Effect of subcutaneous insulin detemir on glucose flux, lipolysis and electroencephalography in type 1 diabetes.

The aim of the present study was to investigate the effects of subcutaneous detemir on glucose flux, lipid metabolism and brain function. Twelve people with type 1 diabetes received, in random order, 0.5 units/kg body weight detemir or NPH insulin. Glucose concentration was clamped at 5 mmol/l then increased to 10 mmol/l. Glucose production rate (glucose Ra), glucose uptake (glucose Rd) and glycerol production (glycerol Ra) were measured with a constant intravenous infusion of [6,6(2) H(2)]glucose and [(2)H(5)]glycerol. Electroencephalography direct current (DC) and alternating current (AC) potentials were measured. While detemir induced similar effects on glucose Ra, glucose Rd and glycerol Ra during euglycaemia compared with NPH, it triggered a distinct negative shift in DC potentials, with a significant treatment effect in frontal cerebrocortical channels (p < 0.001). AC spectral power showed significant differences in theta and alpha frequencies during euglycaemia (p = 0.03). Subcutaneous detemir exerts different effects on brain function when compared with NPH in people with type 1 diabetes. This may be an important mechanism behind the limitation of weight gain with detemir.

Effect of subcutaneous insulin detemir on glucose flux and lipolysis during hyperglycaemia in people with type 1 diabetes.

AIMS: To investigate, using a novel non-steady-state protocol, the differential effects of subcutaneous (s.c.) detemir and NPH insulin on glucose flux and lipid metabolism after insulin withdrawal. METHODS: After a period of insulin withdrawal resulting in whole-blood glucose concentration of 7 mmol/l, 11 participants (five men, mean age 41.0 years, mean body mass index 25 kg/m(2)) with type 1 diabetes (mean glycated haemoglobin concentration 57 mmol/mol, mean diabetes duration 14 years) received 0.5 units per kg body weight s.c. insulin detemir or NPH insulin in random order. Stable isotopes of glucose and glycerol were infused intravenously throughout the study protocol. RESULTS: Glucose concentration decreased after insulin treatment as a result of suppression of endogenous glucose production, which occurred to a similar extent with both detemir and NPH insulin. The rate of glucose disappearance (Rd) was not increased significantly with either type of insulin. When the effect of detemir and NPH insulin on glucose flux at glucose concentrations between 9 and 6 mmol/l was examined, glucose rate of appearance (Ra) was similar with the two insulins; however, glucose Rd was greater with NPH insulin than with detemir at glucose concentrations of 8.0, 8.5, 7.0 and 6.0 mmol/l (p < 0.05) The percentage change in glycerol Ra, a measure of lipolysis, was greater in the NPH group than in the detemir group (p = 0.04). CONCLUSIONS: The results of the study are consistent with the hypothesis that detemir has a lesser effect on the periphery, as evidenced by a lesser effect on peripheral glucose uptake at specific glucose concentrations.

Hepatoselectivity and the evolution of insulin.

In spite of major developments in insulin production, purification, pharmaceutical formulation and methods of delivery, problems remain both in the day to day management of insulin-treated diabetes and with regard to its long-term complications. The risks of hypoglycaemia and weight gain are major concerns particularly for the patient, and the persistence of microvascular and premature macrovascular complications as the main causes of morbidity and mortality in both type 1 and type 2 diabetes is a constant reminder that our therapeutic and management strategies are inadequate. One clear and striking difference between currently available insulin treatments and normal physiology is the relative difference in exposure to insulin of the liver versus peripheral tissues. Hepatoselective insulin analogues have the potential to restore the normal hepatic to peripheral gradient in insulin action. Here, we discuss the possible therapeutic potential that such analogues may have over currently available insulin preparations. These benefits could include a lower risk of hypoglycaemia, less weight gain and a potential reduction in microvascular and macrovascular complications. We explore the evolution of insulin with hepatoselectivity in mind and possible strategies to create hepatoselective insulins.

Insulin degludec improves glycaemic control with lower nocturnal hypoglycaemia risk than insulin glargine in basal-bolus treatment with mealtime insulin aspart in Type 1 diabetes (BEGIN(®) Basal-Bolus Type 1): 2-year results of a randomized clinical trial.

AIMS: The goal of this study was to compare the long-term safety and efficacy of the basal insulin analogue, insulin degludec with insulin glargine (both with insulin aspart) in Type 1 diabetes, over a 2-year time period. METHODS: This open-label trial comprised a 1-year main trial and a 1-year extension. Patients were randomized to once-daily insulin degludec or insulin glargine and titrated to pre-breakfast plasma glucose values of 3.9-4.9 mmol/l. RESULTS: The rate of nocturnal confirmed hypoglycaemia was 25% lower with insulin degludec than with insulin glargine (P = 0.02). Rates of confirmed hypoglycaemia, severe hypoglycaemia and adverse events, and reductions in glycated haemoglobin and fasting plasma glucose were similar between groups. Despite achieving similar glycaemic control, insulin degludec-treated patients used 12% less basal and 9% less total daily insulin than did insulin glargine-treated patients (P < 0.01). CONCLUSIONS: Long-term basal therapy using insulin degludec in Type 1 diabetes required lower doses and was associated with a 25% lower risk for nocturnal hypoglycaemia than insulin glargine.

Can an interprofessional education tool improve healthcare professional confidence, knowledge and quality of inpatient diabetes care: a pilot study?

AIMS: To conduct a pilot study evaluation of an interprofessional education tool that could improve healthcare professional confidence, knowledge and quality of inpatient diabetes care. METHODS: Diabetes specialists designed an education tool for use in the hospital environment to educate qualified pharmacists, nurses, healthcare assistants and junior doctors. The interprofessional learning enabled professionals to learn from and about each other. The education tool was piloted at four hospitals. Diabetes specialists delivered the education programme to 31 healthcare professionals over 8 h either as three individual teaching blocks or a whole day. Healthcare professionals completed a multiple choice questionnaire before and after the education intervention to evaluate acquisition of knowledge. The maximum score was 20. Confidence was evaluated using categorical questions. Diabetes specialists used a clinical audit form before and after the education programme, to evaluate the quality of diabetes care. RESULTS: Healthcare professional's confidence improved from 58 to 94% (P < 0.05) and knowledge improved from 12.4 ± 0.6 to 15.0 ± 0.6 (mean ± sem, P < 0.05). There was a reduction in management errors from 74 to 44% (P < 0.05) and improvement in appropriate blood glucose monitoring from 67 to 92% (P < 0.05). The number of patients with documented foot assessment improved from15 to 33% (P < 0.05). Improvement in the number of appropriate diabetes referrals and reduction in prescribing errors did not reach statistical significance. CONCLUSION: The education tool improved healthcare professional confidence, knowledge and may improve the quality of inpatient diabetes care.

Management of raised glucose, a clinical decision tool to reduce length of stay of patients with hyperglycaemia.

OBJECTIVE: To assess whether the introduction of a management of raised glucose clinical decision tool could improve assessment of patients with hyperglycaemia by non-specialist physicians, leading to early discharge and improved quality of inpatient care. METHODS: Participants were adults aged 18 years or over presenting to the Medical Assessment Unit with a capillary blood glucose level > 11.1 mmol/l. Phase 1 of the study (phase 1) evaluated current clinical practice and potential impact of the clinical decision tool. Phase 2 evaluated the effectiveness of the management of raised glucose tool in clinical practice. Primary outcome measures were inpatient length of stay and same-calendar-day discharges. Secondary outcome measures were diabetes specialist input, patient assessment, intravenous insulin infusion use and patient satisfaction. RESULTS: Implementation of the management of raised glucose clinical decision tool allowed safe, same-calendar-day discharges of 40% of patients with hyperglycaemia as their primary reason for attendance. Median length of stay was lower in the phase 1 than in phase 2 (1.0 vs. 3.5 days, P < 0.01). Early discharge did not result in an increase in readmissions. There was improvement in hyperglycaemia assessment for all patients (P < 0.01), a reduction in the use of intravenous insulin infusions (P < 0.01) and high level of patient satisfaction. CONCLUSION: The management of raised glucose clinical decision tool resulted in a significant increase in the number of same-calendar-day discharges and reduction in hospital length of stay without adverse impact on readmission rates. Additionally, the tool was associated with improvements in inpatient diabetes care and patient satisfaction.

Differential effects of insulin detemir and neutral protamine Hagedorn (NPH) insulin on hepatic glucose production and peripheral glucose uptake during hypoglycaemia in type 1 diabetes.

AIMS/HYPOTHESIS: We compared the symptoms of hypoglycaemia induced by insulin detemir (NN304) (B29Lys(epsilon-tetradecanoyl),desB30 human insulin) and equally effective doses of neutral protamine Hagedorn (NPH) insulin in relation to possible differential effects on hepatic glucose production and peripheral glucose uptake. METHODS: After overnight intravenous infusion of soluble human insulin 18 participants with type 1 diabetes received subcutaneous injections of NPH insulin or insulin detemir (0.5 U/kg body weight) on separate occasions in random order. During the ensuing gradual development of hypoglycaemia cognitive function and levels of counter-regulatory hormones were measured and rates of endogenous glucose production and peripheral glucose uptake continuously evaluated using a primed constant infusion of [6,6-(2)H(2)]glucose. The study was terminated when plasma glucose concentration had fallen to 2.4 mmol/l or had reached a minimum at a higher concentration. RESULTS: During the development of hypoglycaemia no difference between the two insulin preparations was observed in symptoms or hormonal responses. Significant differences were seen in rates of glucose flux. At and below plasma glucose concentrations of 3.5 mmol/l suppression of endogenous glucose production was greater with insulin detemir than with NPH insulin, whereas stimulation of peripheral glucose uptake was greater with NPH insulin than with insulin detemir. CONCLUSIONS/INTERPRETATION: In participants with type 1 diabetes subcutaneously injected insulin detemir exhibits relative hepatoselectivity compared with NPH insulin, but symptoms of hypoglycaemia and hormonal counter-regulation are similar. TRIAL REGISTRATION: ClinicalTrials.gov NCT00760448.

Effects of high-dose growth hormone on glucose and glycerol metabolism at rest and during exercise in endurance-trained athletes.

CONTEXT: Recombinant human-GH (r-hGH), in supraphysiological doses, is self-administered by athletes in the belief that it is performance enhancing. OBJECTIVE: The objective of this study was to determine whether r-hGH alters whole-body glucose and glycerol metabolism in endurance-trained athletes at rest and during and after exercise. DESIGN: This was a 4-wk double-blind placebo-controlled trial. SETTING: This study was conducted at St. Thomas Hospital (London, UK). PARTICIPANTS: Twelve endurance-trained male athletes were recruited and randomized to r-hGH (0.2 U/kg.d) (n = 6) or identical placebo (n = 6) for 4 wk. One (placebo group) withdrew after randomization. INTERVENTION: Intervention was conducted by randomization to r-hGH (0.2 U/kg x d) or identical placebo for 4 wk. MAIN OUTCOME MEASURES: Whole-body rates of appearance (Ra) of glucose and glycerol (an index of lipolysis) and rate of disappearance of glucose were measured using infusions of d-[6-6-2H2]glucose and 2H5-glycerol. RESULTS: Plasma levels of glycerol and free fatty acids and glycerol Ra at rest and during and after exercise increased during r-hGH treatment (P < 0.05 vs. placebo). Glucose Ra and glucose rate of disappearance were greater after exercise during r-hGH treatment (P < 0.05 vs. placebo). Resting energy expenditure and fat oxidation were greater under resting conditions during r-hGH treatment (P < 0.05 vs. placebo). CONCLUSIONS: r-hGH in endurance-trained athletes increased lipolysis and fatty acid availability at rest and during and after exercise. r-hGH increased glucose production and uptake rates after exercise. The relevance of these effects for athletic performance is not known.

Insulin detemir, does a new century bring a better basal insulin?

The treatment of diabetes was revolutionised shortly after the turn of the twentieth century by the extraction and purification of insulin. Methods to protract (i.e. prolong) the action of insulin were developed in the 1930s; little changed in the technology of insulin protraction until the turn of this century when, with renewed interest in the importance of basal insulin in controlling diabetes and thus preventing or delaying complications, technology advanced again. Two new long-acting insulin analogues have come to the market; some may be familiar with insulin glargine, which has been widely used for some years now. This review attempts to describe the novel method of protraction that insulin detemir (launched last summer) employs by albumin binding, to discuss the possible therapeutic benefits of this method of protraction and to describe the findings of studies comparing insulin detemir with other currently available long-acting insulin preparations. The intention of this article is not to review all of the currently available long-acting insulin analogues.

Comparison of the effects on glucose and lipid metabolism of equipotent doses of insulin detemir and NPH insulin with a 16-h euglycaemic clamp.

AIMS/HYPOTHESIS: The association of insulin detemir with non-esterified fatty acid binding sites on albumin may limit its transfer from the circulation into the extravascular extracellular space in adipose tissue and muscle, due to the capillary endothelial cell barrier. In the liver, the open sinusoids may expose hepatocytes to insulin detemir, enabling it to have a greater effect in the liver than in peripheral tissues. METHODS: We investigated the effects of equipotent doses of insulin detemir and NPH insulin on hepatic glucose rate of appearance (Ra), peripheral glucose rate of disposal (Rd) and glycerol Ra (a measure of lipolysis) using stable isotope techniques. We also investigated the effects of these insulins on NEFA concentrations in seven healthy volunteers during a 16-h euglycaemic clamp. A higher dose of insulin detemir was also studied. RESULTS: There was no difference in the glucose infusion profile between insulin detemir and NPH. Insulin detemir had a greater effect on mean suppression of glucose Ra (mean difference 0.24 mg kg(-1) min(-1); CI 0.09-0.39; p<0.01), and minimum glucose Ra, with minimum low dose detemir -0.10+/-0.15 mg.kg(-1).min(-1) and minimum NPH 0.17+/-0.10 mg.kg(-1).min(-1) (p<0.02). However, it had a lesser effect on mean suppression of NEFA concentrations (mean difference -0.10 mmol/l; CI -0.03 to -0.17; ANOVA, p<0.02) than NPH. The effect of insulin detemir on glucose Rd and glycerol Ra was not different from NPH. Following high-dose detemir, total glucose infused and maximum glucose Rd were higher (p<0.02, p<0.03) and plasma NEFA concentrations lower (p<0.01) than with low-dose determir. CONCLUSIONS/INTERPRETATION: This study suggests that insulin detemir, when compared to NPH insulin, has a greater effect on the liver than on peripheral tissues and thus has the potential to restore the physiological insulin gradient.

Effects of growth hormone (GH) replacement therapy on low-density lipoprotein apolipoprotein B100 kinetics in adult patients with GH deficiency: a stable isotope study.

GH replacement therapy has been shown to improve the dyslipidemic condition in a substantial proportion of patients with adult GH deficiency. The mechanisms are not yet fully elucidated. Low-density lipoprotein (LDL) apolipoprotein B100 (apoB) formation and catabolism are important determinants of plasma cholesterol concentrations. This study examined the effect of GH replacement therapy on LDL apoB metabolism using a stable isotope turnover technique. LDL apoB kinetics was determined in 13 adult patients with GH deficiency before and after 3 months GH/placebo treatment in a randomized, double-blind, placebo-controlled study. LDL apoB (13)C-leucine enrichment was determined by isotope-ratio mass spectrometry. Plasma volume was assessed by standardized radionuclide dilution technique. GH replacement therapy significantly decreased LDL cholesterol, LDL apoB concentrations, and LDL apoB pool size compared with placebo. Compared with baseline, GH replacement therapy resulted in a significant increase in plasma volume and fractional catabolic rate, whereas LDL formation rate remained unchanged. LDL lipid content did not significantly change after GH and placebo. This study suggests that short-term GH replacement therapy decreases the LDL apoB pool by increasing removal of LDL particles without changing LDL composition or LDL apoB production rate. In addition, it is possible that the beneficial effects of GH on the cardiovascular system contribute to these findings.

High dose growth hormone exerts an anabolic effect at rest and during exercise in endurance-trained athletes.

The anabolic actions of GH in GH-deficient adults and children are well documented. Replacement with GH in such individuals promotes protein synthesis and reduces irreversible loss of protein through oxidation. Although GH is known to be self-administered by athletes, its protein metabolic effects in this context are unknown. This study was designed to determine whether 4 wk of high dose recombinant human GH (r-hGH) administration altered whole body leucine kinetics in endurance-trained athletes at rest and during and after 30 min of exercise at 60% of maximal oxygen uptake. Eleven endurance-trained male athletes were studied, six randomized to receive r-hGH (0.067 mg/kg.d), and five to receive placebo. Whole body leucine turnover was measured at rest and during and after exercise, using a 5-h primed constant infusion of 1-[(13)C]leucine, from which rates of leucine appearance (an index of protein breakdown), leucine oxidation, and nonoxidative leucine disposal (an index of protein synthesis) were estimated. Under resting conditions, r-hGH administration increased rate of leucine appearance and nonoxidative leucine disposal, and reduced leucine oxidation (P < 0.01). This effect was apparent after 1 wk, and was accentuated after 4 wk, of r-hGH administration (P < 0.05). During and after exercise, GH attenuated the exercise-induced increase in leucine oxidation (P < 0.05). There were no changes observed in placebo-treated subjects compared with the baseline study. We conclude that GH administration to endurance-trained male athletes has a net anabolic effect on whole body protein metabolism at rest and during and after exercise.

Psychological effects of withdrawal of growth hormone therapy from adults with growth hormone deficiency.

OBJECTIVE: Growth hormone (GH) is known to be required for physical well-being. Although it is also widely believed to be important for quality of life (QoL) and psychological health, there is less supportive evidence. The objective of this study was to investigate the psychological effects of discontinuation of GH replacement from adults with severe GH deficiency (GHD). DESIGN: A double-blind, placebo-controlled trial in which GH replacement therapy was discontinued for 3 months from 12 of 21 GH-deficient adults, where nine continued with GH replacement. PATIENTS: GH-treated adults (10 men, 11 women), all with severe GHD (peak GH < 7.7 mU/l on provocative testing), mean age 44.9 years (range 25-68 years). MEASUREMENTS: Semi-structured interviews were given at baseline and end-point plus questionnaires that included a new hormone-deficiency specific, individualized, QoL questionnaire (HDQoL), the General Well-being Index (GWBI), the Well-being Questionnaire (W-BQ12), the Short-Form 36 health status questionnaire (SF-36), the Nottingham Health Profile (NHP) and the General Health Questionnaire (GHQ). RESULTS: Three months after baseline the serum total IGF-I of placebo-treated patients fell from normal, age-related levels (mean 26.6 +/- 13.2 nmol/l) to levels indicative of severe GHD (11.6 +/- 6.6 nmol/l) (P<0.001). Psychological symptoms of GH withdrawal, reported in interviews at end-point by placebo-treated patients, included decreased energy, and increased tiredness, pain, irritability and depression. Patients who believed they knew which treatment they had received correctly identified the treatment (GH or placebo) at end-point (chi2=11.25, P<0.01). Significant between-treatment-group differences in change scores were found for SF-36 General Health (P<0.01), W-BQ12 Energy (P<0.01) and HDQoL do physically (P<0.05), indicating reduced general health, reduced energy and greater perceived impact of hormone deficiency on physical capabilities in the placebo-treated group at end-point relative to GH-treated patients. CONCLUSION: Withdrawal of GH treatment from adults with severe GH deficiency has detrimental psychological effects.

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.

The effect of growth hormone (GH) replacement therapy in adult patients with type 1 diabetes mellitus and GH deficiency.

OBJECTIVES: Specific problems in patients with insulin-dependent diabetes mellitus (IDDM) and GH deficiency are hypoglycaemic attacks, increased insulin sensitivity and loss of energy. These problems may be related to GH deficiency. PATIENTS: GH replacement was initiated in five patients with type 1 diabetes mellitus and GH deficiency for 6 months [four males and one female, mean age 41.6 +/- 3.8 years, mean +/- standard error of the mean (SEM); body mass index (BMI) 22.3 +/- 1.2 kg/m2]. METHODS: Body composition (bioimpedance), metabolic control [haemoglobin A1C (HbA1C)], insulin requirement and frequency of hypoglycaemia were measured, and quality of life was assessed using validated questionnaires. Monthly eye photographs were taken. RESULTS: IGF-I concentrations were below the age-adjusted range at baseline and increased significantly following GH replacement therapy [analysis of variance (ANOVA), P < 0.05]. Diabetes control as assessed by HbA1C remained stable (8.2 +/- 0.2 vs. 8.0 +/- 0.4), but needed a 1.75-fold increase in insulin dose/day. Lean body mass tended to increase (P = 0.07) and body fat mass decreased significantly (P > 0.01). Number of severe hypoglycaemic (< 3 mmol/l) attacks decreased significantly (P < 0.04) and quality of life assessed by validated questionnaires improved significantly in all patients [Psychological and General Well-Being Schedule (PGWBS), P < 0.04; Nottingham Health Profile (NHP), P < 0.05]. Monthly eye photographs revealed no changes in the retina in any patients. CONCLUSION: GH replacement therapy has a beneficial effect at the dose used. It restores body composition and decreases frequency and severity of hypoglycaemic episodes, thus improving quality of life. Long-term trials are needed to determine the safety of GH replacement therapy in these patients.

Evaluation of two health status measures in adults with growth hormone deficiency.

OBJECTIVE: To evaluate the psychometric properties of two health status measures for adults with growth hormone deficiency (GHD): Nottingham Health Profile (NHP) and Short-Form Health Survey (SF-36). DESIGN: (1) A cross-sectional survey of adults with treated or untreated GHD to assess reliability and validity of the questionnaires. (2) A randomized, placebo-controlled study of 3 months' GH withdrawal from GH-treated adults to assess the sensitivity of the questionnaires to change. PATIENTS: (1) A cross-sectional survey of 157 patients with severe GHD (peak GH < 10 mU/l on provocative testing), mean age 48.9 years (range 23-70 years), who had either received GH replacement therapy for at least 6 months immediately prior to the study or had not received GH treatment in the previous 6 months. (2) GH treatment was withdrawn from 12 of 21 GH-treated adults, all with severe GHD (peak GH < 7.7 mU/l on provocative testing), mean age 44.9 years (range 25-68 years). MEASUREMENTS: The NHP and SF-36 were used once in the cross-sectional survey, but twice in the GH-withdrawal study, at baseline and end-point (after 3 months). RESULTS: (1) Cross-sectional survey. Both questionnaires had high internal consistency reliability with subscale Cronbach's alphas of > 0.73 (NHP) and > 0.78 (SF-36). Calculation of an NHP Total Score, occasionally reported in the literature, was shown to be inadvisable. Overall, patients with GHD were found to have significantly worse perceived functioning than the UK general population in SF-36 subscales of General Health, Bodily Pain, Social Functioning, Physical Functioning, Role-Emotional, Role-Physical, and Vitality. Although neither questionnaire found significant differences between GH-treated and non-GH-treated patients, there were correlations with duration of GH treatment (P < 0.01) for GH-treated patients in SF-36 Mental Health (r = 0.29, N = 87) and SF-36 Vitality (r = 0.33, N = 88), indicating improvement with increasing treatment duration. The SF-36 was also more sensitive than the NHP to sex differences: men had significantly better health status compared with women (P < 0.05) in all SF-36 subscales but Mental Health, but only in one NHP subscale (Physical Mobility). (2) GH-withdrawal study. Significant between-group differences in change were found in SF-36 General Health [t(17) = 2.76, P = 0.013, two-tailed] and SF-36 Mental Health [t(17) = 2.41, P = 0.027, two-tailed]: patients withdrawn from GH reported reduced general health and mental health at end-point. The NHP found no significant change. CONCLUSIONS: The SF-36 is a better measure than the NHP of health status of people with GH deficiency because of its greater discriminatory power, with ability to detect lesser degrees of disability. It also has superior sensitivity to some subgroup differences and superior sensitivity to change compared with the NHP. The SF-36 is highly acceptable to respondents, and has very good internal consistency reliability. The SF-36 is recommended to measure the health status of adults with GH deficiency.

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.