biostudies-literatureUnknown131(4)Angelidi AMSevere insulin resistance syndromes are a heterogeneous group of rare disorders characterized by profound insulin resistance, substantial metabolic abnormalities, and a variety of clinical manifestations and complications. The etiology of these syndromes may be hereditary or acquired, due to defects in insulin potency and action, cellular responsiveness to insulin, and/or aberrations in adipose tissue function or development. Over the past decades, advances in medical technology, particularly in genomic technologies and genetic analyses, have provided insights into the underlying pathophysiological pathways and facilitated the more precise identification of several of these conditions. However, the exact cellular and molecular mechanisms of insulin resistance have not yet been fully elucidThe Journal of clinical investigation142245https://www.ebi.ac.uk/biostudies/studies/S-EPMC7880309biostudies-literatureSevere insulin resistance syndromes.PMC7880309Filippaios AAngelidi AMMantzoros CSfalseSevere insulin resistance syndromes.Severe insulin resistance syndromes are a heterogeneous group of rare disorders characterized by profound insulin resistance, substantial metabolic abnormalities, and a variety of clinical manifestations and complications. The etiology of these syndromes may be hereditary or acquired, due to defects in insulin potency and action, cellular responsiveness to insulin, and/or aberrations in adipose tissue function or development. Over the past decades, advances in medical technology, particularly in genomic technologies and genetic analyses, have provided insights into the underlying pathophysiological pathways and facilitated the more precise identification of several of these conditions. However, the exact cellular and molecular mechanisms of insulin resistance have not yet been fully elucid2021-01-01T00:00:00Z2021 Feb2025-04-04T19:53:48.892Z2025-04-04T19:53:48.892ZS-EPMC78803093358668110.1172/jci14224510.1172/JCI142245