Lifestyle genomics and the metabolic syndrome: A review of genetic variants that influence response to diet and exercise interventions.

Metabolic syndrome (MetS) comprises a cluster of risk factors that includes central obesity, dyslipidemia, impaired glucose homeostasis and hypertension. Individuals with MetS have elevated risk of type 2 diabetes and cardiovascular disease; thus placing significant burdens on social and healthcare systems. Lifestyle interventions (comprised of diet, exercise or a combination of both) are routinely recommended as the first line of treatment for MetS. Only a proportion of people respond, and it has been assumed that psychological and social aspects primarily account for these differences. However, the etiology of MetS is multifactorial and stems, in part, on a person's genetic make-up. Numerous single nucleotide polymorphisms (SNPs) are associated with the various components of MetS, and several of these SNPs have been shown to modify a person's response to lifestyle interventions. Consequently, genetic variants can influence the extent to which a person responds to changes in diet and/or exercise. The goal of this review is to highlight SNPs reported to influence the magnitude of change in body weight, dyslipidemia, glucose homeostasis and blood pressure during lifestyle interventions aimed at improving MetS components. Knowledge regarding these genetic variants and their ability to modulate a person's response will provide additional context for improving the effectiveness of personalized lifestyle interventions that aim to reduce the risks associated with MetS.

Patient experiences of a lifestyle program for metabolic syndrome offered in family medicine clinics: a mixed methods study.

BACKGROUND: Patient perspectives on new programs to manage metabolic syndrome (MetS) are critical to evaluate for possible implementation in the primary healthcare system. Participants' perspectives were sought for the Canadian Health Advanced by Nutrition and Graded Exercise (CHANGE) study, which enrolled 293 participants, and demonstrated 19% reversal of MetS after 1 year. The main purpose of this study was to examine participants' perceptions of their experiences with the CHANGE program, enablers and barriers to change. METHODS: A convergent parallel mixed methods design combined patients' perspectives collected by questionnaires (n = 164), with insights from focus groups (n = 41) from three sites across Canada. Qualitative data were thematically analyzed using interpretative description. Insights were organized within a socio-ecologic framework. RESULTS: Key aspects identified by participants included intra-individual factors (personal agency, increased time availability), inter-individual factors (trust, social aspects) and organizational factors (increased mental health support, tailored programs). CONCLUSION: Results revealed participants' overall support for the CHANGE program, especially the importance of an extended program under the guidance of a family physician along with a skilled and supportive team. Team delivery of a lifestyle program in primary care or family medicine clinics is a complex intervention and use of a mixed methods design was helpful for exploring patient experiences and key issues on enablers and barriers to health behavior change.

A randomized trial of supplemental parenteral nutrition in underweight and overweight critically ill patients: the TOP-UP pilot trial.

BACKGROUND: Nutrition guidelines recommendations differ on the use of parenteral nutrition (PN), and existing clinical trial data are inconclusive. Our recent observational data show that amounts of energy/protein received early in the intensive care unit (ICU) affect patient mortality, particularly for inadequate nutrition intake in patients with body mass indices (BMIs) of <25 or >35. Thus, we hypothesized increased nutrition delivery via supplemental PN (SPN) + enteral nutrition (EN) to underweight and obese ICU patients would improve 60-day survival and quality of life (QoL) versus usual care (EN alone). METHODS: In this multicenter, randomized, controlled pilot trial completed in 11 centers across four countries, adult ICU patients with acute respiratory failure expected to require mechanical ventilation for >72 hours and with a BMI of <25 or ≥35 were randomized to receive EN alone or SPN + EN to reach 100% of their prescribed nutrition goal for 7 days after randomization. The primary aim of this pilot trial was to achieve a 30% improvement in nutrition delivery. RESULTS: In total, 125 patients were enrolled. Over the first 7 post-randomization ICU days, patients in the SPN + EN arm had a 26% increase in delivered calories and protein, whereas patients in the EN-alone arm had a 22% increase (both p < 0.001). Surgical ICU patients received poorer EN nutrition delivery and had a significantly greater increase in calorie and protein delivery when receiving SPN versus medical ICU patients. SPN proved feasible to deliver with our prescribed protocol. In this pilot trial, no significant outcome differences were observed between groups, including no difference in infection risk. Potential, although statistically insignificant, trends of reduced hospital mortality and improved discharge functional outcomes and QoL outcomes in the SPN + EN group versus the EN-alone group were observed. CONCLUSIONS: Provision of SPN + EN significantly increased calorie/protein delivery over the first week of ICU residence versus EN alone. This was achieved with no increased infection risk. Given feasibility and consistent encouraging trends in hospital mortality, QoL, and functional endpoints, a full-scale trial of SPN powered to assess these clinical outcome endpoints in high-nutritional-risk ICU patients is indicated-potentially focusing on the more poorly EN-fed surgical ICU setting. TRIAL REGISTRATION: NCT01206166.

The CHANGE program: Exercise intervention in primary care.

PROBLEM ADDRESSED: Primary care settings require a feasible program for integrating lifestyle interventions, which can reverse metabolic abnormalities, for patients in practice. OBJECTIVE OF PROGRAM: To integrate a lifestyle intervention program into existing primary care clinics with an interprofessional approach that includes dietitians and kinesiologists. PROGRAM DESCRIPTION: Canadian Health Advanced by Nutrition and Graded Exercise (CHANGE) provides a personalized approach to nutrition and exercise modification focusing on patients with metabolic syndrome. With CHANGE, exercise intervention is individualized (ie, tailored to individual preferences) and graded (ie, intensity is built up slowly over time); supervision and implementation of the program is conducted in a collaborative fashion between the family physician and the kinesiologist. Patients undergo an initial fitness assessment that determines their baseline aerobic, strength, and flexibility scores, and the same assessment is performed at 3 months and at 12 months. CONCLUSION: The CHANGE program demonstrates how interprofessional primary care teams can support patients with metabolic syndrome in achieving their health goals. By including dietitians and kinesiologists in primary care settings to work alongside family doctors, many barriers to lifestyle interventions can be overcome. The team's collaborative understanding of the patient combined with the patient's own sense of urgency for change creates the opportunity for the formation of new healthy lifestyle habits. Although results are preliminary, CHANGE appears to be a feasible, implementable, and effective program.

Enteral versus parenteral nutrition in critically ill patients: an updated systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Enteral nutrition (EN) is recommended as the preferred route for early nutrition therapy in critically ill adults over parenteral nutrition (PN). A recent large randomized controlled trial (RCT) showed no outcome differences between the two routes. The objective of this systematic review was to evaluate the effect of the route of nutrition (EN versus PN) on clinical outcomes of critically ill patients. METHODS: An electronic search from 1980 to 2016 was performed identifying relevant RCTs. Individual trial data were abstracted and methodological quality of included trials scored independently by two reviewers. The primary outcome was overall mortality and secondary outcomes included infectious complications, length of stay (LOS) and mechanical ventilation. Subgroup analyses were performed to examine the treatment effect by dissimilar caloric intakes, year of publication and trial methodology. We performed a test of asymmetry to assess for the presence of publication bias. RESULTS: A total of 18 RCTs studying 3347 patients met inclusion criteria. Median methodological score was 7 (range, 2-12). No effect on overall mortality was found (1.04, 95 % CI 0.82, 1.33, P = 0.75, heterogeneity I(2) = 11 %). EN compared to PN was associated with a significant reduction in infectious complications (RR 0.64, 95 % CI 0.48, 0.87, P = 0.004, I(2) = 47 %). This was more pronounced in the subgroup of RCTs where the PN group received significantly more calories (RR 0.55, 95 % CI 0.37, 0.82, P = 0.003, I(2) = 0 %), while no effect was seen in trials where EN and PN groups had a similar caloric intake (RR 0.94, 95 % CI 0.80, 1.10, P = 0.44, I(2) = 0 %; test for subgroup differences, P = 0.003). Year of publication and methodological quality did not influence these findings; however, a publication bias may be present as the test of asymmetry was significant (P = 0.003). EN was associated with significant reduction in ICU LOS (weighted mean difference [WMD] -0.80, 95 % CI -1.23, -0.37, P = 0.0003, I(2) = 0 %) while no significant differences in hospital LOS and mechanical ventilation were observed. CONCLUSIONS: In critically ill patients, the use of EN as compared to PN has no effect on overall mortality but decreases infectious complications and ICU LOS. This may be explained by the benefit of reduced macronutrient intake rather than the enteral route itself.

Factors associated with nutritional decline in hospitalised medical and surgical patients admitted for 7 d or more: a prospective cohort study.

This prospective cohort study was conducted in eighteen Canadian hospitals with the aim of examining factors associated with nutritional decline in medical and surgical patients. Nutritional decline was defined based on subjective global assessment (SGA) performed at admission and discharge. Data were collected on demographics, medical information, food intake and patients' satisfaction with nutrition care and meals during hospitalisation; 424 long-stay (≥7 d) patients were included; 38% of them had surgery; 51% were malnourished at admission (SGA B or C); 37% had in-hospital changes in SGA; 19·6% deteriorated (14·6% from SGA A to B/C and 5% from SGA B to C); 17·4% improved (10·6% from SGA B to A, 6·8% from SGA C to B/A); and 63·0 % patients were stable (34·4% were SGA A, 21·3% SGA B, 7·3% SGA C). One SGA C patient had weight loss ≥5%, likely due to fluid loss and was designated as stable. A subset of 364 patients with admission SGA A and B was included in the multiple logistic regression models to determine factors associated with nutritional decline. After controlling for SGA at admission and the presence of a surgical procedure, lower admission BMI, cancer, two or more diagnostic categories, new in-hospital infection, reduced food intake, dissatisfaction with food quality and illness affecting food intake were factors significantly associated with nutritional decline in medical patients. For surgical patients, only male sex was associated with nutritional decline. Factors associated with nutritional decline are different in medical and surgical patients. Identifying these factors may assist nutritional care.

The Integrated Nutrition Pathway for Acute Care (INPAC): Building consensus with a modified Delphi.

BACKGROUND: Malnutrition is commonly underdiagnosed and undertreated in acute care patients. Implementation of current pathways of care is limited, potentially as a result of the perception that they are not feasible with current resources. There is a need for a pathway based on expert consensus, best practice and evidence that addresses this crisis in acute care, while still being feasible for implementation. METHODS: A modified Delphi was used to develop consensus on a new pathway. Extant literature and other resources were reviewed to develop an evidence-informed background document and draft pathway, which were considered at a stakeholder meeting of 24 experts. Two rounds of an on-line Delphi survey were completed (n = 28 and 26 participants respectively). Diverse clinicians from four hospitals participated in focus groups to face validate the draft pathway and a final stakeholder meeting confirmed format changes to make the pathway conceptually clear and easy to follow for end-users. Experts involved in this process were researchers and clinicians from dietetics, medicine and nursing, including management and frontline personnel. RESULTS: 80% of stakeholders who were invited, participated in the first Delphi survey. The two rounds of the Delphi resulted in consensus for all but two minor components of the Integrated Nutrition Pathway for Acute Care (INPAC). The format of the INPAC was revised based on the input of focus group participants, stakeholders and investigators. CONCLUSIONS: This evidence-informed, consensus based pathway for nutrition care has greater depth and breadth than prior guidelines that were commonly based on systematic reviews. As extant evidence for many best practices is absent, the modified Delphi process has allowed for consensus to be developed based on better practices. Attention to feasibility during development has created a pathway that has greater implementation potential. External validation specifically with practitioner groups promoted a conceptually easy to use format. Test site implementation and evaluation is needed to identify resource requirements and demonstrate process and patient reported outcomes resulting from embedding INPAC into clinical practice.

Development of a Dietary Management Care Map for Metabolic Syndrome.

Metabolic syndrome (MetS) refers to a particular cluster of metabolic abnormalities (hypertension, dyslipidemia, type 2 diabetes, and visceral fat deposition) that can lead to a 1.5- to 2-fold increased relative risk of cardiovascular disease. Various combinations of healthier eating patterns and increased physical activity have been shown to improve metabolic abnormalities and reduce MetS prevalence. Dietitians who counsel MetS patients are challenged to integrate guidance from various medical management guidelines and research studies with effective behavioural change strategies and specific advice on what food and eating pattern changes will be most effective, feasible, and acceptable to clients. As part of a demonstration project that is currently underway, we developed a care map (decision aid) that represents the key decision processes involved in diet counselling for MetS. The care map is based on evidence from both clinical and health behaviour change studies and expert consensus and has undergone limited dietitian review. It is being used to help project dietitians clearly articulate their specific food intake change goals. Additional studies to directly compare counselling strategies could inform future development of the map. In the meantime, dietitians may find this care map helpful in clarifying counselling goals and strategies in this client group.

Exploratory analysis of the variable response to an intensive lifestyle change program for metabolic syndrome.

BACKGROUND: Substantial variability in response to lifestyle interventions has been recognized for many years, and researchers have begun to disentangle sources of error from inherent differences in individual responsiveness. The objective of this secondary analysis of an intensive lifestyle intervention (diet and exercise) for metabolic syndrome (MetS) was to identify potentially important differences among study completers grouped by treatment response as measured by change in a continuous metabolic syndrome score (Gurka/MetS). METHODS: All study completers from a 12-month primary care study were categorized into one of five groups according to change in the Gurka/MetS score. A change of 0.4 in z-score defined clinically relevant change in line with results of previous studies. Repeated measures analysis of variance was used to examine cardiovascular disease risk and individual clinical indicators of MetS over 12 months, looking for differences in response over time by the five groups. RESULTS: Of 176 participants, 50% (n = 88) had stable scores, 10% (n = 18) had relevant change scores in the first 3 months only and reverted toward baseline, 20% (n = 35) achieved meaningful change over the whole study, 11% (n = 20) had a delayed response at 3-12 months, and 9% (n = 15) demonstrated worsening scores. Significant differential patterns were noted for groups over the duration of the intervention (p < .001). Improvement in diet quality and fitness scores were similar across all groups. Other available variables were tested and did not account for the differences. CONCLUSION: Work is needed to identify key factors that account for differences in responses to lifestyle interventions that can be used to guide treatment decisions for intensive lifestyle interventions for this common condition. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01616563; first registered June 12, 2012.

Malnutrition, fatigue, frailty, vulnerability, sarcopenia and cachexia: overlap of clinical features.

PURPOSE OF REVIEW: Malnutrition, fatigue, frailty, vulnerability, sarcopenia and cachexia all phenotypically present with the same features because they are subject to the operation of similar mechanistic factors. However, the conditions referred to above differ by which mechanism dominates the cause of the clinical condition. This review discusses the overlap and differences, which distinguish as well as unite these different conditions and allow a rationale for treatment. RECENT FINDINGS: In the continuum of malnutrition, cachexia, sarcopenia and frailty the recent activities focus on two areas. The first is a better understanding of the mechanisms of cachexia and sarcopenia and frailty. In particular, the differential effects of cytokines on muscle and on the hypothalamic system. The effects of inactivity promoting the loss of body mass in cachexia and sarcopenia as well as the positive effects of exercise. The second is the development of a synthesis of available literature to develop consensus documents about the definition, causes, diagnosis and treatment of cachexia, sarcopenia and frailty. SUMMARY: Loss of body tissues resulting in wasting is a common phenotype for several different conditions which can be caused by a combination of reduced food intake, excessive requirements, altered metabolism, sepsis, trauma, ageing and inactivity. They have been referred to loosely as malnutrition but in not all will respond to simply providing nutrients. In this review the common features and the differences as they relate to cause and response to treatment are discussed.