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      Effects of medium chain triglycerides supplementation on insulin sensitivity and beta cell function: A feasibility study

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          Abstract

          Objective

          Medium chain triglycerides (MCT) have unique metabolic properties which may improve insulin sensitivity (Si) and beta cell function but data in humans are limited. We conducted a 6-week clinical trial of MCT oil supplementation.

          Methods

          22 subjects without diabetes (8 males, 14 females, mean ± standard error age 39±2.9 years, baseline BMI 27.0±1.4 kg/m 2) were counseled to maintain their body weight and physical activity (PA) during the trial. Dietary intake, PA data, body composition, and resting energy expenditure (REE) were obtained through dietary recall, international PA questionnaire, dual x-ray absorptiometry, and indirect calorimetry, respectively. MCT prescriptions were given based on REE and PA to replace part of dietary fat with 30 grams of MCT per 2000 kcal daily. Insulin-modified frequently sampled intravenous glucose tolerance tests were performed before and after MCT to measure changes in Si, acute insulin response (AIR), disposition index (DI), and glucose effectiveness (Sg).

          Results

          MCT were well tolerated and weight remained stable (mean change 0.3 kg, p = 0.39). Fasting REE, respiratory quotient, and body composition were stable during the intervention. There were no significant changes in mean fasting glucose, insulin, insulin resistance, fasting total ketones, Si, AIR, DI, Sg, leptin, fructosamine, and proinsulin. The mean change in Si was 0.5 10 −4 min -1 per mU/L (95% CI: -1.4, 2.4), corresponding to a 12% increase from baseline, and the range was -4.7 to 12.9 10 −4 min -1 per mU/L. Mean total adiponectin decreased significantly from 22925 ng/mL at baseline to 17598 ng/mL at final visit (p = 0.02). The baseline clinical and laboratory parameters were not significantly associated with the change in Si.

          Discussion

          There were a wide range of changes in the minimal model parameters of glucose and insulin metabolism in subjects following 6 weeks of MCT as an isocaloric substitution for part of usual dietary fat intake. Since this was a single-arm non-randomized study without a control group, it cannot be certain whether these changes were due to MCT so further randomized controlled trials are warranted.

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          Most cited references54

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          Insulin resistance and risk of congestive heart failure.

          Diabetes and obesity are established risk factors for congestive heart failure (CHF) and are both associated with insulin resistance. To explore if insulin resistance may predict CHF and may provide the link between obesity and CHF. The Uppsala Longitudinal Study of Adult Men, a prospective, community-based, observational cohort in Uppsala, Sweden. We investigated 1187 elderly (>or=70 years) men free from CHF and valvular disease at baseline between 1990 and 1995, with follow-up until the end of 2002. Variables reflecting insulin sensitivity (including euglycemic insulin clamp glucose disposal rate) and obesity were analyzed together with established risk factors (prior myocardial infarction, hypertension, diabetes, electrocardiographic left ventricular hypertrophy, smoking, and serum cholesterol level) as predictors of subsequent incidence of CHF, using Cox proportional hazards analyses. First hospitalization for heart failure. One hundred four men developed CHF during a median follow-up of 8.9 (range, 0.01-11.4) years. In multivariable Cox proportional hazards models adjusted for established risk factors for CHF, increased risk of CHF was associated with a 1-SD increase in the 2-hour glucose value of an oral glucose tolerance test (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.08-1.93), fasting serum proinsulin level (HR, 1.29; 95% CI, 1.02-1.64), body mass index (HR, 1.35; 95% CI, 1.11-1.65), and waist circumference (HR, 1.36; 95% CI, 1.10-1.69), whereas a 1-SD increase in clamp glucose disposal rate decreased the risk (HR, 0.66; 95% CI, 0.51-0.86). When adding clamp glucose disposal rate to these models as a covariate, the obesity variables were no longer significant predictors of subsequent CHF. Insulin resistance predicted CHF incidence independently of established risk factors including diabetes in our large community-based sample of elderly men. The previously described association between obesity and subsequent CHF may be mediated largely by insulin resistance.
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            Flavonoids, Dairy Foods, and Cardiovascular and Metabolic Health

            A growing body of nutritional science highlights the complex mechanisms and pleiotropic pathways of cardiometabolic effects of different foods. Among these, some of the most exciting advances are occurring in the area of flavonoids, bioactive phytochemicals found in plant foods; and in the area of dairy, including milk, yogurt, and cheese. Many of the relevant ingredients and mechanistic pathways are now being clarified, shedding new light on both the ingredients and the pathways for how diet influences health and well-being. Flavonoids, for example, have effects on skeletal muscle, adipocytes, liver, and pancreas, and myocardial, renal, and immune cells, for instance, related to 5'-monophosphate-activated protein kinase phosphorylation, endothelial NO synthase activation, and suppression of NF-κB (nuclear factor-κB) and TLR4 (toll-like receptor 4). Effects of dairy are similarly complex and may be mediated by specific amino acids, medium-chain and odd-chain saturated fats, unsaturated fats, branched-chain fats, natural trans fats, probiotics, vitamin K1/K2, and calcium, as well as by processing such as fermentation and homogenization. These characteristics of dairy foods influence diverse pathways including related to mammalian target of rapamycin, silent information regulator transcript-1, angiotensin-converting enzyme, peroxisome proliferator-activated receptors, osteocalcin, matrix glutamate protein, hepatic de novo lipogenesis, hepatic and adipose fatty acid oxidation and inflammation, and gut microbiome interactions such as intestinal integrity and endotoxemia. The complexity of these emerging pathways and corresponding biological responses highlights the rapid advances in nutritional science and the continued need to generate robust empirical evidence on the mechanistic and clinical effects of specific foods.
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              MINMOD Millennium: a computer program to calculate glucose effectiveness and insulin sensitivity from the frequently sampled intravenous glucose tolerance test.

              The Bergman Minimal Model enables estimation of two key indices of glucose/insulin dynamics: glucose effectiveness and insulin sensitivity. In this paper we describe MINMOD Millennium, the latest Windows-based version of minimal model software. Extensive beta testing of MINMOD Millennium has shown that it is user-friendly, fully automatic, fast, accurate, reproducible, repeatable, and highly concordant with past versions of MINMOD. It has a simple interface, a comprehensive help system, an input file editor, a file converter, an intelligent processing kernel, and a file exporter. It provides publication-quality charts of glucose and insulin and a table of all minimal model parameters and their error estimates. In contrast to earlier versions of MINMOD and some other minimal model programs, Millennium provides identified estimates of insulin sensitivity and glucose effectiveness for almost every subject.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: ResourcesRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: Project administrationRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: Resources
                Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administration
                Role: ConceptualizationRole: Funding acquisitionRole: Project administrationRole: ResourcesRole: Software
                Role: Data curationRole: Investigation
                Role: InvestigationRole: Methodology
                Role: Formal analysisRole: Investigation
                Role: Formal analysisRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: VisualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: ResourcesRole: SoftwareRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: Project administrationRole: ResourcesRole: SoftwareRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                23 December 2019
                2019
                : 14
                : 12
                : e0226200
                Affiliations
                [1 ] Department of Medicine, Section of Endocrinology, Diabetes, Nutrition and Weight Management, Boston University, MA, United States of America
                [2 ] Department of Medicine, Section of Endocrinology, Diabetes and Nutrition and Weight Management, Nutrition and Weight Management Center, Boston Medical Center, Boston, MA, United States of America
                [3 ] Boston University School of Medicine, Boston, MA, United States of America
                [4 ] Department of Biostatistics, Boston University School of Public Health, Boston, MA, United States of America
                University of Alabama at Birmingham, UNITED STATES
                Author notes

                Competing Interests: Dr. Apovian has participated on advisory boards for Nutrisystem, Zafgen, Sanofi-Aventis, Orexigen, EnteroMedics, GI Dynamics, Gelesis, Novo Nordisk, Bariatrix, Xeno Biosciences, Rhythm Pharmaceuticals, Eisai, and Scientific Intake; received research funding from Aspire Bariatrics, GI Dynamics, Takeda, the Vela Foundation, Gelesis, Energesis, Coherence Lab and Novo Nordisk; and owned stock in Science-Smart LLC. These disclosures do not constitute a competing interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

                Author information
                http://orcid.org/0000-0002-8838-2992
                http://orcid.org/0000-0002-5467-1630
                http://orcid.org/0000-0002-8029-1922
                Article
                PONE-D-19-13049
                10.1371/journal.pone.0226200
                6927614
                31869355
                3a0b9f84-55f2-4bdf-a162-990239e164cb
                © 2019 Thomas et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 30 May 2019
                : 20 November 2019
                Page count
                Figures: 1, Tables: 3, Pages: 16
                Funding
                Funded by: National Institutes of Health
                Award ID: UL1TR001430
                Funded by: National Institutes of Health
                Award ID: P30DK046200
                Funded by: National Institutes of Health
                Award ID: T32DK007201
                Award Recipient :
                CA received a grant from the Boston University Clinical and Translational Science Institute (UL1TR001430, https://www.bu.edu/ctsi/) along with internal funding from the Department of Medicine ( http://www.bumc.bu.edu/medicine/). DT was supported in part by the National Institutes of Health [UL1TR001430, P30DK046200, T32DK007201]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Endocrinology
                Diabetic Endocrinology
                Insulin
                Biology and Life Sciences
                Biochemistry
                Hormones
                Insulin
                Biology and Life Sciences
                Biochemistry
                Lipids
                Oils
                Biology and Life Sciences
                Physiology
                Immune Physiology
                Cytokines
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