Compensatory changes in energy balance during dapagliflozin treatment in type 2 diabetes mellitus: a randomised double-blind, placebo-controlled, cross-over trial (ENERGIZE)-study protocol.

Autor:	Rajeev SP; Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.; Diabetes and Endocrinology Research Group, Clinical Sciences Centre, Aintree University Hospital NHS Foundation Trust, Liverpool, UK., Sprung VS; Diabetes and Endocrinology Research Group, Clinical Sciences Centre, Aintree University Hospital NHS Foundation Trust, Liverpool, UK.; Department of Musculoskeletal Biology II, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK., Roberts C; Department of Psychological Sciences, Institute of Psychology, Health and Society, University of Liverpool, Liverpool, UK., Harrold JA; Department of Psychological Sciences, Institute of Psychology, Health and Society, University of Liverpool, Liverpool, UK., Halford JC; Department of Psychological Sciences, Institute of Psychology, Health and Society, University of Liverpool, Liverpool, UK., Stancak A; Department of Psychological Sciences, Institute of Psychology, Health and Society, University of Liverpool, Liverpool, UK., Boyland EJ; Department of Psychological Sciences, Institute of Psychology, Health and Society, University of Liverpool, Liverpool, UK., Kemp GJ; Department of Musculoskeletal Biology II, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.; Magnetic Resonance and Image Analysis Research Centre (MARIARC), University of Liverpool, Liverpool, UK., Cuthbertson DJ; Diabetes and Endocrinology Research Group, Clinical Sciences Centre, Aintree University Hospital NHS Foundation Trust, Liverpool, UK.; Department of Musculoskeletal Biology II, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK., Wilding JP; Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.; Diabetes and Endocrinology Research Group, Clinical Sciences Centre, Aintree University Hospital NHS Foundation Trust, Liverpool, UK.
Jazyk:	angličtina
Zdroj:	BMJ open [BMJ Open] 2017 Jan 27; Vol. 7 (1), pp. e013539. Date of Electronic Publication: 2017 Jan 27.
DOI:	10.1136/bmjopen-2016-013539
Abstrakt:	Introduction: Sodium glucose cotransporter 2 (SGLT2) inhibitors are effective blood-glucose-lowering medications with beneficial effects on body weight in patients with type 2 diabetes mellitus (T2DM). However, observed weight loss is less than that predicted from quantified glycosuria, suggesting a compensatory increase in energy intake or a decrease in energy expenditure. Studies using dual-energy X-ray absorptiometry (DEXA) have suggested most body weight change is due to loss of adipose tissue, but organ-specific changes in fat content (eg, liver, skeletal muscle) have not been determined. In this randomised, double-blind, placebo-controlled crossover study, we aim to study the compensatory changes in energy intake, eating behaviour and energy expenditure accompanying use of the SGLT2 inhibitor, dapagliflozin. Additionally, we aim to quantify changes in fat distribution using MRI, in liver fat using proton magnetic resonance spectroscopy ( 1 H-MRS) and in central nervous system (CNS) responses to food images using blood oxygen level dependent (BOLD) functional MRI (fMRI). Methods and Analysis: This outpatient study will evaluate the effect of dapagliflozin (10 mg), compared with placebo, on food intake and energy expenditure at 7 days and 12 weeks. 52 patients with T2DM will be randomised to dapagliflozin or placebo for short-term and long-term trial interventions in a within participants, crossover design. The primary outcome is the difference in energy intake during a test meal between dapagliflozin and placebo. Intake data are collected automatically using a customised programme operating a universal eating monitor (UEM). Secondary outcomes include (1) measures of appetite regulation including rate of eating, satiety quotient, appetite ratings (between and within meals), changes in CNS responses to food images measured using BOLD-fMRI, (2) measures of energy expenditure and (3) changes in body composition including changes in liver fat and abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Ethical Approval: This study has been approved by the North West Liverpool Central Research Ethics Committee (14/NW/0340) and is conducted in accordance with the Declaration of Helsinki and the Good Clinical Practice (GCP). Trial Registration Number: ISRCTN14818531. EUDRACT number 2013-004264-60. Competing Interests: JW has acted as a consultant, received institutional grants and given lectures on behalf of pharmaceutical companies developing or marketing medicines used for the treatment of diabetes, specifically AstraZeneca, Boehringer Ingelheim, Janssen Pharmaceuticals, Lilly, Novo Nordisk and Sanofi &Takeda. DJC has competing interests with AstraZeneca, Boehringer Ingelheim, Janssen Pharmaceuticals, Lilly & Novo Nordisk. JCGH has acted as a consultant for Orexigen and Novo Nordisk. Other authors have no competing interests. (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)
Databáze:	MEDLINE
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