Diabetic ketoacidosis: continuous subcutaneous infusion of insulin increases the risk.

Clinical bottom line (level 1a)

  1. Patients who have intensive insulin therapy are at increased risk of severe hypoglycaemia (NNH = 4 at unknown) , and ketoacidosis (NNH = 25 at years) .
  2. There is no clear effect on mortality.
  3. Patients on continuous insulin infusions are at increased risk of ketoacidosis (NNH = 26 at years) . There is no clear increase in ketoacidosis for patients on multiple daily injections.
Egger et al: Diabetic Medicine 1997; 14: 919-928
Expires October 2003

The study

Systematic review of randomised controlled trials of
  • Patients: insulin-dependent diabetes mellitus
  • Intervention: intensified insulin treatment regimens compared with conventional treatment
  • Outcome: mortality, hypoglycaemia, ketoacidosis


    • Articles found in English using MEDLINE, ? (search terms: not detailed ) and references from earlier systematic review together with hand searching Diabetes, Diabetologia, Diabetes Care and Diabetic Medicine. Authors were contacted for unpublished studies.

    Selection criteria: as above
    Appraisal criteria: assessed with pre-determined criteria though these were not applied blindly or independently
    Articles excluded if: uncertain

    Fourteen studies were included. 1028 patients were allocated to intensive treatment and 1039 to conventional treatment.
    The test for heterogeneity was significant when pump and multiple injection studies were combined (p=0.06; p<0.1 usually taken to be significant in this situation).

    The evidence

    Outcome Time to outcome CER OR
    (95% CI)    		 NNH
    (95% CI)
    severe hypoglycaemia 2-6 years 315/1039
    (30.3%)    		 2.88
    (2.38 to 3.48)     		4
    (3 to 5)
    ketoacidosis 2-6 years 67/1039
    (6.4%)    		 1.70
    (1.25 to 2.31)     		25
    (14 to 67)
    death from all causes 2-6 years 11/1039
    (1.1%)    		 1.29
    (0.65 to 2.55)     		330
    (NNT = 270 to infinity;
    NNH = 63 to infinity)
    a priori sub-group analysis: ketoacidosis: multiple injections 2-6 years 2/132
    (1.5%)    		 1.08
    (0.24 to 4.82)     		840
    (NNT = 87 to infinity;
    NNH = 19 to infinity)
    a priori sub-group: ketoacidosis: insulin pumps 2-6 years 6/701
    (0.86%)    		 5.76
    (2.88 to 11.5)     		26
    (12 to 64)

    Comments

    1. This analysis looked purely at adverse events.
    2. Unpublished studies were sought, and there was no attempt to assess publication bias.
    3. Not clear if studies of each type of intensive treatment are heterogeneous (if so pooling of data would be inappropriate).
    4. No significant difference in fatal events rates was noted; however it is salutary to recall that an individual not participating in the trial died during the conduct of the DCCT as a result of a hypoglycaemia-induced motor vehicle accident involving an intensively treated patient.

    Citation

    1. Egger M, Davey Smith G, Stettler C, et al: Risk of adverse effects of intensified treatment in insulin dependent diabetes mellitus: a meta-analysis. Diabetic Medicine 1997; 14: 919-928
    Contributor: Richard Hardern and Chris Ball, July 2000
    Reviewer: Sean F. Dinneen

    Clinical Question.
    Patient diabetes mellitus
    Intervention or Exposure intensified insulin regimen
    Comparison conventional treatment
    Outcome mortality, hypoglycaemia, ketoacidosis