Background The human amylase gene (AMY1) has broad copy number (CN) variation that may associate with BMI. Methods DNA was extracted from urine (n=74) and serum (n=6) samples (‘ProFiMet’ cohort), and buccal (n=17) samples (Oral Starch Challenge [OSC] cohort), and assessed for AMY1 CN by droplet digital PCR. Association of AMY1 CN with comprehensive markers of metabolic status (ProFiMet cohort) were analysed with Pearson Correlation Coefficients (CC). For the healthy, euglycemic OSC cohort, glycemic response to OSC was analysed with independent-sample t-tests (subgroups: high AMY1 CN 9-12, n=10; low AMY1 CN 4-6, n=7). Results There were significant inverse correlations of AMY1 CN with total visceral fat volume (CC -0.33; P=0.004), and positive correlations of AMY1 CN with oral glucose insulin sensitivity score (OGIS [derived from OGTT], CC 0.26; P=0.02), serum HDL-cholesterol (CC 0.325; P=0.003), and serum adiponectin (CC 0.249; P=0.026). Linear regression multivariate analysis (adiponectin as dependent variable), showed independent association of adiponectin with AMY1 CN (Beta=0.29; P=0.03). There were no significant associations between AMY1 CN and clamp-derived M-value, homeostasis model assessment of insulin resistance (IR), hepatic endogenous glucose production, fecal floral signature or macronutrient dietary preference. Delta (mean) change in blood glucose concentration (fasting to 30-min post-OSC), was significantly greater in the high vs low AMY1 CN subgroups (mean 1.7mmol/l [SEM 0.6] vs 0.9mmol/l [SEM 0.9] respectively; p=0.016). Conclusions High AMY1 CN associates with favourable metabolic profile (lower visceral fat volume; higher serum adiponectin; enhanced glucose absorption following oral glucose and OSC), but not with whole-body or hepatic IR.

No abstract

Leptin circulates in serum bound to high molecular weight proteins. Hypothesizing that leptin binding proteins may regulate the functional efficiency of leptin, we characterized auxologic and hormonal factors that influence leptin binding in three disparate groups: normal adolescents, obese children, and teenagers with type I diabetes mellitus (IDDM). Specific leptin binding activity (sLBA) was assessed by column chromatography after incubation of serum with 125I-leptin in the presence and absence of excess unlabeled leptin. Mean sLBA was 17.0 +/- 7% (SD) in the healthy adolescents (n=41), 6.6 +/-4.3% in the obese children (n=26), and 14.9 +/-7.3% in the diabetic teenagers (n=17). At any value of sLBA, obese children had higher serum leptin levels than non-obese adolescents or diabetic teenagers, consistent with "leptin resistance" in the obese group. sLBA was higher in males than in females only in those with diabetes (18.6 +/- 7.3 vs 10.9 +/- 5.1%, p<0.05). sLBA correlated inversely with serum insulin-like growth factor-I values in the normal group (r= -0.45, p<0.01) and with insulin in the obese children (r= -0.53, p<0.01). There was no correlation between sLBA or serum leptin values and HbA1c, in the diabetic group. The serum leptin concentration was the principal determinant explaining the total variability of sLBA in all three cohorts. However, body mass index (BMI = weight/ height2) accounted for more of the total variability of percent specific binding in the healthy adolescents than in the other groups. We conclude that sLBA reflects circulating leptin levels, body composition, and hormonal milieu. Thus, in addition to leptin, qualitative and quantitative characteristics of leptin binding may play a physiological role in the regulation of appetite and in the "leptin resistance" of obesity.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.