Prediction of cardiometabolic health through changes in plasma proteins with intentional weight loss in the DiRECT and DIADEM-I randomised clinical trials of type 2 diabetes remission

Sattar, N. et al. (2023) Prediction of cardiometabolic health through changes in plasma proteins with intentional weight loss in the DiRECT and DIADEM-I randomised clinical trials of type 2 diabetes remission. Diabetes Care, 46(11), pp. 1949-1957. (doi: 10.2337/dc23-0602) (PMID:37756566) (PMCID:PMC10628468)

Abstract

OBJECTIVE To determine the extent to which changes in plasma proteins, previously predictive of cardiometabolic outcomes, predict changes in two diabetes remission trials. RESEARCH DESIGN AND METHODS We applied SomaSignal predictive tests (each derived from ∼5,000 plasma protein measurements using aptamer-based proteomics assay) to baseline and 1-year samples of trial intervention (Diabetes Remission Clinical Trial [DiRECT], n = 118, and Diabetes Intervention Accentuating Diet and Enhancing Metabolism [DIADEM-I], n = 66) and control (DiRECT, n = 144, DIADEM-I, n = 76) group participants. RESULTS Mean (SD) weight loss in DiRECT (U.K.) and DIADEM-I (Qatar) was 10.2 (7.4) kg and 12.1 (9.5) kg, respectively, vs. 1.0 (3.7) kg and 4.0 (5.4) kg in control groups. Cardiometabolic SomaSignal test results showed significant improvement (Bonferroni-adjusted P < 0.05) in DiRECT and DIADEM-I (expressed as relative difference, intervention minus control) as follows, respectively: liver fat (−26.4%, −37.3%), glucose tolerance (−36.6%, −37.4%), body fat percentage (−8.6%, −8.7%), resting energy rate (−8.0%, −5.1%), visceral fat (−34.3%, −26.1%), and cardiorespiratory fitness (9.5%, 10.3%). Cardiovascular risk (measured with SomaSignal tests) also improved in intervention groups relative to control, but this was significant only in DiRECT (DiRECT, −44.2%, and DIADEM-I, −9.2%). However, weight loss >10 kg predicted significant reductions in cardiovascular risk, −19.1% (95% CI −33.4 to −4.91) in DiRECT and −33.4% (95% CI −57.3, −9.6) in DIADEM-I. DIADEM-I also demonstrated rapid emergence of metabolic improvements at 3 months. CONCLUSIONS Intentional weight loss in recent-onset type 2 diabetes rapidly induces changes in protein-based risk models consistent with widespread cardiometabolic improvements, including cardiorespiratory fitness. Protein changes with greater (>10 kg) weight loss also predicted lower cardiovascular risk, providing a positive outlook for relevant ongoing trials.

• Item Type: Articles
• Additional Information: DIADEM-I was funded by the Qatar National Research Fund through the National Priorities Research Program grant (NPRP 8-912- 3-192) awarded to S.T. S.T., O.C., and H.Z. were supported by funding from the Biomedical Research Program by the Qatar Foundation to Weill Cornell Medicine Qatar. N.S. is supported by the British Heart Foundation Research Excellence Award (RE/18/6/34217).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Lean, Professor Michael and Welsh, Professor Paul and Sattar, Professor Naveed
• Authors: Sattar, N., Taheri, S., Astling, D. P., Chadwick, J., Hinterberg, M. A., Holmes, M. V., Troth, E. V., Welsh, P., Zaghloul, H., Chagoury, O., Lean, M., Taylor, R., and Williams, S.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Diabetes Care
• Publisher: American Diabetes Association
• ISSN: 0149-5992
• ISSN (Online): 1935-5548
• Published Online: 26 September 2023
• Copyright Holders: Copyright: © 2023 by the American Diabetes Association
• First Published: First published in Diabetes Care 46(11): 1949–1957
• Publisher Policy: Reproduced in accordance with the publisher copyright policy

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
303944		BHF Centre of Excellence	Colin Berry	British Heart Foundation (BHF)	RE/18/6/34217	SCMH - Cardiovascular & Metabolic Health