Insulin resistance contributes to the metabolic defects in
non-insulin-dependent diabetes mellitus (
NIDDM).
Anorectic agents have been shown to improve
insulin action in
NIDDM, irrespective of
weight reduction. The
serotonin-reuptake inhibiting agent
fluoxetine has recently been recognized as an
anorectic agent. The effect of
fluoxetine on
insulin action has not yet been determined. In a double blind placebo controlled crossover study, we examined hepatic and peripheral
insulin action by the sequential hyperinsulinemic euglycemic clamp technique with infusion of 3-3H-glucose in eight obese
NIDDM and in eight obese nondiabetics, matched for age, sex and body mass index.
Body weight was kept constant. After 14 days of
fluoxetine, 60 mg daily, in
NIDDM half-maximal peripheral
glucose uptake was achieved at a lower
insulin level than after placebo (ED50pgu 180.5 +/- 25.8 vs 225.3 +/- 39.9 mU/l, P less than 0.05), but not in nondiabetics (140 +/- 15.3 vs 135.3 +/- 22.2 mU/l, n.s.). Maximal peripheral
glucose uptake (Vmaxpgu) did not change significantly. Basal hepatic
glucose production (HGP) was reduced after
fluoxetine in both
NIDDM (9.45 vs 10.37 mumol/kg/min) and in nondiabetics (8.57 vs 9.16 mumol/kg/min), although the difference was only significant in nondiabetics (P less than 0.05). Multivariate analysis disclosed no differences in the effect of
fluoxetine between
NIDDM and nondiabetics. When nondiabetics and
NIDDM were considered together, only the most
insulin-resistant individuals demonstrated a decrease in ED50pgu (P less than 0.001). Likewise, only the individuals with the most outspoken hepatic
insulin resistance demonstrated a decrease in
insulin level, at which hepatic
glucose production is completely suppressed (HGP0) (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)