The Helsinki Policemen Study [25], the Busselton Study [26], the Wisconsin Epidemiologic Study [27], and the RISC study [28] showed that high plasma insulin, fasting or after oral glucose load, was associated with increased risk of major CHD events independently of other conventional cardiovascular risk factors (including blood glucose, cholesterol, triglycerides, blood pressure, indices of obesity, smoking, and physical activity). Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.