At the end of the 4-year trial, 44.2% of participants had no polyps, 38.6% had ≥ 1 adenoma, 16.3% had multiple adenomas, 10.8% had high risk adenoma, and 5.3% had ≥ 1 advanced adenoma (). Adenoma recurrence was more common in men, but less common in users of supplements and in women who used hormone therapy (). Furthermore, individuals with multiple, high risk, or advanced adenoma recurrence were older than those without polyps ().
Statistically significant, though weak, correlations were observed for serum concentrations of C-peptide with adiponectin (rSpearman = -0.16), homocysteine (r = 0.24), and leptin (r = 0.25), and between leptin and homocysteine (r = - 0.16). The serum concentrations of adiponectin and leptin at T1 were highly correlated with those at T4 (r = 0.68 and r = 0.82; respectively). On average, females had higher serum concentrations of adiponectin and leptin and lower concentrations of C-peptide and homocysteine (). With regard to race, Caucasians had higher concentrations of adiponectin. There was a curvilinear relationship between the four serum indicators and age with lower concentrations in the first quartile (36 to 56 years old) and similar concentrations in the other three quartiles (57 to 87 years old); the relationship was only statistically significant in males (data not shown). BMI was positively associated with serum leptin (r = 0.38), C-peptide (r = 0.39), and weakly correlated with homocysteine (r = 0.11); furthermore, physical activity was mildly inversely related to leptin (r = -0.25) and C-peptide (r = -0.15).
Medians (interquartile ranges) of serum adiponectin, leptin, C-peptide, and homocysteine concentrations at T1, by characteristics of participants at T1 in the control arm of the Polyp Prevention Trial (n = 627)
Those in the highest, versus the lowest, intake quartile of fiber, fruits & vegetables, and flavonols had lower serum concentrations of C-peptide (: 1.27 vs. 1.44 ng/mL for fiber, 1.23 vs. 1.45 ng/mL for fruits & vegetables; 1.21 vs. 1.47 ng/mL for flavonols) and homocysteine (12.6 vs. 13.9 μM/L for fiber, 12.0 vs. 13.9 μM/L for fruits & vegetables; 12.1 vs. 13.4 μM/L for flavonols), whereas % calories from fat were positively associated with C-peptide (1.44 vs. 1.26 ng/mL) and homocysteine (13.5 vs. 12.7 μM/L; ). Serum homocysteine concentrations were weakly inversely correlated with folate consumption from foods (r = -0.14) and from supplements (r = -0.23). Multivariate regression models of serum indicators by dietary exposure were not mutually adjusted for all dietary variables (% calories from fat, fiber, fruits & vegetables, flavonols, and dry beans) because of the high correlations among them, especially between fiber and fruits & vegetables (r = 0.76), fiber and fat (r = -0.59), and flavonols and dry beans (r = 0.62).
Individuals without polyp recurrence after four years had the highest leptin and the lowest homocysteine concentrations in serum (). For homocysteine, higher concentrations were observed with increasing adenoma number and more advanced adenoma type, whereas no gradual differences were found for leptin.
Medians (interquartile ranges) of serum adiponectin, leptin, C-peptide, and homocysteine concentrations at T1 in the control arm of the Polyp Prevention Trial by adenoma recurrence at T4*
Although there was no association for adiponectin or C-peptide and adenoma recurrence (), we observed a statistically significant inverse association between serum leptin concentrations and advanced adenoma recurrence (3rd vs. 1st tertile, OR = 0.22, 95% CI: 0.06-0.79). High homocysteine concentrations were positively associated with any (4th vs. 1st quartile, OR = 2.21, 95% CI: 1.27-3.86) and multiple adenoma recurrence (OR = 2.11, 95% CI: 1.01-4.40), and there was a suggestive positive association between high homocysteine concentrations and high risk adenoma recurrence (OR = 2.11, 95% CI: 0.89-4.97; ).
Association between serum adiponectin, leptin, C-peptide, and homocysteine at T1 and adenoma recurrence at T4* (n = 519)
Mutually adjusting multivariate regression models of adenoma recurrence by serum indicators or using the covariates reported at T1 (rather than baseline) did not substantially change the risk estimates (results not shown). The association between leptin and advanced adenoma recurrence (OR = 0.27, 95% CI: 0.07-0.98; Ptrend = 0.04) and between homocysteine and any adenoma recurrence attenuated but remained statistically significant (OR = 1.67, 95% CI: 1.02-2.75; Ptrend = 0.04) when the reference group was no adenoma recurrence, as opposed to the “no polyp” group was used for the main analyses.
There was no interaction between BMI or physical activity and serum adiponectin, leptin, C-peptide, or homocysteine concentrations and adenoma recurrence. Although there was no interaction between sex and adiponectin, C-peptide, or homocysteine, there was an interaction between sex and leptin (PInteraction for any adenoma = 0.01 and PInteraction for multiple adenoma = 0.06). In males, we observed a non-significant inverse association between serum leptin concentration and any (4th vs. 1st gender specific quartile, OR = 0.53, 95% CI: 0.25-1.12; P for trend = 0.03) and multiple adenoma recurrence (OR = 0.42, 95% CI: 0.17-1.08; P for trend = 0.08). In contrast, leptin concentrations in females had a non-significant positive association with any (OR = 1.44, 95% CI: 0.52-4.02; P for trend = 0.27) and multiple adenoma recurrence (OR = 3.16, 95% CI: 0.74-13.6; P for trend = 0.06), respectively.
An increase in serum leptin concentrations from T1 to T4 was associated with a statistically significantly increased risk of any (4th vs. 1st quartile, OR = 1.74, 95% CI: 1.04-2.93, Ptrend = 0.03) and multiple adenoma recurrence (OR = 2.19, 95% CI: 1.08-4.44, Ptrend = 0.04), which was not modified by sex (results not shown). In males, an increase in leptin concentration was positively significant associated with any (OR = 2.71, 95% CI: 1.41-5.22, Ptrend = 0.008) and multiple adenoma recurrence (OR = 3.54, 95% CI: 1.36-9.22, Ptrend = 0.03); the same trend was observed in women but did not reach statistical significance (ORany recurrence = 1.77, 95% CI: 0.72-4.31, Ptrend = 0.26; ORmultiple recurrence = 1.72, 95% CI: 0.55-5.37, Ptrend = 0.48) (results not shown). We found no association for change in adiponectin concentration between T1 and T4.