Effect of changing the amount and type of fat and carbohydrate on insulin sensitivity and cardiovascular risk: the RISCK (Reading, Imperial, Surrey, Cambridge, and Kings) trial1234

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Background: Insulin sensitivity (Si) is improved by weight loss and exercise, but the effects of the replacement of saturated fatty acids (SFAs) with monounsaturated fatty acids (MUFAs) or carbohydrates of high glycemic index (HGI) or low glycemic index (LGI) are uncertain.

Objective: We conducted a dietary intervention trial to study these effects in participants at risk of developing metabolic syndrome.

Design: We conducted a 5-center, parallel design, randomized controlled trial [RISCK (Reading, Imperial, Surrey, Cambridge, and Kings)]. The primary and secondary outcomes were changes in Si (measured by using an intravenous glucose tolerance test) and cardiovascular risk factors. Measurements were made after 4 wk of a high-SFA and HGI (HS/HGI) diet and after a 24-wk intervention with HS/HGI (reference), high-MUFA and HGI (HM/HGI), HM and LGI (HM/LGI), low-fat and HGI (LF/HGI), and LF and LGI (LF/LGI) diets.

Results: We analyzed data for 548 of 720 participants who were randomly assigned to treatment. The median Si was 2.7 × 10−4 mL · μU−1 · min−1 (interquartile range: 2.0, 4.2 × 10−4 mL · μU−1 · min−1), and unadjusted mean percentage changes (95% CIs) after 24 wk treatment (P = 0.13) were as follows: for the HS/HGI group, −4% (−12.7%, 5.3%); for the HM/HGI group, 2.1% (−5.8%, 10.7%); for the HM/LGI group, −3.5% (−10.6%, 4.3%); for the LF/HGI group, −8.6% (−15.4%, −1.1%); and for the LF/LGI group, 9.9% (2.4%, 18.0%). Total cholesterol (TC), LDL cholesterol, and apolipoprotein B concentrations decreased with SFA reduction. Decreases in TC and LDL-cholesterol concentrations were greater with LGI. Fat reduction lowered HDL cholesterol and apolipoprotein A1 and B concentrations.

Conclusions: This study did not support the hypothesis that isoenergetic replacement of SFAs with MUFAs or carbohydrates has a favorable effect on Si. Lowering GI enhanced reductions in TC and LDL-cholesterol concentrations in subjects, with tentative evidence of improvements in Si in the LF-treatment group. This trial was registered at clinicaltrials.gov as ISRCTN29111298.

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1

From the Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, United Kingdom (SAJ, CSM, MDC, and LJB); the Hugh Sinclair Unit of Human Nutrition, The University of Reading, Reading, United Kingdom (JAL and CMW); the Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom (BAG); the Nutrition and Dietetic Research Group, Imperial College London, London, United Kingdom (GSF); and the Nutritional Sciences Division, Kings College London, London, United Kingdom (TABS).

2

RISCK is an acronym derived from the study center names: Reading, Imperial, Surrey, Cambridge, and Kings.

3

Supported by the UK Food Standards Agency (project NO2031). Foods were supplied by Unilever Food and Health Research Institute (Unilever R&D, Vlaardingen, Netherlands), Cereal Partners UK (Welwyn Garden City, Hertfordshire, United Kingdom), Grampian (Banff, United Kingdom), Weetabix Ltd (Kettering, United Kingdom), and Sainsbury’s Supermarkets Ltd (London, United Kingdom).

4

Address correspondence to SA Jebb, MRC Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge CB1 9NL, United Kingdom. E-mail: [email protected].

Copyright © 2010 American Society for Nutrition. Published by Elsevier Inc.