Cardiovascular Disease Risk Factor Responses to a Type 2 Diabetes Care Model Including Nutritional Ketosis at One Year: An Open Label, Non-Randomized, Controlled Study

Abstract

Background

Cardiovascular disease (CVD) is a leading cause of death among adults with type 2 diabetes mellitus (T2D). We recently reported that glycemic control in patients with T2D can be significantly improved through a continuous care intervention (CCI) including nutritional ketosis. The purpose of this study was to examine CVD risk factors in this cohort.

Methods

We investigated CVD risk factors in patients with T2D who participated in a one year open label, non-randomized, controlled study. The CCI group (n = 262) received treatment from a health coach and medical provider. A usual care (UC) group (n = 87) was independently recruited to track customary T2D progression. Circulating biomarkers of cholesterol metabolism and inflammation, blood pressure (BP), carotid intima media thickness (cIMT), multi-factorial risk scores and medication use were examined.

Results

The CCI group consisted of 262 patients (baseline mean(SD): age 54(8) y, BMI 40.4(8.8) kg/m²). Intention-to-treat analysis (% change) revealed the following at 1-year with P values < 0.0019 indicating statistical significance after adjustment for multiple comparisons: total LDL-particles (LDL-P) (−4.9%, P=0.02), small LDL-P (−20.8%, P=1.2×10⁻¹²), LDL-P size (+1.1%, P=6.0×10⁻¹⁰), ApoB (−1.6%, P=0.37), ApoA1 (+9.8%, P<10⁻¹⁶), ApoB/ApoA1 ratio (−9.5%, P=1.9×10⁻⁷), triglyceride/HDL-C ratio (−29.1%, P<10⁻¹⁶), large VLDL-P (−38.9%, P=4.2×10⁻¹⁵), and LDL-C (+9.9%, P=4.9×10⁻⁵). Additional effects were reductions in blood pressure, high sensitivity C-reactive protein, and white blood cell count (all P<1×10⁻⁷) while cIMT was unchanged. The 10-year atherosclerotic cardiovascular disease (ASCVD) risk score decreased −11.9% (P=4.9×10⁻⁵). Antihypertensive medication use was discontinued in 11.4 % of CCI participants (P=5.3×10⁻⁵). The UC group of 87 patients (baseline mean(SD): age 52(10)y, BMI 36.7(7.2) kg/m²) showed no significant changes. After adjusting for baseline differences when comparing CCI and UC groups, significant improvements for the CCI group included small LDL-P, ApoA1, triglyceride/HDL-C ratio, HDL-C, hs-CRP, and ASCVD score. The CCI group showed a greater rise in LDL-C.

Conclusions

A continuous care treatment including nutritional ketosis in patients with T2D improved most biomarkers of CVD risk after one year. The increase in LDL-cholesterol appeared limited to the large LDL subfraction. LDL particle size increased, total LDL-P and ApoB were unchanged, and inflammation and blood pressure decreased.

Trial registration

Clinicaltrials.gov: NCT02519309. Registered 10 August 2015