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) trial

Abstract

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.

FIGURE 1.

CONSORT (CONsolidated Standards of Reporting Trials) diagram of subject flow throughout the trial. HS/HGI, high–saturated fatty acid and high–glycemic index diet (reference); HM/HGI, high–monounsaturated fatty acid and HGI diet; HM/LGI, HM and low–glycemic index diet; LF/HGI, low-fat and HGI diet; LF/LGI, LF and LGI diet.

FIGURE 2.

Mean (±SEM) changes in cholesterol, apolipoprotein B (ApoB), and apolipoprotein A1 (ApoA1) after consumption of diets low in saturated fatty acids (SFA) that were high in monounsaturated fatty acids or low in fat compared with a control saturated fat–rich diet. A: Total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), and TC:HDL cholesterol ratio after consumption of diets low in SFA that were high in monounsaturated fatty acids (HM; n = 227; filled bars) or low in fat (LF; n = 236; hatched bars) compared with a control SFA-rich diet (n = 85; open bars). Values below the bars indicate statistical significance from the SFA diet, and values below horizon bars indicate statistical significance between HM and LF diets (ANCOVA). B: Plasma ApoB, ApoA1, and the ApoB:ApoA1 ratio (ApoB/ApoA1) after consumption of HM (n = 227; filled bars) or LF (n = 236; hatched bars) diets compared with an SFA diet (n = 85; open bars). Values below the bars indicate statistical significance from the SFA diet, and values below horizon bars indicate statistical significance between HM and LF diets (ANCOVA).

FIGURE 3.

Mean (±SEM) changes in total cholesterol (TC) compared with predicted changes from the Keys equation (27). Overall test of significance, P < 0.001 (ANCOVA). HS/HGI, high–saturated fatty acid and high–glycemic index diet; HM/HGI, high–monounsaturated fatty acid and HGI diet; HM/LGI, HM and low-GI diet; LF/HGI, low-fat and HGI diet; LF/LGI, LF and LGI diet.