2009

Patients with Turner syndrome have a high incidence of metabolic abnormalities

Syed Sara , MacDougall Jane , Simpson Helen

Objectives: A retrospective review of adult patients with Turner syndrome (TS) attending a joint Turner syndrome clinic.Methods: Sixty-two adult patients with TS clinic were identified. Data was collected from case notes and electronic records.Results: Diagnosis was prenatal/at birth in 20%, 1–10 years in 29%, 11–20 years in 47% and after 21 years in one patient. Common presenting complaints were short stature (51%) and p...

ea0021p156 | Diabetes and metabolism | SFEBES2009

Impact of extra cellular matrix changes on adipogenesis

Zhang Lei , Steadman Robert , de Lloyd Anna , Ham Jack , Rees Aled , Ludgate Marian

Obesity (excess adipose tissue generated by hypertrophy and hyperplasia) predisposes to poor health. Adipogenesis (hyperplasia) involves the differentiation of adherent preadipocytes into non-adherent adipocytes and is accompanied by alterations to the extracellular matrix of which hyaluronan (HA) is a component. Used in vitro to promote lineage specific differentiation, little is known of HA’s role in adipogenesis. We hypothesise that HA modifications must occur d...

ea0021p157 | Diabetes and metabolism | SFEBES2009

The hyperphagic effect of ghrelin is inhibited by diets high in fat in mice

Gardiner James , Campbel Daniel , Kent Aysha , Patterson Michael , Ghatei Mohammed , Bloom Stephen , Bewick Gavin

Background and aims: Ghrelin is the only known peripheral hormone, which increases food intake. It is released from the stomach and is thought to function as a meal initiator and signal of energy deficit. We used bacterial artificial chromosome transgenesis to generate a mouse model with increased ghrelin expression and production in stomach and brain. These mice exhibited increased circulating bioactive ghrelin and as expected were hyperphagic and glucose intolerant. We hypot...

ea0021p158 | Diabetes and metabolism | SFEBES2009

Nuf mice with an activating calcium sensing receptor mutation, Leu723Gln, have a metabolic acidosis and impaired urinary acidification

Hannan Fadil , Nesbit M Andrew , Esapa Chris , Di Pretoro Simona , Lyon Mary , Cox Roger , Thakker Rajesh

The calcium sensing receptor (CaSR) is a G protein coupled receptor that is expressed in type A intercalated cells of the distal convoluted tubule and cortical collecting ducts, where it is involved in renal proton excretion. We have therefore investigated the Nuf mouse, which has an activating CaSR mutation (Leu723Gln) that leads to hypocalcaemia, hypercalciuria, renal calcification, a urinary concentrating defect, and cataracts, for disturbances in acid-base homeostasis. Mic...

ea0021p159 | Diabetes and metabolism | SFEBES2009

Brain natriuretic peptide shows no response to acute hypobaric hypoxia in humans

Woods David , Hooper Tim , Mellor Adrian , Hodkinson Pete , Wakeford Rob , Peaston Bob , Ball Steve , Green Nic

Background: Effective acclimatization to high altitude involves a natriuresis and diuresis facilitated by a suppressed aldosterone. Acute mountain sickness (AMS) is common but poorly understood. A cardiac hormone, brain natriuretic peptide (BNP), is released primarily in response to cardiomyocyte stretch but animal models suggest BNP secretion is also stimulated by acute hypoxia. An increase in BNP causes a diuresis, natriuresis and a reduction in aldosterone. We hypothesized ...

ea0021p160 | Diabetes and metabolism | SFEBES2009

Total pancreatectomy and pancreatic islet autotransplantation in patient with intractable pain caused by chronic pancreatitis

Han Thang , Abdurahman Shna , Jones Gareth , Kumar Anila , Lowdell Mark , Pratt Julian , Powis Stephen , Rolles Keith , Rosenthal Miranda , Press Martin , Kurzawinski Tomasz

Total pancreatectomy for chronic pancreatic pain is often deferred because it leaves the patient with unstable insulin-dependent diabetes. NICE (2008) has recently approved pancreatectomy with simultaneous islet autotransplantation and we here describe our first case. A 49-year-old female with a 6-year history of intractable, opioid requiring abdominal pain had become depressed to the point of suicide attempts. Imaging showed pancreatic atrophy and duct irregularity (subsequen...

ea0021p161 | Diabetes and metabolism | SFEBES2009

Weight and glycaemic outcomes following bariatric surgery in people with type 2 diabetes

Demssie Yared N , Jawaheer Jhalini , Farook Seleena , New John P , Syed Akheel A

Bariatric surgery in people with morbid obesity results in effective long-term weight loss, and resolution or reduction in the severity of several co-morbid conditions. The majority of obese people with type 2 diabetes who undergo bariatric surgery, achieve remission of their diabetes or a significant reduction of their glucose lowering therapy in the long-term. We conducted a retrospective observational study to assess changes in body weight and glycaemic control in obese typ...

ea0021p162 | Diabetes and metabolism | SFEBES2009

Effect of Ramadan fasting on glycaemic control in type 2 diabetic patients on oral hypoglacaemic agents

Norouzy Abdolreza , Nematy Mohsen , Sabery Maryam , Reza Mohajeri Mohammad , Shakeri Farnaz , Yari Sara

Ramadan is a month for Muslims during which they abstain from eating, drinking and smoking from dawn to sunset. The recommendations regarding the safety of fasting for type 2 diabetic patients have been based on expert opinion rather than evidence based medicine and sometimes controversial. In this study, we looked at the effect of Ramadan fasting on glycaemic control of type 2 diabetic patients on oral hypoglycaemic agents.Eighty-eight diabetic patients...

ea0021p163 | Diabetes and metabolism | SFEBES2009

An exploration of the predictive factors for the early pleiotropic responses to exenatide therapy in patients with type 2 diabetes mellitus

Barber Thomas , Reddy Narendra , Begbie Helen , Sophal Naseem , McCulloch Carol , Rogers Angela , Naziat Auditi , Ghosh Diptendra , Mukhtar Mamoun , Simpson Hugh

Aims: Our aim was to explore predictive factors for the pleiotropic responses to exenatide during the first 12 weeks of therapy, and associations between these responses.Methods: This was an observational study based on patients (n=83) with type 2 diabetes mellitus (T2D) in whom exenatide had been added to existing oral hypoglycaemic therapy. Exenatide was administered subcutaneously (5 mcg bd for the first month, 10 mcg bd thereafter). Data colle...

ea0021p164 | Diabetes and metabolism | SFEBES2009

Expression of store-operated Orai channels in normal and diabetic kidney

Green Andrew , Bhandari Sunil , Watson Neil , Atkin Steve , Xu Shang-Zhong

Cytosolic calcium signalling controls a vast number of cellular functions, such as contraction, secretion, cell growth and cell division. The increase of [Ca2+]i evoked by G-protein coupled receptor activation has two closely related components, i.e. the rapid phase of inositol 1,4,5-triphosphate-mediated Ca2+ release from ER stores, and followed by Ca2+ entry through store-operated channels (SOCs) in plasma membrane. Orai and STIM p...

ea0021p165 | Diabetes and metabolism | SFEBES2009

Metabolic phenotype in brothers' of women with polycystic ovarian syndrome

Siddiqui Mohammad , Gupta Mukul , Wangnoo Subhash

Women with polycystic ovary syndrome (PCOS) have twice the risk for metabolic syndrome (MetS) compared to women from the general population. Mothers and sisters of affected women also have an increased prevalence of MetS. We undertook this study to evaluate whether these abnormalities are also present in brothers’ of affected women.Design and setting: A total of 59 brothers (age ≥18 and ≤40 years) of women with PCOS and 59 healthy men (o...

ea0021p166 | Diabetes and metabolism | SFEBES2009

Nuf mice with an activating calcium-sensing receptor mutation, Leu723Gln, have impaired glucose tolerance and reduced insulin secretion

Hannan Fadil , Nesbit M Andrew , Bentley Liz , Cox Roger , Thakker Rajesh

The calcium-sensing receptor (CaSR) is a G protein coupled receptor that is expressed widely, including pancreatic beta cells where it has been shown to modulate insulin secretion in vitro. However, the role of the CaSR in regulating in vivo insulin secretion and glucose homeostasis remains unknown. We have therefore investigated the Nuf mouse, which has an activating CaSR mutation (Leu723Gln), to determine whether abnormal CaSR function in vivo affects gl...

ea0021p167 | Diabetes and metabolism | SFEBES2009

Liraglutide prevents endothelial damage triggered by glucose oscillations

Schisano Bruno , Radford Claire , Harte Allison , Mc Ternan Phillip , Ceriello A

Background: Since it has been shown that markers of oxidative stress persist in endothelial cells that have been exposed for a prolonged time to chronic constant high glucose levels, long after glucose normalization, a phenomenon defined as ‘metabolic memory’, evaluation of chronic exposure to oscillating high glucose, its impact on the induction of cellular stress markers and the onset of a ‘metabolic memory’ might be of pivotal interest. In doing so we al...

ea0021p168 | Diabetes and metabolism | SFEBES2009

Glucocorticoid and insulin regulation of lipid metabolism in human adipocytes

Gathercole Laura , Bujalska Iwona , Morgan Stuart , Hauton Dave , Stewart Paul , Tomlinson Jeremy

Patients with glucocorticoid excess develop a phenotype characterized by central obesity, however, the impact of glucocorticoids upon the processes that regulate lipid accumulation has not been fully explored. We hypothesize that intracellular generation of cortisol from cortisone by 11b-hydroxysteroid dehydrogenase type 1 (11bHSD1) is an important regulator of lipid metabolism.In adipocytes, acetyl-CoA carboxylase 1 and 2 (ACC1/2) convert acetyl-CoA to ...

ea0021p169 | Diabetes and metabolism | SFEBES2009

MOPDII and Alstrom syndrome: two centrosomopathies featuring severe insulin resistance and impaired adipogenesis

Huang-Doran Isabel , Porter Keith , O'Rahilly Stephen , Jackson Andrew , Semple Robert

Genetic defects in PCNT, encoding the centrosomal protein pericentrin, cause a rare syndrome of primordial dwarfism, skeletal dysplasia and facial dysmorphism, known as Majewski Osteodysplastic Primordial Dwarfism Type II (MOPDII). We now report that 11 out of 15 patients with PCNT defects had clinical and/or biochemical evidence of severe insulin resistance (IR), many also with severe dyslipidaemia; the remaining four were under 4 years-old. The metabolic profil...

ea0021p170 | Diabetes and metabolism | SFEBES2009

A novel syndrome of IGF1 and insulin supersensitivity

Huang-Doran Isabel , Groeneveld Matthijs , Chandrasekera Hemantha , Porter Keith , O'Rahilly Stephen , McNulty Sid , Furlong Niall , Semple Robert

GH-secreting pituitary adenomas are by far the commonest cause of acromegalic soft tissue overgrowth. However the differential diagnosis includes pseudoacromegaly in rare patients with severe insulin resistance, with or without lipodystrophy, and some congenital overgrowth syndromes such as Sotos’ syndrome, due to mutations in the NSD1 gene. We now report the case of two siblings, born to non consanguinous, clinically unaffected Europid parents, with childhood over...

ea0021p171 | Diabetes and metabolism | SFEBES2009

Biomarkers of the hypothalamic-pituitary-adrenal (HPA) axis for analysis of in vivo 11β-hydroxysteroid dehydrogenase 1 inhibition

Harno Erika , Yu Alice , Leighton Brendan , Turnbull Andrew , White Anne

Inhibition of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) as a means of reducing tissue corticosteroids is showing marked potential as a treatment for type 2 diabetes. However, reduction in tissue corticosteroids may lead to upregulation of the HPA axis. Therefore this study investigates the effect of 11β-HSD1 inhibition on HPA axis biomarkers and examines whether time of dosing impacts on the biomarkers.C57Bl6/Jax mice were fed 60% kcal...

ea0021p172 | Diabetes and metabolism | SFEBES2009

Aldosterone production by the mouse adrenal gland is compromised by a high fat diet and 11β-hydroxysteroid dehydrogenase type 1 deficiency

Nilsson Frida , Morrison Hamish , Ramage Lynne , Morton Nicholas , Seckl Jonathan , Morley Steven , Kenyon Christopher

Deficiency of the intracellular glucocorticoid (GC) reactivating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) invokes compensatory activation of the HPA axis. Nevertheless, 11β-HSD1−/− mice resist dietary-induced obesity indicating that target tissues are protected from GC actions. Since endocrine adaptation to diet is mediated by altered HPA activity, we investigated whether the adrenal response to high fat (HF) diet is compr...

ea0021p173 | Diabetes and metabolism | SFEBES2009

Transdermal delivery of insulin using amidated pectin hydrogel patches

Tufts Mark , Musabayane Cephas

In type 1 diabetes mellitus, tight glycaemic control is required to attenuate chronic complications and often requires daily injectable insulin therapy, which can result in non-compliance because of patient discomfort. As a result of this, some studies are concerned with optional routes of insulin administration. In our laboratory, we have developed amidated pectin (polygalacturonic acid) hydrogel beads for oral insulin administration. The aim of present was to investigate whe...

ea0021p174 | Diabetes and metabolism | SFEBES2009

Low testosterone level is associated with significant increase in mortality in patients with type 2 diabetes

Muraleedharan Vakkat , Marsh Hazel , Jones Hugh

Background: In men with type 2 diabetes there is high prevalence of low levels of testosterone. There is accumulating evidence that low testosterone levels are associated with greater morbidity and mortality. There is no published data regarding mortality among men with type 2 diabetes in relation to testosterone levels.Aim: We report preliminary findings from our 4 to 7 years follow up study to examine the effect of baseline testosterone on all cause mo...

ea0021p175 | Diabetes and metabolism | SFEBES2009

The effects of plant derived oleanolic acid bioactive compound on glycogenic enzymes in streptozotocin-induced diabetic rats

Cephas Musabayane , Ngubane Phikelelani , Masola Bubuya

We have reported that the anti-hyperglycaemic effects of Syzygium cordatum leaf triterpene mixtures (oleanolic acid (OA) and ursolic acid) in streptozotocin (STZ)-induced diabetic rats are mediated in part via increased hepatic glycogen synthesis. To further elucidate the mechanism(s) of the hypoglycaemic effects of the triterpene, this study investigated the effects of plant derived OA on glycogenic enzyme activities in STZ-induced diabetic rats. Pure OA was obtained f...

ea0021p176 | Diabetes and metabolism | SFEBES2009

Testosterone replacement may be beneficial in hypogonadal men with cardiovascular disease

Muraleedharan Vakkat , Dugdale Caroline , Stanworth Roger , Jones Hugh

Hypogonadism is more prevalent in populations with type 2 diabetes (T2D) and/or cardiovascular disease (CVD) and is associated with increase in all-cause and CVD mortality. Testosterone replacement therapy (TRT) improves visceral adiposity, insulin resistance, glycemia, lipids inflammatory cytokines and cardiac ischaemia. The long-term safety of TRT in men with CVD and/or T2D is not known and the British National formulary advises use with caution these groups.<p class="ab...

ea0021p177 | Diabetes and metabolism | SFEBES2009

Mice harbouring the familial juvenile hyperuricaemic nephropathy disease-causing uromodulin (Tamm--Horsfall glycoprotein) mutation Cys125Arg, have a urine concentrating defect, progressive renal failure, and altered uric acid handling

Piret Sian , Reed Anita , Nesbit M Andrew , Hough Tertius , Bentley Liz , Cox Roger , Thakker Rajesh

Familial juvenile hyperuricaemic nephropathy (FJHN), an autosomal dominant disorder characterised by raised serum urate, reduced fractional excretion of uric acid (FEUA), a urine concentrating defect, and progressive renal failure, is caused by mutations in the UMOD gene, encoding uromodulin (Tamm–Horsfall glycoprotein). The FJHN-causing UMOD mutations are missense mutations (>90%) or inframe deletions (<10%), and none result in prematurely truncated...

ea0021p178 | Diabetes and metabolism | SFEBES2009

Investigating the role of ventromedial hypothalamic glucose-sensing neurones in the response to hypoglycaemia

Richardson Errol , Sufyan Hussain Syed , Robert Counsell John , Bewick Gavin , Bloom Stephen , Gardiner James

Hypoglycaemia and hypoglycaemia unawareness severely limit the optimal management of diabetes mellitus and cause recurrent morbidity and even mortality in intensively controlled patients. Altered hypothalamic glucose sensing has been implicated in the development of defective counter regulatory responses to insulin induced hypoglycaemia and hypoglycaemic unawareness. This change in hypothalamic glucose sensing has been attributed, at least in part, to an increase in glucokinas...

ea0021p179 | Diabetes and metabolism | SFEBES2009

Functional muscarinic acetylcholine receptors are expressed in white and brown adipose tissue

Stephens Mark , Rees Aled , Ludgate Marian

Both brown (BAT) and white (WAT) adipose tissue have neuroanatomically well characterized sympathetic innervation (with activation initiating lipid mobilization), but little evidence to support the presence of a (putatively counter-regulatory) parasympathetic input.Parasympathetic actions are mediated through muscarinic acetylcholine receptors (mAChR). The mouse 3T3-L1 (white fat-derived) cell line expresses M1, M3 and M4 mAChR during differen...

ea0021p180 | Diabetes and metabolism | SFEBES2009

Impact of glucocorticoids upon lipogenesis and β-oxidation in skeletal muscle

Morgan Stuart , Gathercole Laura , Stewart Paul , Smith Dave , Tomlinson Jeremy

Glucocorticoid excess is characterized by increased adiposity, skeletal myopathy and insulin resistance. Although there is a strong inverse correlation between intramuscular triglyceride (IMTG) levels and insulin sensitivity, the impact of glucocorticoids upon the processes that regulate skeletal muscle lipid metabolism has not been explored.Mouse C2C12 skeletal myocytes were grown to confluence and differentiated into myotubes in chemically defined medi...

ea0021p181 | Diabetes and metabolism | SFEBES2009

The influence of HIV status and antiretroviral (ARV) therapy on expression of genes related to mitochondrial metabolism in human adipose tissue (AT)

McGee Kirsty , Boothby Meg , Harte Alison , Tomlinson Jeremy , Hill Margaret , Gathercole Laura , Kumar Sudhesh , Shahmanesh Mohsen , McTernan Philip

Background and aims: The mechanisms in HIV by which mitochondrial dysfunction occurs, leading to impaired energy homeostasis and metabolic regulation, are unclear; although similarities are noted in T2DM. Therefore, we investigated the effect of HIV status and ARV therapy on several mitochondrial and nuclear encoded genes related to mitochondrial metabolism and energy homeostasis.Materials and methods: Subcutaneous AT biopsies from the ileac crest were o...

ea0021p182 | Diabetes and metabolism | SFEBES2009

Deficiency in 11β-hydroxysteroid dehydrogenase type 1 reduces systemic inflammation and inflammatory cell infiltration in atherosclerotic lesions of ApoE−/− mice

Kipari Tiina , Man Tak-Yung , Hadoke Patrick , White Christopher , Chapman Karen , Seckl Jonathan

High plasma levels of glucocorticoids cause metabolic disease (central obesity, hypertension, diabetes) and increase risk of cardiovascular disease. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates glucocorticoids in intact cells, converting inert cortisone (11-dehydrocorticosterone in rodents) into active cortisol (corticosterone in rodents). Recent work has shown the pathological importance of elevated adipose tissue 11β-HSD1 expression in develo...

ea0021p183 | Diabetes and metabolism | SFEBES2009

Short sleep duration is independently associated with obesity in with Type 2 diabetes

Tahrani Abd , Begum Safia , Mughal Shanaz , Dubb Kiran , Banerjee Dev , Thomas G Neil , Ali Asad , Jose Biju , Piya Milan , Stevens Martin , Barnett Anthony , Taheri Shahrad

Background: From population studies, short and long sleep duration are associated with obesity. This association has not been studied in patients with type 2 diabetes (T2D).Methods: Design: Cross-sectional study of adult T2D patients recruited randomly from outpatient department of a large UK tertiary centre. Patients with known sleep-related disorders were excluded. Data were collected during one-to-one interviews. Sleep duration assessment: 7-day sleep...

ea0021p184 | Diabetes and metabolism | SFEBES2009

Vitamin D status relates to premature aortic sclerosis in South Asians -- a novel risk factor for cardiovascular disease?

Webb David , Davies Melanie , Khunti Kamlesh

Background: South Asians are at higher risk of vascular disease than the indigenous UK population. Susceptibility to conventional cardiovascular risk factors does not entirely account for this discrepancy. Vitamin D deficiency within this group may be an important patho-physiological contributor and an overlooked treatable cardiovascular risk factor.Aims: To determine whether serum 25-(OH) Vitamin D concentration independently associates with a surrogate...

ea0021p185 | Diabetes and metabolism | SFEBES2009

Diet-induced obesity in C57Bl/6 mice is associated with sex-specific changes in glucocorticoid metabolism

Dakin Rachel , Hadoke Patrick , Seckl Jonathan , Walker Brian , Drake Amanda

Although obesity affects men and women, the risks of associated metabolic disturbances (e.g. type 2 diabetes) differ between the sexes. Altered peripheral glucocorticoid metabolism may underpin the metabolic consequences of obesity; however, most research exploring this has focused on male animals. This study used a mouse model to investigate the hypothesis that alterations in glucocorticoid metabolism caused by diet-induced obesity (DIO) will be more profound in males than in...

ea0021p186 | Diabetes and metabolism | SFEBES2009

Circadian rhythmicity is altered in hepatic corticosterone-related genes from diet induced obese mice

Harno Erika , Yu Alice , Brown Henry , Turnbull Andrew , Leighton Brendan , White Anne

Increased corticosterone (cortisol in humans) in liver has important adverse effects on glucose metabolism and is therefore a target for diabetes treatments. The functional effects of corticosterone depend on circulating levels as well as tissue regeneration by 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) and inactivation by steroid 5-α-reductase type I (5αR). This study investigates how obesity affects diurnal changes in circulating corticosterone, the ge...

ea0021p187 | Diabetes and metabolism | SFEBES2009

Down-regulation of adipose 11βHSD1 mediates the insulin sensitising effects of salicylate in obesity

Nixon Mark , Livingstone Dawn , Andrew Ruth , Walker Brian

Anti-inflammatory salicylates improve insulin sensitivity, however the mechanism remains unclear. We have observed down-regulation of the glucocorticoid regenerating enzyme 11β-hydroxysteroid dehydrogenase 1 (11βHSD1) by salicylates in cultured adipocytes and in human adipose tissue after oral salsalate therapy, consistent with known transcriptional regulation of 11βHSD1 by pro-inflammatory cytokines. Since inhibition of 11βHSD1 improves insulin sensitivity...