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J. Clin. Med. 2019, 8(2), 141;

Data Independent Acquisition Mass Spectrometry Can Identify Circulating Proteins That Predict Future Weight Loss with a Diet and Exercise Programme

The School of Medical Sciences and Manchester Academic Health Sciences Centre, University of Manchester, Manchester M13 9PL, UK
Department of Diabetes and Endocrinology, Salford Royal Hospital, Salford M6 8HD, UK
Stoller Biomarker Discovery Centre, University of Manchester, Manchester M13 9PL, UK
SAS Peptide Hormone Section, Part of Berkshire and Surrey Pathology Services, Royal Surrey County Hospital, Guildford GU2 7XX, UK
The George Alleyne Chronic Disease Research Centre, Caribbean Institute for Health Research (CAIHR), The University of the West Indies, Bridgetown BB11115, Barbados
The Prevent Breast Cancer Research Unit, The Nightingale Centre, Manchester University NHS Foundation Trust, Manchester M23 9LT, UK
Manchester Breast Centre, Manchester Cancer Research Centre, University of Manchester, 555 Wilmslow Rd, Manchester M20 4GJ, UK
NIHR Manchester Biomedical Research Centre, University of Manchester, Manchester M13 9WU, UK
Authors to whom correspondence should be addressed.
Received: 21 December 2018 / Revised: 22 January 2019 / Accepted: 23 January 2019 / Published: 25 January 2019
(This article belongs to the Special Issue Type 2 Diabetes: Update on Pathophysiology and Treatment)
PDF [1031 KB, uploaded 11 February 2019]


We investigated biological determinants that would associate with the response to a diet and weight loss programme in impaired glucose regulation (IGR) people using sequential window acquisition of all theoretical fragment ion spectra (SWATH) mass spectrometry (MS), a data acquisition method which complement traditional mass spectrometry-based proteomics techniques. Ten women and 10 men with IGR underwent anthropometric measurements and fasting blood tests. SWATH MS was carried out with subsequent immunoassay of specific peptide levels. After a six-month intervention, 40% of participants lost 3% or more in weight, 45% of patients remained within 3% of their starting weight and 15% increased their weight by 3% or more. Hemoglobin A1c (HbA1C) level was reduced with weight loss with improvements in insulin sensitivity. SWATH MS on pre-intervention samples and subsequent principal component analysis identified a cluster of proteins associated with future weight loss, including insulin-like growth factor-II (IGF-II) and Vitamin D binding protein. Individuals who lost 3% in weight had significantly higher baseline IGF-II levels than those who did not lose weight. SWATH MS successfully discriminated between individuals who were more likely to lose weight and potentially improve their sensitivity to insulin. A higher IGF-II baseline was predictive of success with weight reduction, suggesting that biological determinants are important in response to weight loss and exercise regimes. This may permit better targeting of interventions to prevent diabetes in the future. View Full-Text
Keywords: IGR; lifestyle change; proteomics; SWATH MS IGR; lifestyle change; proteomics; SWATH MS

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Malipatil, N.; Fachim, H.A.; Siddals, K.; Geary, B.; Wark, G.; Porter, N.; Anderson, S.; Donn, R.; Harvie, M.; Whetton, A.D.; Gibson, M.J.; Heald, A. Data Independent Acquisition Mass Spectrometry Can Identify Circulating Proteins That Predict Future Weight Loss with a Diet and Exercise Programme. J. Clin. Med. 2019, 8, 141.

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