Study Participants

Table 1. Table 1. Baseline Characteristics of the Patients.

Among the 50 participants who began the study, 4 withdrew during the first 8 weeks, while they were on the very-low-energy diet. An additional 7 participants did not lose the required 10% of body weight. During the 12-month follow-up period, 5 participants withdrew. Baseline characteristics of all participants who commenced the study and of those who completed it are shown in Table 1. There were no significant differences in any baseline measurements between those who did and those who did not complete the study, but there was a trend toward a younger age among participants who did not complete the study.

Body Measurements

Figure 1. Figure 1. Mean (±SE) Changes in Weight from Baseline to Week 62. The weight-loss program was started at week 0 and completed at week 10. ITT denotes intention to treat.

Changes in body weight (Figure 1) were significant in both the intention-to-treat analysis and the analysis that included only those participants who completed the study. Although male participants were significantly heavier than female participants throughout the study period (mean [±SD] baseline weight, 105.9±12.6 kg vs. 90.5±11.0 kg; P<0.001), the pattern of weight change was similar for men and women; consequently, the data were combined for the purposes of analysis.

Table 2. Table 2. Changes in Body Measurements.

Changes in anthropometric measurements for the participants who completed the study are shown in Table 2. The mean weight loss at the end of week 10 was 13.5±0.5 kg (14.0% of initial weight). All anthropometric measurements decreased significantly between weeks 0 and 10 and remained significantly below baseline values at week 62. Only data from the 34 patients who completed the study are included in the analyses that follow.

Hormonal Regulators of Appetite

Leptin

During the weight-loss period, mean fasting plasma levels of leptin decreased by 64.5±3.4% (P<0.001). Levels rose between weeks 10 and 62, but at week 62, they remained 35.5±4.7% below baseline levels (P<0.001). Reductions in leptin levels from baseline at weeks 10 and 62 remained significant when adjusted for fat mass, and the ratio of leptin to fat mass was significantly lower at week 10 than at week 62 (Table 1 in the Supplementary Appendix). Percentage reductions in leptin and weight correlated strongly at week 10 (r=0.78, P<0.001) and week 62 (r=0.78, P<0.001). There was a strong linear relationship between the log-transformed percentage of leptin regained and weight regained, indicating that leptin levels and body weight rose concurrently.

Gastrointestinal Hormones

Figure 2. Figure 2. Mean (±SE) Fasting and Postprandial Levels of Ghrelin, Peptide YY, Amylin, and Cholecystokinin (CCK) at Baseline, 10 Weeks, and 62 Weeks.

Mean fasting and postprandial levels of ghrelin, peptide YY, amylin, and cholecystokinin are shown in Figure 2. (Fig. 1 in the Supplementary Appendix provides these data for the remaining hormones studied, and Table 1 in the Supplementary Appendix provides information on the area under the curve and the median percentage changes in biochemical values from baseline.)

The linear mixed-effect analysis of hormone levels according to postprandial period and study week revealed that postprandial changes were highly significant for each hormone studied (P<0.001 for all comparisons). The interaction between the postprandial period and study week was not significant for ghrelin, peptide YY, GLP-1, cholecystokinin, or pancreatic polypeptide, suggesting that there were similar patterns of postprandial hormone suppression or secretion at baseline and at weeks 10 and 62. For each of these hormones, however, each week was highly significant (P≤0.001 for ghrelin, peptide YY, pancreatic polypeptide, and cholecystokinin; P=0.008 for GLP-1), indicating differences in absolute hormone levels at each study week.

Mean levels of ghrelin rose significantly with weight loss (P<0.001 for the change from baseline to week 10). Although ghrelin levels fell between week 10 and week 62 (P<0.001), the mean level remained significantly higher at 62 weeks than at baseline (P<0.001). For peptide YY, mean levels were significantly lower at weeks 10 and 62 than at baseline (P<0.001 for both comparisons), with levels that were significantly lower at week 62 than those at week 10 (P=0.004). For amylin, the interaction between postprandial period and study week was close to being significant (P=0.05). Fasting levels of amylin declined significantly with weight loss (P=0.008 for the change from baseline to week 10; P=0.05 for the change from baseline to week 62). The reduction from baseline in amylin secretion within the first 30 minutes after eating was significant at week 10 (P=0.002) and approached significance at week 62 (P=0.08). The mean level of cholecystokinin was significantly lower at weeks 10 and 62 than at baseline (P<0.001 and P=0.04, respectively), with no significant difference in levels between weeks 10 and 62.

For gastric inhibitory polypeptide, the interaction between postprandial period and study week was significant (P=0.02), owing to the greater secretion of this hormone in the first 60 minutes after meals at weeks 10 and 62 than at baseline (P=0.004 and P<0.001, respectively). Mean levels of gastric inhibitory polypeptide did not differ significantly between weeks 10 and 62. Mean levels of GLP-1 did not change significantly between baseline and week 10; the levels at week 62 were slightly but significantly lower than baseline levels (P=0.005).

Decreases in insulin levels after weight loss were evident, and the interaction between postprandial period and study week was significant (P<0.001), with significant reductions in meal-stimulated insulin release 30 and 60 minutes after eating, both from baseline to week 10 (P<0.001 for the two postprandial comparisons) and from baseline to week 62 (P<0.001 for the comparison at 30 minutes; P=0.01 for the comparison at 60 minutes). Mean levels of pancreatic polypeptide were significantly higher at week 10 and week 62 than at baseline (P=0.008 and P=0.002, respectively), with no significant difference between levels at weeks 10 and 62.

Appetite

Figure 3. Figure 3. Mean (±SE) Fasting and Postprandial Ratings of Hunger and Desire to Eat at Baseline, 10 Weeks, and 62 Weeks. Ratings were based on a visual-analogue scale ranging from 0 to 100 mm. Higher numbers indicate greater hunger or desire.

Figure 3 shows mean ratings, on a visual-analogue scale, of fasting and postprandial hunger and desire to eat at baseline and at weeks 10 and 62. (Additional ratings are available in Fig. 2 and Table 2 in the Supplementary Appendix.) The linear mixed-effect analysis revealed that mean ratings of hunger, desire and urge to eat, and prospective consumption were significantly higher at weeks 10 and 62 than at baseline (P<0.001 for all comparisons), with no significant differences between mean ratings at weeks 10 and 62 and no significant interactions between postprandial period and study week. Ratings for preoccupation with thoughts of food, as compared with baseline ratings, tended to increase at week 10 (P=0.09) and were significantly increased at week 62 (P=0.008). Mean ratings for fullness did not change significantly from baseline to week 10 or week 62 but were significantly lower at week 62 than at week 10 (P=0.03).