Very Low Carbohydrate Diet Associated With Reduced Levels of Small LDL Particles inType 2 Diabetes

A long-term very low carbohydrate dietary intervention was associated with a reduction in the concentration of small LDL particles in patients with type 2 diabetes.

A long-term very low carbohydrate dietary intervention was associated with a reduction in the concentration of small low density lipoprotein (LDL) particles in patients with type 2 diabetes (T2D), according to a study published in Cardiovascular Diabetology.

In this open-label, non-randomized, controlled trial, 349 patients with T2D and a body mass index >25 kg/m2 were recruited for between 2015 and 2018. Participants self-selected to follow a very low carbohydrate diet under guidance (intervention group; n=262) or to continue usual care (n=87). The intervention group was recommended to consume daily <30 g of carbohydrates and 1.5 g/kg of protein. Diets were adjusted based on blood beta-hydroxybutyrate concentration. Participants were assessed at baseline, 1, and 2 years for anthropometric and lipoprotein characteristics.

At study conclusion 194 and 68 participants in the intervention and usual care groups, respectively remained in the study. The 2 cohorts were well balanced for all characteristics except ethnicity and small high-density lipoprotein cholesterol (HDL-c) 2a+3.

Concentrations of lipids, lipoproteins, apoproteins, blood pressure, carotid-artery intima-media thickness (CIMT), and need for lipid-lowering or anti-hypertensive medications did not change over the 2 years of study in the usual care group.

At 2 years, in the intervention group, overall concentrations of LDL-cholesterol (LDL-c) increased (change from baseline, 10.3; 95% CI, -62.8 to 83.4 nmol/L), and triglycerides and blood pressure decreased. In this group, use of antihypertensive (P =1.0×10-3), particularly diuretics (P =7.0×10-3) and lipid-lowering (P =8.0 x10-3) medications were decreased at 2 years.

After 2 years of diet, levels of remnant cholesterol (-22.4%; P =3.1×107), LDL-c IIIb (-23.1%; P =1.0×103), and very small LDL-c IVa-c (-6.8%; P =7.4×107) decreased, and those of apolipoprotein A1 (10.9%; P =1.4×107), intermediate-density lipoprotein cholesterol (IDL-c; 24.6%; P =2.0×1010), large LDL-c I (29.1%; P =2.4×108), and LDL-c peak diameter (2.0%; P =1.9×1010) increased in the intervention group.

Stratified by change in LDL-c, the high and low responders had significantly different overall lipoprotein profiles (Pillai’s Trace, 0.66; F, 5.09; P =6.0×106).

Change of body mass index over the study was positively correlated with levels of triglycerides, large and very large-density lipoprotein cholesterol, LDL-c IIIa, and LDL-c IIb, and negatively correlated with HDL-c, IDL-c II, and HDL2b. Participants who maintained blood beta-hydroxybutyrate concentrations ³0.5 mM had greater changes in HDL-c, IDL-c II, LDL-c I, triglycerides, and mid-zone particle fraction concentrations.

This study was limited by the lack of tight control of food consumption in both groups.

A very low carbohydrate diet among patients with T2D likely did not alter CVD risk. The patients who maintained a dietary intervention over 2 years did not have increased total LDL-c particle numbers or CIMT.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Athinarayanan S J, Hallberg S J, McKenzie A L, et al. Impact of a 2‑year trial of nutritional ketosis on indices of cardiovascular disease risk in patients with type 2 diabetes. Cardiovasc Diabetol. 2020;19(1):208. doi:10.1186/s12933-020-01178-2