title: Effect of fructose consumption on insulin sensitivity in nondiabetic subjects: a systematic review and meta-analysis of diet-intervention trials.
abstract: 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.
  
  
  
  We searched MEDLINE, EMBASE, and the Cochrane Library for relevant trials on the basis of predetermined eligibility criteria. Two investigators independently performed the study selection, quality assessment, and data extraction. Results were pooled with the use of the generic inverse-variance method with random effects weighting and were expressed as mean differences (MDs) or standardized mean differences (SMDs) with 95% CIs.
  
  
  
  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.
authors.affiliation: Departments of Endocrinology and Metabolism, k.w.terhorst@amc.nl.
authors.forename: Kasper W
authors.identifier: 0000-0002-0502-4023
authors.initials: KW
authors.lastname: Ter Horst
authors.affiliation: Departments of Endocrinology and Metabolism.
authors.forename: Merle R
authors.initials: MR
authors.lastname: Schene
authors.affiliation: Medical Informatics, and.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Holman
authors.affiliation: Medicine, Academic Medical Center, Amsterdam, Netherlands.
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Romijn
authors.affiliation: Departments of Endocrinology and Metabolism.
authors.forename: Mireille J
authors.initials: MJ
authors.lastname: Serlie
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D016208:Databases, Factual; D003920:Diabetes Mellitus; D004032:Diet; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D005215:Fasting; D005632:Fructose / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D016032:Randomized Controlled Trials as Topic
chemical_list: D001786:Blood Glucose; D004040:Dietary Carbohydrates; D007328:Insulin; D005632:Fructose
keywords: fructose; glucose clamp; glucose disposal; insulin; insulin resistance; meta-analysis