Drug points: Rapidly reversible increase in insulin requirement with interferon

BMJ 1996;313:92 (13 July)

Drug points

Rapidly reversible increase in insulin requirement with interferon

We report a case of a 66 year old man with maturity onset diabeteswho developed a rapidly reversible increase in insulin requirementwhile receiving interferon alfa 2a for hepatitis C.

The patient's diabetes had been well controlled for three yearson a total of 62 units of Mixtard daily (glycosylated haemoglobin7-9%). His other medications were spironolactone 100 mg twicedaily and bumetanide 1 mg daily.

After three months of treatment with interferon alfa, 5 000000 U subcutaneously three times weekly, his blood glucose concentrationwas 50.4 mmol/l, necessitating a progressive increase in hisinsulin dose. After six months of interferon treatment he wasadmitted to hospital with vomiting, anorexia, and dehydration.He was then receiving a total of 118 units of Mixtard daily.Interferon was discontinued, as there was no change in his liverfunction values during treatment (table 1). Within eight dayshis insulin requirement had fallen to 24 units Mixtard daily.Subsequent follow up showed only a modest increase in insulinrequirement to 28 units Mixtard daily.

Table 1--Liver function values during and after treatment with interferon alfa for
hepatitis C
--------------------------------------------------------------------------------------------
                                   Time after introduction            5 months
Laboratory results       --------------------------------------------   after
(normal range)              2 weeks      3 months      6 months       withdrawal
--------------------------------------------------------------------------------------------
Albumin (36-52 g/l)            32           36            35              26
(gamma)-Glutamyltransferase
  (5-50 IU/l)                  39           36            47              22
Alanine aminotransferase
  (5-40 IU/l)                  33           41            24              24
Aspartate
  aminotransferase
  (10-35 IU/l)                 49           41            35              27
Bilirubin (3-20 µmol/l)     58           59            36              40
Alkaline phosphatase
  (60-300 IU/l)               176          247           247             175

Autoimmune phenomena during treatment with interferon alfa arewell recognised. Development of insulin dependent diabetes withseroconversion for islet cell antibodies during interferon alfatherapy for hepatitis C has been reported.¹ However, impairedglucose tolerance during treatment with interferon alfa hasalso been shown in healthy subjects² and in a patient with chronichepatitis B³; in these cases an autoimmune mechanism is lesslikely.

To our knowledge this is the first reported case of an increasein insulin requirement associated with interferon alfa therapywhich was rapidly reversible on withdrawal of interferon. Thissuggests that impaired glucose tolerance rather than an autoimmunephenomenon explained the increase. We recommend that in patientswith chronic liver disease and diabetes or impaired glucosetolerance interferon alfa should be used with caution and bloodglucose monitored regularly.--STEWART CAMPBELL, E H MCLAREN,B J DANESH, Department of Medicine, Stobhill NHS Trust, GlasgowG21 3UW

Stewart Campbell, E H Mclaren, B J Danesh