Endocrine Abstracts

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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 ...

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...

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 ...

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...

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...

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...

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...

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 ...

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...

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...

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...

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...

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...

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...

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...

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...

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 ...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...