The effect of traditional diet on glucose homoeostasis in carriers and non-carriers of a common TBC1D4 variant in Greenlandic Inuit: a randomised crossover study.

Consumption of traditional foods is decreasing amid a lifestyle transition in Greenland as incidence of type 2 diabetes (T2D) increases. In homozygous carriers of a TBC1D4 variant, conferring postprandial insulin resistance, the risk of T2D is markedly higher. We investigated the effects of traditional marine diets on glucose homoeostasis and cardio-metabolic health in Greenlandic Inuit carriers and non-carriers of the variant in a randomised crossover study consisting of two 4-week dietary interventions: Traditional (marine-based, low-carbohydrate) and Western (high in imported meats and carbohydrates). Oral glucose tolerance test (OGTT, 2-h), 14-d continuous glucose and cardio-metabolic markers were assessed to investigate the effect of diet and genotype. Compared with the Western diet, the Traditional diet reduced mean and maximum daily blood glucose by 0·17 mmol/l (95 % CI 0·05, 0·29; P = 0·006) and 0·26 mmol/l (95 % CI 0·06, 0·46; P = 0·010), respectively, with dose-dependency. Furthermore, it gave rise to a weight loss of 0·5 kg (95 % CI; 0·09, 0·90; P = 0·016) relative to the Western diet and 4 % (95 % CI 1, 9; P = 0·018) lower LDL:HDL-cholesterol, which after adjustment for weight loss appeared to be driven by HDL elevation (0·09 mmol/l (0·03, 0·15), P = 0·006). A diet-gene interaction was indicated on insulin sensitivity in the OGTT (p = 0·093), which reflected a non-significant increase of 1·4 (-0·6, 3·5) mmol/l in carrier 2-h glucose. A Traditional diet marginally improved daily glycaemic control and plasma lipid profile compared with a Westernised diet in Greenlandic Inuit. Possible adverse effects on glucose tolerance in carriers of the TBC1D4 variant warrant further studies.

High-protein diet during pulmonary rehabilitation in patients with chronic obstructive pulmonary disease.

INTRODUCTION: The prevalence of cachexia in patients with chronic obstructive pulmonary disease (COPD) is high and associated with reduced quality of life, increased mortality and morbidity. We aimed to test the effect of a high protein diet combined with exercise on fat-free mass (FFM), functional capacity, symptom burden and dyspnoea. METHODS: Outpatients with COPD and severe or very severe (GOLD grade III-IV) disease and malnutrition commencing pulmonary rehabilitation were randomised to a high-protein diet or standard care. FFM was measured by bio-impedance analysis (BIA), mid-upper arm circumference (MUAC) and mid-thigh circumference (MTC), peripheral muscle function by six-minute walking distance (6MWD) and handgrip strength (HGS), symptoms by the COPD Assessment Trial (CAT) and dyspnoea by the Medical Research Council dyspnoea scale and Borg scores; all at baseline and after 12 weeks. RESULTS: Ten out of 13 randomised patients completed the trial. The intervention group was superior to the control group with respect to 6MWD (97 ± 93 m, p = 0.04) at 12 weeks. No differences were observed between the groups in HGS, anthropometrics, symptom burden or dyspnoea. CONCLUSION: In patients with COPD attending rehabilitation, a high protein diet combined with physical exercise had a clinically relevant effect on walking distance. FUNDING: none. TRIAL REGISTRATION: NCT04888182.

Effects of Postdischarge High-Protein Oral Nutritional Supplements and Resistance Training in Malnourished Surgical Patients: A Pilot Randomized Controlled Trial.

The presence of malnutrition is increasingly becoming a postdischarge problem in surgical patients. We aimed to investigate whether oral nutritional supplements combined with resistance training could minimize skeletal muscle atrophy in surgical patients after discharge. This randomized controlled study was conducted at the Department of Surgery, National Hospital of Faroe Islands from 2018 to 2020. A total of 45 patients aged 37−74 years participated and were allocated to one of three groups: diet (DI; n = 13), exercise and diet (EX + DI; n = 16), or control (CON; n = 16). The intervention period lasted 8 weeks. The intervention groups received individual dietary counselling and a protein-rich oral nutritional supplement twice a day containing 22 g of protein/day. Patients in the EX + DI group were assigned to resistance training sessions. Patients in the CON group received standard care. The primary outcome was change in lean body mass (LBM). Secondary outcomes were change in body weight, handgrip strength, quality of life, surgery-related side effects, energy and protein intake, length of stay and one-year mortality. To estimate within-group changes, linear mixed models including group−time interactions as fixed effects and patients as random effects were fitted. Within-group change in LBM was 233, 813 and 78 g in the DI, EX + DI and CON groups, respectively, with no significant between-group difference (p > 0.05). Pain score declined more (p = 0.04) in the EX + DI group compared with the CON group. Body weight, handgrip strength, quality of life and surgery-related side effects did not differ between groups. At the end of study, mean cumulative weight change in the DI and EX + DI groups was 0.4% and 1.6%, respectively, whereas the CON group experienced a weight loss of −0.6%. No significant difference in primary outcome between groups was noted. However, our results indicate some benefits from exercise and nutrition for malnourished surgical patients.

Correlates of Pancreatic Enzyme Replacement Therapy Intake in Adults with Cystic Fibrosis: Results of a Cross-Sectional Study.

Most people with cystic fibrosis (pwCF) develop pancreatic insufficiency and are treated with pancreatic enzyme replacement therapy (PERT). We aimed to describe the use of PERT and assess the correlates of PERT dose in adult pwCF. In a cross-sectional study at the Copenhagen CF Centre, the participants reported PERT intake, gastrointestinal (GI) symptoms and the use of concomitant treatments. Demographic and clinical characteristics were extracted from the Danish CF Registry. We used linear regression to assess the correlates of PERT dose per kg bodyweight (U-lipase/kg). We included 120 pwCF with a median age of 32.9 years, 46% women and 72% F508delta homozygote. The PERT dose ranged from 0 to 6160 U-lipase/kg per main meal (mean 1828; SD 1115). The PERT dose was associated with participants' sex (men vs. women: 661; 95% CI: 302; 1020 U-lipase/kg), age (-16; 95% CI: -31; -1 U-lipase/kg per year) and weight (-45; 95% CI: -58; -31 U-lipase/kg per kg). Having less frequent constipation and being lung transplanted were also associated with a higher PERT dose. A third of participants did not take PERT for snacks, and this was associated with the frequency of diarrhoea. These findings indicate that PERT intake may be improved to reduce GI symptoms.

Animal-based food choice and associations with long-term weight maintenance and metabolic health after a large and rapid weight loss: The PREVIEW study.

BACKGROUND & AIMS: Low-energy diet replacement is an effective tool to induce large and rapid weight loss and improve metabolic health, but in the long-term individuals often experience significant weight regain. Little is known about the role of animal-based foods in weight maintenance and metabolic health. We aimed to examine longitudinal associations of animal-based foods with weight maintenance and glycaemic and cardiometabolic risk factors. We also modelled replacement of processed meat with other high-protein foods. METHODS: In this secondary analysis, longitudinal data were analysed from 688 adults (26-70 years) with overweight and prediabetes after 8-week low-energy diet-induced weight loss (≥8% of initial body weight) in a 3-year, multi-centre, diabetes prevention study (PREVIEW). Animal-based food consumption, including unprocessed red meat, processed red meat, poultry, dairy products, fish and seafood, and eggs, was repeatedly assessed using 4-day food records. Multi-adjusted linear mixed models and isoenergetic substitution models were used to examine the potential associations. RESULTS: The available-case analysis showed that each 10-g increment in processed meat, but not total meat, unprocessed red meat, poultry, dairy products, or eggs, was positively associated with weight regain (0.17 kg⋅year-1, 95% CI 0.10, 0.25, P < 0.001) and increments in waist circumference, HbA1c, and triacylglycerols. The associations of processed meat with HbA1c or triacylglycerols disappeared when adjusted for weight change. Fish and seafood consumption was inversely associated with triacylglycerols and triacylglycerol-glucose index, independent of weight change. Modelled replacement of processed meat with isoenergetic (250-300 kJ·day-1 or 60-72 kcal·day-1) dairy, poultry, fish and seafood, grains, or nuts was associated with -0.59 (95% CI -0.77, -0.41), -0.66 (95% CI -0.93, -0.40), -0.58 (95% CI -0.88, -0.27), and -0.69 (95% CI -0.96, -0.41) kg·year-1 of weight regain, respectively (all P < 0.001) and significant improvements in HbA1c, and triacylglycerols. CONCLUSIONS: Higher intake of processed meat, but not total or unprocessed red meat, poultry, dairy products, or eggs may be associated with greater weight regain and more adverse glycaemic and cardiometabolic risk factors. Replacing processed meat with a wide variety of high-protein foods, including unprocessed red meat, poultry, dairy products, fish, eggs, grains, and nuts, could improve weight maintenance and metabolic health after rapid weight loss. This study was registered as ClinicalTrials.gov, NCT01777893.

Adherence to a Plant-Based Diet and Consumption of Specific Plant Foods-Associations with 3-Year Weight-Loss Maintenance and Cardiometabolic Risk Factors: A Secondary Analysis of the PREVIEW Intervention Study.

Plant-based diets are recommended by dietary guidelines. This secondary analysis aimed to assess longitudinal associations of an overall plant-based diet and specific plant foods with weight-loss maintenance and cardiometabolic risk factors. Longitudinal data on 710 participants (aged 26-70 years) with overweight or obesity and pre-diabetes from the 3-year weight-loss maintenance phase of the PREVIEW intervention were analyzed. Adherence to an overall plant-based diet was evaluated using a novel plant-based diet index, where all plant-based foods received positive scores and all animal-based foods received negative scores. After adjustment for potential confounders, linear mixed models with repeated measures showed that the plant-based diet index was inversely associated with weight regain, but not with cardiometabolic risk factors. Nut intake was inversely associated with regain of weight and fat mass and increments in total cholesterol and LDL cholesterol. Fruit intake was inversely associated with increments in diastolic blood pressure, total cholesterol, and LDL cholesterol. Vegetable intake was inversely associated with an increment in diastolic blood pressure and triglycerides and was positively associated with an increase in HDL cholesterol. All reported associations with cardiometabolic risk factors were independent of weight change. Long-term consumption of nuts, fruits, and vegetables may be beneficial for weight management and cardiometabolic health, whereas an overall plant-based diet may improve weight management only.

N-3 fatty acid EPA supplementation in cancer patients receiving abdominal radiotherapy - A randomised controlled trial.

BACKGROUND & AIMS: Malnutrition occurs frequently in patients with cancer during and after radiotherapy to the gastrointestinal (GI) and pelvic area and can lead to negative outcomes. N-3 fatty acids from fish, especially eicosapentaenoic acid (EPA) may possess anticachectic properties. The aim of this study was to investigate the effect of two nutritional interventions; dietary counselling and a daily oral nutritional supplement (ONS) containing 33.8 g of protein and 2.2 g EPA and 1.1 g docosahexaenoic acid (DHA) or standard care, including dietary counselling and protein supplementation when needed. METHODS: Outpatients commencing radiotherapy to the GI area were randomized to receive dietary counselling and daily supplementation over a 5-7-week period or standard care. Outcome parameters were measured at baseline (onset of radiotherapy), week 5, and 12 weeks after commencing radiotherapy, with one additional measurement of body weight at week 2. Quality of life (QoL) was measured using the EORTC QLQ-C30 questionnaire. Radiotherapy-related side effects were assessed using a questionnaire developed specifically for this study. Data from a historical control group collected in a previous observational study were included in this study to compare incidence of weight loss. RESULTS: In total, 30 patients were recruited to this study and 26 patients were enrolled and randomised. The rate of withdrawals was 7.7% at week 2, 15.4% at week 5, and 19.2% at week 12. In total, 22 patients completed the intervention. All the patients in the ONS-group and 85% in the control group experienced weight-loss. Using the intention to treat principle, there were no significant differences between groups in any of the outcomes. All patients experienced side effects. Five out of 11 patients consumed more than 75% of prescribed dose of the fish oil enriched oral nutritional supplement. Post hoc analysis showed that at week 2 the weight changed in high-compliant patients was +1.7% (1.0-2.6) compared with -0.7% (-2.8 to -0.1) in low compliant patients (p < 0,01). The results indicated a dose-response relationship, as correlation analysis recovered a significant positive correlation between weight change and compliance to the fish oil enriched nutritional supplement at both week 2 and 5 (p < 0.05 and p < 0.01, respectively), but not at week 12, indicating a dose-response relationship during radiotherapy but not after. The proportion of patients experiencing weight loss throughout the study period was higher in this study (84.2%) than in the historical control group (73%) (p<0.05%). CONCLUSION: This study showed no effect from dietary counselling and intended protein/fish-oil supplementation on weight loss, quality of life, and nutritional intake, micronutrient status in plasma or radiotherapy-related side effects compared to the control group. However, the compliance to the fish oil enriched oral nutritional supplement was low. Post hoc analysis of dose-response relations indicate a positive correlation between the compliance and the ability to reduce weight loss in cancer patients during radiotherapy treatment. TRIAL REGISTRATION CLINICALTRIALS. GOV IDENTIFIER: NCT04687124.

What is the promise of personalised nutrition?

Personalised nutrition (PN) is an emerging field that bears great promise. Several definitions of PN have been proposed and different modelling approaches have been used to claim PN effects. We tentatively propose to group these approaches into two categories, which we term outcome-based and population reference approaches, respectively. Understanding the fundamental differences between these two types of modelling approaches may allow a more realistic appreciation of what to expect from PN interventions presently and may be helpful for designing and planning future studies investigating PN interventions.

The role of a traditional and western diet on glucose homeostasis in Greenlandic Inuit carriers and non-carriers of type 2 diabetes variant in the TBC1D4 gene: A protocol for a randomized clinical trial.

INTRODUCTION: The lifestyle of Inuit in Greenland and worldwide is undergoing a transition from a fisher-hunter to a westernized society and meanwhile the prevalence of type-2 diabetes (T2D) has increased dramatically. Studies have shown that a common nonsense p.Arg684Ter variant in TBC1D4, which is frequent in Greenland, confers genetic susceptibility towards high risk of T2D. The aim of the study is to investigate whether a traditional marine diet, with high fat and low carbohydrate, will improve glycemic control in Greenland Inuit compared to a western diet. Moreover, we want to examine if the response is more pronounced in carriers of the p.Arg684Ter variant. MATERIALS AND METHODS: We will conduct a randomized, clinical cross-over trial with two dietary intervention periods of four weeks duration. The diet intervention comprise provision of >20E% and instruction for the remaining part of the diet. We expect to include 30 homozygous carriers and 30 homozygous non-carriers of the p.Arg684Ter variant, aged 18-80 years, across three Greenlandic towns. The primary outcome is plasma (p)-glucose 2 h post an oral glucose tolerance test and we aim to have 80% power, at α = 0.05, to detect a difference of 1.1 mmol/L. We will also include supporting measures of glucose homeostasis, assess other markers of the metabolic syndrome and perform metabolome and microbiome profiling. The statistical analysis will be performed as complete case analyses using linear mixed models. ETHICS AND DISSEMINATION: The study received approval by the Ethics Committee of Greenland (KVUG 2018-26) and will be disseminated via international peer-reviewed journal articles and conferences. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov identifier no. NCT04011904.

Sagittal abdominal diameter and waist circumference appear to be equally good as identifiers of cardiometabolic risk.

BACKGROUND AND AIMS: Body mass index (BMI) and waist circumference (WC) are commonly used markers of cardiometabolic risk. However, sagittal abdominal diameter (SAD) has been proposed as a possibly more sensitive marker of intra-abdominal obesity. We investigated differences in how SAD, WC, and BMI were correlated with cardiometabolic risk markers. METHODS AND RESULTS: This cross-sectional study investigated anthropometric and metabolic baseline measurements of individuals from six trials. Multiple linear regression and (partial) correlation coefficients were used to investigate associations between SAD, WC, and BMI and cardiometabolic risk markers, including components of the metabolic syndrome as well as insulin resistance, blood lipids, and lowgrade inflammation. In total 1516 mostly overweight or obese individuals were included in the study. SAD was significantly more correlated with TG than WC for all studies, and overall increase in correlation was 0.05 (95% CI (0.02; 0.08). SAD was significantly more correlated with the markers TG and DBP 0.11 (95% CI (0.08, 0.14)) and 0.04 (95% CI (0.006, 0.07), respectively compared to BMI across all or most studies. CONCLUSION: This study showed that no single anthropometric indicator was consistently more strongly correlated across all markers of cardiometabolic risk. However, SAD was significantly more strongly correlated with TG than WC and significantly more strongly correlated with DBP and TG than BMI.

Fish oil supplementation in cancer patients. Capsules or nutritional drink supplements? A controlled study of compliance.

BACKGROUND & AIMS: Fish-oil, rich in Omega-3 long chain polyunsaturated fatty acids (n-3 LC PUFAs), may in high doses inhibit the development or progression of cancer cachexia. However, poor compliance to oral nutritional supplements is a well-known problem. We aimed to investigate acceptability and compliance to a nutritional drink with fish-oil compared to an equivalent dose of fish-oil administered as capsules in patients receiving chemotherapy for GI tract cancers. Moreover, we aimed to investigate, if there was a difference between a nutritional drink or capsules with respect to nutritional status and side effects. Finally, we aimed to examine, if n-3 LC PUFAs affect leukocyte and platelet counts, and markers of dose-limiting toxicities of chemotherapy. METHODS: We consecutively included 41 patients with advanced cancer in the controlled study. Patients were allocated (not randomized) to ingest either 10 capsules/day for four weeks or 400 mL/day of a nutritional drink with same dose of n-3 LC PUFA dose. Compliance was assessed by daily self-registration and n-3 LC PUFAs in whole blood. Side effects were assessed by 10 cm visual analog scales. RESULTS: Compliance and daily consumption of n-3 LC PUFAs were 96.4% (94.1-99.3) and 4.8 (4.7-4.9) g/day in the capsule group and 80.8 (55.4-93.6) % and 4.0 (2.8-4.7) g/day in the group, respectively (p ≤ 0.02). We found no differences between the groups with respect to changes in whole blood n-3 LC PUFAs, weight, nutritional status, acceptability or side effects. However, in the capsule group the whole blood n-3 LC PUFAs correlated negatively with the increase in nausea (rs = -0.39, p = 0.05), but not in the nutritional drink group. Nausea, reduced appetite and loose stools were of greatest importance for the deviations from recommended doses. The number of capsules had a negative impact on acceptability and compliance, whereas this was mainly related to taste and texture in the nutritional drink group. No changes in median thrombocyte or leukocyte blood counts were observed. CONCLUSIONS: Fish oil in capsules appeared to result in better compliance compared to a nutritional drink with an equivalent dose of n-3 LC PUFAs. However, capsules and the drink did not differ with respect to the effect on nutritional status or side effects. TRIAL REGISTRATION CLINICALTRIALS. GOV IDENTIFIER: NCT03751384.

Higher Protein Intake Is Not Associated with Decreased Kidney Function in Pre-Diabetic Older Adults Following a One-Year Intervention-A Preview Sub-Study.

Concerns about detrimental renal effects of a high-protein intake have been raised due to an induced glomerular hyperfiltration, since this may accelerate the progression of kidney disease. The aim of this sub-study was to assess the effect of a higher intake of protein on kidney function in pre-diabetic men and women, aged 55 years and older. Analyses were based on baseline and one-year data in a sub-group of 310 participants included in the PREVIEW project (PREVention of diabetes through lifestyle Intervention and population studies in Europe and around the World). Protein intake was estimated from four-day dietary records and 24-hour urinary urea excretion. We used linear regression to assess the association between protein intake after one year of intervention and kidney function markers: creatinine clearance, estimated glomerular filtration rate (eGFR), urinary albumin/creatinine ratio (ACR), urinary urea/creatinine ratio (UCR), serum creatinine, and serum urea before and after adjustments for potential confounders. A higher protein intake was associated with a significant increase in UCR (p = 0.03) and serum urea (p = 0.05) after one year. There were no associations between increased protein intake and creatinine clearance, eGFR, ACR, or serum creatinine. We found no indication of impaired kidney function after one year with a higher protein intake in pre-diabetic older adults.

A systematic review and meta-analysis of nutrition therapy compared with dietary advice in patients with type 2 diabetes.

Background: Despite recommendations, many patients with type 2 diabetes receive dietary advice from nurses or doctors instead of individualized nutrition therapy (INT) that is provided by a dietitian.Objective: We performed a meta-analysis to compare the effect of INT that is provided by a registered dietitian with the effect of dietary advice that is provided by other healthcare professionals.Design: A systematic review was conducted of Cochrane library databases, EMBASE, CINAHL, and MEDLINE in the period 2004-2017 for guidelines, reviews, and randomized controlled trials (RCTs) that assessed the outcomes glycated hemoglobin (HbA1c), weight, body mass index (BMI; in kg/m2), and LDL cholesterol. Risk of bias and the quality of evidence were assessed according to the Grading of Recommendations Assessment, Development and Evaluation guidelines.Results: We identified 5 RCTs comprising 912 participants in total. In the first year of intervention (at 6 or 12 mo), nutrition therapy compared with dietary advice was followed by a 0.45% (95% CI: 0.36%, 0.53%) lower mean difference in HbA1c, a 0.55 (95% CI: 0.02, 1.1) lower BMI, a 2.1-kg (95% CI: 1.2-, 2.9-kg) lower weight, and a 0.17-mmol/L (95% CI: 0.11-, 0.23-mmol/L) lower LDL cholesterol. No longer-term data were available. Some of the included studies had a potential bias, and therefore, the quality of the evidence was low or moderate. In addition, it was necessary to pool primary and secondary outcomes.Conclusions: INT that is provided by a dietitian compared with dietary advice that is provided by other health professionals leads to a greater effect on HbA1c, weight, and LDL cholesterol. Because of the potential bias, we recommend considering nutrition therapy that is provided by a dietitian as part of lifestyle intervention in type 2 diabetes, but further randomized studies are warranted.

A Protein Diet Score, Including Plant and Animal Protein, Investigating the Association with HbA1c and eGFR-The PREVIEW Project.

Higher-protein diets have been advocated for body-weight regulation for the past few decades. However, the potential health risks of these diets are still uncertain. We aimed to develop a protein score based on the quantity and source of protein, and to examine the association of the score with glycated haemoglobin (HbA1c) and estimated glomerular filtration rate (eGFR). Analyses were based on three population studies included in the PREVIEW project (PREVention of diabetes through lifestyle Intervention and population studies in Europe and around the World): NQplus, Lifelines, and the Young Finns Study. Cross-sectional data from food-frequency questionnaires (n = 76,777 subjects) were used to develop a protein score consisting of two components: 1) percentage of energy from total protein, and 2) plant to animal protein ratio. An inverse association between protein score and HbA1c (slope -0.02 ± 0.01 mmol/mol, p < 0.001) was seen in Lifelines. We found a positive association between the protein score and eGFR in Lifelines (slope 0.17 ± 0.02 mL/min/1.73 m², p < 0.0001). Protein scoring might be a useful tool to assess both the effect of quantity and source of protein on health parameters. Further studies are needed to validate this newly developed protein score.