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Biomedical subjects

D B Dunger

Publications and source records attributed to D B Dunger.

At least 109 records · Page 6Linked to original sources
PubMed1997

Treatment of radiation-induced growth hormone deficiency with growth hormone-releasing hormone.

UNLABELLED: In children with hypothalamic causes for GH deficiency there are theoretical reasons why a GHRH analogue might be better than conventional GH therapy in promoting growth. OBJECTIVE: We have aimed to determine the efficacy and safety of growth hormone-releasing hormone (GHRH) (1-29)-NH2 given as a twice daily subcutaneous injection in the treatment of growth failure in children with radiation-induced GH deficiency. DESIGN: A multicentre study comparing growth before and after 1 year of treatment with GHRH (1-29)-NH2, 15 micrograms/kg twice daily, by subcutaneous injection in children with radiation-induced GH deficiency. On completion of the study year all children were treated with GH (0.5 U/kg/week) and growth parameters were documented over the next year. PATIENTS: Nine children (six boys) with radiation-induced GH deficiency following cranial (n = 4) or craniospinal (n = 5) irradiation for a brain tumour distant from the hypothalamic-pituitary axis (n = 8) or prophylaxis against central nervous system leukaemia (n = 1) were studied. All were prepubertal when the study commenced, which was at least 2 years from radiotherapy. MEASUREMENTS: Anthropometry and pubertal staging were carried out at 3-monthly intervals and bone age estimations at 6-monthly intervals (TW2 method). Pretreatment standing height velocities were compared with values during the year of GHRH treatment and then after the first year of GH therapy. In those that had received craniospinal irradiation, a change in leg-length Standard deviation score (SDS) was noted before and after GHRH therapy. Changes in skin-fold thickness and bone age during the GHRH study year were documented. Adverse events and 3-monthly measurements of clinical chemistry, haematology, lipid profile and thyroid function were recorded. RESULTS: There was a significant increase in height velocity from 3.3 (SD 1.1) cm/year before treatment, to 6.0 (SDS 1.5) cm/year after 1 year of GHRH treatment (P = 0.004). GHRH maintained or improved the leg length SDS in children who had received craniospinal irradiation. Bone age increased by a mean of 1.1 years/chronological year during treatment with GHRH. Subsequent height velocity during 1 year of GH therapy was 7.5 (SD 1.5)cm/year. No adverse changes in biochemical or hormonal analyses were noted or adverse events that could be attributed to GHRH therapy. One child went into puberty during the GHRH study year and three were pubertal during the first year of GH therapy. CONCLUSION: In cranially irradiated children, GHRH was effective in increasing growth velocity but this was less than that seen in response to GH therapy, although it matched that in children with isolated idiopathic GH deficiency treated with the same dose and schedule of GHRH administration.

Age Determination by Skeleton↗
PubMed1997

Relation between insulin-like growth factor-I, body mass index, and clinical status in cystic fibrosis.

OBJECTIVES: Despite improved nutrition and intensive treatment, subjects with cystic fibrosis have difficulty in maintaining anabolism during intercurrent infections, which can result in reduced body mass index and impaired skeletal growth. Insulin-like growth factor-I (IGF-I) and its binding protein IGFBP3 are sensitive to changes in nutritional status. The aim of this study was to determine the relation between circulating concentrations of these peptides, body mass index, and clinical status in cystic fibrosis. METHODS: Serum concentrations of IGF-I and IGFBP3 were measured in 197 subjects (108 males, 89 females; mean age 9.69 years, range 0.41-17.9 years) and these data were analysed with respect to body mass index, pubertal stage, and clinical status as assessed by Shwachman score and forced expiratory volume in one second (FEV1). RESULTS: The mean height SD score of the children studied was -0.2 (SD 1.14) and the body mass index SD score -0.26 (1.4). The body mass index SD score declined with increasing age (r = -0.18) and paralleled changes in IGF-I concentrations, which also declined. The IGF-I SD score (calculated from control data) correlated with age (r = -0.53). The abnormalities were most obvious during late puberty, when IGF-I and IGFBP3 concentrations were significantly reduced compared with those in control subjects matched for pubertal stage. The IGF-I SD score correlated with height SD score (r = 0.14) and the decline in IGF-I concentrations with the fall in body mass index SD score (r = 0.42). IGF-I SD scores also correlated with the Shwachman score (r = 0.33) and FEV1 (r = 0.17). CONCLUSIONS: The close relation between declining IGF-I and IGFBP3 concentrations and body mass index in patients with cystic fibrosis may simply reflect poor nutritional status and insulin hyposecretion. Nevertheless, IGF-I deficiency could also contribute towards the catabolism observed in these patients, and IGF-I SD scores correlated with other measures of clinical status such as the Shwachman score and FEV1.

Adolescent↗
PubMed1997

The use of an automated microsampling system for the characterization of growth hormone pulsatility in newborn babies.

To overcome the difficulties of studying hormone pulsatility in the newborn, we have developed an automated microsampling system that permits the measurement of hormones in small prediluted samples of blood (40 microL) taken at 10-min intervals over 12 h. The system has been validated in adult volunteers, and the error attributable to the dilution was <4%. Using this method in 10 preterm babies, we have been able to describe pulsatile changes in GH and have demonstrated a clear postprandial elevation in GH levels peaking 60 min after a feed. Fourier transform analysis indicated a pulse periodicity of 180 min in babies who were appropriate for gestational age (n = 6), but faster, co-dominant pulse periodicities of 90-100 and 140 min in babies who were small for gestational age (weight and length below the 10th centile) (n = 4). There was no significant difference between mean, peak, and baseline GH levels between the two groups.

Adult↗
PubMed1996

Examination of two genetic polymorphisms within the renin-angiotensin system: no evidence for an association with nephropathy in IDDM.

Premature cardiovascular disease is common in insulin-dependent diabetic (IDDM) patients who develop diabetic nephropathy. Genetic polymorphism within the renin-angiotensin system has been implicated in the aetiology of a number of cardiovascular disorders; these loci are therefore candidate genes for susceptibility to diabetic renal disease. We have examined the angiotensin converting enzyme insertion/deletion polymorphism and angiotensinogen methionine 235 threonine polymorphism in a large cohort of Caucasian patients with IDDM and diabetic nephropathy. Patients were classified as having nephropathy by the presence of persistent dipstick positive proteinuria (in the absence of other causes), retinopathy and hypertension (n = 242). Three groups were examined for comparison: ethnically matched non-diabetic subjects (n = 187); a geographically defined cohort of newly diagnosed diabetic patients (n = 341); and IDDM patients with long duration of disease (> 15 years) and no evidence of overt nephropathy (n = 166). No significant difference was seen in distribution of angiotensin converting enzyme or angiotensinogen genotypes between IDDM patients with nephropathy and recently diagnosed diabetic subjects (p = 0.282 and 0.584, respectively), nor the long-duration non-nephropathy diabetic subjects (p = 0.701 and 0.190, respectively). We conclude that these genetic loci are unlikely to influence susceptibility to diabetic nephropathy in IDDM in the United Kingdom.

Adult↗
PubMed1996

Growth hormone insulin-like growth factor I axis in insulin-dependent diabetes mellitus.

Growth hormone (GH) hypersecretion and relative insulin-like growth factor I (IGF-I) deficiency have been implicated in the development of insulin resistance, poor metabolic control, and impaired growth during puberty in insulin-dependent diabetes mellitus (IDDM). Portal levels of insulin are critical for the integrity of the hepatic GH receptor and suppression of the inhibitory IGF-binding protein I. Increasing insulin doses during puberty will result in adequate portal levels of insulin and thus restore IGF-I levels and IGF bioactivity, but at the risk of nocturnal hypoglycaemia and weight gain. Restoration of normal circulating levels of IGF-I using the recombinant peptide will lead to reductions in GH levels and improved insulin sensitivity. Given as a daily subcutaneous injection, low-dose recombinant human IGF-I (40 micrograms/kg/day) could prove to be a useful adjunct to standard insulin therapy during puberty in IDDM. The reduced and more stable insulin requirement might reduce the risks of nocturnal hypoglycaemia and weight gain. However, whereas intensified insulin therapy will reduce the risk of microangiopathic complications, the benefits of combination therapy have not been proven. The role of recombinant human IGF-I in the treatment of IDDM needs to be tested by long-term controlled trials.

Blood Glucose↗
PubMed1996

The short-term effects of growth hormone therapy on height velocity and cardiac ventricular wall thickness in children with Noonan's syndrome.

Noonan's syndrome (NS) is associated with short stature and cardiac defects. Small studies reported linear growth increases with recombinant human GH (rhGH) therapy, but also raised concerns related to the anabolic effects of rhGH and the possible progression of ventricular hypertrophy. We report a multicenter study examining the efficacy and safety of rhGH (4 IU/m2.day, sc) in children with NS. Entry criteria were: NS confirmed by single observer, height SD score less than -2(UK Height Standards 1990), prepubertal, and normal maximal left ventricular (LV) wall thickness less than 1 cm by 2-dimensional echocardiography. Thirty subjects were recruited (19 males and 11 females), aged 8.9 +/- 0.5 yr (range, 4.8-13.7 yr). Growth was monitored for 12 months before and at 3-month intervals during therapy. Measurements of maximal LV wall thickness were taken at 0 and 12 months. Serum insulin-like growth factor I(IGF-I), IGF-II, and IGF-binding protein-3 levels were determined at 0, 3, 6, 9, and 12 months. Ten subjects with NS (4 females and 6 males), aged 8.8 +/- 0.7 yr (range, 6.3-11.8 yr), were monitored over the same period as a comparison group. In the treatment group, 27 subjects completed 12 months of therapy. Height SD score increased from -3.01 +/- 0.10 to -2.36 +/- 0.10 (P < 0.0001) after 12 months; height velocity (HV) increased from 4.9 +/- 0.2 to 8.9 +/- 0.3 cm/yr at 6 months and 8.1 +/- 0.4 cm/yr (P < 0.0001) from 6-12 months. The HV SD score increased from -0.7 +/- 0.15 to +2.42 +/- 0.32 over 12 months (P < 0.0001). The increase in HV was more than 2 cm/yr in 24 patients. IGF-I increased from 121 +/- 13 to 240 +/- 22 micrograms/L at 12 months (P < 0.0001), and IGF-binding protein-3 increased from 2.65 +/- 0.20 to 4.01 +/- 0.42 mg/L at 12 months (P = 0.0009). In the comparison group, there was no change in height SD score (-2.03 +/- 0.19), HV (4.4 +/- 0.24 CM/yr), or HV SD score (- 1.08 +/- 0.21). There was no increase in mean maximal LV wall thickness during the study in either the treatment group (12 month values were 0.63 +/- 0.02 cm at the mitral valve level and 0.66 +/- 0.02 cm at the papillary muscle level) or in the comparison group (0.63 +/- 0.04 cm at the mitral valve level and 0.61 +/- 0.03 cm at the papillary muscle level). In conclusion, rhGH was effective in 24 of the treated patients; these subjects achieved a significant increase in height SD score and HV over 1 yr. Abnormal anabolic effects of rhGH on myocardial thickness were not confirmed, and no patient developed features of hypertrophic cardiomyopathy.

Adolescent↗
PubMed1996

Diminished thyroxine-binding globulin in pubertal diabetic children.

OBJECTIVE: To determine the effect of diabetes on thyroid hormone and thyroxine-binding globulin (TBG) concentrations during puberty. RESEARCH DESIGN AND METHODS: Total thyroxine (TT4), free thyroxine (FT4), and TBG levels of 171 thyroid microsomal antibody-negative subjects with normal thyroid-stimulating hormone (TSH) levels were measured and compared with those of nondiabetic adolescents. A random subset of 68 diabetic patients (40 boys and 28 girls) and 51 control subjects (24 boys and 27 girls) were analyzed for puberty-related changes. RESULTS: Most TT4 levels of diabetic subjects (80% of girls and 63% of boys) were below the 50th percentile for the normal range. TT4 increased with age in girls (r = 0.25, P < 0.04) but not in boys. FT4 was within normal limits in both sexes. TBG measurements were below the 50th percentile and 20% were below the 95% CI for both sexes; TT4 correlated with TBG in boys (r = 0.54, P < 0.001) and in girls (r = 0.58, P < 0.001). Duration of diabetes had no effect, whereas TT4 and FT4 levels were higher in girls with the lowest HbA1 levels (r = -0.29, P < 0.01 and r = -0.45, P < 0.01). Levels of TBG were reduced for all male pubertal stages (P < 0.01) and for early and late female pubertal stages (P < 0.01). There was no direct relationship between glucose control or the duration of diabetes and levels of TBG. CONCLUSIONS: Because TT4 levels are low and correlate with the low levels of TBG, it is important to measure free thyroid hormone and TSH levels in diabetic adolescents to establish euthyroidism.

Adolescent↗
PubMed1996

Recombinant IGF-I therapy in insulin-dependent diabetes mellitus.

Recombinant insulin-like growth factor-I (IGF) has both anabolic and insulin-like effects. In adolescent insulin-dependent diabetes mellitus (IDDM), the GH/IGF-I axis is abnormal, with elevation of growth hormone (GH) secretion and subnormal IGF-I levels. The elevated GH levels contribute to pubertal insulin resistance, making glycaemic control difficult to achieve. Theoretically, rhIGF-I could replace IGF-1 and lower GH by negative feedback effects, hence improving glycaemic control. Two preliminary studies are described in this paper. In the first study, rhIGF-I 40 micrograms/kg s.c. was given as an adjunct to insulin at 1800 h. RhIGF-I induced a significant fall in mean overnight GH secretion and in the insulin infusion rate required to maintain euglycaemia. In the second study, rhIGF-I was given in a dose of 40 micrograms/kg s.c. for 1 month. The dose of isophane insulin fell during puberty, as did HbA1c. These preliminary studies suggest that rhIGF-I given in conjunction with regular insulin therapy may reverse abnormalities in the GH/IGF-I axis and therefore contribute to improvement of glycaemic control in adolescents with IDDM.

Adolescent↗
PubMed1996

Serum insulin-like growth factor II levels in normal adolescents and those with insulin dependent diabetes mellitus.

OBJECTIVE: Unlike IGF-I and its principal binding proteins, data regarding IGF-II levels have not been well defined in normal subjects and those with insulin-dependent diabetes mellitus (IDDM). We have therefore measured IGF-II, as well as IGF-I, and IGFBP-3, levels in a large cohort of subjects with IDDM and in age/sex matched controls. PATIENTS: One hundred and fourteen patients with IDDM (57 males, 57 females) and 89 control subjects (49 males, 40 females). MEASUREMENTS: Random blood samples were obtained from each subject for the measurement of IGF-II, IGF-I and IGFBP-3 levels. RESULTS: Mean values of IGF-II (+/- SEM) were 630 (+/- 27.8) micrograms/l and 646 (+/- 32.3) micrograms/l in female and male controls, compared to 569 (+/- 23.3) micrograms/l and 623.3 (+/- 28.1) micrograms/l in female and male diabetics respectively. IGF-II levels did not differ significantly between the sexes or show any change with transition through puberty in either control or diabetic groups. In contrast, IGF-I levels increased through puberty peaking at stages 3-5 in controls (P < 0.001) and G4-5 (P = 0.002) in diabetic males but not females. IGF-I levels in all diabetics were generally lower than in controls, differences reaching significance at G4-5 in males (P = 0.002) and B5 in females (P = 0.002). IGFBP-3 levels did not show any variation with puberty stage in diabetics, in contrast to controls where levels increased, peaking at G4-5 in males (P = 0.001) and B3 in females. IGFBP-3 levels were lower in diabetics of both sexes and at all stages compared to controls (P range 0.047 to < 0.001). Multiple regression analysis revealed significant correlations between IGF-II and IGFBP-3 (F = 20.1, P = < 0.001) and reaffirmed previously observed associations for IGF-I and IGFBP-3. The sum of IGF-I and IGF-II (expressed as nmol/l) correlated with IGFBP-3; r = 0.47 in controls and 0.60 in diabetics. CONCLUSIONS: Insulin-dependent diabetes mellitus is not associated with any significant changes in IGF-II levels during puberty. The binding of IGFBP-3 for both IGF-I and IGF-II is unaltered by insulin-dependent diabetes mellitus.

Adolescent↗
PubMed1995

Insulin-like growth factors (IGFs) and IGF-I treatment in the adolescent with insulin-dependent diabetes mellitus.

Insulin-dependent diabetes mellitus (IDDM) during adolescence is associated with complex derangements of the growth hormone (GH)/insulin-like growth factor (IGF) axis. Despite GH hypersecretion, IGF-I levels and IGF bioactivity are reduced. The diabetogenic effects of GH are well established, and GH hypersecretion has been implicated in the deterioration in glycemic control during adolescence and in the development of microangiopathy. Insulin deficiency or reduced portal delivery of insulin plays a central role in the development of these abnormalities, and although continuous subcutaneous insulin delivery may improve plasma IGF-I levels, it does not necessarily suppress GH levels. Recombinant IGF-I has been proposed as an adjunct to conventional insulin therapy, as restoring circulating IGF-I levels might lead to GH suppression. Placebo-controlled studies have shown a consistent reduction in GH secretion and related improvements in insulin sensitivity following a single subcutaneous IGF-I injection (40 micrograms/kg). Repeated daily subcutaneous IGF-I administration for 1 month resulted in a sustained increase in IGF-I levels, as well as a reduction in GH secretion and insulin requirements. There was no increase in hypoglycemia or other adverse effects. Recombinant IGF-I used in conjunction with insulin may therefore provide an additional approach to the management of IDDM during adolescence, allowing correction of abnormalities in the GH/IGF axis and leading to improved control and, hence, reduced risk of long-term complications. However, this hypothesis needs to be rigorously tested in long-term placebo-controlled studies.

Adolescent↗
PubMed1995

The effects of repeated daily recombinant human insulin-like growth factor I administration in adolescents with type 1 diabetes.

Reduced insulin-like growth factor bioactivity has been linked to poor metabolic control and growth hormone hypersecretion in adolescents with Type 1 diabetes. The safety and efficacy of recombinant human insulin-like growth factor I administered subcutaneously in a dose of 40 micrograms kg-1 for 28 days was studied in a group of 6 adolescent male subjects with Type 1 diabetes (aged 13.6-19.4 years, puberty stage 3-5). After a 4-week run-in period (week -4 day 0) recombinant human insulin-like growth factor I was administered for 4 weeks (day 0 to week +4) before a run-out of a further 4 weeks duration (week +4 to +8). HbA1c levels were measured throughout the study and overnight profiles were undertaken to study levels of insulin-like growth factor 1, insulin-like growth factor binding protein-3, and growth hormone concentrations (week -1, day 0, and week +4). The injections were well tolerated and hypoglycaemia was not problematic at any stage of the study. Recombinant insulin-like growth factor I administration appeared to lead to a sustained increase in insulin-like growth factor I levels (week -1; 198 +/- 16 ng ml-1, week +4; 422 +/- 18 ng ml-1, mean +/- SEM; p = 0.03). Insulin-like growth factor binding protein-3 concentrations (n = 6) increased in 5 subjects (week -1; 4.5 +/- 0.3 micrograms ml-1, week +4; 5.1 +/- 0.4 micrograms ml-1) and mean overnight growth hormone decreased (week -1; 14.0 +/- 3.1 mUI-1, week +4; 7.6 +/- 1.7 mUI-1) during the period of study but these differences were not statistically significant. HbA1c levels fell significantly at the time of rhIGF-I administration (day 0; 10.4 +/- 1.9% vs week +4; 9.4 +/- 1.9%; p = 0.03) despite a reduction in subcutaneous isophane insulin dose from 0.50 +/- 0.02 U kg-1 to 0.41 +/- 0.02 U kg-1 (p = 0.03). There was no significant change in biochemical and haematological indices, glomerular filtration rate or urinary albumin excretion. The restoration of IGF-I levels in adolescents with Type 1 diabetes may have a beneficial impact on glycaemic control.

Aged↗
PubMed1995

Sodium-lithium countertransport in children with diabetes and their families.

Abnormalities of sodium-lithium countertransport have been extensively implicated in adult primary hypertension and a relationship between sodium-lithium countertransport and family history of hypertension in children has been previously found. More recently it has been suggested that increased sodium-lithium countertransport may play a part in the pathogenesis of nephropathy in insulin dependent diabetes mellitus (IDDM). Children and adolescents with IDDM and their family members were studied. In those with IDDM (n = 36, median age 14.6 years, range 9.5-19.2 years) there was no relationship between sodium-lithium countertransport (range 0.098-0.585 mmol/l red blood cells/hour) and age, blood pressure as expressed by systolic or diastolic SD scores, glycated haemoglobin, serum lipids, or intracellular sodium concentration. A positive relationship (rs = 0.44) was found between sodium-lithium countertransport and early morning urinary albumin to urinary creatinine ratio (UA/UC), expressed as the logarithm of the geometric mean of two consecutive samples, for each individual (range 0.4-22 mg/mmol). Sodium-lithium countertransport was increased in those with IDDM compared with their non-diabetic siblings, in a paired analysis (n = 26). There was no relationship between UA/UC in the children with diabetes and sodium-lithium countertransport in their parents. These studies in this population of diabetic children indicate that increased sodium-lithium countertransport may play a part in the early stages of the development of nephropathy in IDDM.

Adolescent↗
PubMed1995

The Oxford growth study: a district growth surveillance programme 1988-1994.

OBJECTIVES: To develop a method of community based growth assessment. SETTING: Oxford District, United Kingdom. METHODS: A system of growth surveillance involving a community consultant paediatrician, a paediatric endocrinologist, a clinical auxologist, a project coordinator, and the many primary health care teams was started. Letters and meetings were arranged to introduce the programme to general practitioners and health visitors, emphasising the importance of growth assessment in normal child development. They were asked to measure all children as part of their routine developmental checks at 3 and 4.5 years of age. Community growth assessment clinics staffed by an experienced auxologist were established. Children whose heights were more than two standard deviation (SD) scores below the mean or whose height SD score decreased between the two ages were referred to the clinic. Any child whose height was more than 3 SD scores below the mean was referred directly to the paediatric endocrinologist. Those seen in the community clinics were followed up for a year and if their velocity was > 25th centile, karyotype normal, and bone age appropriately delayed, they were discharged to the general practitioner for further follow up. Any child with an annual velocity < 25th centile was referred to the endocrinologist. RESULTS: Of 20,338 children monitored, 260 (1.3%) had heights > -2 SD scores. Seventy six were lost to follow up, 35 were measuring errors, 69 were already seeing a paediatrician, leaving 80 children to be evaluated. Of these, 69 were "short normals" and 11 were newly identified diagnoses. CONCLUSIONS: This system of secondary referral keeps normal healthy children out of hospital, avoids unnecessary over-investigation, reduces travel and anxiety for families, avoids filling specialist clinics with normal children, and provides an inexpensive system of growth surveillance.

Analysis of Variance↗
PubMed1994

Presentation and progress of childhood diabetes mellitus: a prospective population-based study. The Bart's-Oxford Study Group.

We surveyed the clinical presentation, initial management and subsequent course of a prospectively registered, population-based cohort of 230 patients with Type 1 (insulin-dependent) diabetes mellitus diagnosed before age 21 years in the Oxford Regional Health Authority area in 1985 and 1986. Clinical details from the time of diagnosis were available on 219 patients. Thirty-four (16%) were in severe ketoacidosis with pH less than 7.10 or plasma bicarbonate less than 10 mmol/l, and 21 (10%) had mild to moderate ketoacidosis with pH 7.10-7.35 or plasma bicarbonate 10-21 mmol/l. One child died in ketoacidosis. Presentation in severe ketoacidosis was most common in children under age 5 years (p < 0.05), and ketoacidosis of any degree was less frequent in older children (0.05 < p < 0.01) and those with a parent or sibling with diabetes (p < 0.01). Within 4 years of diagnosis, 55 of 211 patients (26%) experienced severe hypoglycaemia, which in 31 (15%) led to one or more admissions. Readmission for unstable glycaemic control excluding acute hypoglycaemia occurred at least once within 1 year of diagnosis in 13% and within 4 years in 28%, and was more common in girls, in children aged less than 10 years at diagnosis, and those with a history of severe hypoglycaemia. A second cohort of 97 similar patients was recruited in 1990. The rates of admission at diagnosis (79%), severe ketoacidosis (13%) and mild to moderate ketoacidosis (13%) did not differ from the 1985/1986 cohort.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

The effects of recombinant human insulin-like growth factor I on growth hormone secretion in adolescents with insulin dependent diabetes mellitus.

OBJECTIVE: It has been proposed that low IGF-I levels and reduced IGF-I bioactivity may lead to elevated GH levels in adolescents with insulin dependent diabetes (IDDM). We have therefore studied the effects of human recombinant insulin-like growth factor I (rhIGF-I) administration on GH levels and GH secretion in adolescents with IDDM. PATIENTS: Nine late pubertal adolescents (four male and five female) with IDDM. DESIGN: A double-blind placebo controlled study of rhIGF-I administered subcutaneously in a dose of 40 micrograms/kg body weight at 1800 h. MEASUREMENTS: IGF-I and GH concentrations were measured at regular intervals throughout the study. Twenty-two hour GH secretory rates were calculated by deconvolution analysis. Overnight GH profiles were analysed by distribution analysis, and Fourier transformations were performed on both overnight GH concentrations and GH secretory rates. RESULTS: Mean IGF-I levels over the 22-hour study period were significantly elevated following rhIGF-I administration (350 +/- 26 vs 205 +/- 21 micrograms/l (mean +/- SEM), P < 0.01). Mean 22-hour GH levels were reduced following rhIGF-I administration (19.4 +/- 4.0 compared with 33.6 +/- 5.8 mU/l; P = 0.01). Distribution analysis demonstrated that the reduction in GH levels was due to changes in the proportion of values at both high and low concentrations. Deconvolution analysis also revealed a significant overall reduction in GH secretory rate following IGF-I administration (1.81 +/- 0.30 vs 2.98 +/- 0.47 mU/min, P = 0.01) which was still apparent during the final 5.5 hours of the study period (1.51 +/- 0.30 vs 2.76 +/- 0.61 mU/min, P = 0.02). The dominant periodicity of GH secretory episodes as determined by Fourier transformation was between 120 and 180 minutes after both IGF-I and placebo. CONCLUSIONS: In late pubertal adolescents with IDDM the rise in IGF-I levels following rhIGF-I administration in a subcutaneous dose of 40 micrograms/kg body weight leads to a significant reduction in GH levels and GH secretory rate. The reduction in GH secretion is due to changes in pulse amplitude rather than frequency. A reduction in GH secretion was apparent at the beginning and also towards the end of the 22-hour study period.

Adolescent↗
PubMed1994

Loss of the normal relationships between growth hormone, growth hormone-binding protein and insulin-like growth factor-I in adolescents with insulin-dependent diabetes mellitus.

OBJECTIVE: It has been proposed that the dissociation between growth hormone secretion and insulin-like growth factor-I (IGF-I) concentrations in insulin-dependent diabetes mellitus arises because of partial resistance at the GH receptor. In order to explore this hypothesis further we have examined the relations between IGF-I, GH-binding protein (GHBP), and GH secretion in normal subjects and patients with diabetes during puberty. DESIGN AND SUBJECTS: Blood samples for the estimation of IGF-I and GHBP levels were obtained from 104 patients with diabetes and 89 puberty matched controls. Thirty-four of the controls and 42 of the patients with diabetes also underwent an overnight GH secretory profile with measurements of GH every 15-20 minutes between 2000 and 0800 h. RESULTS: In multivariate analysis using sex, puberty stage, and presence or absence of diabetes as dependent variables, diabetes was associated with increased GH levels (F = 23.04, P < 0.001), reduced IGF-I (F = 10.89, P < 0.001), and reduced GHBP levels (F = 31.36, P < 0.001). A negative relation between GH and GHBP levels (r = -0.44, P < 0.01) was found in normal subjects but this was absent in those with diabetes. Both GHBP and IGF-I levels in the diabetic subjects were correlated with total insulin dose (r = 0.4, P < 0.001, and r = 0.46, P < 0.001, respectively). Yet there was no direct correlation between GHBP and IGF-I concentrations. The variation in IGF-I levels was also related to glycosylated haemoglobin levels in the diabetics (r = -0.27, P = 0.01). In a stepwise multiple regression analysis insulin dose contributed 23%, HbA1 4.4% and C-peptide levels 3.7% to the variation in IGF-I levels. CONCLUSIONS: In adolescents with insulin dependent diabetes mellitus, the elevated GH concentrations are associated with low circulating IGF-I and GHBP concentrations and the normal reciprocal relation between GHBP and GH is no longer evident. Although IGF-I and GHBP are both related to insulin dose, there is no direct correlation between these variables. This may indicate that GHBP reflects GH receptor numbers but not necessarily post receptor events, and the weak positive correlation between GH and IGF-I indicates that increased growth hormone secretion may compensate for reduced receptor numbers.

Adolescent↗