Objective: We analysed the kinetics and effects of glibenclamide (Gb) on glucose, insulin and proinsulin secretion in two ethnic groups
(10 in each) of type-2 diabetic patients, one of Caucasian, the other of Chinese origin.
Background: Diabetes mellitus type 2 is a global disease affecting all ethnic groups. There are ethnic differences in both the prevalence
and metabolic characteristics of the disease. Important interethnic pharmacodynamic and pharmacokinetic differences have been
reported for several drugs. With few exceptions, detailed studies on sulphonylurea are lacking.
Material and methods: The patients were studied on two occasions when either no Gb (control) or 1.25 mg Gb was administered i.v., immediately
before the administration of a 75-g oral glucose tolerance test. Concentrations of insulin and proinsulin were determined
by means of radioimmunoassay without cross-reactivities. Gb concentration was determined using high-performance liquid chromatography.
Pharmacodynamic results were calculated using net areas under the curves, with basal values set as zero. A P value less than 0.05 was considered significant.
Results: When glucose was administered orally without Gb, Chinese patients had higher plasma glucose increases at 10 min (7.6 mmol/l × min
vs 2.6 mmol/l × min) and higher increases of plasma insulin levels than Caucasians at both 10 min (198 pmol/l × min vs 54 pmol/l × min)
and 30 min (2286 pmol/l × min vs 1198 pmol/l × min). When Gb was administered, the plasma glucose increases were reduced,
and the increases of serum insulin and proinsulin levels were greater in both ethnic groups. Compared with the basal values
(−1 min), proinsulin/insulin ratios (RPI) were lowest at 10–30 min, followed by an increase. Chinese patients had higher increases
of serum insulin levels at 10 min (1109 pmol/l × min vs 550 pmol/l × min) and a lower RPI at 30 min (6.0% vs 7.6%) and 240 min
(15.0% vs 21.0%) relative to Caucasians. Serum Gb data were best fitted to a biexponential i.v. model. There were no interethnic
differences in any of the pharmacokinetic parameters.
Conclusion: In summary, following oral glucose administration without Gb, Chinese type-2 diabetic patients had higher plasma insulin
levels but also higher plasma glucose levels during the first 10 min, which might reflect reduced insulin sensitivity or more
rapid glucose absorption. Gb augmented glucose-induced release of both insulin and proinsulin in both ethnic groups; the effect
on insulin secretion was more pronounced. In conclusion, minor pharmacodynamic but no pharmacokinetic differences were found
between the two groups. It seems appropriate to employ the same dosage principles when using Gb in Caucasians and Chinese.
Key words Glibenclamide - Insulin - Proinsulin
Received: 15 June 1999 / Accepted in revised form: 9 August 1999