An important defect in insulin-dependent diabetes mellitus (IDDM) is t
hat 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 treatm
ent of IDDM patients with intravenous insulin in pulses, with the aim
of achieving high portal-vein concentrations during and after a glucos
e 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 hy
poglycaemic reactions. The intermittent therapy consisted of 7-10 puls
es of intravenous insulin, infused while the patient was ingesting car
bohydrate, primarily glucose, during the first hour of a 3 h treatment
; three treatments were given in a day. After 2 consecutive days' trea
tment, patients were treated for 1 day per week. No patient was withdr
awn from the study. At the time of this analysis the duration of inter
mittent 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 = 0.000
3). During the same time the frequencies of major and minor hypoglycae
mic 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 o
f saline rather than insulin pulses would have led to unacceptable hyp
erglycaemia we opted for a historical control design. The absence of a
true control group limits the interpretation of these preliminary res
ults, but we believe further studies of hepatic and muscle metabolism
before and after long-term intermittent intravenous insulin therapy wo
uld be worth while.