Insulin resistance in uremia

R. A. DeFronzo, A. Alvestrand, D. Smith, R. Hendler, E. Hendler, J. Wahren

Research output: Contribution to journalArticlepeer-review

486 Scopus citations


Tissue sensitivity to insulin was examined with the euglycemic insulin clamp technique in 17 chronically uremic and 36 control subjects. The plasma insulin concentration was raised by ~100 μU/ml and the plasma glucose concentration was maintained at the basal level with a variable glucose infusion. Under these steady-state conditions of euglycemia, the glucose infusion rate is a measure of the amount of glucose taken up by the entire body. In uremic subjects insulin-mediated glucose metabolism was reduced by 47% compared with controls (3.71±0.20 vs. 7.38±0.26 mg/kg.min; P<0.001). Basal hepatic glucose production (measured with [3H]-3-glucose) was normal in uremic subjects (2.17±0.04 mg/kg.min) and suppressed normally by 94±2% following insulin administration. In six uremic and six control subjects, net splanchnic glucose balance was also measured directly by the hepatic venous catheterization technique. In the postabsorptive state splanchnic glucose production was similar in uremics (1.57±0.03 mg/kg.min) and controls (1.79±0.20 mg/kg.min). After 90 min of sustained hyperinsulinemia, splanchnic glucose balance reverted to a net uptake which was similar in uremics (0.42±0.11 mg/kg.min) and controls (0.53±0.12 mg/kg.min). In contrast, glucose uptake by the leg was reduced by 60% in the uremic group (21±1 vs 52±8 μmol/ of leg wt; P<0.005) and this decrease closely paralleled the decrease in total glucose metabolism by the entire body. These results indicate that: suppression of hepatic glucose production by physiologic hyperinsulinemia is not impaired by uremia, insulin-mediated glucose uptake by the liver is normal in uremic subjects, and tissue insensitivity to insulin is the primary cause of insulin resistance in uremia.

Original languageEnglish (US)
Pages (from-to)563-568
Number of pages6
JournalUnknown Journal
Issue number2
StatePublished - 1981
Externally publishedYes

ASJC Scopus subject areas

  • General Medicine


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