Impact of a 2-year trial of nutritional ketosis on indices of cardiovascular disease risk in patients with type 2 diabetes

Shaminie J Athinarayanan,Sarah King,James P Mccarter,Amy L Mckenzie,Jeff S Volek,Ronald M Krauss,Sarah J Hallberg,Katharina Lechner,Stephen D Phinney

doi:10.1186/s12933-020-01178-2

Abstract

BackgroundWe 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).MethodsAnalyses 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.ResultsAt 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.ConclusionConsumption 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.

Highlights

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 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)
CVD risk markers, and average carotid-artery intima-media thickness (CIMT) were similar between continuous care intervention (CCI) and usual care (UC), except for body mass index (BMI) (Additional file 1: Table S1)
Baseline levels of lipoprotein subclasses were similar between CCI and UC groups, except for mid-zone and small HDL 2a + 3 which were significantly lower in the CCI group

Summary

Introduction

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). Multiple studies have found that therapeutic carbohydrate restriction significantly improves a number of CVD risk factors [5,6,7], including elevated triglycerides and small dense LDL, low HDL-C, and markers of non-alcoholic fatty liver disease [8, 9]. Very low carbohydrate diets that achieve nutritional ketosis have been shown to be of benefit in diabetes management, with effects including improvements in weight, HbA1c, triglycerides and HDL-C [5, 18] Such diets often result in increased concentrations of LDL-C [18, 19], which has raised concerns regarding an adverse effect on CVD risk

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Results

Discussion

Conclusion