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Biomedical subjects

J L Day

Publications and source records attributed to J L Day.

At least 19 recordsLinked to original sources

Diabetic neuropathic cachexia and acute bilateral cataract formation following rapid glycaemic control in a newly diagnosed type 1 diabetic patient.

In patients with Type 1 diabetes mellitus (DM), the development of complications within the first few years of diagnosis is very unusual and the development of complications within weeks of commencement of insulin therapy is exceptional. Diabetic neuropathic cachexia, unlike the other more common neuropathies associated with diabetes, is a rare form of peripheral neuropathy characterized by profound weight loss, painful dysaesthesias over the limbs and trunk with spontaneous resolution usually occurring within a year. The morphologically distinct diabetic or metabolic cataract in patients with newly diagnosed Type 1 DM is also a rare complication. We describe the first case of a young man with newly diagnosed Type 1 DM who developed these two rare complications within 3 months of diagnosis and insulin therapy commencement. Rapid development of complications in this patient raises two possibilities, i.e. a probable link between the pathophysiology of these two complications following rapid glycaemic control, and a subset of patients with unusual susceptibility to complications. We re-emphasize the need for vigilant monitoring of complications in young diabetic patients, even in the first few years of their disease. In particular, young patients with visual impairment should be evaluated carefully for evidence of treatable eye complications.

Adult↗

A modal Pritchard approximation for computing array element mutual impedance.

An investigation into the applicability and accuracy of Pritchard's approximation for closely packed transducer arrays is undertaken. A new, "modal" Pritchard approximation is developed, based upon normal modes of the acoustic medium, and is tested for arrays of acoustically hard spheres to ascertain its accuracy in determining the mutual acoustic radiation impedance between array elements. For ka approximately 1, it is found that the modal Pritchard approximation works quite well in approximating the mutual radiation impedance of a two-element array, even for relatively close spacing; but for arrays of three or more scatterers in close proximity the approximation may have relatively large errors. The effect of neglecting inter-element scattering is analyzed for the monopole-to-monopole scattering of various configurations of a three-element array and a sixteen-element double line array.

Journal Article↗

Impaired glucose tolerance and fasting hyperglycaemia have different characteristics.

AIMS: Use of the oral glucose tolerance test (OGTT) to define glucose intolerance in the general population may bias towards selection of those with insulin resistance. Beta cell function and insulin resistance markers were analysed in four groups: controls (n = 101); fasting hyperglycaemia (FH, n 45); impaired glucose tolerance; (IGT, n = 16) and those with features of both FH and IGT ('Both', n = 30). METHODS: Subjects underwent an OGTT. Plasma glucose, fasting lipid profiles, fasting, 30 and 120 min insulin were measured and beta cell function (% B) and insulin sensitivity (% S) assessed by homeostatic model assessment (HOMA) RESULTS: The FH group compared to controls had a significantly lower % B. The IGT group compared to controls had features of insulin resistance (higher body mass index (BMI), systolic blood pressure and 2 h insulin concentration). Subjects with 'both' IGT and FH had features of insulin resistance (higher BMI, systolic and diastolic blood pressure and triglyceride concentration) as well as beta cell dysfunction with a lower % B and 30 min insulin-glucose ratio compared to controls. There was a preponderance of males in this group. In all, 192 subjects' 30-min insulin concentration and incremental insulin response showed only a significantly negative correlation with fasting glucose concentration. In a linear regression analysis, a low 30-min insulin-glucose ratio was only a significant factor in the fasting glucose model. Thus, higher fasting glucose concentrations appear to be associated with beta cell dysfunction. However, HbA1 only showed a significant correlation with 120-min glucose, not fasting glucose concentration. CONCLUSIONS: In those with milder degrees of glucose intolerance, FH is associated with beta cell dysfunction and those with IGT and a relatively 'normal' fasting glucose have features of the insulin resistance syndrome.

Aged↗

Reactive oxygen species (ROS) production and the outcome of diagnostic tests of sperm function.

Washed sperm suspensions from 64 out of 89 (72%) randomly selected infertility patients produced detectable reactive oxygen species (ROS) compared to 17 out of 67 (25%) prospective semen donors (p < 0.01, Chi-square test). Among patients, the median sperm concentration in ejaculates which yielded sperm suspensions that generated detectable levels of ROS was lower than in those which did not: 36.2 (15.63-57.64) vs. 71.5 (22-108) x 10(6)/mL, respectively (median (interquartile range), p < 0.05, Kruskal-Wallis test). In samples that produced ROS, the basal rate of production and the rates after stimulation with 50 mumol N-formyl met leu phe (N-FMLP) l-1 or with 100 nmol phorbol 12-myristate 13-acetate (PMA) l-1 were significantly and inversely correlated with sperm concentration in the ejaculate (r = -0.43, -0.41 and -0.35, respectively, p < 0.01 Spearman's rank correlation). The rate of ROS production showed no relationship to the motility of spermatozoa in semen, whether evaluated visually or via computer assisted semen analysis. However, there was a significant negative correlation (r = -0.370) between the motile, normal sperm concentration (MNSC) and basal ROS production, and when stimulated with N-FMLP (r = -0.311) or with PMA (r = -0.249) (all p < 0.05). In patient samples that generated detectable ROS, the ability of the spermatozoa to retain motility for 24 h after preparation on a 40/80% Percoll gradient was negatively correlated with basal ROS production (r = -0.310, p < 0.05). ROS production was also related to the outcome of in vitro sperm mucus penetration tests. Unstimulated levels of ROS production showed a significant (p < 0.05), negative correlation with the number of progressively motile spermatozoa present in mucus after 15 (r = -0.379) and 60 (r = -0.362) min. These results suggest that sperm samples with increased ROS tend to have poor semen quality and reduced performance in a number of routine, diagnostic sperm function tests.

Adult↗

Development of a questionnaire identifying factors responsible for successful self-management of insulin-treated diabetes.

Education and psychosocial factors are widely believed to contribute to diabetes control. However, there is no systematic way of measuring or recording these factors, or for transfer of information to future care-givers. We developed a 41-question questionnaire to measure the skills and contributory factors to self-management in diabetes, and examined the relationship between these factors and glycaemic control. The questionnaire was assessed for construct validity, and for content validity by independent diabetes health professionals, and easily completed by 128 insulin-treated diabetic patients (mean age 42 +/- 13 (SD) yr, diabetes duration 17 +/- 9 yr, HbA, 10.5 +/- 1.8%). Principle Components Factor analysis revealed nine factors explaining 63% of variance (Eigen values 1.2-5.8). Five of these were significantly related to HbA1. These were: practical self-management skills, p < 0.001; emotional adjustment, p < 0.002; perceived goals, p < 0.01; perceived self-efficacy, p < 0.005; and costs-benefit analysis, p < 0.01. Multiple regression revealed that these five predictor variables (factors) explain 21% of variance in HbA1, combined r = 0.46. The questionnaire also distinguished between patients with good and poor control (HbA1 8.2 vs 13.4%, p < 0.001), p for differences in question responses, 0.014-0.001. Four factors (lifestyle, influence of other people, diet concerns, and weight concerns) were unrelated to HbA1. In conclusion, we have developed a single, patient-completed questionnaire of high content and construct validity, which identifies alterable factors (in contrast to fixed demographic variables) which may be specifically targeted in individual patients on the one hand to improve glycaemic control and, on the other, to enable more satisfactory adjustment to life with diabetes. It may be used in day-to-day practice to identify patient needs, and their barriers to effective self-management, and to transfer this information to future care-givers.

Adult↗

Why should patients do what we ask them to do?

Many factors contribute to patients' self-management success. In the main these are attitudes, beliefs or perceptions of the patients rather than demographic characteristics. Patients do need not only to acquire knowledge and self-management abilities, but also the desire to apply them on a life-long basis. They require understanding and support. Education is a life-long process. All those involved in care need training in the educational process. Both the targets set and achieved by the patients need regular assessment. It is critical to perform a comprehensive assessment of the influencing factors. Conclusions are drawn on the consequences for relief education.

Diabetes Mellitus↗

Microvascular response to tissue injury and capillary ultrastructure in the foot skin of type I diabetic patients.

1. Microvascular blood flow responses to injury and capillary ultrastructure were assessed by laser Doppler flowmetry and detailed light and electron microscopy respectively in skin biopsied from 28 patients with insulin-dependent diabetes and 17 control subjects. 2. The hyperaemic response induced by biopsy (P < 0.001) and heating to 44 degrees C (P < 0.001) was significantly lower in the diabetic patients and showed progressive impairment with the severity of complications (P < 0.001). 3. Skin capillary basement membrane thickness was significantly increased in the diabetic patients (P < 0.001) and also increased with the severity of complications (P < 0.002). Both the luminal area (P < 0.001) and the endothelial cell outer perimeter (P < 0.002), measures of luminal and capillary size, respectively, were significantly reduced in all diabetic patients. 4. Basement membrane thickness was related significantly to the impaired hyperaemic response to both biopsy (P < 0.01) and thermal injury (P < 0.01). 5. Our findings support the hypothesis that structural abnormalities, which are characterized by an early reduction in capillary size and later thickening of basement membrane, form an important mechanism for the impaired hyperaemic response in diabetic patients.

Adult↗

Effect of sulphonylurea therapy on plasma insulin, intact and 32/33 split proinsulin in subjects with type 2 diabetes mellitus.

This study was undertaken to clarify the effect of sulphonylurea therapy on beta cell function in 27 subjects with newly diagnosed Type 2 diabetes mellitus. Plasma glucose, insulin, intact and 32/33 split proinsulin were measured at diagnostic OGTT. After 8-12 weeks on a conventional diet, subjects with a fasting glucose > 9 mmol l-1 (n = 12) were commenced on sulphonylurea therapy. At diagnosis, the sulphonylurea requiring group were more hyperglycaemic (p < 0.0001), less obese (p < 0.05) and more insulin deficient with a lower 30 min insulin (p < 0.0002) than the diet group. Following dietary intervention in the sulphonylurea group, weight remained unchanged but there was a reduction in fasting glucose (p < 0.009). Fasting insulin, intact proinsulin, and 32/33 split proinsulin remained unchanged. After 12 weeks of sulphonylurea therapy there was a weight gain of 1.5 kg (p < 0.01), but a reduction in fasting glucose (p < 0.0001). Fasting insulin and intact proinsulin increased (p < 0.004) but 32/33 split proinsulin remained unchanged. There was a significant increase in both the fasting insulin to glucose ratio (p < 0.005), and intact to 32/33 split proinsulin ratio (p < 0.02). Final fasting glucose following sulphonylurea therapy was positively correlated with the initial intact and 32/33 split proinsulin and the fasting glucose following dietary treatment. It is clear from this work that sulphonylureas have a complex effect on beta cell physiology and as well as stimulating release of insulin they increase the release of intact proinsulin but not that of 32/33 split proinsulin, hence they increase the intact to 32/33 split proinsulin ratio.

Aged↗

Loss of the first phase insulin response to intravenous glucose in subjects with persistent impaired glucose tolerance.

Loss of the first phase insulin response to intravenous glucose is one of the earliest detectable defects of beta cell dysfunction in Type 2 diabetes mellitus. Impaired glucose tolerance (IGT) is considered a prediabetic condition, therefore loss of first phase insulin secretion in subjects with IGT would suggest beta cell dysfunction as an early lesion in the development of Type 2 diabetes. Three groups of subjects were studied, 7 subjects with persistent IGT (classified as having IGT at two 75 g oral glucose tolerance tests (OGTT) done 6 months apart), 6 subjects with transient IGT (IGT at the first OGTT, but normal glucose tolerance at a repeat OGTT 6 months later), and 7 normal controls. First phase insulin secretion was studied using an intravenous glucose tolerance test with arterialized blood sampling. Fasting, 3, 4 and 5 min samples were assayed for glucose and insulin (specific two-site immunoradiometric assay). The fasting insulin was similar in all three groups, however the 3 min insulin response was significantly lower in those with persistent impaired glucose tolerance (p < 0.02). Thus subjects with persistent impaired glucose tolerance demonstrated loss of the first phase insulin response as an early indicator of beta cell dysfunction while subjects with transient IGT had a normal insulin response to intravenous glucose. During the OGTT, the 30 min glucose was not significantly different (p = 0.1) but the 30 min insulin to glucose ratio was significantly lower in subjects with persistent IGT (p < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Community screening for non-insulin-dependent diabetes mellitus: self-testing for post-prandial glycosuria.

Recent requirements of the GP contract have included the testing of random urine samples from all patients aged 16-75 years for glycosuria. As a means of detecting diabetes this will be both inefficient and wasteful of resources, because of the method employed and age group screened. We examined a simple method for screening large populations for non-insulin-dependent diabetes mellitus using self-testing for post-prandial glycosuria, and compared its performance to that using fasting plasma glucose and haemoglobin A1. The study involved five general practices, screening over 13,000 subjects aged between 45 and 70 years. Of the 13,795 subjects screened, 10,348 responded (75%). Glycosuria was detected in 343 subjects (3.3%), of whom 330 (95.9%) attended for oral glucose tolerance testing. Of these 99 (30%) had newly diagnosed diabetes, 56 (17%) had impaired glucose tolerance. A further 65 subjects were identified as having diabetes but were not on a register of cases. Prevalence of diabetes in this age group rose from 2.26% to 4.1%. In a normal population control group (442 subjects from Ely), this system gave a sensitivity of 43%, specificity of 98% and positive predictive value of 53%, and compared favourably to the use of a fasting plasma glucose of 6 mmol/l, which gave a sensitivity of 65%, but only a specificity of 64% and positive predictive value of 9%. These results support the use of this simple system in large population screening for diabetes.

Aged↗

Insulin deficiency rather than hyperinsulinaemia in newly diagnosed type 2 diabetes mellitus.

This paper reports beta cell function as assessed during OGTT using specific IRMAs for insulin, intact and 32/33 split proinsulin in subjects with newly diagnosed Type 2 diabetes matched to normal controls. The relationships between insulin and the proinsulins to risk factors for cardiovascular disease were also examined. Similar fasting insulin concentrations but lower 30-min post-glucose-load insulin concentrations were found in diabetic subjects (mean +/- SEM 143 +/- 12 pmol-1 vs 304 +/- 19 (p < 0.001). Subjects with diabetes had increased fasting intact (10.6 +/- 1.1 pmol-1 vs 3.3 +/- 0.2, p < 0.001) and 32/33 split proinsulin concentrations (8.1 +/- 0.9 pmol-1 vs 2.2 +/- 0.3, p < 0.0001). Beta cell dysfunction, as expressed by a reduction in the 30-min insulin to glucose ratio (9.4 +/- 1 vs 34.8 +/- 2.3, p < 0.0001) and an increase in the fasting percentage of total proinsulin-like to total insulin-like molecules (24.5 +/- 9% vs 11.6 +/- 5, p < 0.001), was present in subjects with diabetes. In diabetic subjects beta cell dysfunction and insulin deficiency increased relative to the degree of fasting hyperglycaemia. It seems clear that beta cell dysfunction and insulin deficiency are major features of Type 2 diabetes. Only the fasting concentration of 32/33 split proinsulin positively correlated with both the waist/hip ratio (r = 0.36, p < 0.001), diastolic blood pressure (r = 0.23, p < 0.01) in addition to plasma triglyceride concentration (r = 0.46, p < 0.001). It is questionable whether hyperinsulinaemia plays a pathogenic role in cardiovascular disease in subjects with glucose intolerance.

Blood Glucose↗

Insulin deficiency and increased plasma concentration of intact and 32/33 split proinsulin in subjects with impaired glucose tolerance.

In order to determine insulin status and beta cell function during the oral glucose tolerance test (OGTT), in impaired glucose tolerance (IGT), 51 such subjects and matched controls, identified during a population survey for diabetes, underwent a 75 g OGTT. Fasting, 30 min and 2 h insulin and intact proinsulin, and fasting and 2 h 32/33 split proinsulin, were measured by specific two-site immunoradiometric assays. The subjects with IGT had higher fasting (geometric mean +/- SD, 5.0 +/- 4.0 pmol-1 vs 2.9 +/- 1.7, p < 0.02) and 2 h intact proinsulin (23 +/- 14 vs 14 +/- 12, p < 0.0001), and fasting (3.2 +/- 3 pmol-1 vs 1.8 +/- 1.8, p < 0.0007) and 2 h 32/33 split proinsulin (18.3 +/- 19 pmol-1 vs 6.6 +/- 15, p < 0.0001). Despite higher plasma glucose concentrations, the IGT group had similar fasting insulin, lower 30 min insulin (216 +/- 124 pmol-1 vs 278 +/- 130, p < 0.02), and a lower 30 min insulin/glucose ratio (23.7 +/- 2.1 vs 34.8 +/- 2.3, p < 0.002). The percentage of fasting proinsulin-like to total insulin-like molecules was higher in those with IGT (15.3 +/- 8% vs 11.6 +/- 8, p < 0.04). After 6 months, at repeat OGTT, the same subjects with IGT were classified as 'persisters' or 'reverters'. The persister (24/51 47.1%), at initial OGTT, had a higher 2 h glucose level, a greater BMI and higher systolic blood pressure, but other parameters were similar to the reverters.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗

Skin epidermal thickness and vascular density in type 1 diabetes.

Epidermal skin thickness and vascular density were assessed in skin biopsies obtained from the dorsum of the foot in 28 Type 1 diabetic patients and 17 normal control subjects, matched for age. Epidermal skin thickness did not differ significantly between control subjects (74 +/- 4 (+/- SE) microns) and diabetic patients (78 +/- 4 microns). It was not related to the duration of diabetes and presence of complications. Neither small (capillary) nor large (arteriole/venule) vessel densities differed significantly between control subjects (59 +/- 6 mm-2 and 19 +/- 2 mm-2) and diabetic patients (65 +/- 4 mm-2 and 22 +/- 3 mm-2). Vessel densities were unrelated to the duration of diabetes and presence of complications.

Adult↗

Benefits provided by an integrated education and clinical diabetes centre: a follow-up study.

The effects of a new integrated system of diabetes care with an enhanced role of the diabetes specialist nurse based in a purposed design diabetes centre, on diabetes control, attendance and cancellation rates, and admission for diabetic emergencies have been reviewed. Glycaemic control was examined in: (a) a cohort of 163 insulin-treated and 47 non-insulin treated diabetic subjects (age < 65 years) studied prospectively before and 3 years following the introduction of a new system of care; (b) a second cohort of more elderly patients aged greater than 65 years studied for the 3 years after the change over; (c) a cross-sectional study of the clinic population (n = 700) the year before and 3 years after the changeover; (d) a group of patients attending standard unaltered clinics in the same district (n = 157). Significant and sustained falls in HbA1 were observed in all groups of subjects attending the centre, with the means for those aged less than 65 falling from 11.9 +/- 2.3% to 9.9 +/- 1.9% and for those aged over 65 from a mean of 11.7 +/- 2.0% to 10.3 +/- 2.3%, 3 years later. The cross-sectional study provided similar results with a mean HbA1 of 12.2 +/- 3.0% prior to changeover and 10.4 +/- 4.4%, 3 years later. Smaller but significant changes were observed in patients continuing to attend the routine clinic (from 12.2 +/- 2.3% to 11.3 +/- 2.6%) over a similar period. Yearly admission rates for ketoacidosis and hypoglycaemia fell from 44 and 23, to 33 and 5 per annum, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Patient experience with a jet injector.

The acceptability of a jet injector compared with disposable syringes for insulin injections was assessed in 10 people with Type 1 diabetes. The majority considered disposable syringes easier to use and either less painful or no more painful than jet injections. Given the choice only 1 of the 8 people completing the study would continue using the jet injector.

Adult↗

New device to improve the accuracy of bedside blood glucose tests.

A new device to improve the accuracy of blood glucose measurements with glucose-oxidase reagent strips is described. The device ensures that an adequate amount of blood is applied onto the reagent pad when the strip is fully inserted. When the strip is withdrawn, the pad is automatically wiped, and so the reaction can be accurately timed. The device also reduces the risk of blood contamination of other surfaces. Use of a prototype of this device enabled more accurate measurement of blood glucose on general wards.

Blood Chemical Analysis↗