Publications by authors named "Efthimia Karra"

19 Publications

  • Page 1 of 1

A UK nationwide study of people with type 1 diabetes admitted to hospital with COVID-19 infection.

Diabetologia 2021 May 8. Epub 2021 May 8.

Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.

Aims/hypothesis: The aim of this work was to describe the clinical characteristics of adults with type 1 diabetes admitted to hospital and the risk factors associated with severe coronavirus disease-2019 (COVID-19) in the UK.

Methods: A retrospective cohort study was performed using data collected through a nationwide audit of people admitted to hospital with diabetes and COVID-19, conducted by the Association of British Clinical Diabetologists from March to October 2020. Prespecified demographic, clinical, medication and laboratory data were collected from the electronic and paper medical record systems of the participating hospitals by local clinicians. The primary outcome of the study, severe COVID-19, was defined as death in hospital and/or admission to the adult intensive care unit (AICU). Logistic regression models were used to generate age-adjusted ORs.

Results: Forty UK centres submitted data. The final dataset included 196 adults who were admitted to hospital and had both type 1 diabetes and COVID-19 on admission (male sex 55%, white 70%, with mean [SD] age 62 [19] years, BMI 28.3 [7.3] kg/m and last recorded HbA 76 [31] mmol/mol [9.1 (5.0)%]). The prevalence of pre-existing microvascular disease and macrovascular disease was 56% and 39%, respectively. The prevalence of diabetic ketoacidosis on admission was 29%. A total of 68 patients (35%) died or were admitted to AICU. The proportions of people that died were 7%, 38% and 38% of those aged <55, 55-74 and ≥75 years, respectively. BMI, serum creatinine levels and having one or more microvascular complications were positively associated with the primary outcome after adjusting for age.

Conclusions/interpretation: In people with type 1 diabetes and COVID-19 who were admitted to hospital in the UK, higher BMI, poorer renal function and presence of microvascular complications were associated with greater risk of death and/or admission to AICU. Risk of severe COVID-19 is reassuringly very low in people with type 1 diabetes who are under 55 years of age without microvascular or macrovascular disease. IN PEOPLE WITH TYPE 1 DIABETES AND COVID-19 ADMITTED TO HOSPITAL IN THE UK, BMI AND ONE OR MORE MICROVASCULAR COMPLICATIONS HAD A POSITIVE ASSOCIATION AND LOW SERUM CREATINE LEVELS HAD A NEGATIVE ASSOCIATION WITH DEATH/ADMISSION TO INTENSIVE CARE UNIT AFTER ADJUSTING FOR AGE.
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http://dx.doi.org/10.1007/s00125-021-05463-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106514PMC
May 2021

-Induced Acute Psychosis: A Novel Cause of Acute Psychosis.

Case Rep Infect Dis 2021 4;2021:6649717. Epub 2021 Mar 4.

Physicians' Clinic, London W1G 7AE, UK.

Background: Infections have long been linked to psychosis and categorised within "secondary" psychoses. To date, there have been few reports of psychosis linked to brucellosis. This case report aims to present one such case. . A 31-year-old man was admitted to a general hospital with pyrexia, severe right upper quadrant pain, and an acute psychosis following a two-week holiday in South East Asia and the Mediterranean. Serological tests revealed that he had brucellosis. Following antibiotic treatment, the psychotic symptoms abated and he was discharged within ten days of hospitalisation.

Conclusions: This case of organic psychosis highlights the importance of considering brucellosis as a rare cause of acute psychosis. The exact mechanism of -induced psychosis remains unclear.
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http://dx.doi.org/10.1155/2021/6649717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954612PMC
March 2021

Protracted ketonaemia in hyperglycaemic emergencies in COVID-19: a retrospective case series.

Lancet Diabetes Endocrinol 2020 08 1;8(8):660-663. Epub 2020 Jul 1.

Department of Diabetes and Endocrinology, Royal Free Hospital, Royal Free London NHS Foundation Trust, London NW3 2QG, UK. Electronic address:

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http://dx.doi.org/10.1016/S2213-8587(20)30221-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329282PMC
August 2020

A severe case of methaemoglobinaemia in a Brazilian hairdresser.

BMJ Case Rep 2020 Jan 21;13(1). Epub 2020 Jan 21.

Endocrinology and Diabetes, Royal Free Hospital, Hampstead, London, UK.

Methaemoglobinaemia is an extremely rare condition with multiple causes, both genetic and acquired. We present a severe case of methaemoglobinaemia occurring in a Brazilian hairdresser working in the UK. She presented after several days of preparing popular 'Brazilian blowdry' treatments for customers at a hair salon. She had been exposed to multiple volatile chemicals, including formaldehyde, without any respiratory protection, and we postulate that this may have caused her illness. If so, this would be the first published case of methaemoglobinaemia caused by exposure to the volatile components of beauty products.
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http://dx.doi.org/10.1136/bcr-2019-232735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7021157PMC
January 2020

New diagnosis of hyperthyroidism in primary care.

BMJ 2018 Aug 24;362:k2880. Epub 2018 Aug 24.

Royal Free London NHS Trust, London, UK.

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http://dx.doi.org/10.1136/bmj.k2880DOI Listing
August 2018

Management of patients with thyroid eye disease.

Br J Hosp Med (Lond) 2016 Jan;77(1):C6-9

Consultant Physician in Diabetes and Endocrinology at University College London Hospital, London.

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http://dx.doi.org/10.12968/hmed.2016.77.1.C6DOI Listing
January 2016

Clinical assessment of patients with thyroid eye disease.

Br J Hosp Med (Lond) 2016 Jan;77(1):C2-5

Consultant Physician in Diabetes and Endocrinology at University College London Hospital, London.

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http://dx.doi.org/10.12968/hmed.2016.77.1.C2DOI Listing
January 2016

Resolution of acute inflammation bridges the gap between innate and adaptive immunity.

Blood 2014 Sep 8;124(11):1748-64. Epub 2014 Jul 8.

Division of Medicine, Centre for Clinical Pharmacology and Therapeutics, University College London, London, United Kingdom;

Acute inflammation is traditionally characterized by polymorphonuclear leukocytes (PMN) influx followed by phagocytosing macrophage (Mφs) that clear injurious stimuli leading to resolution and tissue homeostasis. However, using the peritoneal cavity, we found that although innate immune-mediated responses to low-dose zymosan or bacteria resolve within days, these stimuli, but not hyperinflammatory stimuli, trigger a previously overlooked second wave of leukocyte influx into tissues that persists for weeks. These cells comprise distinct populations of tissue-resident Mφs (resMφs), Ly6c(hi) monocyte-derived Mφs (moMφs), monocyte-derived dendritic cells (moDCs), and myeloid-derived suppressor cells (MDSCs). Postresolution mononuclear phagocytes were observed alongside lymph node expansion and increased numbers of blood and peritoneal memory T and B lymphocytes. The resMφs and moMφs triggered FoxP3 expression within CD4 cells, whereas moDCs drive T-cell proliferation. The resMφs preferentially clear apoptotic PMNs and migrate to lymph nodes to bring about their contraction in an inducible nitric oxide synthase-dependent manner. Finally, moMφs remain in tissues for months postresolution, alongside altered numbers of T cells collectively dictating the magnitude of subsequent acute inflammatory reactions. These data challenge the prevailing idea that resolution leads back to homeostasis and asserts that resolution acts as a bridge between innate and adaptive immunity, as well as tissue reprogramming.
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http://dx.doi.org/10.1182/blood-2014-03-562710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4383794PMC
September 2014

Differential effects of laparoscopic sleeve gastrectomy and laparoscopic gastric bypass on appetite, circulating acyl-ghrelin, peptide YY3-36 and active GLP-1 levels in non-diabetic humans.

Obes Surg 2014 Feb;24(2):241-52

Centre for Obesity Research Department of Medicine, University College London, Rayne Institute, 5, University Street, WC1E 6JJ, London, UK.

Laparoscopic Roux-en-Y gastric bypass (LRYGBP) reduces appetite and induces significant and sustainable weight loss. Circulating gut hormones changes engendered by LRYGBP are implicated in mediating these beneficial effects. Laparoscopic sleeve gastrectomy (LSG) is advocated as an alternative to LRYGBP, with comparable short-term weight loss and metabolic outcomes. LRYGBP and LSG are anatomically distinct procedures causing differential entero-endocrine cell nutrient exposure and thus potentially different gut hormone changes. Studies reporting the comparative effects of LRYGBP and LSG on appetite and circulating gut hormones are controversial, with no data to date on the effects of LSG on circulating peptide YY3-36 (PYY3-36) levels, the specific PYY anorectic isoform. In this study, we prospectively investigated appetite and gut hormone changes in response to LRYGBP and LSG in adiposity-matched non-diabetic patients. Anthropometric indices, leptin, fasted and nutrient-stimulated acyl-ghrelin, active glucagon-like peptide-1 (GLP-1), PYY3-36 levels and appetite were determined pre-operatively and at 6 and 12 weeks post-operatively in obese, non-diabetic females, with ten undergoing LRYGBP and eight adiposity-matched females undergoing LSG. LRYGBP and LSG comparably reduced adiposity. LSG decreased fasting and post-prandial plasma acyl-ghrelin compared to pre-surgery and to LRYGBP. Nutrient-stimulated PYY3-36 and active GLP-1 concentrations increased post-operatively in both groups. However, LRYGBP induced greater, more sustained PYY3-36 and active GLP-1 increments compared to LSG. LRYGBP suppressed fasting hunger compared to LSG. A similar increase in post-prandial fullness was observed post-surgery following both procedures. LRYGBP and LSG produced comparable enhanced satiety and weight loss. However, LSG and LRYGBP differentially altered gut hormone profiles.
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http://dx.doi.org/10.1007/s11695-013-1066-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3890046PMC
February 2014

Contribution of 32 GWAS-identified common variants to severe obesity in European adults referred for bariatric surgery.

PLoS One 2013 7;8(8):e70735. Epub 2013 Aug 7.

Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.

The prevalence of severe obesity, defined as body mass index (BMI) ≥ 35.0 kg/m(2), is rising rapidly. Given the disproportionately high health burden and healthcare costs associated with this condition, understanding the underlying aetiology, including predisposing genetic factors, is a biomedical research priority. Previous studies have suggested that severe obesity represents an extreme tail of the population BMI variation, reflecting shared genetic factors operating across the spectrum. Here, we sought to determine whether a panel of 32 known common obesity-susceptibility variants contribute to severe obesity in patients (n = 1,003, mean BMI 48.4 ± 8.1 kg/m(2)) attending bariatric surgery clinics in two European centres. We examined the effects of these 32 common variants on obesity risk and BMI, both as individual markers and in combination as a genetic risk score, in a comparison with normal-weight controls (n = 1,809, BMI 18.0-24.9 kg/m(2)); an approach which, to our knowledge, has not been previously undertaken in the setting of a bariatric clinic. We found strong associations with severe obesity for SNP rs9939609 within the FTO gene (P = 9.3 × 10(-8)) and SNP rs2815752 near the NEGR1 gene (P = 3.6 × 10(-4)), and directionally consistent nominal associations (P<0.05) for 12 other SNPs. The genetic risk score associated with severe obesity (P = 8.3 × 10(-11)) but, within the bariatric cohort, this score did not associate with BMI itself (P = 0.264). Our results show significant effects of individual BMI-associated common variants within a relatively small sample size of bariatric patients. Furthermore, the burden of such low-penetrant risk alleles contributes to severe obesity in this population. Our findings support that severe obesity observed in bariatric patients represents an extreme tail of the population BMI variation. Moreover, future genetic studies focused on bariatric patients may provide valuable insights into the pathogenesis of obesity at a population level.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0070735PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3737377PMC
August 2014

Appetite, energy intake, and PYY3-36 responses to energy-matched continuous exercise and submaximal high-intensity exercise.

Appl Physiol Nutr Metab 2013 Sep 22;38(9):947-52. Epub 2013 Apr 22.

a School of Sport, Exercise, and Health Sciences, Loughborough University, Leicestershire LE11 3TU, UK.

High-intensity intermittent exercise induces physiological adaptations similar to energy-matched continuous exercise, but the comparative appetite and energy balance responses are unknown. Twelve healthy males (mean ± SD: age, 22 ± 3 years; body mass index, 23.7 ± 3.0 kg·m(-2); maximum oxygen uptake, 52.4 ± 7.1 mL·kg(-1)·min(-1)) completed three 8 h trials (control, steady-state exercise (SSE), high-intensity intermittent exercise (HIIE)) separated by 1 week. Trials commenced upon completion of a standardized breakfast. Exercise was performed from hour 2 to hour 3. In SSE, 60 min of cycling at 59.5% ± 1.6% of maximum oxygen uptake was performed. In HIIE, ten 4-min cycling intervals were completed at 85.8% ± 4.0% of maximum oxygen uptake, with a 2-min rest between each interval. A standardized lunch and an ad libitum afternoon meal were provided at hours 3.75 and 7, respectively. Appetite ratings and peptide YY3-36 concentrations were measured throughout each trial. Appetite was acutely suppressed during exercise, but more so during HIIE (p < 0.05). Peptide YY3-36 concentrations increased significantly upon cessation of exercise in SSE (p = 0.002), but were highest in the hours after exercise in HIIE (p = 0.05). Exercise energy expenditure was not different between HIIE and SSE (p = 0.649), but perceived exertion was higher in HIIE (p < 0.0005). Ad libitum energy intake did not differ between trials (p = 0.833). Therefore, relative energy intake (energy intake minus the net energy expenditure of exercise) was lower in the SSE and HIIE trials than in the control trial (control, 4759 ± 1268 kJ; SSE, 2362 ± 1224 kJ; HIIE, 2523 ± 1402 kJ; p < 0.0005). An acute bout of energy-matched continuous exercise and HIIE were equally effective at inducing an energy deficit without stimulating compensatory increases in appetite.
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http://dx.doi.org/10.1139/apnm-2012-0484DOI Listing
September 2013

A link between FTO, ghrelin, and impaired brain food-cue responsivity.

J Clin Invest 2013 Aug 15;123(8):3539-51. Epub 2013 Jul 15.

Centre for Obesity Research, University College London, London, United Kingdom.

Polymorphisms in the fat mass and obesity-associated gene (FTO) are associated with human obesity and obesity-prone behaviors, including increased food intake and a preference for energy-dense foods. FTO demethylates N6-methyladenosine, a potential regulatory RNA modification, but the mechanisms by which FTO predisposes humans to obesity remain unclear. In adiposity-matched, normal-weight humans, we showed that subjects homozygous for the FTO "obesity-risk" rs9939609 A allele have dysregulated circulating levels of the orexigenic hormone acyl-ghrelin and attenuated postprandial appetite reduction. Using functional MRI (fMRI) in normal-weight AA and TT humans, we found that the FTO genotype modulates the neural responses to food images in homeostatic and brain reward regions. Furthermore, AA and TT subjects exhibited divergent neural responsiveness to circulating acyl-ghrelin within brain regions that regulate appetite, reward processing, and incentive motivation. In cell models, FTO overexpression reduced ghrelin mRNA N6-methyladenosine methylation, concomitantly increasing ghrelin mRNA and peptide levels. Furthermore, peripheral blood cells from AA human subjects exhibited increased FTO mRNA, reduced ghrelin mRNA N6-methyladenosine methylation, and increased ghrelin mRNA abundance compared with TT subjects. Our findings show that FTO regulates ghrelin, a key mediator of ingestive behavior, and offer insight into how FTO obesity-risk alleles predispose to increased energy intake and obesity in humans.
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http://dx.doi.org/10.1172/JCI44403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3726147PMC
August 2013

Differential pre-mRNA splicing regulates Nnat isoforms in the hypothalamus after gastric bypass surgery in mice.

PLoS One 2013 20;8(3):e59407. Epub 2013 Mar 20.

Centre for Obesity Research, Rayne Institute, Department of Medicine, University College London, London, United Kingdom.

Background: Neuronatin (NNAT) is an endoplasmic reticulum proteolipid implicated in intracellular signalling. Nnat is highly-expressed in the hypothalamus, where it is acutely regulated by nutrients and leptin. Nnat pre-mRNA is differentially spliced to create Nnat-α and -β isoforms. Genetic variation of NNAT is associated with severe obesity. Currently, little is known about the long-term regulation of Nnat.

Methods: Expression of Nnat isoforms were examined in the hypothalamus of mice in response to acute fast/feed, chronic caloric restriction, diet-induced obesity and modified gastric bypass surgery. Nnat expression was assessed in the central nervous system and gastrointestinal tissues. RTqPCR was used to determine isoform-specific expression of Nnat mRNA.

Results: Hypothalamic expression of both Nnat isoforms was comparably decreased by overnight and 24-h fasting. Nnat expression was unaltered in diet-induced obesity, or subsequent switch to a calorie restricted diet. Nnat isoforms showed differential expression in the hypothalamus but not brainstem after bypass surgery. Hypothalamic Nnat-β expression was significantly reduced after bypass compared with sham surgery (P = 0.003), and was positively correlated with post-operative weight-loss (R(2) = 0.38, P = 0.01). In contrast, Nnat-α expression was not suppressed after bypass surgery (P = 0.19), and expression did not correlate with reduction in weight after surgery (R(2) = 0.06, P = 0.34). Hypothalamic expression of Nnat-β correlated weakly with circulating leptin, but neither isoform correlated with fasting gut hormone levels post- surgery. Nnat expression was detected in brainstem, brown-adipose tissue, stomach and small intestine.

Conclusions: Nnat expression in hypothalamus is regulated by short-term nutrient availability, but unaltered by diet-induced obesity or calorie restriction. While Nnat isoforms in the hypothalamus are co-ordinately regulated by acute nutrient supply, after modified gastric bypass surgery Nnat isoforms show differential expression. These results raise the possibility that in the radically altered nutrient and hormonal milieu created by bypass surgery, resultant differential splicing of Nnat pre-mRNA may contribute to weight-loss.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0059407PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3603916PMC
September 2013

Acromegaly.

Br J Hosp Med (Lond) 2012 Aug;73(8):C119-23

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http://dx.doi.org/10.12968/hmed.2012.73.sup8.c119DOI Listing
August 2012

Diet and gastrointestinal bypass-induced weight loss: the roles of ghrelin and peptide YY.

Diabetes 2011 Mar 3;60(3):810-8. Epub 2011 Feb 3.

Centre for Obesity Research, Department of Medicine, University College London, Rayne Institute, London, UK.

Objective: Bariatric surgery causes durable weight loss. Gut hormones are implicated in obesity pathogenesis, dietary failure, and mediating gastrointestinal bypass (GIBP) surgery weight loss. In mice, we determined the effects of diet-induced obesity (DIO), subsequent dieting, and GIBP surgery on ghrelin, peptide YY (PYY), and glucagon-like peptide-1 (GLP-1). To evaluate PYY's role in mediating weight loss post-GIBP, we undertook GIBP surgery in PyyKO mice.

Research Design And Methods: Male C57BL/6 mice randomized to a high-fat diet or control diet were killed at 4-week intervals. DIO mice underwent switch to ad libitum low-fat diet (DIO-switch) or caloric restriction (CR) for 4 weeks before being killed. PyyKO mice and their DIO wild-type (WT) littermates underwent GIBP or sham surgery and were culled 10 days postoperatively. Fasting acyl-ghrelin, total PYY, active GLP-1 concentrations, stomach ghrelin expression, and colonic Pyy and glucagon expression were determined. Fasting and postprandial PYY and GLP-1 concentrations were assessed 30 days postsurgery in GIBP and sham pair-fed (sham.PF) groups.

Results: DIO progressively reduced circulating fasting acyl-ghrelin, PYY, and GLP-1 levels. CR and DIO-switch caused weight loss but failed to restore circulating PYY to weight-appropriate levels. After GIBP, WT mice lost weight and exhibited increased circulating fasting PYY and colonic Pyy and glucagon expression. In contrast, the acute effects of GIBP on body weight were lost in PyyKO mice. Fasting PYY and postprandial PYY and GLP-1 levels were increased in GIBP mice compared with sham.PF mice.

Conclusions: PYY plays a key role in mediating the early weight loss observed post-GIBP, whereas relative PYY deficiency during dieting may compromise weight-loss attempts.
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http://dx.doi.org/10.2337/db10-0566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3046841PMC
March 2011

Mechanisms facilitating weight loss and resolution of type 2 diabetes following bariatric surgery.

Trends Endocrinol Metab 2010 Jun 3;21(6):337-44. Epub 2010 Feb 3.

Department of Medicine, University College London, Centre for Obesity Research, 5 University Street, London WC1E 6JJ, United Kingdom.

Bariatric surgery is the most effective treatment modality for obesity, resulting in durable weight loss and amelioration of obesity-associated comorbidities, particularly type 2 diabetes mellitus (T2DM). Moreover, the metabolic benefits of bariatric surgery occur independently of weight loss. There is increasing evidence that surgically induced alterations in circulating gut hormones mediate these beneficial effects of bariatric surgery. Here, we summarise current knowledge on the effects of different bariatric procedures on circulating gut hormone levels. We also discuss the theories that have been put forward to explain the weight loss and T2DM resolution following bariatric surgery. Understanding the mechanisms mediating these beneficial outcomes of bariatric surgery could result in new non-surgical treatment strategies for obesity and T2DM.
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http://dx.doi.org/10.1016/j.tem.2010.01.006DOI Listing
June 2010

The role of gut hormones in the regulation of body weight and energy homeostasis.

Mol Cell Endocrinol 2010 Mar 27;316(2):120-8. Epub 2009 Jun 27.

Centre for Diabetes and Endocrinology, Department of Medicine, University College London, London, United Kingdom.

Obesity is one of the greatest public health challenges of the 21st century with 1.6 billion adults currently classified as being overweight and 400 million as obese. Obesity is causally associated with type 2 diabetes, hypertension, cardiovascular disease, obstructive sleep apnoea and certain forms of cancer and is now one of the leading causes of mortality and morbidity worldwide. The gastrointestinal tract is the largest endocrine organ in the body producing hormones that have important sensing and signaling roles in regulating body weight and energy expenditure. The last decade has witnessed a marked increase in our understanding of the role of gut hormones in energy homeostasis. Consequently, strategies aimed at modulating circulating gut hormone concentrations or targeting their receptors are being developed as potential pharmacotherapies for obesity. This review summarizes the current knowledge regarding the mechanisms, sites of action and effects of the anorectic gut hormones peptide tyrosine-tyrosine (PYY), pancreatic polypeptide (PP), oxyntomodulin, and amylin and of the unique orexigenic hormone, ghrelin.
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http://dx.doi.org/10.1016/j.mce.2009.06.010DOI Listing
March 2010

Subject standardization, acclimatization, and sample processing affect gut hormone levels and appetite in humans.

Gastroenterology 2009 Jun 21;136(7):2115-26. Epub 2009 Feb 21.

Centre for Diabetes and Endocrinology, Department of Medicine, University College London, Rayne Institute, London, United Kingdom.

Background & Aims: Gut hormones represent attractive therapeutic targets for the treatment of obesity and type 2 diabetes. However, controversy surrounds the effects that adiposity, dietary manipulations, and bariatric surgery have on their circulating concentrations. We sought to determine whether these discrepancies are due to methodologic differences.

Methods: Ten normal-weight males participated in a 4-way crossover study investigating whether fasting appetite scores, plasma acyl-ghrelin, active glucagon-like peptide-1 (GLP-1), and peptide YY3-36 (PYY3-36) levels are altered by study-induced stress, prior food consumption, and sample processing.

Results: Study visit order affected anxiety, plasma cortisol, and temporal profiles of appetite and plasma PYY3-36, with increased anxiety and cortisol concentrations on the first study day. Plasma cortisol area under the curve (AUC) correlated positively with plasma PYY3-36 AUC. Despite a 14-hour fast, baseline hunger, PYY3-36 concentrations, temporal appetite profiles, PYY3-36 AUC, and active GLP-1 were affected by the previous evening's meal. Sample processing studies revealed that sample acidification and esterase inhibition are required when measuring acyl-ghrelin and dipeptidyl-peptidase IV inhibitor addition for active GLP-1. However, plasma PYY3-36 concentrations were unaffected by addition of dipeptidyl-peptidase IV.

Conclusions: Accurate assessment of appetite, feeding behavior, and gut hormone concentrations requires standardization of prior food consumption and subject acclimatization to the study protocol. Moreover, because of the labile nature of acyl-ghrelin and active GLP-1, specialized sample processing needs to be undertaken.
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http://dx.doi.org/10.1053/j.gastro.2009.02.047DOI Listing
June 2009

The role of peptide YY in appetite regulation and obesity.

J Physiol 2009 Jan 8;587(1):19-25. Epub 2008 Dec 8.

Centre for Diabetes and Endocrinology, Department of Medicine, University College London, 5 University Street, London WC1E 6JJ, UK.

The last decade has witnessed a marked increase in our understanding of the importance of gut hormones in the regulation of energy homeostasis. In particular, the discovery that the gut hormone peptide YY 3-36 (PYY3-36) reduced feeding in obese rodents and humans fuelled interest in the role of PYY3-36 in body weight regulation. Pharmacological and genetic approaches have revealed that the Y2-receptor mediates the anorectic effects of PYY3-36 whilst mechanistic studies in rodents identified the hypothalamus, vagus and brainstem regions as potential sites of action. More recently, using functional brain imaging techniques in humans, PYY3-36 was found to modulate neuronal activity within hypothalamic and brainstem, and brain regions involved in reward processing. Several lines of evidence suggest that low circulating PYY concentrations predispose towards the development and or maintenance of obesity. Subjects with reduced postprandial PYY release exhibit lower satiety and circulating PYY levels that correlate negatively with markers of adiposity. In addition, mice lacking PYY are hyperphagic and become obese. Conversely, chronic PYY3-36 administration to obese rodents reduces adiposity, and transgenic mice with increased circulating PYY are resistant to diet-induced obesity. Moreover, there is emerging evidence that PYY3-36 may partly mediate the reduced appetite and weight loss benefits observed post-gastric bypass surgery. Taken together these findings, coupled with the retained responsiveness of obese subjects to the effects of PYY3-36, suggest that targeting the PYY system may offer a therapeutic strategy to help treat obesity.
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http://dx.doi.org/10.1113/jphysiol.2008.164269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2670018PMC
January 2009