A dual sugar challenge test for lipogenic sensitivity to dietary fructose

Abstract

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.

Figures

Fig. 1.

Increase in percentage DNL by the MIDA method (top) and percentage palmitate (16:0, bottom) in VLDL TG before and after repeated oral doses of fructose given over 6 h (mean ± se).

Fig. 2.

Significant positive correlation between the absolute difference (Δ) in DNL between T = 0 and 8 h measured by MIDA and by fatty acid analysis of the percentage palmitate (16:0) in VLDL TG.

Fig. 3.

Statistically significant positive correlation between AUC percentage palmitate (16:0) in VLDL TG and fasting insulin.

Fig. 4.

Time course of changes in percentage palmitate (16:0) in VLDL TG after single oral boluses of fructose 0.5 g/kg (open circles); fructose 0.5 g/kg + glucose 0.5 g/kg (closed triangles); fructose 1 g/kg + glucose 1 g/kg (open triangles); and glucose 75 g, ∼1 g/kg (closed circles). Data are shown as mean ± se.

Fig. 5.

Δ for percentage palmitate (16:0) in VLDL TG before and after OGTT screening test (glucose, 75 g; average, 0.8 g/kg), F (fructose, 0.5 g/kg), F:G (fructose, 0.5 g/kg, glucose 0.5 g/kg), and 2X F:G (fructose, 1 g/kg, and glucose, 1 g/kg). Data are presented as mean ± sd. All fructose-containing test means were significantly different from the OGTT mean (repeated measures ANOVA, P < 0.05). One outlier was excluded from the statistical comparisons of F vs. F:G and F:G vs. 2X F:G (paired Student's t test).