Human ultralente insulin.

Holman, Rury R.; Steemson, J; Darling, Pauline B.; Reeves, W G

doi:10.1136/bmj.288.6418.665

Cited by 38 publications

(19 citation statements)

References 11 publications

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“…Howevel; HPB insulin is still significantly more immunogenic than human insulin of equivalent purity and formulation since the change to human insulin produced a further fall in insulin antibody levels in both Starter and Switch groups. This is in keeping with a previous study in which there was a significant fall in antibody level on transfer from highly purified beef to human ultralente insulin [13]. The three aminoacid residues by which beef differs from human insulin (AS, A10 and B30) are relatively close together on the surface of the bovine insulin molecule [14] and create sufficient alteration to induce an immune response greater than that seen with human insulin.…”

Section: Discussionsupporting

confidence: 90%

Immunogenicity of highly purified bovine insulin: a comparison with conventional bovine and highly purified human insulins

et al. 1985

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Summary, Twenty-six Type1 diabetic patients previously treated for 10-20 months with twice daily conventional bovine isophane insulin (containing at least 1000 ppm proinsulin) were changed to highly purified (< 1 ppm proinsulin) bovine isophane for 6 months (Switch group). Insulin antibody levels fell significantly from a geometric mean of 14.9 to 9.1 l-tg/1. Thirty-two patients with newly diagnosed Type 1 diabetes were treated with the same highly purified bovine isophane insulin twice daily for 6 months (Starter group). Their insulin antibody levels rose from a geometric mean of 1.9 to 8.2 ~tg/1 in contrast to values of 1.4 rising to 16.3 ~tg/1 in an age and sex matched historical control group treated from diagnosis only with twice daily conventional bovine isophane insulin. Lipoatrophy at injection sites developed in three (9%) in the Starter group treated with highly purified bovine isophane compared to 7 (22%) of those on conventional bovine isophane. Insulin dose and diabetic control did not differ between the groups. Starter and Switch groups were subsequently treated with semi-synthetic human isophane insulin for 6 months during which insulin antibody levels fell significantly from a geometric mean of 8.5 to 4.4 ~tg/1 (p< 0.001). We conclude that bovine insulin purified to less than 1 ppm proinsulin is significantly less immunogenic than its conventional proinsulin contaminated counterpart but even at this level of purity is still more immunogenic than human insulin of equivalent purity.Key words: Immunogenicity, Bovine insulin, Lipoatrophy, Insulin antibodies, Human insulin Previous studies [1][2][3] have shown that bovine insulin purified by sequential recrystallisation to > 1000ppm proinsulin (conventional bovine insulin) is much more immunogenic that its highly purified ( < 1 ppm proinsulin) porcine counterpart. Not only are levels of insulin antibody higher but antibodies to C-peptide and other islet proteins are often present after using the conventional preparation [3][4][5][6]. We previously studied patients on conventional bovine soluble and isophane insulins who were transferred to equivalent bovine preparations purified to a proinsulin content of 20-40 ppm [7]. This significantly reduced antibodies reactive with C peptide but did not change insulin antibody levels. It left open the question of whether bovine insulin is inherently more immunogenic than pork or human because the "purified" bovine still contained significantly more proinsulin than the porcine with which it was compared. In the present study we have examined the immunogenicity of highly purified bovine isophane insulin (containing < 1 ppm proinsulin) and compared it with a conventional bovine isophane and semi-synthetic human isophane insulin. Patients Switch groupTwenty-six patients with Type 1 diabetes were treated from diagnosis 10-20 months earlier with twice daily conventional bovine (CB) isophane insulin only. They and the other patients reported in this paper had all been started on insulin as outpatients and had never rec...

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Section: Discussionsupporting

confidence: 90%

Immunogenicity of highly purified bovine insulin: a comparison with conventional bovine and highly purified human insulins

et al. 1985

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“…This conclusion should be limited to beef ultralente, since debate continues as to whether pork and human ultralente preparations will yield insulin profiles equivalent to those observed with beef preparations. 10 "…”

Section: Methodsmentioning

confidence: 98%

Use of Beef Ultralente for Basal Insulin Delivery: Plasma Insulin Concentrations After Chronic Ultralente Administration in Patients with IDDM

Rizza

O’Brien

1986

Diabetes Care

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Ultralente has been used as the basal component of intensive insulin therapy programs. To determine the degree to which a single daily subcutaneous injection of beef ultralente provides stable basal insulin concentrations, plasma free insulin concentrations were measured in six insulin-dependent diabetic patients over a 40-h period. All short-acting insulin was withheld during this interval. Each patient had been maintained on a chronic ultralente based program before study. Little if any evidence of a temporal peak in plasma insulin concentrations was observed. Although considerable variation in plasma insulin concentrations was observed in one individual, beef ultralente provided relatively stable plasma insulin concentrations in the group as a whole. Beef ultralente appears to be a reasonable insulin preparation to use as the basal component in an intensive insulin therapy program.

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“…There is greater variability in ultralente duration and peak effect compared with NPH insulin [39]. Human ultralente has been used as a basal insulin [41]; however, others have not found it to be satisfactory in meeting basal insulin requirements [40,42]. When used as the only long-acting insulin, it is often Figure 1.…”

Section: Basal Insulinsmentioning

confidence: 99%

Intensive diabetes management in pediatric patients

2001

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Intensive diabetes management requires frequent home glucose monitoring, multiple daily insulin injections or chronic subcutaneous insulin infusion, and adjustments of insulin doses in response to changes in blood glucose levels, food intake, and exercise. It also requires a periodic review of previous glucose results to recognize patterns of hyper- or hypoglycemia. The goals of intensive management are age dependent. In young children, avoidance of severe hypoglycemia is the major goal. In older children and adolescents, lowering hemoglobin A(1c) becomes an increasingly important goal. In children of all ages, the ability to have a flexible lifestyle and meal plan is often a priority. This article provides a brief overview of the rationale for implementing intensive diabetes management in pediatric patients, and practical guidelines for implementation.

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Human ultralente insulin.

Abstract: The greater solubility of human insulin and its possible faster action have led to doubts about whether a suf-

Cited by 38 publications

References 11 publications

Immunogenicity of highly purified bovine insulin: a comparison with conventional bovine and highly purified human insulins

Immunogenicity of highly purified bovine insulin: a comparison with conventional bovine and highly purified human insulins

Use of Beef Ultralente for Basal Insulin Delivery: Plasma Insulin Concentrations After Chronic Ultralente Administration in Patients with IDDM

Intensive diabetes management in pediatric patients

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