A dual sugar challenge test for lipogenic sensitivity to dietary fructose

J Clin Endocrinol Metab. 2011 Mar;96(3):861-8. doi: 10.1210/jc.2010-2007. Epub 2011 Jan 20.


Context: Increased hepatic de novo lipogenesis (DNL) in response to dietary sugar is implicated in dyslipidemia, fatty liver, and insulin resistance.

Objective: The aim of the study was to develop a simple outpatient tolerance test for lipogenic sensitivity to dietary sugar.

Design and setting: In inpatients given repeated doses of fructose, protocol 1 compared the acute increase in DNL determined from the percentage of palmitate ("new palmitate") and the percentage of isotopically labeled palmitate ("%DNL") in very low-density lipoprotein triglyceride (TG). Protocol 2 compared the increase in new palmitate in outpatients given three different sugar beverages in a randomized crossover design.

Participants: There were 15 lean and overweight volunteers in protocol 1 and 15 overweight volunteers in protocol 2.

Interventions: In protocol 1, subjects received 1.4 g/kg fructose in divided oral doses over 6 h; in protocol 2, subjects received 0.5 g/kg fructose, 0.5 g/kg fructose plus 0.5 g/kg glucose, or 1 g/kg fructose plus 1 g/kg glucose each as a single oral bolus.

Main outcome measures: We measured the increase in DNL by two methods.

Results: After repeated doses of fructose, new palmitate was significantly correlated with the increase in %DNL (Δ, r = 0.814; P < 0.001) and with fasting insulin levels (area under the curve, r = 0.754; P = 0.001). After a single sugar dose, new palmitate showed a dose effect and was greater after fructose plus glucose. Very low-density lipoprotein TG and total TG significantly increased in both protocols.

Conclusions: A single oral bolus of fructose and glucose rapidly increases serum TG and TG palmitate in overweight subjects. A dual sugar challenge test could prove useful to identify individuals at risk for carbohydrate-induced dyslipidemia and other adverse effects of increased DNL.

Trial registration: ClinicalTrials.gov NCT00234156 NCT00535535.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / anatomy & histology
  • Adult
  • Blood Glucose / metabolism
  • Cross-Over Studies
  • Diet
  • Dietary Carbohydrates / pharmacology*
  • Fatty Acids / metabolism
  • Female
  • Fructose / pharmacology*
  • Glucose / pharmacology
  • Humans
  • Isotope Labeling
  • Lipid Metabolism / drug effects*
  • Lipoproteins, VLDL / blood
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Middle Aged
  • Overweight / metabolism
  • Palmitates / blood
  • Triglycerides / blood
  • Young Adult


  • Blood Glucose
  • Dietary Carbohydrates
  • Fatty Acids
  • Lipoproteins, VLDL
  • Palmitates
  • Triglycerides
  • Fructose
  • Glucose

Associated data

  • ClinicalTrials.gov/NCT00234156
  • ClinicalTrials.gov/NCT00535535