A Clinical Approach to Severe Insulin Resistance

The 2007 document outlines the diagnostic and therapeutic challenges of severe insulin resistance, a rare cause of type 2 diabetes. It presents a case study of a 13-year-old girl who developed severe insulin resistance, as indicated by an oral glucose tolerance test, and was later found to have a novel mutation in the PPARG gene and a second mutation in the PPP1R3A gene. The document highlights the clinical features of severe insulin resistance, including diabetes mellitus, hypoglycemia, acanthosis nigricans, and hyperandrogenism, and discusses the classification of severe insulin resistance syndromes. It emphasizes the use of the hyperinsulinaemic euglycaemic clamp and simpler tests like the oral glucose tolerance test for measuring insulin sensitivity. Management strategies include improving insulin sensitivity through leptin replacement therapy for patients with low leptin levels, immunosuppression, insulin sensitizers like metformin and thiazolidinediones, lifestyle changes, and treatments for associated conditions using antiandrogens, oestrogen/progestagen combinations, and lipid-lowering medications.