Author: "A. Margot Umpleby" / Topic: business - Searchworks@Jio Institute Digital Library Search Results

42 results on '"A. Margot Umpleby"'

1. Metformin increases fasting glucose clearance and endogenous glucose production in non-diabetic individuals

Author: Lucy Coppin, A. Margot Umpleby, Ewan R. Pearson, Nicola Jackson, Andrea Mari, and Laura J. Mccreight
Subjects: Adult, Blood Glucose, Male, Glucose Clearance, medicine.medical_specialty, Endogenous glucose production, Endocrinology, Diabetes and Metabolism, Endogeny, Glucose clearance, Glucose production, Fasting glucose, Young Adult, Mixed-meal test, Internal medicine, Research Letter, Internal Medicine, Humans, Medicine, Stable isotopes, business.industry, Fasting, Human physiology, Metformin, Endocrinology, Diabetes Mellitus, Type 2, Female, business, Non diabetic, medicine.drug
Published: 2019
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2. Exploring the determinants of ethnic differences in insulin clearance between men of Black African and White European ethnicity

Author: Oluwatoyosi Bello, Fariba Shojaee-Moradie, Janet L. Peacock, Stephanie A. Amiel, Meera Ladwa, Louise M Goff, Riccardo C. Bonadonna, Olah Hakim, Maria Linda Boselli, and A. Margot Umpleby
Subjects: Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Adipose tissue, Black People, Inflammation, Type 2 diabetes, Endocrinology, Insulin resistance, Downregulation and upregulation, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Ethnicity, Humans, Insulin, Adiponectin, business.industry, General Medicine, medicine.disease, Diabetes Mellitus, Type 2, medicine.symptom, Insulin Resistance, business
Abstract: Aim People of Black African ancestry, who are known to be at disproportionately high risk of type 2 diabetes (T2D), typically exhibit lower hepatic insulin clearance compared with White Europeans. However, the mechanisms underlying this metabolic characteristic are poorly understood. We explored whether low insulin clearance in Black African (BA) men could be explained by insulin resistance, subclinical inflammation or adiponectin concentrations. Methods BA and White European (WE) men, categorised as either normal glucose tolerant (NGT) or with T2D, were recruited to undergo the following: a mixed meal tolerance test with C-peptide modelling to determine endogenous insulin clearance; fasting serum adiponectin and cytokine profiles; a hyperinsulinaemic–euglycaemic clamp to measure whole-body insulin sensitivity; and magnetic resonance imaging to quantify visceral adipose tissue. Results Forty BA (20 NGT and 20 T2D) and 41 WE (23 NGT and 18 T2D) men were studied. BA men had significantly lower insulin clearance (P = 0.011) and lower plasma adiponectin (P = 0.031) compared with WE men. In multiple regression analysis, ethnicity, insulin sensitivity and plasma adiponectin were independent predictors of insulin clearance, while age, visceral adiposity and tumour necrosis factor alpha (TNF-α) did not significantly contribute to the variation. Conclusion These data suggest that adiponectin may play a direct role in the upregulation of insulin clearance beyond its insulin-sensitising properties.
Published: 2021

3. A randomised, controlled, double blind study to assess mechanistic effects of combination therapy of dapagliflozin with exenatide QW versus dapagliflozin alone in obese patients with type 2 diabetes mellitus (RESILIENT): study protocol

Author: Victoria S. Sprung, John P.H. Wilding, Joanne A. Harrold, Emily Brown, Graham J. Kemp, Andrej Stancak, Moon Wilton, A. Margot Umpleby, Malcolm Burgess, Daniel J. Cuthbertson, Elaine Howarth, and Jason C.G. Halford
Subjects: 0301 basic medicine, medicine.medical_specialty, Combination therapy, Adipose tissue, 030209 endocrinology & metabolism, Type 2 diabetes, Placebo, RC1200, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Weight loss, Internal medicine, Medicine, Dapagliflozin, business.industry, Type 2 Diabetes Mellitus, General Medicine, medicine.disease, 030104 developmental biology, chemistry, medicine.symptom, business, Exenatide, medicine.drug
Abstract: IntroductionThe newer glucose-lowering therapies for type 2 diabetes (T2D), the glucagon-like peptide-1 receptor agonists (GLP1-RAs) and the sodium-glucose co-transporter 2 inhibitors (SGLT2i), have additional clinical benefits beyond improving glycaemic control; promoting weight loss, addressing associated cardiovascular risk factors and reducing macrovascular and microvascular complications. Considering their independent mechanisms of actions, there is a potential for significant synergy with combination therapy, yet limited data exist. This 32-week randomised, double-blind, placebo-controlled trial will gain mechanistic insight into the effects of coadministration of exenatide QW, a weekly subcutaneous GLP1-RA, with dapagliflozin, a once daily oral SGLT2i, on the dynamic, adaptive changes in energy balance, total, regional and organ-specific fat mass and multiorgan insulin sensitivity.Methods and analysis110 obese patients with diagnosed T2D (glycated haemoglobin, HbA1c ≥48 mmol/mol) will be treated for 32 weeks with dapagliflozin (10 mg once daily either alone or in combination with exenatide QW (2 mg once weekly); active treatments will be compared with a control group (placebo tablet and sham injection). The primary objective of the study is to compare the adjusted mean reduction in total body fat mass (determined by dual-energy X-ray absorptiometry, DEXA) from baseline following 32 weeks of treatment with exenatide QW and dapagliflozin versus dapagliflozin alone compared with control (placebo). Secondary outcome measures include changes in (1) energy balance (energy intake and energy expenditure measured by indirect calorimetry); (2) appetite (between and within meals) and satiety quotient; (3) body composition including visceral adipose tissue, subcutaneous adipose tissue, liver and pancreatic fat. Exploratory outcome measures include metabolic changes in hepatic and peripheral insulin sensitivity (using a two-stage hyperinsulinaemic, euglycaemic clamp), central nervous system responses to food images using blood oxygen level-dependent (BOLD) functional MRI (fMRI) and changes in cardiovascular function (using transthoracic echocardiography, cardiac MR and duplex ultrasonography).Ethics and disseminationThis study has been approved by the North West Liverpool Central Research Ethics Committee (14/NW/1147) and is conducted in accordance with the Declaration of Helsinki and the Good Clinical Practice. Results from the study will be published in peer-reviewed scientific and open access journals and/or presented at scientific conferences and summarised for distribution to the participants.Trial sponsorUniversity of Liverpool.Trial registration numberISRCTN 52028580; EUDRACT number 2015-005242-60.
Published: 2021

4. Adiponectin is associated with insulin sensitivity in white European men but not black African men

Author: Oluwatoyosi Bello, Fariba Shojaee-Moradie, Nicola Jackson, Stephanie A. Amiel, Louise M Goff, Olah Hakim, Geoffrey Charles-Edwards, A. Margot Umpleby, Janet L. Peacock, and Meera Ladwa
Subjects: Adult, Blood Glucose, Male, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Black People, Adipokine, Adipose tissue, 030209 endocrinology & metabolism, Inflammation, Type 2 diabetes, White People, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal medicine, Internal Medicine, Humans, Medicine, 030212 general & internal medicine, Aged, Adiponectin, business.industry, Incidence, Leptin, Insulin, Middle Aged, medicine.disease, United Kingdom, Diabetes Mellitus, Type 2, Female, Resistin, Insulin Resistance, medicine.symptom, business, Biomarkers
Abstract: AIMS We aimed to assess ethnic differences in inflammatory markers and their relationships with insulin sensitivity and regional adiposity between white European and black African men. METHODS A total of 53 white European and 53 black African men underwent assessment of inflammatory markers alongside Dixon-magnetic resonance imaging to quantify subcutaneous and visceral adipose tissue and intrahepatic lipid. A hyperinsulinaemic-euglycaemic clamp was used to measure whole-body and adipose tissue insulin sensitivity. To assess ethnic differences in relationships, the statistical significance of an interaction term between adipokines and ethnic group was tested in multivariable regression models. RESULTS The black African men exhibited significantly lower adiponectin and tumour necrosis factor-α (TNF-α) and greater interleukin-10 (IL-10) compared to white European men (all p
Published: 2021
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5. The fat mass and obesity-associated (FTO) gene allele rs9939609 and glucose tolerance, hepatic and total insulin sensitivity, in adults with obesity

Author: Valdemar Grill, A. Margot Umpleby, Ann Kristin Hjelle de Soysa, Fariba Shojaee-Moradie, Ingrid Løvold Mostad, Mette Langaas, and Anida Jakic
Subjects: Male, Physiology, Epidemiology, medicine.medical_treatment, Adipose tissue, Biochemistry, FTO gene, Body Mass Index, Fats, Endocrinology, Glucose Metabolism, Genotype, Medicine and Health Sciences, Insulin, Glucose Tolerance, Multidisciplinary, Organic Compounds, Monosaccharides, Middle Aged, Lipids, Chemistry, Liver, Physiological Parameters, Adipose Tissue, Connective Tissue, Physical Sciences, Carbohydrate Metabolism, Medicine, Female, Anatomy, Research Article, Adult, medicine.medical_specialty, Science, Carbohydrates, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Carbohydrate metabolism, Insulin resistance, Internal medicine, Glucose Intolerance, medicine, Humans, Obesity, Alleles, Diabetic Endocrinology, business.industry, Organic Chemistry, Body Weight, Chemical Compounds, Biology and Life Sciences, medicine.disease, Hormones, Glucose, Metabolism, Biological Tissue, Basal (medicine), Medical Risk Factors, Glucose Clamp Technique, Insulin Resistance, business
Abstract: The objective of the study was to assess associations of the rs9939609 FTO allele to glucose tolerance, hepatic and total insulin sensitivity (IS) in individuals with obesity. From a low-dose hyperinsulinemic euglycemic clamp with glucose-tracer, hepatic IS was assessed by rates of basal and suppressed glucose appearance (Ra), a measure of endogenous glucose production (EGP), and the hepatic insulin resistance index (HIR). Total IS was assessed by rates of glucose infusion (GIR), disappearance (Rd), and metabolic clearance (MCR). From a meal test we assessed IS by the Matsuda index and glucose tolerance by glucose and insulin measurements in the fasted state and postprandially for 2.5 h. The meal test was performed in 97 healthy individuals with BMI ≥35 in similar-sized risk-allele groups (n = 32 T/T, 31 A/T, and 34 A/A), and 79 of them performed the clamp. We analyzed outcomes separately for males and females, and adjusted glucose Ra, Rd, MCR, GIR, and HIR for fat mass. We did not find genotype effects on EGP. Among males, genotype A/A was associated with a significantly lower glucose Rd, MCR, and Matsuda index score relative to genotype T/T. Glucose tolerance was significantly lower in males with genotype A/T vs. T/T and A/A. For females, there were no genotype effects on hepatic or total IS, or on glucose tolerance. Independently of genotypes, females displayed a significantly better hepatic and total IS, and better glucose tolerance than males. We conclude that in subjects with similar obesity we did not register any FTO risk-allele effect on hepatic IS. A FTO risk-allele effect on total IS was registered in males only, findings which need to be reproduced in further studies. Results confirm marked differences in IS between the biological sexes and extend present knowledge by demonstrating a lower endogenous glucose production in females vs. males in uniformly obese individuals. Copyright: © 2021 de Soysa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Published: 2021

6. Investigation of the mechanism of action of duodenal mucosal resurfacing in insulin resistant women with polycystic ovarian syndrome. the DOMINO multicentre randomised controlled trial

Author: Channa N. Jayasena, Yun Miao, Belén Pérez-Pevida, Nicola Jackson, Vasha Kaur, Davinder Bansi, Georgios K. Dimitriadis, Alexander D. Miras, Barbara A. Fielding, Frederick Mears, Lisa Webber, Margot Umpleby, Danielle Bate, Danai Balfoussia, Lucy Coppin, Brett Johnson, and Harpal Randeva
Subjects: medicine.medical_specialty, Mechanism of action, Randomized controlled trial, law, business.industry, Internal medicine, medicine, Insulin resistant, medicine.symptom, business, Gastroenterology, Domino, law.invention
Published: 2020
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7. Metabolic effects of an SGLT2 inhibitor (dapagliflozin) during a period of acute insulin withdrawal and development of ketoacidosis in people with type 1 diabetes

Author: Robert Garesse, Fariba Shojaee-Moradie, David Russell-Jones, Melanie J. Davies, Mary Stevenage, Sigurd Johnsen, Roselle Herring, Nicola Jackson, A. Margot Umpleby, Agampodi Mendis, and Barbara A. Fielding
Subjects: Advanced and Specialized Nursing, Insulin pump, medicine.medical_specialty, Type 1 diabetes, business.industry, Endocrinology, Diabetes and Metabolism, Insulin, medicine.medical_treatment, 030209 endocrinology & metabolism, medicine.disease, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Basal (medicine), chemistry, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Ketone bodies, Lipolysis, 030212 general & internal medicine, Dapagliflozin, business
Abstract: OBJECTIVE To determine the effect of the sodium–glucose cotransporter 2 inhibitor dapagliflozin on glucose flux, lipolysis, and ketone body concentrations during insulin withdrawal in people with type 1 diabetes. RESEARCH DESIGN AND METHODS A double-blind, placebo-controlled crossover study with a 4-week washout period was performed in 12 people with type 1 diabetes using insulin pump therapy. Participants received dapagliflozin or placebo in random order for 7 days. Stable isotopes were infused to measure the glucose Ra, Rd, and lipolysis. At isotopic steady state, insulin was withdrawn, and the study was terminated after 600 min or earlier if blood glucose reached 18 mmol/L, bicarbonate 5.0 mmol/L. RESULTS At baseline, glucose Ra was significantly higher for the dapagliflozin group than the placebo group. Following insulin withdrawal, plasma glucose concentrations at the end point were significantly lower with dapagliflozin than placebo and glucose Rd area under the curve (AUC)0–180 min and β-hydroxybutyrate (BOHB) AUC0–180 min were significantly higher. There was a small but significantly higher glycerol Ra (measure of lipolysis) AUC0–180 min with dapagliflozin. Nonesterified fatty acid concentrations were not different between treatments. When divided by BMI >27 and CONCLUSIONS During insulin withdrawal, the increase in BOHB with dapagliflozin may be partially due to increased lipolysis. However, reduced renal excretion, reduced BOHB uptake by peripheral tissues, or a metabolic switch to increased ketogenesis within the liver may also play a role.
Published: 2020
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8. HDL-apoA-I kinetics in response to 16 wk of exercise training in men with nonalcoholic fatty liver disease

Author: Martin Whyte, John Wright, Sharaf E Sharaf, Jimmy D. Bell, Fariba Shojaee-Moradie, Graham J. Kemp, Daniel J. Cuthbertson, A. Margot Umpleby, Roselle Herring, Nicola Jackson, E. Louise Thomas, and Mark Barrett
Subjects: Adult, Male, medicine.medical_specialty, Waist, Apolipoprotein B, Physiology, Endocrinology, Diabetes and Metabolism, Intra-Abdominal Fat, Lipoproteins, VLDL, Insulin resistance, Interquartile range, Non-alcoholic Fatty Liver Disease, Physiology (medical), Internal medicine, Nonalcoholic fatty liver disease, Weight Loss, Medicine, Aerobic exercise, Humans, Exercise, Triglycerides, biology, Apolipoprotein A-I, business.industry, Cholesterol, HDL, nutritional and metabolic diseases, Metabolism, Middle Aged, medicine.disease, Kinetics, Endocrinology, Treatment Outcome, Liver, biology.protein, lipids (amino acids, peptides, and proteins), business, Lipoproteins, HDL, Body mass index
Abstract: Nonalcoholic fatty liver disease (NAFLD) is characterized by low-circulating concentration of high-density lipoprotein cholesterol (HDL-C) and raised triacylglycerol (TAG). Exercise reduces hepatic fat content, improves insulin resistance and increases clearance of very-low-density lipoprotein-1 (VLDL1). However, the effect of exercise on TAG and HDL-C metabolism is unknown. We randomized male participants to 16 wk of supervised, moderate-intensity aerobic exercise ( n = 15), or conventional lifestyle advice ( n = 12). Apolipoprotein A-I (apoA-I) and VLDL-TAG and apolipoprotein B (apoB) kinetics were investigated using stable isotopes (1-[13C]-leucine and 1,1,2,3,3-2H5 glycerol) pre- and postintervention. Participants underwent MRI/spectroscopy to assess changes in visceral fat. Results are means ± SD. At baseline, there were no differences between exercise and control groups for age (52.4 ± 7.5 vs. 52.8 ± 10.3 yr), body mass index (BMI: 31.6 ± 3.2 vs. 31.7 ± 3.6 kg/m2), and waist circumference (109.3 ± 7.5 vs. 110.0 ± 13.6 cm). Percentage of liver fat was 23.8 (interquartile range 9.8–32.5%). Exercise reduced body weight (101.3 ± 10.2 to 97.9 ± 12.2 kg; P < 0.001) and hepatic fat content [from 19.6%, interquartile range (IQR) 14.6–36.1% to 8.9% (4.4–17.8%); P = 0.001] and increased the fraction HDL-C concentration (measured following ultracentrifugation) and apoA-I pool size with no change in the control group. However, plasma and VLDL1-TAG concentrations and HDL-apoA-I fractional catabolic rate (FCR) and production rate (PR) did not change significantly with exercise. Both at baseline (all participants) and after exercise there was an inverse correlation between apoA-I pool size and VLDL-TAG and -apoB pool size. The modest effect of exercise on HDL metabolism may be explained by the lack of effect on plasma and VLDL1-TAG.
Published: 2020

9. Author response for 'Insulin clearance as the major player in the hyperinsulinaemia of black African men without diabetes'

Author: Marietta Stadler, Stephanie A. Amiel, Linda Boselli, A. Margot Umpleby, Louise M Goff, Geoff Charles-Edwards, Janet L. Peacock, Oluwatoyosi Bello, Meera Ladwa, Fariba Shojaee-Moradie, Riccardo C. Bonadonna, and Olah Hakim
Subjects: medicine.medical_specialty, Endocrinology, Black african, business.industry, Insulin, medicine.medical_treatment, Diabetes mellitus, Internal medicine, medicine, business, medicine.disease
Published: 2020
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10. Rifaximin in non-alcoholic steatohepatitis: An open-label pilot study

Author: Nicola Jackson, Jeremy Cobbold, Stephen R. Atkinson, Elaine Holmes, Fariba Shojaee-Moradie, Jimmy D. Bell, Ann Smith, Simon D. Taylor-Robinson, Robert D. Goldin, Mark Thursz, E. Louise Thomas, Michael S. Yee, Julie Stove, Julie Fitzpatrick, A. Margot Umpleby, Julian R. Marchesi, Sann N. Wai, and Quentin M. Anstee
Subjects: 0301 basic medicine, medicine.medical_specialty, Cirrhosis, Hepatology, business.industry, Urinary system, medicine.disease, Gastroenterology, Rifaximin, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, Infectious Diseases, Insulin resistance, chemistry, Diabetes mellitus, Internal medicine, medicine, 030211 gastroenterology & hepatology, Metabolic syndrome, Steatosis, Steatohepatitis, business
Abstract: Aim Gut microbial dysbiosis is implicated in the pathogenesis of non-alcoholic steatohepatitis (NASH). We investigated downstream effects of gut microbiota modulation on markers of hepatic inflammation, steatosis, and hepatic and peripheral insulin sensitivity in patients with NASH using rifaximin therapy. Methods Patients with biopsy-proven NASH and elevated aminotransferase values were included in this open-label pilot study, all receiving 6 weeks rifaximin 400 mg twice daily, followed by a 6-week observation period. The primary endpoint was change in alanine aminotransferase (ALT) after 6 weeks of rifaximin. Secondary endpoints were change in hepatic lipid content and insulin sensitivity measured with a hyperinsulinemic–euglycemic clamp. Results Fifteen patients (13 men and 2 women) with a median (range) age of 46 (32–63) years were included. Seven had diabetes on oral hypoglycemic medications and 8 had no diabetes. After 6 weeks of therapy, no differences were seen in ALT (55 [33–191] vs. 63 [41–218] IU/L, P = 0.41), peripheral glucose uptake (28.9 [19.4–48.3] to 25.5 [17.7–47.9] μmol/kg/min, P = 0.30), hepatic insulin sensitivity (35.2 [15.3–51.7]% vs. 30.0 [10.8–50.5]%, P = 0.47), or hepatic lipid content (21.6 [2.2–46.2]% vs. 24.8 [1.7–59.3]%, P = 0.59) before and after rifaximin treatment. After 12 weeks from baseline, serum ALT increased to 83 (30–217) IU/L, P = 0.02. There was a significant increase in the homeostasis model assessment–estimated insulin resistance index (P = 0.05). The urinary metabolic profile indicated a significant reduction in urinary hippurate with treatment, which reverted to baseline after cessation of rifaximin, although there was no consistent difference in relative abundance of fecal microbiota with treatment. Conclusion These data do not indicate a beneficial effect of rifaximin in patients with NASH.
Published: 2017
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11. Blueberries improve biomarkers of cardiometabolic function in participants with metabolic syndrome-results from a 6-month, double-blind, randomized controlled trial

Author: Magdalena Minnion, Colin D. Kay, Bernadette O. Fernandez, Amy Jennings, Anne Marie Minihane, Peter J. Curtis, A. Margot Umpleby, Eric B. Rimm, Aedin Cassidy, Mia S. Meiss, Vera van der Velpen, Lindsey Berends, John F. Potter, Mark L. Evans, Martin Feelisch, Evans, Mark [0000-0001-8122-8987], and Apollo - University of Cambridge Repository
Subjects: Male, 0301 basic medicine, Blueberry Plants, Medicine (miscellaneous), Blood Pressure, Type 2 diabetes, Lipoprotein particle, Prospective Studies, Pulse wave velocity, 2. Zero hunger, Metabolic Syndrome, education.field_of_study, Nutrition and Dietetics, Heart, Middle Aged, 3. Good health, metabolic syndrome, blueberry anthocyanins, flavonoids, cardiovascular disease risk, anthocyanin-derived phenolic acid metabolites, Original Research Communications, Female, medicine.medical_specialty, Statin, medicine.drug_class, Population, Pulse Wave Analysis, Anthocyanin-Derived Phenolic Acid Metabolites, Blueberry Anthocyanins, 03 medical and health sciences, Insulin resistance, Double-Blind Method, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Humans, education, Aged, Flavonoids, 030109 nutrition & dietetics, business.industry, Cholesterol, HDL, Cholesterol, LDL, Cardiovascular Disease Risk, medicine.disease, Editor's Choice, Apolipoproteins, 030104 developmental biology, Endocrinology, Fruit, Arterial stiffness, Insulin Resistance, Metabolic syndrome, business, Biomarkers
Abstract: BACKGROUND: Anthocyanin-rich blueberry intake is associated with reduced type 2 diabetes and cardiovascular disease (CVD) risk in prospective studies, although long-term randomized controlled trials (RCTs) have not been conducted in at-risk populations.OBJECTIVE: In the longest-duration RCT to date, we examined the effect of 6-mo blueberry intake on insulin resistance and cardiometabolic function in metabolic syndrome.METHODS: A double-blind, parallel RCT (n = 115; age 63 ± 7 y; 68% male; body mass index 31.2 ± 3.0 kg/m2) was conducted, which fed 2 dietarily achievable blueberry intakes [equivalent to 1/2 and 1 cup/d (75/150 g)] compared with matched placebo. Insulin resistance was assessed via the homeostasis model assessment of insulin resistance (primary endpoint) and confirmed by [6-6-2H2]-glucose-labeled, 2-step hyperinsulinemic clamp (n = 20). Clinically relevant cardiometabolic endpoints [including flow-mediated dilatation, augmentation index, lipoprotein status (by nuclear magnetic resonance spectroscopy), and nitric oxide (NO)-related metabolite assay] and anthocyanin metabolism were assessed.RESULTS: A daily intake of 1 cup of blueberries improved endothelial function (flow-mediated dilatation: +1.45%; 95% CI: 0.83%, 2.1%; P = 0.003), systemic arterial stiffness (augmentation index: -2.24%; 95% CI: -3.97%, -0.61%; P = 0.04) and attenuated cyclic guanosine monophosphate concentrations. In statin nonusers (n = 71), elevated high-density lipoprotein cholesterol (+0.08 mmol/L; P = 0.03), high-density lipoprotein particle density (+0.48n, ×10-6; P = 0.002) and apolipoprotein A-I (+0.05 g/L; P = 0.01) concentrations were observed following the 1-cup/d intervention. Treatment compliance was 94.1% (wrapper returns) and total concentrations of anthocyanin-derived phenolic acid metabolites significantly increased, dose-dependently, in serum and 24-h urine (P < 0.01 and P < 0.001, respectively). Insulin resistance, pulse wave velocity, blood pressure, NO, and overall plasma thiol status were unaffected. Likewise, a half cup per day had no effect on any biomarkers.CONCLUSIONS: Despite insulin resistance remaining unchanged we show, to our knowledge, the first sustained improvements in vascular function, lipid status, and underlying NO bioactivity following 1 cup blueberries/d. With effect sizes predictive of 12-15% reductions in CVD risk, blueberries should be included in dietary strategies to reduce individual and population CVD risk. This study was registered at clinicaltrials.gov as NCT02035592.
Published: 2019
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12. Ethnic differences in beta cell function occur independently of insulin sensitivity and pancreatic fat in black and white men

Author: Louise M Goff, A. Margot Umpleby, Maria Linda Boselli, Meera Ladwa, Riccardo C. Bonadonna, Stephanie A. Amiel, Oluwatoyosi Bello, Fariba Shojaee-Moradie, Geoff Charles-Edwards, Olah Hakim, and Janet L. Peacock
Subjects: Male, insulin secretion, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, body fat distribution, Type 2 diabetes, ethnic groups, Diseases of the endocrine glands. Clinical endocrinology, chemistry.chemical_compound, Insulin resistance, Internal medicine, Diabetes mellitus, medicine, Humans, Insulin, C-peptide, business.industry, RC648-665, medicine.disease, Black or African American, Cross-Sectional Studies, Metabolism, Endocrinology, Postprandial, Diabetes Mellitus, Type 2, type 2, chemistry, diabetes mellitus, Insulin Resistance, Beta cell, business, Body mass index
Abstract: IntroductionIt is increasingly recognized that type 2 diabetes (T2D) is a heterogenous disease with ethnic variations. Differences in insulin secretion, insulin resistance and ectopic fat are thought to contribute to these variations. Therefore, we aimed to compare postprandial insulin secretion and the relationships between insulin secretion, insulin sensitivity and pancreatic fat in men of black West African (BA) and white European (WE) ancestry.Research design and methodsA cross-sectional, observational study in which 23 WE and 23 BA men with normal glucose tolerance, matched for body mass index, underwent a mixed meal tolerance test with C peptide modeling to measure beta cell insulin secretion, an MRI to quantify intrapancreatic lipid (IPL), and a hyperinsulinemic-euglycemic clamp to measure whole-body insulin sensitivity.ResultsPostprandial insulin secretion was lower in BA versus WE men following adjustment for insulin sensitivity (estimated marginal means, BA vs WE: 40.5 (95% CI 31.8 to 49.2) × 103 vs 56.4 (95% CI 48.9 to 63.8) × 103 pmol/m2 body surface area × 180 min, p=0.008). There was a significantly different relationship by ethnicity between IPL and insulin secretion, with a stronger relationship in WE than in BA (r=0.59 vs r=0.39, interaction p=0.036); however, IPL was not a predictor of insulin secretion in either ethnic group following adjustment for insulin sensitivity.ConclusionsEthnicity is an independent determinant of beta cell function in black and white men. In response to a meal, healthy BA men exhibit lower insulin secretion compared with their WE counterparts for their given insulin sensitivity. Ethnic differences in beta cell function may contribute to the greater risk of T2D in populations of African ancestry.
Published: 2021
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13. Black African men with early type 2 diabetes have similar muscle, liver and adipose tissue insulin sensitivity to white European men despite lower visceral fat

Author: Fariba Shojee-moradie, Nicola Jackson, Louise M Goff, Oluwatoyosi Bello, Olah Hakim, Janet L. Peacock, K. George M.M. Alberti, Stephanie A. Amiel, Cynthia Mohandas, and A. Margot Umpleby
Subjects: Male, 0301 basic medicine, Endocrinology, Diabetes and Metabolism, Adipose tissue, Type 2 diabetes, Adipose insulin sensitivity, 0302 clinical medicine, ETHNIC-DIFFERENCES, London, Ethnicity, Insulin, RACIAL-DIFFERENCES, Visceral fat, NON-HISPANIC WHITES, AMERICAN CHILDREN, RISK, ENDOGENOUS GLUCOSE-PRODUCTION, Isotope, WOMEN, Middle Aged, Glucose clamp technique, Insulin sensitivity, Magnetic Resonance Imaging, medicine.anatomical_structure, Liver, Area Under Curve, Body Composition, Life Sciences & Biomedicine, Adult, medicine.medical_specialty, Adolescent, Skeletal muscle insulin sensitivity, Lipolysis, Black People, 030209 endocrinology & metabolism, Intra-Abdominal Fat, White People, Article, 1117 Public Health and Health Services, Young Adult, 03 medical and health sciences, Endocrinology & Metabolism, Insulin resistance, LIPID-METABOLISM, Tracer, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Humans, Obesity, Muscle, Skeletal, Aged, OBESE BLACK, Science & Technology, business.industry, Skeletal muscle, 1103 Clinical Sciences, Black African, medicine.disease, Non-Hispanic whites, Hepatic insulin sensitivity, 030104 developmental biology, Endocrinology, Diabetes Mellitus, Type 2, Africa, Glucose Clamp Technique, 1114 Paediatrics and Reproductive Medicine, Insulin Resistance, business, RESISTANCE
Abstract: Aims/hypothesis Type 2 diabetes is more prevalent in black African than white European populations although, paradoxically, black African individuals present with lower levels of visceral fat, which has a known association with insulin resistance. Insulin resistance occurs at a tissue-specific level; however, no study has simultaneously compared whole body, skeletal muscle, hepatic and adipose tissue insulin sensitivity between black and white men. We hypothesised that, in those with early type 2 diabetes, black (West) African men (BAM) have greater hepatic and adipose tissue insulin sensitivity, compared with white European men (WEM), because of their reduced visceral fat. Methods Eighteen BAM and 15 WEM with type 2 diabetes underwent a two-stage hyperinsulinaemic–euglycaemic clamp with stable glucose and glycerol isotope tracers to assess tissue-specific insulin sensitivity and a magnetic resonance imaging scan to assess body composition. Results We found no ethnic differences in whole body, skeletal muscle, hepatic or adipose tissue insulin sensitivity between BAM and WEM. This finding occurred in the presence of lower visceral fat in BAM (3.72 vs 5.68 kg [mean difference −1.96, 95% CI −3.30, 0.62]; p = 0.01). There was an association between skeletal muscle and adipose tissue insulin sensitivity in WEM that was not present in BAM (r = 0.78, p
Published: 2018
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14. Lixisenatide reduces chylomicron triacylglycerol due to increased clearance

Author: Nicola Jackson, Fariba Shojaee-Moradie, Sharaf E Sharaf, Martin Whyte, Jeewaka Mendis, David Russell-Jones, A. Margot Umpleby, Barbara A. Fielding, Roman Hovorka, Hovorka, Roman [0000-0003-2901-461X], and Apollo - University of Cambridge Repository
Subjects: Blood Glucose, Male, medicine.medical_specialty, Very low-density lipoprotein, Metabolic Clearance Rate, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Clinical Biochemistry, 030209 endocrinology & metabolism, Type 2 diabetes, 030204 cardiovascular system & hematology, Biochemistry, Glucagon-Like Peptide-1 Receptor, 03 medical and health sciences, Lixisenatide, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Double-Blind Method, Diabetes mellitus, Internal medicine, Chylomicrons, Medicine, Humans, Hypoglycemic Agents, Clinical Research Articles, Triglycerides, Cross-Over Studies, Gastric emptying, business.industry, Insulin, Lipids and Cardiovascular, Biochemistry (medical), Middle Aged, medicine.disease, Postprandial Period, Crossover study, Postprandial, Treatment Outcome, chemistry, Diabetes Mellitus, Type 2, Gastric Emptying, business, Peptides
Abstract: Context Glucagon-like peptide-1 (GLP-1) agonists control postprandial glucose and lipid excursion in type 2 diabetes; however, the mechanisms are unclear. Objective To determine the mechanisms of postprandial lipid and glucose control with lixisenatide (GLP-1 analog) in type 2 diabetes. Design Randomized, double-blind, cross-over study. Setting Centre for Diabetes, Endocrinology, and Research, Royal Surrey County Hospital, Guildford, United Kingdom. Patients Eight obese men with type 2 diabetes [age, 57.3 ± 1.9 years; body mass index, 30.3 ± 1.0 kg/m2; glycosylated hemoglobin, 66.5 ± 2.6 mmol/mol (8.2% ± 0.3%)]. Interventions Two metabolic studies, 4 weeks after lixisenatide or placebo, with cross-over and repetition of studies. Main Outcome Measures Study one: very-low-density lipoprotein (VLDL) and chylomicron (CM) triacylglycerol (TAG) kinetics were measured with an IV bolus of [2H5]glycerol in a 12-hour study, with hourly feeding. Oral [13C]triolein, in a single meal, labeled enterally derived TAG. Study two: glucose kinetics were measured with [U-13C]glucose in a mixed-meal (plus acetaminophen to measure gastric emptying) and variable IV [6,6-2H2]glucose infusion. Results Study one: CM-TAG (but not VLDL-TAG) pool-size was lower with lixisenatide (P = 0.046). Lixisenatide reduced CM [13C]oleate area under the curve (AUC)60–480min concentration (P = 0.048) and increased CM-TAG clearance, with no effect on CM-TAG production rate. Study two: postprandial glucose and insulin AUC0–240min were reduced with lixisenatide (P = 0.0051; P < 0.05). Total glucose production (P = 0.015), rate of glucose appearance from the meal (P = 0.0098), and acetaminophen AUC0–360min (P = 0.006) were lower with lixisenatide than with placebo. Conclusions Lixisenatide reduced [13C]oleate concentrations, derived from a single meal in CM-TAG and glucose rate of appearance from the meal through delayed gastric emptying. However, day-long CM production, measured with repeated meal feeding, was not reduced by lixisenatide and decreased CM-TAG concentration resulted from increased CM-TAG clearance., Using stable isotopes, lixisenatide acutely slowed gastric emptying, lowering postprandial TAG levels. A more prolonged effect of reduced chylomicron TAG was from increased clearance.
Published: 2018

15. Associations Between Pancreatic Lipids and β-Cell Function in Black African and White European Men With Type 2 Diabetes

Author: K. George M.M. Alberti, Olah Hakim, Zoya Billoo, Alexander Sunderland, Riccardo C. Bonadonna, Linda Boselli, A. Margot Umpleby, Louise M Goff, Stephanie A. Amiel, Janet L. Peacock, Geoff Charles-Edwards, and Cynthia Mohandas
Subjects: Male, insulin secretion, medicine.medical_specialty, β cell function, Black african, Cross-sectional study, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Clinical Biochemistry, Adipose tissue, Black People, 030209 endocrinology & metabolism, Context (language use), Type 2 diabetes, 030204 cardiovascular system & hematology, Intra-Abdominal Fat, Biochemistry, White People, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal medicine, Diabetes mellitus, Insulin-Secreting Cells, London, Ethnicity, medicine, Humans, Insulin, Pancreas, Aged, beta-cell function, business.industry, pancreatic fat, African, Biochemistry (medical), Health Status Disparities, lipotoxicity, Middle Aged, medicine.disease, Lipids, Magnetic Resonance Imaging, Cross-Sectional Studies, Diabetes Mellitus, Type 2, sense organs, business
Abstract: Context: Intrapancreatic lipid (IPL) has been linked with beta-cell dysfunction. Black populations suffer disproportionately from type 2 diabetes (T2D) and show distinctions in beta-cell function compared to Whites.Objective: We aimed to quantify IPL in White European (WE) and Black West African (BWA) men with early T2D, and to investigate relationships between IPL and beta-cell insulin secretory function (ISF).Design, Setting and Participants: We performed a cross-sectional assessment of 18 WE and 19 BWA middle-aged men with early T2D as part of the South London Diabetes and Ethnicity Phenotyping (Soul-Deep) study.Main Outcome Measures: Participants underwent Dixon magnetic resonance imaging to determine IPL in the pancreatic head, body, and tail, and subcutaneous and visceral adipose tissue volumes. Modelled first-phase and second-phase ISF were comprehensively determined using c-peptide measurements during a 3-hour meal tolerance test and a 2-hour hyperglycemic clamp test.Results: WE men had higher mean IPL than BWA men (P=0.029), mainly due to higher IPL in the pancreatic head in WE men (P=0.009). Mean IPL was inversely associated with orally stimulated first-phase ISF in WE but not BWA men (WE: r=-0.554, P=0.026; BWA: r=-0.183, P=0.468); there was no association with orally stimulated second-phase ISF in either WE or BWA men. No significant associations were found between mean IPL and intravenously stimulated ISF.Conclusions: IPL is lower in BWA than WE men with early T2D, and the lack of inverse association with orally stimulated first phase ISF in BWA men indicates that IPL may be a less important determinant of the development of T2D in BWA compared to WE men.
Published: 2018
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16. Ethnic differences in insulin secretory function between black African and white European men with early type 2 diabetes

Author: Fariba Shojee-moradie, Riccardo C. Bonadonna, Louise M Goff, Cynthia Mohandas, Nicola Jackson, Stephanie A. Amiel, Linda Boselli, A. Margot Umpleby, K. George M.M. Alberti, and Janet L. Peacock
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, Time Factors, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Population, Incretin, Administration, Oral, Black People, 030209 endocrinology & metabolism, Type 2 diabetes, Gastric Inhibitory Polypeptide, White People, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Gastric inhibitory polypeptide, Diabetes mellitus, Internal medicine, Insulin Secretion, Internal Medicine, medicine, Humans, education, education.field_of_study, C-Peptide, business.industry, Insulin, Area under the curve, food and beverages, Glucose Tolerance Test, Middle Aged, medicine.disease, 030104 developmental biology, Glucose, Diabetes Mellitus, Type 2, Area Under Curve, Glucose Clamp Technique, Administration, Intravenous, business, Body mass index
Abstract: AimTo test the hypothesis that men of black (West) African ethnicity (black African men [BAM]) with early type 2 diabetes (T2D) would have greater insulin secretory deficits compared with white European men (WEM), following prediabetic hypersecretion.MethodsIn 19 BAM and 15 WEM, matched for age, body mass index and duration of diabetes, we assessed and modelled insulin secretory responses to hyperglycaemia stimulated intravenously (hyperglycaemic clamp) and orally (meal tolerance test).ResultsWith similar post‐challenge glucose responses, BAM had lower second‐phase C‐peptide responses to intravenous glucose (BAM 70.6 vs WEM 115.1 nmol/L/min [ratio of geometric mean 0.55, 95% confidence interval {CI} 0.37, 0.83]; P = .006) and to oral glucose (BAM 65.4 vs WEM 88.5 nmol/L/min [mean difference −23.2, 95% CI −40.0, −6.3]; P = .009). Peripheral insulin response in BAM to oral glucose was preserved (BAM 47.4 vs WEM 59.4 nmol/L/min [ratio of geometric mean 0.89, 95% CI 0.59, 1.35]; P = .566), with relative reductions in insulin clearance (BAM 506.2 vs WEM 630.1 mL/m2 BSA/min [mean difference −123.9, 95% CI −270.5, 22.6]; P = .095), associated with enhanced incretin responses (gastric inhibitory polypeptide incremental area under the curve: BAM 46.8 vs WEM 33.9 μg/L/min [mean difference 12.9, 95% CI 2.1, 23.7]; P = .021).ConclusionsIn early T2D, BAM had significantly lower insulin secretory responses to intravenous and oral stimulation than WEM. Lower insulin clearance, potentially driven by increased incretin responses, may act to preserve peripheral insulin concentrations. Tailoring early management strategies to reflect distinct ethnic‐specific pathophysiology may improve outcomes in this high‐risk population.
Published: 2017
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17. Exercise training reverses endothelial dysfunction in nonalcoholic fatty liver disease

Author: Daniel J. Cuthbertson, Paul G. Richardson, Helen Jones, N. Timothy Cable, Fariba Shojaee-Moradie, A. Margot Umpleby, Christopher J. A. Pugh, Victoria S. Sprung, Daniel J. Green, and Graham J. Kemp
Subjects: Male, medicine.medical_specialty, Pathology, Brachial Artery, Endothelium, Physiology, Vasodilation, Disease, Gastroenterology, Non-alcoholic Fatty Liver Disease, Physiology (medical), Internal medicine, Nonalcoholic fatty liver disease, medicine, Humans, Risk factor, Endothelial dysfunction, Exercise, business.industry, Exercise therapy, Middle Aged, medicine.disease, Exercise Therapy, medicine.anatomical_structure, Adipose Tissue, Liver, Female, Endothelium, Vascular, Cardiology and Cardiovascular Medicine, business, Liver pathology
Abstract: Nonalcoholic fatty liver disease (NAFLD) is an independent risk factor for cardiovascular disease (CVD). Endothelial dysfunction is an early manifestation of atherosclerosis and an important prognostic marker for future cardiovascular events. The aim of this study was twofold: to examine 1) the association between liver fat, visceral adipose tissue (VAT), and endothelial dysfunction in obese NAFLD patients and 2) the impact of supervised exercise training on this vascular defect. Brachial artery endothelial function was assessed by flow-mediated dilatation (FMD) in 34 obese NAFLD patients and 20 obese controls of similar age and cardiorespiratory fitness [peak oxygen uptake (V̇o2 peak)] (48 ± 2 vs. 47 ± 2 yr; 27 ± 1 vs. 26 ± 2 ml·kg−1·min−1−1). Magnetic resonance imaging and spectroscopy quantified abdominal and liver fat, respectively. Twenty-one NAFLD patients completed either 16 wk of supervised moderate-intensity exercise training ( n = 13) or conventional care ( n = 8). Differences between NAFLD and controls were compared using independent t-tests and effects of interventions by analysis of covariance. NAFLD patients had higher liver fat [11.6% (95% CI = 7.4, 18.1), P < 0.0005] and VAT [1.6 liters (95% CI = 1.2, 2.0), P < 0.0001] than controls and exhibited impaired FMD compared with controls [−3.6% (95% CI = −4.9, −2.2), P < 0.0001]. FMD was inversely correlated with VAT ( r = −0.54, P = 0.001) in NAFLD, although the impairment in FMD remained following covariate adjustment for VAT [3.1% (95% CI = 1.8, 4.5), P < 0.001]. Exercise training, but not conventional care, significantly improved V̇o2 peak [9.1 ml·kg−1·min−1 (95% CI = 4.1, 14.1); P = 0.001] and FMD [3.6% (95% CI = 1.6, 5.7), P = 0.002]. Endothelial dysfunction in NAFLD cannot be fully explained by excess VAT but can be reversed with exercise training; this has potential implications for the primary prevention of CVD in NAFLD.
Published: 2014
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18. Ethnic differences in hepatic, pancreatic, muscular and visceral fat deposition in healthy men of white European and black west African ethnicity

Author: Esma Bulut, Geoff Charles-Edwards, Janet L. Peacock, Meera Ladwa, A. Margot Umpleby, Oluwatoyosi Bello, Louise M Goff, Olah Hakim, Dimitra Christodoulou, Stephanie A. Amiel, and Haris Shuaib
Subjects: Adult, Male, Adolescent, Endocrinology, Diabetes and Metabolism, Ethnic group, Physiology, Adipose tissue, 030209 endocrinology & metabolism, Type 2 diabetes, Intra-Abdominal Fat, Ectopic fat, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Diabetes mellitus, Ethnicity, Internal Medicine, medicine, Humans, 030212 general & internal medicine, Intramyocellular lipids, Young adult, Aged, business.industry, African, nutritional and metabolic diseases, Type 2 Diabetes Mellitus, General Medicine, Middle Aged, medicine.disease, Black or African American, West african, business, human activities, Lipotoxicity
Abstract: Aims We aimed to assess ethnic differences in visceral adipose tissue (VAT), intrahepatic (IHL), intrapancreatic (IPL) and intramyocellular lipids (IMCL) between healthy white European (WE) and black west African (BWA) men. Methods 23 WE and 20 BWA men underwent Dixon-magnetic resonance imaging to quantify VAT, IHL and IPL; and proton-magnetic resonance spectroscopy to quantify IMCL. Insulin sensitivity and beta-cell function were determined using homeostasis model assessment (HOMA-2). Results BWA men exhibited significantly lower VAT (P = 0.021) and IHL (P = 0.044) than WE men, but comparable IPL (P = 0.92) and IMCL (P = 0.87). VAT was associated with IPL in both ethnicities (WE: P
Published: 2019
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19. Insulin Detemir Reduces Weight Gain as a Result of Reduced Food Intake in Patients With Type 1 Diabetes

Author: Richard H. Jones, K. Backhouse, Ben Sheldon, Nicola Jackson, Fariba Shojaee-Moradie, David Russell-Jones, Sigurd Johnsen, Sunil Zachariah, and A. Margot Umpleby
Subjects: Adult, Blood Glucose, Male, medicine.medical_specialty, Food intake, endocrine system diseases, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Insulin, Isophane, Weight Gain, Eating, Insulin Detemir, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Humans, Hypoglycemic Agents, Insulin, In patient, Original Research, Insulin detemir, Advanced and Specialized Nursing, Type 1 diabetes, Cross-Over Studies, business.industry, Clinical Care/Education/Nutrition/Psychosocial Research, nutritional and metabolic diseases, medicine.disease, Crossover study, Insulin, Long-Acting, Diabetes Mellitus, Type 1, Endocrinology, Female, medicine.symptom, Energy Intake, business, Weight gain, hormones, hormone substitutes, and hormone antagonists, medicine.drug
Abstract: OBJECTIVE Insulin detemir lacks the usual propensity for insulin to cause weight gain. We investigated whether this effect was a result of reduced energy intake and/or increased energy expenditure. RESEARCH DESIGN AND METHODS A 32-week, randomized crossover design trial was undertaken in 23 patients with type 1 diabetes. Patients on a basal-bolus regimen (with insulin aspart as the bolus insulin) were randomly assigned to insulin detemir or NPH insulin as a basal insulin for 16 weeks, followed by the other basal insulin for 16 weeks. At the end of each 16-week period, total energy expenditure, resting energy expenditure, diet-induced thermogenesis, activity energy expenditure, energy intake, weight change, glycemic control, hypoglycemic episodes, and hormones that affect satiety and fuel partitioning were measured. RESULTS After 16 weeks, weight change was −0.69 ± 1.85 kg with insulin detemir and +1.7 ± 2.46 kg with NPH insulin (P < 0.001). Total energy intake was significantly less with insulin detemir (2,016 ± 501 kcal/day) than with NPH insulin (2,181 ± 559 kcal/day) (P = 0.026). There was no significant difference in any measure of energy expenditure, HbA1c percentage, or number of hypoglycemic episodes. Leptin was lower and resistin was higher with insulin detemir compared with NPH insulin (P = 0.039, P = 0.047). After the meal, ghrelin and pancreatic polypeptide levels (P = 0.002, P = 0.001) were higher with insulin detemir. CONCLUSIONS The reduced weight gain with insulin detemir compared with NPH insulin is attributed to reduced energy intake rather than increased energy expenditure. This may be mediated by a direct or indirect effect of insulin detemir on the hormones that control satiety.
Published: 2011
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20. Impact of Growth Hormone and Dehydroepiandrosterone on Protein Metabolism in Glucocorticoid-Treated Patients

Author: A. Margot Umpleby, Ken K. Y. Ho, Donald J. Chisholm, Gudmundur Johannsson, and Morton G. Burt
Subjects: Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Protein metabolism, Dehydroepiandrosterone, Context (language use), Biochemistry, chemistry.chemical_compound, Endocrinology, Leucine, Prednisone, Diabetes mellitus, Internal medicine, medicine, Humans, Wasting, Aged, Cross-Over Studies, business.industry, Biochemistry (medical), Proteins, Middle Aged, medicine.disease, Glucose, Clinical research, chemistry, Growth Hormone, Female, medicine.symptom, Energy Metabolism, business, Glucocorticoid, medicine.drug
Abstract: Context: Chronic pharmacological glucocorticoid (GC) use causes substantial morbidity from protein wasting. GH and androgens are anabolic agents that may potentially reverse GC-induced protein loss. Objective: Our objective was to assess the effect of GH and dehydroepiandrosterone (DHEA) on protein metabolism in subjects on long-term GC therapy. Design: This was an open, stepwise GH dose-finding study (study 1), followed by a randomized cross-over intervention study (study 2). Setting: The studies were performed at a clinical research facility. Patients and Intervention: In study 1, six subjects (age 69 ± 4 yr) treated with long-term (>6 months) GCs (prednisone dose 8.3 ± 0.8 mg/d) were studied before and after two sequential GH doses (0.8 and 1.6 mg/d) for 2 wk each. In study 2, 10 women (age 71 ± 3 yr) treated with long-term GCs (prednisone dose 5.4 ± 0.5 mg/d) were studied at baseline and after 2-wk treatment with GH 0.8 mg/d, DHEA 50 mg/d, or GH and DHEA (combination treatment). Main Outcome Measure: Changes in whole body protein metabolism were assessed using a 3-h primed constant infusion of 1-[13C]leucine, from which rates of leucine appearance, leucine oxidation, and leucine incorporation into protein were estimated. Results: In study 1, GH 0.8 and 1.6 mg/d significantly reduced leucine oxidation by 19% (P = 0.03) and 31% (P = 0.02), and increased leucine incorporation into protein by 10% (P = 0.13) and 19% (P = 0.04), respectively. The lower GH dose did not cause hyperglycemia, whereas GH 1.6 mg/d resulted in fasting hyperglycemia in two of six subjects. In study 2, DHEA did not significantly change leucine metabolism alone or when combined with GH. Blood glucose was not affected by DHEA. Conclusion: GH, at a modest supraphysiological dose of 0.8 mg/d, induces protein anabolism in chronic GC users without causing diabetes. DHEA 50 mg/d does not enhance the effect of GH. GH may safely prevent or reverse protein loss induced by chronic GC therapy.
Published: 2008
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21. GH secretion in acute exercise may result in post-exercise lipolysis

Author: Helen Simpson, Catherine Charlton, A. Margot Umpleby, Claire Pentecost, Jamie Wee, Fariba Shojaee-Moradie, Nicola Jackson, and M Stolinski
Subjects: Adult, Glycerol, Male, Aging, medicine.medical_specialty, Time Factors, Epinephrine, Lipolysis, Rest, Endocrinology, Diabetes and Metabolism, Physical Exertion, Growth hormone, Body Mass Index, Norepinephrine, Catecholamines, Oxygen Consumption, Endocrinology, Isotopes, Internal medicine, Post exercise, medicine, Humans, Insulin, Exercise, Physiological Phenomena, Young male, Physical Education and Training, business.industry, Age Factors, Area under the curve, Middle Aged, Growth hormone secretion, Bicycling, Growth Hormone, Body Composition, Exercise Test, business, Production rate
Abstract: Exercise is a potent stimulator of growth hormone (GH) secretion. We hypothesised that after a short bout of intense exercise GH may increase lipolysis during recovery. In 7 moderately trained young male subjects (21.8 +/- 0.5 years) and 7 moderately trained older male subjects (56.0 +/- 1.0 years) [(2)H(5)] glycerol was infused for 370min to measure glycerol production rate (R(a)), a measure of lipolysis. At 130 min subjects exercised on a cycle ergonometer for 20 min at 70% V(O2 max), followed by rest for 220 min. On a separate occasion the study was repeated in the young subjects with a 1h GH infusion (4microgkg(-1)h(-1)) at 130 min instead of exercise. In response to exercise, catecholamines (p0.02) and glycerol R(a) (p0.01) increased, peaking during exercise. GH concentration increased in response to exercise (p0.01), peaking after exercise (150-160 min) in both groups with no significant difference in peak response between groups. A post-exercise rise in glycerol R(a) was demonstrated in both groups peaking at 265-295 min in the older group (p0.002, peak vs. basal) and continuing to rise until 370 min in the young group (p0.01, peak vs. basal). The timing and magnitude of this was reproduced with the GH infusion. There was a significant correlation between the peak GH response to exercise and the post-exercise rise in glycerol R(a) measured as area under the curve (r=0.57, p0.04). In conclusion, this study provides evidence that the GH response to acute exercise may increase lipolysis during recovery.
Published: 2005
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22. Combined growth hormone/insulin-like growth factor I in addition to glutamine-supplemented TPN results in net protein anabolism in critical illness

Author: Peter H. Sönksen, D. F. Treacher, Paul V. Carroll, A. Margot Umpleby, David Russell-Jones, and Nicola Jackson
Subjects: Adult, Male, medicine.medical_specialty, Critical Care, Physiology, Critical Illness, Glutamine, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Protein metabolism, Nutritional Status, Body Mass Index, chemistry.chemical_compound, Insulin-like growth factor, Physiology (medical), Intensive care, Internal medicine, Humans, Medicine, Prospective Studies, Insulin-Like Growth Factor I, Aged, business.industry, Proteins, Middle Aged, Respiration, Artificial, Protein catabolism, Endocrinology, Parenteral nutrition, chemistry, Growth Hormone, Lean body mass, Wounds and Injuries, Female, Parenteral Nutrition, Total, business, Hormone
Abstract: Protein loss leading to reduced lean body mass is recognized to contribute to the high levels of morbidity and mortality seen in critical illness. This prospective, randomized, controlled study compared the effects of conventional parenteral nutrition (TPN), glutamine-supplemented (0.4 g·kg-1·day-1) TPN (TPNGLN), and TPNGLN with combined growth hormone (GH, 0.2 IU·kg-1·day-1) and IGF-I (160 μg·kg-1·day-1) on protein metabolism in critical illness. Nineteen mechanically ventilated subjects [64 ± 3 yr, body mass index (BMI) 23.8 ± 1.3, kg/m2] were initially studied in the fasting state ( study 1) and subsequently after 3 days of nutritional with/without hormonal support ( study 2). All had recently been admitted to the ICU and the majority were postemergency abdominal surgery (APACHE II 17.5 ± 1.0). Protein metabolism was assessed using a primed constant infusion of [1-13C]leucine. Conventional TPN contained mixed amino acids, Intralipid, and 50% dextrose. TPNGLN, unlike TPN alone, resulted in an increase in plasma glutamine concentration (∼50%, P < 0.05). Both TPN and TPNGLN decreased the rate of protein breakdown (TPN 15%, P < 0.002; TPNGLN 16%, P < 0.05), but during these treatments the patients remained in a net negative protein balance. Combined treatment with TPNGLN + GH/IGF-I increased plasma IGF-I levels (10.3 ± 0.8 vs. 48.1 ± 9.1 nmol/l, study 1 vs. study 2, P < 0.05), and in contrast to therapy with nutrition alone, resulted in net protein gain (-0.75 ± 0.14 vs. 0.33 ± 0.12 g protein·kg-1·day-1, study 1 vs. study 2, P < 0.05). Therapy with GH/IGF-I + TPNGLN, unlike nutrition alone, resulted in net positive protein balance in a group of critically ill patients.
Published: 2004
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23. Oral estrogen antagonizes the metabolic actions of growth hormone in growth hormone-deficient women

Author: Ken K. Y. Ho, Ailish G. Nugent, David M. Hoffman, Margot Umpleby, Mark W. Duncan, and Troels Wolthers
Subjects: Adult, Medroxyprogesterone, medicine.medical_specialty, Physiology, medicine.drug_class, Endocrinology, Diabetes and Metabolism, Population, Administration, Oral, Administration, Cutaneous, Hypopituitarism, Route of administration, Transdermal estrogen, Double-Blind Method, Lipid oxidation, Leucine, Oral administration, Physiology (medical), Internal medicine, medicine, Humans, Insulin-Like Growth Factor I, education, Transdermal, education.field_of_study, Cross-Over Studies, Dose-Response Relationship, Drug, Estradiol, Progesterone Congeners, Human Growth Hormone, business.industry, Proteins, Estrogens, Middle Aged, Lipid Metabolism, Endocrinology, Estrogen, Growth Hormone, Female, business, Hormone
Abstract: We have determined whether oral estrogen reduces the biological effects of growth hormone (GH) in GH-deficient (GHD) women compared with transdermal estrogen treatment. In two separate studies, eight GHD women randomly received either oral or transdermal estrogen for 8 wk before crossing over to the alternate route of administration. The first study assessed the effects of incremental doses of GH (0.5, 1.0, 2.0 IU/day for 1 wk each) on insulin-like growth factor I (IGF-I) levels during each estrogen treatment phase. The second study assessed the effects of GH (2 IU/day) on lipid oxidation and on protein metabolism using the whole body leucine turnover technique. Mean IGF-I level was significantly lower during oral estrogen treatment ( P < 0.05) and rose dose dependently during GH administration by a lesser magnitude ( P < 0.05) compared with transdermal treatment. Postprandial lipid oxidation was significantly lower with oral estrogen treatment, both before ( P < 0.05) and during ( P < 0.05) GH administration, compared with transdermal treatment. Protein synthesis was lower during oral estrogen both before and during GH administration ( P < 0.05). Oral estrogen antagonizes several of the metabolic actions of GH. It may aggravate body composition abnormalities already present in GHD women and attenuate the beneficial effects of GH therapy. Estrogen replacement in GHD women should be administered by a nonoral route.
Published: 2001
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24. Recombinant human insulin-like growth factor-I (rhIGF-I) therapy in adults with type 1 diabetes mellitus: effects on IGFs, IGF-binding proteins, glucose levels and insulin treatment

Author: Elaine L. Alexander, Virginia A. Egel, David Russell-Jones, Kathleen V. Callison, Margot Umpleby, Peter H. Sönksen, and Paul V. Carroll
Subjects: Type 1 diabetes, medicine.medical_specialty, biology, Anabolism, business.industry, Endocrinology, Diabetes and Metabolism, Growth factor, medicine.medical_treatment, Insulin, medicine.disease, Insulin-like growth factor-binding protein, Endocrinology, Internal medicine, Insulin-like growth factor 2, Blood plasma, medicine, biology.protein, business, Pancreatic hormone
Abstract: OBJECTIVE Insulin-like growth factor-I (IGF-I) has both insulin-like and anabolic actions but unlike insulin, IGF-I circulates bound to a number of specific binding proteins that regulate its availability and activity. Patients with type 1 diabetes mellitus have low levels of circulating IGF-I despite increased growth hormone (GH) secretion, and are a group that may benefit from rhIGF-I therapy. Understanding the relationship between IGF-I and its binding proteins is necessary to appreciate the actions of exogenously administered rhIGF-I. Therefore, we examined the effects of 19 days' subcutaneous administration of rhIGF-I (50 μg/kg BID) on the levels of IGF-I, IGF-II and the IGF-binding proteins (IGFBPs), as well as the daily dose of insulin necessary to maintain glycaemic control in patients with type 1 diabetes mellitus. DESIGN AND PATIENTS This was an open study, and the patients were studied initially while resident (days 1–5) in the hospital and thereafter (days 6–24) as outpatients. Serum was collected at baseline and at intervals throughout the study for the measurement of total IGF-I, IGF-II, IGFBP-1, -2, -3, free insulin and growth hormone (GH). Daily insulin doses and glucometer readings were recorded throughout the study. The changes in each of these variables were examined. The subjects were six adults (35.3 ± 4.0 years, mean ± SE), with type 1 diabetes, and all had reasonable glycaemic control (HbA1c 7.2 ± 0.5%). RESULTS rhIGF-I administration increased circulating total IGF-I over two-fold (15.3 ± 1.9 vs. 33.7 ± 5.4 nmol/l, mean ± SEM, P
Published: 1998
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25. rhIGF-I Administration Reduces Insulin Requirements, Decreases Growth Hormone Secretion, and Improves the Lipid Profile in Adults With IDDM

Author: David B. Dunger, Paul V. Carroll, Gill S Ward, David Russell-Jones, Elaine L. Alexander, Stephen Imuere, Peter H. Sönksen, and Margot Umpleby
Subjects: Adult, Blood Glucose, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Placebo, chemistry.chemical_compound, Internal medicine, Internal Medicine, medicine, Humans, Insulin, Insulin-Like Growth Factor I, Pancreatic hormone, Glycemic, Chemotherapy, medicine.diagnostic_test, Human Growth Hormone, business.industry, Lipids, Growth hormone secretion, Diabetes Mellitus, Type 1, Endocrinology, Fructosamine, chemistry, Female, Energy Metabolism, business, Lipid profile
Abstract: IDDM is associated with elevated circulating levels of growth hormone (GH) and reduced insulin-like growth factor I (IGF-I). GH antagonizes the action of insulin-increasing insulin requirements in IDDM. The effects of subcutaneously administered rhIGF-I on glycemie control, insulin requirements, and GH secretion were studied in eight adults with IDDM. Patients received either placebo or rhIGF-I (50 pg/kg b.i.d.) for 19 days in a randomized, double-blind, parallel-design, placebo-controlled trial. Overnight GH, plasma glucose, free insulin, IGF-I, fructosamine, and lipid profiles were assessed during this period. rhIGF-I therapy increased IGF-I concentration from 117.1 ± 14.2 (mean ± SE) ng/ml (baseline) to 310.5 ± 40.6 and 257.1 ± 41.2 ng/ml on day 5 (P < 0.01 vs. baseline) and day 20 (P < 0.01 vs. baseline), respectively. After 19 days of rhIGF-I treatment, fructosamine concentrations were unchanged compared with baseline (439 ± 32 vs. 429 ± 35 μmol/l, day –1 vs. day 20, respectively), yet insulin requirements were decreased by ∼45% (0.67 ± 0.08 vs. 0.36 ± 0.07 U · kg−1 · day−1, day –1 vs. day 19, respectively, P < 0.005). After 4 days of rhIGF-I therapy, there was a decrease in free insulin levels (8.38 ± 1.47 vs. 4.98 ± 0.84 mU/l, P < 0.05), mean overnight GH concentration (12.6 ± 3.3 vs. 3.8 ± 2.1 mU/l, P = 0.05), and total cholesterol and triglycerides (4.68 ± 0.31 vs. 4.25 ± 0.35 mmol/l, P < 0.05, 1.27 ± 0.19 vs. 0.95 ± 0.21 mmol/l, P < 0.001, respectively). There was no change in any variable in the placebo-treated patients. This study demonstrates that subcutaneous administration of rhIGF-I decreases insulin requirements and improves the plasma lipid profile while maintaining glycemie control in adults with IDDM. The excess nocturnal release of GH, characteristic of IDDM, is also decreased by rhIGF-I therapy. Exogenous rhIGF-I therapy may have a role in the treatment of adults with IDDM, particularly in the setting of abnormal lipids and a high insulin requirement.
Published: 1997
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26. Exercise training improves cutaneous microvascular function in nonalcoholic fatty liver disease

Author: Paul G. Richardson, Helen Jones, N. Timothy Cable, Graham J. Kemp, Christopher J. A. Pugh, Victoria S. Sprung, Daniel J. Green, A. Margot Umpleby, and Daniel J. Cuthbertson
Subjects: Adult, Male, medicine.medical_specialty, Pathology, Hot Temperature, Physiology, Endocrinology, Diabetes and Metabolism, Microcirculation, Oxygen Consumption, Forearm, Non-alcoholic Fatty Liver Disease, Risk Factors, Physiology (medical), Internal medicine, Nonalcoholic fatty liver disease, medicine, Laser-Doppler Flowmetry, Humans, Microvessel, Skin, business.industry, Fatty liver, Cardiorespiratory fitness, Blood flow, Middle Aged, medicine.disease, Exercise Therapy, Fatty Liver, medicine.anatomical_structure, Treatment Outcome, Cardiovascular Diseases, Dilator, Cardiology, Female, business, Risk Reduction Behavior
Abstract: The leading causes of mortality in nonalcoholic fatty liver disease (NAFLD) relate to cardiovascular disease (CVD). The contribution of nitric oxide (NO) to endothelial function, a surrogate of CVD risk, is currently unknown in NAFLD. We hypothesize that NO-mediated cutaneous microvessel function would be impaired in NAFLD compared with controls and that exercise would enhance microvessel function compared with conventional care. Thirteen NAFLD patients (aged 50 ± 3 yr, BMI 31 ± 1 kg/m2) and seven controls (48 ± 4 yr, 30 ± 2 kg/m2) were studied. NAFLD patients were randomized to either 16 wk of exercise or conventional care. Cutaneous microvessel function was examined using laser Doppler flowmetry combined with intradermal microdialysis of NG-monomethyl-l-arginine to assay the NO dilator response to local forearm heating. Magnetic resonance imaging and spectroscopy quantified abdominal and liver fat, respectively, and cardiorespiratory fitness was assessed. Differences in NO contribution to cutaneous blood flow between NAFLD and control individuals and between interventions were analyzed using general linear modeling. NO contribution to cutaneous blood flow was similar between NAFLD and controls ( P = 0.47). Cardiorespiratory fitness was greater following exercise training compared with conventional care. NO contribution to cutaneous blood flow in response to heating at 42°C was 20.4% CVCmax (95% CI = 4.4, 36.4) greater following exercise training compared with conventional care ( P = 0.02). Exercise training improves cutaneous microvascular NO function in NAFLD patients. The benefit of exercise training compared with conventional care strongly supports a role for exercise in the prevention of CVD in NAFLD.
Published: 2013

27. Improvements In Liver Fat And Endothelial Function Following Supervised Exercise Training Are Not Sustained One-Year After The Cessation Of Supervision In Non-Alcoholic Fatty Liver Disease

Author: Andrew Irwin, Paul G. Richardson, Fariba Shojaee-Moradie, Daniel J. Green, Daniel J. Cuthbertson, Helen Jones, Christopher J. A. Pugh, Margot Umpleby A, Graham J. Kemp, Sprung, and Timothy Cable N
Subjects: 0301 basic medicine, medicine.medical_specialty, business.industry, Fatty liver, 030209 endocrinology & metabolism, Physical Therapy, Sports Therapy and Rehabilitation, Non alcoholic, Disease, medicine.disease, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Internal medicine, Liver fat, Physical therapy, Medicine, Orthopedics and Sports Medicine, business, Supervised exercise
Published: 2016
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28. Insulin-sensitizing effects on muscle and adipose tissue after dietary fiber intake in men and women with metabolic syndrome

Author: Cyrille Debard, Hubert Vidal, Fariba Shojaee-Moradie, John Wright, M. Denise Robertson, David Russell-Jones, Emmanuelle Loizon, and A. Margot Umpleby
Subjects: Adult, Dietary Fiber, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Biopsy, Clinical Biochemistry, Gene Expression, Context (language use), Real-Time Polymerase Chain Reaction, Biochemistry, Zea mays, law.invention, Membrane Potentials, Endocrinology, Insulin resistance, Randomized controlled trial, law, Internal medicine, Diabetes mellitus, medicine, Humans, Single-Blind Method, RNA, Messenger, Aged, Metabolic Syndrome, business.industry, Insulin, Muscles, Biochemistry (medical), Type 2 Diabetes Mellitus, Glucose clamp technique, Middle Aged, medicine.disease, Lipid Metabolism, Diet, Glucose, Adipose Tissue, Liver, Glucose Clamp Technique, Cytokines, Female, Metabolic syndrome, Insulin Resistance, business, Biomarkers
Abstract: Context: Dietary fibers have been associated with a reduced incidence of type 2 diabetes mellitus in epidemiological studies; however, the precise mechanisms are unknown. Objective: The objective of the study was to evaluate the efficacy and site of action of an insoluble dietary fiber derived from maize (HAM-RS2) in improving insulin resistance in subjects at increased risk of type 2 diabetes mellitus. Design: This study was a randomized, controlled crossover, dietary intervention study. Setting: The study was conducted at the Centre for Diabetes, Endocrinology, and Research, Royal Surrey County Hospital, Guildford, United Kingdom. Participants: Fifteen men and women with insulin resistance participated in the study. Intervention: The intervention included 40 g/d HAM-RS2 compared with a matched placebo for 8 wk. Main Outcome Measures: After each supplement, participants underwent a two-step hyperinsulinemic-euglycemic clamp study with the addition of glucose tracers; a meal tolerance test; arteriovenous sampling across forearm muscle tissue; and a sc adipose tissue biopsy for assessment of gene expression. Results: There was enhanced uptake of glucose into the forearm muscle measured by arteriovenous sampling (65 ± 15% increase after resistant starch; P < 0.001). Adipose tissue function was also affected, with enhanced fatty acid suppression after HAM-RS2 treatment and an increase in gene expression for hormone sensitive lipase (P = 0.005), perilipin (P = 0.011), lipoprotein lipase (P = 0.014), and adipose triglyceride lipase (P = 0.03) in biopsy samples. There was no effect on the insulin sensitivity of hepatic glucose production or plasma lipids after HAM-RS2. Conclusion: HAM-RS2 improved peripheral but not hepatic insulin resistance and requires further study as an intervention in patients with or at risk for type 2 diabetes.
Published: 2012

29. Effects of three weeks of mild sleep restriction implemented in the home environment on multiple metabolic and endocrine markers in healthy young men

Author: Derk-Jan Dijk, A. Margot Umpleby, M. Denise Robertson, and David Russell-Jones
Subjects: Adult, Leptin, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Blood Pressure, Type 2 diabetes, Bedtime, Young Adult, Endocrinology, Internal medicine, medicine, Humans, Longitudinal Studies, Sleep restriction, Adiponectin, business.industry, Body Weight, Actigraphy, Glucose clamp technique, medicine.disease, Sleep in non-human animals, Sleep deprivation, Body Composition, Glucose Clamp Technique, Sleep Deprivation, medicine.symptom, Insulin Resistance, business, Sleep
Abstract: Objectives: Evidence for a causal relationship between sleep-loss and metabolism is derived primarily from short-term sleep deprivation studies in the laboratory. The objective of this study was to investigate whether small changes in sleep duration over a three week period while participants are living in their normal environment lead to changes in insulin sensitivity and other metabolic parameters. Methods: Nineteen healthy, young, normal-weight men were randomised to either sleep restriction (habitual bedtime minus 1.5 h) or a control condition (habitual bedtime) for three weeks. Weekly assessments of insulin sensitivity by hyperinsulinaemic-euglycaemic clamp, anthropometry, vascular function, leptin and adiponectin were made. Sleep was assessed continuously using actigraphy and diaries. Results: Assessment of sleep by actigraphy confirmed that the intervention reduced daily sleep duration by 01:19 ± 00:15 (SE; p < 0.001). Sleep restriction led to changes in insulin sensitivity, body weight and plasma concentrations of leptin which varied during the three week period. There was no effect on plasma adiponectin or vascular function. Conclusions: Even minor reductions in sleep duration lead to changes in insulin sensitivity, body weight and other metabolic parameters which vary during the exposure period. Larger and longer longitudinal studies of sleep restriction and sleep extension are warranted. © 2013 Elsevier Inc.
Published: 2012

30. Hormone replacement therapy and physical function in healthy older men. Time to talk hormones?

Author: Peter H. Sönksen, Finbarr C. Martin, Manthos G. Giannoulis, A. Margot Umpleby, and K. Sreekumaran Nair
Subjects: Adult, Male, medicine.medical_specialty, Aging, Sarcopenia, Hormone Replacement Therapy, Endocrinology, Diabetes and Metabolism, Reviews, Anabolic Agents, Muscle hypertrophy, Endocrinology, Insulin resistance, Internal medicine, medicine, Humans, Testosterone, Hormone replacement therapy, Muscle Strength, Insulin-Like Growth Factor I, Muscle, Skeletal, Exercise, Aged, Aged, 80 and over, Muscle adaptation, business.industry, Human Growth Hormone, Middle Aged, medicine.disease, Androgens, Body Composition, Drug Therapy, Combination, business, Hormone
Abstract: Improving physical function and mobility in a continuously expanding elderly population emerges as a high priority of medicine today. Muscle mass, strength/power, and maximal exercise capacity are major determinants of physical function, and all decline with aging. This contributes to the incidence of frailty and disability observed in older men. Furthermore, it facilitates the accumulation of body fat and development of insulin resistance.Muscle adaptation to exercise is strongly influenced by anabolic endocrine hormones and local load-sensitive autocrine/paracrine growth factors. GH, IGF-I, and testosterone (T) are directly involved in muscle adaptation to exercise because they promote muscle protein synthesis, whereas T and locally expressed IGF-I have been reported to activate muscle stem cells. Although exercise programs improve physical function, in the long-term most older men fail to comply. The GH/IGF-I axis and T levels decline markedly with aging, whereas accumulating evidence supports their indispensable role in maintaining physical function integrity.Several studies have reported that the administration of T improves lean body mass and maximal voluntary strength in healthy older men. On the other hand, most studies have shown that administration of GH alone failed to improve muscle strength despite amelioration of the detrimental somatic changes of aging. Both GH and T are anabolic agents that promote muscle protein synthesis and hypertrophy but work through separate mechanisms, and the combined administration of GH and T, albeit in only a few studies, has resulted in greater efficacy than either hormone alone. Although it is clear that this combined approach is effective, this review concludes that further studies are needed to assess the long-term efficacy and safety of combined hormone replacement therapy in older men before the medical rationale of prescribing hormone replacement therapy for combating the sarcopenia of aging can be established.
Published: 2012

31. Impact of acute and chronic low-dose glucocorticoids on protein metabolism

Author: A. Margot Umpleby, Donald J. Chisholm, Gudmundur Johannsson, Ken K. Y. Ho, and Morton G. Burt
Subjects: Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Prednisolone, Clinical Biochemistry, Protein metabolism, Context (language use), Biochemistry, chemistry.chemical_compound, Endocrinology, Prednisone, Leucine, Internal medicine, medicine, Humans, Longitudinal Studies, Therapeutic Glucocorticoid, Glucocorticoids, Aged, Carbon Isotopes, business.industry, Biochemistry (medical), Proteins, Middle Aged, Protein catabolism, Cross-Sectional Studies, Metabolism, chemistry, Regression Analysis, Female, business, Oxidation-Reduction, Glucocorticoid, medicine.drug
Abstract: Context: High-dose glucocorticoids cause acute protein loss by increasing protein breakdown and oxidation. Whether lower glucocorticoid doses, typical of therapeutic use, induce sustained catabolism has not been studied. Objective: Our objective was to assess the effect of acute and chronic therapeutic glucocorticoid doses on protein metabolism. Design and Setting: We conducted an open longitudinal and a cross-sectional study at a clinical research facility. Patients and Intervention: Ten healthy subjects were studied before and after a short course of prednisolone (5 and 10 mg/d sequentially for 7 d each). Twelve subjects with inactive polymyalgia rheumatica receiving chronic (>12 months) prednisone (mean = 5.0 ± 0.8 mg/d) were compared with 12 age- and gender-matched normal subjects. Main Outcome Measure: Whole-body protein metabolism was assessed using a 3-h primed constant infusion of 1-[13C]leucine, from which rates of leucine appearance (leucine Ra, an index of protein breakdown), leucine oxidation (Lox, index of protein oxidation) and leucine incorporation into protein (LIP, index of protein synthesis) were estimated. Results: Prednisolone induced an acute significant increase in Lox (P = 0.008) and a fall in LIP (P = 0.08) but did not affect leucine Ra. There was no significant difference between the effects of the 5- and 10-mg prednisolone doses on leucine metabolism. In subjects receiving chronic prednisone therapy, leucine Ra, Lox, and LIP were not significantly different from normal subjects. Conclusion: Glucocorticoids stimulate protein oxidation after acute but not chronic administration. This time-related change suggests that glucocorticoid-induced stimulation of protein oxidation does not persist but that a metabolic adaptation occurs to limit protein loss.
Published: 2007

32. Low-density lipoprotein apolipoprotein B100 turnover in hypopituitary patients with GH deficiency: a stable isotope study

Author: A. Margot Umpleby, Peter H. Sönksen, Nicola Jackson, Anthony S. Wierzbicki, Peter J. Lumb, Emanuel Christ, Michael Stolinski, David Russell-Jones, and M.H. Cummings
Subjects: Adult, Male, medicine.medical_specialty, Apolipoprotein B, Hormone Replacement Therapy, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Hypopituitarism, Body Mass Index, chemistry.chemical_compound, Endocrinology, Apolipoproteins E, Internal medicine, medicine, Humans, Apolipoproteins B, Dyslipidemias, chemistry.chemical_classification, Carbon Isotopes, Sex Characteristics, biology, business.industry, Cholesterol, Human Growth Hormone, Age Factors, Fatty acid, Hormone replacement therapy (menopause), General Medicine, Middle Aged, medicine.disease, Lipids, Lipoproteins, LDL, chemistry, Low-density lipoprotein, Growth Hormone, biology.protein, lipids (amino acids, peptides, and proteins), Female, business, Body mass index, Lipoprotein
Abstract: Background: Epidemiological studies suggest that hypopituitary patients have an increased risk for cardiovascular mortality. The dyslipidaemia associated with this condition is often characterised by an increase in total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol (LDL-C) and may contribute to these findings. The underlying mechanisms are not fully elucidated.Materials and Methods: LDL apolipoprotein B (apoB) production rate and metabolic clearance rate were measured in seven patients with hypopituitarism (including GH deficiency) under stable conventional replacement therapy (three males and four females; age 40–16.1 years; body mass index 29.0–6.1 kg/m2(means ±s.d.)) and seven age-, gender- and body mass index-matched control subjects with an infusion of 1-13C-leucine. Fasting lipid profile and lipid composition of LDL were also measured.Results: Fasting TC, triglycerides (TG), high-density lipoprotein-C, LDL-C and free fatty acid concentrations were not different between hypopituitary patients and control subjects. LDL-TG (P< 0.006) and LDL-TG/LDL apoB ratio (P< 0.02) were significantly increased in hypopituitary patients. LDL apoB pool size was not statistically different between patients and control subjects. In the hypopituitary patients, LDL apoB metabolic clearance rate (P< 0.05) and LDL apoB production rate (P< 0.02) were lower than in the control subjects.Conclusions: The present results suggest that LDL apoB turnover and LDL composition is altered in hypopituitary patients. Whether these findings explain the increased risk for cardiovascular disease in hypopituitary patients remains to be established.
Published: 2006

33. Effects of growth hormone and/or testosterone on very low density lipoprotein apolipoprotein B100 kinetics and plasma lipids in healthy elderly men: a randomised controlled trial

Author: Manthos G. Giannoulis, Fariba Shojaee-Moradie, A. Margot Umpleby, Peter H. Sönksen, Nicola Jackson, and Finbarr C. Martin
Subjects: Male, medicine.medical_specialty, Very low-density lipoprotein, Apolipoprotein B, Endocrinology, Diabetes and Metabolism, Lipoproteins, VLDL, Placebo, Endocrinology, Double-Blind Method, Internal medicine, Medicine, Humans, Testosterone, Insulin-Like Growth Factor I, Aged, Aged, 80 and over, biology, business.industry, Catabolism, Human Growth Hormone, Metabolism, Lipids, Recombinant Proteins, Apolipoprotein B-100, biology.protein, Body Composition, lipids (amino acids, peptides, and proteins), Leucine, business, Lipoprotein
Abstract: Objective: To assess the effects of low dose recombinant growth hormone (GH), testosterone (T) and combined GH and T, on lipid profiles and very low density lipoprotein apolipoprotein B (VLDL apoB) metabolism. Design and patients: Sixty-nine healthy elderly men (65–80 yr) were studied in a six month double-blind, placebo-controlled trial. Participants were randomised to placebo GH and placebo T (P), GH and placebo T (GH), T and placebo GH (T) or GH and T (GHT). Measurements: Plasma lipid profiles were assessed before treatment and at 6 months. VLDL apoB absolute secretion rate (ASR) and fractional catabolic rate (FCR) were measured in a subset of 21 men: P (n = 5); GH (n = 5); T (n = 6); GHT (n = 5), with an infusion of 1- 13 C leucine. Fat mass (FM) was measured by DEXA and intra-abdominal fat (IAF) by CT scan. Results: IGF-I levels increased in the GH and GHT (P < 0.001) groups: testosterone increased in the T (P = 0.029) and GHT (P = 0.05) groups. There was no change in total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, apolipoprotein AI, apolipoprotein B or lipoprotein(a) in the GH, GHT or T groups. In the subset of 21 men, IGF-I levels increased similarly with GH and GHT (P < 0.01) but T levels increased only with T (P < 0.03). FM and IAF decreased significantly only with GHT (P < 0.01, P = 0.01). Treatment with GH, T or GHT had no effect on VLDL apoB ASR or VLDL FCR. Conclusion: Co-administration of GH and T in near physiological doses in healthy elderly men resulted in favourable changes in body composition without altering the plasma lipid profile or VLDL apoB metabolism. � 2006 Elsevier Ltd. All rights reserved.
Published: 2006

34. The Effects of Growth Hormone and/or Testosterone in Healthy Elderly Men: A Randomized Controlled Trial

Author: Claire Pentecost, Margot Umpleby, Manthos G. Giannoulis, Peter H. Sönksen, Finbarr C. Martin, Louise Breen, Martin Whyte, Carolyn V. McMillan, and Clare Bradley
Subjects: Male, medicine.medical_specialty, medicine.drug_class, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Context (language use), Placebo, Biochemistry, law.invention, Endocrinology, Randomized controlled trial, Double-Blind Method, law, Internal medicine, Surveys and Questionnaires, medicine, Humans, Testosterone, Insulin-Like Growth Factor I, Adverse effect, Muscle, Skeletal, Aged, Aged, 80 and over, Faculty of Science\Psychology, Hand Strength, business.industry, Human Growth Hormone, Biochemistry (medical), Androgen, Somatropin, Physical Fitness, Lean body mass, Body Composition, Quality of Life, business
Abstract: Context: Declines in GH and testosterone (Te) secretion may contribute to the detrimental aging changes of elderly men.Objective: To assess the effects of near-physiological GH with/without Te administration on lean body mass, total body fat, midthigh muscle cross-section area, muscle strength, aerobic capacity, condition-specific quality of life (Age-Related Hormone Deficiency-Dependent Quality of Life questionnaire), and generic health status (36-Item Short-Form Health Survey) of older men.Design, Settings, and Participants: A 6-month, randomized, double-blind, placebo-controlled trial was performed on 80 healthy, community-dwelling, older men (age, 65–80 yr).Interventions: Participants were randomized to receive 1) placebo GH or placebo Te, 2) recombinant human GH (rhGH) and placebo Te (GH), 3) Te and placebo rhGH (Te), or 4) rhGH and Te (GHTe). GH doses were titrated over 8 wk to produce IGF-I levels in the upper half of the age-specific reference range. A fixed dose of Te (5 mg) was given by transdermal patches.Results: Lean body mass increased with GHTe (P = 0.008) and GH (P = 0.004), compared with placebo. Total body fat decreased with GHTe only (P = 0.02). Midthigh muscle (P = 0.006) and aerobic capacity (P < 0.001) increased only after GHTe. Muscle strength changes were variable; one of six measures significantly increased with GHTe. Significant treatment group by time interactions indicated an improved Age-Related Hormone Deficiency-Dependent Quality of Life questionnaire score (P = 0.007) in the GH and GHTe groups. Bodily pain increased with GH alone, as determined by the Short-Form Health Survey (P = 0.003). There were no major adverse effects.Conclusion: Coadministration of low dose GH with Te resulted in beneficial changes being observed more often than with either GH or Te alone.
Published: 2006

35. Dose-dependent effects of recombinant human insulin-like growth factor (IGF)-I/IGF binding protein-3 complex on overnight growth hormone secretion and insulin sensitivity in type 1 diabetes

Author: Rakesh Amin, Kevin C.J. Yuen, Tero Saukkonen, Charles Fox, Carlo L. Acerini, A. Margot Umpleby, Martin White, Rachel M. Williams, and David B. Dunger
Subjects: Adult, Blood Glucose, Male, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Clinical Biochemistry, Dawn phenomenon, Biochemistry, Endocrinology, Insulin resistance, Double-Blind Method, Diabetes mellitus, Internal medicine, medicine, Humans, Insulin, Insulin-Like Growth Factor I, Pancreatic hormone, Mecasermin, Type 1 diabetes, Sex Characteristics, Cross-Over Studies, Dose-Response Relationship, Drug, business.industry, Human Growth Hormone, Biochemistry (medical), medicine.disease, Growth hormone secretion, Recombinant Proteins, Diabetes Mellitus, Type 1, Insulin-Like Growth Factor Binding Protein 3, Female, business, medicine.drug
Abstract: GH hypersecretion in type 1 diabetes has been implicated in the pathogenesis of insulin resistance, and microangiopathic complications, and may result from reduced circulating IGF levels. We examined the effects of recombinant human (rh)IGF-I [complexed in equimolar ratio with rhIGF binding protein (BP)-3 (rhIGF-I/IGFBP-3)] replacement on overnight GH levels and insulin sensitivity in type 1 diabetes. Fifteen subjects, 13-24 yr old (10 male), were given rhIGF-I/IGFBP-3 or placebo as a daily sc injection for 2 d. After the second injection overnight, insulin requirements for euglycemia were determined (0400-0800 h), followed by a 4-h, two-step (insulin, 0.6 and 1.5 mU/kg.min) hyperinsulinemic euglycemic [90 mg/dl (5 mmol/liter)] clamp. In each subject, the protocol was repeated on three occasions in random order. Seven subjects received placebo and rhIGF-I/IGFBP-3 (0.1 mg/kg.d and 0.4 mg/kg.d), and eight subjects received placebo and rhIGF-I/IGFBP-3 (0.2 mg/kg.d and 0.8 mg/kg.d). We found dose-dependent increases in circulating IGF-I and IGFBP-3 concentrations after rhIGF-I/IGFBP-3. These were paralleled by significant reductions in mean overnight GH levels and GH pulse amplitude. We also observed dose-dependent effects of rhIGF-I/IGFBP-3 on overnight insulin requirements for euglycemia, with reductions of up to 41%. Insulin sensitivity, defined by M-values, was improved with rhIGF-I/IGFBP-3 (0.4 and 0.8 mg/kg.d). Thus, restoration of circulating IGF-I and IGFBP-3 levels with rhIGF-I/IGFBP-3 suppresses GH secretion in adolescents with type 1 diabetes, leading to reduced insulin requirements and improvements in insulin sensitivity.
Published: 2004

36. Changes in free rather than total insulin-like growth factor-I enhance insulin sensitivity and suppress endogenous peak growth hormone (GH) release following short-term low-dose GH administration in young healthy adults

Author: Linda Fryklund, David B. Dunger, Kevin C.J. Yuen, Margot Umpleby, and Jan Frystyk
Subjects: Adult, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Clinical Biochemistry, Endogeny, Carbohydrate metabolism, Placebo, Biochemistry, Drug Administration Schedule, Insulin-like growth factor, Endocrinology, Double-Blind Method, Reference Values, Internal medicine, medicine, Humans, Insulin, Insulin-Like Growth Factor I, Cross-Over Studies, Dose-Response Relationship, Drug, Pulse (signal processing), business.industry, Human Growth Hormone, Biochemistry (medical), Somatropin, Growth Hormone, Glucose Clamp Technique, Liberation, Female, business
Abstract: High-dose GH administration is commonly associated with impaired insulin sensitivity (S(I)) in humans. Paradoxically we have shown that low-dose GH (1.7 microg/kg.d) administration enhances beta-cell function in young healthy adults. In the present double-blind, placebo-controlled, cross-over study, we explored the physiological effects of this low GH dose on glucose metabolism in 12 young healthy adults (seven males, 19-29 yr). At pretreatment and after each 14-d treatment block, overnight metabolic profiles were assessed followed by a hyperinsulinemic euglycemic clamp, whereas fasting blood samples were collected weekly. In subjects treated with GH first (group A, n = 6), GH treatment increased total IGF-I (P0.05) and IGF binding protein-3 (P0.01) after 7 d, but these levels subsequently returned to pretreatment levels after 14 d. In contrast, free IGF-I increased (P0.05), and overnight GH pulse peak amplitude decreased (P0.01) after 14 d. In subjects treated with placebo first (group B, n = 6), all biochemical parameters were unchanged after placebo treatment, whereas the changes in free and total IGF-I were similar to those of group A after GH treatment. Combined clamp data from both groups A and B (n = 12) showed that 14-d GH treatment decreased overnight plasma insulin levels (P0.02) and hepatic glucose appearance (P0.05) and increased S(I) (P0.01). Of note, the GH-induced changes in S(I) positively correlated with the changes in free IGF-I (r = 0.72, P0.01). In conclusion, low-dose GH administration enhanced S(I) and suppressed endogenous peak GH release, and we hypothesize that these effects are the direct result of increased serum levels of free IGF-I.
Published: 2004

37. The effect of a six-month exercise program on very low-density lipoprotein apolipoprotein B secretion in type 2 diabetes

Author: Peter H. Sönksen, Saima Alam, A. Margot Umpleby, M Stolinski, Claire Pentecost, Richard H. Jones, and M. A. Boroujerdi
Subjects: Adult, Blood Glucose, Male, medicine.medical_specialty, Very low-density lipoprotein, Time Factors, Apolipoprotein B, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Physical exercise, Type 2 diabetes, Lipoproteins, VLDL, Biochemistry, Endocrinology, Insulin resistance, Internal medicine, medicine, Diabetes Mellitus, Aerobic exercise, Humans, Obesity, Aged, Apolipoproteins B, biology, business.industry, Biochemistry (medical), nutritional and metabolic diseases, VO2 max, Middle Aged, medicine.disease, Lipids, Exercise Therapy, Kinetics, Diabetes Mellitus, Type 2, Physical Fitness, biology.protein, Body Composition, Quality of Life, lipids (amino acids, peptides, and proteins), Female, Insulin Resistance, business, Lipoprotein
Abstract: The dyslipidemia and insulin resistance of type 2 diabetes can be improved by aerobic exercise. The effect of 6 months supervised exercise on very low-density lipoprotein (VLDL) apolipoprotein B metabolism was investigated in patients with type 2 diabetes. Moderately obese patients (n = 18) were randomized into supervised (n = 9) and unsupervised (n = 9) exercise groups. All patients were given a training session and a personal exercise program and asked to exercise four times per week at 70% maximal oxygen uptake for 6 months. Patients in the supervised group had a weekly session with an exercise trainer. VLDL apolipoprotein (apo)B metabolism was measured with an infusion of 1-13C leucine before and after 6 months of the exercise program.Supervised exercise for 6 months resulted in a significant within-group decrease in percent hemoglobin A1c (P < 0.001), body fat (P < 0.004), nonesterified fatty acid (P < 0.04), and triglycerides (P < 0.05) and an increase in insulin sensitivity (P < 0.01). There was a decrease in VLDL apoB pool size (160.8 ± 42.6 to 84.9 ± 23.2 mg, P < 0.01) and VLDL apoB secretion rate (11.3 ± 2.6 to 5.5 ± 2.0 mg/kg·d, P < 0.05) with no change in fractional catabolic rate. In a between-group comparison, the decrease in VLDL apoB secretion rate in the supervised group did not achieve significance. This study demonstrates that in type 2 diabetes, a supervised exercise program reduces VLDL apoB pool size, which may be due to a decrease in VLDL apoB secretion rate.
Published: 2004

38. 40(th) EASD Annual Meeting of the European Association for the Study of Diabetes : Munich, Germany, 5-9 September 2004

Author: S. Artigas, A V Dreval, Mark I. McCarthy, C Watson, Peter H. Bennett, M Quint, Y Ikeda, E Alpert, F Schiele, H Sekihara, Erik Gylfe, P Lowe, J Kuhlmann, Alain Golay, V Longo, Shahidul Alam Khan Akm., L G Mantovani, M Zawodniak-Szalapska, G Winkler, T Harrity, L Virág, U Johne, Kuo S-W., Linda C Tapsell, J Rodriguez, Michel Komajda, K Kankova, Carole A. Cull, M Sporna, E Estilles, U Ribel, M C Spruce, E Buzzigoli, T Prazak, J K McLaughlin, M K Lingohr, M Lim, F Calara, A Siebenhofer, G Meregalli, Roberto Anichini, A D Baron, R Kurashvili, P C Butler, G I Fantus, T. E. De Gooyer, Park Y-M., R. Walther, S Heinrich, Agnieszka Zawiejska, S Mukherjee, Nikolaos Papanas, G Wong, Ian D. Caterson, David M. Maahs, Shuichi Kaneko, Alexandra E. Butler, Francisco Javier Ampudia-Blasco, O N Kong, Attali J-R., C A Hedman, K Oshinyemi, Nicolle Müller, I C Cranston, N Okumus, M V Vlaiculescu, Balasubramanian Ravikumar, W W Cheatham, K Mukasa, K B Biswas, Annunziata Lapolla, Phil McEwan, G Mader, Gilles Chassot, Dragi Anevski, Werner A. Scherbaum, M Donath, C Hesselmann, R A Gandhi, David E. Moller, Ezio Bonifacio, C Garcia, V Ifandi, P Hornnes, Nieuwenhoven Fav., C Puech, S Pérez-Del-Pulgar, Kim S-R., G Hines, C Rubio Terrés, Michael Gaster, N. Hosszufalusi, A Scholze, Andrew A. Young, Stavros Liatis, F Hariri, S Tan, Paul Valensi, Allan E. Karlsen, J Kim, E. Moberg, J Kaiser, L Berman, G Nelson, A Altkrüger, P Kothare, D B Cook, S Doran, G. van Dijk, Shahnaz Shahinfar, Kim C-S., P Stahl, M Manousaki, S Sigrist, S K Lim, M. P. Stern, A Guberti, C Rezzani, J McKenney, Karl Thomaseth, Sofia Carlsson, M Julia, R Brillante, I Rubesova, T Darkow, E Matsumoto, Wendy M. Macfarlane, M Di Martino, G Bardini, Rossella Menghini, D Duhot, E Farcasiu, Annalisa Natalicchio, I Lindner, J Buvat, Christian L. Brand, Harry Dorchy, Iwona Pietrzak, Z T Luo, P Home, M Ekelund, Jesper Gromada, Kristine Færch, F Piarulli, H Kim, R Mentel, Zsuzsanna K. Zsengellér, Dullaart Rpf., Anton Luger, Thomas A. Pearson, V Manicardi, P Rösen, Feng Y-M., R Morganti, Lars Hansen, Demuth H-U., Haruo Kasai, A Shostak, Rudi Steffensen, G Taylor, Markolf Hanefeld, C Santini, E Hamaguchi, Roberto Miccoli, F Storms, M Cooper, Y Lee, Allison E. Aiello, P Smith, T Suehiro, K Treece, M Waluś, Timothy A Welborn, Simone Baltrusch, E Kontela, S Chai, J Crean, H Yokoyama, Johan G. Eriksson, Rafael Hernández Hernández, J Rodríguez-Saldaña, M P Tornero, G Formoso, D. Lovell, E Bingham, A Mylonakis, M Manteghetti, D Fedele, Antonio Martín-Duce, Ralph A. DeFronzo, D Salcedo, Kurt Højlund, Antonio Petrone, Sheu Whh., C Gutierrez, Flavia Pricci, S Kurita, Z G Abbas, M M Benedetti, Philippe A. Halban, Daniel J. Cox, O Ljungkvist, Justine Davies, J Palsgaard, Lars Sjöström, E Bosi, L Janin-Manificat, W. F. Kelly, M. Fernandez, E Colak, O V Mulyarchik, B Kronshage, F Lang, M Erfurth, Takashi Kadowaki, N Jendrike, U Walter, J Wishart, Y. Neye, D Kim, N Furuhashi, M Barsotti, D Florow, L Ke, L Borgquist, N C Jackson, Ffolliott M. Fisher, V Baskar, K Yoshioka, Bryan A. Wolf, G Chabrier, R Skoumal, Livio Luzi, H Kose, I Pharisien, B. Klein, H Winiarska, M C Johnson, L Griffiths, Nonna Kravchun, C Combe, Baptist Gallwitz, J Zdychova, L Skorda, Jorma Ilonen, W Gao, I N Steen, A Terrinoni, P D Ambery, W Kern, C M Kusminski, Cho M-H., Paolo Pozzilli, Louise G. Grunnet, E Schönle, David R Matthews, Robert W. Taylor, Y Cohen, Kim H-S., M P Eccles, N B Tutuncu, D McDowell, Richard M. Bergenstal, K Takamatsu, T Steiner, Jaan Palgi, Valdemar Grill, N Niculescu, G Federici, S Lehto, P. M. McKeigue, M Barone, Michael E. Trautmann, S Smirnov, J Mannion, M Eto, C Rousseau, M Conti, C S Ernest, Antonio Ceriello, D H Schweitzer, Jung E-D., Andreas Festa, Avijit Lahiri, A Shepelkevich, A Murro, A Kollmann, Jonathan R.S. Arch, R Landgraf, Son H-Y., I Engelsberger, E Agardh, S Rodríguez-Mulero, P J Kraml, K Lee, D. F. Du Toit, E Kim, G Fadini, Williams Ajk., Philip Home, M B Antcieferov, C Perlemoine, D Perrea, Song X-L., D Ruggieri, Krister Bokvist, Heidi Sørensen, Bilbao, G Yoshino, J P Taylor, Shen H-M., S M Furier, R Urquhart, J Wohlgelernter, Jianping Weng, T. Baba, Q Hong, C Silva, Castaigne J-P., M Felaco, X X Zhang, M Jaroň, Milla Rosengård-Bärlund, J G Papp, Toshio Miyata, Lervang H-H., Park M-K., I Kinalska, A Long, Oomen Phn., N Kogawa, Ippolita Patrizia Patera, S. Karadeniz, Dinesh Selvarajah, D S Chung, A Wensaas, Richard Imrich, M Recasens, J Ruxer, O Buchea, E Wilpart, S P Stepanenko, Le Ttd., H Ohgawara, Mariaconsuelo Valentini, A Mondok, M Peltonen, Marianne O. Larsen, K Chatzianagnostou, Agneta Ståhle, A L Ferrari, L Bordier, F Maingrette, A Matsuda, G Vukomanovic, Jakob D. Wikstrom, T Yamakita, E Gorostiaga, J Jin, B Gopalan, Heinz Drexel, S Hewitt, Rury R. Holman, C Dieterle, T L Ruchti, N Asatiani, M Sidira, A Iezzi, A J Sommerfield, D Châtenet, M L Olsen, R Bergemann, C Koehler, T L Kuraeva, B Balas, Christian Berne, E Santos-Mazo, G Smith, A Siejka, R Kožnarová, A Mattina, S Sheikh, A Adomeit, M Rasmussen, J. Fagerudd, N Busciantella Ricci, Nuria Vilarrasa, E Hammar, T L Thoms, L Aydın, Ron G. Rosenfeld, A Nikolajuk, R Gos, C L Morgan, H L Yu, D Dheelchand, S Ramrath, N Boudriga, Jerome I. Rotter, C Jahannault, W M Weston, Folke Lindgärde, M Hertlova, D Knight, A Monroy-Mayorga, E Pardini, A Chamson-Reig, B Franke, Janie McCluskey, Joseph Bryan, C Nikolopoulou, Christie M. Ballantyne, Fausto Santeusanio, L Pegoraro, M Lee, A Klimenko, S Jaiveer, K. Pettersson-Fernholm, Michael A. Nauck, A Ekbom-Schnell, G Deferrari, Riccardo Schiaffini, S. Pampanelli, Khan Aka., David Hopkins, Maija Wessman, M Kamarinos, Noh J-H., O Ebisui, K McCarroll, Jeppe Sturis, Peter Nowotny, N Gorbenko, Åke Sjöholm, David G. Maggs, A E Halseth, B Cresci, A A Ortiz-Gress, A Korakovouni, O Matejkova, C E Mogensen, C J Lin, Ramon Gomis, H Seaman, C Granier, Yang C-H., F Assah, O Sanchez, Fausto Machicao, Peter G. Morris, Alberto Ortiz, A Giardinelli, D Bracaglia, A Gonzalo, S Pavlatos, Andreas Lechner, F Canovic, L Sjolind, Allan Vaag, Birgitte Bruun Nielsen, David A. Ziegler, Vito Lampasona, R Gershoni-Baruch, A. Dei Cas, H Renz, E Mena, Matthew Waltham, Kim D-M., H Levanen, D D Mick, Valentina Alexandrovna Peterkova, E Meskhishvili, Sarah Nutland, R Bustani, John R. Lindsay, M Christoforidou, A Abicht, E Harno, K Cyganek, A Fitchet, S Neelotpol, P Nikishin, P Serradas, J Hinrichsen, M Halvorson, M Chovatia, B Voet, Jinny Willis, E Parretti, M Haslbeck, M Wellard, L Teng, Julio Wainstein, J S Fischer, K. Lalic, D Roggenland, I Gich, R Anwar, Maurizio Cassader, D Serota, X J Li, R J Schotzinger, Vilmundur Gudnason, Björn Zethelius, S A Wootton, W Andrzejewski, R Rezsohazy, R Gao, T Klimentova, T Mazurek, I Bruckner, C Dohrmann, R E James, G daSilva Xavier, Kim S-Y., A Dorca, Stuart J. Pocock, Terri J. Allen, I Giovos, P B Parab, N H Andersen, P Fotinakis, Miriam Cnop, H Lee, Norbert Tennagels, Omorodola I. Abatan, F Ailett, I. Lager, D Manzella, H Hut, Larry A. Distiller, G Lip, Lim S-K., Rong Zhang, T Tsuno, Steen Knudsen, M. Bajardi, Manuel Benito, Dai Sugimoto, Melvin J. Prince, D W Dunstan, D Rankins, K A Majali, G Ozansoy, Isabella Russo, S Uçak, G Annuzzi, R Talar-Wojnarowska, K Lange, S Neugebauer-Baba, Campbell H. Thompson, Eric Renard, P. D. Mountjoy, Z Morrison, Elizabeth A. Davis, Franco Cavallo, C Corvaja, R Antuña, Craig John Currie, H Linnebjerg, He Y-L., A J Palmer, Mariola R. Chacón, H Malinska, M. Jones, R Lichnovská, K Mandes, Paolo Tessari, T Mokhort, A Laina, H. L. Y. Chan, I Schmidt, R Banks, Richard G. IJzerman, L Ksinantova, G Setti, H Vaudry, A Gallo, V Spallone, Chen J-W., Thomas Danne, A Chong, M Hallschmid, S Aczel, S Hulme, N Islam, M Hosoi, P M Ternan, P Di Bartolo, N Bishara, T Shibasaki, Martin A. Osterhoff, Im S-S., M Jecht, T Hamaguchi, S Mattera, K Ways, Elizabeth Northam, U Rajala, Reinhard W. Holl, L Yang, S Panaiotopoulos, K Horvath, R Kluge, Thora B. Bodvarsdottir, Y Dong, Irene Alemanno, C McDougall, Reimar W. Thomsen, M Campbell, W Rabl, John Öhrvik, Yuichiro Yamada, Paola Ungaro, W Benzer, Mike Sampson, Roberto Trevisan, R G Radu, Aas A-M., P E Lobo, Ricardo Scott, S M Son, Josephine M. Forbes, T A Hillier, K L Wyne, Louis L. Nguyen, J Farmer, M H Tan, Kwon H-S., J Yang, L Sandvik, Franco Folli, A K Jenum, M Nguyen, W Pratipanawatr, A L Frederiksen, Rebecca Smith, Lee H-J., A Schäfer, C Manuelli, G S Denver, T Vukovich, B Maceira, K Matsumoto, K. Chokkalingam, Nurcan Üçeyler, P Modi, Timothy M. Morgan, S Mertens, B M Singh, Michaela Riedl, K Iso, C Cucurullo, G. F. Bottazzo, M Calvani, K Hur, J Wetzels, Kazuhiro Takahashi, Y Aso, H Stammer, M G Masding, Fitsum Guebre-Egziabher, J L González-Sánchez, L Armstrong, Alberto Maran, Peter G.F. Swift, S S Popovic, J Starczynski, E Vitacolonna, Luigi Laviola, R W Gelling, Marina Cardellini, D Barilla, Rosa de Diego Martínez, W H Landschulz, Anne Mette Rosenfalck, R K Wong, Kevin E. Schneider, K Peros, Giuseppe Nanni, F Zhang, I Rákóczi, T Iburi, M Nakhjavani, X Q Zhang, S Tournis, Per Lav Madsen, Graham A. Hitman, A. Tura, K Laubner, N D Kostic, Lawrence M. Dolan, R. Sinha Roy, J A Wagner, J. Tuomilehto, J Hauptman, M Abdel-Ghany, D Lacombe, Toralph Ruge, Johannes A Maassen, Triantafyllos Didangelos, K Sasaki, I Argüelles, Klaus Levin, C Popow, Emanuel Christ, R Chetty, L Baillet-Blanco, Jo-Ann Salmon, T Mine, James L. Trevaskis, I Franke, J Gorski, E A Andrianova, A Dayan, A Caballero, Aleksandra Gilis-Januszewska, M Yasujima, Z Kasalová, C.D.A. Stehouwer, F. K. Gorus, G A Nichols, A Glowania, David P. Strachan, P Fredlund, N. F. da Silva, P Reboldi, M Sausbier, K H Groenier, G Stuccio, N Guttman, K R Ahmed, A D Ristic, T Kapellen, J Coutcher, Aldo V. Greco, Oswald Wagner, A Zagayko, Maria Alevizaki, B B Zhang, W F Ferris, Jenny Fredriksson, Lois Jovanovic, J Hänninen, R De Giglio, Kazuo Yagui, O Potterat, P Hamliton, R E Scranton, B Mankovsky, A Stylianou, B Fellström, Abdel-Wahab Yha., M Kitagawa, Katherine L. Baldock, F R Johnson, F Baigts, S D'Addato, F J Sanz, A Mistry, S D Wise, T Pratipanawatr, U R Fölsch, James R.C. Parkinson, Claudia Sommer, C Park, F E Griffiths, M L Martí, R Demirtunc, S Taniguchi, J Lundkvist, T Siegmund, Juan Sztajzel, C Dienesch, F Baumgartner, L Scalone, T M Mckolanis, K Otake, Ullrik Pedersen-Bjergaard, T M Vriesendorp, Michael B. Wheeler, Henry Schmitt, Peter Hovind, S Lange, Stephane Roze, L. Van Gaal, B Klaproth, Anthony E. Civitarese, D Eckland, A Dagar, D F Hopkins, Kari Stefansson, C Gonzalez-Yanes, B Meyboom-de Jong, D. J. Betteridge, K Buhling, M Crepaldi, Ana M. Wägner, L Renna, L Volpe, R McBride, V Corbo, E O Brennesvik, R P Hayes, R Abdollahnia, G Viviani, C F Liew, Francisco Pérez-Bravo, Jeffrey Baron, Brian M. Frier, H H Samira, D Szentendrei, K. J. Schjoedt, W K Waldhäusl, D Gniuli, D Zou, G Tschank, V Urbančič, A L Nolan, Albertini J-P., J Malcomson, M Larbig, C Cheyssac, K Aurich, C M Kesson, S Heller, Maija E. Miettinen, R F Luco, Adrian J. Cameron, Luigi Mattiello, Z. Metelko, X E Zhang, M Parramón, I. G. Obrosova, J Fruchart, M Ilic, Björn Eliasson, Gilles Chatellier, M A Martín, D M Kendall, Holger Luthman, V F Varillas, D Maccubbin, Jang S-A., Amalia Gastaldelli, E Salzsieder, P. de Mol, A Yoshida, H D Lindner, D Gostiljac, M Just, Pan C-Y., J M Fujitaki, G Eiermann, K Bergenheim, A D Frick, A Agacdiken, K Varytimiadis, K Cseh, D A Jackson, S Calderari, Dena G. Hernandez, H M Liebich, K Min, F. de Zegher, Bernd Kulzer, K Han, Ulrich A. Müller, D Marrero, H Hatakeyama, René Koopman, Doo H-K., Petr Wohl, P. Sharp, P Forder, Thor Aspelund, N Meneveau, R M Schmülling, R Aubert, Thom Sam., H Youshikawa, M Ankelo, D Bowden, I Kelly, Frédéric Fumeron, M Sartini, Robert S. Sherwin, L Varadhan, A Criscimanna, John Betteridge, V Jelic, M Bartnik, N Lemke, B Ursø, A Bertoldo, A M Owona, H Okochi, L Pérez-Tamajó, S L Monfre, Daniel Brandhorst, K T Legg, Andries J. Smit, Veronica Sancho, Masashi Hirai, C Klein, Paul J. Thornalley, A Chaidaroglou, K Miura, B Zinman, O M Dvoynishnikova, J Plank, Jan Bolinder, C Lush, B Rubi, R Pozzilli, M Bashir, S A Shtandel, F Mosca, A Naskalska, Josef Vcelak, U Sausbier, P Cavaiani, T U Baehring, Michele Solimena, P Formisano, M Rastaldi, Bernard Thorens, J Ruzzin, E Arbit, M. Hori, Torkel B. Brismar, E Soltes Rak, A Filo, P Heinke, Matthew P. Coghlan, M Masotti, I Perevozskaya, K Ahn, I Moules, K Van Dyck, I Goldstein, Z Mathe, G Z Zhao, S Fajardo, J Taylor, S Chrul, J C Pareja, D Hadjidakis, A J Scheen, N Siddiqua, D C Cavan, R Grella, Krabbe S, H J Rochlitz, A E Hinkkanen, W Wilpshaar, Richard Stevens, M Dreyer, S Hara, X Wang, Melania Manco, D Gillen, Magalie A. Ravier, Olli Simell, John C. Lawrence, Kohnert K-D., Agardh C-D., A Berghold, L Kristensen, Grant Sfa., N Gursoy, Leif Groop, N Freemantle, Anja Schweizer, L Pala, Legros J-J., C. Di Pietro, N. Yamamoto, J Magyar, B Nikolovski, H Ikeda, D Lee, Bruce A. Buckingham, A O Wollitzer, I Kennedy, C Ernest, Neville H. McClenaghan, S Tanaka, Asimina Mitrakou, T Heinze, W Kerner, Moeenaldeen Al-Sayed, Charles Thivolet, L Klaff, A Miconi, Cristina Valeri, J. O. Christensen, K. Ekberg, A Jardine, T Endo, X Zhang, D F Child, A Kienitz, D K Seidel, H. Tada, Sylvie Abouna, Cyrus Cooper, Catherine R Chittleborough, Roberta Assaloni, S Corbi, A K Bose, K Ozawa, C Ahn, K A Deans, G Jackowski, Martin Gibson, Patrick McElduff, O A Mojiminiyi, Manuel Serrano-Ríos, O Dupuy, A L Davydov, Iwar Klimes, Sten-Anders Ivarsson, N Ichino, R Matsutomo, E R Smith, A Stefanovska, B Dehmel, K Koniavitou, E Agascioglu, M Hatazaki, J. M. Gibson, T Yada, P Ribaux, M Rupnik, K Fridell, G Scutaru, L Chugunova, Henrietta Mulnier, A Kendereski, H Lehnert, C Billi, M Sobczak, Francisco M-Mj., L K Archibald, S Sukumvanich, David B. Dunger, I. Benke, G Yillar, N Stingemore, J. M. Boavida, Y Shi, Jimmy D. Bell, L Bozzetto, Andrew J. Ahmann, E Jebens, J Keiding, Elena Henkel, Mark Fineman, J F McRae, Carol Forsblom, S Martemucci, Lourdes Ibáñez, P G Prieto, L Ringholm Nielsen, S Pratas, B von Stritzky, Julio Rosenstock, Lee K-W., J Stocks, L J Strow, I Samarguliani, L Wennekes, R Cheung, Abhishek Nag, Roberto Gambino, Y Suleymanoglu, E Murphy, T T Durck, M F Peyrot, Y Unno, Alexander Mayorov, Eleuterio Ferrannini, D. C. Rao, D Neely, H Karunajeewa, J Palmisano, Julia B. Lewis, M Ravid, G Pons, E Junca, P Vexiau, S Sailesh, D K Miloslavskiy, O N Bondarenko, U Smith, S Torri, Constantine Tsigos, Cesario Bianchi, Mattia Locatelli, D Jaquet, Virpi Lindi, M Moroi, M E Tushuizen, P Pelicci, R Scognamiglio, Pal Pacher, S M Thyssen, A Péterfalvi, Y Ho, S Guntram, L Romics, T Nakagami, Clive S. Cockram, Irina Kowalska, K Brodbeck, Gojka Roglic, J. Dörig, Lise Tarnow, Therese Tillin, A López-Alba, Martin Krššák, Moses Elisaf, S Hata, D P Snoeck, D Schmoll, O V Udovichenko, A Scaramuzza, J Paul, John H. Fuller, Nicholas Katsilambros, Michele Muggeo, Pia Ekbom, Piero Marchetti, V Melki, C Bailleau, H Stavrianos, A D'Errico, Geremia B. Bolli, Amabile Maier, Kelter A-R., Anders Green, Q J Morélis, Steffen Thiel, C Watkins, R C Cheung, A Clark, Elvira Fioriti, N Ari, Nam J-Y., Y Cottin, L G Krinelke, H Al Mohammedi, Simon C. Fleming, C Jones, Z Kerényi, Ahn Y-H., Meile M-J., P Nánási, M Graner, V Canonico, Gangnerau M-N., Hugh R. Taylor, Giovanni Sartore, A. Dejgaard, Carol Kelley, S. Ali, Stéphane Dalle, Jeffrey S. Gonzalez, Elena Šeböková, Alexander Beck, Ingo B. Leibiger, M Rosu, C Pencea, Werner Waldhäusl, Kaltenbacher M-C., R Butzer, S Thore, Adam G. Tabak, Angelo Avogaro, E Standi, Boris Kovatchev, O Bradescu, Patrizia Dentelli, A Fujita, C Verri, R Chlup, Prasad Ydm., S V Hörsten, van der Merwe M-T., D Hilliard, W Klein, D Worthley, M Udvardy, Berit R. Jensen, A D'Avanzo, J Monaghan, K P Yeo, Guivarch P-H., B Bauduceau, D Weghuber, P Tatti, J Ybarra, S Gwozdziewiczová, E Gasparini, B Saltin, Charlotte Granhall, Howard Leventhal, R Marin, M Tumiati, Cicero Afg., L Csémy, B Berger, S Mikros, D Dall'Asta, M Shahmanesh, Y G Vasiljev, F Potthoff, H S Randeva, G De Berardis, J O Logan, K Warncke, P Uitterlinden, E Rehring, K Gilmore, K Shankhdhar, V V Bojko, M Vahatalo, E A Korolyova, D Wiemann, P G Lankisch, D Hendrie, F Galtier, M Rybarczyk, Gisela Dahlquist, N N Rudovich, G Stein, A Liebl, F Tan, A Westerlund, S Gronemann, I Franklin, Jonathan A. Prince, Peter Arner, E Skliros, T. Sparre, M Vigas, Maddalena Trombetta, L. Bjerre Knudsen, A C Sima, I Dubroca, Alastair Gray, I Weets, R Ferraresi, Schauer Ujw., E. Leinonen, S Corazza, Jonathan Levy, P K Prakash, R Guzder, S. Barnhill, John Blangero, J Herreros, G. de Vries, Cheng Ptw., A Macías-Batista, K. Capito, R Thomas, G Thomas, G Boemi, Lotte Pietraszek, Pierre Fontaine, I Holme, J Smedegaard, C A Harrop, U Helwig, B Levy, A P Gribben, Hiroto Furuta, P Beckett, S Giannini, Ruth L. Coleman, Eva Fernqvist-Forbes, N Cugnardey, A Dumas, Jane Pinaire, S E Hofer, D Shimono, Erik H. Serné, Alain D. Baron, C Battista, M Tanen, M Klementova, V Adams, J Komorowski, Antonio Nicolucci, E. C. Burns, H Sydall, M G Fanara, M G Giovannitti, N Okabayashi, Magdalena Szurkowska, I A Eroshkin, M. I. J. Uusitupa, D Ma, C C Dieguez, J Sutcliffe-Goulden, A V Gaddi, Michał Arabski, Serge Halimi, Wendy C. Burns, S Seclén, H Sugano, A Vinterby, K Backx, L F Diaconu, Fernando Gomez-Peralta, O'Harte Fpm., G Lepeniotis, D Laune, H Kvasničková, N H Wallén, G Boner, G Cieślik, Robert Hermann, Paul Q. Thomas, Y Kumon, Maria Maiello, M Atkins, Kenneth A. Earle, Guowang Xu, H Y Bae, I Reynisdottir, D Perez, D E Cannon, P Fabietti, I Geronooz, J Østergaard, K J Jeitler, S Skourtis, A Zambanini, A Saemann, K Kuboki, Helen L. Lutgers, A C Thai, Arne Melander, D Pinkowski, S G Straub, S A Wolfe-Coote, A Totora, Hayley Dickinson, A Lindenmair, A Ginis, I Faturos, F Van Eylen, C Huard, F Fu, N Wang, B M Rasmussen, Angela Napoli, L Granato, Markus M. Lerch, M. Frandsen, A Lyras, Lawrence S. Phillips, J Mabley, R Goldschmeding, B K Kilhovd, W Liu, Greg Poffenberger, P Cipriano, Anna Maria Charlotte K Lindqvist, A Matsuzawa, J Wang, T Yu, M S Pepper, Lena M. Thorn, Y Sakamoto, Blanche Schwappach, Anna L. Gloyn, P Dupraz, A. M. Schmidt, M Psallas, V Tsirimbis, Carl D. Langefeld, D Sass, H E Scholtz, M. Cailleau, Lauren Julia Brown, K Phillips, M. Iezzi, C Jayawarna, Eleni Anastasiou, R Lobmann, R Lundershausen, H Fujiwara, H R Nan, I C Smith, I A Karpova, A Navazio, S Kang, T. Hansen, T Watanabe, Gang Hu, Malik Rja., T Kennedy-Martin, Ulla M Smidt, J.M. Dekker, A A Fisher, H Liu, R E Pratley, B Sun, C Fledelius, J F Raposo, R Langham, Ahn S-Y., B R Waterhouse, Shaoping Deng, W Ricart, S V Melnichenko, Henrike Sell, M. Tomalino, N Takeda, Paola Massucco, A Harlan, W Henrich, C D Byrne, R Junik, Khalid Hussain, D Pop Gorceva, Torben Hansen, C Ritterath, K Ogawa, D V Phan, Bradley S Metcalf, Robb E. Moses, Juan P. Frias, Hitoshi Ishii, C Brisard, P Wolkow, H H Maurer, Ingo Rustenbeck, Juris J. Meier, Octavian Savu, S D Lin, V B Bregovski, A Fox, S Cicala, M. Koenen, L Vignati, O de Divitiis, Constantin Ionescu-Tirgoviste, Kilian Rittig, J Song, Riccardo Candido, F Cohen-Boulakia, U Shankhdhar, P Jahan, Antonio Tiengo, E Liepinsh, C Álvarez, Sigurd Lenzen, James E. Foley, A. del Arco, M A Maitan, U Mollenhauer, M A Na, A Beha, B Aicher, Gabriele Meyer, E Sommariva, J Åman, B Gmeinhart, Theede A-M., Bjorn Bolinder, Giulio Ceolotto, S Sbrana, F Biarnes, Damini Dey, Barbara Thorand, H H Klein, Juliana C.N. Chan, L Piconi, S Gudbjornsdottir, E Bobbioni-Harsch, Joanna Polanska, Cristian Serafinceanu, S Gambardella, Olivier Huber, J D Brunzell, T Nagasawa, Loretta Vileikyte, A Szocs, H Löwel, Z Lin, Anders Juul, H Tsuneki, L Sauriol, G Siebert, Marit E. Jørgensen, K Matthies, Brian D. Green, P Jurowski, Z Gao, M Furuya, Silvia Manfrini, Efthymios Motakis, E Souvatzoglou, Qian Y-Z., Byun S-H., T Nguyen, M R Anwar, Geltrude Mingrone, B. Idzior-Walus, Mamas A. Mamas, G Scholl-Schilling, C Bittner, A E Raptis, L Laghi, Murray Stewart, M Orel, Janet M. 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D, Torjesen, P, Kilhovd, B, Berg, T, Sandvik, L, Hanssen, K, Mentink, C, Donchenko, G, Stepanenko, S, Maingrette, F, Deng, H, Lindenmair, A, Freudenthaler, A, Baumgartner parzer, S, Nizheradze, K, Khoruzhenko, A, Tronko, N, Sheu, W, Ou, H, Shen, H, Lin, T, Wu, H, Yang, C, Mogylnytska, L, Schmoelzer, I, Davies, J, Band, M, Struthers, A, Prázný, M, Škrha, J, Kasalová, Z, Neelotpol, S, Jahan, P, Kauschke, S, Harrop, C, Schäfer, A, Widder, J, Eigenthaler, M, Walter, U, Uchimura, I, Ikebukuro, M, Kaibara, M, Hirata, M, Helal, R, Pervin, F, Yang, X, Jansson, P, Nagaev, I, Jack, M, Carvalho, E, Sunnerhagen, K, Cam, M, Cushman, S, Smith, U, Creely, S, Farmer, J, Gustafson, B, Kusminski, C, Krusinova, E, Wohl, P, Klementova, M, Lanska, V, Mcdougall, C, Kelly, I, Abbas, Z, Lutale, J, Archibald, L, Karunajeewa, H, Stingemore, N, Stuccio, G, Mcgechie, D, Muller, L, Hak, E, Goudzwaard, W, Montorsi, F, Homering, M, Sprenger, K, Goldstein, I, Asnaghi, V, Ferrari, G, Rastaldi, M, Gabellini, D, Dell'Antonio, G, Maestroni, A, Ruggieri, D, Luzi, L, Piemonti, L, Zerbini, G, Anafaroglu, I, Tutuncu, N, Sultana, M, Siddiqua, N, Iwasaki, T, Nakajima, A, Yoneda, M, Mukasa, K, Tanaka, S, and Sekihara, H
Subjects: 0303 health sciences, medicine.medical_specialty, business.industry, EASD, Endocrinology, Diabetes and Metabolism, Human physiology, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Family medicine, Internal Medicine, Medicine, business, 030217 neurology & neurosurgery, 030304 developmental biology
Published: 2004

39. Prandial Hypertriglyceridemia in Metabolic Syndrome Is Due to an Overproduction of Both Chylomicron and VLDL Triacylglycerol. Diabetes 2013;62:4063-4069

Author: Yuying Ma, A. Margot Umpleby, Roman Hovorka, Fariba Shojaee-Moradie, and Shaoying Lou
Subjects: medicine.medical_specialty, business.industry, Endocrinology, Diabetes and Metabolism, Hypertriglyceridemia, VLDL triacylglycerol, medicine.disease, Endocrinology, Internal medicine, Diabetes mellitus, Internal Medicine, Medicine, Metabolic syndrome, business, Overproduction, Chylomicron
Published: 2014
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40. Insulin sensitivity of glucose transport and glucose disposal during IVGTT

Author: Roman Hovorka, Margot Umpleby, Romulus S. Tudor, Fariba Shojaee-Moradie, Ian J. Gowrie, Nicola Jackson, Richard H. Jones, Ludovic J. Chassin, and Paul V. Carroll
Subjects: medicine.medical_specialty, business.industry, Endocrinology, Diabetes and Metabolism, Glucose transporter, Glucose disposal, Insulin sensitivity, General Medicine, medicine.disease, Endocrinology, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, business
Published: 2000
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41. The effect of oral glucose on responses to hypoglycaemia: A possible role for the portal glucose sensor?

Author: Stephanie A. Amiel, Margot Umpleby, A Pernet, D Smith, M. Rosenthal, H Reid, and Emma Bingham
Subjects: medicine.medical_specialty, Endocrinology, business.industry, Endocrinology, Diabetes and Metabolism, Diabetes mellitus, Internal medicine, Internal Medicine, Medicine, General Medicine, Oral glucose, business, medicine.disease
Published: 2000
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42. External validation of the fatty liver index and lipid accumulation product indices, using H-1-magnetic resonance spectroscopy, to identify hepatic steatosis in healthy controls and obese, insulin-resistant individuals

Author: Helen Jones, E. Louise Thomas, Daniel J. Cuthbertson, A. Margot Umpleby, Daniel Lythgoe, Jimmy D. Bell, Andreas Pfeiffer, Graham J. Kemp, Victoria S. Sprung, Fariba Shoajee-Moradie, Rebecca Dobson, and Martin O. Weickert
Subjects: Adult, Male, Pathology, medicine.medical_specialty, Magnetic Resonance Spectroscopy, Endocrinology, Diabetes and Metabolism, Gastroenterology, RC1200, Endocrinology, Insulin resistance, Non-alcoholic Fatty Liver Disease, Internal medicine, medicine, Health Status Indicators, Humans, Obesity, Adiposity, Receiver operating characteristic, business.industry, Fatty liver, fungi, Case-control study, Type 2 Diabetes Mellitus, General Medicine, Middle Aged, Lipid Metabolism, medicine.disease, Liver, Case-Control Studies, Cohort, Female, Insulin Resistance, Steatosis, business, Lipid Accumulation Product
Abstract: Background and aimsSimple clinical algorithms including the fatty liver index (FLI) and lipid accumulation product (LAP) have been developed as surrogate markers for non-alcoholic fatty liver disease (NAFLD), constructed using (semi-quantitative) ultrasonography. This study aimed to validate FLI and LAP as measures of hepatic steatosis, as determined quantitatively by proton magnetic resonance spectroscopy (1H-MRS).MethodsData were collected from 168 patients with NAFLD and 168 controls who had undergone clinical, biochemical and anthropometric assessment. Values of FLI and LAP were determined and assessed both as predictors of the presence of hepatic steatosis (liver fat >5.5%) and of actual liver fat content, as measured by 1H-MRS. The discriminative ability of FLI and LAP was estimated using the area under the receiver operator characteristic curve (AUROC). As FLI can also be interpreted as a predictive probability of hepatic steatosis, we assessed how well calibrated it was in our cohort. Linear regression with prediction intervals was used to assess the ability of FLI and LAP to predict liver fat content. Further validation was provided in 54 patients with type 2 diabetes mellitus.ResultsFLI, LAP and alanine transferase discriminated between patients with and without steatosis with an AUROC of 0.79 (IQR=0.74, 0.84), 0.78 (IQR=0.72, 0.83) and 0.83 (IQR=0.79, 0.88) respectively although could not quantitatively predict liver fat. Additionally, the algorithms accurately matched the observed percentages of patients with hepatic steatosis in our cohort.ConclusionsFLI and LAP may be used to identify patients with hepatic steatosis clinically or for research purposes but could not predict liver fat content.

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