Short-term high-calorie high-fat feeding induces hyperinsulinemia and blunts skeletal muscle microvascular blood flow in healthy humans.

Skeletal muscle microvascular blood flow (MBF) plays an important role in glucose disposal in muscle. Impairments in muscle MBF contribute to insulin resistance and prediabetes. Animal studies show that short-term (3 day) high-fat feeding blunts skeletal muscle MBF before impairing insulin-stimulated glucose disposal. It is not known whether this occurs in humans. We investigated the temporal impact of a 7-day high-calorie high-fat (HCHF) diet intervention (+52% kJ; 41% fat) on fasting and postprandial cardiometabolic outcomes in 14 healthy adults (18-37 yr). Metabolic health and vascular responses to a mixed-meal challenge (MMC) were measured at pre (day 0)-, mid (day 4)- and post (day 8)-intervention. There were no significant differences in body weight, body fat %, fasting blood glucose, and fasting plasma insulin concentrations at pre-, mid- and postintervention. Compared with preintervention there was a significant increase in insulin (but not glucose) total area under the curve in response to the MMC at midintervention (P = 0.041) and at postintervention (P = 0.028). Unlike at pre- and midintervention, at postintervention muscle MBF decreased at 60 min (P = 0.024) and 120 min (P = 0.023) after the MMC. However, macrovascular blood flow was significantly increased from 0 to 60 min (P < 0.001) and 120 min (P < 0.001) after the MMC at pre-, mid- and postintervention. Therefore, short-term HCHF feeding in healthy individuals leads to elevated postprandial insulin but not glucose levels and a blunting of meal-induced skeletal muscle MBF responses but not macrovascular blood flow responses.NEW & NOTEWORTHY This is the first study to investigate skeletal muscle microvascular blood flow (MBF) responses in humans after short-term high-calorie high-fat (HCHF) diet. The main findings were that HCHF diet causes elevated postprandial insulin in healthy individuals within 3 days and blunts meal-induced muscle MBF within 7 days, despite no impairments in postprandial glucose or macrovascular blood flow.

Cross-sectional associations of dietary patterns characterized by fat type with markers of cardiometabolic health.

BACKGROUND AND AIMS: Individual dietary fats can differentially impact on cardiometabolic health. However, their impact within a dietary pattern is not well understood, and warrants comparison with diet quality scores with a dietary fat focus. The aim of this study was to investigate cross-sectional associations between a posteriori dietary patterns characterized by fat type and cardiometabolic health markers, and compare these with two diet quality scores. METHODS AND RESULTS: UK Biobank adults with ≥two 24-h dietary assessments and data on cardiometabolic health were included (n = 24 553; mean age: 55.9 y). A posteriori dietary patterns (DP1; DP2) were generated through reduced rank regression (response variables: SFA, MUFA, PUFA). Mediterranean Diet Score (MDS) and Dietary Approaches to Stop Hypertension (DASH) dietary patterns were created. Multiple linear regression analyses were used to investigate associations between standardized dietary patterns and cardiometabolic health (total cholesterol, HDL-C, LDL-C and VLDL-C cholesterol, triglycerides, C-reactive protein [CRP], glycated hemoglobin [HbA1c]). DP1, positively correlated with SFAs, MUFAs and PUFAs, characterized by higher nuts, seeds and vegetables intake and lower fruits and low-fat yoghurt intake, was associated with lower HDL-C (ß: -0.07; 95% CI: -0.10, -0.03) and triglycerides (-0.17; -0.23, -0.10) and higher LDL-C (0.07; 0.01,0.12), CRP (0.01; 0.01, 0.03) and HbA1c (0.16; 0.11,0.21). DP2, positively correlated with SFAs, negatively correlated with PUFAs, characterized by higher butter and high-fat cheese intake and lower nuts, seeds and vegetable intake, was associated with higher total cholesterol (0.10; 0.01, 0.21), VLDL-C (0.05; 0.02, 0.07), triglycerides (0.07; 0.01, 0.13), CRP (0.03; 0.02, 0,04) and HbA1c (0.06; 0.01, 0.11). Higher adherence to MDS and DASH was associated with favorable cardiometabolic health markers concentration. CONCLUSIONS: Irrespective of the method used, dietary patterns that encourage healthy fat consumption were associated with favorable cardiometabolic health biomarkers. This study strengthens the evidence for incorporation of dietary fat type into policy and practice guidelines for CVD prevention.

Dietary patterns, genetic risk, and incidence of obesity: Application of reduced rank regression in 11,735 adults from the UK Biobank study.

Few studies have derived dietary patterns based on intake of discretionary foods and beverages and examined associations with genetic risk and obesity. We examined associations between dietary patterns based on discretionary foods, saturated fatty acids (SFA), and fiber, with a polygenetic risk score (PRS) for obesity and risk of overall obesity, central obesity and high body fat (BF) up to 9.7 years later. Data from 11,735 adults from the UK Biobank cohort study were used. Dietary patterns were derived from 24-h dietary assessments using reduced rank regression (response variables: discretionary foods and beverages [%E]; SFA [%E]; fiber density [g/MJ]). Cox proportional hazard models were used to investigate associations between dietary patterns and incident overall obesity, central obesity and high BF, with interactions by PRS. Three dietary patterns (DP) were identified. DP1, correlated positively with discretionary foods and SFA, inversely with fiber, was associated with higher risk of central obesity (hazard ratio: 1.08; 95% confidence interval: 1.02, 1.14). DP2, correlated positively with discretionary foods and fiber, inversely with SFA, was not associated with obesity incidence. DP3, correlated positively with SFA and fiber, inversely with discretionary foods, was associated with lower risk of central obesity (hazard ratio: 0.92; 95% confidence interval: 0.87, 0.98). There was limited evidence of interactions with PRS. A dietary pattern high in high-SFA and low-fiber discretionary foods and beverages was associated with higher risk of obesity, independent of genetic predisposition.

Energy-dense dietary patterns high in free sugars and saturated fat and associations with obesity in young adults.

PURPOSE: To derive dietary patterns based on dietary energy density (DED), free sugars, SFA, and fiber and investigate association with odds of overweight/obesity in young adults. METHODS: Cross-sectional data from 625 young Australian adults (18-30 years) were used. Dietary patterns were derived using reduced rank regression based on dietary data from a smartphone food diary using DED, free sugars, SFA, and fiber density as response variables. Multivariable logistic regression was used to investigate associations between dietary patterns and odds of self-reported overweight/obesity (BMI ≥ 25 kg/m2). RESULTS: Two dietary patterns were identified (DP1 and DP2). DP-1 was positively correlated with DED, free sugars, and SFA, and inversely correlated with fiber density. It was characterized by higher sugar-sweetened beverages intake and lower vegetable intake, and associated with higher odds of overweight/obesity (OR: 1.22; 95% CI 1.05, 1.42). DP-2 was positively correlated with fiber density and free sugars, and inversely correlated with DED and SFA. It was characterized by higher sugar-sweetened beverages intake and lower non-lean red meat intake, and was not significantly associated with overweight/obesity. CONCLUSION: An energy-dense dietary pattern high in free sugars and SFA and low in fiber was associated with higher odds of obesity in young adults. These findings support dietary interventions that target reductions in energy-dense foods and sugar-sweetened beverages.

Associations between dietary patterns, FTO genotype and obesity in adults from seven European countries.

PURPOSE: High-fat and low-fibre discretionary food intake and FTO genotype are each associated independently with higher risk of obesity. However, few studies have investigated links between obesity and dietary patterns based on discretionary food intake, and the interaction effect of FTO genotype are unknown. Thus, this study aimed to derive dietary patterns based on intake of discretionary foods, saturated fatty acids (SFA) and fibre, and examine cross-sectional associations with BMI and waist circumference (WC), and interaction effects of FTO genotype. METHODS: Baseline data on 1280 adults from seven European countries were included (the Food4Me study). Dietary intake was estimated from a Food Frequency Questionnaire. Reduced rank regression was used to derive three dietary patterns using response variables of discretionary foods, SFA and fibre density. DNA was extracted from buccal swabs. Anthropometrics were self-measured. Linear regression analyses were used to examine associations between dietary patterns and BMI and WC, with an interaction for FTO genotype. RESULTS: Dietary pattern 1 (positively correlated with discretionary foods and SFA, and inversely correlated with fibre) was associated with higher BMI (ß:0.64; 95% CI 0.44, 0.84) and WC (ß:1.58; 95% CI 1.08, 2.07). There was limited evidence dietary pattern 2 (positively correlated with discretionary foods and SFA) and dietary pattern 3 (positively correlated with SFA and fibre) were associated with anthropometrics. FTO risk genotype was associated with higher BMI and WC, with no evidence of a dietary interaction. CONCLUSIONS: Consuming a dietary pattern low in discretionary foods and high-SFA and low-fibre foods is likely to be important for maintaining a healthy weight, regardless of FTO predisposition to obesity. TRIAL REGISTRATION: Clinicaltrials.gov NCT01530139. Registered 9 February 2012 https://clinicaltrials.gov/ct2/show/NCT01530139.

Dietary Patterns Characterized by Fat Type in Association with Obesity and Type 2 Diabetes: A Longitudinal Study of UK Biobank Participants.

BACKGROUND: The fat type consumed is considered a risk factor for developing obesity and type 2 diabetes (T2D). However, these associations have not been investigated using a dietary patterns approach, which can capture combinations of foods and fat type consumed. OBJECTIVES: This study aimed to investigate associations between dietary patterns with varying proportions of SFAs, MUFAs, or PUFAs and obesity, abdominal obesity, and self-reported T2D incidence. METHODS: This study included UK Biobank participants with 2 or more 24-h dietary assessments, free from the outcome of interest at recruitment, and with outcome data at follow-up (n = 16,523; mean follow-up: 6.3 y). Reduced rank regression was used to derive dietary patterns with SFAs, MUFAs, and PUFAs (% of energy intake) as response variables. Logistic regression, adjusted for sociodemographic and health characteristics, was used to investigate the associations between dietary patterns and obesity [BMI (kg/m2) ≥30], abdominal obesity (waist circumference; men: ≥102 cm; women: ≥88 cm) and T2D incidence. RESULTS: Two dietary patterns, DP1 and DP2, were identified: DP1 positively correlated with SFAs (r = 0.48), MUFAs (r = 0.67), and PUFAs (r = 0.56), characterized by higher intake of nuts, seeds, and butter and lower intake of fruit and low-fat yogurt; DP2 positively correlated with SFAs (r = 0.76) and negatively with PUFAs (r = -0.64) and MUFAs (r = -0.01), characterized by higher intake of butter and high-fat cheese and lower intake of nuts and seeds. Only DP2 was associated with higher obesity and abdominal obesity incidence (OR: 1.24; 95% CI: 1.02, 1.45; and OR: 1.19; 95% CI: 1.02, 1.38, respectively). Neither of the dietary patterns was associated with T2D incidence. CONCLUSIONS: These findings provide evidence that a dietary pattern characterized by higher SFA and lower PUFA foods is associated with obesity and abdominal obesity incidence, but not T2D.

Dietary patterns, malnutrition, muscle loss and sarcopenia in cancer survivors: findings from the UK Biobank.

PURPOSE: To identify dietary patterns derived from protein, polyunsaturated fatty acids (PUFA) and vitamin D and examine associations with malnutrition, low muscle mass and sarcopenia in cancer survivors. METHODS: This cross-sectional study included cancer survivors (n = 2415) from the UK Biobank (age [mean ± SD] 59.7 ± 7.1 years; 60.7% female). The Oxford WebQ 24-h dietary assessment estimated food and nutrient intakes. Reduced rank regression derived dietary patterns (response variables: protein [g/kg/day], PUFA [g/day] and vitamin D [µg/day]). Adjusted logistic regression analysis examined associations between dietary patterns and malnutrition, low muscle mass and sarcopenia. RESULTS: Three dietary patterns were identified: (i) 'high oily fish and nuts', characterised by higher oily fish and nuts and seeds intake; (ii) 'low oily fish', characterised by lower oily fish intake and higher potato intake; and (iii) 'meat and dairy', characterised by higher intake of meat, poultry and dairy. Eighteen percent of participants were malnourished, 5% had low muscle mass and 6.5% had sarcopenia. Odds of being malnourished were significantly lower with adherence to a 'high oily fish and nuts' pattern (OR: 0.57; 95% CI: 0.50, 0.65) and 'low oily fish' pattern (OR: 0.81; 95% CI: 0.73, 0.90). The 'meat and dairy' pattern was not associated with malnutrition. No dietary patterns were associated with low muscle mass or sarcopenia. CONCLUSIONS: Energy-rich dietary patterns were associated with lower odds of malnutrition in cancer survivors but did not influence muscle mass or sarcopenia risk. IMPLICATIONS FOR CANCER SURVIVORS: Better understanding of dietary patterns may improve cancer-related outcomes for cancer survivors.

Novel approach to investigate the association between type 2 diabetes risk and dietary fats in a dietary pattern context: a scoping review.

The effect of dietary fat on type 2 diabetes (T2D) risk is unclear. A posteriori dietary pattern methods have been increasingly used to investigate how dietary fats impact T2D risk. However, the diverse nutrients, foods and dietary patterns reported in these studies requires examination to better understand the role of dietary fats. This scoping review aimed to systematically search and synthesize the literature regarding the association between dietary patterns characterized by dietary fats and T2D risk using reduced rank regression. Medline and Embase were searched for cross-sectional, cohort or case-control studies published in English. Of the included studies (n = 8), five high-fat dietary patterns, mostly high in SFA, were associated with higher T2D risk or fasting glucose, insulin and Homeostasis Model Assessment (HOMA) levels. These were mostly low-fiber (n = 5) and high energy-density (n = 3) dietary patterns characterized by low fruit and vegetables intake, reduced fat dairy products and higher processed meats and butter intake. Findings from this review suggest that a posteriori dietary patterns high in SFA that increase T2D risk are often accompanied by lower fruits, vegetables and other fiber-rich foods intake. Therefore, healthy dietary fats consumption for T2D prevention should be encouraged as part of a healthful dietary pattern.

Longitudinal Associations Between Fat-Derived Dietary Patterns and Early Markers of Cardiovascular Disease Risk in the UK Biobank Study.

Background Although the impact of dietary fats on cardiovascular disease (CVD) risk is widely researched, longitudinal associations between dietary patterns (DPs) based on fat type and early markers of CVD risk remain unclear. Methods and Results UK Biobank participants (46.9% men, mean age 55 years) with data on early markers of CVD risk (n=12 706) were followed longitudinally (2014-2020; mean 8.4 years). Two DPs (DP1, DP2) were derived using reduced rank regression (response variables: monounsaturated fat, polyunsaturated fat, and saturated fat based on two 24-hour dietary assessments. Multivariable logistic and linear regression were used to investigate associations between DPs and odds of elevated CVD risk (using the nonlaboratory Framingham Risk Score) and changes in early CVD markers, respectively. DP1 (characterized by higher nuts and seeds and lower fruit and legumes intake) was positively correlated with saturated fat, monounsaturated fat, and polyunsaturated fat; DP2 (characterized by higher butter and high-fat cheese, lower nuts and seeds intake) was positively correlated with saturated fat and negatively with polyunsaturated fat and monounsaturated fat. DP2 was associated with slightly higher odds of elevated CVD risk (odds ratio, 1.04 [95% CI, 1.00-1.07]). DP1 was associated with higher diastolic blood pressure (ß, 0.20 [95% CI, 0.01-0.37]) and lower cardiac index (ß, -0.02 [95% CI, -0.04 to -0.01]); DP2 was associated with higher carotid intima medial thickness (ß, 1.80 [95% CI, 0.01-3.59]) and lower left ventricular ejection fraction (ß, -0.15 [95% CI, -0.24 to -0.07]) and cardiac index (ß, -0.01 [95% CI, -0.02 to -0.01]). Conclusions This study suggests small but statistically significant associations between DPs based on fat type and some early markers of CVD risk. Further research is needed to confirm these associations.

Associations between three diet quality indices, genetic risk and body composition: A prospective cohort study.

BACKGROUND & AIMS: Diet and genetic predisposition to adiposity are independent predictors of body composition, yet few cohort studies have examined the association between overall diet quality indices, genetic risk and body composition. This study examined the prospective association of three diet quality indices and a polygenic risk score (PRS) with trunk fat mass, total fat mass, lean mass and bone mineral content. METHODS: Adults from UK Biobank cohort were included. Dietary intake was assessed using the Oxford WebQ and three diet quality indices calculated: Recommended Food Score (RFS); Mediterranean Diet Score (MDS); Healthy Diet Indicator (HDI). Bioimpedance data were available for trunk fat, total fat and lean mass (kg). Trunk fat mass (kg), total fat mass (kg) and lean mass (kg) were assessed using bioelectrical impedance (BIA) in 17,478 adults. Bone mineral content (g) was available from dual energy x-ray absorptiometry (DXA) scans in 11,887 participants. Linear regression analyses, adjusted for demographic and lifestyle confounders, were used to estimate prospective associations between each diet quality index and body composition outcomes. A PRS created from 97 adiposity-related single nucleotide polymorphisms was used to examine interaction effects. RESULTS: A total of 17,478 adults (M = 55.9, SD 7.5 years) were followed up for up to 10 years. RFS, HDI and MDS were inversely associated with trunk fat (RFS: B -0.29; 95% CI: -0.33, -0.25; HDI: -0.23; -0.27, -0.19; MDS: -0.22; -0.26, -0.18), total fat (RFS: B -0.49; 95% CI: -0.56, -0.42; HDI: -0.38; -0.45, -0.32; MDS: -0.38; -0.44, -0.32) and lean (RFS: B -0.10; 95% CI: -0.14, -0.06; HDI: -0.07; -0.11, -0.03; MDS: -0.07; -0.11, -0.04) mass. Diet quality was positively associated with bone mineral content (RFS: B 8.23; 95% CI: 2.14, 14.3; HDI: 6.77; 1.00, 12.5). There was evidence of non-linear associations between diet quality (RFS and HDI only) and trunk fat (p < 0.01) and total fat mass (p < 0.05). There was limited evidence PRS was associated with body composition, with interaction effects of PRS and HDI (p-interaction = 0.039) and MDS (p-interaction = 0.031) on total fat mass. CONCLUSION: Higher diet quality was associated with lower trunk fat, total fat and lean mass, regardless of the diet quality index examined (RFS, HDI or MDS), while higher diet quality (RFS and HDI only) was associated with higher bone mineral content. The benefit of higher diet quality on reducing total fat mass was most evident in individuals with higher generic risk of adiposity. These findings underscore the importance of a high-quality diet for maintaining optimal body composition, particularly in individuals with genetic pre-disposition to adiposity.

Is vascular insulin resistance an early step in diet-induced whole-body insulin resistance?

There is increasing evidence that skeletal muscle microvascular (capillary) blood flow plays an important role in glucose metabolism by increasing the delivery of glucose and insulin to the myocytes. This process is impaired in insulin-resistant individuals. Studies suggest that in diet-induced insulin-resistant rodents, insulin-mediated skeletal muscle microvascular blood flow is impaired post-short-term high fat feeding, and this occurs before the development of myocyte or whole-body insulin resistance. These data suggest that impaired skeletal muscle microvascular blood flow is an early vascular step before the onset of insulin resistance. However, evidence of this is still lacking in humans. In this review, we summarise what is known about short-term high-calorie and/or high-fat feeding in humans. We also explore selected animal studies to identify potential mechanisms. We discuss future directions aimed at better understanding the 'early' vascular mechanisms that lead to insulin resistance as this will provide the opportunity for much earlier screening and timing of intervention to assist in preventing type 2 diabetes.

FADS Polymorphism, Omega-3 Fatty Acids and Diabetes Risk: A Systematic Review.

The role of n-3 long chain polyunsaturated fatty acids (LC n-3 PUFA) in reducing the risk of type 2 diabetes (T2DM) is not well established. The synthesis of LC n-3 PUFA requires fatty acid desaturase enzymes, which are encoded by the FADS gene. It is unclear if FADS polymorphism and dietary fatty acid intake can influence plasma or erythrocyte membrane fatty acid profile and thereby the risk of T2DM. Thus, the aim of this systematic review was to assess the current evidence for an effect of FADS polymorphism on T2DM risk and understand its associations with serum/erythrocyte and dietary LC n-3 PUFA. A systematic search was performed using PubMed, Embase, Cochrane and Scopus databases. A total of five studies met the inclusion criteria and were included in the present review. This review identified that FADS polymorphism may alter plasma fatty acid composition and play a protective role in the development of T2DM. Serum and erythrocyte LC n-3 PUFA levels were not associated with risk of T2DM, while dietary intake of LC n-3 PUFA was associated with lower risk of T2DM in one study only. The effect of LC n-3 PUFA consumption on associations between FADS polymorphism and T2DM warrants further investigation.