insulin allergy is an important clinical problem , and causes insulin resistance and instability of glycemic control1 . to date , definitive options for treating insulin allergy have not been established . glucagonlike peptide1 ( glp1 ) analogs promote endogenous insulin secretion and suppress secretion of glucagon from the pancreatic islets . hence , glp1 analogs are considered as a therapeutic option for patients with severe insulin allergy . in the present case report , we describe a patient with severe insulin allergy complicated with type b insulin resistance syndrome , whose condition was successfully controlled by liraglutide . a 72yearold woman ( body mass index 21.7  kg / m ) was diagnosed with type 2 diabetes at 60  yearsofage , and received glibenclamide . she had begun insulin therapy at 66  yearsofage . after the initiation of insulin therapy , she noticed local itchy whealflare reactions at the injection sites within 1  min of injection , which lasted for a couple of hours . she had been undergoing treatment with four daily insulin injections : three injections of insulin aspart before breakfast ( 62  units ) , lunch ( 64  units ) and dinner ( 54  units ) , respectively , and one of neutral protamine hagedorn insulin ( 50  units ) before breakfast . despite this , control of her blood glucose remained difficult , and she had been experiencing frequent repeated hypoglycemic and hyperglycemic episodes . on admission , a skin biopsy was taken from a large plaque of injection sites on the abdominal wall , and histological examination revealed a remarkable accumulation of inflammatory cells around blood vessels and massive deposition of adjacent connective tissue in deeper dermal areas , symptomatic of severe insulin allergy ( figure  1 ) . as antiinsulin receptor antibody was detected in her serum , she was unexpectedly diagnosed with type b insulin resistance syndrome . furthermore , she was found to have a high titer of circulating polyclonal antiinsulin antibodies with a low affinity constant and high binding capacity , as evaluated by scatchard analysis ( figure  2 ) . gliclazide ( 40  mg / day ) , acarbose ( 300  mg / day ) , metformin ( 750  mg / day ) and pioglitazone ( 30  mg / day ) were introduced in combination with insulin therapy , all of which were ineffective . finally , we decided to initiate intravenous methylprednisolone therapy ( 500  mg / day for 3  days ) followed by oral prednisolone therapy ( 30  mg / day ) . after introduction of steroid therapy , the allergic skin reaction disappeared immediately accompanied by reduced subcutaneous induration . serum levels of insulinspecific immunoglobulin e ( ige ) decreased from 1.27 to 0.44  ua / ml and hba1c level fell progressively to 7.1% after 18  months ( figure  3 ) . at this point , the patient wished to cease insulin injection because of repeated hypoglycemia . as her endogenous insulin secretion was still preserved ( urinary cpeptide : 63.7  g / day ) , we introduced liraglutide after 18  months from starting steroid therapy while tapering prednisolone to 2  mg / day . liraglutide was initiated at 0.3  mg / day , and was increased to a maintenance dose of 0.9  mg / day in conjunction with gliclazide ( 20  mg / day ) . after the introduction of liraglutide , she did not show any allergic reactions , hence , the use of prednisolone was terminated . continuous glucose monitoring clearly showed a dosedependent striking improvement of glycemic control by liraglutide ( figure  4 ) . thereafter , hba1c was maintained at approximately 7.0% with liraglutide ( 0.9  mg / day ) and gliclazide ( 20  mg / day ) . histological slide of a skin biopsy obtained from an allergic skin reaction on the injection site . congestion of different inflammatory cells in blood vessels with emission in the adjacent connective tissue of deeper dermal parts was observed ( indicated by arrows ; hematoxylin  eosin staining ) . b / f : bound / free insulin . changes of insulin dose and glycohemoglobin ( hba1c ) during the time course . the amount of steroid is shown at the top . representative daily profile of blood glucose levels after withdrawal of insulin therapy ( continuous glucose monitoring ) . many factors were considered to be involved in the insulin resistance and glycemic instability of the present case . type b insulin resistance syndrome is sometimes accompanied by other autoimmune disorders , and the present patient had a history of rheumatoid arthritis that might correspond to type b insulin resistance syndrome . however , evidence of hyperinsulinemia , such as acanthosis nigricance , had not been previously confirmed . adverse immune reaction leads to instability of glycemic control through two different mechanisms in patients treated with insulin therapy , namely , antiinsulin antibodies and insulin allergy . recent studies have shown that antiinsulin antibodies raised in response to repeated insulin injection can induce hypoglycemia through a mechanism similar to that of insulin autoimmune syndrome ( ias)2 . scatchard analysis of antiinsulin antibodies showed that the present patient possessed polyclonal antibodies , which have similar characteristics to ias ( figure  2 ) . generally , an allergic skin reaction at an insulin injection site is classified as an igedependentimmediate type of allergy , impairing the action of exogenous insulin and promoting degradation and/or disrupting absorption of insulin5 . after initiation of steroid therapy , skin lesions immediately improved , accompanied by a gradual reduction in blood glucose levels , suggesting that skin lesions were associated with impaired insulin absorption . along with improvement in glycemic control , serum levels of insulinspecific ige decreased , indicating that insulin allergy was a major contributor to glycemic instability in this patient . steroid therapy did not alter binding of antiinsulin antibodies to insulin ( data not shown ) . investigation of the distinctive binding specificity of the antiinsulin antibodies against endogenous and exogenous insulin will be required to elucidate the role of antiinsulin antibodies . as long as endogenous insulin secretion is preserved , glp1 analogs might be effective in patients with insulin allergy . as anticipated , liraglutide effected marked improvement in hyperglycemia and stabilized glycemic episodes without hypoglycemia ( figure  4 ) . to our knowledge , this is the first report showing the usefulness of liraglutide in patients with type 2 diabetes whose glycemic control is affected by severe insulin allergy .
abstracta 72yearold woman presented with repeated hypoglycemic and hyperglycemic episodes because of an insulin allergy . on admission , she was diagnosed with type b insulin resistance syndrome . 
 she was also found to have antiinsulin antibodies . 
 after steroid therapy , glycemic control improved dramatically accompanied by the disappearance of the insulin allergy . 
 we then introduced liraglutide , which successfully stabilized her glycemic episodes without allergic reactions . 
 liraglutide might be useful to treat patients with severe insulin allergy .