McCarter, J. P. | Search bioRxiv

bioRxiv2018

Digitally-Supported Continuous Care Intervention Including Individualized Nutritional Ketosis Significantly Improves Surrogate Markers of Non-Alcoholic Fatty Liver Disease (NAFLD) and Liver Fibrosis in Patients with Type 2 Diabetes: An Open Label, Non-Randomized, Controlled Study

ObjectiveOne-year of comprehensive continuous care intervention (CCI) through nutritional ketosis improves HbA1c, body weight and liver enzymes among type 2 diabetes (T2D) patients. Here, we report the effect of the CCI on surrogate scores of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis. MethodsThis was a non-randomized longitudinal study, including adults with T2D who were self-enrolled to the CCI (n=262) or to receive usual care (UC, n=87) during one year. A NAFLD liver fat score [N-LFS] > -0.640 defined the presence of fatty liver. A NAFLD fibrosis score [NFS] of > 0.675 identified subjects with advanced fibrosis. Changes in N-LFS and NFS at one year were the main endpoints. ResultsAt baseline, NAFLD was present in 95% of patients in the CCI and 90% of patients in the UC. At one year, weight loss of > 5% was achieved in 79% of patients in the CCI vs. 19% of patients in UC (P<0.001). N-LFS mean score was reduced in the CCI group (-1.95{+/-}0.22, P<0.001) whereas it was not changed in the UC (0.47{+/-}0.41, P=0.26) (CCI vs. UC, P<0.001). NFS was reduced in the CCI group (-0.65{+/-}0.06, P<0.001) compared with UC (0.26{+/-}0.11, P=0.02) (P<0.001 between two groups). In the CCI group, the percentage of individuals with a low probability of advanced fibrosis increased from 18% at baseline to 33% at 1 year (P<0.001). ConclusionsOne year of a digitally-supported CCI significantly improved surrogates of NAFLD and advanced fibrosis in patients with type 2 diabetes. DATA SHARINGData sets and statistical code used for the current study are available from the corresponding author on reasonable request. Article Summary Strengths and limitations of this studyO_LIThis study highlights the beneficial effect of the CCI on NAFLD in high risk patients with T2D C_LIO_LIThis study also identifies positive associations between glycemic improvements and improvements in ALT levels C_LIO_LIThe assessment of resolution of steatosis and fibrosis is limited by the sensitivity and specificity of the non-invasive markers used in the study C_LIO_LIThe patients were restricted in their carbohydrate intake and monitored for their nutritional ketosis state, but dietary energy, macronutrient and micronutrient intakes were not assessed. C_LI

clinical trials↗

bioRxiv2018

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

Background\n\nCardiovascular 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.\n\nMethods\n\nWe 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.\n\nResults\n\nThe 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.\n\nConclusions\n\nA 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.\n\nTrial registration\n\nClinicaltrials.gov: NCT02519309. Registered 10 August 2015

clinical trials↗