INS and obesity due to melanocortin 4 receptor deficiency: Plasma S1P levels were found to be significantly elevated in subjects with obesity compared with lean healthy subjects (~28%; p < 0.01), and were positively correlated with the percentage of total body fat, BMI, waist circumference, fasting insulin, insulin resistance score (HOMA-IR), HbA1c (hemoglobin A1c), and total and LDL cholesterol [22].