Mechanism of hyperglycemia and response to treatment with an inhibitor of fatty acid oxidation in a patient with insulin resistance due to antiinsulin receptor antibodies.
Severe hyperglycemia and insulin resistance due to antiinsulin receptor antibodies developed over a period of 3 months in a 50-yr-old insulin-requiring diabetic patient. The hyperglycemia resulted from overproduction of glucose due to excessive rates of glycogenolysis and gluconeogenesis rather than decreased glucose utilization. Treatment with methyl-2-tetradecylglycidate, an inhibitor of fatty acid oxidation, resulted in a decrease in plasma glucose concentration. This was associated with a decrease in the rate of glucose production due to decreases in both gluconeogenesis and glycogenolysis rates, as well as an increase in the respiratory quotient. Plasma glucose concentrations continued to respond to the drug for the next 2 months until the sudden development of terminal hypoglycemia. The hypoglycemic action of the drug is consistent with the existence of an insulin-independent effect of fatty acid oxidation on glucose metabolism in man.
D000273:Adipose Tissue / Q000378:metabolism; D000409:Alanine / Q000378:metabolism; D004852:Epoxy Compounds / Q000627:therapeutic use*; D004912:Erythrocytes / Q000378:metabolism; D004988:Ethers, Cyclic / Q000627:therapeutic use*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005947:Glucose / Q000096:biosynthesis; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy* / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D066298:In Vitro Techniques; D007330:Insulin Antibodies / Q000032:analysis*; D007333:Insulin Resistance; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D011422:Propionates / Q000627:therapeutic use*; D011972:Receptor, Insulin / Q000276:immunology
D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D007330:Insulin Antibodies; D007773:Lactates; D011422:Propionates; D019344:Lactic Acid; D011972:Receptor, Insulin; D005947:Glucose; C017522:methyl 2-tetradecylglycidate; D000409:Alanine