Abstract
Adiposity is associated with an increased risk of type 2 diabetes (T2D) and cardiovascular disease. It is likely that a change in circulating proteins plays a role in obesity-related disease risk. This study aimed to triangulate evidence from randomized controlled trials of caloric restriction and bariatric surgery, along with a Mendelian randomisation (MR) study to characterise the effects of BMI on proteins in circulation.
Data were used from the intervention arm of the Diabetes Remission Clinical Trial (DiRECT, N=119). Here, participants with overweight/obesity (baseline mean BMI 35.0 kg/m2, SD 4.6 kg/m2) underwent the CounterWeight Plus weight management programme, consisting of a low energy total diet replacement (TDR). Plasma samples were taken at baseline and after 1-year and SomaLogic was used to quantify plasma proteins. Data were also utilised from a pilot sample release as part of an ongoing trial of surgically induced weight loss (N=119). Serum samples were donated at baseline and 3-years post bariatric surgery; serum proteins were measured by the Olink Explore 1536 panel. Protein outcomes were inverse rank normal transformed and linear mixed models used to determine proteins associated with the weight loss interventions (3 types of bariatric surgery). Proteins with consistent evidence across both trials were looked up in our previously published MR analysis, which used a UK blood donor cohort, INTERVAL (N=2729), to estimate the causal effect of BMI on circulating plasma proteins.
1496 proteins out of 4601 were altered with the TDR intervention (p
This study utilized three independent cohorts and distinct analytical approaches to explore the effect of BMI on circulating proteins. Observing consistency across such analyses provides greater confidence that the effects we see reflect genuine physiological responses to differential BMI. We also observe discordance between association results that hint at intervention specific signals; these will form the focus of future work.
Data were used from the intervention arm of the Diabetes Remission Clinical Trial (DiRECT, N=119). Here, participants with overweight/obesity (baseline mean BMI 35.0 kg/m2, SD 4.6 kg/m2) underwent the CounterWeight Plus weight management programme, consisting of a low energy total diet replacement (TDR). Plasma samples were taken at baseline and after 1-year and SomaLogic was used to quantify plasma proteins. Data were also utilised from a pilot sample release as part of an ongoing trial of surgically induced weight loss (N=119). Serum samples were donated at baseline and 3-years post bariatric surgery; serum proteins were measured by the Olink Explore 1536 panel. Protein outcomes were inverse rank normal transformed and linear mixed models used to determine proteins associated with the weight loss interventions (3 types of bariatric surgery). Proteins with consistent evidence across both trials were looked up in our previously published MR analysis, which used a UK blood donor cohort, INTERVAL (N=2729), to estimate the causal effect of BMI on circulating plasma proteins.
1496 proteins out of 4601 were altered with the TDR intervention (p
This study utilized three independent cohorts and distinct analytical approaches to explore the effect of BMI on circulating proteins. Observing consistency across such analyses provides greater confidence that the effects we see reflect genuine physiological responses to differential BMI. We also observe discordance between association results that hint at intervention specific signals; these will form the focus of future work.
| Original language | English |
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| Publication status | Published - 28 Oct 2022 |
