Abstract P277: ‘Catalytic’ Doses of Fructose Improve Glycemic Control but Not Insulin Resistance: A Systematic Review and Meta-Analysis of Controlled Feeding Trials

Abstract

Objective: Contrary to concerns that fructose may have adverse metabolic effects, an emerging literature has shown that low-dose fructose at a level obtainable from fruit ( < 40-g/day) may benefit glycemic control. This effect appears to be mediated by upregulation of glucokinase, leading to increased hepatic glycogen synthesis. Whether this ‘catalytic’ mechanism of fructose will manifest as an increase in hepatic insulin sensitivity is unclear. To address this question, we synthesized evidence from controlled feeding trials assessing the effect of small ‘catalytic’ fructose doses on HbA1c, fasting blood glucose, and homeostasis model assessment of insulin resistance (HOMA-IR). Methods: We searched MEDLINE, EMBASE, and Cochrane Library through October 6, 2015. We included controlled feeding trials of > 7 days investigating the effect of small ‘catalytic’ fructose doses ( < 40-g/day) in isoenergetic exchange for other carbohydrates. Two independent reviewers extracted relevant data and risk of bias (Cochrane Risk of Bias Tool). Data were pooled using the generic inverse variance method and expressed as mean differences (MD) with 95% confidence intervals (CIs). Heterogeneity was assessed (Cochran Q statistic) and quantified (I 2 statistic). Results: Nine trials (n= 153) met the eligibility criteria. ‘Catalytic’ doses of fructose significantly reduced HbA1c (MD= -0.40% [95% CI -0.72 to -0.08%]) and fasting blood glucose (MD= -0.18 mmol/L [95% CI -0.35 to -0.02 mmol/L]). There was no effect on HOMA-IR (MD= 0.04 [95% CI -0.14 to 0.22]). Limitations: The available trials were small (median sample size, n= 20) and of short duration (median follow-up, 2 weeks). Conclusion: Pooled analyses indicate that small ‘catalytic’ doses of fructose in isoenergetic exchange for other carbohydrates improve aspects of glycemic control, but the effect does not appear to be mediated through an improvement in hepatic insulin sensitivity. There is a need for larger and longer ( > 6 months) high quality randomized trials to confirm these results.