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Biomedical subjects

P H Sonksen

Publications and source records attributed to P H Sonksen.

At least 19 recordsLinked to original sources
PubMed2005

Gender differences in growth hormone response to exercise before and after rhGH administration and the effect of rhGH on the hormone profile of fit normal adults.

OBJECTIVES: Exercise is a potent physiological stimulus of GH secretion. We hypothesized that exogenous recombinant human growth hormone (rhGH) administration through an increase in GH and IGF-I levels would blunt the GH response to exercise. The aim of the study was to examine and compare the impact of rhGH on the exercise-induced GH response in healthy normal men and women. DESIGN AND MEASUREMENTS: Sixty-nine subjects (36 men, 33 women) were randomized to receive low-dose rhGH (0.1 U/kg/day), high dose rhGH (0.2 U/kg/day), or placebo. Subjects were matched for age (24 +/- 3.1), and body mass index (BMI). rhGH was given as a single subcutaneous (s.c.) injection for the first 28 days. All subjects exercised to exhaustion (maximal oxygen consumption--VO2max) before rhGH treatment (Test 1), and on day 28 (Test 2). GH was measured before exercise (time 0), immediately after exercise (time 0') and at 15, 30, 60, 90 and 120 min postexercise. Baseline IGF-I levels were measured before exercise on days 0 and 28. RESULTS: Baseline IGF-I levels showed no gender differences (42.3 women vs. 38.8 nmol/l men) but basal GH values were higher in women (9.9 vs. 1.8 mU/l, P < 0.001). The areas under the GH response curve, for Test 1 were similar in men and women. Peak GH values were higher in women than men (37.9 vs. 23.5 mU/l, but this did not quite reach statistical significance (P = 0.055). In men, administration of rhGH resulted in a significant increase in IGF-I levels over the basal state in both the LD and HD groups (P < 0.0001). In women, the increase in lGF-I levels reached significance only in the HD group (P < 0.0001). On day 28, GH secretion in response to exercise was calculated from the areas under the GH response curve correcting for an exogenous rhGH component (delta AUC). In men, the delta AUC, for Test 2 were similar in all three groups. In women, the delta AUC was higher in the placebo group, than in the HD group (P < 0.02). Free T4 levels decreased significantly in men, and free T3 increased in both men and women, in HD group after the rhGH administration. TSH levels were suppressed only in women. No changes in sex hormones were found in men or women in any of the treatment groups. Conclusions In terms of IGF-I, men are more responsive to rhGH treatment than women. In addition, as men, but not women, were able to overcome the negative feedback control of the elevated IGF-I levels, it seems that exercise may be a more robust stimulus to GH release in men compared to women.

Adult↗
PubMed2003

Effect of growth hormone (GH) on glycerol and free fatty acid metabolism during exhaustive exercise in GH-deficient adults.

GH is an important regulator of fat metabolism at rest, but it is not known whether it regulates fat metabolism during exercise. To determine whether physiologic concentrations of GH influence fat metabolism during exercise, we randomized 16 GH-deficient adults, receiving long-term (mean duration, 5 yr) GH replacement, to either continue GH (n = 8) or receive identical placebo (n = 8) for a 3-month period. Metabolic studies, at rest, during and following exhaustive exercise were carried out at baseline and at the end of the 3 months. The rate of appearance of glycerol (glycerol Ra, an index of lipolysis) and free fatty acids (FFA, FFA Ra) and the rate of disappearance of FFA (FFA Rd) in the plasma were measured using infusions of (2)H(5)-glycerol and 1-(13)C-palmitic acid. Changes in body composition were assessed using dual-energy x-ray absorptiometry scanning and anthropometric measurements. In the baseline studies, exercise resulted in an increase in plasma glycerol and FFA concentrations, glycerol Ra, FFA Ra, and FFA Rd (P < 0.001). Three months of GH withdrawal resulted in reductions in plasma glycerol and FFA, glycerol Ra, FFA Ra, and FFA Rd at rest (P < 0.05 vs. baseline) and during exercise (P < 0.05 vs. baseline and vs. GH treated). Lean body mass decreased after 3 months of GH withdrawal, but total body fat, trunk fat, waist circumference, and the sum of skinfold thicknesses increased after 3 months of GH withdrawal (P < 0.05 vs. baseline and vs. GH treated). Fasting insulin and homeostasis model assessment of insulin resistance decreased after 3 months of GH withdrawal (P < 0.05 vs. baseline and vs. GH treated). In summary, GH withdrawal for 3 months resulted in reductions in release of glycerol and FFA into the circulation and uptake of FFA into the tissues during intense exercise. These changes were accompanied by reduced lean body mass and increased total body and trunk fat. Further studies are required to determine whether reduced mobilization of fat during exercise contributes to reduced exercise capacity and increased body fat in GH-deficient adults.

Absorptiometry, Photon↗
PubMed2002

Does GH replacement therapy in adult GH-deficient patients result in recurrence or increase in size of pituitary tumours?

OBJECTIVE: Hypopituitary GH-deficient patients have an increased cardiovascular mortality and GH replacement in this population has resulted in considerable therapeutic benefit. GH replacement involves administration of a potentially mitogenic substance to patients with a previous or residual pituitary tumour. Our objective was to evaluate whether GH replacement results in an increase in the size of pituitary tumours. METHODS: This was a non-randomised observational study on patients recruited from the endocrine clinic. All subjects had GH deficiency, proven on an insulin tolerance test and were divided into those who were or were not receiving long-term GH replacement. Comparison of change in pituitary size was made with interval radiological imaging of the pituitary. RESULTS: Seventy-five patients (40 men and 35 women) were in the study, 47 were on long-term GH replacement and there were 28 controls. The average length of treatment for the treated group was 3.6 patient years. Thirty-nine patients in the treated group had at least 2 years of GH treatment between imaging studies of the pituitary. Two patients in the treated group had an increase in pituitary size (non-functioning adenomas) and two in the control group (one functioning and one non-functioning adenoma adenoma). None of these four patients required further treatment. There was no statistically significant difference between the two groups. CONCLUSION: Using a representative cohort of hypopituitary patients attending an endocrine clinic, GH replacement was not associated with an increased pituitary tumour recurrence rate. Although the results are not conclusive, in the period of observation GH had little adverse effect but longer studies are required to be certain.

Adult↗
PubMed2001

Insulin, growth hormone and sport.

This review examines some interesting 'new' histories of insulin and reviews our current understanding of its physiological actions and synergy with GH in the regulation of metabolism and body composition. It reviews the history of GH abuse that antedates by many years the awareness of endocrinologists to its potent anabolic actions. Promising methods for detection of GH abuse have been developed but have yet to be sufficiently well validated to be ready for introduction into competitive sport. So far, there are two promising avenues for detecting GH abuse. The first uses immunoassays that can distinguish the isomers of pituitary-derived GH from the monomer of recombinant human GH. The second works through demonstrating circulating concentrations of one or more GH-sensitive substances that exceed the extremes of normal physiological variability. Both methods require blood rather than urine samples. The first method has a window of opportunity lasting about 24 h after an injection and is most suitable for 'out of competition' testing. The second method has reasonable sensitivity for as long as 2 weeks after the last injection of GH and is uninfluenced by extreme exercise and suitable for post-competition samples. This method has a greater sensitivity in men than in women. The specificity of both methods seems acceptably high but lawyers need to decide what level of scientific probability is needed to obtain a conviction. Both methods need further validation before implementation. Research work carried out as part of the fight against doping in sport has opened up a new and exciting area of endocrinology.

Aging↗
PubMed2000

Cutis verticis gyrata of the scalp in a patient with autosomal dominant insulin resistance syndrome.

Cutis verticis gyrata (CVG) is a rare disorder; it is characterized by thickening of the scalp which becomes raised to form ridges and furrows resembling the cerebral gyri. We report a case of CVG associated with the autosomal dominant insulin resistance syndrome. This syndrome is characterized by obesity, mild mental retardation, delayed puberty, acanthosis nigricans and hyperinsulinaemia. The association of CVG and autosomal dominant insulin resistance has not been previously described.

Adult↗
PubMed1999

The effects of 10 years of recombinant human growth hormone (GH) in adult GH-deficient patients.

The long term effects of GH replacement in adult GH-deficient (GHD) patients have not yet been clarified. We studied 21 GHD adults who originally took part in a randomized, double blind, placebo-controlled trial of GH treatment in 1987. After completion of that trial, 10 patients received continuous GH replacement for the subsequent 10 yr, whereas 11 did not. A group of 11 age- and sex-matched normal controls were also studied in 1987 and 1997. Lean body mass, as assessed by total body potassium measurement and computed tomography scanning of the dominant thigh, increased in the GH-treated group (P < 0.01 for both) only (P < 0.05 between groups for total body potassium). Low density lipoprotein cholesterol decreased in the GH-treated group (P < 0.05) only. Carotid intima media thickness was significantly greater (P < 0.05) in the untreated group than in the GH-treated group. Assessment of psychological well-being using the Nottingham Health Profile revealed improvement in overall score, energy levels, and emotional reaction in the GH-treated group compared with those in the untreated group (P < 0.02). In conclusion, GH treatment for 10 yr in GHD adults resulted in increased lean body and muscle mass, a less atherogenic lipid profile, reduced carotid intima media thickness, and improved psychological well-being.

Adult↗
PubMed1998

Effect of growth hormone treatment on postprandial protein metabolism in growth hormone-deficient adults.

Growth hormone (GH) treatment of GH-deficient adults increases lean body mass. To investigate this anabolic effect of GH, body composition and postabsorptive and postprandial protein metabolism were measured in 12 GH-deficient adults randomized to placebo or GH treatment. Protein metabolism was measured after an infusion of [1-13C]leucine before and after a standard meal at 0 and 2 mo. After 2 mo, there was an increase in lean body mass in the GH group (P < 0. 05) but no change in the placebo group. In the postabsorptive state, there was increased nonoxidative leucine disappearance (NOLD; a measure of protein synthesis) and leucine metabolic clearance rate and decreased leucine oxidation in the GH group (P < 0.05) but no change in the placebo group. After the meal, there was an increase in NOLD and oxidation in all studies (P < 0.05), but the increase in NOLD, measured as area under the curve, was greater in the GH group (P < 0.05). This study clearly demonstrates for the first time that the increase in protein synthesis in the postabsorptive state after GH treatment of GH-deficient adults is maintained in the postprandial state.

Adult↗
PubMed1997

Growth hormone secretion in the elderly: ageing and the somatopause.

The syndrome associated with lack of growth hormone (GH) in adults can be reversed by treatment with recombinant human GH (rhGH) with apparently beneficial clinical effects. This syndrome is strikingly similar to the characteristics of normal older adults which are known as the somatopause. GH secretion and insulin-like growth factor I levels are reduced in healthy older people and it has been suggested that the somatopause is an age-related GH deficiency state. This review describes the physiological control of GH secretion in adults and seeks an explanation for the age-related decline, considering the impact of other factors such as nutrition and mobility, and particularly whether exercise offers a physiological approach to changing both the GH decline and the somatopause. The benefits and side-effects of treatment with rhGH for normal older people or older patients facing catabolic stresses are reviewed together with alternative approaches to stimulate GH such as GH-releasing hormone and the new pharmaceutical GH secretagogues.

Aged↗
PubMed1997

Growth hormone therapy may benefit protein metabolism in mitochondrial encephalomyopathy.

Mitochondrial encephalomyopathy is a genetic disorder for which there is at present no cure. Conventional treatment regimes may not be effective in preventing weight loss and muscle wasting in many patients. Recombinant human GH has been shown to have anabolic effects on protein metabolism and to reduce muscle wasting in various diseases. We have treated a patient known to have myoclonus, epilepsy with ragged red fibres (MERRF) with a high protein diet for 1 month followed by a high protein diet and GH therapy for 1 month. To assess the benefit of these treatments the patient underwent whole body protein turnover, myometric and body composition studies at baseline, following the high protein diet (100 g/day) and following GH therapy. Whole body protein synthesis (and protein breakdown) increased following a high protein intake and was further enhanced by treatment with GH and in a high protein diet. Body composition did not change significantly following treatment with either the high protein diet or GH but there was an improvement in muscle performance following GH treatment. Mitochondrial encephalomyopathy, a wasting disorder, may be a disease in which the known protein anabolic effect of GH may have a therapeutic benefit.

Body Composition↗
PubMed1997

Evaluating the terminology requirements to support multi-disciplinary diabetes care.

Diabetes mellitus is a multi-system disease requiring lifetime multi-disciplinary care, which has proven individual and economic benefits. The delivery of service involves co-operation and communication between patient, carer and health care professionals, and systematic auditing of processes and outcomes. Sustained improvement necessitates regular data acquisition, aggregation and analysis. The terminology requirements to support patient-centred records and identified datasets are examined, and differences in purpose and scope highlighted. The many stakeholders involved in diabetes care have their own sublanguages and terminology requirements which need harmonising around a common core. The problems and solutions of accommodating these needs are explored in relation to the Read Thesaurus.

Databases, Factual↗
PubMed1996

Posterior pituitary ectopia and hypopituitarism--magnetic resonance appearances of four cases and a review of the literature.

In four patients presenting in childhood with varying degrees of hypopituitarism, magnetic resonance imaging (MRI) showed a reduction in size of the normal pituitary fossa contents and an absent or very narrow stalk. A high signal intensity, enhancing area at the base of the stalk, having the appearances and signal characteristics of the posterior pituitary, was seen in each case. We discuss the case histories and MR findings in our patients and review the relevant literature.

Child↗
PubMed1995

A simulation model for glucose kinetics and estimates of glucose utilization rate in type 1 diabetic patients.

A glucose kinetic model is described that contains insulin-independent and insulin-dependent pathways of glucose uptake and includes a saturating flux term for glucose transport into the cells by the glucose transporters. The rate of glucose utilization was estimated in control subjects and diabetic patients by use of a bolus of [3-3H]glucose. Diabetic patients were studied after three regimens of insulin therapy: 1) after 24 h of insulin withdrawal, 2) after conventional insulin therapy, and 3) after an overnight insulin infusion such that plasma glucose was maintained between 4 and 6 mmol/l. In addition, the model was used to simulate published results from glucose clamp experiments with a range of glycemic levels and insulin concentrations. Estimates of glucose utilization flux in diabetic patients and model simulation suggest that high plasma glucose concentrations in uncontrolled diabetic patients can be attributed to a high glucose production rate by the liver associated with a reduction in glucose metabolic clearance rate due to relative saturation of the available pool of glucose transporters.

Adolescent↗
PubMed1994

Glyoxalase system in clinical diabetes mellitus and correlation with diabetic complications.

1. The metabolism of methylglyoxal by the glyoxalase system may be linked to the development of diabetic complications. The glyoxalase system was characterized in blood samples from patients with insulin-dependent diabetes mellitus (n = 43), patients with non-insulin-dependent diabetes mellitus (n = 107) and 21 normal healthy control subjects. 2. The concentrations of glyoxalase metabolites, methylglyoxal, S-D-lactoylglutathione and D-lactate, were increased in diabetic patients, relative to normal control subjects: methylglyoxal [median, range (n) pmol/g], insulin-dependent patients, 470.7, 85.6-1044.3 (42), P < 0.001, non-insulin-dependent patients, 286.8, 54.7-2370 (105), P < 0.001, control subjects, 79.8, 25.3-892.9 (21); S-D-lactoylglutathione [mean +/- SD (n)pmol/10(6) erythrocytes], combined diabetic patients, 3.37 +/- 0.85 (24), control subjects 4.76 +/- 1.95 (8) P < 0.05; D-lactate [mean +/- SD or median, range (n)nmol/g], insulin dependent patients, median 18.3, 5.7-57.4 (42), P < 0.001, non-insulin-dependent patients, 20.0 +/- 8.9, 2.6-48.4 (105), P < 0.001, control subjects 9.7 +/- 4.3, 1.8-19.7 (21). The reduced glutathione concentrations in blood samples from the insulin-dependent and non-insulin-dependent diabetic patient groups were not different from the control group values (P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Effects of insulin-like growth factor-I (IGF-I), insulin and combined IGF-I-insulin infusions on protein metabolism in dogs.

The effect of infusions of recombinant insulin-like growth factor-I (IGF-I) (34, 103 or 688 pmol min-1 kg-1), insulin (3.4, 10.3 or 68.8 pmol min-1 kg-1) or combined infusions (34 pmol IGF-I + 3.4 pmol min-1 kg-1 insulin or 103 pmol IGF-I + 3.4 pmol min-1 kg-1 insulin) on protein metabolism, using an infusion of [1-14C]leucine was investigated in anaesthetized fasted dogs. Leucine concentration, production rate (measure of protein degradation), oxidation rate and non-oxidative disappearance rate (measure of protein synthesis) were decreased in a similar dose dependent manner by the IGF-I and insulin infusions (P < 0.01). The decrease in these measurements of leucine metabolism were greater following 34 pmol IGF-I + 3.4 pmol insulin than with either component infused alone (P < 0.05). Free fatty acid concentrations were decreased by all insulin doses (P < 0.01) but only by 103 and 688 pmol min-1 kg-1 insulin-like growth factor (P < 0.05, P < 0.01). These data demonstrate that IGF-I, like insulin, has a dose dependent effect on protein metabolism and that combined insulin and IGF-I infusions have additive effects on protein metabolism.

Animals↗
PubMed1994

A compartmental model for simulation of IGF-I kinetics and metabolism.

A compartmental model for the simulation of in-vivo insulin-like growth factor one (IGF-I) kinetics and metabolism is presented. The model is based on the concept that IGF binding proteins (IGFBPs) act as a reservoir for IGF-I in plasma, thereby restricting its access to the extravascular space. The model is divided into two subsystems; a binding model for IGF-I and IGFBP, and an IGF-I clearance model, which includes the binding of IGF-I to IGF-I receptors. The non-linear differential equations describing the model are based on the law of mass action. Given the steady state condition, the linearized form of the model, describing tracer kinetics of IGF-I and IGFBPs is developed. It is demonstrated that using the available data, it is possible to assign values to the model parameters, thereby allowing simulation of the model to obtain information not accessible by direct observation.

Animals↗
PubMed1993

A multicentre study of the prevalence of diabetic peripheral neuropathy in the United Kingdom hospital clinic population.

A cross-sectional multicentre study of randomly selected diabetic patients was performed using a standardised questionnaire and examination, to establish the prevalence of peripheral neuropathy in patients attending 118 hospital diabetes clinics in the UK. Vibration perception threshold was performed in two centres to compare with the clinical scoring systems. A total of 6487 diabetic patients were studied. 53.9% male, median age 59 years (range 18-90 years). 37.4% Type 1 (insulin-dependent) diabetes mellitus, with a median duration of diabetes 8 years (0-62 years). The overall prevalence of neuropathy was 28.5% (27.4-29.6%) (95% confidence interval) in this population. The prevalence in Type 1 diabetic patients was 22.7% (21.0-24.4%) and in Type 2 (non-insulin-dependent) diabetic patients it was 32.1% (30.6-33.6%). The prevalence of diabetic peripheral neuropathy increased with age, from 5% (3.1-6.9%) in the 20-29 year age group to 44.2% (41.1-47.3%) in the 70-79 year age group. Neuropathy was associated with duration of diabetes, and was present in 20.8% (19.1-22.5%) of patients with diabetes duration less than 5 years and in 36.8% (34.9-38.7%) of those with diabetes duration greater than 10 years. Mean vibration perception threshold measured at the great toe was 21.1 +/- 13.5 SD volts and correlated with the neuropathy disability score, r = 0.8 p < 0.001. In conclusion, diabetic peripheral neuropathy is a common complication associated with diabetes. It increases with both age and duration of diabetes, until it is present in more than 50% of Type 2 diabetic patients aged over 60 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗