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. 2023 Nov 1;46(11):1949-1957.
doi: 10.2337/dc23-0602.

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

Naveed Sattar  1 , Shahrad Taheri  2   3   4 , David P Astling  5 , Jessica Chadwick  5 , Michael A Hinterberg  5 , Michael V Holmes  6 , Emma V Troth  5 , Paul Welsh  1 , Hadeel Zaghloul  3   4 , Odette Chagoury  2   3   4 , Mike Lean  1 , Roy Taylor  7 , Steve Williams  5
Affiliations

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

Naveed Sattar et al. Diabetes Care. .

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.

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Conflict of interest statement

Duality of Interest. N.S. has consulted for and/or received speaker fees from Abbott Laboratories, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceutical, Janssen, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi and received grant support paid to his university from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche Diagnostics outside the submitted work. SomaLogic Operating Co., Inc., funded the costs of the proteomic assays and the biomarker measurements, and S.W., M.A.H., J.C., D.P.A., and E.V.T. are employees of the company. No other potential conflicts of interest relevant to this article were reported.

Figures

None
Graphical abstract
Figure 1
Figure 1
Relative predicted changes over 1 year during DiRECT (left) and DIADEM-I (right) for eight SomaSignal proteomic tests, with stratification by control (no dietary intervention), dietary intervention with up to 10 kg weight loss observed, and dietary intervention with ≥10 kg weight loss observed. Point estimates are relative percent change for predictive results with continuous outcomes, or change in proportion for binary status tests, with horizontal bars showing 95% CI of estimates. Glucose Tolerance and Liver Fat tests show the change in the percentage of participants predicted as glucose intolerant and having some excess liver fat, respectively.
Figure 2
Figure 2
Longitudinal changes from baseline for each of the SomaSignal tests in DIADEM-I. The thin lines are the individual trajectories for each subject, the thick lines are the fits from a repeated-measures model, and the ribbons are the 95% CI from the model fit. The control arm is colored purple, and the treatment arm is colored teal.
See this image and copyright information in PMC

References

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