New classification and diagnostic criteria for insulin resistance syndrome

Abstract

This report of a working group established by the Japan Diabetes Society proposes a new classification and diagnostic criteria for insulin resistance syndrome. Insulin resistance syndrome is defined as a condition characterized by severe attenuation of insulin action due to functional impairment of the insulin receptor or its downstream signaling molecules. This syndrome is classified into two types: genetic insulin resistance syndrome, caused by gene abnormalities, and type B insulin resistance syndrome, caused by autoantibodies to the insulin receptor. Genetic insulin resistance syndrome includes type A insulin resistance as well as Donohue and Rabson-Mendenhall syndromes, all of which are caused by abnormalities of the insulin receptor gene; conditions such as SHORT syndrome caused by abnormalities of PIK3R1, which encodes a regulatory subunit of phosphatidylinositol 3-kinase; conditions caused by abnormalities of AKT2, TBC1D4, or PRKCE; and conditions in which a causative gene has not yet been identified. Type B insulin resistance syndrome is characterized by severe impairment of insulin action due to the presence of insulin receptor autoantibodies. Cases in which hypoglycemia alone is induced by autoantibodies that stimulate insulin receptor were not included in Type B insulin resistance syndrome.

INSR novel mutations identified in a Chinese family with severe INSR-related insulin resistance syndromes: A case report

“…Hereditary insulin resistance syndromes include genetic syndromes caused by INSR mutations, SHORT syndromes caused by PIK3R1 abnormalities, and conditions caused by AKT2 , TBC1D4 , or PRKCE abnormalities. [1]…”

“…Hereditary insulin resistance syndromes include genetic syndromes caused by INSR mutations, SHORT syndromes caused by PIK3R1 abnormalities, and conditions caused by AKT2, TBC1D4, or PRKCE abnormalities. [1] INSR is a cell surface heterotetrameric glycoprotein and is a member of the class II receptor tyrosine kinase superfamily. It comprises 2 extracellular α subunits and 2 transmembrane β subunits joined by disulfide bonds, in which the α subunit is the hormone-binding site and the β subunit contains the tyrosine kinase domain.…”

“…Abnormalities in the insulin receptor gene ( INSR ) can cause genetic insulin resistance, including DS, Rabson–Mendenhall syndrome (RMS), and type A insulin resistance, which are identified by the severity of the receptor function defect and unique physical characteristics of the affected individual. [1] DS, with an incidence of approximately 1 in 4 million births, is the most severe syndrome. [2] It is characterized by intrauterine and postnatal growth retardation, coarse facial features, severe insulin resistance, and fasting hypoglycemia.…”

A Novel Mutation in the INSR Gene Causes Severe Insulin Resistance and Rabson–Mendenhall Syndrome in a Paraguayan Patient

“…RMS can appear in a variety of ways, and the severity of the condition can vary from person to person [ 1 , 9 , 13 ]. While some patients present with milder forms of the disorder, others may have more severe manifestations such as early-onset diabetes, severe insulin resistance, and recurrent infections [ 12 , 14 , 15 ]. It can be difficult to make a diagnosis because RMS’s clinical features may also overlap with those of other metabolic and genetic disorders [ 16 , 17 , 18 ].…”

“…Clinical features, such as the presence of acanthosis nigricans, insulin resistance, and dental abnormalities, as well as laboratory tests that confirm hyperglycemia and hyperinsulinemia, are used to make the diagnosis of RMS [ 15 , 19 , 20 ]. The diagnosis is confirmed through genetic testing and the identification of a specific variant in the INSR gene [ 21 , 22 ].…”