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Diet strongly affects human health, partly by modulating gut microbiome composition. We used diet inventories and 16S rDNA sequencing to characterize fecal samples from 98 individuals. Fecal communities clustered into enterotypes distinguished primarily by levels of Bacteroides and Prevotella. Enterotypes were strongly associated with long-term diets, particularly protein and animal fat (Bacteroides) versus carbohydrates (Prevotella). A controlled-feeding study of 10 subjects showed that microbiome composition changed detectably within 24 hours of initiating a high-fat/low-fiber or low-fat/high-fiber diet, but that enterotype identity remained stable during the 10-day study. Thus, alternative enterotype states are associated with long-term diet.

Impaired insulin sensitivity increases the risk of cardiovascular disease. Although calorie restriction and weight loss increase insulin sensitivity, the effects of modifying macronutrient composition on insulin sensitivity are uncertain. The purpose of this study is to determine the effects on insulin sensitivity of a carbohydrate-rich diet (CARB; similar to the Dietary Approaches to Stop Hypertension [DASH] diet), a protein-rich diet (PROT; protein predominantly from plant sources), and an unsaturated fat-rich diet (UNSAT; predominantly monounsaturated). This study was a randomized, controlled, three-period, crossover feeding study. The study participants were 164 individuals with prehypertension or stage 1 hypertension without diabetes. Diets were administered for 6 weeks each, with a washout period between diets of 2-4 weeks. Weight was held constant throughout the study. For our primary outcome, we calculated the quantitative insulin sensitivity check index (QUICKI) using the end-of-period fasting serum glucose and insulin. QUICKI is a validated measure of insulin sensitivity. The primary analyses used generalized estimating equations. At baseline, mean (SD) BMI was 30.2 (6.1) kg/m(2), and mean (SD) QUICKI was 0.35 (0.04). The UNSAT diet increased QUICKI by 0.005, more than the CARB diet (P = 0.04). PROT had no significant effect compared with CARB. A diet that partially replaces carbohydrate with unsaturated fat may improve insulin sensitivity in a population at risk for cardiovascular disease. Given the well-recognized challenges of sustaining weight loss, our results suggest an alternative approach for improving insulin sensitivity.

Dietary intake of saturated fat is a likely contributor to nonalcoholic fatty liver disease (NAFLD) and insulin resistance, but the mechanisms that initiate these abnormalities in humans remain unclear. We examined the effects of a single oral saturated fat load on insulin sensitivity, hepatic glucose metabolism, and lipid metabolism in humans. Similarly, initiating mechanisms were examined after an equivalent challenge in mice. Fourteen lean, healthy individuals randomly received either palm oil (PO) or vehicle (VCL). Hepatic metabolism was analyzed using in vivo 13C/31P/1H and ex vivo 2H magnetic resonance spectroscopy before and during hyperinsulinemic-euglycemic clamps with isotope dilution. Mice underwent identical clamp procedures and hepatic transcriptome analyses. PO administration decreased whole-body, hepatic, and adipose tissue insulin sensitivity by 25%, 15%, and 34%, respectively. Hepatic triglyceride and ATP content rose by 35% and 16%, respectively. Hepatic gluconeogenesis increased by 70%, and net glycogenolysis declined by 20%. Mouse transcriptomics revealed that PO differentially regulates predicted upstream regulators and pathways, including LPS, members of the TLR and PPAR families, NF-κB, and TNF-related weak inducer of apoptosis (TWEAK). Saturated fat ingestion rapidly increases hepatic lipid storage, energy metabolism, and insulin resistance. This is accompanied by regulation of hepatic gene expression and signaling that may contribute to development of NAFLD.REGISTRATION. ClinicalTrials.gov NCT01736202. Germany: Ministry of Innovation, Science, and Research North Rhine-Westfalia, German Federal Ministry of Health, Federal Ministry of Education and Research, German Center for Diabetes Research, German Research Foundation, and German Diabetes Association. Portugal: Portuguese Foundation for Science and Technology, FEDER - European Regional Development Fund, Portuguese Foundation for Science and Technology, and Rede Nacional de Ressonância Magnética Nuclear.

Aim Evidence of a possible connection between gut microbiota and several physiological processes linked to type 2 diabetes is increasing. However, the effect of multi-strain probiotics in people with type 2 diabetes remains unclear. This study investigated the effect of multi-strain microbial cell preparation—also refers to multi-strain probiotics—on glycemic control and other diabetes-related outcomes in people with type 2 diabetes. Design A randomized, double-blind, parallel-group, controlled clinical trial. Setting Diabetes clinic of a teaching hospital in Kuala Lumpur, Malaysia. Participants A total of 136 participants with type 2 diabetes, aged 30–70 years, were recruited and randomly assigned to receive either probiotics ( n  = 68) or placebo ( n  = 68) for 12 weeks. Outcomes Primary outcomes were glycemic control-related parameters, and secondary outcomes were anthropomorphic variables, lipid profile, blood pressure and high-sensitivity C-reactive protein. The Lactobacillus and Bifidobacterium quantities were measured before and after intervention as an indicator of successful passage of the supplement through gastrointestinal tract. Statistical analysis Intention-to-treat (ITT) analysis was performed on all participants, while per-protocol (PP) analysis was performed on those participants who had successfully completed the trial with good compliance rate. Results With respect to primary outcomes, glycated hemoglobin decreased by 0.14 % in the probiotics and increased by 0.02 % in the placebo group in PP analysis ( p  < 0.05, small effect size of 0.050), while these changes were not significant in ITT analysis. Fasting insulin increased by 1.8 µU/mL in placebo group and decreased by 2.9 µU/mL in probiotics group in PP analysis. These changes were significant between groups at both analyses ( p  < 0.05, medium effect size of 0.062 in PP analysis and small effect size of 0.033 in ITT analysis). Secondary outcomes did not change significantly. Probiotics successfully passed through the gastrointestinal tract. Conclusion Probiotics modestly improved HbA1c and fasting insulin in people with type 2 diabetes.

Background/Objectives: Snacks contribute toward a significant proportion of human total daily energy intake. This study investigated the effects of almonds, a satiating and nutrient-rich, common snack, on postprandial glycemia, appetite, short-term body weight and fasting blood parameters when consumed with meals or alone as a snack. Methods: This was a 4-week randomized, parallel-arm study that entailed consuming almonds (43 g/day) with breakfast (BF) or lunch (LN), alone as a morning (MS) or afternoon (AS) snack or no almonds (CL). Participants ( N =137) with increased risk for type 2 diabetes completed an oral glucose tolerance test (OGTT) and acute-feeding session at baseline, followed by almond consumption for 4 weeks before repeating the OGTT and acute-feeding trials. Anthropometric, biochemical and appetite responses were assessed. Results: Almonds lowered serum glucose responses postprandially. Effects were most prominent in the snack groups. Almonds, consumed as snacks, also reduced hunger and desire to eat during the acute-feeding session. After 4 weeks, anthropometric measurements and fasting blood biochemistries did not differ from the control group or across intervention groups. Without specific guidance, daily energy intake was reduced to compensate for energy from the provided almonds. Dietary monounsaturated fat and α-tocopherol intakes were significantly increased in all almond groups. Conclusion: Almonds provide post-ingestive metabolic and appetitive benefits and did not increase the risk for weight gain. This suggests that almonds may be a healthful snack option.

Aims/hypothesisEnergy-dense nutrition generally induces insulin resistance, but dietary composition may differently affect glucose metabolism. This study investigated initial effects of monounsaturated vs saturated lipid meals on basal and insulin-stimulated myocellular glucose metabolism and insulin signalling.MethodsIn a randomised crossover study, 16 lean metabolically healthy volunteers received single meals containing safflower oil (SAF), palm oil (PAL) or vehicle (VCL). Whole-body glucose metabolism was assessed from glucose disposal (Rd) before and during hyperinsulinaemic–euglycaemic clamps with d-[6,6-2H2]glucose. In serial skeletal muscle biopsies, subcellular lipid metabolites and insulin signalling were measured before and after meals.ResultsSAF and PAL raised plasma oleate, but only PAL significantly increased plasma palmitate concentrations. SAF and PAL increased myocellular diacylglycerol and activated protein kinase C (PKC) isoform θ (p < 0.05) but only PAL activated PKCɛ. Moreover, PAL led to increased myocellular ceramides along with stimulated PKCζ translocation (p < 0.05 vs SAF). During clamp, SAF and PAL both decreased insulin-stimulated Rd (p < 0.05 vs VCL), but non-oxidative glucose disposal was lower after PAL compared with SAF (p < 0.05). Muscle serine1101-phosphorylation of IRS-1 was increased upon SAF and PAL consumption (p < 0.05), whereas PAL decreased serine473-phosphorylation of Akt more than SAF (p < 0.05).Conclusions/interpretationLipid-induced myocellular insulin resistance is likely more pronounced with palmitate than with oleate and is associated with PKC isoforms activation and inhibitory insulin signalling.Trial registrationClinicalTrials.gov.NCT01736202.FundingGerman Federal Ministry of Health, Ministry of Culture and Science of the State North Rhine-Westphalia, German Federal Ministry of Education and Research, European Regional Development Fund, German Research Foundation, German Center for Diabetes Research.

Background: Excessive energy intake and obesity lead to the metabolic syndrome (MetS). Dietary saturated fatty acids (SFAs) may be particularly detrimental on insulin sensitivity (SI) and on other components of the MetS. Objective: This study determined the relative efficacy of reducing dietary SFA, by isoenergetic alteration of the quality and quantity of dietary fat, on risk factors associated with MetS. Design: A free-living, single-blinded dietary intervention study. Subjects and Methods: MetS subjects (n = 417) from eight European countries completed the randomized dietary intervention study with four isoenergetic diets distinct in fat quantity and quality: high-SFA; high-monounsaturated fatty acids and two low-fat, high-complex carbohydrate (LFHCC) diets, supplemented with long chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs) (1.2 g per day) or placebo for 12 weeks. SI estimated from an intravenous glucose tolerance test (IVGTT) was the primary outcome measure. Lipid and inflammatory markers associated with MetS were also determined. Results: In weight-stable subjects, reducing dietary SFA intake had no effect on SI, total and low-density lipoprotein cholesterol concentration, inflammation or blood pressure in the entire cohort. The LFHCC n-3 PUFA diet reduced plasma triacylglycerol (TAG) and non-esterified fatty acid concentrations (P<0.01), particularly in men. Conclusion: There was no effect of reducing SFA on SI in weight-stable obese MetS subjects. LC n-3 PUFA supplementation, in association with a low-fat diet, improved TAG-related MetS risk profiles. International Journal of Obesity (2011) 35, 800-809; doi:10.1038/ijo.2010.209; published online 12 October 2010

Relative to diets enriched in palmitic acid (PA), diets rich in oleic acid (OA) are associated with reduced risk of type 2 diabetes. To gain insight into mechanisms underlying these observations, we applied comprehensive lipidomic profiling to specimens collected from healthy adults enrolled in a randomized, crossover trial comparing a high-PA diet to a low-PA/high-OA (HOA) diet. Effects on insulin sensitivity (SI) and disposition index (DI) were assessed by intravenous glucose tolerance testing. In women, but not men, SI and DI were higher during HOA. The effect of HOA on SI correlated positively with physical fitness upon enrollment. Principal components analysis of either fasted or fed-state metabolites identified one factor affected by diet and heavily weighted by the PA/OA ratio of serum and muscle lipids. In women, this factor correlated inversely with SI in the fasted and fed states. Medium-chain acylcarnitines emerged as strong negative correlates of SI, and the HOA diet was accompanied by lower serum and muscle ceramide concentrations and reductions in molecular biomarkers of inflammatory and oxidative stress. This study provides evidence that the dietary PA/OA ratio impacts diabetes risk in women.

This randomized trial compared the effect of reduced-calorie diets with various compositions of fat, protein, and carbohydrates on weight loss over a 2-year period. Compliance with the diets was not high. No significant differences in weight loss were observed among the various diets. Reduced-calorie diets appear to have similar effects on weight loss regardless of their particular compositions. This randomized trial compared the effect of reduced-calorie diets with various compositions of fat, protein, and carbohydrates on weight loss over a 2-year period. No significant differences in weight loss were observed among the various diets. There is intense debate about what types of diet are most effective for treating overweight — those that emphasize protein, those that emphasize carbohydrates, or those that emphasize fat. 1 – 3 Several trials showed that low-carbohydrate, high-protein diets resulted in more weight loss over the course of 3 to 6 months than conventional high-carbohydrate, low-fat diets, 4 – 12 but other studies did not show this effect. 13 – 17 A smaller group of studies that extended the follow-up to 1 year did not show that low-carbohydrate, high-protein diets were superior to high-carbohydrate, low-fat diets. 6 , 10 , 16 , 18 – 21 In contrast, other researchers found that . . .

Objectives To quantify global consumption of key dietary fats and oils by country, age, and sex in 1990 and 2010. Design Data were identified, obtained, and assessed among adults in 16 age- and sex-specific groups from dietary surveys worldwide on saturated, omega 6, seafood omega 3, plant omega 3, and trans fats, and dietary cholesterol. We included 266 surveys in adults (83% nationally representative) comprising 1 630 069 unique individuals, representing 113 of 187 countries and 82% of the global population. A multilevel hierarchical Bayesian model accounted for differences in national and regional levels of missing data, measurement incomparability, study representativeness, and sampling and modelling uncertainty. Setting and population Global adult population, by age, sex, country, and time. Results In 2010, global saturated fat consumption was 9.4%E (95%UI=9.2 to 9.5); country-specific intakes varied dramatically from 2.3 to 27.5%E; in 75 of 187 countries representing 61.8% of the world’s adult population, the mean intake was <10%E. Country-specific omega 6 consumption ranged from 1.2 to 12.5%E (global mean=5.9%E); corresponding range was 0.2 to 6.5%E (1.4%E) for trans fat; 97 to 440 mg/day (228 mg/day) for dietary cholesterol; 5 to 3,886 mg/day (163 mg/day) for seafood omega 3; and <100 to 5,542 mg/day (1,371 mg/day) for plant omega 3. Countries representing 52.4% of the global population had national mean intakes for omega 6 fat ≥5%E; corresponding proportions meeting optimal intakes were 0.6% for trans fat (≤0.5%E); 87.6% for dietary cholesterol (<300 mg/day); 18.9% for seafood omega 3 fat (≥250 mg/day); and 43.9% for plant omega 3 fat (≥1,100 mg/day). Trans fat intakes were generally higher at younger ages; and dietary cholesterol and seafood omega 3 fats generally higher at older ages. Intakes were similar by sex. Between 1990 and 2010, global saturated fat, dietary cholesterol, and trans fat intakes remained stable, while omega 6, seafood omega 3, and plant omega 3 fat intakes each increased. Conclusions These novel global data on dietary fats and oils identify dramatic diversity across nations and inform policies and priorities for improving global health.