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An open parallel trial with glipizide or tolbutamide was carried out in a cohort of 29 comparable maturity-onset diabetic patients. Eighteen of these individuals were studied in detail. During six months of active drug therapy the mean decrease in fasting serum glucose levels on glipizide was 25 +/- 2% versus 17 +/- 2% on tolbutamide (p less than 0.025). Decreases in post prandial glucose levels were 12.2 and 10.4%. Glucose disappearance rates (Kg) during the sixth month of treatment with both drugs increased significantly: on glipizide from 0.47 +/- 0.04%/min to 0.85 +/- 0.08%/min(p less than 0.005), and on tolbutamide from 0.47 +/- 0.08%/min to 0.70 +/- 0.11%/min (p less than 0.01). Early and late insulin release (summed increases over basal for 2--10 min and 10--60 min) during intravenous glucose tolerance testing increased during glipizide, but not during tolbutamide therapy. Post prandial insulin increments over basal during an oral glucose tolerance test also increased during glipizide, but not tolbutamide therapy. Both drugs were comparable with regard to efficacy and safety; however, only glipizide had chronic effects upon insulin secretion.

We postulated that human insulin of recombinant DNA origin would be a poor immunogen and might prove to be less immunogenic than purified pork insulin. Results are reported for 100 diabetic subjects not previously treated with insulin. Individuals completed the first 12 months of a clinical trial of human insulin of recombinant DNA origin. These patients are contrasted with 121 similar individuals who are taking part in a trial of purified pork insulin. Prior to therapy, species-specific binding of 125I human insulin and pork insulins and insulin bound to antibody were undetectable in all individuals. In patients treated with human insulin of recombinant DNA origin, binding of 125I human insulin increased to 10 +/- 1.2% at 12 months versus increases in binding of 125I pork insulin in pork insulin-treated patients to 12.6 +/- 1.4% (NS). Mean percentages of species-specific binding tended to reach a plateau in the human insulin-treated group but continued to increase in the pork insulin group (p less than 0.001). Median bound values were nil throughout in patients treated with human insulin, but increased to 52 mU/l in the pork insulin group with significantly less bound insulin seen in the former group at all visits (p less than 0.001). The percentage of individuals who remained antibody free at 12 months, as indicated by bound insulin, was 56% in the human insulin-treated patients and 40% in the patients treated with pork insulin (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

The acute effects of glucagon (mol. wt. 3500) and its interactions with insulin were studied in the forearm during eight studies in seven normal, post-absorptive males. The protocol consisted of a 2 h baseline, 1 h glucagon perfusion (mean glucagon increment, 691 +/- 50 pg/ml), 1 h perfusion of both insulin and glucagon (mean insulin increment of 105 insulin and glucagon (mean insulin increment of 105 /- 13 mU/l) and a 30 min recovery period. Simultaneous arterial (A), deep venous (DV), and superficial venous (SV) blood samples were obtained at 30 min intervals. Perfusion of glucagon resulted in a decrease in (A-DV) non-esterified fatty acids of -0.128 +/- 0.057 mmol/l (n = 7, p less than 0.05) and (A-SV) non-esterified fatty acids of -0.081 +/- 0.36 mol/l (n = 7, p less than 0.05), as well as a change in deep compartment uptake of glycerol after 60 min of -0.044 +/- 0.019 mumol/min/100 ml of forearm tissue (n=6, p less than 0.05), indicating increased lipolysis. There was also a decrease in net glucose uptake as reflected by a change in (A-Dids of -0.081 +/- 0.36 mol/l (n = 7, p less than 0.05), as well as a change in deep compartment uptake of glycerol after 60 min of -0.044 +/- 0.019 mumol/min/100 ml of forearm tissue (n=6, p less than 0.05), indicating increased lipolysis. There was also a decrease in net glucose uptake as reflected by a change in (A-Dids of -0.081 +/- 0.36 mol/l (n = 7, p less than 0.05), as well as a change in deep compartment uptake of glycerol after 60 min of -0.044 +/- 0.019 mumol/min/100 ml of forearm tissue (n=6, p less than 0.05), indicating increased lipolysis. There was also a decrease in net glucose uptake as reflected by a change in (A-DV) of -0.24 +/- 0.09 mmol/l (n = 7, p less than 0.025) and (A-SV) of 0.10 +/- 0.05 mmol/l (n = 7, p less than 0.05). There was also a net decrease in deep arteriovenous differences of potassium in six of seven subjects. Insulin levels, similar to those found after a meal, rapidly reversed the effects of glucagon on non-esterified fatty acid, glucose and potassium. These effects persisted throughout the recovery period.