Normal Effect of Insulin to Stimulate Leg Blood Flow in NIDDM

Abstract

In patients with non-insulin-dependent diabetes mellitus (NIDDM), a decreased effect of insulin in stimulating leg blood flow (LBF) has been reported. We reinvestigated the effect of insulin on LBF and validated our data by use of other measures. Eight healthy men (control group) and seven men with NIDDM were studied (age 59 ± 1 and 58 ± 3 years, weight 83 ± 3 and 86 ± 6 kg, fat-free mass 66 ± 1 and 64 ± 3 kg, respectively [mean ± SE, all P > 0.05]; body mass index 26 ± 1 and 29 ± 1 kg/m2, fasting plasma insulin 72 ± 7 and 187 ± 22 pmol/l, fasting plasma glucose 5.8 ± 0.2 and 10.2 ± 1.7 mmoM [all P < 0.05]). A three-step hyperinsulinemic glucose clamp (ambient glucose level) was performed, combined with catheterization of an artery and both femoral veins. Expiratory air was collected, LBF was measured by thermodilution, and blood was sampled and analyzed for oxygen content. Insulin concentration was increased to 416 ± 22 and 509 ± 43 (step I), 1,170 ± 79 and 1,299 ± 122 (step II), and 15,936 ± 1,126 and 16,524 ± 1,916 (step III) pmol/l in control and NIDDM subjects, respectively (P > 0.05). LBF increased similarly (P > 0.05) in the two groups (from 287 ± 23 and 302 ± 12 [basal] to 308 ± 31 and 362 ± 9 [I], 371 ± 29 and 409 ± 17 [II], and 434 ± 32 and 472 ± 29 [III] ml min−1 leg−1 in control and NIDDM subjects, respectively). Leg oxygen uptake always increased in the face of constant venous Po2 (JP > 0.05; 4.3 ± 0.2 and 4.5 ± 0.2 [basal], 4.3 ± 0.2 and 4.6 ± 0.2 [I], 4.8 ± 0.2 and 4.6 ± 0.2 [II], and 4.7 ± 0.1 and 4.4 ± 0.2 [III] kPa in control and NIDDM subjects, respectively). Both leg and whole body O2 uptake increased similarly in the two groups. In conclusion, at ambient glucose levels, the effect of insulin in stimulating LBF is normal in NIDDM. Moreover, insulin-mediated vasodilation is closely linked to muscle metabolic rate.