Hypoglycaemia induced by exogenous insulin - 'human' and animal insulin compared

Cm. Airey et al., Hypoglycaemia induced by exogenous insulin - 'human' and animal insulin compared, DIABET MED, 17(6), 2000, pp. 416-432
Citations number
Categorie Soggetti
Endocrynology, Metabolism & Nutrition
Journal title
ISSN journal
0742-3071 → ACNP
Year of publication
416 - 432
SICI code
Aims A systematic review of the literature was carried out to examine wheth er published evidence suggests a difference in the frequency and awareness of hypoglycaemia induced by 'human' and animal insulin. Methods The review identified randomized controlled trials and studies of o ther designs including observational comparisons, case series and case repo rts in which the use of 'human' insulin was compared to animal insulin in p eople with diabetes. These were identified from bibliographic databases and hand-searches of key journals. The main outcome measures were frequency, s everity, awareness and symptoms of insulin induced hypoglycaemia. Results Fifty-two randomized controlled trials, 37 of double-blind design, were identified which included one or more of the relevant outcome measures . Of these, 21 specifically investigated hypoglycaemic frequency and awaren ess as primary outcomes (six in people with previously reported reduced hyp oglycaemic awareness). The remainder of the identified trials reported hypo glycaemic outcomes as a secondary or incidental outcome during comparative investigations of efficacy or immunogenicity. Seven of the double-blind stu dies reported differences in frequency of hypoglycaemia or awareness of sym ptoms, although none of the studies which selected subjects on the basis of previously reported impaired awareness demonstrated significant difference s between insulin species. Four of the unblinded trials reported difference s in hypoglycaemia. This reached statistical significance in two of the stu dies. A further 56 studies of other designs and case reports were considere d. In addition to the 10 case reports describing individuals with impaired hypoglycaemic awareness, nine studies reported differences in the incidence and manifestation of hypoglycaemia during 'human' insulin treatment. Notab ly, none of the four population time trend studies found any relationship b etween the increasing use of 'human' insulin and hospital admission for hyp oglycaemia or unexplained death among those with diabetes. The largest case series could find no support for the hypothesis that an influence of treat ment with 'human' insulin on hypoglycaemia had contributed to any of the 50 deaths investigated. When all types of studies considered are ranked in or der of rigour (according to the accepted 'hierarchy of evidence'), it is th e least rigorous which lend most support to the notion that treatment with 'human' insulin has an effect on the frequency, severity or symptoms of hyp oglycaemia. Conclusions Evidence does not support the contention that treatment with 'h uman' insulin per se affects the frequency, severity or symptoms of hypogly caemia. However, a number of studies, mainly those of less rigorous design, describe an effect when people are transferred from animal insulin to 'hum an' insulin. It is not possible to state how common this is or whether the phenomenon is specific to 'human' insulin or an effect resulting from stric ter glycaemic control (perhaps compounded, in some cases, by neurological c omplications in long-standing diabetes). This remaining uncertainty makes i t essential that insulin from animal sources continues to be available so t hat clinicians and patients may retain this choice of treatment.