Improving Appropriate Use of Peripherally Inserted Central Catheters Through a Statewide Collaborative Hospital Initiative: A Cost-Effectiveness Analysis.

BACKGROUND: Quality improvement (QI) programs require significant financial investment. The authors evaluated the cost-effectiveness of a physician-led, performance-incentivized, QI intervention that increased appropriate peripherally inserted central catheter (PICC) use. METHODS: The authors used an economic evaluation from a health care sector perspective. Implementation costs included incentive payments to hospitals and costs for data abstractors and the coordinating center. Effectiveness was calculated from propensity score-matched observations across two time periods for complications (venous thromboembolism [VTE], central line-associated bloodstream infection [CLABSI], and catheter occlusion): preintervention period (January 2015 through December 2016) and intervention period (January 2017 through December 2021). Cost-effectiveness was presented as the cost-offset per averted complication, reflecting the health care costs avoided due to having lower complication rates. RESULTS: Across 35 hospitals, this study sampled 17,418 PICCs placed preintervention and 26,004 placed during the intervention period. PICC complications decreased significantly following the intervention. CLABSIs decreased from 2.1% to 1.5%, VTEs from 3.2% to 2.3%, and catheter occlusions from 10.8% to 7.0% (all p < 0.01). Estimated number of complications prevented included 871 CLABSIs, 2,535 VTEs, and 8,743 catheter occlusions. Project implementation costs were $31.8 million, and the cost-offset related to avoided complications was $64.4 million. Each participating hospital averaged $932,073 in cost-offset over seven years, and the average cost-offset per complication averted was $2,614 (95% CI [confidence interval] $2,314-$3,003). CONCLUSION: A large-scale, multihospital QI initiative to improve appropriate PICC use yielded substantial return on investment from cost-offset of prevented complications.

The case for a ketogenic diet in the management of kidney disease.

Ketogenic diets have been widely used for weight loss and are increasingly used in the management of type 2 diabetes. Despite evidence that ketones have multiple positive effects on kidney function, common misconceptions about ketogenic diets, such as high protein content and acid load, have prevented their widespread use in individuals with impaired kidney function. Clinical trial evidence focusing on major adverse kidney events is sparse. The aim of this review is to explore the effects of a ketogenic diet, with an emphasis on the pleiotropic actions of ketones, on kidney health. Given the minimal concerns in relation to the potential renoprotective effects of a ketogenic diet, future studies should evaluate the safety and efficacy of ketogenic interventions in kidney disease.

Impact of Glucagon-Like Peptide 1 Agonist Deprescription in Type 2 Diabetes in a Real-World Setting: A Propensity Score Matched Cohort Study.

INTRODUCTION: Glucagon-like peptide 1 receptor agonists (GLP-1) elicit substantial reductions in glycemia and body weight in people with type 2 diabetes (T2D) and obesity, but existing data suggest the therapy must be continued indefinitely to maintain clinical improvements. Given the high cost and poor real-world persistence of GLP-1, an effective therapy that enables deprescription with sustained clinical improvements would be beneficial. Thus, the purpose of this real-world study was to assess the effect of GLP-1 deprescription on glycemia and body weight following co-therapy with carbohydrate restricted nutrition therapy (CRNT) supported via telemedicine in a continuous remote care model. METHODS: A retrospective, propensity score matched cohort study among patients with T2D at a telemedicine clinic was conducted. Patients in whom GLP-1 were deprescribed (DeRx; n = 154) were matched 1:1 with patients in whom GLP-1 were continued (Rx). HbA1c and body weight at enrollment in clinic (pre-CRNT), at date of deprescription or index date (derx/ID), and at 6 and 12 months (m) post-derx/ID were utilized in this study. RESULTS: No regression in weight was observed following deprescription with > 70% maintaining ≥ 5% weight loss 12 m post-derx/ID. HbA1c rose 6 m and 12 m post-derx/ID in both DeRx and Rx cohorts, but most patients maintained HbA1c < 6.5%. HbA1c and body weight measured 6 m and 12 m following derx/ID did not significantly differ between cohorts and were improved at derx/ID and at follow-up intervals compared to pre-CRNT. CONCLUSION: These results demonstrate the potential for an alternate therapy, such as CRNT supported via telemedicine, to enable maintenance of weight loss and glycemia below therapeutic targets following discontinuation of GLP-1 therapy.

Impact of the COVID-19 Pandemic on the Effectiveness of a Metabolic Health Telemedicine Intervention for Weight Loss: A Propensity Score Matching Analysis.

Background: Coronavirus disease 2019 (COVID-19) pandemic public health measures such as stay-at-home and mandatory work-from-home orders have been associated with obesogenic lifestyle changes, increased risk of weight gain, and their metabolic sequelae. We sought to assess the impact of this pandemic on weight loss from a telemedicine-delivered very-low-carbohydrate intervention targeting nutritional ketosis (NKI). Methods: A total of 746 patients with a BMI ≥25kg/m2, enrolled between January and March 2020 and treated for at least 1 year with the NKI, were classified as pandemic cohort (PC). A separate cohort of 699 patients who received 1 year of the NKI in the preceding years, enrolled between January and March 2018, were identified as pre-pandemic cohort (Pre-PC). Demographic and clinical data were obtained from medical records to compare the cohorts and assess the outcomes. Using propensity score matching (PSM), balanced and matched groups of 407 patients in the Pre-PC and 407 patients in the PC were generated. Longitudinal change in absolute weight and percentage weight change from baseline to 1 year were assessed. Results: Weight significantly decreased in both PC and Pre-PC at 3, 6, 9, and 12 months. The weight loss trajectory was similar in both PC and Pre-PC with no significant weight differences between the two cohorts at 3, 6, 9, and 12 months. On an average, the PC lost 7.5% body weight while the Pre-PC lost 7.9% over 1 year, and the percent weight loss did not differ between the two cohorts (p = 0.50). Conclusion: A very-low-carbohydrate telemedicine intervention delivered comparable and medically significant weight loss independent of pandemic stress and lifestyle limitations.

Continuous care intervention with carbohydrate restriction improves physical function of the knees among patients with type 2 diabetes: a non-randomized study.

BACKGROUND: In a previous study, we assessed a novel, remotely monitored carbohydrate restricted diet regimen including nutritional ketosis in patients with type 2 diabetes and reported significant improvements in weight, glycemic control, abdominal fat and inflammation from baseline to 2 years. Knee outcome measures were collected as a secondary outcome in the trial. This study aims to assess the effect of this intervention on knee functional scores and to identify if changes in weight, central abdominal fat (CAF), glycemic status and high sensitivity C-reactive protein (hsCRP) were associated with its improvement. METHODS: This prospective analysis included continuous care intervention (CCI, n = 173) and usual care (UC, n = 69) trial participants with type 2 diabetes that reported knee pain at baseline. Knee outcome measures included the Knee injury and Osteoarthritis Outcome Score (KOOS) pain, symptoms, activities of daily living (ADL), sports and recreation function, and knee-related quality of life subscales, and total KOOS score were assessed from baseline to 2 years. Missing data at each time point were replaced with multiple imputation under the assumption of missing at random. To assess if the primary analysis of the knee scores changed under plausible missing not at random assumptions, sensitivity analysis was also performed using pattern mixture models. In CCI, we also assessed factors associated with the improvement of knee scores. RESULTS: In the primary analysis, CCI participants demonstrated a statistically significant improvement in total KOOS and all KOOS individual subscale scores at 1 year and maintained through 2 years as opposed to UC patients who showed no significant changes from baseline to 2 years. The significant improvement in total KOOS and its individual subscale scores from baseline to 2 years remained relatively stable in CCI in the sensitivity analysis under different missing not at random scenarios confirming the robustness of the findings from the primary analysis. Approximately 46% of the CCI participants met the 10 points minimal clinically important change at 2 years. A reduction in CAF was associated with improvement in total KOOS and KOOS ADL, while a decrease in hsCRP was associated with improvement in KOOS symptoms scores. CONCLUSION: A very low carbohydrate intervention including nutritional ketosis resulted in significant improvements in knee pain and function among patients with T2D. The improvements in knee function were likely secondary to a reduction in central adiposity and inflammation. Future research on the applicability of this intervention in radiographically confirmed OA patients is important. TRIAL REGISTRATION: Clinical trial registration: NCT02519309 (10/08/2015).

Depressive symptoms improve over 2 years of type 2 diabetes treatment via a digital continuous remote care intervention focused on carbohydrate restriction.

Depressive symptoms are prevalent among people with type 2 diabetes (T2D) and, even at low severity levels, are associated with worse diabetes outcomes. Carbohydrate restriction is an effective treatment for T2D but its long-term impacts on depressive symptoms are unclear. In the current study we explored changes in depressive symptoms over 2 years among 262 primarily non-depressed T2D patients participating in a continuous remote care intervention emphasizing carbohydrate restriction. Subclinical depressive symptoms decreased over the first 10 weeks and reductions were maintained out to 2 years. Increased frequency of blood ketone levels indicative of adherence to low carbohydrate eating predicted decreases in depressive symptoms. Concerns have been raised with recommending restrictive diets due to potential negative impacts on quality-of-life factors such as mood; however, results of the current study support positive rather than negative long-term impacts of closely monitored carbohydrate restriction on depressive symptoms.

Student-resourced service delivery of occupational therapy rehabilitation groups: patient, clinician and student perspectives about the ingredients for success.

BACKGROUND: A number of innovative models of student practice placements are emerging due to pressures on universities to provide quality practice placements and on health services to deliver rehabilitation efficiently, safely and cost-effectively. The student-resourced service delivery (SRSD) group program is one such model in occupational therapy. There is a paucity of research evidence to guide services in planning, implementing and evaluating the SRSD model. OBJECTIVE: The study aimed to explore and identify the factors that key stakeholders perceived as contributing to the successful development and implementation of the occupational therapy student-resourced service delivery group programs. METHODS: Participants in this multi-site study were rehabilitation inpatients, clinicians, Clinical Education Liaison Managers and students completing practice placement in the student-resourced service delivery group program. Data were collected using face-to-face semi-structured interviews and focus groups. RESULTS: A total of 83 participants consented to the study. Four themes emerged from the data. Planning needs to be an iterative process that commences before and continues during the program. Support processes need to be established for students and clinicians during and across placements. The creation of an engaging, client-relevant and graded group dynamic is critical for success. Establishing a culture whereby groups are valued by the clients, therapy and multidisciplinary teams is important. CONCLUSIONS: The above-mentioned factors were perceived as contributing to successful operationalisation of a student-resourced service delivery group program, and may be helpful when developing student-resourced service delivery professional practice placements in other settings.IMPLICATIONS FOR REHABILITATIONStudent-resourced service delivery of groups are one way to achieve additional professional practice placements for students and delivery of therapy services for patients.Ongoing investment for planning and preparation, provision of continual support for students, a culture of valuing groups and students, and creating a group dynamic that engages group participants were perceived by stakeholders as key ingredients for successful implementation of the student-resourced service delivery group model.Clinicians and educators are encouraged to use the perceived success factors identified in this study as a resource for future student-resourced service delivery program development.

Reduced COVID-19 severity elicited by weight loss from a medically supervised ketogenic diet in a geographically diverse ambulatory population with type 2 diabetes and obesity.

Objective: To investigate factors associated with COVID-19 severity in ambulatory individuals with type 2 diabetes mellitus (T2DM) and obesity treated with a medically supervised ketogenic diet (MSKD). Research design and methods: In this real-world, retrospective, exploratory analysis, multivariate modelling was used to assess clinical factors associated with hospitalisation for COVID-19 in a geographically diverse outpatient population with T2DM treated virtually. Results: Leading up to COVID-19 onset, non-hospitalised patients had higher average ketones (0.64 vs 0.52 mmol/L; p=0.016) and greater weight loss (6.8% vs 4.2%; p=0.009) compared with those hospitalised. Greater weight loss was significantly associated with lower likelihood of hospitalisation (adjusted OR=0.91, p=0.005), controlling for enrolment demographics and medical characteristics. Conclusions: Therapies such as MSKD, which elicit rapid, significant weight loss, may favourably impact COVID-19 hospitalisation rate and severity in individuals with T2DM and obesity.

Nutritional ketosis to treat pulmonary hypertension associated with obesity and metabolic syndrome: a case report.

Metabolic syndrome is characterized by insulin resistance/hyperinsulinemia, atherogenic dyslipidemia (elevated triglycerides, low HDL), and hyperglycemia. The high prevalence of metabolic syndrome in pulmonary hypertension leads to the hypothesis that metabolic syndrome may play a contributing role in pulmonary hypertension and heart failure with preserved ejection fraction pathogenesis. We present a 62-year-old woman with morbid obesity, mild pre-capillary pulmonary hypertension, and metabolic syndrome. Her metabolic syndrome was treated with a medically-supervised ketogenic diet delivered by a telehealth healthcare team via a continuous remote care platform. Following one year of treatment, metabolic syndrome was reversed, leading to successful weight loss concurrent with hemodynamic improvement. This case highlights the feasibility of using a nutritional strategy to treat pulmonary hypertension associated with obesity and metabolic syndrome, common contributors to group 2 and 3 pulmonary hypertension. We bring this case and technique to the pulmonary hypertension community to share a tool in our therapeutic toolkit and highlight the importance of nutritional advice extending beyond telling a patient they should lose weight to invoking a rational strategy. We argue that strategic nutritional intervention through reversal of her metabolic syndrome using a medically-supervised ketogenic diet is a safe and effective treatment strategy in metabolic syndrome-associated pulmonary hypertension.

Type 2 Diabetes Prevention Focused on Normalization of Glycemia: A Two-Year Pilot Study.

The purpose of this study is to assess the effects of an alternative approach to type 2 diabetes prevention. Ninety-six patients with prediabetes (age 52 (10) years; 80% female; BMI 39.2 (7.1) kg/m2) received a continuous remote care intervention focused on reducing hyperglycemia through carbohydrate restricted nutrition therapy for two years in a single arm, prospective, longitudinal pilot study. Two-year retention was 75% (72 of 96 participants). Fifty-one percent of participants (49 of 96) met carbohydrate restriction goals as assessed by blood beta-hydroxybutyrate concentrations for more than one-third of reported measurements. Estimated cumulative incidence of normoglycemia (HbA1c <5.7% without medication) and type 2 diabetes (HbA1c ≥6.5% or <6.5% with medication other than metformin) at two years were 52.3% and 3%, respectively. Prevalence of metabolic syndrome, class II or greater obesity, and suspected hepatic steatosis significantly decreased at two years. These results demonstrate the potential utility of an alternate approach to type 2 diabetes prevention, carbohydrate restricted nutrition therapy delivered through a continuous remote care model, for normalization of glycemia and improvement in related comorbidities.

Implementing a Skin-to-Skin Care and Parent Touch Initiative in a Tertiary Cardiac and Surgical Neonatal Intensive Care Unit.

BACKGROUND: Skin-to-skin care (SSC) has been integrated as an essential component of developmental care for preterm infants. Despite documented benefits, SSC is not routinely practiced in the cardiac and surgical neonatal intensive care unit, with a predominantly term population, due to staff apprehension, patient factors and acuity, and environmental constraints. PURPOSE: The purpose of this quality improvement project was to increase SSC, parental holds, and parent touch events for infants in our cardiac and surgical neonatal intensive care unit. When traditional SSC was not possible, alternative holds and alternative parent touch (APT) methods were encouraged. METHODS: Quality improvement and qualitative descriptive methodology were utilized to assess baseline, develop education and practice changes, and evaluate the use of SSC, holds, and APT methods at 12 and 18 months postintervention. Implementation included educational tools and resource development, simulations, peer champions, in-class teaching, and team huddles. Decisions around the type of hold and parent touch were fluid and reflected complex infant, family, staff, and physical space needs. FINDINGS: Given its initial scarcity, there was an increased frequency of SSC and variety of holds or APT events. Staff survey results indicated support for the practice and outlined persistent barriers. IMPLICATIONS FOR PRACTICE: Skin-to-skin care, holds, and APT practices are feasible and safe for term and preterm infants receiving highly instrumented and complex cardiac and surgical care. IMPLICATIONS FOR RESEARCH: Future research regarding the intervention's impact on neurodevelopmental outcomes of infants and on parent resilience in the surgical and cardiac neonatal intensive care unit is warranted.

Impact of a 2-year trial of nutritional ketosis on indices of cardiovascular disease risk in patients with type 2 diabetes.

BACKGROUND: We have previously reported that in patients with type 2 diabetes (T2D) consumption of a very low carbohydrate diet capable of inducing nutritional ketosis over 2 years (continuous care intervention, CCI) resulted in improved body weight, glycemic control, and multiple risk factors for cardiovascular disease (CVD) with the exception of an increase in low density lipoprotein cholesterol (LDL-C). In the present study, we report the impact of this intervention on markers of risk for atherosclerotic cardiovascular disease (CVD), with a focus on lipoprotein subfraction particle concentrations as well as carotid-artery intima-media thickness (CIMT). METHODS: Analyses were performed in patients with T2D who completed 2 years of this study (CCI; n = 194; usual care (UC): n = 68). Lipoprotein subfraction particle concentrations were measured by ion mobility at baseline, 1, and 2 years and CIMT was measured at baseline and 2 years. Principal component analysis (PCA) was used to assess changes in independent clusters of lipoprotein particles. RESULTS: At 2 years, CCI resulted in a 23% decrease of small LDL IIIb and a 29% increase of large LDL I with no change in total LDL particle concentration or ApoB. The change in proportion of smaller and larger LDL was reflected by reversal of the small LDL subclass phenotype B in a high proportion of CCI participants (48.1%) and a shift in the principal component (PC) representing the atherogenic lipoprotein phenotype characteristic of T2D from a major to a secondary component of the total variance. The increase in LDL-C in the CCI group was mainly attributed to larger cholesterol-enriched LDL particles. CIMT showed no change in either the CCI or UC group. CONCLUSION: Consumption of a very low carbohydrate diet with nutritional ketosis for 2 years in patients with type 2 diabetes lowered levels of small LDL particles that are commonly increased in diabetic dyslipidemia and are a marker for heightened CVD risk. A corresponding increase in concentrations of larger LDL particles was responsible for higher levels of plasma LDL-C. The lack of increase in total LDL particles, ApoB, and in progression of CIMT, provide supporting evidence that this dietary intervention did not adversely affect risk of CVD.

Impact of Nutrient Intake on Hydration Biomarkers Following Exercise and Rehydration Using a Clustering-Based Approach.

We investigated the impact of nutrient intake on hydration biomarkers in cyclists before and after a 161 km ride, including one hour after a 650 mL water bolus consumed post-ride. To control for multicollinearity, we chose a clustering-based, machine learning statistical approach. Five hydration biomarkers (urine color, urine specific gravity, plasma osmolality, plasma copeptin, and body mass change) were configured as raw- and percent change. Linear regressions were used to test for associations between hydration markers and eight predictor terms derived from 19 nutrients merged into a reduced-dimensionality dataset through serial k-means clustering. Most predictor groups showed significant association with at least one hydration biomarker: 1) Glycemic Load + Carbohydrates + Sodium, 2) Protein + Fat + Zinc, 3) Magnesium + Calcium, 4) Pinitol, 5) Caffeine, 6) Fiber + Betaine, and 7) Water; potassium + three polyols, and mannitol + sorbitol showed no significant associations with any hydration biomarker. All five hydration biomarkers were associated with at least one nutrient predictor in at least one configuration. We conclude that in a real-life scenario, some nutrients may serve as mediators of body water, and urine-specific hydration biomarkers may be more responsive to nutrient intake than measures derived from plasma or body mass.

High-Risk Atherosclerosis and Metabolic Phenotype: The Roles of Ectopic Adiposity, Atherogenic Dyslipidemia, and Inflammation.

Current algorithms for assessing risk of atherosclerotic cardiovascular disease (ASCVD) and, in particular, the reliance on low-density lipoprotein (LDL) cholesterol in conditions where this measurement is discordant with apoB and LDL-particle concentrations fail to identify a sizeable part of the population at high risk for adverse cardiovascular events. This results in missed opportunities for ASCVD prevention, most notably in those with metabolic syndrome, prediabetes, and diabetes. There is substantial evidence that accumulation of ectopic fat and associated metabolic traits are markers for and pathogenic components of high-risk atherosclerosis. Conceptually, the subset of advanced lesions in high-risk atherosclerosis that triggers vascular complications is closely related to a set of coordinated high-risk traits clustering around a distinct metabolic phenotype. A key feature of this phenotype is accumulation of ectopic fat, which, coupled with age-related muscle loss, creates a milieu conducive for the development of ASCVD: atherogenic dyslipidemia, nonresolving inflammation, endothelial dysfunction, hyperinsulinemia, and impaired fibrinolysis. Sustained vascular inflammation, a hallmark of high-risk atherosclerosis, impairs plaque stabilization in this phenotype. This review describes how metabolic and inflammatory processes that are promoted in large measure by ectopic adiposity, as opposed to subcutaneous adipose tissue, relate to the pathogenesis of high-risk atherosclerosis. Clinical biomarkers indicative of these processes provide incremental information to standard risk factor algorithms and advanced lipid testing identifies atherogenic lipoprotein patterns that are below the discrimination level of standard lipid testing. This has the potential to enable improved identification of high-risk patients who are candidates for therapeutic interventions aimed at prevention of ASCVD.

Lifestyle factors and high-risk atherosclerosis: Pathways and mechanisms beyond traditional risk factors.

Despite major efforts to reduce atherosclerotic cardiovascular disease (ASCVD) burden with conventional risk factor control, significant residual risk remains. Recent evidence on non-traditional determinants of cardiometabolic health has advanced our understanding of lifestyle-disease interactions. Chronic exposure to environmental stressors like poor diet quality, sedentarism, ambient air pollution and noise, sleep deprivation and psychosocial stress affect numerous traditional and non-traditional intermediary pathways related to ASCVD. These include body composition, cardiorespiratory fitness, muscle strength and functionality and the intestinal microbiome, which are increasingly recognized as major determinants of cardiovascular health. Evidence points to partially overlapping mechanisms, including effects on inflammatory and nutrient sensing pathways, endocrine signalling, autonomic function and autophagy. Of particular relevance is the potential of low-risk lifestyle factors to impact on plaque vulnerability through altered adipose tissue and skeletal muscle phenotype and secretome. Collectively, low-risk lifestyle factors cause a set of phenotypic adaptations shifting tissue cross-talk from a proinflammatory milieu conducive for high-risk atherosclerosis to an anti-atherogenic milieu. The ketone body ß-hydroxybutyrate, through inhibition of the NLRP-3 inflammasome, is likely to be an intermediary for many of these observed benefits. Adhering to low-risk lifestyle factors adds to the prognostic value of optimal risk factor management, and benefit occurs even when the impact on conventional risk markers is discouragingly minimal or not present. The aims of this review are (a) to discuss novel lifestyle risk factors and their underlying biochemical principles and (b) to provide new perspectives on potentially more feasible recommendations to improve long-term adherence to low-risk lifestyle factors.

Long-Term Effects of a Novel Continuous Remote Care Intervention Including Nutritional Ketosis for the Management of Type 2 Diabetes: A 2-Year Non-randomized Clinical Trial.

Purpose: Studies on long-term sustainability of low-carbohydrate approaches to treat diabetes are limited. We previously reported the effectiveness of a novel digitally-monitored continuous care intervention (CCI) including nutritional ketosis in improving weight, glycemic outcomes, lipid, and liver marker changes at 1 year. Here, we assess the effects of the CCI at 2 years. Materials and methods: An open label, non-randomized, controlled study with 262 and 87 participants with T2D were enrolled in the CCI and usual care (UC) groups, respectively. Primary outcomes were retention, glycemic control, and weight changes at 2 years. Secondary outcomes included changes in body composition, liver, cardiovascular, kidney, thyroid and inflammatory markers, diabetes medication use and disease status. Results: Reductions from baseline to 2 years in the CCI group resulting from intent-to-treat analyses included: HbA1c, fasting glucose, fasting insulin, weight, systolic blood pressure, diastolic blood pressure, triglycerides, and liver alanine transaminase, and HDL-C increased. Spine bone mineral density in the CCI group was unchanged. Use of any glycemic control medication (excluding metformin) among CCI participants declined (from 55.7 to 26.8%) including insulin (-62%) and sulfonylureas (-100%). The UC group had no changes in these parameters (except uric acid and anion gap) or diabetes medication use. There was also resolution of diabetes (reversal, 53.5%; remission, 17.6%) in the CCI group but not in UC. All the reported improvements had p < 0.00012. Conclusion: The CCI group sustained long-term beneficial effects on multiple clinical markers of diabetes and cardiometabolic health at 2 years while utilizing less medication. The intervention was also effective in the resolution of diabetes and visceral obesity with no adverse effect on bone health. Clinical Trial Registration: Clinicaltrials.gov NCT02519309.

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 patients enrolled 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.

Post hoc analyses of surrogate markers of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis in patients with type 2 diabetes in a digitally supported continuous care intervention: an open-label, non-randomised controlled study.

OBJECTIVE: One year of comprehensive continuous care intervention (CCI) through nutritional ketosis improves glycosylated haemoglobin(HbA1c), body weight and liver enzymes among patients with type 2 diabetes (T2D). 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-randomised longitudinal study, including adults with T2D who were self-enrolled to the CCI (n=262) or to receive usual care (UC, n=87) during 1 year. An NAFLD liver fat score (N-LFS) >-0.640 defined the presence of fatty liver. An NAFLD fibrosis score (NFS) of >0.675 identified subjects with advanced fibrosis. Changes in N-LFS and NFS at 1 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 1 year, weight loss of ≥5% was achieved in 79% of patients in the CCI versus 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). CONCLUSIONS: One year of a digitally supported CCI significantly improved surrogates of NAFLD and advanced fibrosis in patients with T2D. TRIAL REGISTRATION NUMBER: NCT02519309; Results.

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-2). 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 × 10-12), 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 participants [baseline mean (SD): age 52 (10) year, BMI 36.7 (7.2) kg m-2] 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.