To the Editor:Hereditary severe insulin resistance syndrome(H-SIRS)shows a wide and variable clinical spectrum and results in severe complications in the endocrinological and cardiovascular systems.Multiple treatments...To the Editor:Hereditary severe insulin resistance syndrome(H-SIRS)shows a wide and variable clinical spectrum and results in severe complications in the endocrinological and cardiovascular systems.Multiple treatments are recommended to control hyperglycemia in H-SIRS,including dietary intervention,insulin therapy,insulin sensitization,and recombinant human insulin-like growth factor-1(rhIGF-1)administration.[1]However,the heterogeneous etiology of H-SIRS leads to poor glycemic control in patients with different mutations,requiring multiple antihyperglycemic medications.This study described two cases diagnosed with H-SIRS and the treatment effect of multi-drug therapy and sodium-glucose cotransporter 2 inhibitor(SGLT2i)monotherapy.展开更多
Severe insulin resistance has been linked to some of the most globally prevalent disorders,such as diabetes mellitus,nonalcoholic fatty liver disease,polycystic ovarian syndrome,and hypertension.Hereditary severe insu...Severe insulin resistance has been linked to some of the most globally prevalent disorders,such as diabetes mellitus,nonalcoholic fatty liver disease,polycystic ovarian syndrome,and hypertension.Hereditary severe insulin resistance syndrome(H-SIRS)is a rare disorder classified into four principal categories:primary insulin receptor defects,lipodystrophies,complex syndromes,and obesity-related H-SIRS.Genes such as INSR,AKT2,TBC1D4,AGPAT2,BSCL2,CAV1,PTRF,LMNA,PPARG,PLIN1,CIDEC,LIPE,PCYT1A,MC4R,LEP,POMC,SH2B1,RECQL2,RECQL3,ALMS1,PCNT,ZMPSTE24,PIK3R1,and POLD1 have been linked to H-SIRS.Its clinical features include insulin resistance,hyperglycemia,hyperandrogenism,severe dyslipidemia,fatty liver,abnormal topography of adipose tissue,and low serum leptin and adiponectin levels.Diagnosis of H-SIRS is based on the presence of typical clinical features associated with the various H-SIRS forms and the identification of mutations in H-SIRS-linked genes by genetic testing.Diet therapy,insulin sensitization,exogenous insulin therapy,and leptin replacement therapy have widely been adopted to manage H-SIRS.The rarity of H-SIRS,its highly variable clinical presentation,refusal to be tested for genetic mutations by patients’family members who are not severely sick,unavailability of genetic testing,and testing expenses contribute to the delayed or underdiagnoses of H-SIRS.Early diagnosis facilitates early management of the condition,which results in improved glycemic control and delayed onset of diabetes and other complications related to severe insulin resistance.The use of updated genetic sequencing technologies is recommended,and long-term studies are required for genotype–phenotype differentiation and formulation of diagnostic and treatment protocols.展开更多
基金National Natural Science Foundation of China(Nos.8217033609,81770880,and 81970762)Science&Technology Department of Hunan Province(Nos.2020SK2080 and 2015JC3012)Science&Technology Department of Changsha City(Nos.k1906019 and kq190111)
文摘To the Editor:Hereditary severe insulin resistance syndrome(H-SIRS)shows a wide and variable clinical spectrum and results in severe complications in the endocrinological and cardiovascular systems.Multiple treatments are recommended to control hyperglycemia in H-SIRS,including dietary intervention,insulin therapy,insulin sensitization,and recombinant human insulin-like growth factor-1(rhIGF-1)administration.[1]However,the heterogeneous etiology of H-SIRS leads to poor glycemic control in patients with different mutations,requiring multiple antihyperglycemic medications.This study described two cases diagnosed with H-SIRS and the treatment effect of multi-drug therapy and sodium-glucose cotransporter 2 inhibitor(SGLT2i)monotherapy.
基金supported by the National Natural Science Foundation of China(No.8217033609,81770880,81800788,and 81970762)the Science&Technology Department of Hunan Province(China)(No.2020SK2080,and 2015JC3012)Changsha Science&Technology(China)(No.k1906019,and kq1901118).
文摘Severe insulin resistance has been linked to some of the most globally prevalent disorders,such as diabetes mellitus,nonalcoholic fatty liver disease,polycystic ovarian syndrome,and hypertension.Hereditary severe insulin resistance syndrome(H-SIRS)is a rare disorder classified into four principal categories:primary insulin receptor defects,lipodystrophies,complex syndromes,and obesity-related H-SIRS.Genes such as INSR,AKT2,TBC1D4,AGPAT2,BSCL2,CAV1,PTRF,LMNA,PPARG,PLIN1,CIDEC,LIPE,PCYT1A,MC4R,LEP,POMC,SH2B1,RECQL2,RECQL3,ALMS1,PCNT,ZMPSTE24,PIK3R1,and POLD1 have been linked to H-SIRS.Its clinical features include insulin resistance,hyperglycemia,hyperandrogenism,severe dyslipidemia,fatty liver,abnormal topography of adipose tissue,and low serum leptin and adiponectin levels.Diagnosis of H-SIRS is based on the presence of typical clinical features associated with the various H-SIRS forms and the identification of mutations in H-SIRS-linked genes by genetic testing.Diet therapy,insulin sensitization,exogenous insulin therapy,and leptin replacement therapy have widely been adopted to manage H-SIRS.The rarity of H-SIRS,its highly variable clinical presentation,refusal to be tested for genetic mutations by patients’family members who are not severely sick,unavailability of genetic testing,and testing expenses contribute to the delayed or underdiagnoses of H-SIRS.Early diagnosis facilitates early management of the condition,which results in improved glycemic control and delayed onset of diabetes and other complications related to severe insulin resistance.The use of updated genetic sequencing technologies is recommended,and long-term studies are required for genotype–phenotype differentiation and formulation of diagnostic and treatment protocols.
