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Prediction of Cardiometabolic Health Through Changes in Plasma Proteins With Intentional Weight Loss in the DiRECT and DIADEM-I Randomized Clinical Trials of Type 2 Diabetes Remission

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posted on 2023-09-26, 13:29 authored by Naveed Sattar, Shahrad Taheri, David P. Astling, Jessica Chadwick, Michael A Hinterberg, Michael V Holmes, Emma V. Troth, Paul Welsh, Hadeel Zaghloul, Odette Chagoury, Mike Lean, Roy Taylor, Steve Williams

Objective: To determine to what extent changes in plasma proteins, previously predictive of cardiometabolic outcomes, predict changes in two diabetes remission trials.

Research Design and Methods: SomaSignal® predictive tests (each derived from ~5000 plasma proteins measurements using aptamer-based proteomics assay) were assessed in baseline and 1-year samples in trials (DiRECT n=118, DIADEM-I n=66) and control (DiRECT n=144, DIADEM-I n=76) participants.

Results: Mean weight losses in DiRECT (UK) and DIADEM-I (Qatar) were 10.2 (SD 7.4) kg and 12.1 (SD 9.5) kg, respectively, versus 1.0 (3.7) kg and 4.0 (SD 5.4) kg in control groups. Cardiometabolic SomaSignal tests improved significantly (Bonferroni-adjusted p< 0.05) in DiRECT and DIADEM-I (expressed as relative difference in 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 metabolic rate (-8.0%, -5.1%), visceral fat (-34.3%, -26.1%) and cardiorespiratory fitness (+9.5%, +10.3%). Cardiovascular risk (measured by SomaSignal tests) also improved in interventions groups relative to control but significant only in DiRECT (DiRECT: -44.2%, DIADEM-I: -9.2%). However, weight loss >10kg predicted significant reductions in CV risk of -19.1% (CI -33.4 to -4.91) in DiRECT and -33.4% (CI -57.3, -9.6) in DIADEM-I. DIADEM-I also demonstrated rapid emergence of metabolic improvements at 3 months.

Conclusion: 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 larger (>10kg) weight loss also predicted lower cardiovascular risk, providing a positive outlook for relevant ongoing trials.

Funding

DIADEM-I was funded by the Qatar National Research Fund through the National Priorities Research Program grant (NPRP 8–912–3–192) awarded to ST. ST, OC, and HZ were supported by funding from the Biomedical Research Program by the Qatar Foundation to Weill Cornell Medicine Qatar (WCMQ). The statements made in this publication are solely the responsibility of the authors. NS is supported by the British Heart Foundation Research Excellence Award (RE/18/6/34217).

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