title: Effects of Saturated Fat, Polyunsaturated Fat, Monounsaturated Fat, and Carbohydrate on Glucose-Insulin Homeostasis: A Systematic Review and Meta-analysis of Randomised Controlled Feeding Trials.
abstract: BACKGROUND
  Effects of major dietary macronutrients on glucose-insulin homeostasis remain controversial and may vary by the clinical measures examined. We aimed to assess how saturated fat (SFA), monounsaturated fat (MUFA), polyunsaturated fat (PUFA), and carbohydrate affect key metrics of glucose-insulin homeostasis.
  
  
  RESULTS
  We systematically searched multiple databases (PubMed, EMBASE, OVID, BIOSIS, Web-of-Knowledge, CAB, CINAHL, Cochrane Library, SIGLE, Faculty1000) for randomised controlled feeding trials published by 26 Nov 2015 that tested effects of macronutrient intake on blood glucose, insulin, HbA1c, insulin sensitivity, and insulin secretion in adults aged ≥18 years. We excluded trials with non-isocaloric comparisons and trials providing dietary advice or supplements rather than meals. Studies were reviewed and data extracted independently in duplicate. Among 6,124 abstracts, 102 trials, including 239 diet arms and 4,220 adults, met eligibility requirements. Using multiple-treatment meta-regression, we estimated dose-response effects of isocaloric replacements between SFA, MUFA, PUFA, and carbohydrate, adjusted for protein, trans fat, and dietary fibre. Replacing 5% energy from carbohydrate with SFA had no significant effect on fasting glucose (+0.02 mmol/L, 95% CI = -0.01, +0.04; n trials = 99), but lowered fasting insulin (-1.1 pmol/L; -1.7, -0.5; n = 90). Replacing carbohydrate with MUFA lowered HbA1c (-0.09%; -0.12, -0.05; n = 23), 2 h post-challenge insulin (-20.3 pmol/L; -32.2, -8.4; n = 11), and homeostasis model assessment for insulin resistance (HOMA-IR) (-2.4%; -4.6, -0.3; n = 30). Replacing carbohydrate with PUFA significantly lowered HbA1c (-0.11%; -0.17, -0.05) and fasting insulin (-1.6 pmol/L; -2.8, -0.4). Replacing SFA with PUFA significantly lowered glucose, HbA1c, C-peptide, and HOMA. Based on gold-standard acute insulin response in ten trials, PUFA significantly improved insulin secretion capacity (+0.5 pmol/L/min; 0.2, 0.8) whether replacing carbohydrate, SFA, or even MUFA. No significant effects of any macronutrient replacements were observed for 2 h post-challenge glucose or insulin sensitivity (minimal-model index). Limitations included a small number of trials for some outcomes and potential issues of blinding, compliance, generalisability, heterogeneity due to unmeasured factors, and publication bias.
  
  
  CONCLUSIONS
  This meta-analysis of randomised controlled feeding trials provides evidence that dietary macronutrients have diverse effects on glucose-insulin homeostasis. In comparison to carbohydrate, SFA, or MUFA, most consistent favourable effects were seen with PUFA, which was linked to improved glycaemia, insulin resistance, and insulin secretion capacity.
authors.affiliation: Medical Research Council Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Fumiaki
authors.identifier: http://orcid.org/0000-0002-6841-8396
authors.initials: F
authors.lastname: Imamura
authors.affiliation: Tufts Friedman School of Nutrition Science & Policy, Boston, Massachusetts, United States of America.
authors.forename: Renata
authors.initials: R
authors.lastname: Micha
authors.affiliation: George Institute for Global Health, The University of Sydney, Sydney Medical School, Camperdown, Australia.
authors.forename: Jason H Y
authors.initials: JH
authors.lastname: Wu
authors.affiliation: Department of Epidemiology, Human Genetics & Environmental Sciences, The University of Texas Health Science Center at Houston, Houston, Texas, United States of America.
authors.forename: Marcia C
authors.initials: MC
authors.lastname: de Oliveira Otto
authors.affiliation: Department of Neurology, University of Miami Miller School of Medicine/Jackson Memorial Hospital, Miami, Florida, United States of America.
authors.forename: Fadar O
authors.identifier: http://orcid.org/0000-0003-2167-5034
authors.initials: FO
authors.lastname: Otite
authors.affiliation: Department of Global Health and Population, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Ajibola I
authors.identifier: http://orcid.org/0000-0002-6632-613X
authors.initials: AI
authors.lastname: Abioye
authors.affiliation: Tufts Friedman School of Nutrition Science & Policy, Boston, Massachusetts, United States of America.
authors.forename: Dariush
authors.initials: D
authors.lastname: Mozaffarian
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis* / Q000502:physiology; D004040:Dietary Carbohydrates / Q000009:adverse effects*; D005224:Fats, Unsaturated / Q000009:adverse effects*; D005229:Fatty Acids, Monounsaturated / Q000009:adverse effects*; D005231:Fatty Acids, Unsaturated / Q000009:adverse effects*; D006442:Glycated Hemoglobin / Q000032:analysis; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000097:blood* / Q000502:physiology; D016032:Randomized Controlled Trials as Topic
chemical_list: D001786:Blood Glucose; D004040:Dietary Carbohydrates; D005224:Fats, Unsaturated; D005229:Fatty Acids, Monounsaturated; D005231:Fatty Acids, Unsaturated; D006442:Glycated Hemoglobin; D007328:Insulin; C517652:hemoglobin A1c protein, human