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Biomedical subjects

J A Galloway

Publications and source records attributed to J A Galloway.

54 records · Page 3Linked to original sources
PubMedDate not supplied

Factors in the survival of patients with insulin-requiring diabetes for 50 years.

Ninety-seven diabetic patients who had taken insulin for 50 yr and longer were surveyed by questionnaire to identify factors that might explain their unusual longevity. The analysis suggested that the long survival of this group was related to the following: maintenance of normal or near normal body weight, regular contact with a personal physician, periodic blood glucose determinations, frequent urine testing, regular exercise, and longevity of the parents and grandparents. The results support the conclusion that careful management of diabetes favors longevity.

Aged↗
PubMedDate not supplied

Insulin treatment for the early 80s: facts and questions about old and new insulins and their usage.

Recent data now emphasize the importance of blood glucose control as a means of forestalling diabetic microvascular disease. As a result, attempts are being made to optimize conventional insulin therapy, and new modes of insulin delivery (e.g., pumps) are being adopted. Also, improvements in manufacturing technology have resulted in the commercial availability of porcine insulin, which is highly effective in preventing the complications of insulin therapy in those patients receiving only this material. Human insulin, produced biosynthetically in bacteria using recombinant DNA technology, is now being tested. While these developments in insulin and its administration offer great promise to the diabetic patient, many more studies will be needed to determine their absolute clinical benefits.

Animals↗
PubMedDate not supplied

The plasma glucose response of normal fasting subjects to neutral regular and NPH biosynthetic human and purified pork insulins.

Using doses of 0.1 and 0.15 U/kg, the hypoglycemic activities of neutral regular and NPH biosynthetic human insulin (BHI) and purified pork insulin were compared in normal fasting subjects. Neutral regular insulin was administered by the intravenous and subcutaneous routes and NPH subcutaneously. Comparison of the plasma glucose curves disclosed no statistically significant differences between the maximum effects and the length of time to achieve the maximum effect. Moreover, a dose-response difference between 0.1 and 0.15 U/kg could not established. It is concluded that the hypoglycemic activities of neutral regular and NPH BHI and purified pork insulin are the same.

Animals↗
PubMedDate not supplied

Factors influencing the absorption, serum insulin concentration, and blood glucose responses after injections of regular insulin and various insulin mixtures.

Normal fasting subjects received regular insulin and mixtures of regular with NPH or lente to assess the effects of the combinations on serum insulin concentrations (SIC) and blood glucose responses (BGR). In addition, the influence of concentration, depth, and method and site of administration was investigated. In studies of mixtures of regular with NPH and with lente, it was observed that the regular: lente ratio needed to achieve peak SIC was higher than with the regular: NPH combination. Increased SIC, including either the peak and/or the time interval required to achieve the peak, were related to the depth and site (deltoid and abdominal greater than anterior thigh or buttocks). Assuming linear kinetics of absorption, significant quantities of insulin fail to reach the serum. Marked intra- and intersubject variations in SIC and BGR to regular, NPH, and lente insulins were observed.

Biological Availability↗
PubMedDate not supplied

Immunologic improvement resulting from the transfer of animal insulin-treated diabetic subjects to human insulin (recombinant DNA).

To study the immunologic effects of transfer of patients from animal insulins to human insulin (recombinant DNA), a double-blind comparative trial was begun in over 300 patients. Preliminary results are reported in 116 individuals. After maintenance on purified pork or mixed beef-pork insulins (PPI or MBP) for a minimum of 6 mo, 116 patients were either switched to human insulin or maintained on their previous insulin. Antibody levels were assessed at a baseline visit and then monthly. In PPI-maintained individuals as well as those switched to human insulin there was a significant decrease in qualitative antibody binding as indicated by species-specific binding of 125I beef and human insulins (SBB and SBH), both P less than 0.005. Quantitative binding, as indicated by bound insulin levels, decreased to a much greater extent in patients switched to human insulin, 52% versus 31%, P less than 0.005. Parameters derived from formal antibody titration did not change. In patients maintained on MBP, bound insulin decreased (-36% at 6 mo, P less than 0.002). When switched from MBP to human insulin, there was a marked reduction in all parameters of binding, both qualitative and quantitative: SBP, -68%; SBH, -61%; SBB, -57%; bound insulin, -67% (all P less than 0.001) and decreases in high- and low-affinity binding capacities (P less than 0.02). Thus, for patients treated previously with nonhomologous insulins, transfer to human insulin may result in significant immunologic improvement in anti-insulin antibody levels.

Adult↗
PubMedDate not supplied

Development of IgE antibodies to human (recombinant DNA), porcine, and bovine insulins in diabetic subjects.

Thirty-one previously untreated diabetic individuals received only human insulin (recombinant DNA) for 1 yr with no adverse reactions. The development of serum IgE antibodies to human, porcine, and bovine insulins was assessed by a sepharose radioallergoabsorbent test (RAST). Immunoglobulin (total Ig antibody) binding was assessed by a nonabsorbed species-specific radioimmunoassay. During therapy 2 patients developed IgE antibodies to human insulin as well as increased total Ig binding. The IgE antibodies to human insulin cross-reacted with porcine and bovine insulins, were transient, and were not accompanied by insulin allergy. Ig binding to insulin developed and persisted in 11 of the human insulin-treated diabetics. In comparison, 62 previously untreated diabetic persons received only purified porcine insulin (PPI, less than 5 ppm proinsulin, N = 40) or a mixed bovine-porcine insulin (proinsulin less than 50 ppm, N = 21). Increased Ig antibody developed in 16 of 21 patients receiving mixed bovine-porcine insulin and 25 of 41 PPI-treated patients (P less than 0.05). Seven of 41 PPI-treated patients and 4 of 21 mixed bovine-porcine-treated patients developed anti-insulin IgE antibodies, which were transient in 4 and persisted in 6 diabetic patients. IgE antibody levels did not correlate with total Ig antibody. These data suggest that IgE and total Ig antibodies develop less often after human insulin treatment. Also, the immunoregulation mechanisms responsible for anti-insulin IgE antibody synthesis differ from those regulating other Ig that bind to insulins. Since none of the patients in this study have developed clinical manifestations of insulin allergy or resistance, the clinical relevance of the antibody data must remain speculative.

Adult↗
PubMedDate not supplied

Clinical pharmacologic studies with human insulin (recombinant DNA).

Normal fasting subjects were used to study the pharmacokinetics of human insulin (recombinant DNA). Purified pork insulin (PPI) was used as a control agent. There was no difference in serum concentrations between neutral regular human insulin and PPI after intravenous administration. When given subcutaneously, peak concentrations are occasionally higher for human insulin than for PPI. The bioavailability indices for the two insulins are essentially the same. NPH human insulin produced a slightly higher serum concentration after 4 h than did NPH PPI. Studies with 70/30 NPH-regular mixtures suggest that the affinity of protamine for human insulin is less than that for PPI. The serum insulin concentrations after lente human insulin and PPI were not different. These studies, and a review of the published clinical pharmacologic literature, indicate that when present the differences between human insulin and PPI are minimal.

Animals↗
PubMedDate not supplied

The U.S. "new patient" and "transfer" studies.

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.

Adult↗
PubMedDate not supplied

The therapeutic efficacy of human insulin (recombinant DNA) in patients with insulin-dependent diabetes mellitus: a comparative study with purified porcine insulin.

The therapeutic efficacy of human insulin (recombinant DNA) was compared with that of purified porcine insulin (PPI) in seven male subjects with previously treated insulin-dependent diabetes mellitus. In a random crossover design the patients received either PPI or human insulin during one of two consecutive 7-day periods of intensive insulin therapy. Control was evaluated on days 6 and 13. Tissue sensitivity and responsiveness to the study insulins were determined by insulin dose-response studies performed using the euglycemic glucose clamp on days 7 and 14. Insulin dose and all measures of control on days 6 and 13 were not statistically different between treatments. When the insulin dose-response studies during each treatment were compared there were no differences between them. Thus, in previously treated patients with insulin-dependent diabetes, undergoing brief but intensive insulin therapy with continuous subcutaneous insulin infusion, human insulin is as clinically efficacious as PPI. Furthermore, insulin sensitivity and responsiveness, as assessed by dose-response studies during the euglycemic glucose clamp were equivalent for both insulins.

Adolescent↗