Skip to main content
NCBI home page
The BMJ logoLink to The BMJ
. 1991 Sep 14;303(6803):617–621. doi: 10.1136/bmj.303.6803.617

Risk of severe hypoglycaemia in insulin treated diabetic patients transferred to human insulin: a case control study.

M Egger 1, G D Smith 1, H Imhoof 1, A Teuscher 1
PMCID: PMC1671049  PMID: 1932902

Abstract

OBJECTIVE--To examine whether transfer from animal insulin to human insulin is associated with an increased risk of severe hypoglycaemia. DESIGN--Matched case-control study of insulin treated diabetic patients admitted to hospital because of hypoglycaemia during 1984-7, the period when human insulin was introduced into treatment. SETTING--Case admissions and control admissions were obtained from eight public hospitals within the Swiss canton of Berne and a second control group comprised members of the Bernese section of the Swiss Diabetes Association. SUBJECTS--94 patients with insulin treated diabetes with a total of 112 admissions for hypoglycaemia during 1984-7 (case admissions), 182 patients with insulin treated diabetes seen in the same hospitals for reasons other than hypoglycaemia with a total of 225 admissions (control admissions), and 86 insulin treated diabetic patients who were members of the Bernese section of the Swiss Diabetes Association. MAIN OUTCOME MEASURES--Type of insulin used at time of admission, glycaemic control as measured by amount of glycated haemoglobin or glucose concentration; severity of hypoglycaemia. RESULTS--Treatment with human insulin at admission was more common in cases than controls (52/112 (46%) admissions v 77/225 (34%); p = 0.003). 116 out of 129 (90%) of admissions taking human insulin had been transferred from animal insulin, mainly because of non-availability of porcine insulins. The ratio of rate of hypoglycaemia in those taking human insulin to the rate in those taking animal insulin was 2.4 (95% confidence interval 1.3 to 4.4). Other risk factors for hypoglycaemia were a history of hypoglycaemic coma (rate ratio of history to no history 3.8, 2.3 to 6.4) and good glycaemic control (rate ratio of good to poor control 3.9, 1.4 to 7.5). With multivariate analysis the increase in rate ratio associated with use of human insulin rose to 3.0 (1.4 to 6.4). Comparison with the diabetes association controls also showed an increased risk associated with use of human insulin (2.2; 1.1 to 4.8). CONCLUSIONS--Transfer of treatment from animal insulin to human insulin was associated with an increased risk of severe hypoglycaemia. Caution should be exercised when transferring diabetic patients to human insulin. Further studies are required to elucidate why this effect occurs.

Full text

PDF
617

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Berger W. G., Althaus B. U. Reduced awareness of hypoglycemia after changing from porcine to human insulin in IDDM. Diabetes Care. 1987 Mar-Apr;10(2):260–261. doi: 10.2337/diacare.10.2.260. [DOI] [PubMed] [Google Scholar]
  2. Berger W., Keller U., Honegger B., Jaeggi E. Warning symptoms of hypoglycaemia during treatment with human and porcine insulin in diabetes mellitus. Lancet. 1989 May 13;1(8646):1041–1044. doi: 10.1016/s0140-6736(89)92444-6. [DOI] [PubMed] [Google Scholar]
  3. Casparie A. F., Elving L. D. Severe hypoglycemia in diabetic patients: frequency, causes, prevention. Diabetes Care. 1985 Mar-Apr;8(2):141–145. doi: 10.2337/diacare.8.2.141. [DOI] [PubMed] [Google Scholar]
  4. Clark A. J., Adeniyi-Jones R. O., Knight G., Leiper J. M., Wiles P. G., Jones R. H., Keen H., MacCuish A. C., Ward J. D., Watkins P. J. Biosynthetic human insulin in the treatment of diabetes. A double-blind crossover trial in established diabetic patients. Lancet. 1982 Aug 14;2(8294):354–357. doi: 10.1016/s0140-6736(82)90548-7. [DOI] [PubMed] [Google Scholar]
  5. Cryer P. E. Human insulin and hypoglycemia unawareness. Diabetes Care. 1990 May;13(5):536–538. doi: 10.2337/diacare.13.5.536. [DOI] [PubMed] [Google Scholar]
  6. Diabetes Control and Complications Trial (DCCT): results of feasibility study. The DCCT Research Group. Diabetes Care. 1987 Jan-Feb;10(1):1–19. doi: 10.2337/diacare.10.1.1. [DOI] [PubMed] [Google Scholar]
  7. Egger M., Smith G. D., Teuscher A. U., Teuscher A. Influence of human insulin on symptoms and awareness of hypoglycaemia: a randomised double blind crossover trial. BMJ. 1991 Sep 14;303(6803):622–626. doi: 10.1136/bmj.303.6803.622. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Egger M., Teuscher A., Berger W. G. Re: Hypoglycaemia (un)awareness: human vs animal insulin. Diabetologia. 1988 Jul;31(7):453–454. doi: 10.1007/BF00271592. [DOI] [PubMed] [Google Scholar]
  9. Gorden P. Human insulin and hypoglycemia. N Engl J Med. 1990 Apr 5;322(14):1007–1008. doi: 10.1056/NEJM199004053221413. [DOI] [PubMed] [Google Scholar]
  10. Greenland S., Thomas D. C. On the need for the rare disease assumption in case-control studies. Am J Epidemiol. 1982 Sep;116(3):547–553. doi: 10.1093/oxfordjournals.aje.a113439. [DOI] [PubMed] [Google Scholar]
  11. Heine R. J., van der Heyden E. A., van der Veen E. A. Responses to human and porcine insulin in healthy subjects. Lancet. 1989 Oct 21;2(8669):946–949. doi: 10.1016/s0140-6736(89)90955-0. [DOI] [PubMed] [Google Scholar]
  12. Hepburn D. A., Eadington D. W., Patrick A. W., Colledge N. R., Frier B. M. Symptomatic awareness of hypoglycaemia: does it change on transfer from animal to human insulin? Diabet Med. 1989 Sep-Oct;6(7):586–590. doi: 10.1111/j.1464-5491.1989.tb01233.x. [DOI] [PubMed] [Google Scholar]
  13. Nilsson A., Tideholm B., Kalén J., Katzman P. Incidence of severe hypoglycemia and its causes in insulin-treated diabetics. Acta Med Scand. 1988;224(3):257–262. doi: 10.1111/j.0954-6820.1988.tb19370.x. [DOI] [PubMed] [Google Scholar]
  14. Peacock I., Tattersall R. B., Taylor A., Douglas C. A., Reeves W. G. Effects of new insulins on insulin and C-peptide antibodies, insulin dose, and diabetic control. Lancet. 1983 Jan 22;1(8317):149–152. doi: 10.1016/s0140-6736(83)92756-3. [DOI] [PubMed] [Google Scholar]
  15. Pickup J. Human insulin. Br Med J (Clin Res Ed) 1986 Jan 18;292(6514):155–157. doi: 10.1136/bmj.292.6514.155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Potter J., Clarke P., Gale E. A., Dave S. H., Tattersall R. B. Insulin-induced hypoglycaemia in an accident and emergency department: the tip of an iceberg? Br Med J (Clin Res Ed) 1982 Oct 23;285(6349):1180–1182. doi: 10.1136/bmj.285.6349.1180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Rodrigues L., Kirkwood B. R. Case-control designs in the study of common diseases: updates on the demise of the rare disease assumption and the choice of sampling scheme for controls. Int J Epidemiol. 1990 Mar;19(1):205–213. doi: 10.1093/ije/19.1.205. [DOI] [PubMed] [Google Scholar]
  18. Sackett D. L. Bias in analytic research. J Chronic Dis. 1979;32(1-2):51–63. doi: 10.1016/0021-9681(79)90012-2. [DOI] [PubMed] [Google Scholar]
  19. Schlesselman J. J. Sample size requirements in cohort and case-control studies of disease. Am J Epidemiol. 1974 Jun;99(6):381–384. doi: 10.1093/oxfordjournals.aje.a121625. [DOI] [PubMed] [Google Scholar]
  20. Smith G. D., Phillips A. Declaring independence: why we should be cautious. J Epidemiol Community Health. 1990 Dec;44(4):257–258. doi: 10.1136/jech.44.4.257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Stephenson J., Fuller J. Hypoglycaemia as cause of death in human insulin era. Lancet. 1990 Mar 17;335(8690):661–661. doi: 10.1016/0140-6736(90)90448-e. [DOI] [PubMed] [Google Scholar]
  22. Teuscher A., Berger W. G. Hypoglycaemia unawareness in diabetics transferred from beef/porcine insulin to human insulin. Lancet. 1987 Aug 15;2(8555):382–385. doi: 10.1016/s0140-6736(87)92394-4. [DOI] [PubMed] [Google Scholar]

Articles from BMJ : British Medical Journal are provided here courtesy of BMJ Publishing Group

RESOURCES