Cholestatic jaundice following chlorpropamide self-poisoning.
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Adult↗
Biomedical subjects
B M Frier
Publications and source records attributed to B M Frier.
Exocrine pancreatic function in juvenile-onset diabetes mellitus.
Exocrine pancreatic function was studied in 20 juvenile-onset diabetics, seven maturity-onset diabetics, and five patients with diabetes secondary to chronic pancreatitis. The results were compared with 13 non-diabetic controls. The outputs of bicarbonate, trypsin, and amylase were reduced in the diabetic patients in response to intravenous secretin and CCK-PZ. In the juvenile-onset group, exocrine pancreatic secretory capacity was reduced in 80% of the patients, and the severity of the reduction was related to the duration of the diabetes. The reduction in pancreatic secretory capacity must be taken into consideration when interpreting pancreatic exocrine function in patients with diabetes.
Adolescent↗
Letter: Cerebral oedema in diabetic ketoacidosis.
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Bicarbonates↗
Cerebral oedema in diabetic ketoacidosis.
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Adult↗
Uncomplicated hyperparathyroidism.
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Abdomen↗
Scrotal gangrene in asymptomatic myeloma.
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Aged↗
Evaluation of serum markers of neuronal damage following severe hypoglycaemia in adults with insulin-treated diabetes mellitus.
BACKGROUND: Neurone-specific enolase (NSE) and protein S-100 (S-100) may be used as markers of acute neuronal damage in humans with neurological disorders. METHOD: To evaluate their use following a single episode of severe hypoglycaemia (defined as an episode requiring external assistance to aid recovery), serum concentrations of NSE and S-100 were measured following hypoglycaemia which had not caused persistent neurological impairment in 16 patients with insulin-treated diabetes (the 'hypo' subjects), and in three diabetic patients who died following severe hypoglycaemia. The serum proteins were also measured in 10 subjects with insulin-treated diabetes who had not experienced an episode of severe hypoglycaemia within the preceding year (the 'control' subjects). RESULTS: No differences in serum concentrations of NSE and S-100 were observed between the 'control' and the 'hypo' subjects at either 36 hours or seven days after the episode of severe hypoglycaemia (p>0.05). However, in two of the three subjects who died following hypoglycaemia, serum concentrations of the markers were markedly elevated. CONCLUSIONS: Any neuronal injury occurring during severe hypoglycaemia that is not associated with persistent neurological deficit is insufficient to provoke elevation of these serum markers. However, the measurement of serum concentrations of NSE and S-100 may have a prognostic role in evaluating clinical outcome following severe hypoglycaemia which is associated with neurological damage.
Adult↗
Symptomatic and counterregulatory hormonal responses to acute hypoglycaemia induced by insulin aspart and soluble human insulin in Type 1 diabetes.
BACKGROUND: The aim of this study was to assess hypoglycaemia awareness with the insulin analogue, insulin aspart. The counterregulatory hormonal and symptomatic responses to hypoglycaemia induced by insulin aspart were compared with soluble human insulin in a double-blind, randomised, two-period crossover trial in patients with Type 1 diabetes. The primary objective was to compare the blood glucose threshold for autonomic activation during hypoglycaemia induced by insulin aspart and soluble human insulin. Secondary objectives were to compare the counterregulatory, symptomatic and physiological responses to hypoglycaemia. METHODS: 20 patients were screened, 17 were randomised and 16 completed the study. Acute hypoglycaemia was induced by intravenous infusion of insulin aspart or soluble human insulin (100 U ml(-1) at a rate of 2 mU kg(-1) min(-1)). RESULTS: No statistical difference between insulin aspart and soluble human insulin was shown for the primary blood glucose endpoint; mean arterialised blood glucose concentrations (+/-SD) at the onset of autonomic activation were 1. 88+/-0.39 mmol L(-1) for insulin aspart and 1.89+/-0.43 mmol L(-1) for soluble human insulin (not significant). No statistical differences were observed between the two insulins for the secondary endpoints: counterregulatory hormonal responses, autonomic responses, hypoglycaemia symptom scores, cognitive function and blood glucose responses. No serious adverse events were reported during the study. CONCLUSIONS: Insulin aspart and soluble human insulin elicit the same counterregulatory and symptomatic responses to acute hypoglycaemia in patients with Type 1 diabetes.
Adolescent↗
Severe hypoglycaemia in patients with type 1 diabetes and impaired awareness of hypoglycaemia: a comparative study of insulin lispro and regular human insulin.
OBJECTIVE: To assess the potential of insulin lispro to limit the frequency of severe hypoglycaemia without compromising glycaemic control in a cohort of patients with type 1 diabetes who are at a high risk of severe hypoglycemia. Research design and methods An open-label, randomised, 12-month comparative crossover study of insulin lispro and regular human insulin was performed in 33 patients with type 1 diabetes with impaired hypoglycaemia awareness. The efficacy of each treatment was evaluated by glycaemic control (HbA(1c)), eight-point home blood glucose profiles, and the frequency and severity of hypoglycaemic episodes and quality of life. RESULTS: Eighteen (55%) patients experienced one or more episodes of severe hypoglycaemia in the 48 weeks of study. There was a trend to a lower incidence of severe hypoglycaemia during treatment with insulin lispro in comparison with regular human insulin (55 vs 84 episodes, p=0.087). This resulted principally from a 47% lower incidence of nocturnal severe hypoglycaemia with insulin lispro (25 vs 47 episodes, p=0.11). The lower frequency of severe hypoglycaemia associated with insulin lispro was not explained by differences in glycated haemoglobin between insulin treatments (HbA(1c) 9.1% insulin lispro vs 9.3% regular human insulin). CONCLUSIONS: In individuals with type 1 diabetes, who have impaired awareness of hypoglycaemia, treatment with insulin lispro may be associated with a lower incidence of severe hypoglycaemia manifested predominantly through less frequent nocturnal episodes. Insulin lispro may have a beneficial role in the management of patients with diabetes at risk of severe hypoglycaemia, although a larger study is required to confirm these findings.
Adult↗
Raised liver associated enzyme activity and post-prandial bile acid concentrations in sera from treated diabetic outpatients.
Aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transferase activities were measured in sera from 411 diabetic outpatients and were raised in 26 (6.4%), 34 (8.3%) and 62 (15.2%) patients, respectively. Serum total bile acid concentrations were raised in 4 patients (1%). Percentage glycated hemoglobin A1, serum fructosamine concentration and plasma glucose concentration were also measured. No relationship between the presence of raised enzyme activity and mature age, short duration of diabetic treatment regimen or glycemic control was found. Twenty-six patients with an alanine aminotransferase activity greater than 60 U/l were reviewed at 23 +/- 6.5 weeks. The activity of this enzyme had fallen to within the reference interval in 15 (58%). In the other 11 patients, its median activity was 75 U/l (range 51-181 U/l). Median gamma-glutamyl transferase activity had risen in these 11 patients from 78 U/l to 93 U/l (P less than 0.01). No statistical differences in treatment regimen or glycemic control were found between these two groups. Raised liver-associated enzyme activity in treated stabilised diabetic outpatients should therefore not be attributed to poor glycemic control or diabetic treatment regimen.
Alanine Transaminase↗
Observations on the metabolic basis for altered insulin dose distribution in diabetic pregnancy.
Insulin requirements are known to increase during pregnancy, but it has not been reported whether this relates to prandial or basal requirements, or to a change in insulin pharmacokinetics. In nine unselected pregnant patients the pattern of this increase was that of a large increase in the total morning dose and a reduction in the evening dose of intermediate acting insulin, in order to maintain good control while avoiding nocturnal hypoglycaemia. 24 h metabolic profiles were carried out in these patients in the third trimester of pregnancy. Plasma free insulin profiles reflected the dosage patterns and there was no change in insulin metabolic clearance rate in pregnancy. Pregnant diabetic patients had a broad peak of free insulin concentration around lunchtime followed by a steady fall until next morning. Blood lactate and alanine were higher than normal and 3-hydroxybutyrate lower than is usually seen in non-pregnant diabetic patients. The observations suggest that there may be differential changes in insulin sensitivity in diabetic pregnancy between the fed and fasting states, and that the therapeutic response to this causes a measurable metabolic change.
3-Hydroxybutyric Acid↗
Lawrence Lecture. Hypoglycaemia and diabetes.
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Adrenal Glands↗
The effects of diabetes and autonomic neuropathy on parotid salivary flow in man.
Stimulated parotid salivary flow studies were performed on 20 non-diabetic subjects and on 30 patients with insulin-dependent diabetes mellitus who had been screened for autonomic neuropathy using tests of cardiovascular reflexes. Electrical gustometry was performed to detect the taste threshold. The stimulated parotid salivary flow rates of diabetics with no autonomic neuropathy or early parasympathetic autonomic dysfunction alone were similar to those of non-diabetic subjects. Diabetic patients with established parasympathetic autonomic neuropathy had significantly higher salivary flow rates as did those with combined sympathetic and parasympathetic neuropathies. Taste thresholds did not correlate either with the duration of the diabetes or with the presence of autonomic neuropathy. The cause of the increased salivary flow associated with diabetic autonomic neuropathy is unclear. It may represent the removal of a neural inhibitory mechanism which modulates salivary flow, or the effects of long-standing diabetes on salivary secretion.
Adult↗
Symptomatic awareness of hypoglycaemia: does it change on transfer from animal to human insulin?
A retrospective survey of symptomatic awareness of hypoglycaemia was performed in 189 randomly selected patients with insulin-treated diabetes who had been transferred from highly purified animal insulins to human insulin in the preceding 24 months. Of the 189 patients 44 (23%) complained of chronic hypoglycaemic unawareness, unrelated to ambient blood glucose control, before change of insulin species. Only 12 of the remaining 145 patients reported a reduction in awareness of hypoglycaemia following transfer to human insulin (6% of the whole group), while 6 (3%) reported an increase in awareness following the transfer. The 12 patients reporting reduced awareness had a mean duration of diabetes of 24 +/ 10 years compared to a duration of 15 +/- 10 years in the patients with normal awareness. The mean glycosylated haemoglobin concentrations were similar in all of the groups of patients. Six patients had developed total loss of awareness of the onset of hypoglycaemia, with all but one patient having suffered multiple episodes of severe hypoglycaemia. This reduced hypoglycaemic awareness on human insulin therapy was not associated with any significant improvement in blood glucose control.
Adult↗
Unawareness of hypoglycaemia in insulin-treated diabetic patients: prevalence and relationship to autonomic neuropathy.
Three-hundred and two insulin-treated diabetic patients were questioned about hypoglycaemia using a structured questionnaire interview. Two-hundred and twenty-six patients (75%) had normal symptomatic awareness, 48 (16%) had partial awareness, 21 (7%) had absent awareness of hypoglycaemia, and 7 (2%) denied ever experiencing hypoglycaemia. Patients with complete loss of awareness of hypoglycaemia had diabetes of longer duration; none had a HbA1 concentration within the non-diabetic range. Loss of awareness of hypoglycaemia was associated with an increased incidence of severe hypoglycaemia, 19 (91%) of the patients with absent awareness, and 33 (69%) with partial awareness of hypoglycaemia experiencing severe hypoglycaemia over 1 year compared with only 41 (18%) of patients with normal awareness of hypoglycaemia (p less than 0.001). Cardiovascular autonomic function tests were performed in 226 (75% of the whole group). Of the patients who had diabetes for more than 15 years, 54% (n = 39) with normal awareness of hypoglycaemia, compared with 59% (n = 10) with absent awareness of hypoglycaemia, had evidence of cardiovascular autonomic impairment (NS). Seven (41%) of the 17 patients with absent awareness of hypoglycaemia and diabetes of greater than 15 years duration had no evidence of autonomic dysfunction. Loss of hypoglycaemia awareness is a common problem in patients with insulin-treated diabetes of long duration, is associated with an increased incidence of severe hypoglycaemia, but is not invariably associated with abnormal cardiovascular autonomic function tests.
Adolescent↗
Classification of symptoms of hypoglycaemia in insulin-treated diabetic patients using factor analysis: relationship to hypoglycaemia unawareness.
The allocation of some symptoms of acute hypoglycaemia to autonomic and neuroglycopenic groups has proved problematical, with possible misinterpretation of studies which depend upon the use of diverse symptom questionnaires. Two hundred and ninety-five randomly selected insulin-treated diabetic patients were asked to report the symptoms which they usually experienced and believed to be caused by hypoglycaemia. Sweating, trembling, inability to concentrate, weakness, hunger and blurred vision were the most frequently reported symptoms. To classify symptoms of hypoglycaemia objectively, Factor Analysis was used to identify related symptoms which grouped together. This resulted in five groups or clusters of symptoms, four of which could be denominated as groups with a presumed common aetiology, and were labelled: 'neuroglycopenic', 'general malaise', 'autonomic', 'motor dysfunction', and 'sensory dysfunction'. The groups of symptoms derived by Factor Analysis were assessed in relation to partial or absent symptomatic awareness of hypoglycaemia based on historical evidence from the 295 insulin-treated diabetic patients. Neuroglycopenic symptoms were reported more commonly by the patients who had reported partial awareness of hypoglycaemia (number of symptoms 2.6 +/- 1.8 (mean +/- SD] than by the patients who had reported normal hypoglycaemia awareness (1.4 +/- 1.5 symptoms) (p less than 0.05). By contrast autonomic symptoms were reported less frequently by the patients who had reported absent hypoglycaemia awareness (1.3 +/- 1.4 symptoms) than by those with normal awareness (2.2 +/- 1.4 symptoms) (p less than 0.05), which was similar to the number of autonomic symptoms reported by the patients who had partial hypoglycaemia awareness (2.1 +/- 1.3 symptoms).
Analysis of Variance↗
Diabetic lipohypertrophy delays insulin absorption.
The effect of lipohypertrophy at injection sites on insulin absorption has been studied in 12 insulin-dependent diabetic patients. The clearance of 125I-insulin from sites with lipohypertrophy was significantly slower than from complementary nonhypertrophied sites (% clearance in 3 h, 43.8 +/- 3.5 +/- SEM) control; 35.3 +/- 3.9 lipohypertrophy, P less than 0.05). The degree of the effect was variable but sufficient in several patients to be of clinical importance. Injection-site lipohypertrophy is another factor that modifies the absorption of subcutaneously injected insulin.
Adipose Tissue↗
Urinary excretion of beta-thromboglobulin and N-acetyl-beta-D-glucosaminidase in type 1 diabetes: potential indicators of early nephropathy?
While microalbuminuria indicates the glomerular damage of early diabetic nephropathy, tubular abnormalities also occur at an early stage of diabetic renal disease. Urinary excretion of beta-thromboglobulin (BTG) and N-acetyl-beta-D-glucosaminidase (NAG) was measured in 132 normotensive Type 1 (insulin-dependent) diabetic patients with no evidence of overt renal disease, of whom 35 had microalbuminuria and the remainder had normal urinary albumin excretion. Of 21 patients in whom there was a detectable urinary BTG concentration, only 8 (38%) had a concurrently abnormal urinary albumin excretion. NAG excretion was elevated in 22 (63%) of the 35 patients with microalbuminuria; significant associations were also identified between urinary NAG excretion and smoking habit (x2 = 12.7, p less than 0.001) and glycated haemoglobin (r = 0.49, p less than 0.01). It is concluded that measurement of urinary BTG is not of sufficient sensitivity to be of value in the detection of early diabetic renal disease, but measurement of urinary NAG may be of value in the detection of diabetic nephropathy at a potentially reversible stage.
Acetylglucosaminidase↗