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Biomedical subjects

R C Turner

Publications and source records attributed to R C Turner.

At least 217 records · Page 12Linked to original sources

Ultralente based insulin regimens--clinical applications, advantages and disadvantages.

The prolonged action of daily injections of beef ultralente insulin provides a source for the basal, steady state insulin supply which diabetics need in addition to their meal requirements. The complete distinction between basal and meal insulin requirements, provided by two or three injections of soluble insulin per day, allows simple rules to guide both the physician and patient. Thus, the required ultralente dose needs to be continued daily, irrespective of illness or missing meals, whereas the soluble insulin requirements are given according to meals. When starting ultralente insulin therapy a loading dose is required. The doses of ultralente and soluble insulin needed for different severities of diabetes and degrees of insulin resistance can be predicted. A simple regimen to cover the decreasing insulin requirements of newly presenting, ketotic juvenile-onset diabetics has been developed. During surgical operations the continued basal insulin supply, from ultralente insulin, greatly facilitates diabetes control. Whilst many patients have improved nocturnal blood glucose control after transfer to ultralente insulin, optimal control of diabetes sometimes remains difficult in view of the pre-breakfast plasma glucose rise and the longer action of subcutaneous soluble insulin than the physiological meal insulin response. Purified monocomponent beef ultralente insulin is antigenic, and human ultralente insulin might be advantageous.

Diabetes Mellitus↗

Plasma somatomedin activity and diabetic retinopathy.

Somatomedin activity was measured by a rabbit chondrocyte bioassay in plasma of adult patients with insulin-dependent diabetes of 11-28 years duration. Mean somatomedin activity in patients with background or proliferative retinopathy, assessed by ophthalmoscopy or fluorescein angiography, was 1.42 +/- 0.65 U/ml (n = 20) which was significantly greater than in age- and weight-matched control subjects (1.05 +/- 0.22 U/ml, n = 9). In contrast, somatomedin activity was not raised in patients who had no retinopathy (1.16 +/- 0.33 U/ml, n = 10). Diabetic patients with retinopathy also showed the greatest differences between repeat samples suggesting wider fluctuations in plasma somatomedin levels. Plasma growth hormone and glucose measured either simultaneously with somatomedin or during a 12-24 h profile were not different when diabetics with or without retinopathy were compared. The somatomedins have mitogenic actions in vivo on a variety of connective tissues. The possibility that this may extend to retinal vessels should be further evaluated.

Adult↗

Plasma haemostatic factors and diabetic retinopathy.

Plasma coagulation factors were measured in twelve male insulin-dependent diabetics with no retinopathy, ten with background and ten with proliferative retinopathy and ten non-diabetics. Factor VIII pro-coagulant activities (VIII:C), ristocetin cofactor activities and factor VIII-related antigen concentrations (VIIIR:ag) were significantly related to the severity of diabetic retinopathy (P less than 0.025, trend test). The mean ratio of VIII:C/VIIIR:ag was lower in the diabetics with proliferative retinopathy than in the other groups of diabetics (P less than 0.05) or the controls (P less than 0.02). Concentrations of alpha 2 macroglobulin and alpha 1 antitrypsin were highest in diabetics with proliferative retinopathy (0.1 greater than P greater than 0.05, trend test) but mean prothrombin and activated partial thromboplastin times and mean concentrations of alpha 2 antiplasmin, plasminogen activator and antithrombin III were similar in all groups. Concentrations of the platelet-specific protein beta thromboglobulin, though higher in diabetics than controls (P less than 0.005), were not related to retinopathy. The plasma concentrations of coagulation factors did not correlate with creatinine clearance and there were no significant differences between groups in concentrations C-reactive protein; this suggests that the raised concentrations of coagulation factors in diabetics with retinopathy were not a result of associated nephropathy or an 'acute phase protein' response to diabetic tissue damage. Increased coagulation activity in diabetics may contribute to the development of retinopathy.

Adult↗

Pulsatile insulin has greater hypoglycemic effect than continuous delivery.

The relative hypoglycemic effects of pulsatile versus steadily infused insulin have been examined in six normal subjects in whom pancreatic insulin output was suppressed by somatostatin-14. Soluble insulin was infused continuously overnight on one occasion and on another occasion the same quantity was given in pulses of 2-min duration with a gap of 11 min. The mean plasma glucose concentrations were lower when pulsed insulin was given [mean for the last hour: 4.66 +/- 0.08 mmol/L (+/- SEM) versus 5.53 +/- 0.06 mmol/L (+/- SEM) for steady infusion], diverging significantly (P less than 0.05 paired t test) 7 h after the start of the study. The specific binding of 125I(A14)mono-iodo-insulin to monocytes was greater after pulsed insulin (2.9% with pulsed versus 2.4% with steadily infused insulin at tracer-only point; P less than 0.02 paired t test). Thus, intravenous insulin has greater hypoglycemic effect when pulsed, possibly mediated by greater insulin receptor binding.

Adult↗

Insulin treatment of newly-presenting ketotic diabetic patients into the honeymoon period.

Newly-presenting, ketotic juvenile-onset diabetics initially need full insulin replacement, and this has been attempted with ultralente insulin, including a loading dose, to provide the basal insulin requirement, and twice-daily soluble insulin to cover main meals. A simple method has been developed for the patient to reduce the basal and meal-related insulin doses during the stabilisation period, during which insulin production recovers and administered insulin needs fall. The method was applied to 12 patients, whose mean insulin dose was reduced over 4 weeks, from 62 to 33 units/day, with maintenance of good control.

Adolescent↗

Relative contributions of insulin deficiency and insulin resistance in maturity-onset diabetes.

The effects of raised insulin resistance and decreased beta-cell function on basal plasma glucose and insulin concentrations have been estimated by means of a mathematical model which uses the available data on control of glucose and insulin flux. The model shows that near-normal basal plasma insulin levels could be maintained by means of basal hyperglycaemia when beta-cell function is deficient. The hyperglycaemia does not become pronounced until more than 80% of beta-cell function has been lost. However, when only 5-10% of beta-cell remains, plasma insulin levels fall in spite of hyperglycaemic stimulation. Conversely, raised insulin resistance in the absence of decreased beta-cell function induces only a small rise in basal plasma glucose concentrations, which stimulates a compensatory increase in basal plasma insulin concentrations from a normal beta-cell capacity. However, if the beta-cell dysfunction is sufficient to induce a basal plasma glucose concentration of 5-6 mmol/l, a slight rise in insulin resistance causes pronounced basal hyperglycaemia.

Adipose Tissue↗

The effect of initial temperature on free radical decay in PMMA bone cement.

The effect of varying the initial temperature of the components of poly(methyl methacrylate) (PMMA) bone cement has been investigated. Electron paramagnetic resonance (EPR) spectroscopy was used to monitor free radical decay during the curing of the cement. Samples cured in saline at 37 degrees C were found to exhibit first-order decay kinetics for the polymerization radicals for approximately one week after mixing. This indicates that the decay did not take place by combination or disproportionation and was probably due to a transfer process. Decreasing the temperature of the bone cement components prior to mixing resulted in smaller decay rates, but still with first-order kinetics. This decrease in decay rate with lower initial temperature may be due to decreased porosity of the cement, possibly due to decreased monomer evaporation. SEM micrographs of the samples were consistent with this change in porosity.

Bone Cements↗

Twenty-four hour profiles of plasma C-peptide in type 1 (insulin-dependent) diabetic children.

Twenty-four hour profiles of plasma C-peptide, an index of endogenous insulin secretion, were performed in 15 Type 1 (insulin-dependent) diabetic children. Plasma C-peptide was detectable in six children, of whom four ('C-peptide producers') had peak values above normal fasting levels. In each of the six children with residual B cell function, there was a close correlation between plasma C-peptide and simultaneous blood glucose (r greater than 0.50, p less than 0.05). Post-breakfast peak blood glucose was 10.2 +/- 1.7 mmol/l (mean +/- SEM) in the 'C-peptide producers' and 18.7 +/- 1.7 mmol/l in the 11 children with low or no detectable C-peptide. Mean M-value, an index of deviation from an ideal blood glucose, was lower in the 'C-peptide producers' (p less than 0.05). It is concluded that residual functioning B cells in diabetic children behave physiologically in that insulin secretion fluctuates in accordance with the prevailing blood glucose; and that the pattern of action of injected insulin is more critical in non-C peptide producers who lack the post-prandial dampening effect provided by residual endogenous insulin secretion.

Adolescent↗

Low density lipoprotein cholesterol: an association with the severity of diabetic retinopathy.

Diurnal profiles of total and lipoprotein cholesterol and triglycerides were measured in 11 insulin-dependent diabetic subjects without retinopathy, 10 with background and 10 with proliferative retinopathy. The groups were closely matched for age and duration of diabetes. Total cholesterol levels were higher in patients with proliferative (5.6 +/- 0.5 mmol/l) than background (5.1 +/- 0.7 mmol/l) or no retinopathy (4.6 +/- 0.8 mmol/l, trend test; p less than 0.003), due to raised levels of low density lipoprotein (LDL) cholesterol (3.8 +/- 0.9, 3.2 +/- 0.6 and 2.8 +/- 0.8 mmol/l respectively; p less than 0.02). High density lipoprotein (HDL) levels were similar in patients with and without retinopathy and HDL/LDL ratios were lower with more severe retinopathy (p less than 0.025). Cholesterol levels were similar in diabetic subjects without retinopathy and in 12 normal subjects. Triglyceride levels were not related to retinopathy and no measure of plasma lipids correlated with HbA1 or 24-h mean plasma glucose. Total and LDL cholesterol were weakly inversely correlated with creatinine clearance but the association with retinopathy was independent of this effect.

Adult↗

General practice care of non-insulin-dependent diabetes with fasting blood glucose measurements.

Non-insulin-dependent diabetes can be treated using two criteria, the fasting blood glucose concentration and body weight. The feasibility of this means of control, aiming for a fasting blood glucose concentration of less than 6 mmol/liter (108 mg/dl) has been investigated in 10 general practices. Eight practices now use the method routinely. A one-year follow-up in six practices is reported. The number of patients with a fasting blood glucose concentration of less than 108 mg/dl increased from 39 (26 percent) to 65 (59 percent). The mean fasting blood glucose concentration of all 112 patients was significantly (p less than 0.01) decreased from a mean of 148 to 113 mg/dl at three months, and subsequently increased to a still reduced (p less than 0.01) level of 126 mg/dl after one year. The mean hemoglobin A1c level was decreased (p less than 0.01). Six practices preferred to have special clinics at which fasting blood glucose meaurements were taken. Two practices achieved good results with the administration and tests being undertaken by a practical nurse, with supervision from the general practitioner. Assessment of control by four fasting blood glucose determinations a year is less expensive than regular urine tests, and may improve blood glucose control.

Adult↗

Blood viscosity, glycaemic control and retinopathy in insulin-dependent diabetes.

1. In a cross-sectional study, 32 insulin-treated diabetic patients had elevated low shear (27.1 vs 22.1 mPa s, P less than 0.05) and high shear blood compared with 10 non-diabetic controls. After correction to 45% packed cell volume, the abnormality had a tendency to be greater in patients with proliferative (mean low shear viscosity, 30.8 mPa s) than background (29.2 mPa s) or nil/minimal retinopathy (27.6 mPa s, 0.05 less than P less than 0.97, permutational trend test). 2. The fibrinogen levels were higher in the diabetic group (P less than 0.05) and correlated with the low shear blood viscosity (rs = 0.38, P less than 0.05). 3. In a prospective study, 74 insulin-treated diabetic patients with background retinopathy were randomized into two groups. Thirty-six patients were on attempted improved therapy (A group); in these the mean glycosylated haemoglobin (Hb A1c) fell within 1 year (11.6 to 10.1%, P less than 0.001). both the corrected low shear blood and plasma viscosity fell similarly (P less than 0.001). The fall was greater than in those patients who were kept on usual therapy (U group) and whose glycosylated haemoglobin did not change significantly (11.7 to 11.4% over the year. 4. The effect of diabetes on blood viscosity may not be a direct pathological factor, as the same increased viscosity would be produced by a mean increase of 1.7% in packed cell volume, compared with a population range of 14% packed cell volume.

Adult↗

Insulin receptor binding increased by high carbohydrate low fat diet in non-insulin-dependent diabetics.

In comparison to a traditional low carbohydrate diet (LC), the effect of an isocaloric high carbohydrate, high fibre diet (HC) upon the insulin binding to mononuclear blood cells of seven non-insulin-dependent diabetics was examined. Each subject, in random order, took both diets for 6 weeks each. There was no significant difference in weight during either dietary period, but a significant (P less than 0.05) increase in the monocyte insulin binding activity on the HD diet (tracer specific binding: 4.2% HC; 3.5% LC). This was accompanied by a significantly (P less than 0.02) lower fasting plasma glucose concentration (LC = 7.1 mmol/l; HC = 6.1) without a significant change in the fasting plasma insulin level. In contrast to the usual low carbohydrate diet, a high carbohydrate diet tends to correct the lowered insulin receptor status observed in maturity-onset diabetics.

Body Weight↗

Pulsatile, synchronous basal insulin and glucagon secretion in man.

The basal plasma insulin, glucagon, and glucose concentrations of 28 normal subjects were measured at 1-min intervals for periods of 45-120 min. Regular plasma insulin and/or glucagon cycles were detected in 11 subjects by autocorrelation (mean periods 13.1 and 13.7 min, respectively). Individual plasma insulin cycles were defined in all subjects (mean period 10.7 min, amplitude 1.1 mU/L), and were associated, after averaging, with plasma glucagon (amplitude 5.5 pg/ml) and plasma glucose (0.02 mmol/L) cycles. There was a significant correlation between the amplitudes of simultaneous plasma insulin and glucagon cycles (r = 0.23, P = less than 0.05, N = 124). Cross-correlation demonstrated a delay of 2 min between the changes in plasma insulin and glucagon. No comparable oscillations in plasma pancreatic polypeptide were detected. The synchronous pulsatile secretion of glucagon and insulin may be a mechanism by which insulin's hepatic effects are limited, thereby maintaining hepatic glucose production but allowing sufficient peripheral insulin concentrations to inhibit excessive catabolism. The simultaneous pulses of insulin and glucagon may be stimulated by a pacemaker, with the A-B intercellular connections producing insulin and glucagon synchrony.

Adult↗

Genetic susceptibility to the development of retinopathy in insulin-dependent diabetics.

HLA types and blood glucose control were investigated in 127 insulin-dependent diabetics with different grades of severity of retinopathy. The means of all afternoon clinic blood glucose levels from the diagnosis of diabetes were 9.9 +/- 2.1 mmol/L for patients with no retinopathy, 11.8 +/- 2.1 mmol/L for patients with background retinopathy, and 12.4 +/- 2.1 mmol/L for patients with proliferative retinopathy (P less than 0.0001). HLA-DR4 was present in 61 of 87 patients (70%) with background or proliferative retinopathy and 21 of 39 (54%) with no retinopathy. The frequency of HLA-DR4 was lowest in patients with no retinopathy despite "poor control" (mean blood glucose greater than or equal to 11.5 mmol/L) and highest in those who had developed retinopathy despite "good control;" the frequencies of HLA-DR2 showed the reverse pattern. Mantel-Haenszel tests were used to calculate the odds ratios for the presence of retinopathy associated with "poor control" and with HLA-DR4, since each modified the effect of the other. The odds ratio for retinopathy associated with "poor control" was 6.7 (P less than 0.0001). The odds ratio with HLA-DR4 was 3.7 (P less than 0.005). When both risk factors were present, the odds ratio increased to 33.3 (P less than 0.0001). Genetically determined factors appear to influence susceptibility to retinopathy in insulin-dependent diabetics.

Adult↗

Islet changes induced by hyperglycemia in rats. Effect of insulin or chlorpropamide therapy.

To investigate the effect of hyperglycemia on normal islets, rats were made diabetic by a 95% partial pancreatectomy and treated with insulin, saline, or chlorpropamide for 3 mo. Histologic examination and morphometry of the residual pancreas showed islet enlargement and fibrosis that correlated with the mean lasting plasma glucose during the experimental period. Treatment of diabetes with insulin prevented the islet disorganization. The B-cell area per islet remained constant and was not affected by hyperglycemia. Chlorpropamide had little effect on the fasting plasma glucose or islet structure, and no "beta cytotrophic" effect was seen. Chronic hyperglycemia induces islet damage that may affect residual B-cell function in diabetes.

Animals↗