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Biomedical subjects

B M Frier

Publications and source records attributed to B M Frier.

At least 145 records · Page 8Linked to original sources
PubMed1990

Cardiac responses to acute insulin-induced hypoglycemia in humans.

The effects of acute hypoglycemia on the heart and cardiovascular system were examined in humans using radioisotopic techniques, complemented by measurement of heart rate and blood pressure. The heart rate increased from 62 +/- 3 to 87 +/- 3 beats/min in response to hypoglycemia; this increase was accompanied by a significant increase in systolic blood pressure, a fall in diastolic blood pressure, with no change in the mean arterial blood pressure. The left ventricular ejection fraction increased from 47 +/- 3 (SE) to 72 +/- 5% in response to hypoglycemia. The increases in heart rate and ejection fraction were abolished during parenteral nonselective beta-adrenergic blockade with propranolol but were unaffected by either alpha-adrenergic blockade with phentolamine or cholinergic blockade with atropine. During beta-adrenergic blockade, there were significant increases in diastolic and mean arterial blood pressure in response to hypoglycemia. During alpha-adrenergic blockade the systolic, diastolic, and mean arterial pressures fell significantly after hypoglycemia. The blood pressure responses to hypoglycemia were unaffected by cholinergic blockade. Thus the increases in ejection fraction and in heart rate in response to hypoglycemia are mediated by beta-adrenoreceptors, whereas the blood pressure responses to hypoglycemia are mediated by alpha- and by beta-adrenoreceptors.

Acute Disease↗
PubMed1990

Increased collagen-linked fluorescence in skin of young patients with type I diabetes mellitus.

Our objective was to determine whether the fluorescence of skin collagen, which may reflect the accumulation of advanced glycosylation end products, is increased in young patients with type I (insulin-dependent) diabetes. Our study design was a cross-sectional case-control study in a referral-based diabetic clinic in an academic hospital. Study subjects comprised a convenience sample of 18 type I diabetic patients aged 17-30 yr and 8 age-matched healthy control subjects. The fluorescence of collagen was measured in skin biopsy material. Collagen-linked fluorescence (CLF) was increased in diabetic patients (mean 10.5 [range 5.8-15.8] U/mg) compared with control subjects (7.6 [5.6-10.1] U/mg, P less than 0.02). In diabetic patients, CLF was related to age (r = 0.581) and duration of diabetes (r = 0.697) but not concentration of glycosylated hemoglobin (r = 0.082). Partial correlation analysis demonstrated that duration of diabetes is the main factor determining the fluorescence of collagen in these patients. There was a relationship between CLF and presence of diabetic retinopathy after the data were adjusted for patient age and duration of diabetes (P = 0.023). Increased fluorescence of skin collagen can be detected in young type I diabetic patients and is primarily related to duration of diabetes.

Adult↗
PubMed1989

Usefulness of cardiovascular tests of autonomic function in asymptomatic diabetic patients.

A group of five cardiovascular tests of autonomic neural function was studied in 115 asymptomatic insulin-dependent diabetic patients and nine patients with symptoms of diabetic autonomic neuropathy. In the asymptomatic group, 34 patients had one or more abnormal test. R-R variation during deep breathing was most frequently abnormal, but reliance on this test alone to examine parasympathetic function would have missed 12 of the 34 abnormal patients. The two abnormal responses to isometric exercise in this group were probably false-positive results caused by poor patient effort. In the symptomatic patients, R-R variation during deep breathing was abnormal in all nine, the blood pressure response to standing was abnormal in seven, and the response to isometric exercise was abnormal in three. The blood pressure response to isometric exercise is uncomfortable, requires special equipment, and should probably be confined to the assessment of symptomatic patients in a specialist setting.

Adolescent↗
PubMed1989

The role of cortisol in the peripheral granulocyte response to insulin-induced hypoglycaemia in man.

Peripheral blood leukocyte counts and plasma hormonal changes in response to acute insulin-induced hypoglycaemia were examined in 16 patients undergoing assessment of pituitary function. Eight subjects had a normal cortisol secretory response (Group 1), and 8 patients had definite hypopituitarism in whom the cortisol responses were deficient or absent (Group 2). An equivalent degree of hypoglycaemia was achieved in both groups. In Group 1a biphasic rise in leukocyte count occurred following hypoglycaemia, with an early rise in lymphocytes at 15 minutes after the acute hypoglycaemic reaction, and a later rise in granulocytes. A similar rise in lymphocytes was observed in Group 2, but the rise in the granulocyte count was attenuated, increasing from a basal value of 3.6 +/- 0.6 x 10(9) cells/L to a peak of 7.4 +/- 1.1 x 10(9) cells/L, compared with a peak of 11.7 +/- 1.2 x 10(9) cells/L in Group 1 (P less than 0.05). The usual increment in plasma cortisol in response to hypoglycaemia occurred in Group 1, but plasma cortisol did not rise in Group 2. A correlation was observed between the magnitude of the granulocyte rise and the increment in plasma cortisol in individual subjects (r = 0.64, P less than 0.02). This suggests that the rise in peripheral granulocytes following insulin-induced hypoglycaemia in man is mediated by cortisol released from the adrenal gland, following activation of the hypothalamic-pituitary-adrenal axis.

Blood Glucose↗
PubMed1989

Endomyocardial biopsy pathology in insulin-dependent diabetic patients with abnormal ventricular function.

We have previously shown impaired ventricular function in asymptomatic middle-aged type 1 (insulin-dependent) diabetic patients who had no evidence of coronary artery disease. The diabetic patients had normal coronary angiograms but reduced ventricular ejection fraction on exercise. To examine the possible contribution of small vessel disease to this functional abnormality, we compared endomyocardial biopsies from seven symptom-free type 1 diabetic patients with biopsies from seven age- and sex-matched non-diabetic subjects. Interstitial fibrosis was present in three diabetic patients, arteriolar hyalinization in three patients and arteriolar thickening was observed in five patients. Morphometry performed on electron micrographs showed no significant difference in the thickness of the capillary basal lamina between diabetics and controls. While the functional significance of the abnormalities on light microscopy is unclear, our findings indicate that the abnormality of cardiac function described in diabetes is not associated with thickening of the myocardial capillary basal lamina.

Adult↗
PubMed1989

Plasma hepatic glutathione S-transferase concentrations after insulin-induced hypoglycaemia in normal subjects and diabetic patients.

Plasma glutathione S-transferase basic isoenzyme (GST B1) concentrations have been measured by specific radioimmunoassay in Type 1 diabetic patients and in normal subjects, before and after controlled insulin-induced hypoglycaemia, and in a further group of Type 1 diabetic patients in hypoglycaemic coma. The activities of alanine aminotransferase (ALT), aspartate amino-transferase (AST), and gamma-glutamyl transferase (gamma GT) were also measured. GST B1 concentrations were significantly increased 3 h after controlled insulin-induced hypoglycaemia, both in the diabetic patients (p less than 0.02) and in the normal group (p less than 0.05), but the magnitude of the rise did not differ between these two groups. Four of the 9 patients presenting in hypoglycaemic coma had a GST B1 concentration above the reference range. ALT, AST, and gamma GT activities did not rise following hypoglycaemia in any of the groups.

Adolescent↗
PubMed1989

Non-invasive evaluation of cardiac function in young patients with type 1 diabetes.

Cardiac function was evaluated in 40 Type 1 diabetic patients aged less than 30 years and compared with 20 age- and sex-matched control subjects using resting and exercise electrocardiography, and echocardiography. The duration of diabetes was from 0.25 to 25 years (mean 10 years), and few patients had microvascular complications. Left ventricular end-diastolic and end-systolic diameters were similar in both groups, with no significant differences between the groups in mean thickness of the intraventricular septum and the posterior wall of the left ventricle. Fractional shortening and mean velocity of circumferential fibre shortening as indices of ventricular function were similar in both groups. Left ventricular hypertrophy (Minnesota Code 3,1) was observed in the resting electrocardiogram of 22 patients and 12 control subjects (NS), but no other significant abnormalities were observed. One diabetic patient developed asymptomatic ST segment depression during exercise electrocardiography. In conclusion, the chamber size, wall thickness, and systolic function of the left ventricle are normal in most young Type 1 diabetic patients who have few microvascular complications.

Adolescent↗
PubMed1989

The effects of acute insulin-induced hypoglycaemia on renal function in normal human subjects.

The effects of acute insulin-induced hypoglycaemia on renal function were studied in 8 normal male subjects. Plasma glucose (mean (SE) fell from 4.6(0.2) to 1.3(0.2) mmol l(-1), the nadir being coincident with the acute autonomic reaction, and returned to the basal value over the following 120 min. Glomerular filtration rate declined from 118(6) to 95(4) ml min-1 at the glucose nadir (p less than 0.01), and during the recovery phase returned to 118(7) ml min-1 (NS compared with basal). Renal plasma flow fell from 625(38) to 485(27) ml min-1 (p less than 0.01), rising to 545(46) ml min-1 during recovery from hypoglycaemia (NS compared with basal). Following hypoglycaemia, urinary excretion of sodium and dopamine were reduced significantly, but the albumin excretion rate was unchanged. Plasma concentrations of adrenaline, noradrenaline, angiotensin II, and plasma renin activity increased in response to hypoglycaemia. These acute changes in renal function are probably caused by sympatho-adrenal activation and secretion of catecholamines, but other hormones, such as angiotensin II, may be contributory.

Albuminuria↗
PubMed1989

Type 1 diabetes and driving experience: an eight-year cohort study.

The driving habits of 250 drivers with Type 1 diabetes were reviewed 8 years after a previous assessment. At least 45 patients had died and 18 patients could not be traced. A postal questionnaire of the 187 survivors elicited a response from 89%. Fifty-six patients (34%) still held an unrestricted driving licence, demonstrating that a significant proportion of diabetic drivers had not declared diabetes to the licensing authority and/or their motor insurer and continued to ignore the statutory regulations. Fewer patients held Heavy Goods Vehicle licences than 8 years previously. Twenty-four patients had ceased driving as their driving skills had diminished with advancing age and ill health. This was a voluntary decision by all but two patients whose driving licences had been revoked. Thirty-nine patients admitted to a total of 55 road traffic accidents since 1979; 9 accidents (16%) were attributed to hypoglycaemia. Although dependent on patients' honesty and the accuracy of recall, the disclosed accident rates of 4.9 per million miles driven for male drivers and 6.3 per million miles for female drivers are comparable to the accident rate of a non-diabetic driving population of similar age.

Accidents, Traffic↗
PubMed1989

Limited joint mobility, Dupuytren's contracture and retinopathy in type 1 diabetes: association with cigarette smoking.

To examine the associations between cigarette smoking, connective tissue changes, and diabetic retinopathy, a detailed smoking history was elicited from 150 normotensive non-diabetic subjects, and from 266 randomly selected adult patients with Type 1 diabetes, after examination for limited joint mobility, Dupuytren's contracture, and diabetic retinopathy. Mean insulin dose and current glycosylated haemoglobin concentrations were comparable in diabetic smokers and non-smokers. The historical duration of smoking correlated with the duration of diabetes (r = 0.72, p less than 0.001). In diabetic patients limited joint mobility was positively associated with retinopathy, being found in 73/147 (50%) patients with retinopathy compared with 20/114 (18%) without retinopathy (chi 2 = 28.9, p less than 0.001), and also with Dupuytren's contracture, 19/34 (56%) of patients with limited joint mobility having Dupuytren's contracture, compared with 76/232 (33%) of patients without Dupuytren's contracture (chi 2 = 7.05, p less than 0.01). Limited joint mobility was observed in 50% of diabetic smokers compared with 25% of non-smokers (odds ratio = 2.87 (corrected for diabetes duration), 95% confidence interval 1.64-5.01). Diabetic retinopathy was weakly associated with smoking (odds ratio 1.09; 95% confidence interval 0.60-1.96). There was however an increased prevalence of background retinopathy among male smokers (50% vs 29%; chi 2 = 6.88, p less than 0.01). In non-diabetic males limited joint mobility was observed in 37% of smokers but only in 11% of non-smokers (NS), while 33% of smokers and 8% of non-smokers had Dupuytren's contracture (p = 0.012). These results suggest that cigarette smoking contributes to the development of extra-articular connective tissue changes in both diabetic patients and non-diabetic subjects, and possibly to the development of diabetic retinopathy.

Adult↗
PubMed1989

Arginine vasopressin and oxytocin responses to insulin-induced hypoglycemia in type 1 (insulin-dependent) diabetes.

In normal humans, arginine vasopressin and oxytocin are released acutely from the posterior pituitary gland in response to hypoglycemia, and their release may assist counterregulation. The responses of these hormones to insulin-induced hypoglycemia were measured in 16 insulin-dependent diabetic patients with no autonomic neuropathy (8 patients who had been diabetic less than 5 yr and 8 patients who had been diabetic greater than 15 yr) and in 6 normal subjects. The time of the onset of hypoglycemia and the mean blood glucose nadirs were similar in all groups, but the blood glucose recovery was delayed in the diabetic patients. In the normal subjects plasma arginine vasopressin rose from a mean basal value of 0.4 +/- 0.2 (+/- SE) pmol/L to a maximum of 1.3 +/- 0.6 pmol/L, and plasma oxytocin rose from 0.7 +/- 0.1 pmol/L to a maximum of 1.2 +/- 0.2 pmol/L 30 min after the onset of hypoglycemia. The plasma arginine vasopressin and oxytocin concentrations after hypoglycemia were significantly higher in both of the diabetic groups compared with those in the normal group. Arginine vasopressin and oxytocin rose in all control subjects after hypoglycemia. The individual hormonal profiles in the diabetic patients were variable, with an exaggerated rise of oxytocin in some diabetic patients and no rise in others. The arginine vasopressin responses were exaggerated in all of the diabetic patients. There was no correlation between the hormonal responses and the duration of diabetes. The exaggerated plasma arginine vasopressin and oxytocin responses to hypoglycemia in diabetic patients may indicate the failure of a normal inhibitory mechanism which modulates hormonal secretion or a compensatory response to impaired glucose recovery.

Adolescent↗
PubMed1988

Counterregulatory hormonal responses to hypoglycaemia in type 1 (insulin-dependent) diabetes: evidence for diminished hypothalamic-pituitary hormonal secretion.

Acute insulin-induced hypoglycaemia in humans provokes autonomic neural activation and counterregulatory hormonal secretion mediated in part via hypothalamic stimulation. Many patients with Type 1 (insulin-dependent) diabetes have acquired deficiencies of counterregulatory hormonal release following hypoglycaemia. To study the integrity of the hypothalamic-pituitary and the sympatho-adrenal systems, the responses of pituitary hormones, beta-endorphin, glucagon and adrenaline to acute insulin-induced hypoglycaemia (0.2 units/kg) were examined in 16 patients with Type 1 diabetes who did not have autonomic neuropathy. To examine the effect of duration of diabetes these patients were subdivided into two groups (Group 1: 8 patients less than 5 years duration; Group 2: 8 patients greater than 15 years duration) and were compared with 8 normal volunteers (Group 3). The severity and time of onset of hypoglycaemia were similar in all 3 groups, but mean blood glucose recovery was slower in the diabetic groups (p less than 0.01). The mean responses of glucagon, adrenaline, adrenocorticotrophic hormone, prolactin and beta-endorphin were similar in all 3 groups, but the mean responses of growth hormone were lower in both diabetic groups than in the normal group (p less than 0.05). The mean increments of glucagon and adrenaline in the diabetic groups were lower than the normal group, but these differences did not achieve significance; glucagon secretion was preserved in several diabetic patients irrespective of duration of disease. Various hormonal responses to hypoglycaemia were absent or diminished in individual diabetic patients, and multiple hormonal deficiencies could be implicated in delaying blood glucose recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1988

A comparison of treatment with metformin and gliclazide in patients with non-insulin-dependent diabetes.

Twenty-seven obese non-insulin-dependent diabetic patients, treated with dietary carbohydrate restriction and metformin, were recruited from the diabetic outpatient clinic and entered into an open crossover study with gliclazide. Twenty-one patients completed the study. During three months observation on metformin, the mean weight of the group fell by 1.0 kg with 14 patients losing a mean of 1.8 kg with 14 patients losing a mean of 1.8 kg, 3 remaining unchanged and 4 gaining a mean weight of 1.1 kg. Over the subsequent three months on gliclazide, the mean weight of the group rose by 1.4 kg with 16 patients gaining a mean of 2.2 kg, two remaining unchanged and 3 losing a mean of 2.0 kg. In addition, 10 patients were heavier after gliclazide than at the time of recruitment (mean 2.6 kg), 3 were unchanged and 8 had lost weight since commencing the trial (mean 2.1 kg), mostly due to greater loss on metformin than gain on gliclazide. Glycaemic control did not improve significantly during the observed period on metformin but lower concentrations of fasting glucose and total glycosylated haemoglobin were achieved with gliclazide. Mean plasma insulin concentration was significantly higher and mean serum lactate was significantly lower during treatment with gliclazide. In conclusion, gliclazide does not support weight loss in obese non-insulin-dependent diabetic patients to the same extent as metformin but the difference between the two drugs is small. Gliclazide is a suitable oral hypoglycaemic agent for use in the obese diabetic who cannot be controlled by diet alone.

Adult↗
PubMed1988

Glycemic control and raised serum alanine aminotransferase activity in treated diabetes mellitus.

The prevalence of raised serum liver-associated enzyme activity in stabilised, treated diabetic outpatients without concurrent hepatobiliary disease was investigated using a retrospective computer search of biochemical data. The frequency of raised alanine aminotransferase, aspartate aminotransferase, or gamma glutamyl transferase activity found among diabetic, general medical and respiratory outpatients was compared with that found in apparently healthy controls. It was established that a raised activity of any of the three enzymes occurred with a similar frequency in each outpatient group. However, only with alanine aminotransferase did the frequency of elevation (7.1%) in the patients with previously diagnosed hepatobiliary disease exceed that of healthy controls. A raised alanine aminotransferase activity in diabetic outpatients was associated with good glycemic control (hemoglobin A1 less than 8%, p less than 0.02) and treatment with oral hypoglycaemic agents (p less than 0.001).

Alanine Transaminase↗