Long-term intermittent intravenous insulin therapy and type 1 diabetes mellitus

Lancet. 1993 Aug 28;342(8870):515-8. doi: 10.1016/0140-6736(93)91645-3.


An important defect in insulin-dependent diabetes mellitus (IDDM) is that the liver does not meet its full fuel-processing function, because many of the enzymes involved depend on high insulin concentrations in the portal vein. We tried to reactivate the liver by long-term treatment of IDDM patients with intravenous insulin in pulses, with the aim of achieving high portal-vein concentrations during and after a glucose meal. We studied 20 IDDM patients with brittle disease; despite use of a four-injection regimen with manipulation of insulin doses, diet, and physical activity, and frequent clinic visits for at least a year, these patients still had wide swings in blood glucose and frequent hypoglycaemic reactions. The intermittent therapy consisted of 7-10 pulses of intravenous insulin, infused while the patient was ingesting carbohydrate, primarily glucose, during the first hour of a 3 h treatment; three treatments were given in a day. After 2 consecutive days' treatment, patients were treated for 1 day per week. No patient was withdrawn from the study. At the time of this analysis the duration of intermittent treatment ranged from 7 to 71 months (mean 41 [SE 5] months). Haemoglobin A1C concentrations declined from 8.5 (0.4)% at the end of the stabilisation phase to 7.0 (0.2)% at the analysis point (p = 0.0003). During the same time the frequencies of major and minor hypoglycaemic events also fell significantly (major 3.0 [1.1] to 0.1 [0], minor 13.0 [2.6] to 2.4 [0.8] per month; both p < 0.0001). Because the use of saline rather than insulin pulses would have led to unacceptable hyperglycaemia we opted for a historical control design. The absence of a true control group limits the interpretation of these preliminary results, but we believe further studies of hepatic and muscle metabolism before and after long-term intermittent intravenous insulin therapy would be worth while.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Algorithms
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Female
  • Glycated Hemoglobin A / analysis
  • Humans
  • Hypoglycemia / prevention & control
  • Infusions, Intravenous
  • Insulin / administration & dosage*
  • Insulin / pharmacology
  • Insulin / therapeutic use
  • Insulin Infusion Systems*
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Middle Aged
  • Pulsatile Flow
  • Treatment Outcome


  • Glycated Hemoglobin A
  • Insulin