Summary
The therapeutic action of 3.5 mg glibenclamide (HB 420) once a day for six weeks was evaluated in ten mild NlD diabetics previously treated with diet only. Stable HbA1, insulin secretion during hyperglycaemic clamp (100 mg/dl over the baseline in the first study, and at the same level in the second one), peripheral sensitivity expressed as the amount of dextrose infused per Kg per min (M-coefficient), the glucose metabolic clearance rate (MCR) and the M/l ratio were measured. Circulating monocytes were separated to assess insulin binding before and after treatment. The results included a significant decrease in HbA1, (7.5 ± 0.3 against 8.4 ± 0.4%, P < 0.005), increased steady-state (100-120 min.) plasma insulin (31 ± 4.4 against 25.7 ± 3.9 μU/ml), a significant increase in M-coefficient (4.02 ± 0.62 against 2.49 ± 0.31 mg/Kg/min, P < 0.01), and MCR (1.90 ± 0.34 against 1.18 ± 0.18 ml/Kg/min, P < 0.025) and an increase in the M/I ratio (14.6 ± 1.9 against 11.2 ± 1.7). All subjects displayed an increase in total insulin binding (4.03 ± 0.31% against 2.79 ± 0.34%, P < 0.001) and affinity constants (Ke = 8.3 ± 0.6 against 6.6 ± 0.4 × 107 M-1, P < 0.05). Since the M/I ratio increased in only 7/10 subjects and since there was no significant correlations between the percentage increase in M and MCR and the plasma insulin increase, whereas the increase in R0 was significant, it is felt that the euglycaemizing action of low doses of glibenclamide is primarily peripheral. This action appears to be independent on the B-cell effect and may depend on a direct action on the target cells.
Key-Words:
Type 2 Diabetes Mellitus
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Hyperglycaemic Clamp
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Insulin Secretion
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Insulin Receptors
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Glibenclamide
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Insulin Sensitivity
