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.

Methods and findings: 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.

Fig 1. Flow diagram of systematic review of published trials evaluating effects of isocaloric replacement between macronutrient consumption on glucose homeostasis.

*See S3 Text for details of the databases, eligibility criteria, search terms, and prior review articles.

Fig 2. Effects on fasting glucose of isocaloric replacements between carbohydrate (CHO), saturated fat (SFA), monounsaturated fat (MUFA), and polyunsaturated fat (PUFA) in randomised controlled feeding trials.

Values represent pooled mean effects (95% CI) of specified macronutrient replacements, with other macronutrients held constant. *Significant heterogeneity across strata after correction for false-discovery rate (exploration of multiple characteristics for heterogeneity). †Estimates not shown due to wide 95% CIs; see S3 Table for numeric information. 1 mg/dL = 0.0555 mmol/L.

Fig 3. Effects on fasting insulin of isocaloric replacements between carbohydrate (CHO), saturated fat (SFA), monounsaturated fat (MUFA), and polyunsaturated fat (PUFA) in randomised controlled feeding trials.

Values represent pooled mean effects (95% CI) of specified macronutrient replacements, with other macronutrients held constant. No significant sources of heterogeneity were detected. †Estimates not shown due to wide, 95% CIs; see S3 Table for numeric information. 1 μIU/mL = 6 pmol/L.