Abstract
BackgroundEffects 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 FindingsWe 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.ConclusionsThis 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.
Highlights
The prevalence of insulin resistance and type 2 diabetes is rising sharply in most nations globally [1,2], highlighting the need for broad preventive therapies
saturated fat (SFA), or monounsaturated fat (MUFA), most consistent favourable effects were seen with polyunsaturated fat (PUFA), which was linked to improved glycaemia, insulin resistance, and insulin secretion capacity
Dietary guidelines on macronutrient intake to improve glucose-insulin profiles and reduce or prevent type 2 diabetes generally recommend increasing foods rich in monounsaturated fat (MUFA) and reducing saturated fat (SFA) [3,4,5,6]. These guidelines have emphasized the major gaps in established evidence for effects of dietary fats and carbohydrate on glucose-insulin homeostasis, including uncertainty as to whether benefits of MUFA in some trials were confounded by caloric restriction and limited evidence on effects of either polyunsaturated fat (PUFA) or SFA [3,4,5,6,7]
Summary
The prevalence of insulin resistance and type 2 diabetes is rising sharply in most nations globally [1,2], highlighting the need for broad preventive therapies. Prior knowledge has been limited by several factors, including focus on limited metrics to assess glucose-insulin homeostasis (e.g., fasting glucose alone), rather than studying multiple relevant outcomes, such as HbA1c, fasting insulin, insulin resistance, insulin secretion capacity, and post-challenge measures [8]; insufficient statistical power in many smaller trials to confirm important effects; and difficulties in evaluating results of individual trials due to multiple and varying changes in several macronutrients simultaneously [8,9,10,11] Due to these challenges, the effects of dietary fats and carbohydrate on glucose-insulin homeostasis remains uncertain [8]. We aimed to assess how saturated fat (SFA), monounsaturated fat (MUFA), polyunsaturated fat (PUFA), and carbohydrate affect key metrics of glucose-insulin homeostasis
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