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Biomedical subjects

E A Gale

Publications and source records attributed to E A Gale.

At least 73 records · Page 4Linked to original sources
PubMed1992

Loss of regular oscillatory insulin secretion in islet cell antibody positive non-diabetic subjects.

Basal insulin secretion was compared in nine islet-cell antibody positive, non-diabetic first-degree relatives of children with Type 1 (insulin-dependent) diabetes mellitus and nine normal control subjects matched for age, sex and weight. Acute insulin responses to a 25 g intravenous glucose tolerance test were similar in the two groups (243 (198-229) vs 329 (285-380) mU.l-1 x 10 min-1, mean (+/- SE), p = 0.25). Fasting plasma insulin was assayed in venous samples taken at one min intervals for 2 h. Time series analysis was used to demonstrate oscillatory patterns in plasma insulin. Autocorrelation showed that regular oscillatory activity was generally absent in the islet-cell antibody-positive group, whereas a regular 13 min cycle was shown in control subjects (p less than 0.0001). Fourier transformation did, however, show a 13 min spectral peak in the islet-cell antibody positive group, consistent with intermittent pulsatility. We conclude that overall oscillatory patterns of basal insulin secretion are altered in islet-cell antibody positive subjects even when the acute insulin response is within the normal range.

Activity Cycles↗
PubMed1992

Distinct cytoplasmic islet cell antibodies with different risks for type 1 (insulin-dependent) diabetes mellitus.

The cytoplasmic islet cell antibody patterns of sera from islet cell antibody positive non-diabetic and diabetic endocrine autoimmune patients, and newly-diagnosed Type 1 (insulin-dependent) diabetic patients were characterised using four layer immunofluorescence with monoclonal anti-proinsulin or anti-glucagon antibodies. Two distinct islet cell antibody types were identified. One gave a diffuse cytoplasmic staining in both Beta and Alpha cells ('whole' islet pattern), and was not affected by pre-incubation with rat brain homogenate. The other had a granular appearance with staining restricted predominantly to Beta cells ('selective' islet pattern) and was completely inhibited by pre-incubation with rat brain homogenate. Some sera appeared to have a 'mixed' islet pattern, in which glucagon-positive cells gave a weaker cytoplasmic staining than proinsulin-positive cells. The granular 'selective' pattern was found in sera from 19 (79%) of 24 non-diabetic endocrine autoimmune patients, in two (22%) endocrine autoimmune patients who developed Type 1 diabetes (p less than 0.0001 vs non-diabetic endocrine autoimmune patients), and in none of 19 newly-diagnosed diabetic patients. The 'whole' islet pattern was found only in sera from patients who had, or who subsequently progressed to, Type 1 diabetes. This study has identified a novel islet cell antibody specificity and demonstrates that in islet cell antibody positive endocrine autoimmune patients, only islet cell antibodies which stain both Beta and Alpha cells are associated with progression to Type 1 diabetes.

Adult↗
PubMed1992

Early T-cell defects in pre-type 1 diabetes.

Alterations of lymphocyte subsets have been recently reported in pre-type 1 diabetes but the relation with other immunological markers, in particular islet cell antibodies (ICA), is still unknown. In the present study, we have investigated prospectively changes of lymphocyte subsets in 86 first-degree relatives of patients affected by type 1 diabetes and correlated such modifications with ICA titres. Among individuals with persistent ICA, 8 had ICA titres of more than 20 JDF units, 14 had ICA titres between 5 and 20 JDF units and 64 had ICA titres between 0 and 5 JDF units. First-degree relatives with ICA titres of more than 20 JDF units had significantly decreased proportions of CD3 cells. This reduction was predominantly in the CD4 subset, giving rise to a decreased CD4/CD8 lymphocyte ratio. Those with ICA titres between 5 and 20 JDF units showed abnormalities in both CD3 and CD4 lymphocytes, but not in CD4/CD8 lymphocyte ratio. Further characterization of the CD4 cell subset was performed using three other monoclonal antibodies, CD45RO (UCHL1), CD45RA and CD29, phenotyping memory T-cells, the inducer cells of suppressor function and helper-inducer cells, respectively. The proportions of total CD45RO and CD45RA were not significantly different among first-degree relative with distinct ICA titres in a cross-sectional study, whereas a trend towards a reduced proportion of CD4/CD45RA cells was observed. The longitudinal study demonstrated that individuals potentially susceptible to the development of type 1 diabetes and who possess high titres of ICA have impairment of CD4/CD8 lymphocyte ratio, mainly due to a reduction in the CD4 subset.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1992

Immunochemical investigation of insulinomas for islet amyloid polypeptide and insulin: evidence for differential synthesis and storage.

An affinity purified antibody to fragment 14-29 of islet amyloid polypeptide (IAPP) has been prepared. This antibody, which does not cross-react with the related molecule calcitonin gene-related peptide, was used to investigate immunochemically the presence of IAPP in normal and neoplastic human pancreatic endocrine tissue. The pattern of IAPP staining in normal pancreas mirrors that of insulin, although slight differences were observed. In neoplastic tissue, IAPP was found in 16 out of 19 tumours that were positive for insulin, and was absent from one tumour negative for insulin. In some cases there were differences in the staining patterns of IAPP and insulin. These results suggest that the synthesis and secretion of IAPP and insulin are not inter-dependent and support the concept that IAPP has a discrete biological function. Islet amyloid polypeptide was found in six out of six insulinoma amyloid deposits, suggesting that the peptide is an invariable component of these deposits. Over-expression of IAPP, with aberrant processing and/or secretion, may be the causative factor for amyloid deposition in insulinomas and in the islets of type 2 (non-insulin dependent) diabetic patients. Investigation of patients with insulinomas and of insulin cells in culture and tissue sections may help to clarify the biological function of IAPP.

Adenoma, Islet Cell↗
PubMed1992

Identification of genetic susceptibility loci for insulin-dependent diabetes in Sudan.

In this study we report, for the first time, the molecular analysis of HLA-DR and DQ gene frequencies in a large cohort of well-characterized type 1 (insulin-dependent) diabetes mellitus (IDDM) patients (n = 72), and ethnically matched controls (n = 59) collected in sub-Saharan Africa. High molecular mass DNA was prepared and analysed in Southern blots and by oligonucleotide typing. We have shown a strong positive association between IDDM and the Asp 57- DQB1 allele *0201 (DQw2). A rare DR4, DQw2 haplotype was also identified at high frequency in the IDDM cohort. We can now confirm that the association between Asp 57- DQB1 alleles and IDDM, previously reported in ethnically diverse cohorts collected in Western Europe, North America, and South Asia, is also present in an IDDM cohort collected in Africa.

Adolescent↗
PubMed1992

Insulin and growth factors adaptation to normal puberty.

Insulin and IGF-1 production were measured throughout childhood and puberty and into adult life. Basal insulin and IGF-1 secretion increased during puberty, falling back to prepubertal levels in adulthood. However, fasting glucose levels remained constant, implying an increase in tissue resistance to insulin coinciding with puberty.

Adaptation, Physiological↗
PubMed1992

Standardization of IVGTT to predict IDDM.

OBJECTIVE: To review current practice in centers that use the IVGTT for prediction of IDDM. To establish consensus protocol for performance of the test. RESEARCH DESIGN AND METHODS: Postal questionnaires were delivered to 12 centers. RESULTS: Eleven centers used a glucose dose of 0.5 g/kg and 1 used 0.3 g/kg; the dosage in adults was limited to a maximum of 25-50 g in some centers but others applied no upper limit. The glucose concentration of the infusate varied between 20 and 66%. Eight centers injected glucose manually, two used a syringe pump, and two used gravity infusion. The period of infusion ranged from 30 +/- 10 s to 4 +/- 2 min, and time zero was taken as the start (1 center), middle (1 center), or end (10 centers) of the infusion. The potential range in timing of the +1-min sample varied between 1 and 7 min from the start of the infusion. Quality-assurance standards for the insulin assays used were not always appropriate for the fasting and low stimulated range of insulin levels. CONCLUSIONS: The first-phase insulin response to the IVGTT is widely measured as an index of risk of progression to IDDM. We established that methodology varies widely. Because of this, a new standard protocol for use in prediction of IDDM was agreed by an ICARUS working group and is described herein.

Adult↗
PubMed1991

Analysis of HLA-DR and -DQ gene polymorphisms in Sudanese patients with type 1 (insulin-dependent) diabetes.

In this study we report for the first time, the molecular analysis of HLA-DR and -DQ gene frequencies in a large cohort of well characterized type 1 (insulin-dependent) diabetes mellitus (IDDM) patients (n = 72), and ethnically matched controls (n = 59) collected in sub-Saharan Africa. High molecular mass DNA was prepared and analyzed in Southern blots with DRB1, DQA1, and DQB1 probes. By identifying DR and DQ allele-specific restriction fragment length polymorphisms (RFLPs), we have shown a strong positive association between IDDM and the Asp 57- DQB1 allele *0201 (DQw2). A rare DR4, DQw2 haplotype was also identified at high frequency in the IDDM cohort. We can now confirm that the association between Asp 57-DQB1 alleles and IDDM, previously reported in ethnically diverse cohorts collected in Western Europe, North America, and South Asia, is also present in an IDDM cohort collected in Africa.

Adolescent↗
PubMed1991

Ketone infusion lowers hormonal responses to hypoglycaemia: evidence for acute cerebral utilization of a non-glucose fuel.

1. The effect of hyperketonaemia on counter-regulatory hormone responses to hypoglycaemia has been examined in six healthy subjects. 2. A controlled, step-wise reduction in blood glucose concentration was achieved by adjusting the rate of glucose infusion during a primed-continuous infusion of soluble insulin (1.5 m-units min-1 kg-1 body weight, plasma insulin concentration approximately 90 m-units/l). Simultaneous infusion of either saline or beta-hydroxybutyrate (3 mg min-1 kg-1 body weight) was administered in a single-blind fashion, in random order. Despite a need for 40% more glucose during the ketone infusion, an identical fall in blood glucose concentration was achieved in each study. 3. The glycaemic threshold for stimulating an adrenaline response of 0.41 nmol/l was reduced from 3.1 to 2.8 mmol/l (P less than 0.05) during ketone infusion, and that for stimulating a response of more than 50% of basal from 3.6 to 3.1 mmol/l (P less than 0.001). The peak adrenaline response fell from 7.97 to 2.6 nmol/l (P less than 0.04). Peak noradrenaline, cortisol and growth hormone responses were also significantly lower during ketone infusion (P = 0.04, 0.001 and 0.006, respectively). Glucagon responses alone were unaffected by hyperketonaemia. 4. The provision of an alternate metabolic fuel thus produced immediate changes in the neurohumoral responses to hypoglycaemia. This is consistent with the hypothesis that human nervous tissue can metabolize ketones acutely.

3-Hydroxybutyric Acid↗
PubMed1991

Capillary and venous blood glucose measurements using a direct glucose-sensing meter.

The aim of the study was to evaluate the precision and accuracy of the ExacTech home blood glucose meter when used with either capillary or venous blood and to compare this with a reference whole blood glucose assay. Non-fasting glucose measurements were used since a validation study showed no capillary-venous differences between fasting and post-prandial states. In a cross-sectional study, blood was taken from 182 patients and measured in duplicate on three batches of strips. Altogether we analysed 1089 readings. The regression of the data from capillary blood samples (meter vs reference method) had a correlation coefficient, of 0.93, and a mean bias of 0.2 mmol l-1. The corrected 90% confidence interval was +/- 1.5 mmol l-1 overall, and +/- 0.9 mmol l-1 for readings under 7.0 mmol l-1. Regression of the data from venous blood samples (meter vs reference method) had a correlation coefficient of 0.93 and a slope of x 1.1. The corrected 90% confidence interval was +/- 1.7 mmol l-1. Thus venous blood may be used even though the meter is calibrated for capillary samples but the value must be corrected by dividing by 1.1. Error-grid analysis showed that day-to-day clinical decisions could be made on the basis of ExacTech readings, although a diagnosis of borderline diabetes may not be possible.

Blood Glucose↗
PubMed1991

Intraocular pressure and pupillary responses in patients with diabetes mellitus.

Intraocular pressure (IOP) and the mydriatic responses to darkness in 38 diabetic patients have been compared with those of a matched control group of normal subjects. Overall, the diabetic patients had a significantly higher mean IOP than the control group, but this difference was not found in a sub-group of 13 diabetic patients with evidence of autonomic neuropathy. Those diabetic patients with evidence of autonomic neuropathy had a smaller mydriatic response to darkness than the control group, and this test may usefully be added to standard tests of autonomic function in the diagnosis of autonomic neuropathy.

Adolescent↗
PubMed1991

A preliminary study of the ocular hypotensive effects of bromocriptine in diabetic patients with autonomic neuropathy.

The effect of bromocriptine on intraocular pressure has been investigated in a group of 8 diabetic patients with autonomic neuropathy, to test the hypothesis that bromocriptine exerts its ocular hypotensive action through presynaptic dopamine receptors. Bromocriptine eye drops (0.025%) produced a significant fall in intraocular pressure in a control group of 8 matched normal volunteers, but this effect was not seen in the eyes of the diabetic patients. These results are consistent with a presynaptic site of action of bromocriptine.

Adult↗
PubMed1991

Parathyroiditis in the non-obese diabetic mouse--a new finding.

Autoimmune reactions to parathyroid cells have been observed in human autoimmune polyendocrinopathy, but such findings have not been described in animal models of polyendocrine autoimmunity. We report here three cases of lymphocytic infiltrations in 12 parathyroid glands identified in a total of 18 thyroid glands studied in the non-obese diabetic (NOD) mouse. The majority of parathyroid-infiltrating lymphocytes possessed the helper/inducer phenotype as defined by the L3T4 monoclonal antibody. Parathyroiditis was accompanied by lymphocytic thyroiditis only on one occasion, whereas in other cases of thyroiditis, lymphocytic infiltration of the parathyroid was undetectable. We conclude that parathyroiditis in the NOD mouse is part of the wide spectrum of autoimmunity observed in this animal model of diabetes.

Animals↗
PubMed1991

Progression to type I diabetes in autoimmune endocrine patients with islet cell antibodies.

In an 11-yr screening program carried out on serum samples sent to an autoimmune serology laboratory, 158 patients with clinical or subclinical autoimmune endocrine manifestations and islet cell antibodies (ICAs) in the absence of overt diabetes were identified and followed for the development of insulin-dependent (type I) diabetes. Twenty-two (13.9%) developed type I diabetes in a follow-up of up to 12 yr (mean +/- SE 4.8 +/- 3.2 yr). The probability of being free of type I diabetes was 69.8% at 10 yr after the first detection of ICAs. Progression to disease was influenced by 1) the amount of ICAs represented by high titers (63% of those with ICAs greater than or equal to 20 Juvenile Diabetes Foundation units being free of type I diabetes at 10 yr), ICA persistency (59% being free of type I diabetes; P less than 0.02 vs. nonpersistent ICA), and complement-fixing (CF)-ICAs (63% being free of type I diabetes; P less than 0.05 vs. non-CF-ICA); 2) the coexistence of insulin autoantibodies (IAAs) (25% being free of type I diabetes; P less than 0.005 vs. IAA-); and 3) a positive family history (1st-degree relative) for type I diabetes (32% being free of type I diabetes; P less than 0.005 vs. no family history). There was a trend for diabetes to develop earlier in males of a younger age. No relationships were found with the number, type, or clinical expression of the associated autoimmunities or with a family history of such disorders.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Effect of antecedent glucose control on cerebral function during hypoglycemia.

OBJECTIVE: The incidence of both severe and asymptomatic hypoglycemia is increased threefold in intensively treated diabetic patients. To examine whether this reflects cerebral adaptation to low blood glucose levels, we investigated the effect of preceding glycemic experience on hormonal, EEG, and evoked potential responses to experimentally induced hypoglycemia with the slow-fall clamp. RESEARCH DESIGN AND METHODS: Three groups were examined: well-controlled diabetic patients and patients with insulinoma (group 1), poorly controlled diabetic patients (group 2), and nondiabetic subjects (group 3). RESULTS: The glucose threshold for epinephrine release was lower in group 1 (2.3 +/- 0.1 vs. 3.0 +/- 0.3 and 3.1 +/- 0.1 mM, P less than 0.02), and the peak epinephrine response was reduced (1.29 +/- 0.36 vs. 5.48 +/- 1 and 5.62 +/- 1.2 nM, P less than 0.01) compared with groups 2 and 3, whereas symptoms were not perceived until a lower blood glucose level had been reached (2.0 +/- 0.2 vs. 3.3 +/- 0.4 and 2.6 +/- 0.2 mM, P less than 0.01). Other counterregulatory responses were similarly delayed and diminished. In contrast, EEG changes that were compatible with hypoglycemia were detected in all subjects in group 1 (blood glucose 1.9 +/- 0.1 mM) but in only two in group 2 and none in group 3, despite similar blood glucose nadirs. CONCLUSIONS: The glycemic threshold for hormonal responses to hypoglycemia falls in individuals with intensively treated diabetes or insulinomas, but these patients are more likely to develop EEG abnormalities during hypoglycemia. This disparity helps explain the increased vulnerability of intensively treated patients to severe hypoglycemia.

Adult↗
PubMed1991

Persistent normal anion gap acidosis in the recovery phase of diabetic ketoacidosis.

Diabetic ketoacidosis is associated with an increased anion gap but its recovery phase may be complicated by hyperchloraemic acidosis with a normal anion gap. We report a case where this complication developed. There was a delayed return to normal acid-balance, possibly aggravated by administration of hyperchloraemic fluids, and the true diagnosis was overlooked. Measurement of the anion gap remains an important part of the assessment of diabetic acid-base disturbances.

Acid-Base Equilibrium↗
PubMed1990

Quantification of islet-cell antibodies and prediction of insulin-dependent diabetes.

The sensitivity and predictive value of islet-cell antibodies (ICA) for the future onset of insulin-dependent diabetes mellitus (IDDM) were determined in 719 first-degree relatives of IDDM patients. ICA were quantified in Juvenile Diabetes Foundation (JDF) units, by indirect immunofluorescence in serum samples taken during prospective follow-up of up to 10.5 years. The threshold of ICA detection was 4 JDF units. ICA were detected in the first sample of 26 (3.3%) of the relatives, compared with 12 (2.2%) of 540 controls (298 blood donors and 242 healthy children). ICA were detected in follow-up samples from a further 14 relatives. IDDM developed in 14 (35%) of the 40 relatives with detectable ICA at any time and in 2 (0.3%) relatives without detectable ICA. In all 5 relatives with peak ICA levels above 80 JDF units IDDM developed within follow-up of 7 years; survival without IDDM at 10 years was 27% among relatives with peak ICA levels of 20-80 JDF units and 82% for peak ICA levels of 4-20. The predictive value for IDDM development within 10 years ranged from 40% (threshold 4 JDF units) to 100% (80 JDF units) and the sensitivity from 31% (80 JDF units) to 88% (4 JDF units).

Actuarial Analysis↗