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Biomedical subjects

A B Atkinson

Publications and source records attributed to A B Atkinson.

At least 73 records · Page 4Linked to original sources
PubMed1995

Four years' treatment of resistant acromegaly with octreotide.

This study was designed to ascertain the long-term safety and efficacy profile of the somatostatin analogue octreotide as treatment of refractory acromegaly. Eight patients (aged 21-62 years) with persistent growth hormone (GH) elevation (duration 1-15 years) despite previous therapy were studied. Octreotide was given subcutaneously in increasing doses for the first year to a maximum of 500 micrograms three times daily. The dose then was reduced to 200 micrograms three times daily for the next 3 years. At annual assessments, 24-h GH profiles, insulin-like growth factor I (IGF-I) and a side-effect profile including gall-bladder ultrasound were studied. Oral glucose tolerance tests (75 g) were performed basally and after 6 months and 3 years of therapy. Haemoglobin A1 (HbA1) was also assessed. Side effects were recorded. Mean GH (+/- SEM) was 36.0 +/- 9 mU/l basally and was reduced significantly at all subsequent assessments on therapy (4-year mean, 9.4 +/- 2.1 mU/l). The IGF-I level also remained suppressed and was normalized in four of eight patients who remained on octreotide. Fasting plasma glucose and HbA1 were not changed by therapy but 2-h glucose was elevated after 6 months and 3 years (basal mean, 7.6 mmol/l (5.3-9.0 mmol/l); 3-year mean, 10.7 mmol/l (8.4-15.7 mmol/l); p < 0.05). Five patients developed gallstones and in three these had disappeared following 1 year of bile salt dissolution therapy. Octreotide continues to suppress serum GH and IGF-I long term without attenuation of effect. Gallstone formation is a major side effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1995

Mutations in the human Ca(2+)-sensing-receptor gene that cause familial hypocalciuric hypercalcemia.

We report five novel mutations in the human Ca(2+)-sensing-receptor gene that cause familial hypocalciuric hypercalcemia (FHH) or neonatal severe hyperparathyroidism. Each gene defect is a missense mutation (228Arg-->Gln, 139Thr-->Met, 144Gly-->Glu, 63Arg-->Met, and 67Arg-->Cys) that encodes a nonconservative amino acid alteration. These mutations are each predicted to be in the Ca(2+)-sensing receptor's large extracellular domain. In three families with FHH linked to the Ca(2+)-sensing-receptor gene on chromosome 3 and in unrelated individuals probands with FHH, mutations were not detected in protein-coding sequences. On the basis of these data and previous analyses, we suggest that there are a wide range of mutations that cause FHH. Mutations that perturb the structure and function of the extracellular or transmembrane domains of the receptor and those that affect noncoding sequences of the Ca(2+)-sensing-receptor gene can cause FHH.

Calcium↗
PubMed1995

Insulin and C-peptide secretion in non-insulin-dependent diabetes mellitus and its response to dietary therapy.

We studied insulin and C-peptide levels in patients with non-insulin-dependent diabetes mellitus (NIDDM) during standard oral or intravenous glucose tolerance tests (GTT) at the time of diagnosis and after 3 months dietary therapy. On the second occasion they also had an 'augmented' GTT, in which slow intravenous infusion of glucose raised basal plasma glucose to a level similar to that at the time of diagnosis. Eight patients had oral tests, and seven patients intravenous tests. In both groups, dietary therapy significantly reduced fasting and peak plasma glucose (p < 0.05 for oral; p < 0.01 for intravenous GTT). Serum insulin levels during conventional oral GTT were not significantly different after dietary therapy compared to diagnosis, but were significantly higher during the 'augmented' oral GTT (p < 0.05). In those patients who underwent intravenous GTT, there was a significant increase in both the total amount of insulin secreted (0-60 min) and in first-phase insulin secretion (0-10 min) during the 'augmented' test compared to diagnosis (p < 0.01), but first-phase insulin secretion during the conventional intravenous GTT was unchanged. Serum C-peptide responses were also greater during 'augmented' tests (p < 0.05), similar in pattern to serum insulin. There is a relative deficiency in insulin secretion in untreated NIDDM, which can be reversed by dietary therapy. It is essential to study insulin and C-peptide secretion in controlled 'fasting' glucose conditions.

Administration, Oral↗
PubMed1995

Blood pressure responses to phenylephrine infusions in subjects with Cushing's syndrome.

The pathogenesis of the hypertension associated with Cushing's syndrome is not completely understood. Sensitivity to pressor agents may play a role. We have investigated this possibility by measuring blood pressure (BP) during incrementally increasing infusions of the alpha-adrenergic agonist phenylephrine. Ten subjects (8 women: 2 men), aged 40 +/- 5 years (mean +/- s.e.m.) with Cushing's syndrome were studied. All had raised BP but none had received any anti-hypertensive treatment for at least 16 days before study. Ten age- (40 +/- 5 years) and sex-matched control subjects were also studied. At 13.30, 30 min after a light meal, subjects had an intravenous cannula inserted, ECG leads and a sphygomanometer cuff attached, and then rested supine in a quiet room for 30 min. Phenylephrine was then infused incrementally at intervals of 5 min. The doses used were 0.3, 0.6, 0.9, 1.35 and 2 micrograms/kg/min. Basal mean blood pressure (MAP) was 108 +/- 2 mm Hg (mean +/- s.e.m.) in patients and 74 +/- 3 mm Hg in controls (P < 0.05) and pulse rate was 75 +/- 5 and 68 +/- 3 beats/min (NS), respectively). MAP increased and pulse rate decreased linearly with time. The rate of rise of MAP was 1.7 +/- 0.4 mm Hg/min in subjects and 1.1 +/- 0.2 mm Hg/min in controls (NS). The rate of decrease of pulse was significantly more rapid in Cushing's subjects than in controls (1.4 +/- 0.2; 0.6 +/- 0.1 beats/min2; P < 0.05). The lack of any increased BP response to alpha-adrenergic stimulation suggests that altered sensitivity is not a major cause of the increased BP seen in patients with Cushing's syndrome.

Adolescent↗
PubMed1995

Cortisol excretion in essential hypertension.

A number of factors suggest that abnormalities of the adrenal cortex are present in essential hypertension. To determine whether altered cortisol excretion exists in essential hypertension, we have measured urinary free cortisol and cortisol to creatinine ratios in early morning urine specimens for 14 consecutive days. We have established a reference range for these parameters in 26 normotensive subjects. We have also compared these values in nine normotensive subjects and nine patients with essential hypertension closely matched for age, sex and body mass index. In the 26 normotensive subjects, urinary free cortisol was 240 +/- 13 nmol/l (mean +/- s.e.m) and cortisol to creatinine ratio was 22 +/- l. In the nine hypertensive subjects, urinary free cortisol was 238 +/- 48 nmol/l and cortisol to creatinine ratio was 20 +/- 3. We have not demonstrated an abnormality of cortisol excretion in essential hypertension.

Adult↗
PubMed1994

Effects of low dose versus conventional dose thiazide diuretic on insulin action in essential hypertension.

OBJECTIVE: To see whether low dose thiazide diuretics given to patients with essential hypertension might avoid the adverse metabolic consequences seen with conventional doses. DESIGN: Double blind randomised crossover study of two 12 week treatment periods with either low dose (1.25 mg) or conventional dose (5.0 mg) bendrofluazide given after a six week placebo run in period. SETTING: Outpatient clinics serving the greater Belfast area. SUBJECTS: 16 white non-diabetic patients (9 male) under 65 with essential hypertension recruited from general practices within the greater Belfast area. MAIN OUTCOME MEASURES: Systolic and diastolic blood pressure and peripheral and hepatic insulin action. RESULTS: One man failed to complete the study. There were no differences between doses in their effects on systolic and diastolic blood pressure. Bendrofluazide 1.25 mg had substantially less effect on serum potassium concentration than the 5.0 mg dose. There were no intertreatment differences in fasting glucose, insulin, cholesterol, and triglyceride concentrations. Bendrofluazide 5.0 mg significantly increased postabsorptive endogenous glucose production compared with baseline (mean 10.9 (SD 1.2) v 10.0 (0.8) mumol/kg/min), whereas bendrofluazide 1.25 mg did not. Postabsorptive endogenous glucose production was significantly higher with bendrofluazide 5.0 mg compared with 1.25 mg (10.9 (1.2) v 9.9 (0.8) mumol/kg/min) but was suppressed to a similar extent after insulin (bendrofluazide 5.0 mg 2.8 (1.5) mumol/kg/min v bendrofluazide 1.25 mg 2.2 (1.5) mumol/kg/min). Exogenous glucose infusion rates required to maintain euglycaemia were not significantly different between doses and were similar to baseline. CONCLUSIONS: Bendrofluazide 1.25 mg is as effective as conventional doses but has less adverse metabolic effect. In contrast with conventional doses, low dose bendrofluazide has no effect on hepatic insulin action. There is no difference between low and conventional doses of bendrofluazide in their effect on peripheral insulin sensitivity.

Bendroflumethiazide↗
PubMed1994

Is a random urinary albumin concentration a useful screening test in insulin-treated diabetic patients?

The debate continues on how to screen for microalbuminuria in clinical practice in patients with insulin-dependent diabetes mellitus. Our study assesses the value of a spot morning urine specimen obtained at a clinic visit. In 1984, as part of a randomised survey of our diabetes clinic, 43 of 249 patients with insulin treated diabetes mellitus, were found to have microalbuminuria (urinary albumin concentration 35-300 ug ml-1) on a spot morning urine sample. These subjects were compared with an age-matched control group from the 1984 cohort who did not have microalbuminuria. Eight years later, in the group with microalbuminuria, 10 had died compared to six in the control group (p = 0.17) with 62.5% of all deaths being from cardiovascular disease. In the group with microalbuminuria, 10 of 27 still had incipient nephropathy while five had progressed to nephropathy. In the group without microalbuminuria only three of 33 patients had progressed to microalbuminuria while none had progressed to nephropathy. In conclusion a spot morning urine sample is a useful screening test to identify patients at risk of progression to nephropathy.

Albuminuria↗
PubMed1994

The effect of low and high sodium diets on plasma atrial natriuretic factor, the renin-aldosterone system and blood pressure in subjects with essential hypertension.

OBJECTIVE: Increasing dietary sodium intake increases blood pressure in some subjects with essential hypertension. Atrial natriuretic factor (ANF) has a potential role in modifying these changes. The purpose of this study was to observe the blood pressure and plasma ANF responses to low and high sodium diets in subjects with essential hypertension to see if the plasma ANF and blood pressure responses were related. DESIGN: An in-patient study of subjects taking their normal diet (day 1), a 12 mmol sodium diet for 6 days and a 250 mmol diet for 6 days. PATIENTS: Seven men with essential hypertension. MEASUREMENTS: Continuous 24 hour urine collections were analysed for sodium excretion. Blood pressure was recorded at 0900, 1205 and 1700 h on days 1, 7 and 13. Blood was taken at 0900 h (fasting supine overnight) and at 1200 h (after 2 hours erect posture) on the above days for plasma ANF, plasma renin activity (PRA) and serum aldosterone. RESULTS: Urinary sodium excretion was (mean +/- SEM) 11 +/- 1 mmol on day 5 of the low sodium diet, and 294 +/- 17 mmol during the fifth day of the high sodium diet. Plasma ANF (supine and erect) was significantly lower (2.8 +/- 0.6, 1.6 +/- 0.2 pmol/l) on the low sodium diet when compared to the high sodium diet (8.6 +/- 2.4, 5.0 +/- 1.6 pmol/l (P < 0.05)). Supine and erect PRA and serum aldosterone were significantly higher on the low compared to the high sodium diet. Blood pressure responses were heterogeneous rather than bimodal. Mean arterial blood pressure was 107 +/- 3 mmHg on the low sodium diet and 111 +/- 4 mmHg on the high sodium diet (P < 0.05). Changes of blood pressure did not correlate with the changes of plasma ANF. CONCLUSIONS: Failure of plasma atrial natriuretic factor to rise with increasing dietary sodium did not therefore determine the blood pressure response to the change in dietary sodium. No link was established between plasma atrial natriuretic factor response and sodium sensitivity.

Adult↗
PubMed1994

A case of hepatoma associated with hypoglycaemia and overproduction of IGF-II (E-21): beneficial effects of treatment with growth hormone and intrahepatic adriamycin.

We describe a case of recurrent hypoglycaemia associated with a hepatoma. During hypoglycaemia serum insulin was undetectable. Plasma insulin-like growth factor II (IGF-II) was not elevated although 71% of plasma IGF-II was present as big IGF-II (molecular weight 11 kDa) which probably represents a non-glycated form of pro-IGF-II. The GH response to hypoglycaemia was impaired and plasma levels of both IGF-I and the GH-dependent IGF binding protein (IGFBP-3) were low. A recently described unextracted assay directed against the first 21 amino acids of the E-domain (E-21) of proinsulin-like growth factor-II (pro-IGF-II) allows direct plasma estimation (plasma E-21) of larger molecular forms of IGF-II without interference from normal IGF-II and IGF binding proteins. Basal values were grossly elevated (23.7 and 23.8 nmol/l). Treatment with GH led to an increase in the mean plasma glucose across 24 hours (4.25 +/- 0.21 mol/l (mean +/- SEM) before treatment, compared with 4.86 mmol/l +/- 0.17 following GH (P < 0.01)) and a reduction in hypoglycaemic attacks. The treatment was associated with a rise in IGFBP-3 and small increases in insulin like growth factors. Subsequent treatment with the somatostatin analogue octreotide did not produce a significant change in plasma glucose levels or insulin-like growth factors. Two courses of intrahepatic adriamycin restored elevated levels of E-21 to normal. Total IGF-II remained normal and IGF-I increased. GH treatment was successfully withdrawn with no effect on plasma glucose or growth factor levels. The patient remained free from hypoglycaemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗
PubMed1994

The relationship of fasting insulin levels to vascular risk factors in a general practice in Northern Ireland.

OBJECTIVE: To investigate the relationship between insulin and vascular risk factors in a healthy male population at high risk of ischaemic heart disease. DESIGN: Computer-generated random number selection of subjects. SETTING: A suburban general practice population (total practice population 4500) in Northern Ireland. SUBJECTS: Four hundred male subjects, aged 35-65 years, were randomly selected with 273 responding. INTERVENTION: At interview, each subject completed a questionnaire, had blood pressure measured and a 12-lead ECG recorded. The next morning, fasting blood samples were taken and a timed overnight urine collection for the albumin excretion rate was returned. RESULTS: To exclude the confounding effects of other variables on insulin concentrations, a healthy nonobese, nondiabetic, normotensive group with no history of ischaemic heart disease, no family history of diabetes and not taking drugs was identified (n = 120). Within this group there was a significant correlation between insulin and triglyceride (r = 0.30; P < 0.05), high-density lipoprotein (HDL) cholesterol (r = 0.24; P < 0.05) and glucose (r = 0.30; P < 0.05). A group with higher insulin levels (n = 22) were compared to a group with lower insulin levels (n = 22). Serum triglyceride was higher (1.29 +/- 0.1 vs. 1.00 +/- 0.08 mmol L-1; P < 0.05), HDL cholesterol was lower (1.26 +/- 0.06 vs. 1.50 +/- 0.09 mmol L-1; P < 0.05) and plasma glucose higher (5.2 +/- 0.1 vs. 4.9 +/- 0.1 mmol L-1; P < 0.05) in the group with higher insulin levels. CONCLUSIONS: There is a relationship between insulin and triglyceride, HDL cholesterol and glucose but not blood pressure, cholesterol or low-density-lipoprotein (LDL) cholesterol in a healthy population at high risk of ischaemic heart disease.

Adult↗
PubMed1993

Insulin resistance in offspring of hypertensive parents.

OBJECTIVE: To determine if insulin resistance is present in normotensive adults at increased risk of developing hypertension. DESIGN: Normotensive subjects with at least one hypertensive parent were paired with offspring of normotensive parents (controls), being matched for age, sex, social class, and physical activity. SETTING: Outpatient clinic. SUBJECTS: 30 paired subjects (16 men and 14 women) with and without a family history of hypertension, aged 18-32, with a body mass index < 25 kg/m2, with blood pressure < 130/85 mm Hg, and not taking drugs. INTERVENTIONS: Euglycaemic glucose clamp (two hour infusion of insulin 1 mU/kg/min) and intravenous glucose tolerance test (injection of 100 ml 20% glucose). MAIN OUTCOME MEASURES: Insulin mediated glucose disposal and insulin secretion. RESULTS: The offspring of hypertensive parents had slightly higher blood pressure than did the controls (mean 117 (SD 6) v 108 (5) mm Hg systolic, p = 0.013; 76 (7) v 67 (6) mm Hg diastolic, p = 0.017). Their insulin mediated glucose disposal was lower than that of controls (29.5 (6.5) v 40.1 (8.6) mumol/kg/min, p = 0.002), but, after adjustment for blood pressure, the difference was not significant (difference 6.9 (95% confidence interval -1.5 to 15.3), p = 0.10). Insulin secretion in the first hour after injection of glucose was slightly but not significantly higher in the offspring of hypertensive patients (9320 (5484) v 6723 (3751) pmol.min/l). The two groups had similar concentrations of plasma glucose (5.2 (0.3) v 5.1 (0.4) mmol/l), serum cholesterol (4.4 (0.8) v 4.6 (0.8) mmol/l), serum triglyceride (0.89 (0.52) v 0.68 (0.27) mmol/l), and serum low density lipoprotein cholesterol (2.81 (0.65) v 2.79 (0.61) mmol/l). The offspring of hypertensive parents, however, had lower serum concentrations of high density lipoprotein cholesterol (1.24 (0.31) v 1.56 (0.35) mmol/l, p = 0.002) and higher serum concentrations of non-esterified fatty acids (0.7 (0.4) v 0.4 (0.4) mmol/l, p = 0.039). CONCLUSIONS: Young normotensive subjects who are at increased risk of developing hypertension are insulin resistant.

Adolescent↗
PubMed1993

Contribution of glucose/glucose 6-phosphate cycle activity to insulin resistance in type 2 (non-insulin-dependent) diabetes mellitus.

It has been suggested that increased glucose/glucose 6-phosphate substrate cycling impairs net hepatic glucose uptake in Type 2 (non-insulin-dependent) diabetes mellitus and contributes to hyperglycaemia. To investigate glucose/glucose 6-phosphate cycle activity and insulin action in Type 2 diabetes we studied eight patients and eight healthy control subjects, using the euglycaemic glucose clamp and isotope dilution techniques with purified [2-3H]- and [6-3H] glucose tracers, in the post-absorptive state and eight patients and five healthy control subjects during consecutive insulin infusions at rates of 0.4 and 2.0 mU.kg-1 x min-1. [2-3H]glucose and [6-3H]glucose radioactivity in plasma samples were determined using selective enzymatic detritiation, allowing calculation of glucose turnover rates for each isotope, the difference being glucose/glucose 6-phosphate cycling. Endogenous glucose production ([6-3H]glucose) was greater in diabetic than control subjects in the post-absorptive state (15.6 +/- 1.5 vs 11.3 +/- 0.4 mumol.kg-1 x min-1, p < 0.05) and during the 0.4 mU insulin infusion (10.1 +/- 1.3 vs 5.2 +/- 0.3 mumol.kg-1 x min-1, p < 0.01) indicating hepatic insulin resistance. Glucose/glucose 6-phosphate cycling was significantly greater in diabetic than in control subjects in the post-absorptive state (2.6 +/- 0.4 vs 1.6 +/- 0.2 mumol.kg-1 x min-1, p < 0.05) but not during the 0.4 mU insulin infusion (2.0 +/- 0.4 vs 2.0 +/- 0.3 mumol.kg-1 x min-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes Mellitus, Type 2↗
PubMed1993

Microalbuminuria does not predict cardiovascular disease in a normal general practice population.

Recent studies have suggested that microalbuminuria is relatively common (9.4%) in non-diabetic subjects and that it is an excellent marker for increased cardiovascular risk. In an attempt to assess the prevalence of microalbuminuria in Northern Ireland where there is a high incidence of coronary heart disease, we studied 400 males, age 35-65 years, chosen at random from a Belfast general practice. There was a 73% response rate (n = 273). Sixteen per cent of the population has ischaemic heart disease. Microalbuminuria was defined as an increased urinary albumin excretion rate of 20-200 ug min-1. Thirteen subjects (4.7%) had an albumin excretion rate of 20 ug min-1 or more. After exclusion of subjects with diabetes mellitus or renal diseases, the group with microalbuminuria (n = 8), was compared to those without microalbuminuria (n = 256). There was no significant difference in the incidence of ischaemic heart disease between the two groups, nor did the group with microalbuminuria have a more adverse profile of vascular risk factors, apart from serum triglyceride (1.8 +/- 0.2 v 1.3 +/- 0.0 mmol l-1, p < 0.05) and plasma glucose (5.5 +/- 0.3 v 5.1 +/- 0.3 mmol l-1, p < 0.05) levels. We conclude that in a general practice from an area at high risk of ischaemic heart disease, the prevalence of microalbuminuria was low. Contrary to previous reports, microalbuminuria was not helpful in predicting subjects at risk of ischaemic heart disease.

Adult↗
PubMed1993

Assessment of endocrine function after transsphenoidal surgery for Cushing's disease.

OBJECTIVE: We assessed the endocrine outcome after transsphenoidal surgery for Cushing's disease. DESIGN: Five-year (mean) follow-up (range 1 month-12 years) of patients undergoing transsphenoidal surgery for Cushing's disease between 1977 and 1990; review of case notes, current clinical and biochemical assessment including 24-hour urinary free cortisol. SETTING: Northern Ireland. SUBJECTS: Forty-one patients (33F: 8M); mean age at diagnosis 39.1 years (9-72 years). MAIN OUTCOME MEASURES: Measurements of early post-operative 0800 h serum cortisol and 24-hour urinary free cortisol at least 24 hours after withdrawal of oral hydrocortisone therapy. This was followed by low dose dexamethasone testing. Current 24-hour urinary free cortisol measurements. Retrospective definition of cure. RESULTS: Twenty-seven patients were either cured or improved by surgery, 14 were considered definite failures. Of 19 patients cured, eight had unmeasurable early post-operative 0800 h serum cortisol levels while of 15 tested, 13 had complete suppression with dexamethasone and two suppressed normally but to still measurable levels (39 and 60 nmol/l respectively). Seventeen patients in total have subsequently had bilateral adrenalectomy of whom two have developed Nelson's syndrome. Seven of the 41 patients were shown to have definite cyclical cortisol secretion first diagnosed post-operatively in three patients. Hormone deficiency included TSH (5), LH/FSH (1), cortisol (1) and ADH (temporary in 7, permanent in 1). In all, seven patients had some type of permanent hormonal deficiency post-operatively. CONCLUSIONS: Transsphenoidal surgery offers a worthwhile cure rate without the necessity of life-long endocrine therapy. Post-operative endocrine assessment must be rigorous so that early further management can be planned in the significant percentage of patients in whom cure is not achieved. Early complete suppression on low dose dexamethasone testing is very suggestive of cure but repeated and long-term monitoring of 24-hour urinary free cortisol is advisable.

Adenoma↗
PubMed1993

Bilateral adrenalectomy: low mortality and morbidity in Cushing's disease.

OBJECTIVE: We assessed the current role of bilateral adrenalectomy in the overall management strategy of hypercortisolism. DESIGN: Retrospective review of case notes. PATIENTS: Twenty-six patients (20F/6M); mean age 46 years (range 15-70 years), median duration of follow-up 5.25 years (0.6-19.1 years) who had undergone bilateral adrenalectomy at the Royal Victoria Hospital since 1972. Eighteen had had prior transsphenoidal surgery which did not control the hypercortisolism. MEASUREMENTS: Morbidity, mortality, incidence of Nelson's syndrome. RESULTS: Surgery was performed through bilateral postero-lateral incisions (20 patients) or a long epigastric incision (six patients). The mean combined weight of the adrenals at surgery was 11.2 g. Twenty patients received subcutaneous heparin and 18 antibiotic prophylaxis peri and post-operatively. There was no operative mortality. Minor complications included one post-operative wound infection and a small pneumothorax requiring drainage. Major complications occurred in two other patients, both with pre-existing invasive pituitary tumours and considered at high risk because of age and general debility. One patient had a massive pulmonary embolus and the other a subphrenic abscess post-operatively. This latter patient, the only mortality, died from an unrelated cause three years post-operatively. Six patients have subsequently undergone pituitary surgery and three have received external pituitary irradiation therapy for expanding tumours. CONCLUSIONS: Bilateral adrenalectomy, in experienced hands, is a relatively safe and useful management option in patients with hypercortisolism. Growth of a pituitary adenoma post-operatively is now the most worrying complication.

Adolescent↗
PubMed1993

The effect of cortisol on glucose/glucose-6-phosphate cycle activity and insulin action.

Increased glucose/glucose-6-phosphate (G/G6P) substrate cycle activity may be an early marker of disordered hepatic glucose metabolism. To investigate the effects of glucocorticoids on G/G6P cycle activity and insulin resistance, we studied eight normal subjects using the euglycemic glucose clamp technique with high pressure liquid chromatography-purified [2(3)H]- and [6-3H]glucose tracers at insulin infusion rates of 0.4 and 2.0 mU/kg.min after 24-h cortisol (2 micrograms/kg.min) and saline infusions. Endogenous glucose production ([6-3H]glucose) was greater after cortisol than saline in the postabsorptive state (13.3 +/- 0.5 vs. 12.2 +/- 0.5 mumol/kg.min; P < 0.05) and during 0.4-mU insulin infusion (10.5 +/- 0.7 vs. 5.0 +/- 0.8 mumol/kg.min; P < 0.005). During 2.0-mU insulin infusion, endogenous glucose production was suppressed similarly (5.1 +/- 0.4 vs. 4.1 +/- 0.5 mumol/kg.min), but glucose disappearance was less after cortisol than saline (38.7 +/- 3.5 vs. 64.6 +/- 4.3 mumol/kg.min; P < 0.001). G/G6P cycle activity after cortisol and saline was similar in the postabsorptive state and during 0.4 mU insulin. During 2.0 mU insulin, cycle activity was greater after cortisol than saline (3.6 +/- 0.9 vs. 0.8 +/- 0.5 mumol/kg.min; P < 0.005). In conclusion, cortisol induces hepatic insulin resistance without significantly changing G/G6P cycle activity. At high glucose turnover rates, G/G6P cycle activity is increased by cortisol; however, reduced glucose disappearance is the main cause of impaired insulin action.

Absorption↗
PubMed1993

Long-term glycemic control and neurological function in IDDM patients.

OBJECTIVE: To examine the relationship between sensory modalities of neurological function and antecedent glycemic control in IDDM patients. RESEARCH DESIGN AND METHODS: Examinations were conducted on 220 IDDM patients (age at onset < 25 yr, duration < 18 yr) for the presence or absence of the right or left ankle reflex and determination of vibration perception threshold at each medial malleolus and great toe using biothesiometry. These parameters were related to the concurrent HbA1 and to a mean of serial measurements (mean HbA1) over the previous 6 yr. RESULTS: Ankle reflexes were absent in 39 (right ankle) and 41 (left ankle) patients, respectively. Mean (right + left) ankle and toe VPTs were 8.7 +/- 3.6 and 6.3 +/- 4.2 (mean +/- SD) (arbitrary units), respectively. Both the mean and concurrent HbA1 were significantly different in patients with absent ankle reflexes (11.6 +/- 1.9 and 12.2 +/- 2.8%, respectively) compared with present ankle reflexes (10.3 +/- 1.7, 10.3 +/- 2.1%) (P < 0.0001). Similarly, a present ankle reflex was related to mean HbA1 arbitrarily divided into groups < 10, 10-12, > 12% (P = 0.0009). In contrast, mean ankle VPT (8.0 +/- 2.2, 8.8 +/- 3.1, and 10.3 +/- 6.2) and toe VPT (5.5 +/- 2.2, 6.1 +/- 2.9, and 8.5 +/- 8.2) did not increase significantly with poor glycemic control (P > 0.05). Age, right ankle reflex, retinopathy, 24-h urinary albumin excretion rate, and erect systolic blood pressure were the only independent variables predicting the toe VPT using linear regression analysis. CONCLUSIONS: These findings support a role for glycemic control in neurological dysfunction in IDDM patients, but also suggest that other unknown factors may be involved.

Adult↗