High fructose consumption has been suggested to contribute to several features of metabolic syndrome including insulin resistance, but to our knowledge, no previous meta-analyses have investigated the effect of fructose on insulin sensitivity in nondiabetic subjects.
We performed a systematic review and meta-analysis of controlled diet-intervention studies in nondiabetic subjects to determine the effect of fructose on insulin sensitivity.
Twenty-nine articles that described 46 comparisons in 1005 normal-weight and overweight or obese participants met the eligibility criteria. An energy-matched (isocaloric) exchange of dietary carbohydrates by fructose promoted hepatic insulin resistance (SMD: 0.47; 95% CI: 0.03, 0.91; P = 0.04) but had no effect on fasting plasma insulin concentrations (MD: −0.79 pmol/L; 95% CI: −6.41, 4.84 pmol/L; P = 0.78), the homeostasis model assessment of insulin resistance (HOMA-IR) (MD: 0.13; 95% CI: −0.07, 0.34; P = 0.21), or glucose disposal rates under euglycemic hyperinsulinemic clamp conditions (SMD: 0.00; 95% CI: 20.41, 0.41; P = 1.00). Hypercaloric fructose (∼25% excess of energy compared with that of the weight-maintenance control diet) raised fasting plasma insulin concentrations (MD: 3.38 pmol/L; 95% CI: 0.03, 6.73 pmol/L; P < 0.05) and induced hepatic insulin resistance (SMD: 0.77; 95% CI: 0.28, 1.26; P < 0.01) without affecting the HOMA-IR (MD: 0.18; 95% CI: −0.02, 0.39; P = 0.08) or glucose disposal rates (SMD: 0.10; 95% CI: −0.21, 0.40; P = 0.54). Results may have been limited by the low quality, small sample size, and short duration (mostly <60 d) of included trials.
Short-term fructose consumption, in isocaloric exchange or in hypercaloric supplementation, promotes the development of hepatic insulin resistance in nondiabetic adults without affecting peripheral or muscle insulin sensitivity. Larger and longer-term studies are needed to assess whether real-world fructose consumption has adverse effects on insulin sensitivity and long-term outcomes.