Effect of Two Forms of Tenofovir on Duodenal Enterocytes - a Hypothesis for Different Effect of TDF and TAF on Body Weight and Plasma Lipids.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) compared to tenofovir alafenamide (TAF) leads to lower body weight and plasma lipids by an unknown mechanism. We hypothesize that TDF, when absorbed, may damage enterocytes of the proximal duodenum, leading to reduced absorption of nutrients. METHODS: People living with HIV, without significant gastrointestinal symptoms, receiving TDF (n=12) or TAF (n=12) containing regimen underwent esophagogastroduodenoscopies with duodenal biopsies. Plasma/serum concentrations of nutrients absorbed from proximal duodenum and serum intestinal fatty-acid-binding protein (I-FABP), a marker of enterocyte damage, were measured. COX/SDH histochemical staining and electron microscopy (EM) were conducted to evaluate mitochondria. RESULTS: Five patients in TDF (celiac disease (excluded from further analyses), helicobacter gastritis, and three esophagitis) and two in TAF group (two esophagitis) had a pathological finding in esophagogastroduodenoscopy. Villi were flatter (337 (59) vs. 397 (42) µm, p=0.016), crypts non-significantly deeper (200 (46) vs. 176 (27) µm, p=0.2), and villus to crypt ratio lower (1.5 (0.42) vs. 2.5 (0.51), p=0.009) in TDF vs. TAF group. I-FABP concentration was higher in TDF vs. TAF group (3.0 (1.07) vs. 1.8 (0.53) ng/ml, p=0.003). TDF group had numerically but not statistically significantly lower concentrations of folate, vitamins A, B1, D, and E. COX/SDH staining showed signs of mitochondrial damage in 10 participants in TDF and 11 in TAF group. EM studies showed similar mitochondrial damage in both groups. CONCLUSIONS: Duodenal villous alterations may explain TDF-associated decrease in body weight and plasma lipids. Larger studies are needed to evaluate concentrations of nutrients absorbed from duodenum among TDF users.

Healthy dietary pattern is associated with lower glycemia independently of the genetic risk of type 2 diabetes: a cross-sectional study in Finnish men.

PURPOSE: Hyperglycemia is affected by lifestyle and genetic factors. We investigated if dietary patterns associate with glycemia in individuals with high or low genetic risk for type 2 diabetes (T2D). METHODS: Men (n = 1577, 51-81 years) without T2D from the Metabolic Syndrome in Men (METSIM) cohort filled a food-frequency questionnaire and participated in a 2-hour oral glucose tolerance test. Polygenetic risk score (PRS) including 76 genetic variants was used to stratify participants into low or high T2D risk groups. We established two data-driven dietary patterns, termed healthy and unhealthy, and investigated their association with plasma glucose concentrations and hyperglycemia risk. RESULTS: Healthy dietary pattern was associated with lower fasting and 2-hour plasma glucose, glucose area under the curve, and better insulin sensitivity (Matsuda insulin sensitivity index) and insulin secretion (disposition index) in unadjusted and adjusted models, whereas the unhealthy pattern was not. No interaction was observed between the patterns and PRS on glycemic measures. Healthy dietary pattern was negatively associated with the risk for hyperglycemia in an adjusted model (OR 0.69, 95% CI 0.51-0.95, in the highest tertile), whereas unhealthy pattern was not (OR 1.08, 95% CI 0.79-1.47, in the highest tertile). No interaction was found between diet and PRS on the risk for hyperglycemia (p = 0.69 for healthy diet, p = 0.54 for unhealthy diet). CONCLUSION: Our findings suggest that healthy diet is associated with lower glucose concentrations and lower risk for hyperglycemia in men with no interaction with the genetic risk.

Associations of diet quality and food consumption with serum biomarkers for lipid and amino acid metabolism in Finnish children: the PANIC study.

PURPOSE: To investigate the associations of overall diet quality and dietary factors with serum biomarkers for lipid and amino acid metabolism in a general population of children. METHODS: We studied 194 girls and 209 boys aged 6-8 years participating in the Physical Activity and Nutrition in Children study. Food consumption was assessed by 4-day food records and diet quality was quantified by the Finnish Children Healthy Eating Index (FCHEI). Fasting serum fatty acids, amino acids, apolipoproteins, as well as lipoprotein particle sizes were analyzed with high-throughput nuclear magnetic resonance spectroscopy. Data were analyzed using linear regression adjusted for age, sex, and body fat percentage. RESULTS: FCHEI was directly associated with the ratio of polyunsaturated (PUFA) to saturated fatty acids (SFA) (PUFA/SFA), the ratio of PUFA to monounsaturated fatty acids (MUFA) (PUFA/MUFA), the ratio of PUFA to total fatty acids (FA) (PUFA%), the ratio of omega-3-fatty acids to total FA (omega-3 FA%), and inversely associated with the ratio of MUFA to total FA (MUFA%), alanine, glycine, histidine and very-low density lipoprotein (VLDL) particle size. Consumption of vegetable oils and vegetable-oil-based margarine (≥ 60% fat) was directly associated with PUFA/SFA, PUFA/MUFA, PUFA%, the ratio of omega-6 FA to total FA (omega-6 FA%), and inversely associated with SFA, MUFA, SFA to total FA (SFA%), MUFA%, alanine and VLDL particle size. Consumption of high-fiber grain products directly associated with PUFA/SFA, PUFA/MUFA, omega-3 FA%, omega-6 FA%, PUFA% and inversely associated with SFA and SFA%. Fish consumption directly related to omega-3 FA and omega-3 FA%. Consumption of sugary products was directly associated with histidine and VLDL particle size. Vegetable, fruit, and berry consumption had direct associations with VLDL particle size and the ratio of apolipoprotein B to apolipoprotein A1. Consumption of low fat (< 1%) milk was directly associated with phenylalanine. A higher consumption of high-fat (≥ 1%) milk was associated with lower serum MUFA/SFA and higher SFA%. Sausage consumption was directly related to SFA% and histidine. Red meat consumption was inversely associated with glycine. CONCLUSIONS: Better diet quality, higher in intake of dietary sources of unsaturated fat and fiber, and lower in sugary product intake were associated with more favorable levels of serum biomarkers for lipid and amino acid metabolism independent of adiposity. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01803776, registered March 3, 2013.

Use of oral health care services by family caregivers and care recipients: the LENTO intervention.

OBJECTIVE: We aimed to evaluate the impact of an individually tailored preventive oral health intervention on the use of oral health care services by older family caregivers (FCs) and their care recipients (CRs). MATERIAL AND METHODS: A randomized controlled six and 12-month oral health intervention study included FCs and CRs aged ≥65 years living in Eastern Finland. The participants were randomly assigned to an intervention (FCs n = 53, CRs n = 47) and a control (FCs n = 39, CRs n = 35) group. Individually tailored oral health interventions for the FCs provided by a dental hygienist focused on oral hygiene and self-care. Generalized estimating equations were used to analyze the impact of intervention on the change in the use of oral health care services. RESULTS: The intervention had no significant effect on the use of oral health care services by the FCs or their CRs. Traditional factors such as female gender, a higher number of teeth, toothache, no dental fear, and higher morbidity were significantly (p < 0.05) associated with an increased use of oral health care services in the FCs, but not among the CRs. CONCLUSIONS: Individually tailored preventive oral health intervention showed no effect on the use of oral health care services. To promote oral health among the elderly, specific interventions focusing on use of oral health care services are needed. TRIAL REGISTRATION: clinicaltrials.gov/study/NCT04003493.

Prevalence and risk factors of frailty among older family caregivers.

AIM: The aim of this study was to investigate the prevalence of frailty and identify the demographical and clinical factors associated with frailty among older family caregivers. METHOD: The participants of this cross-sectional study were older family caregivers (n = 125) living in Eastern Finland. Data on functional and cognitive status, depressive symptoms, nutritional status, medication, chronic diseases, stroke, and oral health were obtained. The Mini Nutritional Assessment (MNA) was used to evaluate nutritional status. Frailty status was evaluated using the abbreviated comprehensive geriatric assessment (aCGA) scale. RESULTS: Seventy-three percent of caregivers were identified as frail. According to multivariable logistic regression, cataract, glaucoma, or macular degeneration and the MNA score were predictors of frailty. After adjusting for age, gender, and number of own teeth, the MNA score remained a significant predictor of frailty (adjusted OR = 1.22, 95% CI = 1.06, 1.41). As the MNA scores decreased (meaning poorer nutritional status), the risk of frailty increased. CONCLUSIONS: The present study showed that frailty is prevalent among older family caregivers. Recognising older family caregivers with frailty or at risk of frailty is vital. It is essential to acknowledge vision problems' role in frailty and to monitor and support the nutritional status of family caregivers regularly to prevent frailty development.

Sources of vitamin D and determinants of serum 25-hydroxyvitamin D in Finnish adolescents.

PURPOSE: To study the intake and sources of vitamin D and determinants of serum 25-hydroxyvitamin D (S-25(OH)D) in Finnish adolescents. METHODS: We studied 265 adolescents (117 girls) aged 15-17 years attending 8-year examinations of the PANIC Study, assessed diet using food records and other lifestyle factors by questionnaires, and analyzed S-25(OH)D by chemiluminescence immunoassay and determinants of S-25(OH)D using multivariate linear regression. RESULTS: Mean (standard deviation) of total vitamin D intake from food and supplements was 19.2 (13.1) µg/d, and that of dietary vitamin D intake was 9.9 (5.4) µg/d. Milk fortified with vitamin D was the main dietary source of vitamin D, providing 45% of daily intake. Altogether, 29% of the adolescents used no vitamin D supplements and 25% did not meet the recommended total vitamin D intake of 10 µg/d. Mean (standard deviation) of S-25(OH)D was 62.0 (18.8) nmol/l, and S-25(OH)D was < 50 nmol/l in 29.5% of the adolescents. Vitamin D intake from supplements was the main determinant of S-25(OH)D (ß = 0.465, p < 0.001), followed by consumption of milk products (ß = 0.251, p < 0.001), consumption of meat products (ß = 0.179, p = 0.002), travels to sunny countries (ß = 0.178, p = 0.002), and average daylight time (ß = 0.162, p = 0.004). CONCLUSION: Most of the adolescents had vitamin D intake at the recommended level, although a fourth did not meet the recommended total vitamin D intake of 10 µg/d and almost a third had S-25(OH)D < 50 nmol/l. More attention should be paid to the sufficient intake of vitamin D in adolescents who do not use vitamin D supplements or fortified milk products. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01803776, registered March 3, 2013.

Fatty fish consumption reduces lipophilic index in erythrocyte membranes and serum phospholipids.

BACKGROUND AND AIMS: Lipophilic index (LI) has been introduced to assess the overall fatty acid lipophilicity and as a simple estimate of membrane fluidity. However, little is known on effect of diet on LI. We tested if Camelina sativa oil (CSO) high in ALA, fatty fish (FF) or lean fish (LF) affect LI as compared to control diet and, secondarily, if the LI is associated with HDL lipids and functionality and LDL lipidome. METHODS AND RESULTS: We used data from two randomized clinical trials. The AlfaFish intervention lasted 12 weeks and 79 subjects with impaired glucose tolerance were randomized to FF, LF, CSO or control group. In the Fish trial, 33 subjects with myocardial infarction or unstable ischemic heart attack were randomized to FF, LF or control group for 8 weeks. LI was calculated from erythrocyte membrane fatty acids in AlfaFish and from serum phospholipids in Fish trial. HDL lipids were measured using high-throughput proton nuclear magnetic resonance spectroscopy. There was a significant decrease in LI in the FF group in the AlfaFish (fold change 0.98 ± 0.03) and in the Fish trial (0.95 ± 0.04) and the decrease differed from that of control group in both trials and from CSO group in the AlfaFish study. There were no significant changes in LI in LF or CSO groups. The mean diameter of HDL particles and concentration of large HDL particles were inversely associated with LI. CONCLUSION: FF consumption decreased LI indicating better membrane fluidity in subjects with impaired glucose tolerance or coronary heart disease.

Cross-sectional associations between physical fitness and biomarkers of inflammation in children-The PANIC study.

BACKGROUND: Systemic low-grade inflammation has been proposed as an underlying pathophysiological mechanism for cardiometabolic diseases. We investigated the associations of physical fitness with a systemic low-grade inflammatory state in a population sample of children. METHODS: Altogether 391 children aged 6-9 years were examined. Cardiorespiratory fitness (maximal power output, Wmax ) was assessed by a maximal cycle ergometer test and neuromuscular fitness by hand grip strength, sit-up, standing long jump, 50-meter shuttle run, static balance, sit-and-reach, and box and block tests. Body fat percentage (BF%) and lean mass (LM) were assessed by dual-energy X-ray absorptiometry (DXA). High sensitivity C-reactive protein (hs-CRP), leptin, leptin receptor, high molecular weight adiponectin (HMW-adiponectin), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and glycoprotein acetyls (GlycA) were assessed from fasting blood samples. The modified inflammatory score (IS) was calculated using the population-specific z-scores and formula (z hs-CRP + z leptin + z IL-6 + z TNF-α + z GlycA)-z leptin receptor-z HMW-adiponectin. The data were analyzed using linear regression analyses. RESULTS: Higher Wmax /kg of body mass (ß = -0.416, 95% CI = -0.514 to -0.318), higher number of completed sit-ups (ß = -0.147, 95% CI = -0.244 to -0.049), a longer distance jumped in the standing long jump test (ß = -0.270, 95% CI = -0.371 to -0.169), and a shorter time in the 50-meter shuttle run test (ß = 0.123, 95% CI = 0.022 to 0.223) were associated with lower IS. None of these associations remained statistically significant after adjustment for BF%. CONCLUSIONS: Higher physical fitness is associated with a more favorable inflammatory biomarker profile in children. However, the associations were explained by BF%.

High estradiol levels during a long agonist IVF protocol are associated with decreased food intake, higher leptin concentrations, and lower levels of high-sensitivity C-reactive protein.

PURPOSE: To study whether different hormonal phases affect appetite regulation, food intake, and concentrations of leptin, glucagon-like peptide-1 (GLP-1), and high-sensitivity C-reactive protein (hs-CRP) during a long agonist in vitro fertilization (IVF) protocol. METHODS: Fifty-four infertile women were encountered thrice, the first of which was at the beginning of their period (low estradiol). The other two visits were during a gonadotrophin-releasing hormone (GnRH) analog downregulation (low estradiol) and at the end of a follicle-stimulating hormone (FSH) stimulation (high estradiol). The first visit was the reference; the women served as their controls. The concentrations of leptin, GLP-1, and hs-CRP were assessed from plasma. Dietary intake was assessed using food records (FRs). In addition, weight, height, body mass index (BMI), and plasma levels of estradiol, glucose, HbA1c, insulin, and lipids were monitored. Twenty-six of the subjects also had a postprandial test. RESULTS: During the stimulation protocol, leptin concentrations elevated (P < 0.001), and energy intake decreased (P = 0.03), while estradiol levels increased (P < 0.001). GLP-1 levels unchanged (P = 0.75) and hs-CRP (P = 0.03) concentrations diminished, while estradiol levels increased. CONCLUSION: No increased food intake or weight gain occurred during the stimulation protocol; thus, leptin may protect from overeating during high estradiol levels, and leptin resistance may not occur during a short follow-up. Also, a favorable anti-inflammatory effect was detected. During this study, we observed no harmful metabolic effects, which might affect negatively maternal health.

Twelve Weeks of High-Intensity Interval Training Alters Adipose Tissue Gene Expression but Not Oxylipin Levels in People with Non-Alcoholic Fatty Liver Disease.

Lifestyle modifications, including increased physical activity and exercise, are recommended for non-alcoholic fatty liver disease (NAFLD). Inflamed adipose tissue (AT) contributes to the progression and development of NAFLD and oxylipins such as hydroxyeicosatetraenoic acids (HETE), hydroxydocosahexanenoic acids (HDHA), prostaglandins (PEG2), and isoprostanoids (IsoP), which all may play a role in AT homeostasis and inflammation. To investigate the role of exercise without weight loss on AT and plasma oxylipin concentrations in NAFLD subjects, we conducted a 12-week randomized controlled exercise intervention. Plasma samples from 39 subjects and abdominal subcutaneous AT biopsy samples from 19 subjects were collected both at the beginning and the end of the exercise intervention. In the AT of women, a significant reduction of gene expression of hemoglobin subunits (HBB, HBA1, HBA2) was observed within the intervention group during the 12-week intervention. Their expression levels were negatively associated with VO2max and maxW. In addition, pathways involved in adipocyte morphology alterations significantly increased, whereas pathways in fat metabolism, branched-chain amino acids degradation, and oxidative phosphorylation were suppressed in the intervention group (p < 0.05). Compared to the control group, in the intervention group, the ribosome pathway was activated, but lysosome, oxidative phosphorylation, and pathways of AT modification were suppressed (p < 0.05). Most of the oxylipins (HETE, HDHA, PEG2, and IsoP) in plasma did not change during the intervention compared to the control group. 15-F2t-IsoP significantly increased in the intervention group compared to the control group (p = 0.014). However, this oxylipin could not be detected in all samples. Exercise intervention without weight loss may influence the AT morphology and fat metabolism at the gene expression level in female NAFLD subjects.

Nordic dietary patterns and cardiometabolic outcomes: a systematic review and meta-analysis of prospective cohort studies and randomised controlled trials.

AIMS/HYPOTHESIS: Nordic dietary patterns that are high in healthy traditional Nordic foods may have a role in the prevention and management of diabetes. To inform the update of the EASD clinical practice guidelines for nutrition therapy, we conducted a systematic review and meta-analysis of Nordic dietary patterns and cardiometabolic outcomes. METHODS: We searched MEDLINE, EMBASE and The Cochrane Library from inception to 9 March 2021. We included prospective cohort studies and RCTs with a follow-up of ≥1 year and ≥3 weeks, respectively. Two independent reviewers extracted relevant data and assessed the risk of bias (Newcastle-Ottawa Scale and Cochrane risk of bias tool). The primary outcome was total CVD incidence in the prospective cohort studies and LDL-cholesterol in the RCTs. Secondary outcomes in the prospective cohort studies were CVD mortality, CHD incidence and mortality, stroke incidence and mortality, and type 2 diabetes incidence; in the RCTs, secondary outcomes were other established lipid targets (non-HDL-cholesterol, apolipoprotein B, HDL-cholesterol, triglycerides), markers of glycaemic control (HbA1c, fasting glucose, fasting insulin), adiposity (body weight, BMI, waist circumference) and inflammation (C-reactive protein), and blood pressure (systolic and diastolic blood pressure). The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of the evidence. RESULTS: We included 15 unique prospective cohort studies (n=1,057,176, with 41,708 cardiovascular events and 13,121 diabetes cases) of people with diabetes for the assessment of cardiovascular outcomes or people without diabetes for the assessment of diabetes incidence, and six RCTs (n=717) in people with one or more risk factor for diabetes. In the prospective cohort studies, higher adherence to Nordic dietary patterns was associated with 'small important' reductions in the primary outcome, total CVD incidence (RR for highest vs lowest adherence: 0.93 [95% CI 0.88, 0.99], p=0.01; substantial heterogeneity: I2=88%, pQ<0.001), and similar or greater reductions in the secondary outcomes of CVD mortality and incidence of CHD, stroke and type 2 diabetes (p<0.05). Inverse dose-response gradients were seen for total CVD incidence, CVD mortality and incidence of CHD, stroke and type 2 diabetes (p<0.05). No studies assessed CHD or stroke mortality. In the RCTs, there were small important reductions in LDL-cholesterol (mean difference [MD] -0.26 mmol/l [95% CI -0.52, -0.00], pMD=0.05; substantial heterogeneity: I2=89%, pQ<0.01), and 'small important' or greater reductions in the secondary outcomes of non-HDL-cholesterol, apolipoprotein B, insulin, body weight, BMI and systolic blood pressure (p<0.05). For the other outcomes there were 'trivial' reductions or no effect. The certainty of the evidence was low for total CVD incidence and LDL-cholesterol; moderate to high for CVD mortality, established lipid targets, adiposity markers, glycaemic control, blood pressure and inflammation; and low for all other outcomes, with evidence being downgraded mainly because of imprecision and inconsistency. CONCLUSIONS/INTERPRETATION: Adherence to Nordic dietary patterns is associated with generally small important reductions in the risk of major CVD outcomes and diabetes, which are supported by similar reductions in LDL-cholesterol and other intermediate cardiometabolic risk factors. The available evidence provides a generally good indication of the likely benefits of Nordic dietary patterns in people with or at risk for diabetes. REGISTRATION: ClinicalTrials.gov NCT04094194. FUNDING: Diabetes and Nutrition Study Group of the EASD Clinical Practice.

Associations of diet quality, food consumption, eating frequency and eating behaviour with dental caries experience in Finnish children: a 2-year longitudinal study.

We examined cross-sectional and longitudinal associations of dietary factors with caries experience in a population sample of 487 children aged 6-9 years at baseline examinations of the Physical Activity and Nutrition in Children (PANIC) Study. Altogether, 406 of these children attended 2-year follow-up examinations. Food consumption and eating frequency were assessed using 4-day food records, diet quality using the Baltic Sea Diet Score (BSDS) and eating behaviour using the Children's Eating Behavior Questionnaire. Caries experience was examined clinically. The cross-sectional associations of dietary factors with caries experience at baseline were analysed using linear regression and the longitudinal associations of dietary factors with a change in caries experience over follow-up using generalised mixed-effects regression adjusted for other risk factors. A higher consumption of high-fibre grain products (standardised regression coefficient ß = -0·16, P = 0·003) and milk (ß = -0·11, P = 0·025) and higher BSDS (ß = -0·15, P = 0·007) were associated with lower caries experience, whereas a higher consumption of potatoes (ß = 0·11, P = 0·048) and emotional overeating (ß = 0·12, P = 0·025) were associated with higher caries experience. Higher snacking frequency (fixed coefficient ß = 0·07, P = 0·033), desire to drink (ß = 0·10, P = 0·046), slowness in eating (ß = 0·12, P = 0·027) and food fussiness (ß = 0·12, P = 0·018) were associated with higher caries experience, whereas enjoyment of food (ß = -0·12, P = 0·034) and higher BSDS (ß = -0·02, P = 0·051) were associated with lower caries experience.

Individually tailored nutritional guidance improved dietary intake of older family caregivers: a randomized controlled trial.

PURPOSE: Older family caregivers (FCs) are vulnerable to insufficient dietary intake and risk of malnutrition. The aim of this study was to assess the impact of individually tailored nutritional guidance on the dietary intake and nutritional status of older FCs and their care recipients' (CRs') nutritional status. METHODS: This study was a randomized controlled 6-month nutrition intervention in Eastern Finland. The inclusion criteria for FCs were having a home-living CR aged 65 or above and a valid care allowance. The exclusion criterion was CR receiving end-of-life care at baseline. Participants were randomly assigned to an intervention (FCs n = 63, CRs n = 59) and a control (FCs n = 50, CRs n = 48) group. Individually tailored nutritional guidance targeted to FCs was given to an intervention group by a clinical nutritionist. The main outcomes were dietary intake (3-day food record). RESULTS: After the 6-month intervention, 63 FCs and 59 CRs in the intervention group and 50 FCs and 48 CRs in the control group were analyzed. In the intervention group of FCs, the intakes of protein, riboflavin, calcium, potassium, phosphorus, and iodine differed significantly (p < 0.05) compared to the control group. In addition, the intake of vitamin D supplementation improved in the intervention group of the FCs and CRs (p < 0.001). CONCLUSION: Individually tailored nutrition guidance improves the intake levels of crucial nutrients, such as the intake levels of protein, vitamin D, and calcium of the FCs. Further studies are warranted to optimize the methods to improve the nutrition of FCs. Registration number of Clinical Trials: ClinicalTrials.gov NCT04003493 (1 July 2019).

FADS1 rs174550 genotype and high linoleic acid diet modify plasma PUFA phospholipids in a dietary intervention study.

INTRODUCTION: Fatty acid desaturase 1 (FADS1) gene encodes for delta-5 desaturase enzyme which is needed in conversion of linoleic acid (LA) to arachidonic acid (AA). Recent studies have shown that response to dietary PUFAs differs between the genotypes in circulating fatty acids. However, interactions between the FADS1 genotype and dietary LA on overall metabolism have not been studied. OBJECTIVES: We aimed to examine the interactions of FADS1 rs174550 genotypes (TT and CC) and high-LA diet to identify plasma metabolites that respond differentially to dietary LA according to the FADS1 genotype. METHODS: A total of 59 men (TT n = 26, CC n = 33) consumed a sunflower oil supplemented diet for 4 weeks. Daily dose of 30, 40, or 50 ml was calculated based on body mass index. It resulted in 17-28 g of LA on top of the usual daily intake. Fasting plasma samples at the beginning and at the end of the intervention were analyzed with LC-MS/MS non-targeted metabolomics method. RESULTS: At the baseline, the carriers of FADS1 rs174550-TT genotype had higher abundance of long-chain PUFA phospholipids compared to the FADS1 rs174550-CC one. In response to the high-LA diet, LA phospholipids and long-chain acylcarnitines increased and lysophospholipids decreased in fasting plasma similarly in both genotypes. LysoPE (20:4), LysoPC (20:4), and PC (16:0_20:4) decreased and cortisol increased in the carriers of rs174550-CC genotype; however, these genotype-diet interactions were not significant after correction for multiple testing. CONCLUSION: Our findings show that both FADS1 rs174550 genotype and high-LA diet modify plasma phospholipid composition. TRIAL REGISTRATION: The study was registered to ClinicalTrials: NCT02543216, September 7, 2015 (retrospectively registered).

The FADS1 genotypes modify the effect of linoleic acid-enriched diet on adipose tissue inflammation via pro-inflammatory eicosanoid metabolism.

PURPOSE: Fatty acid desaturase (FADS) variants associate with fatty acid (FA) and adipose tissue (AT) metabolism and inflammation. Thus, the role of FADS1 variants in the regulation of dietary linoleic acid (LA)-induced effects on AT inflammation was investigated. METHODS: Subjects homozygotes for the TT and CC genotypes of the FADS1-rs174550 (TT, n = 25 and CC, n = 28) or -rs174547 (TT, n = 42 and CC, n = 28), were either recruited from the METabolic Syndrome In Men cohort to participate in an intervention with LA-enriched diet (FADSDIET) or from the Kuopio Obesity Surgery (KOBS) study. GC and LC-MS for plasma FA proportions and eicosanoid concentrations and AT gene expression for AT inflammatory score (AT-InSc) was determined. RESULTS: We observed a diet-genotype interaction between LA-enriched diet and AT-InSc in the FADSDIET. In the KOBS study, interleukin (IL)1 beta mRNA expression in AT was increased in subjects with the TT genotype and highest LA proportion. In the FADSDIET, n-6/LA proportions correlated positively with AT-InSc in those with the TT genotype but not with the CC genotype after LA-enriched diet. Specifically, LA- and AA-derived pro-inflammatory eicosanoids related to CYP450/sEH-pathways correlated positively with AT-InSc in those with the TT genotype, whereas in those with the CC genotype, the negative correlations between pro-inflammatory eicosanoids and AT-InSc related to COX/LOX-pathways. CONCLUSIONS: LA-enriched diet increases inflammatory AT gene expression in subjects with the TT genotype, while CC genotype could play a protective role against LA-induced AT inflammation. Overall, the FADS1 variant could modify the dietary LA-induced effects on AT inflammation through the differential biosynthesis of AA-derived eicosanoids.

Social and Environmental Determinants of Health Among Family Caregivers of Older Adults.

BACKGROUND: Although the academic literature has focused on family caregivers' health outcomes, little is known about the social and environmental determinants of health and the extent to which they relate to health disparities among family caregivers caring for older adults. OBJECTIVES: The purpose of the study was to describe the prevalence of diseases and the association with social and environmental determinants of health among family caregivers caring for older adults in Finland. METHODS: A cross-sectional analysis was conducted. The study participants were interviewed on sociodemographic factors, comorbidity, and the World Health Organization Quality of Life Questionnaire. Independent-samples t-test, analysis of variance, and chi-square analyses were used to assess the social and environmental factors' association with health outcomes. RESULTS: A total of 126 family caregivers participated in this study. The mean age of study participants was 74.4 years, and most were female, married, and from an urban area. Family caregivers' older age and lower financial satisfaction were the main factors associated with the health inequalities. Older age was associated with age-related eye disorders, hearing impairment, coronary heart disease, and comorbidity. Family caregivers' lower financial satisfaction was associated with diabetes, depression, and higher body mass index. Other factors linked to health disparities were family caregivers' gender, educational attainment, and the municipality of living. DISCUSSION: This study provides evidence about family caregivers' social and environmental determinants of health. To enhance health equity, nurse-led interventions, a life course approach, and intersectional actions are required.

Psychometric evaluation of three-factor eating questionnaire -R18 in aging Finnish men with increased risk for type 2 diabetes.

BACKGROUND: Deeper comprehension of eating-related behaviour (how and why people eat) can reveal new aspects to support health and prevent type 2 diabetes (T2D). However, such research is largely missing in aging men. AIM: The aim was to investigate suitability of the Three-Factor Eating Questionnaire-R18 (TFEQ-R18) in Finnish aging men which is widely used to examine factors: cognitive restraint (CR), uncontrolled eating (UE), and emotional eating (EE). METHODS: Study population consisted of 420 men aged 50-75, who completed the TFEQ-R18 at the baseline of the T2D-GENE lifestyle intervention study. Inclusion criteria were impaired fasting glucose (IFG) and body mass index ≥25 kg/m2. Confirmatory factor analysis was used to study psychometrics (reliability, validity, and model fit) and factor structure of TFEQ-R18. RESULTS: The items loaded to the three factors (CR, UE, EE) as in previous studies, except two items at CR factor and one at UE factor, which were therefore omitted. UE was also discovered split into two sub factors (named as 'craving' and 'loss-of-control'), UE being a higher-order (h) factor. The resultant revised version was named as Three-Factor Eating Questionnaire Revised to 15-items with higher-order factor (TFEQ-R15h). CONCLUSION: The original 18-item version of the TFEQ was not optimal in the population consisting of Finnish aging men with elevated T2D risk. A modified 15-item version of the TFEQ could be used to describe EB in this population instead.

Dietary fat intakes and cardiovascular disease risk in adults with type 2 diabetes: a systematic review and meta-analysis.

PURPOSE: Advice regarding the intake of dietary fats is particularly relevant to those with type 2 diabetes, given their increased risk of cardiovascular disease. METHODS: We have undertaken a systematic review of fat intakes and cardiovascular disease risk in adults with type 2 diabetes using an online search strategy to 24 April 2020, augmented with hand searching. Searches, extraction, and risk of bias assessments were undertaken by two researchers. The quality of evidence was assessed with GRADE protocols. RESULTS: We identified five eligible prospective studies of 22,591 participants followed for on average 9.8 years, and one trial of 14 participants with type 2 diabetes. Limited data were available; however, replacement analyses of saturated fat with polyunsaturated fat (RR for 2% energy replacement 0.87 95% CI: 0.77-0.99) or carbohydrate (RR for 5% energy replacement 0.82 95% CI: 0.67-1.00) was associated with reduced cardiovascular disease occurrence. Higher polyunsaturated: saturated fat intake was also associated with reduced cardiovascular disease occurrence (RR 0.75 95% CI: 0.57-0.98). The quality of evidence was low to very-low. CONCLUSION: Although only limited data were available, replacement of saturated fats with other macronutrients, such as polyunsaturated fats, was associated with reduced cardiovascular disease occurrence. Supporting evidence from research in the general population increases confidence in these findings. Until more data are available to better comment on dietary fat intakes in cardiovascular disease risk of those with type 2 diabetes, it appears appropriate that saturated fats be replaced in the diet with other macronutrients, such as polyunsaturated fats.

The effects of a 2-year physical activity and dietary intervention on plasma lipid concentrations in children: the PANIC Study.

PURPOSE: We studied the effects of a physical activity and dietary intervention on plasma lipids in a general population of children. We also investigated how lifestyle changes contributed to the intervention effects. METHODS: We carried out a 2-year controlled, non-randomized lifestyle intervention study among 504 mainly prepubertal children aged 6-9 years at baseline. We assigned 306 children to the intervention group and 198 children to the control group. We assessed plasma concentrations of total, LDL, HDL, and VLDL cholesterol, triglycerides, HDL triglycerides, and VLDL triglycerides. We evaluated the consumption of foods using 4-day food records and physical activity using a movement and heart rate sensor. We analyzed data using linear mixed-effect models adjusted for age at baseline, sex, and pubertal stage at both time points. Furthermore, specific lifestyle variables were entered in these models. RESULTS: Plasma LDL cholesterol decreased in the intervention group but did not change in the control group ( - 0.05 vs. 0.00 mmol/L, regression coefficient (ß) = - 0.0385, p = 0.040 for group*time interaction). This effect was mainly explained by the changes in the consumption of high-fat vegetable oil-based spreads (ß = - 0.0203, + 47% change in ß) and butter-based spreads (ß = - 0.0294, + 30% change in ß), moderate-to-vigorous physical activity (ß = - 0.0268, + 30% change in ß), light physical activity (ß = - 0.0274, + 29% change in ß) and sedentary time (ß = - 0.0270, + 30% change in ß). The intervention had no effect on other plasma lipids. CONCLUSION: Lifestyle intervention resulted a small decrease in plasma LDL cholesterol concentration in children. The effect was explained by changes in quality and quantity of dietary fat and physical activity. CLINICAL TRIAL REGISTRY NUMBER: NCT01803776, ClinicalTrials.gov.

A 2 year physical activity and dietary intervention attenuates the increase in insulin resistance in a general population of children: the PANIC study.

AIMS/HYPOTHESIS: We studied for the first time the long-term effects of a combined physical activity and dietary intervention on insulin resistance and fasting plasma glucose in a general population of predominantly normal-weight children. METHODS: We carried out a 2 year non-randomised controlled trial in a population sample of 504 children aged 6-9 years at baseline. The children were allocated to a combined physical activity and dietary intervention group (306 children at baseline, 261 children at 2-year follow-up) or a control group (198 children, 177 children) without blinding. We measured fasting insulin and fasting glucose, calculated HOMA-IR, assessed physical activity and sedentary time by combined heart rate and body movement monitoring, assessed dietary factors by a 4 day food record, used the Finnish Children Healthy Eating Index (FCHEI) as a measure of overall diet quality, and measured body fat percentage (BF%) and lean body mass by dual-energy x-ray absorptiometry. The intervention effects on insulin, glucose and HOMA-IR were analysed using the intention-to-treat principle and linear mixed-effects models after adjustment for sex, age at baseline, and pubertal status at baseline and 2 year follow-up. The measures of physical activity, sedentary time, diet and body composition at baseline and 2 year follow-up were entered one-by-one as covariates into the models to study whether changes in these variables might partly explain the observed intervention effects. RESULTS: Compared with the control group, fasting insulin increased 4.65 pmol/l less (absolute change +8.96 vs +13.61 pmol/l) and HOMA-IR increased 0.18 units less (+0.31 vs +0.49 units) over 2 years in the combined physical activity and dietary intervention group. The intervention effects on fasting insulin (regression coefficient ß for intervention effect -0.33 [95% CI -0.62, -0.04], p = 0.026) and HOMA-IR (ß for intervention effect -0.084 [95% CI -0.156, -0.012], p = 0.023) were statistically significant after adjustment for sex, age at baseline, and pubertal status at baseline and 2 year follow-up. The intervention had no effect on fasting glucose, BF% or lean body mass. Changes in total physical activity energy expenditure, light physical activity, moderate-to-vigorous physical activity, total sedentary time, the reported consumption of high-fat (≥60%) vegetable oil-based spreads, and FCHEI, but not a change in BF% or lean body mass, partly explained the intervention effects on fasting insulin and HOMA-IR. CONCLUSIONS/INTERPRETATION: The combined physical activity and dietary intervention attenuated the increase in insulin resistance over 2 years in a general population of predominantly normal-weight children. This beneficial effect was partly mediated by changes in physical activity, sedentary time and diet but not changes in body composition. TRIAL REGISTRATION: ClinicalTrials.gov NCT01803776 Graphical abstract.