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R J Jarrett

Publications and source records attributed to R J Jarrett.

202 records · Page 12Linked to original sources

Biosynthetic human insulin: effect in healthy men on plasma glucose and non-esterified fatty acids in comparison with highly purified pork insulin.

Biosynthetic human insulin (BHI) produced by recombinant DNA technology was administered subcutaneously and intravenously at two dose levels to two groups, each consisting of six normal men. Responses were compared with those for purified pork insulin (PPI) given by the same routes at the same dose levels to the same two groups. The glycemic response to the insulins was similar with a suggestion (seen both with intravenous and subcutaneous administration) that the glycemic depression with BHI was slightly greater at low dose and less at high dose. No significant difference between insulin types was found in the depression of non-esterified fatty acid (NEFA) concentrations, although significant differences between types with low-dose subcutaneous injection emerged during the later phases of the experiment. After termination of high-rate infusion with both insulins, NEFA concentrations rose more rapidly with some overshoot, suggesting that the rate and depth of blood glucose fall in these experiments might have triggered a brisker counterregulatory response. The small differences found between human and pork insulins, although in some cases significant, are unlikely to be of clinical importance.

Adult↗

Plasma insulin and C-peptide after subcutaneous and intravenous administration of human insulin (recombinant DNA) and purified porcine insulin in healthy men.

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.

Animals↗

The role of circulating glucose and triglyceride concentrations and their interactions with other "risk factors" as determinants of arterial disease in nine diabetic population samples from the WHO multinational study.

In 9 of the 14 national samples of diabetic patients assembled for the WHO Multinational Study of Vascular Disease in Diabetes additional laboratory data made it possible to relate manifestations of macrovascular disease to blood glucose concentrations as well as to diabetes duration and to other potential determinants. In five of the samples, serum triglyceride concentrations were also measured and were included in simple and multivariate analyses. Ischemic heart disease defined from Minnesota-coded EKGs and standardized WHO questionnaires was more strongly associated with serum triglyceride concentrations than with serum cholesterol concentrations, an association less notable in non-insulin-dependent diabetic patients. Ischemic heart disease was not related to the single fasting plasma glucose estimated for this study. Stroke and amputation were much more strongly related to the known duration of diabetes than was ischemic heart disease, and they were both related to blood glucose concentration measured at the time of study. Despite major variation in arterial disease prevalence rates between collaborating centers, risk for diabetic women appeared to equal that for diabetic men. The major variation in arterial disease prevalence between national groups could be accounted for only in part by the risk factors studied. Other factors, genetic or more likely environmental, are likely to contribute to the variation in arterial disease susceptibility and, if definable, may be potentially preventable.

Adipose Tissue↗

Perceptions of health.

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Diabetes Mellitus↗