Sarah Hallberg

Improvement in Patient-Reported Sleep in Type 2 Diabetes and Prediabetes Participants Receiving a Continuous Care Intervention with Nutritional Ketosis

Objective Sleep disruption is frequently associated with type 2 diabetes (T2D) and hyperglycemia. We recently reported the effectiveness of a continuous care intervention (CCI) emphasizing nutritional ketosis for improving HbA1c, body weight and cardiovascular risk factors in T2D patients. The present study assessed the effect of this CCI approach on sleep quality using a subjective patient-reported sleep questionnaire. Methods A non-randomized, controlled longitudinal study; 262 T2D and 116 prediabetes patientsenrolled in the CCI and 87 separately recruited T2D patients continued usual care (UC) treatment. Patients completed the Pittsburgh Sleep Quality Index (PSQI) questionnaire. A PSQI score of >5 (scale 0 to 21) was used to identify poor sleepers. Results Global sleep quality improved in the CCI T2D (p<0.001) and prediabetes (p<0.001) patients after one year of intervention. Subjective sleep quality (component 1), sleep disturbance (component 5) and daytime dysfunction (component 7), also showed improvements in the CCI T2D (p<0.01 for sleep quality and sleep disturbance; and p<0.001 for daytime dysfunction) and prediabetes patients (p<0.001 for all three components); compared to the UC T2D group after one year. The proportion of patients with poor sleep quality was significantly reduced after one year of CCI (T2D; from 68.3% at baseline to 56.5% at one year, p=0.001 and prediabetes; from 77.9% at baseline to 48.7% at one year, p<0.001). Conclusion This study demonstrates improved sleep quality as assessed by PSQI in patients with T2D and prediabetes undergoing CCI including nutritional ketosis but not in T2D patients receiving UC. The dietary intervention benefited both sleep quality and the severity of T2D symptoms suggesting that nutritional ketosis improves overall health via multiple mechanisms.

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 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

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

Aims One-year of comprehensive continuous care intervention (CCI) through nutritional ketosis significantly improves HbA1c, body weight and liver enzymes among type 2 diabetes (T2D) patients. Here, we report the effect of CCI on surrogate scores of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis. Materials and methods This was a non-randomized longitudinal study, including adults with T2D who were self-enrolled to CCI (n=262) or to receive usual care (UC, n=87) during 1 year. The NAFLD liver fat score [N-LFS] > -0.640 defined the presence of fatty liver. The 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. Results At 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 with CCI vs. 16% of patients with UC (P<.01). N-LFS mean score levels were significantly reduced in the CCI (-1.85 ± 0.33) compared with UC (+0.19 ± 0.64) (P<.01). NFS was significantly reduced in the CCI group (-.370 ± 0.10, P<0.01) whereas it increased in the UC group (.256 ± 0.20, P=0.21) (P<.01 between two groups). In the CCI group, the presence of advanced fibrosis was reduced from 27% at baseline to 17% at 1 year (P<.01). Conclusions One-year of a digitally supported CCI significantly improved surrogates of NAFLD and advanced fibrosis in type 2 diabetes patients.ABSTRACT Objective One-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. Methods This 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. Results At 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 Conclusions One year of a digitally-supported CCI significantly improved surrogates of NAFLD and advanced fibrosis in patients with type 2 diabetes. DATA SHARING Data 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 study This study highlights the beneficial effect of the CCI on NAFLD in high risk patients with T2D This study also identifies positive associations between glycemic improvements and improvements in ALT levels The assessment of resolution of steatosis and fibrosis is limited by the sensitivity and specificity of the non-invasive markers used in the study The patients were restricted in their carbohydrate intake and monitored for their nutritional ketosis state, but dietary energy, macronutrient and micronutrient intakes were not assessed.

Author Correction: Effectiveness and Safety of a Novel Care Model for the Management of Type 2 Diabetes at 1 Year: An Open-Label, Non-Randomized, Controlled Study

The original version of this article unfortunately contained a mistake.