Abstract

BackgroundDyslipidemia with elevated levels of triacylglycerol-rich lipoproteins (TRL), small-dense LDL (sdLDL) and reduced HDL is linked to hepatic steatosis and promotes atherogenesis in type 2 diabetes (T2D). ObjectiveWe have shown that moderate carbohydrate restriction reduces liver fat in T2D independent of changes in body weight. We tested whether this is accompanied by parallel improvements in plasma lipoprotein subclasses. MethodsWe determined the density profile of circulating lipoproteins in patients with T2D from two previous randomized controlled trials. In the iso-energetic study (‘Iso’), 30 participants were allocated in a cross-over design to 6 + 6 weeks of an isocaloric carbohydrate-reduced high-protein (CRHP, C/P/F=30/30/40 E%) or conventional diabetes (CD, C/P/F=50/17/33 E%) diet aimed at weight maintenance. In the hypo-energetic study (‘Hypo’), 72 participants were allocated in a parallel-group design to 6 weeks of a hypocaloric CRHP or CD diet aimed at matched ∼6% weight loss. Both studies provided all meals from a metabolic kitchen to maximize adherence. ResultsIn the Iso study, the CRHP diet reduced mean (95% CI) TRL (-33 (-48, -14)%) and LDL5 (-16 (-26, -4)%), and increased HDL2/HDL3 (10 (0, 22)%) compared with the CD diet. In the Hypo study, weight loss induced by CRHP diet tended to reduce TRL (-16 (-30, 1)%), reduced LDL5 (-13 (-22, -3)%), and increased HDL2/HDL3 (11 (1, 22)%) compared with an equivalent weight loss induced by CD diet. The CRHP diet decreased intrahepatic triglyceride (IHTG) more than the CD diet (Iso: -55 (-74, -22)%; Hypo: -26 (-45, 0)%), and changes in IHTG correlated directly with changes in TRL and LDL5 (r=0.36-0.55, p<0.01 for all) in both studies. ConclusionsReplacing dietary carbohydrate with protein and fat improves dyslipidemia in T2D independently of changes in body weight, by inducing an atheroprotective shift in the lipoprotein particle profile possibly facilitated by reduced IHTG accumulation. ClinicalTrials.gov registrationNCT02764021; https://clinicaltrials.gov/study/NCT02764021?term=NCT02764021&rank=1 NCT03814694; https://clinicaltrials.gov/study/NCT03814694?term=NCT03814694&rank=1

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