Effect of Isoniazid on Carbohydrate Metabolism in Controls and Diabetics

Abstract

Following the observation that reducing substances were present in the urine of 5 out of 24 tuberculous patients receiving isonicotinic acid hydrazide (isoniazid) it was decided to investigate the nature of this reducing substance and whether isoniazid had any influence on carbohydrate metabolism. The literature contains few references to isoniazid as a reducing substance. In a report on the current status of isoniazid in the treatment of tuberculosis by the Executive Committee of the American Trudeau Society (1952) mention is made of the presence of traces of reducing substances i-n the urine. Their presence was not found by Benson, Stefko, and Roe (1952) (1926) reported that hydrazine derivatives induce hypoglycaemia by injuring the liver and thereby interfering with the formation of liver glycogen. In addition, hydrazine, being a reducing substance, causes the urine to reduce copper solutions. Alloxan and allied compounds induce immediate hypoglycaemia associated with hepatic, renal, and pancreatic islet cell damage followed by permanent diabetes according to the extent of pancreatic islet betacell destruction induced (Dunn, Sheehan, and McLetchie, 1943;Koref, Vargas, Rodriguez, and Telchi, 1944). It is interesting to note that Sollmann (1948) reports that after large doses of morphine the urine often contains reducing substances which are partly morphineglycuronic acid and partly dextrose, and that clinical doses raise the blood sugar for some hours in 10-15% of fasting individuals. This response disappears in a few weeks if the administration is continued. Method of InvestigationThe oral glucose-tolerance test was used to investigate whether isoniazid produced any disturbance in carbohydrate metabolism.The investigation was carried out in two groups of tuberculous patients, the first group consisting of six non-diabetics to serve as "controls" and the second of six diabetics. In these 12 patients the pulmonary tuberculosis was quiescent in three and chronic in three of each group. The following tests were carried out on each patient. Blood plasma isoniazid levels were estimated bv the method described by Mueller and Fox (1951).All of the six diabetics were on a mixed dose of soluble insulin and protamine zinc insulin prior to the tests, but for a week before and during the trial the P'Z.1. was discontinued and S.I. alone was given morning and evening. On the days of tests A, B, and C the morning insulin was not given until after the tests had been completed.

Isoniazid induced childhood diabetes: A rare phenomenon

“…Furthermore, the insulin requirement of diabetic patients may increase while on isoniazid treatment. [ 6 ]…”

Isoniazid and hypoglycaemia in a premature infant

“…Isoniazid molecule contains a hydrazine residue, which provides a dual function: a reducing action and the property of combining with sugars and forming hydrozones and osazones. Isoniazid also interferes with sugars in the Hagedorn and Jensen method of blood sugar determination 3 . In fact, in an animal model, INH has been shown to have a biphasic effect on blood glucose; an initial hypoglycaemia, followed by hyperglycaemia 4 .…”

Review of Drug Interference With Urine Glucose Tests

“…+ + , Interference well documented or expected; + , possible interference, but data are limited or clinical significance is questionable (see text); 0, studies indicate insignificant or no interference; -, interference not reported or studied. mycin, and streptomycin) (31,58,59), isoniazid (18,60,61), lincomycin (62), methenamine mandelate (28), methyldopa (18,63,64), and tetracycline antibiotics (59,65,66). Note that certain injectable preparations of tetracyclines contain large amounts of ascorbic acid, which may affect test results (65).…”