Calorie restriction improves lipid-related emerging cardiometabolic risk factors in healthy adults without obesity: Distinct influences of BMI and sex from CALERIE™ a multicentre, phase 2, randomised controlled trial

Figure 1. CALERIE CONSORT diagram. Reproduced with permission.5

Figure 2. Decision Tree for Statistical Analyses. To control for type-I effect, assessment of each outcome used a hierarchical gatekeeping strategy as illustrated. First, the treatment-by-visit interaction term was tested; if significant, between-group differences at each time point were tested at α=0·05. If not significant, the treatment main effect was tested next; if significant, between-group differences at each time point were tested at α=0·05. If neither of the treatment-by-visit interaction or the treatment main effect were significant, Bonferroni correction was applied at each time point, with p values adjusted by multiplying the nominal p value by the number of tests (truncated at 1·0).

Figure 3. Mean (± SE) Changes in Representative NMR Parameters. The NMR parameter changes (means±SE) by treatment group are shown for (A) the composite inflammatory measure, GlycA, (B) Lipoprotein Insulin Resistance Index (LP-IR), (C) Diabetes Risk Index (DRI), (D) Triglyceride-rich lipoprotein particles (TRLP), (E) HDL particle size, and (F) total branched chain amino acids (BCAA). All comparisons are controlled for baseline values. All p-values reflect Bonferroni corrections, truncated at 1.0, as appropriate (see text). Asterisk indicates p < 0.05 for a significant between-group difference in the change score at the time point. Included figures are meant to demonstrate the range and heterogeneity of alternative responses over time among different parameters.

Figure 4. BMI Effects on Mean (± SE) Changes in NMR Parameters. The NMR parameter changes (means±SE) by treatment group by BMI (22.0–24.9 versus 25.0–27.9 kg/m2) for (A) Lipoprotein Insulin Resistance Index (LP-IR), (B) Large triglyceride-rich lipoprotein (TRL) particles, (C) TRL size (D) HDL particle subtype H5, (E) triglycerides (TG), (F) TRL cholesterol, (G) LDL particles; (H) small LDL particles; (I) glucose, and (J) GlycA. All comparisons are controlled for baseline values. All p-values reflect Bonferroni corrections, truncated at 1.0, as appropriate (see text). Asterisk indicates p < 0.05 for a significant between-group difference in the change score at the time point. Included figures are meant to demonstrate the range and heterogeneity of responses over time among different BMI strata.

Figure 5. Sex by Treatment Effects on Mean (± SE) Changes in NMR Parameters. The NMR parameter changes (means±SE) by treatment group by sex for (A) Lipoprotein Insulin Resistance Index (LP-IR), (B) Large triglyceride-rich lipoprotein (TRL) particles, (C) TRL size, (D) TRL triglycerides (TG), (E) TRL cholesterol, (F) TG, (G) HDL size, and (H) Medium LDL particles. All p-values reflect Bonferroni corrections, truncated at 1.0, as appropriate (see text). Asterisk indicates p < 0.05 for a significant between-group difference in the change score at the time point. Included figures are meant to demonstrate the range and heterogeneity of alternative responses over time within the different sex strata.

Figure 6. Sex Main Effects on Mean (± SE) Changes in NMR Parameters. The NMR parameter changes (means±SE) by treatment group by sex for (A) small LDL particles, (B) GlycA, (C) HDL particle subtype H2 (D) Leucine (E) Glucose. All p-values reflect Bonferroni corrections, truncated at 1.0, as appropriate (see text). Asterisk indicates p < 0.05 for a significant between-group difference in the change score at the time point. Included figures are meant to demonstrate the range and heterogeneity of alternative responses over time within the different sex strata.

Figure 7. Sex by Treatment by Time Effects on Mean (± SE) Changes in NMR Parameters. The NMR parameter changes (means±SE) by treatment group by sex for (A) LDL particles, (B) LDL cholesterol, (C) ApoB, (D) HDL particles (E) small HDL particles (F) small TRL particles, (G) total cholesterol, (H) TRL cholesterol, (I) total branched chain amino acids (BCAA), and (J) Valine. All p-values reflect Bonferroni corrections, truncated at 1.0, as appropriate (see text). Asterisk indicates p < 0.05 for a significant between-group difference in the change score at the time point. Included figures are meant to demonstrate the range and heterogeneity of alternative responses over time within the different sex strata.