Pharmacokinetics of Biosynthetic Human Insulin and Characteristics of Its Effect

Bottermann, P.; Gyaram, H; Wahl, Klaus; Ermler, R.; Lebender, A

doi:10.2337/diacare.4.2.168

Cited by 31 publications

(10 citation statements)

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“…Except for somewhat lower plasma free-insulin levels observed several hours after injection of human insulin, consistent with some reports of a shorter duration of action of subcutaneously injected human insulin (39,40), we found no difference in plasma free-insulin and glucose profiles when purified porcine or human insulin was injected. Similar results have generally been found (41,42) and are readily explained by the fact that these insulins have virtually identical intrinsic activity (41,42) and by the fact that the patients studied have had antibodies that bound porcine and human insulin indistinguishably (43) as in this study.…”

Section: Discussionsupporting

confidence: 91%

Adverse Effects of Insulin Antibodies on Postprandial Plasma Glucose and Insulin Profiles in Diabetic Patients Without Immune Insulin Resistance: Implications for Intensive Insulin Regimens

1987

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To assess the possible influence of moderate titer insulin antibodies on diabetic glycemic control, we examined insulin-antibody equilibrium binding characteristics, postprandial glucose tolerance, and plasma free-insulin profiles after subcutaneous injection of both porcine and human insulin (0.15 U/kg) in 12 patients with insulin-dependent diabetes mellitus under conditions stimulating intensive insulin therapy. The patients' antibodies bound porcine and human insulin indistinguishably, and their plasma glucose and free-insulin profiles after ingestion of a standard meal were similar with both insulins. Initial increases in plasma free-insulin levels after injection of both insulins were negatively correlated with both insulin-antibody binding (r = -.55, P less than .006) and postprandial hyperglycemia (peak level r = -.56, P less than .006); the latter was positively correlated with insulin-antibody binding (r = .48, P less than .02). The effects of insulin antibodies on postprandial plasma free-insulin and glucose levels could be accounted for substantially by the association constant of the high-affinity insulin-antibody binding sites (K1); patients in the highest quartile for K1 had significantly slower initial increments in plasma free insulin (0.31 +/- 0.04 vs. 0.46 +/- 0.06 microU/min, P less than .05) and greater postprandial hyperglycemia (peak value 237 +/- 10 vs. 166 +/- 12 mg/dl, P less than .001) than patients in the lowest quartile. We conclude that moderate insulin-antibody titers commonly found in insulin-treated patients can slow the early increase in plasma free insulin after subcutaneous injection and that this impairs postprandial glucose tolerance; such an effect may limit the effectiveness of intensive insulin therapy.

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Section: Discussionsupporting

confidence: 91%

Adverse Effects of Insulin Antibodies on Postprandial Plasma Glucose and Insulin Profiles in Diabetic Patients Without Immune Insulin Resistance: Implications for Intensive Insulin Regimens

1987

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“…Alternatively, there may be dose-related absorption, lower doses of subcutaneous insulin masking a possible preferential absorption of the human insulin preparation. In this respect, the present study pointed more clearly to differences after injection of 9.6 U (approximately 0.15 U/kg) and the study of Botterman et al 5 …”

Section: Dose Differencessupporting

confidence: 59%

Plasma Insulin and C-Peptide After Subcutaneous and Intravenous Administration of Human Insulin (recombinant DNA) and Purified Porcine Insulin in Healthy Men

et al. 1982

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We have compared the plasma profiles of C-peptide, human insulin (recombinant DNA), and purified porcine insulin of pancreatic origin (PPI) in six nondiabetic men after low-dose (4.8 U) or high-dose (9.6 U) subcutaneous injection and low-rate (1.0 U/h) or high-rate (1.7 U/h) intravenous infusion. There was no significant difference in plasma C-peptide or glucose levels when human insulin was compared with PPI at either dose level for subcutaneous injection or intravenous infusion. Thus, there was equal suppression of endogenous insulin by the two species of exogenous insulin. For low-dose subcutaneous injection there was no significant difference between plasma insulin levels of the two species at single time points or when areas were compared. For high-dose subcutaneous injection mean plasma insulin levels were higher after human insulin than after PPI (20-300 min); this serial difference reached conventional statistical significance at 50 min (P less than 0.05) and 90 min (P less than 0.01). For the area under plasma insulin profiles between 0 and 90 min after high-dose s.c. injection, human insulin was higher than PPI (P = 0.06). There was no significant difference between insulin concentrations after human insulin and PPI given by either low- or high-dose intravenous infusion, except that high-dose PPI values (55-110 min) were slightly but significantly higher after high-dose intravenous infusion. Further comparisons of the pharmacokinetics of human and other species of insulin are, therefore, justified in larger numbers of subjects and particularly in diabetic individuals.

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“…Previous results (Keen, Pickup, Bilous, Glynne, Viberti, Jarrett and Marsden 1980;Raptis, Karaiskos, Enzmann, Hatzidakis, Zoupas, Souvatzoglou, Diamantopoulos and Moulopoulos 1981) suggested that the biosynthetic molecule might be more active than PPI, perhaps due to a higher skin absorption rate of BHI (Bottermann et al 1981). However, the failure to correlate plasma glucose with serum insulin concentration in normal subjects (Galloway, Spradlin, Rott and Fineberg 1981) and the considerable intra-and inter-subject variations indicate that it is unlikely that such differences have a physiological meaning.…”

Section: Discussionmentioning

confidence: 92%

“…Part of those studies either on biochemical or clinical grounds have been already published Received: 5 Dec. 1983 Accepted: 28 May 1984 {Owens, Hayes, Alberti, Jones, Heding, Home and Burrin 1981;DeMeyts, Halban mdHepp 1981 ;Bottermann, Gyaram, Wahl, Ermler and Lebender 1981;Wings, Ehrhardt and Enzmann (1981). However, considerable discrepancies have arisen from the published reports.…”

Section: Introductionmentioning

confidence: 97%

Metabolic and Hormonal Parameters after Insulin- Induced Hypoglycemia in Man, Comparison between Biosynthetic Human Insulin and Purified Pork Insulin

Fernández¹,

Casanueva²,

Devesa³

et al. 1985

Horm Metab Res

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Although clinically undistinguishable, some authors have found important differences in the counter regulatory response between Biosynthetic Human Insulin (BHI) and Purified Pork Insulin (PPI).To reassess the problem 10 healthy volunteers of both sexes underwent paired iv insulin tolerance test with both BHI and PPI (0.10 U/kg b.w.). To check the humoral response the variations of glucose, free fatty acids (FFA), prolactin, growth hormone, ACTH and plasma renin activity were evaluated.Blood glucose depression and further recovery by BHI and PPI administration paralleled each other, so were, prolactin, FFA, and plasma renin activity. A slight secretion of ACTH, and GH was observed under BHI challenge. There were not statistically significant differences between both insulins on any of the six parameters studied.The data do not confirm earlier published reports indicating hormonal and metabolic differences between human and porcine insulin.

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Pharmacokinetics of Biosynthetic Human Insulin and Characteristics of Its Effect

Cited by 31 publications

References 0 publications

Adverse Effects of Insulin Antibodies on Postprandial Plasma Glucose and Insulin Profiles in Diabetic Patients Without Immune Insulin Resistance: Implications for Intensive Insulin Regimens

Adverse Effects of Insulin Antibodies on Postprandial Plasma Glucose and Insulin Profiles in Diabetic Patients Without Immune Insulin Resistance: Implications for Intensive Insulin Regimens

Plasma Insulin and C-Peptide After Subcutaneous and Intravenous Administration of Human Insulin (recombinant DNA) and Purified Porcine Insulin in Healthy Men

Metabolic and Hormonal Parameters after Insulin- Induced Hypoglycemia in Man, Comparison between Biosynthetic Human Insulin and Purified Pork Insulin

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