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Biomedical subjects

R C Turner

Publications and source records attributed to R C Turner.

At least 199 records · Page 11Linked to original sources

Loss of diabetic control and increased protein glycosylation following minor intercurrent infections.

To investigate the effect of intercurrent infections, 30 insulin-dependent diabetics and 12 normal subjects were followed prospectively during one winter, with short-term periods of control being assessed by the degree of glycosylation of plasma proteins. Eight diabetics and 7 normal subjects developed an intercurrent infection. During stable control, the diabetics had a mean +/- 1 S.D. glycosylation of 0.90 +/- 0.06 nmol HMF/mg protein/2 hour incubation, compared with the normal subjects of 0.63 +/- 0.04 nmol HMF/mg protein/2 hour. Following infection, there was no increase in glycosylated plasma protein in the normal subjects, but the diabetics increased at 3 and 6 days to 1.07 +/- 0.17 and 1.12 +/- 0.17 nmol HMF/mg protein/2 hour respectively (p less than 0.05 and p less than 0.01). This was similar to levels (1.09 +/- 0.20 nmol HMF/mg protein/2 hour) found in 12 diabetic subjects admitted to hospital because of marked loss of control with ketonuria. The marked protein glycosylation effect of temporary loss of glucose control following 'minor' intercurrent infections suggests that more attention should be paid to diabetic control during brief illnesses.

Adult↗

A practical guide to basal and prandial insulin therapy.

Separating basal and meal-related insulin requirements allows a systematic approach to subcutaneous insulin therapy. Simple guidelines for both the doctor and patient can cater for the spectrum of severity of diabetes. A non-insulin-dependent diabetic who, despite dieting, continues to have moderate fasting hyperglycaemia (6-10 mmol/l) may need only a basal insulin supplement, whereas a totally insulin-dependent diabetic usually needs similar amounts of basal and meal-related insulin. The likely insulin requirements of individual diabetics can be predicted, including the increased amounts required by obese patients. The algorithms have been developed using ultralente to provide the basal insulin requirement, but the principles and doses probably apply to other similarly long-acting insulins or an insulin pump. The insulin doses can be easily altered for varying lifestyles, including night work, religious fasts or long distance aeroplane travel, and for temporary disturbances such as operations or intercurrent infections.

Algorithms↗

Patient-orientated metered capillary blood collection.

A small collector bottle, with a precision-moulded top, allows capillary blood from a finger-prick to be automatically metered into a diluent for subsequent laboratory analysis. This device, which has been successfully used by patients to obtain full blood counts, glycosylated haemoglobin values and blood glucose measurements, may have wide application.

Blood Cell Count↗

Plasma fibronectin, factor VIII-related antigen and fibrinogen concentrations, and diabetic retinopathy.

Fibronectin and factor VIII-related antigen (VIIIR: AG), which are produced by the endothelium and are involved in cellular adhesion, may have a role in the development of diabetic retinopathy. We have measured plasma levels of these glycoproteins and of fibrinogen in 9 control males, 10 insulin-dependent diabetic males with nil or minimal retinopathy and 10 insulin-dependent diabetic males with proliferative retinopathy. These three groups were closely matched for age, body weight and smoking habit. The diabetics in each retinopathy group had similar duration of disease and insulin doses. There was no significant difference between plasma fibronectin concentrations in the three groups. Both plasma factor VIII-related antigen activity and fibrinogen concentration were higher amongst the diabetic subjects, especially those with proliferative retinopathy. These two latter measures correlated significantly when the diabetics were considered as a single group, whereas they did not correlate with fibronectin. Plasma concentrations of fibrinogen and factor VIII R: AG, but not fibronectin, have an association with diabetic microvascular disease.

Adult↗

Human ultralente insulin.

The greater solubility of human insulin and its possible faster action have led to doubts about whether a sufficiently long acting formulation could be produced to provide a basal supply for diabetics. In a double blind crossover study in 18 diabetics human ultralente insulin was as effective as beef ultralente insulin in controlling basal plasma glucose concentrations (median 5.7 mmol/l (103 mg/100 ml) with human and 6.3 mmol/l (114 mg/100 ml) with beef ultralente insulin respectively). There was no significant difference between human and bovine insulin in the rise in plasma glucose concentration from 0400 to 0700 after an injection the previous morning and no difference between patients receiving an adequate or insufficient dose of human ultralente insulin. Bovine insulin antibody binding was reduced with human insulin (p less than 0.002), which suggests that human insulin is less antigenic than beef insulin. Once daily human ultralente insulin provides a suitable formulation for the basal insulin requirement of diabetics.

Adult↗

Abnormal endothelial release of fibrinolytic activity and fibronectin in diabetic microangiopathy.

Endothelial cell function in Type 1 (insulin-dependent) diabetic patients, both with and without retinopathy, was assessed by measuring the plasma fibrinolytic activity and fibronectin after 10 min venous stasis induced by a sphygmomanometer cuff. After venous stasis, diabetic subjects with proliferative retinopathy had fibrinolytic responses (median 0.13 increasing to 0.26 U/ml) in the low normal range, which were significantly less (p less than 0.005) than control subjects (0.17-0.68 U/ml) and diabetic patients with minimal retinopathy (0.16-0.68 U/ml; p less than 0.01). Plasma fibronectin levels were similar in the different groups, but after venous stasis, rose significantly in the diabetic patients, both in those with proliferative retinopathy (mean 317-399 micrograms/ml; p less than 0.002) and without retinopathy (312-371 micrograms/ml; p less than 0.05) but not in normal subjects (304-333 micrograms/ml). These changes in fibrinolytic activity and fibronectin were independent of blood glucose, glycosylated haemoglobin, or indices of sensory or autonomic nerve function. These disturbances of endothelial function, together with known abnormalities of haemostatic variables and microvascular reflexes, might convert a usually temporary obstruction of capillary blood flow into a pathological capillary closure, and might contribute to the inexorable progression of advanced diabetic microangiopathy in spite of good diabetic control.

Diabetes Mellitus, Type 1↗

Non-uniform distribution of islet amyloid in the pancreas of 'maturity-onset' diabetic patients.

Quantitative morphometry of the pancreases of five 'maturity-onset' diabetic subjects has demonstrated more amyloid in islets of the head, body and tail (where it was found in a mean 29% of the islets occupying a mean 11% islet area) than in islets of the 'pancreatic-polypeptide-rich' lobule of the head (where amyloid was found in a mean of 3% of the islets occupying a mean of 0.7% islet area, both p less than 0.005). The non-uniform amyloid distribution may relate to the hormone content of the islet; the head and tail contained significantly more A, B and D-cells than the pancreatic-polypeptide-rich lobule in both non-diabetic subjects (n = 8) and diabetic patients (n = 5; p less than 0.005). This result is compatible with the previous suggestion that amyloid may be derived from insulin or its precursors.

Aged↗

Iodination of myofibrils and myosin.

The relative reactivity of the tyrosine side chains in the proteins of skeletal muscle myofibrils was determined using iodination techniques. The destruction of ATPase activity of myofibrils and myosin by lactoperoxidase and chloramine-T iodination could be prevented by the attachment of cysteamine to the sulphydryl groups prior to the iodination reaction and subsequent regeneration with thioglycolate or dithiothreitol. Iodination using 1,3,4,6-tetrachloro-3 alpha, 6 alpha-diphenylglycoluril did not require cysteamine treatment for retention of full enzymatic activity. The specific activity of the different proteins varied markedly with desmin, troponin-T, and tropomyosin having the highest labelling with all three iodination procedures. In contrast the myosin light chains had low specific activity when labelled in myofibrils or intact myosin. The isolated light chains, however, were much more highly iodinated. It appears that iodination may be a useful technique for examining protein-protein interactions in the myofibril.

Adenosine Triphosphatases↗

Abnormal dietary regulation of erythrocyte insulin receptor affinity in non-insulin-dependent diabetes mellitus.

Decreased insulin binding to receptors is associated with the insulin resistance of obese and non-obese non-insulin-dependent diabetics. 'Down Regulation' by elevated insulin levels has been suggested as the cause, but factors influencing receptor affinity have not been examined. To investigate the control of receptors in diabetes, 10 non-insulin-dependent diabetics and 10 normal subjects were studied after 6 d on low and 6 d on high calorie diets of fixed composition (700 and 2800 Kcal/70 kg of ideal body weight). The binding of insulin by erythrocytes of non-diabetics, as predicted, increased on the low and decreased on the high calorie diets, due to altered affinity. In contrast, the binding in the diabetics did not change significantly, and the responses to the low and high calorie diets were less than in the normal subjects (P less than 0.05 and P less than 0.001 respectively). Indeed, the insulin binding in all 5 non-obese diabetics changed in the opposite direction (P less than 0.01) to the non-diabetics, whereas the obese diabetics showed a mixed response. The changes in receptor binding in the diabetics was completely unrelated to the diurnal plasma insulin levels during 24 h studies. We conclude that the dietary regulation of erythrocyte insulin receptor affinity in non-insulin-dependent diabetes is abnormal, and insulin receptor affinity is regulated by factors other than insulin. The relation of this abnormality to the insulin resistance needs further investigation.

Aged↗

Medical staff in training to become consultant physicians with an interest in diabetes.

A census in 1982 of 44 registrars and 66 senior registrars each of whom intends to become a 'consultant with an interest in diabetes' revealed that the training posts are geared to produce the 11 consultants appointments per year which currently become available. However, on top of this 'ladder' are 26 senior registrars who are already due for a consultant post. This backlog would appear to be a permanent feature unless extra new consultant posts become available. A newly appointed senior registrar can anticipate an average of 6 years before a consultant appointment. The majority of junior staff approved the current regulations and training programmes, although 87% felt that they received insufficient guidance.

Consultants↗

Severe hypoglycemia and hyperinsulinemia in falciparum malaria.

We studied the occurrence, clinical manifestations, and mechanism of hypoglycemia in patients with falciparum malaria in eastern Thailand. Hypoglycemia, which was often severe and recurrent, occurred in 17 patients, including 12 in a series of 151 patients with cerebral malaria. Thirty episodes were investigated. Plasma concentrations of insulin and C peptide were inappropriately high, and lactate and alanine concentrations were significantly higher than in patients with falciparum malaria who were normoglycemic (P less than 0.05). Sixteen patients had received quinine; plasma quinine and insulin concentrations were correlated at the time of hypoglycemia (P = 0.007). In seven healthy fasting volunteers intravenous quinine increased the mean plasma insulin concentration (+/- S.D.) from 8.9 +/- 3.1 to 17.1 +/- 8.4 mU per liter (P = 0.02) and reduced the mean plasma glucose concentration from 88 +/- 20 to 68 +/- 23 mg per deciliter (P = 0.002). Our observations indicate that in falciparum malaria quinine-induced insulin secretion may precipitate hypoglycemia, but other factors, including the large glucose requirements of the malaria parasites may also contribute. This important complication, associated with pregnancy and severe disease, must be excluded in all patients with falciparum malaria who have impaired or deteriorating consciousness.

3-Hydroxybutyric Acid↗

Maturity onset diabetes of the young is not linked to the insulin gene.

Maturity onset diabetes of the young is inherited as an autosomal dominant condition. Two families with the disease were studied to determine whether the inheritance of this type of diabetes was linked to the insulin gene. A cloned insulin gene probe was hybridised to DNA from the family members and the insulin gene on each chromosome identified by a different fragment length polymorphism. The results showed no linkage between the insulin gene and the inheritance of maturity onset diabetes of the young.

Adolescent↗

Prevention of deterioration of renal and sensory-nerve function by more intensive management of insulin-dependent diabetic patients. A two-year randomised prospective study.

74 insulin-dependent diabetic patients with background retinopathy were randomised to continue with usual diabetic care (group U) or to a more intensive programme (group A) using ultralente insulin as basal cover and soluble insulin at mealtimes. Group A attended the clinic more frequently, received closer dietary supervision, and were taught home blood glucose monitoring. Group A had a significantly lower mean glycosylated haemoglobin level during the study, although the mean level also fell in group U towards the end of year 2. Renal and sensory-nerve function were significantly better preserved in group A than in group U. Significant improvements were also seen in low-density-lipoprotein-cholesterol and whole-blood low-shear viscosity. The rate of progression of retinopathy was similar in both groups. It appears that a modest improvement in diabetic control, obtainable in most clinics, has been associated with a reduction in the progression of diabetic tissue damage.

Blood Glucose↗

Plasma N-acetyl-beta, D-glucosaminidase activities and glycaemia in diabetes mellitus.

The plasma activity of the lysosomal enzyme N-acetyl-beta, D-glucosaminidase (NAGase) has been shown to correlate with hyperglycaemia; their temporal relationships have been investigated. In 12 insulin-treated male diabetic patients, NAGase showed a slight diurnal variation with a nadir at 07.00 h (F = 9.54, p less than 0.001). The mean plasma glucose and NAGase fluctuated similarly (rs = 0.88, p less than 0.01) but did not correlate within individual patients. Normoglycaemia was induced in eight insulin-treated diabetic patients for 4 days but the mean NAGase did not fall significantly. Glycaemic improvement over 3 months was achieved by dietary therapy in 28 newly-presenting non-insulin-dependent diabetic patients: there were significant falls in mean fasting plasma glucose (mean +/- SD: 12.8 +/- 3.3 to 8.3 +/- 3.1 mmol/l; p less than 0.001), glycosylated haemoglobin levels (12.4 +/- 2.4 to 9.3 +/- 2.3%, p less than 0.001) and a corresponding decrease of NAGase (1.5 +/- 0.5 to 1.2 +/- 0.4 mumol 4-nitrophenyl-N-acetyl-beta-D-glucosamide released.h-1.ml-1; p less than 0.001). The change in NAGase correlated with the changes in plasma glucose and glycosylated haemoglobin levels (r = 0.61, p less than 0.025; r = 0.48, p less than 0.05, respectively). Plasma NAGase activity may be influenced by glycaemia in diabetes.

Acetylglucosaminidase↗

Control of pulsatile insulin secretion in man.

Plasma insulin and glucose concentrations were examined in man in a basal state from central venous samples taken at 1-min intervals for up to 2.5 h. Normal subjects have insulin oscillations of mean period 14 min (significant autocorrelation, p less than 0.0001) with changes in concentration of 40% over 7 min. The pulsation frequency was stable through cholinergic, endorphin, alpha-adrenergic or beta-adrenergic blockade, or small perturbations with glucose or insulin. Stimulation of insulin secretion by intravenous glucose, tolbutamide or sodium salicylate increased the amplitude of the insulin oscillations while the frequency remained stable. Patients with a truncal vagotomy or after Whipple's operation had longer-term oscillations of 33 and 37 min periodicity (autocorrelation: p less than 0.0001), with insulin-associated glucose swings four times larger than those of normal subjects. Type 2 (non-insulin-dependent) diabetic patients had a similarly increased insulin-associated glucose swing of six times that seen in normal subjects. The hypothesis is proposed that the 14-min cycle of insulin production is controlled by a 'pacemaker' which assists glucose homeostasis. The longer 33-37-min oscillations, seen in those with denervation, may arise from a limit-cycle of the feedback loop between insulin from the B cells and glucose from the liver. The vagus may provide hierarchical control of insulin release.

Adult↗

Hypernephroma presenting as acute delirium.

We report a case of hypernephroma that presented as acute delirium. There was no evidence of central nervous system metastatic disease and the delirium resolved upon removal of the tumor.

Acute Disease↗