Cardiovascular Disease Risk Factor Responses to a Type 2 Diabetes Care Model Including Nutritional Ketosis Induced by Sustained Carbohydrate Restriction at 1 year: an Open Label, Non-randomized, Controlled Study

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 1 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. A significance level of P < 0.0019 ensured two-tailed significance at the 5% level when Bonferroni adjusted for multiple comparisons.

Results: The CCI group consisted of 262 participants (baseline mean (SD): age 54 (8) year, BMI 40.4 (8.8) kg m). Intention-to-treat analysis (% change) revealed the following at 1-year: total LDL-particles (LDL-P) (- 4.9%, P = 0.02), small LDL-P (- 20.8%, P = 1.2 × 10), LDL-P size (+ 1.1%, P = 6.0 × 10), ApoB (- 1.6%, P = 0.37), ApoA1 (+ 9.8%, P < 10), ApoB/ApoA1 ratio (- 9.5%, P = 1.9 × 10), triglyceride/HDL-C ratio (- 29.1%, P < 10), large VLDL-P (- 38.9%, P = 4.2 × 10), and LDL-C (+ 9.9%, P = 4.9 × 10). Additional effects were reductions in blood pressure, high sensitivity C-reactive protein, and white blood cell count (all P < 1 × 10) while cIMT was unchanged. The 10-year atherosclerotic cardiovascular disease (ASCVD) risk score decreased - 11.9% (P = 4.9 × 10). Antihypertensive medication use was discontinued in 11.4% of CCI participants (P = 5.3 × 10). The UC group of 87 participants [baseline mean (SD): age 52 (10) year, BMI 36.7 (7.2) kg m] 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, hsCRP, and LP-IR score in addition to other biomarkers that were previously reported. 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 1 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.