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Biomedical subjects

P M Bell

Publications and source records attributed to P M Bell.

At least 19 recordsLinked to original sources
PubMed1992

Insulin action and hepatic glucose cycling in essential hypertension.

Peripheral insulin resistance is a feature of essential hypertension, but there is little information about hepatic insulin sensitivity. To investigate peripheral and hepatic insulin sensitivity and activity of the hepatic glucose/glucose 6-phosphate (G/G6P) substrate cycle in essential hypertension, euglycemic glucose clamps were performed in eight untreated patients and eight matched controls at insulin infusion rates of 0.2 and 1.0 mU.kg-1.min-1. A simultaneous infusion of (2(3)H)- and (6(3)H)glucose, combined with a selective detritiation procedure, was used to determine glucose turnover, the difference being G/G6P cycle activity. Endogenous hepatic glucose production (EGP) determined with (6(3)H)glucose was similar in hypertensive and control groups in the postabsorptive state (11.0 +/- 0.3 v 10.9 +/- 0.3 mumol.kg-1.min-1) and with the 0.2 mU insulin infusion (4.9 +/- 0.5 v 4.0 +/- 0.8 mumol.kg-1.min-1). With the 1.0 mU insulin infusion, glucose disappearance determined with (6(3)H)glucose was lower in the hypertensive group (21.8 +/- 2.4 v 29.9 +/- 2.4 mumol.kg-1.min-1, P less than .001). G/G6P cycle activity was similar both in the postabsorptive state (2.2 +/- 0.4 v 2.7 +/- 0.4 mumol.kg-1.min-1) and during insulin infusion (0.2 mU, 2.5 +/- 0.3 v 2.9 +/- 0.4; 1.0 mU, 4.7 +/- 0.3 v 5.3 +/- 1.1 mumol.kg-1.min-1 for hypertensive and control groups, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
PubMed1992

Influence of growth hormone on glucose-glucose 6-phosphate cycle and insulin action in normal humans.

Increased activity of the hepatic glucose-glucose 6-phosphate (G/G-6-P) cycle is associated with hepatic and peripheral insulin resistance in acromegaly. To determine whether a similar association occurs after short-term growth hormone (GH) elevation within the physiological range, two-step euglycemic hyperinsulinemic clamps were performed in normal human males after 12-h GH (2.2 ng.kg-1 x h-1) and control infusions. G/G-6-P cycle activity and endogenous glucose production (EGP) were determined by [2-3H]- and [6-3H]-glucose using labeled exogenous glucose infusions and selective enzymatic detritiation. GH increased levels of circulating lipid intermediates despite a twofold increase in basal insulin (P < 0.005), but plasma glucose, EGP, and G/G-6-P cycle activity were unchanged. GH impaired insulin suppression of EGP and lipid intermediates and impaired insulin stimulation of glucose disposal, but G/G-6-P cycle activity was unchanged. We conclude that increased activity of the G/G-6-P cycle does not contribute to the hepatic insulin resistance induced by GH under these conditions but that changes in fatty acid metabolism may be partly responsible for the impairment in hepatic and peripheral insulin action.

Adult↗
PubMed1991

The effects of low dose insulin infusions on the renin angiotensin and sympathetic nervous systems in normal man.

To examine the effects of physiological insulin concentrations on the renin-angiotensin and sympathetic nervous systems, healthy volunteers were studied by the euglycaemic glucose clamp technique with sequential 60 min 0.5 and 1.0 mU kg-1 min-1 insulin infusions and, subsequently, by a control infusion simulating clamp conditions. Plasma renin activity increased from 0.8 +/- 0.1 ng ml-1 h-1 basally to 1.0 +/- 0.2 ng ml-1 h-1 during the 0.5 mU infusion to 1.4 +/- 0.1 ng ml-1 h-1 during the 1 mU infusion but did not change during control infusion (0.9 +/- 0.3 ng ml-1h-1 to 0.9 +/- 0.2 ng ml-1h-1 to 1.0 +/- 0.1 ng ml-1h-1) (P less than 0.001 insulin vs. control by ANOVAR). Plasma angiotensin II increased during insulin (21.2 +/- 1.8 to 25.2 +/- 2.3 to 29.3 +/- 2.4 pg ml-1) but not during control infusion (24.0 +/- 2.8 to 23.6 +/- 2.6 to 23.5 +/- 2.5 pg ml-1) (P less than 0.001 insulin vs. control). Serum aldosterone did not change significantly during either infusion (insulin: 239 +/- 89 pmol l-1 to 237 +/- 50 pmol l-1 to 231 +/- 97 pmol l-1, control: 222 +/- 79 to 237 +/- 50 to 213 +/- 97 pmol l-1). Plasma noradrenaline increased to a greater extent during insulin (1.03 +/- 0.2 to 1.14 +/- 0.8 to 1.27 +/- 0.17 nmol l-1) than control infusion (0.86 +/- 0.09 to 0.97 +/- 0.09 to 0.99 +/- 0.09 nmol 1-1 (P less than 0.01 insulin vs. control). Changes in mean systolic blood pressure during insulin infusion were significantly different from control (+ 3 vs. -4 mmHg, P less than 0.001). In conclusion acute hyperinsulinaemia within the physiological range increases circulating hormones of the renin-angiotensin and sympathetic nervous systems and also increases systolic blood pressure.

Adult↗
PubMed1991

Basal and stimulated plasma atrial natriuretic factor in patients with type 1 diabetes with and without nephropathy.

Hypertension is linked to the development of nephropathy in Type 1 diabetes. Total exchangeable sodium is elevated in patients with Type 1 diabetes in good metabolic control, and correlates with blood pressure. Atrial natriuretic factor has been shown to have effects on sodium and blood pressure homeostasis in man. Basal and NaCl-stimulated plasma atrial natriuretic factor was therefore studied in 33 patients with Type 1 diabetes. Seventeen had no evidence of nephropathy, 11 had incipient nephropathy (albumin excretion rate 20-199 micrograms min-1) and five had overt nephropathy. Seventeen age- and sex-matched normal control subjects were also studied. Subjects fasted from 2200 h, rose at 0745 h and remained ambulant until 0945 h. After 15 min supine, 2 l 0.15 mmol l-1 NaCl was infused over 4 h. Basal erect (0945 h) plasma atrial natriuretic factor was 4.2 +/- 0.5, 3.5 +/- 0.4, 2.5 +/- 0.2, and 2.5 +/- 0.3 pmol l-1 in the control, non-nephropathic, incipient-nephropathic, and overt nephropathic diabetic groups, respectively (all NS). Levels in all groups increased in response to NaCl infusion, and the responses were not different between groups. Urinary sodium excretion for 12 h before NaCl infusion was not different between groups, but during the 12 h after the start of the infusion was significantly (p less than 0.05) less in the Type 1 diabetic group without nephropathy than in the control group. These results suggest that atrial natriuretic factor does not play a major role in the development of changes in sodium balance which are associated with Type 1 diabetes and nephropathy.

Adult↗
PubMed1991

Diabetes care by general practitioners in Northern Ireland: present state and future trends.

A questionnaire returned by 250 (71.4%) of the 350 general practices in Northern Ireland indicated that although only 34 practices had special arrangements for seeing their diabetic patients, 178 practices stated that they would like to be more involved in the care of their non-insulin-dependent diabetes mellitus (NIDDM) patients. One hundred and eight practices felt the same way about their insulin-dependent diabetes mellitus (IDDM) patients. One hundred practices stated that the partners felt competent to manage their diabetic patients. The main area where general practitioners felt they needed to improve their knowledge was ophthalmology (56 practices). When asked which type of care scheme would appeal most to their practice, 135 practices stated that regular attendance with the general practitioner and annual hospital review would be the preferred arrangement. Overall there was a positive attitude towards increased general practitioner involvement in diabetes care.

Attitude of Health Personnel↗
PubMed1990

Underestimation of glucose turnover determined using [6-3H]glucose tracer in non-steady state. The role of a tritiated tracer impurity.

The use of tritiated glucose tracers may result in underestimation of glucose turnover during hyperinsulinaemic clamps giving paradoxical negative endogenous glucose production rates. While mathematical modelling errors in the analysis of tracer data are major determinants of this underestimate in the non-steady state, the relative importance of tracer contamination under these conditions remains in doubt. We have used high performance liquid chromatography to assess the possible contribution to this problem of a labelled tracer impurity found in [6-3H]glucose. In conventional 4 h hyperinsulinaemic clamps performed in six normal subjects, labelled impurity increased as a percentage of the neutral plasma radioactivity fraction from 5.3 +/- 0.9% after a 2 h equilibration period (0 min) to 13.5 +/- 2.2% at 120 min and 15.4 +/- 2.4% at 240 min, as plasma glucose specific activities fell following the infusion of insulin. Negative endogenous glucose production rates were observed both at 90-120 min (-8.8 +/- 1.6 mumol.kg-1min-1) and at 210-240 min (-8.5 +/- 1.4 mumol.kg-1min-1) implying a persistent underestimate in isotopically determined glucose appearance rate. Using chromatography data to correct for impurity increased glucose appearance rates by 7.9 +/- 2.1% at 120 min and 11.0 +/- 2.5% at 240 min. Purified tracer was then used for a further six clamps. When the conventional protocol was used with unlabelled glucose infusion an obvious negative error persisted only at 90-120 min. In contrast, labelled infusions gave exclusively positive values for endogenous glucose production.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

The assessment of hepatic and peripheral insulin sensitivity in hypertriglyceridemia.

Peripheral insulin resistance is a common finding in hypertriglyceridemia. However, hepatic insulin sensitivity has rarely been investigated. We measured hepatic and peripheral insulin sensitivity in eight nondiabetic, nonobese hypertriglyceridemic subjects (HT) with raised triglyceride concentrations (4.3 +/- 0.6 mmol.L-1, mean +/- SEM) and eight age-, sex-, and weight-matched control subjects (C) with normal triglyceride concentrations (1.2 +/- 0.2 mmol.L-1). Insulin secretion was assessed during a 75-g oral glucose tolerance test (OGTT). Glucose turnover was determined using 3(3H) glucose in the postabsorptive state and during euglycemic glucose clamps at insulin infusion rates of 0.25 and 1.0 mU.kg-1.min-1. At identical fasting glucose concentrations (HT, 5.2 +/- 0.2; C, 5.2 +/- 0.2 mmol.L-1), the glucose responses to OGTT were similar in both groups. Fasting plasma insulin (HT, 8.3 +/- 1.2; C, 4.6 +/- 0.4 mU.L-1; P = .02), and C-peptide (HT, 1.7 +/- 0.2; C, 1.1 +/- 0.1 microgram.L-1; P = .006) concentrations were higher in hypertriglyceridemic subjects. The insulin and C-peptide responses to OGTT were greater in hypertriglyceridemic subjects (insulin, P = .005; C-peptide; P = .01). Hepatic glucose appearance in the postabsorptive state was similar (HT, 11.4 +/- 0.3; C, 10.9 +/- 0.7 mumol.kg-1.min-1; NS). At low insulin concentrations (HT, 20.7 +/- 1.4; C, 20.5 +/- 1.4 mU.L-1), hepatic glucose appearance was equally suppressed (HT, 9.6 +/- 0.9; C, 10.5 +/- 1.3 mumol.kg-1.min-1; NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1990

Somatostatin analogue (SMS 201-995) in resistant acromegaly: a preliminary report.

The results of treating 10 acromegalic patients with octreotide are compared with those of bromocriptine. Bromocriptine (5 mg 4 times daily for 5 weeks) reduced mean growth hormone (GH) concentrations from 60 to 35 mU/l in 8 patients; a further 2 patients were unable to tolerate this dose. Ten patients (8 unresponsive to bromocriptine) received octreotide 100 micrograms 3 times daily, rising to 500 micrograms 3 times daily according to monthly 24-hour GH profiles. Two patients were withdrawn from octreotide therapy; in the remaining 8, mean GH fell from 36 to 11 mU/l after 6 months' therapy (a reduction to 22% of basal concentrations, compared to a reduction to 58% on bromocriptine). Asymptomatic changes of glucose tolerance and the development of gallstones were noted; further information on the latter is urgently required. In summary, the smallest effective dose of octreotide should be used and each patient should be monitored biochemically.

Acromegaly↗
PubMed1990

Immunoglobulin-AST complex.

A case of AST-IgG complex presenting as an isolated AST elevation is described. Measurement of elevated serum AST activity is dependent upon the inclusion of pyridoxal 5-phosphate in the substrate.

Aspartate Aminotransferases↗
PubMed1989

Motor vehicle driving among diabetics taking insulin and non-diabetics.

OBJECTIVE: To determine whether rates of road traffic accidents were higher in diabetics treated with insulin than in non-diabetic subjects. DESIGN: Controlled, five year retrospective survey. SETTING: Diabetic, dermatology, and gastroenterology outpatient clinics. PATIENTS: 596 Diabetics treated with insulin (354 drivers) aged 18-65 attending two clinics and 476 non-diabetic outpatients (302 drivers). MAIN OUTCOME MEASURES: Rates of accidents in diabetic and non-diabetic subjects. RESULTS: A self completed questionnaire was used to record age, sex, driving state, and rates of accidents and convictions for motoring offences among diabetic and non-diabetic volunteers. For the diabetic volunteers further information was obtained on treatment, experience of hypoglycaemia, and declaration of disability to the Driving and Vehicle Licensing Centre and their insurance company. Accident rates were similar (81 (23%) diabetic and 76 (25%) non-diabetic drivers had had accidents in the previous five years). A total of 103 diabetic drivers had recognised hypoglycaemic symptoms while driving during the previous year. Only 12 reported that hypoglycaemia had ever caused an accident. Overall, 249 had declared their diabetes to an insurance company. Of these, 107 had been required to pay an increased premium, but there was no excess of accidents in this group. CONCLUSIONS: Diabetic drivers treated with insulin and attending clinics have no more accidents than non-diabetic subjects and may be penalised unfairly by insurance companies.

Accidents, Traffic↗
PubMed1989

Assessment of the postprandial pattern of glucose metabolism in nondiabetic subjects and patients with non-insulin-dependent diabetes mellitus using a simultaneous infusion of [2(3)H] and [3(3)H] glucose.

Glucose turnover determined with tritiated isotopes of glucose is subject to potential error due to glucose/glucose-6-phosphate cycling and/or cycling through glycogen. To determine the extent to which these processes alter the apparent pattern of postprandial glucose metabolism, we measured glucose turnover simultaneously with [2(3)H] glucose (an isotope that minimally cycles through glycogen but is extensively detritiated during glucose/glucose-6-phosphate cycling) and [3(3)H] glucose (an isotope that is not detritiated during glucose/glucose-6-phosphate cycling but can cycle through glycogen). Glucose turnover was measured in patients with non-insulin-dependent diabetes mellitus (NIDDM) and nondiabetic subjects both before and after ingestion of a carbohydrate meal isotopically with labeled [6(14)C] glucose. In the postabsorptive state hepatic glucose appearance was higher (P less than .05) when determined with [2(3)H] glucose than with [3(3)H] glucose in the diabetic patients, but not in the nondiabetic subjects. After glucose ingestion the integrated responses of glucose appearance, systemic entry of ingested glucose, and hepatic glucose release all were higher (P less than .05) when determined with [2(3)H] glucose compared to [3(3)H] glucose in both the diabetic and nondiabetic subjects. However, the absolute difference between glucose turnover measured with [2(3)H] and [3(3)H] glucose were similar in the diabetic and nondiabetic subjects. Both isotopes provided a similar assessment of postprandial carbohydrate metabolism, indicating that either isotope can be used with equal efficacy to compare postprandial carbohydrate metabolism in patients with NIDDM and nondiabetic subjects.

Adult↗
PubMed1989

Psychomotor performance and counterregulatory responses during mild hypoglycemia in healthy volunteers.

The effect of mild hypoglycemia on psychomotor performance and counterregulatory responses was studied among 12 healthy volunteers. Each volunteer received two modified hyperinsulinemic glucose clamps. One morning, plasma glucose was held constant at euglycemic levels (4.9 mM) for 95 min, and another morning, it was lowered over 35 min and then held constant at hypoglycemic levels (3.4 mM) for 60 min. A battery of psychomotor tests and a questionnaire assessing hypoglycemic symptoms were administered before and repeated during the last 30 min of each clamp. The questionnaire and three selected psychomotor tests were also administered repetitively during the 1st h of each clamp. During the hypoglycemic studies, a rise was seen in plasma epinephrine and pancreatic polypeptide at 45 min. An increase in symptom scores was first recorded at 50 min during the hypoglycemic studies [median 4 (range 0-13) vs. 2 (5-6), P less than .05]. Performance was impaired on two psychomotor tests included in the battery. One was the trail making test on fine motor performance (-19.3 +/- 4.2 targets/min, mean +/- SE vs. 1.2 +/- 4.8 targets/min, P less than .05), and the other was the digit-symbol substitution (DSS) test on information processing and memory (18 +/- 3 vs. 29 +/- 4 symbols/min, P less than .03). Of the tests administered during the 1st h, performance was impaired on the DSS. This impairment became significant at 45 min (14 +/- 4 vs. 22 +/- 4 symbols/min, P less than .005). In conclusion, mild hypoglycemia selectively impairs psychomotor performance in healthy volunteers but not before the onset of glucose counterregulation and warning symptoms.

Adult↗
PubMed1988

Reassessment of enteric endocrine cell hyperplasia in celiac disease.

Celiac disease is characterized by reversible, gluten-induced, architectural abnormalities of the intestinal mucosa. Villus atrophy is compensated for by an increase in the number of proliferating cells and an increase in crypt cell production rate, resulting in increased crypt length and girth. Several authors, employing various methods of quantitation, have reported enteric endocrine cell hyperplasia in celiac disease. The present study has re-evaluated enteric endocrine cell status in this disorder by employing methods of quantitation which more accurately take account of alterations of crypt morphology than those previously used. Numbers of endocrine cells expressed as cells per unit of crypt length are not increased in the celiac biopsies when contrasted with those from controls. Indeed, numbers of cells immunoreactive for gastrin, GIP, motilin and somatostatin were reduced in the celiac mucosa. Endocrine cell hyperplasia in the celiac small bowel is not as marked as was previously thought, and may lag behind that of the enterocyte population.

Adult↗
PubMed1988

Accuracy of blood glucose concentrations determined by four visually read reagent strips.

Two new reagent strips have recently been introduced for blood glucose measurement by direct visual reading. Results obtained with these strips (Glucostix and Hypogard GA) were compared with those obtained using other commonly employed strips (BM-Test-Glycemie 1-44 and Visidex II) and a standard laboratory method. Blood glucose estimations were performed on samples of venous blood drawn from 125 patients attending the diabetic clinic using each of the four strips and the laboratory method. Results obtained with the strips correlated with the laboratory values as follows: BM-Test-Glycemie 1-44, r=0.93; Glucostix r=0.93; Hypogard GA r=0.87 and Visidex II r=0.92. The lower correlation with Hypogard GA reflected consistent underestimation of the laboratory value (slope of regression line = 0.63). Readings in error by 20% or more were: BM-Test-Glycemie 1-44, 14%; Glucostix, 15%; Hypogard GA, 31%, and Visidex II, 14%. With Hypogard GA strips, 57% of readings above 16 mmol/l were inaccurate. We conclude that Hypogard GA strips cannot be recommended for direct visual reading. Acceptable results may, however, be obtained using the other three strips.Reagent strips allow reasonably accurate determinations of blood glucose concentrations when used with a reflectance meter.(1, 2) Nevertheless many diabetic patients prefer to read the reagent strips visually. This method avoids the problems associated with meter calibration, is cheaper and also is more portable. Direct visual readings with BM-Test-Glycemie 1-44 (Boehringer Corporation) and Visidex II (Ames) have been shown to be acceptable in the hands of medical and technical personnel.(3, 4) Recently two new reagent strips have been marketed, Hypogard GA (Hypogard UK Ltd) and Glucostix (Ames), and it is claimed that they are also suitable for direct visual reading. To test the validity of these claims, we have compared results obtained using the newer strips with readings from BM-Test-Glycemie 1-44 and Visidex II and with a standard laboratory method.

Blood Glucose↗
PubMed1987

The effects of hyperglycaemia on isotopic measurement of glucose utilisation using [2(3)H], [3(3)H] and [6(14)C] glucose in patients with type 1 (insulin-dependent) diabetes mellitus.

To determine whether hyperglycaemia alters the accuracy with which [2(3)H] and [3(3)H]glucose reflect glucose turnover measured with [6(14)C]glucose in patients with Type 1 (insulin-dependent) diabetes mellitus, glucose utilisation rates were measured during a simultaneous infusion of [2(3)H], [3(3)H] and [6(14)C]glucose after maintenance of normoglycaemia overnight and when glucose concentrations were clamped at 5.3, 7.5 and 9.7 mmol/l while insulin and glucagon concentrations were held constant. Glucose utilisation rates determined with all three isotopes were comparable in the diabetic patients at all glucose concentrations studied. On the other hand, glucose utilisation rates in nondiabetic subjects determined with [6(14)C]glucose were greater (p less than 0.01) than those determined with [3(3)H]glucose and lower (p less than 0.04) than those determined with [2(3)H]glucose during the 5.3, 7.5 and 9.7 mmol/l clamps. Nevertheless, glucose utilisation rates in the diabetic patients were lower (p less than 0.05) than those in the nondiabetic subjects for each glucose isotope. We conclude that hyperglycaemia does not alter the pattern of metabolism of [2(3)H] or [3(3)H]glucose in patients with Type 1 (insulin-dependent) diabetes mellitus.

Adult↗
PubMed1986

Effects of tolazamide and exogenous insulin on insulin action in patients with non-insulin-dependent diabetes mellitus.

To determine whether sulfonylureas and exogenous insulin have different effects on insulin action, we studied eight patients with non-insulin-dependent diabetes mellitus before and after three months of treatment with tolazamide and exogenous semisynthetic human insulin, using a randomized crossover design. Therapy with tolazamide and therapy with insulin resulted in similar improvement of glycemic control, as measured by a decrease in mean glycosylated hemoglobin (+/- SEM) from 9.4 +/- 0.7 percent to 7.7 +/- 0.5 percent with tolazamide and to 7.1 +/- 0.2 percent with exogenous insulin (P less than 0.01 for both comparisons). Therapy with either tolazamide or exogenous insulin resulted in a similar lowering (P less than 0.05) of postabsorptive glucose-production rates (from 2.3 +/- 0.1 to 2.0 +/- 0.2 and 1.8 +/- 0.1 mg per kilogram of body weight per minute, respectively) but not to normal (1.5 +/- 0.1 mg per kilogram per minute). Both tolazamide and exogenous insulin increased (P less than 0.05) glucose utilization at supraphysiologic insulin concentrations (from 6.2 +/- 0.7 to 7.7 +/- 0.6 mg per kilogram per minute with tolazamide and to 7.8 +/- 0.6 mg per kilogram per minute with exogenous insulin) to nondiabetic rates (7.9 +/- 0.5 mg per kilogram per minute). Neither agent altered erythrocyte insulin binding at physiologic insulin concentrations. We conclude that treatment with sulfonylureas or exogenous insulin results in equivalent improvement in insulin action in patients with non-insulin-dependent diabetes mellitus. Therefore, the choice between these agents should be based on considerations other than their ability to ameliorate insulin resistance.

Blood Glucose↗
PubMed1986

Endocrine and exocrine pancreatic function in treated coeliac disease.

Pancreatic function was assessed prospectively in a group of 18 treated adult coeliac patients, most of whom were asymptomatic. The para-aminobenzoic acid (PABA) test indicated exocrine pancreatic insufficiency in three patients, all of whom had persisting gastrointestinal symptoms. Arginine, 5 g intravenously, was used to stimulate pancreatic islet cells; basal and stimulated concentrations of plasma insulin, C-terminal glucagon, N-terminal glucagon, and blood glucose did not differ from asymptomatic nondiabetic control subjects. After gluten withdrawal, coeliac patients who responded clinically had no evidence of significant pancreatic impairment, but consideration of exocrine pancreatic insufficiency is worthwhile in those patients with persisting symptoms.

4-Aminobenzoic Acid↗