Antibodies Reactive to Leptin in Adults with Type 2 Diabetes and Its Relationship with Clinical, Metabolic and Cardiovascular Risk Parameters.

BACKGROUND AND AIMS: Patients with obesity and type 2 diabetes (T2D) have shown alterations in the affinity of IgG anti-leptin antibodies which are possibly related to metabolic alterations. In the present exploratory study, we analyzed serum samples from adults with T2D classified by body mass index (BMI) and evaluated the relationship of IgG anti-leptin antibodies with body composition, metabolic and cardiovascular risk parameters. METHODS: Serum IgG anti-leptin antibodies (total, free and immune complexes fractions) were measured by in-house ELISA. Body composition, metabolic biomarkers (glucose, glycated hemoglobin, lipid profile, insulin, leptin) and cardiometabolic risk indexes (AIP, HOMA-IR, HOMA-ß) were evaluated in one hundred T2D patients. RESULTS: Patients with T2D and obesity presented a decrease in the percentage of IgG anti-leptin immune complexes compared to patients with T2D and overweight (p < 0.0053). Negative correlations of IgG anti-leptin immune complexes with triglycerides (TG) (r=-0.412, p = 0.023) and VLDL-C (r=-0.611, p = 0.017) were found in normal weight T2D patients. Free IgG anti-leptin antibodies correlated positively with TC (r = 0.390, p = 0.032) and LDL-C (r = 0.458, p = 0.011) in overweight individuals with T2D. Finally, total IgG anti-leptin antibodies correlated positively with leptin hormone levels (r = 0.409, p = 0.024) and negatively with HOMA-IR (r =-0.459, p = 0.012) in T2D patients with obesity. CONCLUSIONS: The decrease of IgG anti-leptin immune complexes observed in patients with T2D and obesity suggests a reduction in antibody affinity to the hormone that may impact its transport and signaling, lipid, lipoprotein and insulin metabolism.

Leptin-reactive antibodies are distinctly correlated with body composition parameters and metabolic risk indexes in children and adolescents.

Studies have demonstrated the presence of low-affinity immunoglobulins (Igs) directed to leptin, a key hormone of the neuroendocrine axis that regulates appetite and metabolism, in adult healthy subjects, patients with obesity, and type 2 diabetes mellitus. In the present exploratory study, IgG leptin-reactive antibodies were analyzed for the first time in children and adolescents according to body mass index (BMI) and were correlated with biochemical profile (lipid profile, insulin, glucose, and leptin) and metabolic risk indexes [homeostasis model assessment for insulin resistance (HOMA-IR), homeostasis model assessment for ß-cell function (HOMA-ß), atherogenic index of plasma (AIP)]. One hundred and thirty-six participants were included (children n = 63, adolescents n = 73). An in-house enzyme-linked immunosorbent assay (ELISA) test was performed to measure IgG anti-leptin antibodies (free, total, and immune complexes). In adolescents, free and total IgG anti-leptin antibodies levels were higher in groups with overweight or obesity than in normal-weight group (P < 0.01), while in children, the total fractions were lower in groups with overweight and obesity than in normal weight (P < 0.02). Immune complexes percentage showed opposite correlations with BMI in children (r = 0.4004, P = 0.0473) and adolescents (r = -0.3983, P = 0.0133). IgG anti-leptin antibodies were also correlated with HOMA-IR in children (r = -0.4569, P = 0.0217) and adolescents (r = -0.3589, P = 0.0316), and with AIP (r = -0.3608, P = 0.0261) in adolescents. Our data suggest that the production and affinity of IgG anti-leptin antibodies can be affected by age, body composition, and metabolic conditions; additionally, in normal conditions, IgG anti-leptin antibodies may have a protective role in insulin resistance and cardiovascular events.

IgG antibodies reacting with ghrelin and leptin are correlated with body composition and appetitive traits in young subjects.

Appetitive traits are important behavioural characteristics affecting eating and body composition. Ghrelin and leptin are two key hormones regulating appetite and metabolism. Recent studies have reported the presence of autoantibodies (autoAbs) directed to ghrelin and leptin in healthy individuals as well as affinity alterations in eating disorders such as anorexia nervosa and hyperphagic obesity. Nevertheless, the relationship of these autoAbs with appetitive traits is unknown. The goals of this exploratory study were to analyze circulating IgG autoAbs reacting to ghrelin and leptin and evaluate their relationship with body composition parameters and appetitive traits. This cross-sectional study included 180 young subjects (20 ± 2 years) that underwent body composition evaluation. Seven appetitive traits were assessed with AEBQ-Esp and were classified as low-score or high-score. A validated in-house ELISA test was performed to measure IgG ghrelin and leptin-reactive autoAbs in its free, total, and immune complexes fractions. Free IgG ghrelin-reactive were significantly higher in women than in men. Immune complexes of IgG-ghrelin were positively correlated with waist-hip ratio in the total cohort. In women, free IgG leptin-reactive were positively correlated with body fat percentage and waist-hip ratio, whereas in men, immune complexes of IgG-leptin were positively correlated with body fat percentage. Women with a low-score for 'enjoyment of food', exhibited higher levels of IgG ghrelin-reactive autoAbs on its free form than the high-score group. Men with a high-score for 'emotional undereating' had higher levels of free IgG leptin-reactive autoAbs than the low-score group. The correlation of these autoAbs with anthropometric parameters and appetitive traits in young subjects support its role as carriers and modulators of the biologic functions of ghrelin and leptin and suggest a novel role in eating behaviour through appetitive traits.