Impact of a 2-year trial of nutritional ketosis on indices of cardiovascular disease risk in patients with type 2 diabet
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ORIGINAL INVESTIGATION
Cardiovascular Diabetology Open Access
Impact of a 2‑year trial of nutritional ketosis on indices of cardiovascular disease risk in patients with type 2 diabetes Shaminie J. Athinarayanan1† , Sarah J. Hallberg1,2,3†, Amy L. McKenzie1, Katharina Lechner4,5, Sarah King6, James P. McCarter7,8, Jeff S. Volek1,9, Stephen D. Phinney1 and Ronald M. Krauss6*
Abstract Background: We have previously reported that in patients with type 2 diabetes (T2D) consumption of a very low carbohydrate diet capable of inducing nutritional ketosis over 2 years (continuous care intervention, CCI) resulted in improved body weight, glycemic control, and multiple risk factors for cardiovascular disease (CVD) with the exception of an increase in low density lipoprotein cholesterol (LDL-C). In the present study, we report the impact of this intervention on markers of risk for atherosclerotic cardiovascular disease (CVD), with a focus on lipoprotein subfraction particle concentrations as well as carotid-artery intima-media thickness (CIMT). Methods: Analyses were performed in patients with T2D who completed 2 years of this study (CCI; n = 194; usual care (UC): n = 68). Lipoprotein subfraction particle concentrations were measured by ion mobility at baseline, 1, and 2 years and CIMT was measured at baseline and 2 years. Principal component analysis (PCA) was used to assess changes in independent clusters of lipoprotein particles. Results: At 2 years, CCI resulted in a 23% decrease of small LDL IIIb and a 29% increase of large LDL I with no change in total LDL particle concentration or ApoB. The change in proportion of smaller and larger LDL was reflected by reversal of the small LDL subclass phenotype B in a high proportion of CCI participants (48.1%) and a shift in the principal component (PC) representing the atherogenic lipoprotein phenotype characteristic of T2D from a major to a secondary component of the total variance. The increase in LDL-C in the CCI group was mainly attributed to larger cholesterol-enriched LDL particles. CIMT showed no change in either the CCI or UC group. Conclusion: Consumption of a very low carbohydrate diet with nutritional ketosis for 2 years in patients with type 2 diabetes lowered levels of small LDL particles that are commonly increased in diabetic dyslipidemia and are a marker for heightened CVD risk. A corresponding increase in concentrations of larger LDL particles was responsible for higher levels of plasma LDL-C. The lack of increase in total LDL particles, ApoB, and in progression of CIMT, provide supporting evidence that this dietary intervention did not adversely affect risk of CVD. Keywords: Type 2 diabetes, Nutritional ketosis, Cardiovascular risk, Lipoprotein sub-fractionation, Atherogenic lipoprotein phenotype
*Correspondence: [email protected] † Shaminie J. Athinarayanan and Sarah J. Hallberg contributed equally to the study 6 School of Medicine, University of California, San Francisco, CA 94143, USA Full list of author information is available at the end of the
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