Biosynthetic Human Insulin in the Treatment of Diabetes

Clark, A. J. L.; Knight, Graham; Wiles, PhilipG; Keen, H.; Ward, J. D.; Cauldwell, J; Adeniyi-Jones, R.; Leiper, J. M.; Jones, R. H.; MacCuish, A. C.; Watkins, P.J.; Glynne, A.; Scotton, JanetB

doi:10.1016/s0140-6736(82)90548-7

Cited by 73 publications

(13 citation statements)

References 11 publications

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“…This possibility is supported by Clark et al 9 ' 10 and our own clinical pharmacologic studies. 3 If the clinical pharmacologic studies have failed to disclose striking or consistent statistically significant differences between human insulin and PPI, why are the two insulins different clinically?…”

Section: Monthly Visits Forsupporting

confidence: 80%

The U.S. “New Patient” and “Transfer” Studies

et al. 1982

Diabetes Care

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The large-scale clinical trials of human insulin (recombinant DNA) in the United States consisted of a "New Patient" study and a "Transfer" study. The "New Patient" study involved 101 patients (38% type I) who have never received insulin and who were treated with human insulin and followed for 6 mo using NPH insulin alone or in combination with Neutral Regular Insulin (NRI). Shortly after treatment, serum glucose and total glycohemoglobin concentration fell. No patients developed insulin lipoatrophy or insulin allergy. Two patients developed insulin hypertrophy; in one, it was transient. Intradermal tests to varying dilutions of human insulin did not change over 6 mo. In addition, there was no evidence of development of antibodies to Escherichia coli polypeptide. Two-hundred-and-forty-three patients, 91% of whom had type I diabetes, were transferred in a controlled double-blind study from mixed beef-pork or purified pork insulin (PPI) either to human insulin or back to their previous insulin treatment and followed for 3 mo. While insulin dosage did not change, there was a slight increase in fasting serum glucose and a statistically significant increase in fasting ketonuria. There was no change in the frequency of the complications of insulin treatment. These limited data are consistent with the conclusion that NPH human insulin is slightly shorter acting than its animal insulin counterparts. Overall, human insulin is a safe, effective insulin.

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Section: Monthly Visits Forsupporting

confidence: 80%

The U.S. “New Patient” and “Transfer” Studies

et al. 1982

Diabetes Care

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“…There were no significant differences in the baseline characteristics between patients who received human insulin first and those who received porcine insulin first (table I). The most notable difference relates to history (2 7) 16 6 2-87 (0 32) [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] (1-20) of recurrent hypoglycaemic coma, with eight of the patients who received human insulin first having experienced recurrent hypoglycaemic coma as compared with four of those who received porcine insulin first (p=0 31).…”

Section: Resultsmentioning

confidence: 99%

Influence of human insulin on symptoms and awareness of hypoglycaemia: a randomised double blind crossover trial.

Egger

Smith

Teuscher

1991

BMJ

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Objective-To investigate the apparent increased risk of severe hypoglycaemia associated with use of human insulin by comparing the pattern of symptoms of hypoglycaemia with human insulin and porcine insulin.Design-Randomised controlled double blind crossover trial of treatment with human insulin and porcine insulin, with two treatment periods of six weeks.Setting-Diabetes outpatient department of a university teaching hospital in Berne, Switzerland.Patients-44 patients (25 men, 19 women) aged 14 to 60 years, with insulin dependent diabetes mellitus. All patients met the following criteria: receiving treatment with fast acting soluble insulin and long acting protamine insulin; performing multiple daily fingerstick blood glucose self measurements; and had stable glycaemic control with about one mild hypoglycaemic episode a week during the preceding two months.Intervention-Patients were randomised to receive either human or porcine insulin for six weeks and were then changed over to the other type of insulin for a further six weeks.Main outcome measure-Questionnaire recording "autonomic" and "neuroglycopenic" symptoms that occurred during hypoglycaemic episodes confirmed by a blood glucose concentration -2-8 mmolIl.Results-Insulin doses and blood glucose, glycated haemoglobin Al,, and fructosamine concentrations were similar during the two treatment periods. 493 questionnaires on hypoglycaemia (234 during treatment with human insulin and 259 during treatment with porcine insulin) were analysed. With human insulin patients were more likely to report lack of concentration (52% v 35%, p=00003) and restlessness (53% v 45%, p=0004) and less likely to report hunger (33% v 42%, p=0-016) than during treatment with porcine insulin. The difference in the pattern of symptoms during the two treatments was similar to that between the 12 patients with a history of recurrent hypoglycaemic coma and the 32 patients without such a history. Conclusions-The pattern of symptoms associated with human insulin could impair patients' ability to take appropriate steps to avoid severe hypoglycaemia. Caution should be exercised when transferring patients from animal insulin to human insulin, and a large scale randomised trial of the two types of insulin may be justified. IntroductionDecreased awareness of hvpoglycaemia in diabetic patients transferred to treatment with human insulin was first reported in 1987 on the basis of retrospective questionnaire surveys. 2 Subsequently, in a randomised double blind crossover trial, hunger and sweating were found to be significantly less common initial symptoms of hypoglycaemia when human insulin, as compared with porcine insulin, was being taken.3 Hunger and sweating were considered to be "warning

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“…1 We report here the first case of the sicca syndrome in a young adult with 3 thalassaemia major and severe iron overload owing to repeated blood transfusions.…”

Section: Introductionmentioning

confidence: 85%