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Biomedical subjects

R B Tattersall

Publications and source records attributed to R B Tattersall.

At least 73 records · Page 4Linked to original sources

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

Twenty-six Type 1 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 (less than 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 micrograms/l. 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 micrograms/l in contrast to values of 1.4 rising to 16.3 micrograms/l 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 micrograms/l (p less than 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.

Animals↗

Insulin dependence: problems with the classification of 100 consecutive patients.

We have evaluated the clinical and immunogenetic features of 100 consecutive patients presenting to an adult diabetic clinic who were judged clinically to need insulin therapy but were not sufficiently ill to be admitted to hospital. Over this same period 15 newly diagnosed patients (aged 13-70 years) were started on insulin as in-patients of whom ten were in ketoacidosis. The 100 out-patients, aged 11-75 years at the time of starting insulin, were followed for at least a year. Fifty-six had islet cell antibodies and/or were heterozygous for HLA DR3 and DR4 (Group A) whereas 44 had neither of these markers (Group B). Islet cell antibodies and/or DR3, DR4 heterozygosity were most common in the 70 patients diagnosed below the age of 40 years but were also found in older patients. Patients in Group A were significantly younger at diagnosis (29 vs. 43 years), had a shorter duration of symptoms (17 vs. 61 weeks), were more likely to have ketonuria, and had a lower random C-peptide level at diagnosis (0.2 vs. 0.31 nmol/l). The two groups could not be distinguished by weight, haemogloblin A1 or blood glucose at diagnosis or by diabetic control or insulin dose after one year. The National Diabetes Data Group (NDDG) definition of insulin dependence stresses the importance of HLA types and islet cell antibodies although we found their prevalence to be low in the 30 patients diagnosed over 40 years who clinically were indistinguishable from the younger patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Vertebral and paravertebral sepsis in diabetes: an easily missed cause of backache.

Vertebral osteomyelitis and epidural abscess are uncommon causes of backache but may have a prediliction for patients with diabetes. We report four cases seen in a diabetic unit over 2 years to emphasize the importance of making a diagnosis as early as possible. We suggest that when a diabetic patient complains of backache the erythrocyte sedimentation rate should be measured since this is the best clue that backache is due to something other than a mechanical derangement.

Abscess↗

The practice of group psychotherapy with adult insulin-dependent diabetics.

The content and dynamics of two 11-session psychotherapy groups led by physicians for 18 adult patients with insulin-dependent diabetes are described as a guide for others wishing to use this form of treatment. Patients had often found that having diabetes alienated family and friends and many saw their illness as a shameful imperfect state which might at any time be exposed publicly, usually as a result of hypoglycaemia. Our therapy groups, although time consuming for busy physicians, were much shorter than conventional psychotherapy groups but were nevertheless effective in that five patients made good use of the sessions and six moderate use. Powerful feelings were expressed, sad stories told, and self-esteem raised by the acceptance that group members experienced. It is stressed that those wishing to lead psychotherapy groups need both training and supervision.

Adult↗

The difficult choice of treatment for poorly controlled maturity onset diabetes: tablets or insulin?

Patients with maturity onset diabetes that is poorly controlled on maximal doses of oral hypoglycaemic agents are difficult to treat. A prospective randomised crossover study was performed in 58 predominantly non-obese patients on maximal doses of glibenclamide or metformin, or both, to find out if insulin would improve control or well being. The patients were given daily injections of up to 48 units of highly purified porcine lente insulin. Glycaemic control was improved by 15% or more in only 18 patients; 14 others felt better but their diabetes was no better controlled. Those whose control was improved by insulin could not be distinguished by age, duration of diabetes, body mass index, or their own treatment preference. C peptide concentrations, however, did help predict the response to insulin, the fasting C peptide to glucose ratio being considerably lower in those patients whose control was better on insulin. These findings suggest that a simple insulin regimen does not necessarily lead to better glycaemic control in maturity onset diabetes. Nevertheless, a trial of insulin is often justified since it poses few practical difficulties and makes some patients feel better even if their control is not improved. A more complex regimen might improve control in more cases, but it might also be less acceptable to older patients.

Adult↗

Factors governing the human immune response to injected insulin.

Seventy-nine patients were observed prospectively during their initial period of treatment with conventional bovine insulins. Insulin antibody levels 6 months after starting insulin therapy did not correlate with age, gender or beta cell function at onset of treatment. Patients who required soluble insulin in addition to isophane insulin developed higher levels of insulin antibody. Patients bearing the HLA-B8, DR3 and C4AQO alleles had lower levels of insulin antibody, whereas those bearing DR7 produced significantly higher levels. Other alleles at the C4A, C4B, C2, factor B or Gm loci did not appear to have a significant effect on insulin antibody production. The hyporesponsiveness of B8/DR3/ C4AQO -positive individuals probably reflects a non-specific abnormality of immunity whereas the enhanced responsiveness of those positive for DR7 suggests the presence of a specific immune response gene for insulin.

Adolescent↗

Seven years experience of home management in pregnancy in women with insulin-dependent diabetes.

Fifty-eight of a consecutive series of 75 pregnancies in women with insulin-dependent diabetes went into the third trimester. Diabetes was managed by home blood glucose monitoring and women were not routinely admitted at any stage before delivery. The mean number of in-patient days before delivery was 15 for the whole series but has been reduced to 9 during the past four years. Each woman performed an average of 171 blood glucose measurements during her pregnancy. Mean blood glucose (including post-prandial levels) fell significantly from 7.9 mmol/l in the first trimester to 7.3 in the second and 6.4 in the third. Mean percentage of haemoglobin A1 was within the normal range in the second and third trimesters. The cesarean section rate was high at 66% but there were no perinatal deaths. Three infants had congenital abnormalities. We conclude that home blood glucose monitoring is a safe and effective way of managing pregnant diabetic women as out-patients. The cost of meters and sticks is repaid many times over in the saving of hospital costs. In addition, home blood glucose monitoring is popular with the patients and many choose to continue it after delivery.

Blood Glucose↗

HLA phenotype and insulin antibody production.

HLA phenotypes have been determined in 79 patients as part of a prospective study of factors governing the immune response to injected insulin. IgG insulin antibody levels 6 months after starting treatment with bovine insulin were significantly higher in patients bearing HLA-DR7 and this in conjunction with the lack of a similar pattern in the IgG response to Helix pomatia haemocyanin, suggests the presence of an immune response gene for insulin. The hyporesponsiveness of HLA-B8/DR3/C4AQ0 positive individuals is more likely to reflect a non-specific abnormality of immunity.

Adolescent↗

Influence of imaginative teaching of diet on compliance and metabolic control in insulin dependent diabetes.

Dietary non-compliance is an important cause of poor metabolic control in insulin dependent diabetes. Patients are often blamed, but teaching methods may be at fault, so a prospective study was set up to compare the effect of three different teaching methods. After a three month run in, 40 adults with longstanding poorly controlled insulin dependent diabetes (mean haemoglobin A1 13.0%) were allocated at random to three teaching methods: conventional diet sheet instruction (group 1); practical lunchtime demonstrations (group 2); videotape education (group 3). Knowledge was assessed by questionnaires, compliance by seven day food records, and glycaemic control by serial glycosylated haemoglobin measurements. During six months of follow up there was no improvement in knowledge, compliance, or HbA1 in group 1, but in groups 2 and 3 both knowledge and compliance improved. In group 2 HbA1 fell to 10.6 (SD 2.1)% and in group 3 to 9.6 (2.3)%. The change in HbA1 showed an appreciable correlation with dietary compliance as judged by day to day consistency in carbohydrate intake. These findings show that new and interesting educational methods can have a major influence on knowledge, compliance, and metabolic control in insulin dependent diabetes.

Adolescent↗

Effects of new insulins on insulin and C-peptide antibodies, insulin dose, and diabetic control.

24 diabetic patients stabilised on conventional bovine insulins and possessing insulin antibodies underwent a study of the immunological and clinical consequences of changes in both purity and species of their insulin preparations. After a 2-month run-in period patients were treated for 3 consecutive 4-month periods with (a) purified bovine insulin (20-40 ppm proinsulin), (b) highly purified porcine insulin, and (c) semisynthetic human insulin, without elective dose changes. Mean insulin antibody levels changed little on purified bovine insulin (22.2 leads to 23.4 micrograms/l) but fell on highly purified porcine (23.4 leads to 12.9 micrograms/l) and remained much the same on Semi-Synthetic human insulin. In contrast, C-peptide antibodies fell significantly and continuously throughout the study. The slower rate of fall in C-peptide antibody levels is likely to be due to the prolonged half-life of circulating exogenous proinsulin in the presence of insulin antibody. Although insulin dose remained constant the incidence of hypoglycaemic episodes did not increase and glycosylated haemoglobin levels rose significantly when patients were on porcine insulin. The deterioration in diabetic control may have been due to greater temporal mismatch between insulin needs and insulin availability with pork or human insulin than with beef insulins, and to reduced insulin antibody levels. The use of purer insulins which more closely resemble the human form can cause a significant reduction in levels of insulin and C-peptide antibodies. Although these changes may have other benefits they do not necessarily produce better diabetic control. Subcutaneous insulin regimens need to be tailored to the individual patient and, indirectly, to his antibody status.

Animals↗

Does diabetic control matter?

Whether achieving normoglycemia is beneficial or dangerous to the diabetic patient has been a matter of debate. The authors explore such issues as the prevention or reversal of complications with tight metabolic control, and the methods currently available to achieve normoglycemia.

Adolescent↗