This observation, taking into account the contributory factor of the substantially longer half-life, 115 min for proinsulin compared with 5 min for insulin [32], and that regular meals are often ingested at 3–4-h intervals during the day, might indicate that meal-induced B-cell strain contributes to raised proinsulin throughout a substantial period of the day in obesity. This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.