The effect of glyburide on glucose metabolism was examined in 10 non-insulin-dependent diabetic subjects (NIDDM) and 7 young, control subjects. After 3 mo of glyburide treatment in NIDDM, fasting plasma glucose declined from 198 to 141 mg/dl (P less than 0.01) without change in fasting insulin levels. Basal hepatic glucose production (HGP) was slightly elevated in NIDDM versus controls (2.35 versus 2.18 mg/kg X min, P = NS) and was positively correlated with the fasting glucose concentration (r = 0.93, P less than 0.001). With chronic glyburide therapy, HGP declined to 1.72 mg/kg X min (P less than 0.01 versus preglyburide) and remained highly correlated with the fasting glucose concentration (r = 0.85, P less than 0.005). Basal glucose clearance in NIDDM was reduced by 48% compared with age-matched controls (1.22 versus 2.32 ml/kg X min, P less than 0.001) and was unchanged after 3 mo of glyburide. Thus, the most important factor responsible for the decline in fasting plasma glucose concentration was an inhibition of hepatic glucose output. The decrease in basal hepatic glucose production and fasting plasma glucose concentration occurred without any change in fasting plasma insulin or C-peptide concentration. Insulin-mediated glucose metabolism (insulin clamp technique) was reduced by 55% in NIDDM (2.91 versus 6.39 mg/kg X min, P less than 0.001). After glyburide, insulin-mediated glucose metabolism increased by 26% to 3.67 mg/kg X min (P less than 0.01). This increase in tissue sensitivity to insulin was unassociated with any change in insulin binding to monocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

The pattern of metastases in patients who died of epidermoid cancer of the head and neck area, between 1954 and 1967, at the Veterans Administration Research Hospital, Chicago, was studied. One hundred fifty‐three patients died of epidermoid cancer of the head and neck; metastases below the clavicles were found in 46.7% of the patients. Fourteen patients, 9.1%, died of a second primary cancer; the lung and esophagus were the most common sites. Patients with distant metastases lived, on the average, 3 months longer from time of diagnosis to death than the patients without distal metastases.

Diabetes mellitus is associated with alterations in hepatic drug metabolizing enzyme activities in experimental animals. To determine whether Type II diabetes or glyburide affect hepatic drug metabolism, the authors used 13C-labeled aminopyrine and caffeine breath tests as in vivo probes of the hepatic cytochrome P450 and P(1)450 enzyme activities respectively in six subjects with Type II diabetes (4 women, 2 men). These subjects had been treated previously with diet, had an age range of 41-63 years, had a body mass index range of 24.1-43.3 kg/m2 and had a mean fasting plasma glucose of 14.6 +/- 1.2 mM and a mean hemoglobin A1c of 12.2 +/- 0.7%. These subjects did not drink alcohol or take drugs known to affect hepatic drug metabolism. The caffeine and aminopyrine breath tests (CBT, ABT) were performed sequentially while fasting before the start of glyburide treatment (5 mg daily) and at weekly intervals for 4 weeks. ABT and CBT values are expressed as cumulative percentage of dose exhaled through 2 hours. Before beginning glyburide, the mean ABT and CBT results were 10.2 +/- 0.7% and 4.2 +/- 0.7% respectively, well within the normal ranges for these tests (ABT 6.5-15%; CBT 2.5-10%). The ABT and CBT values remained unaltered during 4 weeks of glyburide therapy. However, FBS decreased to 10.2 +/- 1.1 mM and HbA1C to 10.1 +/- 0.8% by the end of drug treatment. Type II diabetes that is poorly controlled by diet alone is not associated with alterations of the hepatic drug metabolizing enzymes as judged by the caffeine and aminopyrine breath tests. Furthermore, glyburide does not induce or inhibit the drug metabolizing enzyme systems in the liver, thereby precluding drug-drug interactions of this type.

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