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=1.2x10-12), LDL-P size (+1.1%, P=6.0x10-10), ApoB (-1.6%, P=0.37), ApoA1 (+9.8%, P<10-16), ApoB/ApoA1 ratio (-9.5%, P=1.9x10-7), triglyceride/HDL-C ratio (-29.1%, P<10-16), large VLDL-P (-38.9%, P=4.2x10-15), and LDL-C (+9.9%, P=4.9x10-5). Additional effects were reductions in blood pressure, high sensitivity C-reactive protein, and white blood cell count (all P<1x10-7) while cIMT was unchanged. The 10-year atherosclerotic cardiovascular disease (ASCVD) risk score decreased -11.9% (P=4.9x10-5). Antihypertensive medication use was discontinued in 11.4 % of CCI participants (P=5.3x10-5). 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. Clinical Trial Registration ID #NCT02519309.
