AND Evidence Analysis Worksheet Citation Le K, Ith M, Kreis R, et al.

Fructose overconsumption causes dyslipidemia and ectopic lipid deposition in healthy subjects with and without a family history of type 2 diabetes. Am J ClinNutr. 2009;89: 1760-1765. Crossover design D To assess the effects of fructose on intrahepatocellular lipids (IHCLs) and insulin sensitivity in healthy offspring of patients with type 2 diabetes (OFFT2D) and healthy men without family history of diabetes. Nonsmoking males OFFT2D Subjects in OFFT2D group needed to have at least one parent with type 2 diabetes BMI between 19 and 25 and are moderately physically active Subjects are not taking medication and do not regularly consume alcohol or sugar sweetened beverages. Non specified 24 eligible participants (16 OFFT2D, 8 control) undergo a 7-d isocaloric diet Diet containing 55% carbohydrate, 30% fat, and 15% protein Or isocaloric supplemented with 3.5g fructose 1 kg fat free mass daily (35% energy requirements) 4-5 week washout period separated diets Blood samples drawn from all subjects Independent: OFFT2D, fructose in diet Dependent: Intrahepatocellular lipids (IHCLs), Insulin sensitivity Control variables: Control subjects without OFFT2D Insulin sensitivity was determined with 2-step hyperinsulinemic euglycemic clamp and IHCL and IMCL were determined by proton magnetic resonance spectroscopy Body composition was estimated from subcutaneous skinfoldthickness measurements at the biceps, triceps, subscapular, and suprailiac sites Measurement of all plasma concentrations of glucose, lactate, insulin, NEFAa, B-hydroxybutyric acid, uric acid, total triacylglycerols, alanine aminotransferase, leptin, adiponectin, and VLDL, LDL, and HDL subfractions. Liver, adipose, and whole-body insulin sensitivity were measured for 3 h after initial 2-h tracer infusion Hepatic glucose output (6.6 [ 2H21 glucose; hot infusion model; 22) Lipolysis (plasma NEFA concentration) Colorimetric method to assess plasma concentrations of NEFA and triacylglycerols.

Study Design Class Research Purpose

Inclusion Criteria

Exclusion Criteria Description of Study Protocol

Data Collection Summary

Radioimmunoassay kit used to measured insulin, leptin, and adiponectin Subfractions of lipoproteins separated by ultracentrifugation B- Hydroxybutyric acid and lactate concentrations measured enzymatically Glucose concentrations measured by Beckman glucose analyzer 11 Plasma 6.6-[H21]glucose measured by gas chromatography-mass spectrometry Hepatic de novo lipogenesis was monitored by the ratio of linoleate (18:2n-6) to palmitate (16:0) in VLDL-triacylglycerols H-MRS examinations were performed on a clinical 1.5 T MR scanner with data acquisition except the liver spectra Liver fat content is expressed in units of volume percentage Statistics All data were analyzed by using 2-factor repeated-measures analysis of variance Summary of Results Anthropometric and fasting metabolic variables Body weight increased in both groups after the HFrD HFrD significantly increased fasting plasma total triacylglycerols (P < 0.05) (control: +35%; OFFT2D: +73%) as well as VLDLtriacylglycerols (control: +51%; OFFT2D: +110%) VLDL-triacylglycerols response to HFrD was significantly different between OFFT2D and control groups (P-0.04 for the group x diet interactions) Ratio of 18:2 to 16:0 fatty acids in VLDL-triacylglycerols significantly decreased (P <0.001) after the HFrD from 0.36 + 0.01 to 0.31 + 0.02 in the control group and from 0.35 + 0.01 to 0.27 + 0.01 in the OGGT2D group. This indicated the stimulation of hepatic de novo lipogenesis by the HFrD. The group x diet interaction was significant (P <0.05) for both total and VLDL-TG The effect of fructose was significant as well showing a (P <0.05) for all variables Effects exerted by fructose on plasma VLDL-triacylglycerols were more severe in the OFFT2D group than in the control group Ectopic lipid deposition IHCLs were significantly higher in the OFFT2D than in the control group and increased after the HFrD IHCLs were positivity correlated with fasting plasma VLDLtriacylglycerols after both diets (isocaloric: p -0.59. P <0.005; HFrD: p 0.78, P <0.005) IHCLs changed in VLDL-triacylglycerols after the HFrD (p -0.55, P <0.005) Insulin sensitivity and substrate oxidation

Author Conclusion

Reviewer Comments

Hepatic insulin sensitivity decreased after the HFrD After the HFrD carbohydrate oxidation significantly increased, with concomitant decrease in lipid oxidation in both the OFFT2D and control group 7 day high-frucose diet increased ectopic lipid deposition in liver and muscle and fasting VLDL-triacylglycerols and decreased hepatic insulin sensitivity. Diets with the fructose induced seemed to have a greater magnitude in VLDL-triacylglycerols in OFFT2D group Strengths: Taking numerous measurements to obtain data Limitations: No specifications on exclusion criteria Small sample size Limited tables provided to help reader understand all the results Fructose being administered as part of a hypercaloric diet this meant that is wasnt possible to determine whether the increase in IHCLs was due to energy overconsumption or specific effects of fructose Limited data on effects of fructose compared with those of glucose or starch on IHCLs in humans Funding source Not available