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Biomedical subjects

B M Frier

Publications and source records attributed to B M Frier.

At least 109 records · Page 6Linked to original sources

Coagulation and fibrinolytic systems in type I diabetes: effects of venous occlusion and insulin-induced hypoglycaemia.

1. The effects of venous occlusion on the coagulation and fibrinolytic systems were investigated in six patients with type 1 (insulin-dependent) diabetes and 11 age- and sex-matched non-diabetic control subjects. The coagulation parameters (fibrinogen, prothrombin time, partial thromboplastin time with kaolin, von Willebrand factor antigen) did not differ between patients and control subjects either before or after 20 min of venous occlusion. No rise was observed in von Willebrand factor antigen after venous occlusion in either group. 2. In the diabetic patients, chronic activation of the fibrinolytic system was found at baseline, which was indicated by a shortened euglobulin lysis time (P < 0.01), increased tissue plasminogen activator activity (P < 0.05) and decreased plasminogen activator inhibitor type 1 antigen level (P < 0.05), when compared with control subjects. In both groups venous occlusion resulted in significant increments in all measurements, except plasminogen activator inhibitor type 1 antigen level. The post-occlusion values did not differ between the two groups, except the plasminogen activator inhibitor type 1 antigen level, which remained significantly lower in the diabetic patients. The mean increments in each parameter did not differ between the two groups. 3. Coagulation and fibrinolysis were assessed in response to acute insulin-induced hypoglycaemia. Von Willebrand factor antigen levels increased significantly in both groups, with no difference in maximal increments. Significant activation of the fibrinolytic system occurred in response to hypoglycaemia, demonstrated by shortened euglobulin lysis time and increased fibrin plate lysis, tissue plasminogen activator antigen level and tissue plasminogen activator activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Changes in the anterior chamber of the eye during acute hypoglycaemia in humans.

1. The changes in the volume and depth of the anterior chamber of the eye during acute insulin-induced hypoglycaemia were examined in nine healthy non-diabetic subjects (aged 23-31 years). The dimensions of the anterior chamber of the eye were measured by a photogrammetric technique, with Polaroid photographs taken of the lower half of the mid-sagittal plane of the eye at an angle of 55 degrees at a magnification of x16. Photographs were taken before and at regular intervals after the induction of acute hypoglycaemia using an infusion of unmodified (soluble) insulin at 2.5 m-units min-1 kg-1. Plasma adrenaline was measured regularly throughout the study. 2. Plasma glucose fell from 4.5 +/- 0.2 mmol/l (mean +/- SEM) to a nadir of 1.0 +/- 0.1 mmol/l (P < 0.01), which coincided with the onset of the acute autonomic reaction. Plasma adrenaline rose from 0.3 +/- 0.1 nmol/l to a peak of 3.2 +/- 0.6 nmol/l (P < 0.01) at 15 min after the autonomic reaction. 3. The volume of the anterior chamber decreased by 8.2% from 284.7 +/- 21.5 microliters at baseline to 264.5 +/- 17.0 microliters (P < 0.01) at the onset of the autonomic reaction. No significant alteration in axial anterior chamber depth was evident, but peripheral anterior depth decreased from 2.25 +/- 0.20 mm at baseline to 2.07 +/- 0.14 mm (P < 0.05) at the onset of the autonomic response.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Urinary dopamine response to angiotensin II is not abnormal in type 1 (insulin-dependent) diabetes mellitus.

To examine the interaction between angiotensin II (ANGII) and dopamine in type 1 diabetes mellitus, urinary dopamine excretion was examined during ANGII infusion in 15 diabetic patients and 10 control subjects after pretreatment with lithium 750 mg and placebo. The antinatriuretic response and the urinary dopamine response to ANGII did not differ within or between the two groups on each study day. No correlation was observed between the decrements in urinary sodium excretion and urinary dopamine output during ANGII infusion in either group. The effect of insulin on urinary dopamine excretion was studied separately in seven non-diabetic subjects; sodium and potassium retention occurred during a hyperinsulinaemic euglycaemic clamp, but urinary dopamine did not change. The data suggest that the relationship between urinary sodium excretion and tubular dopamine synthesis remains normal in early type 1 diabetes mellitus both at baseline and during the antinatriuresis induced by angiotensin II. The cause of the reduction in urinary dopamine during ANGII infusion is unclear, but is probably not mediated directly by changes in proximal tubular sodium transport.

Adult↗

Physiological, symptomatic and hormonal responses to acute hypoglycaemia in type 1 diabetic patients with autonomic neuropathy.

The effects of peripheral autonomic neuropathy on the symptomatic, physiological, and hormonal responses to acute insulin-induced hypoglycaemia were studied in two groups of patients with Type 1 diabetes, matched for age, duration of diabetes, and prevailing glycaemic control. A group of eight patients who gave a history of normal awareness of hypoglycaemia and had normal cardiovascular autonomic function tests were compared to a group of six patients who had symptoms of autonomic dysfunction and gross abnormalities of cardiovascular autonomic function tests. An additional two patients with autonomic neuropathy who also had hypoglycaemia unawareness were studied. Acute hypoglycaemia was induced by intravenous infusion of insulin (2.5 mU kg-1 min-1) and the onset of the acute autonomic reaction (R) was identified objectively by the sudden rise in heart rate and onset of sweating. Cognitive function and hypoglycaemia symptom scores were estimated serially, and plasma counterregulatory hormones were measured. Acute autonomic activation was observed to occur in all subjects in response to hypoglycaemia and commenced at similar venous plasma glucose concentrations in both groups (neuropathic patients: 1.6 +/- 0.2 mmol l-1 vs non-neuropathic patients 1.6 +/- 0.2 mmol l-1, p = 0.9,). In the neuropathic patients plasma adrenaline responses were significantly lower at all time points from time R until time R + 30 min (MANOVA for repeated measures, F = 19.4, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Frequency and symptoms of hypoglycaemia experienced by patients with type 2 diabetes treated with insulin.

This study ascertained the prevalence of severe hypoglycaemia and loss of awareness of hypoglycaemia in patients with Type 2 diabetes treated with insulin. One hundred and four sequentially selected Type 2 diabetic patients were compared with 104 patients with Type 1 diabetes who were matched for duration of insulin therapy. The patients were interviewed using a standardized questionnaire. During treatment with insulin, 18 Type 2 patients had experienced fewer than two episodes of hypoglycaemia, while 86 had experienced two or more episodes; 80 (93%) reported normal awareness, six (7%) reported partial awareness, and none had absent awareness of hypoglycaemia. All 86 Type 1 diabetic patients matched to the 86 Type 2 patients had experienced multiple episodes of hypoglycaemia; 71 (83%) had normal awareness, 14 (16%) had partial awareness and one patient (1%) reported absent awareness of hypoglycaemia. The Type 1 patients who had altered awareness of hypoglycaemia had longer duration of diabetes and insulin therapy (normal awareness: 5 (1-17) years (median (range)) vs partial awareness: 9 (3-18) years, p < 0.01). Similarly, Type 2 patients with altered awareness had longer duration of diabetes (normal awareness: 11 (2-25) years vs partial awareness: 19 (8-24) years, p < 0.02) and had received insulin for longer (normal awareness: 3 (1-18) years vs partial awareness: 12 (6-17) years, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Frequency and morbidity of severe hypoglycaemia in insulin-treated diabetic patients.

To estimate the frequency and morbidity of insulin-induced hypoglycaemia, a retrospective survey was undertaken of the frequency of severe hypoglycaemia in 600 randomly selected patients with insulin-treated diabetes who were attending a large diabetic outpatient clinic in a teaching hospital. The resulting morbidity (hypoglycaemia-related injuries, convulsions, and road traffic accidents) was ascertained in 302 patients. One hundred and seventy-five (29.2%) of the 600 patients reported a total of 964 episodes of severe hypoglycaemia in the preceding year, giving an overall frequency for the group of 1.60 episodes patient-1year-1. The frequency of severe hypoglycaemia which was documented in 544 Type 1 (ketosis prone) diabetic patients was double that observed in a subgroup of 56 Type 2 diabetic patients who were being treated with insulin (1.70 vs 0.73 episodes patient-1year-1). In the subset of 302 patients, those who had experienced severe hypoglycaemia had greater morbidity associated with an estimated rate of injury of 0.04 injuries person-1year-1. Twenty (6.6%) patients reported a total of 37 convulsions associated with hypoglycaemia, 5 of which had occurred in the preceding year (0.02 convulsions person-1year-1). Five patients reported road traffic accidents in the preceding year which had been caused by hypoglycaemia. The only reliable predictors of severe hypoglycaemia were a history of previous severe hypoglycaemia (p < 0.001), a history of hypoglycaemia-related injury (p < 0.001) or convulsion (p < 0.001), and the duration of insulin therapy (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Accidents↗

Severe hypoglycemia and intelligence in adult patients with insulin-treated diabetes.

The IQ scores (WAIS-R) of 100 patients with insulin-treated diabetes (aged 25-52 yr) were compared with those of 100 healthy control subjects who were matched to the diabetic patients for sex, age, education, and social class. The diabetic group had lower WAIS-R performance and verbal IQ scores than the control group (P = 0.017 and P = 0.033, respectively) after controlling for premorbid IQ. The extent of the difference was modest, representing approximately 33% of an SD in IQ. When frequency of severe hypoglycemia was controlled for the difference in performance IQ between the diabetic patient group and the control group was abolished, whereas the difference between the groups in verbal IQ persisted. It is hypothesised that cumulative severe hypoglycemia might be the major factor in the slight performance IQ differences between diabetic patients and control subjects. The origin of the verbal IQ differences, although obscure, might be related to the social impact of the disorder.

Adult↗

Pancreatic and pituitary hormonal responses to insulin-induced hypoglycaemia during muscarinic cholinergic blockade in man.

To investigate the role of muscarinic cholinergic mechanisms in mediating the pancreatic and pituitary hormonal responses to hypoglycaemia, six normal subjects were studied during acute insulin-induced hypoglycaemia under control conditions, and during blockade with intravenous atropine. During atropine blockade the response of pancreatic polypeptide was suppressed while the maximum response of plasma glucagon was significantly higher. The increment in plasma vasopressin was also increased significantly during cholinergic blockade. During blockade with atropine the responses of plasma prolactin was reduced, with a slight but significant reduction in the growth hormone response, and although a similar maximum response of plasma ACTH was achieved, this rise was delayed. These results implicate involvement of a cholinergic muscarinic inhibitory and stimulatory mechanisms in regulating the responses of pancreatic and pituitary hormones to hypoglycaemia.

Adrenocorticotropic Hormone↗

Changes in renal function during acute insulin-induced hypoglycaemia in patients with type 1 diabetes.

The effect of acute hypoglycaemia on renal function was examined in eight male patients with Type 1 diabetes who had normal urinary albumin excretion. Insulin was given as a bolus intravenous injection (0.125 U kg-1) and plasma glucose fell to a nadir of 1.6 (SE 0.2) mmol l-1, with all patients experiencing an acute autonomic reaction. Renal plasma flow fell from 674 (106) to 540 (198) ml min-1 during hypoglycaemia (p less than 0.01) and returned to 655 (181) ml min-1 (NS vs baseline). Glomerular filtration rate (GFR) declined from 143 (23) to 110 (36) ml min-1 during hypoglycaemia (p less than 0.02), rising to 150 (44) ml min-1 in the recovery period (NS vs baseline). The urinary flow rate and urinary albumin excretion rate both fell significantly in response to hypoglycaemia (10.6 (1.2) to 4.7 (1.1) ml min-1; p less than 0.002, and 46.2 (10.6) to 26.0 (10.5) micrograms min-1, respectively). Urinary dopamine excretion also declined, from 322 (37) to 211 (29) mumol min-1 (p less than 0.005) but sodium excretion was unchanged. Plasma adrenaline concentration (0.2 (0.03) to 1.7 (0.4) nmol l-1; p less than 0.01) and plasma renin activity (0.49 (0.13) to 1.08 (0.17) ng-Ang 1 l-1 h-1; p less than 0.01) increased during hypoglycaemia, but changes in plasma noradrenaline and angiotensin II levels did not attain significance. These acute changes in renal function, observed during hypoglycaemia in diabetic patients, may result from direct stimulation of the efferent sympathetic nerves to the kidney, complemented by the hormonal changes induced by hypoglycaemia.

Adult↗

Hospital in-patient statistics underestimate the morbidity associated with diabetes mellitus.

Hospital in-patient statistics are an important outcome measurement in the assessment of the morbidity associated with diabetes mellitus. A prospective study of 157 consecutive admissions over a 28-day period compared diagnoses obtained from the clinical records with the ICD9 coding of the same admissions recorded at the Information and Statistics Division of the Scottish Health Service. Sixty-one percent of all discharge summaries omitted the diagnosis of diabetes. Even when admission was principally related to diabetes complications, 47% of medical and 88% of surgical discharge summaries omitted diabetes as a diagnostic category. ICD9 coding underestimated the percentage of admissions accounted for by diabetic patients by 100% (2.8 vs 5.6%) and as a result underestimated bed occupancy by over 200% (4.3 vs 13.7%), and is thus failing to fulfil its potential as a demographic and epidemiological record of resource use by disease classification.

Adolescent↗

Oral disorders associated with diabetes mellitus.

The protean manifestations of diabetes include various associated oral disorders such as sialosis, xerostomia, impairment of taste, and localized infections of which oral candidosis is the most commonly observed. The association of specific oral diseases and diabetes is of importance both in the detection of undiagnosed diabetes and in the elucidation of the pathogenesis of various oro-facial diseases. The clinical features and possible causes of oral disorders recognized to be associated with diabetes are reviewed with emphasis on good oral hygiene in the diabetic patient.

Candidiasis↗

Suppression of plasma intact parathyroid hormone levels during insulin-induced hypoglycemia in humans.

The adrenergic control of intact PTH secretion was investigated by measuring its plasma concentration during insulin-induced hypoglycemia in normal human subjects under control conditions (n = 12) and after alpha (n = 5)- or beta (n = 6)-adrenoceptor blockade. Blood samples were taken at baseline, at the time of the acute hypoglycemic reaction, and at regular intervals for 60 min thereafter. Plasma concentrations of intact PTH, catecholamines, total calcium, magnesium, albumin, phosphate, and glucose were measured in all subjects, and plasma ionized calcium was also assayed in three subjects during acute hypoglycemia without pharmacological blockade. At the time of the acute hypoglycemic reaction, the plasma concentration of intact PTH in the control subjects fell to 60.8% of baseline values and was accompanied by a small but significant increase in plasma total calcium. Intact PTH concentrations remained suppressed after the plasma calcium concentration had returned to normal. The two groups of subjects who were exposed to adrenoceptor blockade exhibited a reduced fall in plasma intact PTH and showed no significant increase in plasma total calcium. Therefore, insulin-induced acute hypoglycemia was associated with a fall in plasma intact PTH. Adrenoceptor blockade reduced, but did not abolish, the response, suggesting that other factors are involved.

Adult↗

Vascular endothelial cell antibodies in diabetic patients. Association with diabetic retinopathy.

OBJECTIVE: To determine the incidence of antiendothelial cell antibodies in diabetic patients with and without retinopathy. RESEARCH DESIGN AND METHODS: The study consisted of 70 insulin-dependent diabetic (IDDM) subjects, 36 non-insulin-dependent diabetic (NIDDM) subjects, and 40 nondiabetic control subjects. Blood samples were obtained from diabetic patients and control subjects and patients with background and proliferative retinopathy were identified. RESULTS: Vascular endothelial cell (VEC) antibodies were examined in the sera of 36 NIDDM subjects, 70 IDDM subjects, and 40 nondiabetic control subjects by indirect immunofluorescence. VEC antibodies were present in 5 of 40 (12%) control subjects, 7 of 23 (30%) newly diagnosed IDDM patients, 6 of 17 (35%) IDDM patients without retinopathy, 12 of 18 (67%) IDDM patients with background retinopathy (P less than 0.05), and 9 of 12 (75%) IDDM patients with proliferative retinopathy (P less than 0.01). Three of 13 (23%) NIDDM patients with retinopathy and 6 of 23 (26%) without retinopathy were VEC antibody positive. No associations were observed between the presence of VEC antibodies and either the quality of glycemic control or the duration of diabetes. A significant association between VEC antibodies and large-vessel disease was found in IDDM patients with retinopathy (P less than 0.05). CONCLUSIONS: Antibodies directed against vascular endothelial cells may play a role in the development of microvascular, and possibly macrovascular, disease in diabetes.

Adult↗