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.