Sabine Steffens
The discovery of uncommon human metabolic disorders caused by a single gene defect has not only improved the diagnosis and clinical care of these patients, but it has also provided important biological insights into the pathophysiology of the metabolic syndrome, which is becoming more and more common. Obesity, which is fuelled by calorie excess and decreased physical activity, is a risk factor for type 2 diabetes and insulin resistance. However, it can be challenging to separate important events in the metabolic syndrome's aetiology from compensatory effects and epiphenomena. The three human monogenic illnesses that cause severe, non-syndromic obesity, pancreatic beta cell variants of early-onset diabetes, and severe insulin resistance are described in this article. The primary defect is known in these patients who have single-gene defects causing their exaggerated metabolic disorder. It is emphasised what they can teach us about the common metabolic syndrome's molecular pathogenesis today.