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  • 1
    ISSN: 1432-1041
    Keywords: glipizide ; diabetes Type 2 ; C-peptide plasma level ; insulin plasma level ; sulphonylurea ; insulin secretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Peripheral blood glucose, plasma insulin and C-peptide levels were investigated after giving a standardized breakfast (500 kcal, 60g carbohydrates) to 10 nonobese Type 2 diabetic patients previously treated by diet alone. Each patient received at random, at 1 week intervals, either 5 mg glipizide (meal + glipizide) or a placebo (meal alone) 30 min before breakfast. Basal values of blood glucose, plasma insulin and C-peptide were similar on both occasions. After meal + glipizide, the blood glucose increase was sharply limited whereas the rise in plasma insulin was steeper and reached twice as high a level. In contrast, the rise in plasma C-peptide was similar in both conditions. Consequently, the areas under the curves (0–300 min) showed a marked reduction in blood glucose after meal + glipizide (2289±149 versus 3101±169 mmol·min/l; 2p〈0.001), associated with a significant increase in plasma insulin (14219±3261 versus 7591±1173 µU·min/ml; 2p〈0.025) but no significant change in plasma C-peptide (342±45 versus 326±34 pmol·min/ml; N.S.). The insulin/C-peptide molar ratio was thus significantly increased after meal + glipizide (0.41±0.06 versus 0.23±0.04 at the 60th min; 2p〈0.02). The dissociation between the responses of insulin and C-peptide suggests that a single dose of 5 mg glipizide in Type 2 diabetic subjects may enhance availability of peripheral insulin by extrapancreatic mechanism(s). This phenomenon may result in a higher circulating level of the hormone and therefore represent a further mode of action of sulphonylureas. Finally, the usual concept that peripheral insulin levels reflect true insulin secretion may be misleading in studies dealing with sulphonylureas.
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  • 2
    ISSN: 1432-1041
    Keywords: glibenclamide ; acarbose ; kinetics ; alpha-glucosidase inhibitor ; blood glucose control ; plasma insulin ; Type 2 diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A single dose of glibenclamide 5 mg was administered to six Type 2 diabetics, randomly treated for 7 days either with acarbose (3×100 mg daily) or with placebo. The serum concentration of the drug was measured for 10 h. Peak concentrations, times-to-peak concentration, elimination half-lives and the extent of bioavailability of the drug were not significantly modified by acarbose. The combined administration of glibenclamide and acarbose resulted in a modest improvement in the blood glucose profile after breakfast and lunch, together with a significant diminution in plasma insulin. Thus, acarbose appears a useful additional treatment for Type 2 diabetics already receiving sulphonylurea derivatives.
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  • 3
    ISSN: 1432-1041
    Keywords: human insulin ; diabetes control ; blood glucose ; free insulin ; biosynthetic insulin ; semisynthetic insulin ; monocomponent insulin ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sixteen hospitalized insulin requiring diabetics treated with a single daily subcutaneous injection were randomly allocated either to a mixture of porcine Actrapid+Lente MC or a mixture of Regular+NPH—Biosynthetic human insulin (Study 1). In Study 2, 10 patients receiving two daily insulin injections were treated at random with either porcine Actrapid+Monotard, or Actrapid+Monotard—Semisynthetic human insulin or Regular+NPH—Biosynthetic human insulin. Once an optimal insulin regimen was obtained, circadian blood glucose and plasma free insulin profiles (7–9 time points) were determined with the two (Study 1) or three (Study 2) insulin preparations, keeping the doses of insulin constant. In Study 1 no significant difference in blood glucose (BG) or plasma free insulin (FIRI) profiles was observed. The mean daily blood glucose, the mean amplitude of glycaemic excursions (MAGE), the index of blood glucose control (M-value of Schlichtkrull), as well as the post-breakfast increases in blood glucose and mean free IRI, were similar with both types of insulin. In Study 2, BG and FIRI profiles were also similar, except for a significantly lower (p〈0.02) BG at 8.30 p.m. with both human insulins. No significant differences were found in free IRI at that time. Mean BG, M index, MAGE and mean FIRI were similar but the postbreakfast increase was significantly smaller with SHI. In conclusion, the pharmacokinetics of animal monocomponent, semisynthetic and biosynthetic human insulin appear similar, but evening BG control was better with both types of human insulins given twice daily.
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