FOREARM METABOLISM IN OBESITY AND ITS RESPONSE TO INTRA-ARTERIAL INSULIN. CHARACTERIZATION OF INSULIN RESISTANCE AND EVIDENCE FOR ADAPTIVE HYPERINSULINISM*

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Abstract
Forearm metabolism was investigated in 6 young obese subjects to determine what departures from normal are found in obesity, and what light this may shed on adaptation to substrate excess. Basal metabolism (glucose and K uptake and lactate production by muscle and free fatty acid release from adipose tissue) in obese subjects resembles that of normal subjects in whom insulin is infused intra-arterially. These observations, confirmed by assay of plasma insulin concen-tration, make it likely that hyperinsulinism accompanies early obesity. Obese subjects resist all effects of exogenous insulin (administered by close intra-arterial injection) on forearm metabolism. A completely satisfying explanation of this phenomenon is not readily apparent, although it is possible that insulin resistance in obesity is simply a manifestation of tolerance to chronic (endogenous) administration of insulin. These studies may provide a link in the chain of evidence incriminating obesity as a precursor of adult stable diabetes.