Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 21
Filter
1.
Obesity (Silver Spring) ; 22(3): 781-5, 2014 Mar.
Article in English | MEDLINE | ID: mdl-23839907

ABSTRACT

OBJECTIVE: Dopamine is a neurotransmitter that mediates the reward value of food. Methylphenidate (MPH) selectively binds and inhibits the dopamine transporter, thus increasing brain dopamine levels shortly after oral administration. This investigation studied whether a single dose of MPH decreases energy intake (EI) in obese teenagers compared to placebo (P). METHODS: This study used a single-blind, placebo-controlled, within subject design. Teenagers with body mass index (BMI) ≥95th percentile underwent two identical meal tests (P or MPH) after a 10 h fast in random order. Food was weighed before and after the meals, and EI was calculated as energy content/gram of consumed foods. Total and macronutrient EI (mean ± SD) were analyzed by Mann-Whitney U and Wilcoxon tests. RESULTS: Twenty-two subjects (15 females, 7 males) completed the study. Participants were 13.4 ± 2.2 years old and had BMI 34.9 ± 10.7 kg/m². EI from fat (167 vs. 203 kcal, P = 0.03) and carbohydrates (311 vs. 389 kcal, P = 0.04) was decreased for MPH compared to P meals, with a trend in decreased total EI (545 vs. 663 kcal, P = 0.06). CONCLUSION: A single dose of MPH decreases EI from fat and carbohydrates in obese adolescents. This effect underscores the importance of central dopamine signaling on eating behavior.


Subject(s)
Dietary Carbohydrates/administration & dosage , Dietary Fats/administration & dosage , Methylphenidate/administration & dosage , Obesity/drug therapy , Adolescent , Black or African American , Body Mass Index , Child , Dietary Proteins/administration & dosage , Dopamine Plasma Membrane Transport Proteins/genetics , Dopamine Plasma Membrane Transport Proteins/metabolism , Dose-Response Relationship, Drug , Energy Intake , Female , Humans , Insulin/blood , Male , Meals , Single-Blind Method , White People
2.
J Pediatr Endocrinol Metab ; 14(3): 267-77, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11308044

ABSTRACT

OBJECTIVE: A 12-week trial with insulin and rhIGF-I compared to insulin and placebo was conducted in patients with type 1 diabetes mellitus aged 11-66 years. We present the efficacy and safety data pertinent to the younger subset of participants (11-21 years). STUDY DESIGN: The patients were randomized to receive s.c. insulin and either placebo or rhIGF-I at one of the following doses (microg/kg): 40 a.m./40 p.m., 80 a.m./40 p.m. or 80 a.m./60 p.m.). RESULTS: The average decrease of HbA1c from baseline was higher (-1.3 +/- 0.2%) in the rhIGF-I treated group compared to the placebo group (-0.6 +/- 0.3%; p <0.05). This was associated with a significant decrease in daily insulin dose (U) of both Regular (rhIGF-I: -7 +/- 1; placebo: -1 +/- 1; p <0.01) and NPH (rhIGF-I: -4 +/- 2; placebo: +5 +/- 3; p <0.05). The incidence of hypoglycemia and weight gain were not increased. Edema, jaw pain and tachycardia were associated with rhIGF-I treatment, particularly at doses higher than 40 microg/kg b.i.d. Dose-related early worsening of retinopathy was observed in 11/55 patients in the rhIGF-I group, with resolution in the majority of them in the follow-up photographs. CONCLUSIONS: These findings suggest a possible role for rhIGF-I co-therapy in adolescents and young adults with type 1 diabetes mellitus.


Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Glycated Hemoglobin/analysis , Hypoglycemia/blood , Insulin-Like Growth Factor I/therapeutic use , Insulin/therapeutic use , Adolescent , Adult , Child , Diabetes Mellitus, Type 1/blood , Drug Therapy, Combination , Female , Humans , Insulin/administration & dosage , Insulin-Like Growth Factor I/administration & dosage , Male , Recombinant Proteins/administration & dosage , Recombinant Proteins/therapeutic use
3.
J Autoimmun ; 12(4): 279-87, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10330299

ABSTRACT

We report here our prospective study of 15,224 non-diabetic, first-degree relatives of probands with immune-mediated (type 1) diabetes (IMD), of which 135 were found to eventually develop diabetes. We determined islet cell, insulin, GAD65, insulinoma-associated antigen-2 and 2beta autoantibodies (ICA, IAA, GAD65A, IA-2A and IA-2betaA), on the first available serum samples. The latter three autoantibodies were however assayed on subsets of the relatives with and without ICA, IAA and/or GAD65A, plus most of the relatives who developed diabetes. Of the relatives who progressed to diabetes, 94% had at least one of these autoantibodies on the first screening, while ICA proved to be the most sensitive single marker (sensitivity 74%). Risk of diabetes was however negligible when ICA was found in the absence of the others (5-year risk=5.3%), but increased dramatically whenever two or more autoantibodies were present (5-year risk=28.2% and 66.2%, respectively). The most predictive combination of markers was ICA plus IA-2A and/or IA-2beta A. Loss of first phase insulin release to IVGTT also occurred only in those ICA-positive relatives who had one or more of the other autoantibodies. The data suggests that significant beta-cell damage is seen only when the underlying autoimmunity has spread to multiple antigenic islet cell determinants. Combinations of the autoantibodies occurred most often in relatives with the highest risk HLA-DR/DQ phenotypes. These data document that only relatives positive for at least two or more of these five autoantibodies are at significant risk of diabetes themselves. Intervention trials for the prevention of type 1 diabetes could be designed based on testing for these autoantibodies alone, without the need for HLA typing and IVGTT testing.


Subject(s)
Autoantibodies/blood , Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 1/immunology , Glutamate Decarboxylase/immunology , Insulin/immunology , Protein Tyrosine Phosphatases/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , HLA-DQ Antigens/genetics , HLA-DQ beta-Chains , Humans , Infant , Infant, Newborn , Male , Middle Aged , Protein Tyrosine Phosphatase, Non-Receptor Type 1
4.
Diabetes Care ; 22(4): 585-92, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10189536

ABSTRACT

OBJECTIVE: To study the effects of 12 weeks of cotherapy with recombinant human IGF-I (rhIGF-I) and insulin on glycemic control in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: The study population consisted of 223 patients who ranged in age from 11-66 years and were randomized in a double-blind study to receive 12 weeks of treatment with twice-daily subcutaneous injections of placebo (n = 54), or rhIGF-I at a dose (A.M/P.M) of 40/40 micrograms/kg (n = 56), 80/40 micrograms/kg (n = 57), or 80/60 micrograms/kg (n = 56), while continuing to receive standard insulin therapy. Patients were instructed to test blood glucose levels four times daily and adjust insulin doses to optimize blood glucose control. HbAlc, insulin requirements, body weight, and parameters of the IGF-IGF-binding protein axis were assessed before and during treatment. RESULTS: All groups were comparable at baseline with respect to mean age, gender distribution, duration of diabetes, HbAlc, and BMI. Cotherapy with rhIGF-I/insulin produced a mean decrease in HbAlc of 1.2%, compared with a 0.7% decrease in HbAlc for patients receiving intensified insulin therapy alone (P < or = 0.01). Subjects receiving rhIGF-I/insulin cotherapy also decreased their daily insulin usage by 11-19%, compared with a 7% increase in insulin usage reported by the placebo group. Moreover, the incidence of hypoglycemia was similar in subjects treated with rhIGF-I/Insulin cotherapy compared with those treated with insulin alone, despite the better glycemic control of the former group. The 40/40 dose of rhIGF-I was well tolerated. Higher doses of rhIGF-I did not further improve efficacy yet were associated with unacceptable levels of adverse events, including edema, jaw pain, and early worsening of retinopathy. CONCLUSIONS: These results demonstrate that rhIGF/insulin cotherapy improves glycemic control in patients with type 1 diabetes better than optimized insulin management alone; longer-term trials would be required to determine an acceptable benefit-risk profile.


Subject(s)
Blood Glucose/metabolism , Diabetes Mellitus, Type 1/drug therapy , Insulin-Like Growth Factor I/therapeutic use , Insulin/therapeutic use , Adult , Diabetes Mellitus, Type 1/blood , Diabetic Retinopathy/prevention & control , Drug Therapy, Combination , Female , Humans , Insulin-Like Growth Factor I/genetics , Male , Recombinant Proteins/genetics , Recombinant Proteins/therapeutic use
5.
J Clin Endocrinol Metab ; 82(4): 1181-7, 1997 Apr.
Article in English | MEDLINE | ID: mdl-9100593

ABSTRACT

Patients with insulin-dependent diabetes mellitus (IDDM) exhibit abnormalities in the GH/insulin-like growth factor (IGF) axis, including GH hypersecretion, low serum IGF-I and IGF-binding protein-3 (IGFBP-3) levels, and elevated IGFBP-1 levels. We recently demonstrated that in IDDM, dual hormonal replacement therapy with insulin plus recombinant human IGF-I (rhIGF-I) improves glycemic control better than insulin alone. To determine whether the addition of rhIGF-I therapy to insulin therapy also corrects GH/IGF/ IGFBP abnormalities, we examined the effects of chronic combined rhIGF-I/insulin therapy on key components of the somatotropin axis. Forty-three pediatric IDDM patients were randomly assigned to groups receiving daily, fasting subcutaneous injections of placebo or rhIGF-I (80 micrograms.kg.day) for 28 days, while continuing to receive splitmix insulin therapy and intensive outpatient management. rhIGF-I therapy corrected IGF-I deficiency, suppressed IGFBP-1 levels (P < 0.01), and induced a trend toward lower circulating GH levels throughout the study. rhIGF-I therapy also induced an approximate 50% decrease in IGF-II levels (P < 0.001) and an approximate 70% increase in IGFBP-2 levels (P < 0.05). Serum IGFBP-3 levels, normal before treatment, remained normal during rhIGF-I administration. All effects were apparent during the first week of rhIGF-I therapy and persisted throughout treatment. Because improvements in the GH/ IGF axis abnormalities and in glycemic control were greater in subjects receiving combined rhIGF-I and insulin, these data strongly support the concept that dual hormonal replacement in IDDM may offer distinct therapeutic advantages over insulin monotherapy.


Subject(s)
Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/drug therapy , Human Growth Hormone/blood , Insulin-Like Growth Factor Binding Proteins/blood , Insulin-Like Growth Factor I/therapeutic use , Insulin/therapeutic use , Somatomedins/metabolism , Adolescent , Child , Drug Therapy, Combination , Female , Humans , Male , Recombinant Proteins
6.
Diabetes Care ; 20(3): 374-80, 1997 Mar.
Article in English | MEDLINE | ID: mdl-9051390

ABSTRACT

OBJECTIVE: To examine if dual replacement with insulin and rhIGF-I, recombinant human insulin-like growth factor I (rhIGF-I) may be safe and result in improved metabolic control and reduced insulin usage. RESEARCH DESIGN AND METHODS: Forty-three patients with IDDM were randomized to receive a daily injection of rhIGF-I (80 mcg/kg s.c.) or placebo while on conventional insulin therapy for 4 weeks. Insulin was adjusted in the attempt to achieve predetermined goal glycemic values. Free and total IGF-I, four daily blood glucoses, and HbA1c were measured. RESULTS: Before randomization, placebo and rhIGF-I groups exhibited low plasma levels of free and total IGF-I, which increased toward normal levels during the treatment period only in the rhIGF group. The regression curve obtained from the average of daily blood glucose measurements indicated that the glycemic profile, overlapping in the lead-in period, exhibited a downward trend in the rhIGF-I group during the treatment period. Mean blood glucose level during the last 10 days of treatment was lower in the rhIGF-I groups (174 +/- 37 vs. 194 +/- 32 mg/dl). HbA1c level was reduced by more than one-half percent more in the rhIGF-I group (-1.85%) than in the control group (-1.3%). The dose of regular insulin was significantly lower in the rhIGF-I group (0.2 +/- 0.1 vs. 0.28 +/- 0.1 U. kg-1. 10 days-1 in the placebo group; P < 0.05). CONCLUSIONS: rhIGF-I in combination with conventional insulin treatment ameliorated the low plasma total and free IGF-I levels and was well tolerated in IDDM. There was a trend toward improved glycemic control, while the regular insulin dose was significantly decreased.


Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Hypoglycemic Agents/therapeutic use , Insulin-Like Growth Factor I/therapeutic use , Insulin/therapeutic use , Adolescent , Blood Glucose/analysis , Blood Glucose/metabolism , Blood Glucose Self-Monitoring , Child , Drug Therapy, Combination , Female , Humans , Insulin-Like Growth Factor I/analysis , Insulin-Like Growth Factor I/metabolism , Male , Recombinant Proteins/therapeutic use , Safety , Time Factors , Treatment Outcome
7.
J Clin Endocrinol Metab ; 80(12): 3739-43, 1995 Dec.
Article in English | MEDLINE | ID: mdl-8530627

ABSTRACT

The international community of diabetologists is rapidly becoming involved in intervention trials aimed at preventing insulin-dependent diabetes in high risk relatives. Whereas age and relationship to a proband with insulin-dependent diabetes mellitus interacting with detected islet cell autoantibodies (ICA) are risk factors, their independent contribution to that risk remains unclear. In a prospective study of 6851 nondiabetic relatives of 2742 probands conducted between 1979-1993, we found age, but not relationship, to be a dramatic risk variable in ICA-positive persons as estimated by the Cox regression model. The 5-yr risk of insulin-dependent diabetes mellitus was 66% for those found to have ICA detectable before age 10 yr, falling progressively to less than 16% for ICA-positive relatives over age 40 yr. In ICA-negative relatives, age and relationship are independent prognostic variables.


Subject(s)
Aging/physiology , Diabetes Mellitus, Type 1/genetics , Family , Adolescent , Adult , Antibodies/analysis , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Islets of Langerhans/immunology , Male , Prognosis , Prospective Studies , Regression Analysis , Risk Factors
8.
J Diabetes Complications ; 9(3): 194-7, 1995.
Article in English | MEDLINE | ID: mdl-7548985

ABSTRACT

Hematuria is not described as a common finding in diabetic nephropathy, and may suggest nondiabetic renal disease. We reviewed the records of 59 children and adolescents with insulin-dependent diabetes mellitus referred to the Children's Kidney Center from 1983 to 1992. Fifty-two patients had clinical and/or biopsy evidence of diabetic nephropathy; 18/52 (35%) had microscopic hematuria at the time of referral. Patients with hematuria on presentation were referred for: hypertension (61%), proteinuria (61%), and decreased glomerular filtration rate (GFR) (11%). For patients without hematuria on presentation, reasons for referral included hypertension (79%), proteinuria (56%), and decreased GFR (3%). When comparing patients with and without hematuria, those with hematuria had a significantly longer duration of diabetes (12.8 +/- 3.1 versus 10.8 +/- 3.7 years, p < 0.05). The groups did not differ significantly with regard to age (18.3 +/- 1.8 versus 17.1 +/- 2.9 years), height (162.2 +/- 10.4 versus 159.3 +/- 11.3 cm), weight (63.9 +/- 10.9 versus 59.4 +/- 14.8 kg), systolic blood pressure (137.2 +/- 11.9 versus 133.2 +/- 13.2 mm Hg), diastolic blood pressure (85.6 +/- 7.6 versus 83.9 +/- 13.4 mm Hg), serum creatinine (1.0 +/- 0.18 versus 1.0 +/- 0.43 mg/dL), blood urea nitrogen (15 +/- 5 versus 13 +/- 4 mg/dL), glomerular filtration rate (117 +/- 34 versus 117 +/- 46 mL/min/1.73 m2), 24-h urine protein (2311 +/- 3862 versus 570 +/- 476 mg/day), or microalbuminuria (75 +/- 41 versus 34 +/- 35 micrograms/min). We detected a significant association between retinopathy and microscopic hematuria (sensitivity 47%, specificity 82%, p < 0.05), but no association between labstix proteinuria or sex and hematuria.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Diabetes Mellitus, Type 1/urine , Diabetic Nephropathies/physiopathology , Diabetic Nephropathies/urine , Hematuria , Adolescent , Age of Onset , Blood Urea Nitrogen , Child , Creatinine/blood , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/physiopathology , Diabetic Angiopathies/physiopathology , Diabetic Angiopathies/urine , Diabetic Nephropathies/blood , Diabetic Retinopathy/epidemiology , Diabetic Retinopathy/urine , Diastole , Glomerular Filtration Rate , Humans , Hypertension/physiopathology , Hypertension/urine , Proteinuria , Systole
9.
Clin Pediatr (Phila) ; 34(1): 12-7, 1995 Jan.
Article in English | MEDLINE | ID: mdl-7720322

ABSTRACT

To document the incidence of microalbuminuria in children and adolescents with longstanding insulin-dependent diabetes mellitus (IDDM) and to compare the clinical characteristics and determinant risk factors of those with and without microalbuminuria, 135 adolescent patients with IDDM for 5 years or longer were evaluated. The study population was divided on the basis of microalbumin excretion into normal (< 20 micrograms/min), incipient (20-200 micrograms/min), and overt (> 200 micrograms/min) nephropathy groups. There were 106 patients in the normal group, 24 patients in the incipient group, and five in the overt nephropathy group. Glycosylated hemoglobin, cholesterol concentration, and glomerular filtration rate (GFR) were analyzed. The incidence of incipient and overt nephropathy was 17.8% and 3.7%, respectively. Mean cholesterol concentration in the incipient and overt nephropathy groups (208 +/- 39 mg/dL [5.4 +/- 1.0 mmol/L]) and 227 +/- 49 mg/dL [5.9 +/- 1.3 mmol/L], respectively) was significantly higher than the normal group (186 +/- 37 mg/dL [4.8 +/- 0.9 mmol/L] P < 0.05). Similarly, systolic and diastolic blood pressures were significantly higher in the incipient and overt nephropathy groups compared to the normal group. This study confirms the high incidence of incipient and overt nephropathy in adolescents with IDDM early in the course of the disease.


Subject(s)
Albuminuria/diagnosis , Diabetes Mellitus, Type 1/diagnosis , Diabetic Nephropathies/diagnosis , Adolescent , Albuminuria/urine , Cohort Studies , Diabetes Mellitus, Type 1/urine , Diabetic Nephropathies/urine , Female , Humans , Kidney Function Tests , Male , Reference Values , Risk Factors , Serum Albumin/analysis
10.
Pediatr Res ; 34(4): 435-8, 1993 Oct.
Article in English | MEDLINE | ID: mdl-8255673

ABSTRACT

The output of urinary IGF-II was measured by RIA in 12-h overnight urine samples obtained from 22 preterm and 15 full-term infants, 40 normal children, 18 children with growth hormone (GH) deficiency, and 25 patients with idiopathic short stature. GH deficiency was defined as a peak to GH provocative tests < or = 9.9 micrograms/L during two provocative tests. The authenticity of urinary IGF-II was confirmed by size exclusion chromatography. Statistical analysis was performed by one-way analysis of variance using the Student Neuman-Keuls test to detect intergroup differences at the level of p < 0.05. The preterm and full-term infants excreted significantly higher amounts of urinary IGF-II (18.4 +/- 1.7 and 5.7 +/- 1.0 pmol/kg, respectively) compared with normal children (2.4 +/- 0.25 pmol/kg; p < 0.001). The output of urinary IGF-II in preterm infants was greater than that observed in full-term infants (F = 84.7, p < 0.001). The control children excreted significantly more IGF-II (2.4 +/- 0.2 pmol/kg) than children with GH deficiency (0.9 +/- 0.1 pmol/kg) or idiopathic short stature (1.0 +/- 0.1 pmol/kg; F = 13.5; p < 0.001). Analysis of urinary IGF-II excretion based on creatinine output yielded similar results. Data on urinary IGF-I and GH previously published were correlated and compared with the excretion pattern of urinary IGF-II.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Growth Disorders/urine , Growth Hormone/deficiency , Growth Hormone/urine , Infant, Newborn/urine , Infant, Premature/urine , Insulin-Like Growth Factor II/urine , Analysis of Variance , Body Height , Child , Chromatography, Gel , Female , Humans , Infant , Male , Reference Values
11.
Diabetes Care ; 16(8): 1067-70, 1993 Aug.
Article in English | MEDLINE | ID: mdl-8375234

ABSTRACT

OBJECTIVE: To assess the validity of two equations: K x height/serum creatinine (KL/Cr; K = 0.55 for females 1-18 yr of age and 0.7 for males 12-18 yr of age) and (140 - age) x weight/72 x creatinine (x0.85 for women; Cockroft-Gault) in estimating glomerular filtration rate in children and adolescents with IDDM. RESEARCH DESIGN AND METHODS: From the records of the Children's Hospital Diabetes Clinic, we selected 70 patients with GFR determined by 99mTc-labeled DTPA plasma clearance, stable renal function, and simultaneous measurements of height, weight, blood pressure, HbA1c, and plasma creatinine. We compared DTPA-GFR with estimated GFR from KL/Cr and Cockroft-Gault equations for three groups: all patients, patients with DTPA-GFR < or = 140 ml.min-1 x 1.73 m-2, and patients with DTPA-GFR > 140 ml.min-1 x 1.73 m-2. RESULTS: For all patients, mean values for DTPA-GFR = 147 (95% confidence interval, 139-155), for KL/Cr = 118 (110-125), and for Cockroft-Gault = 84 ml.min-1 x 1.73 m-2 (78-90). For patients with DTPA-GFR < or = 140, DTPA-GFR = 123 (117-128), KL/Cr = 110 (100-119), and Cockroft-Gault = 92 (82-102). For patients with DTPA-GFR > 140, DTPA-GFR = 167 (158-177), KL/Cr = 125 (114-136), and Cockroft-Gault = 77 (71-84). Linear regression analysis showed significant (P < 0.05) relationships for KL/Cr only in patients with DTPA-GFR < or = 140 (r = 0.29), for Cockroft-Gault in all patients (r = -0.46), and for patients with DTPA-GFR < or = 140 (r = -0.31). Determination of a revised K for use in KL/Cr from individual calculations of K (DTPA-GFR x Cr/L) yielded an average value of 0.70 (SD = 0.11). With the use of K = 0.7, the mean KL/Cr value for patients with DTPA-GFR < or = 140 ml.min-1 x 1.73 m-2 was 125 +/- 27 (95% confidence interval, 115-135), compared with a DTPA-GFR value of 123 +/- 14 (95% confidence interval, 117-128). CONCLUSIONS: KL/Cr and Cockroft-Gault do not accurately estimate DTPA plasma clearance. We recommend the use of K equal to 0.70 when estimating GFR in children and adolescents with IDDM and DTPA-GFR < or = 140 using KL/Cr and do not recommend the use of the KL/Cr (for patients with DTPA-GFR > 140) or the Cockroft-Gault equation in this population.


Subject(s)
Body Height , Body Weight , Creatinine/blood , Diabetes Mellitus, Type 1/physiopathology , Glomerular Filtration Rate , Adolescent , Adult , Blood Pressure , Child , Diabetes Mellitus, Type 1/blood , Glycated Hemoglobin/analysis , Humans , Prognosis , Regression Analysis , Technetium Tc 99m Pentetate
12.
Clin Pediatr (Phila) ; 31(9): 542-5, 1992 Sep.
Article in English | MEDLINE | ID: mdl-1468171

ABSTRACT

Urinary growth hormone (GH) and insulin-like growth factor I (IGF-I) excretion profiles were compared in children receiving biosynthetic GH. Group 1 included 18 healthy controls. Group 2 included nine children given biosynthetic GH three times a week. Group 3 included 14 children given daily GH injections. Overnight urine samples were collected for three consecutive nights in all groups. No significant day-to-day variation in urinary GH output was observed in group 1. In group 2, urinary GH output was significantly higher on day one following injection than on days two and three. Urine GH outputs in group 2 were significantly lower on days two and three than the values observed on all days in group 3. Throughout the three-day study, subjects in group 3 excreted similar amounts of GH significantly higher than those of controls. Urinary IGF-I output (nmol/kg) was similar on all three study days in groups 1 and 3. Group 2 had significantly lower urinary IGF-I output on day three compared with day one. Urinary IGF-I output on day three was also significantly lower in group 2 than in group 3. We conclude that urinary GH and IGF-I outputs are influenced by the frequency of GH administration.


Subject(s)
Growth Hormone/urine , Insulin-Like Growth Factor I/urine , Adolescent , Body Weight , Child , Creatinine/urine , Female , Growth Hormone/administration & dosage , Humans , Injections, Subcutaneous , Male , Radioimmunoassay , Recombinant Proteins/administration & dosage
13.
Diabetes Care ; 15(4): 490-4, 1992 Apr.
Article in English | MEDLINE | ID: mdl-1499463

ABSTRACT

OBJECTIVE: To compare the urinary output of insulinlike growth factor I (IGF-I) and growth hormone (GH) in prepubertal and pubertal children with insulin-dependent diabetes mellitus (IDDM) versus nondiabetic subjects and to analyze the relationship between the urinary excretion of these peptides and degree of metabolic control. RESEARCH DESIGN AND METHODS: Group 1 included 30 IDDM patients who had had diabetes for 4.9 +/- 0.7 yr and had normal renal function (mean age 11.6 +/- 0.9 yr); group 2 consisted of 31 control subjects (mean age 9.2 +/- 0.6 yr). Sensitive radioimmunoassays were used to measure IGF-I and GH in urine aliquots from 12-h timed overnight collections that had been dialyzed, concentrated 50-fold, and lyophilized. RESULTS: Significantly lower IGF-I and GH outputs per kilogram body weight per 12 h were observed in IDDM subjects compared with control subjects. When data were expressed per kilogram of body weight, no difference was observed between the urinary output of IGF-I and GH between prepubertal and pubertal subjects within group 1 or group 2. The prepubertal children had significantly lower HbA1 than the pubertal population; however, no correlation was found between urinary output of IGF-I or GH and HbA1. A positive correlation was observed between urinary IGF-I and GH (r = 0.85, P less than .001). CONCLUSIONS: Patients with long-standing IDDM excrete significantly lower urinary levels of IGF-I and GH compared with normal subjects. Serial measurements of these peptides from onset of IDDM are needed to define whether the changes observed are present at diagnosis or are secondary to duration of disease.


Subject(s)
Diabetes Mellitus, Type 1/urine , Growth Hormone/urine , Insulin-Like Growth Factor I/urine , Puberty/urine , Child , Female , Humans , Male , Radioimmunoassay , Reference Values
14.
Pediatr Res ; 29(6): 619-22, 1991 Jun.
Article in English | MEDLINE | ID: mdl-1866220

ABSTRACT

Twelve-h overnight urine and serum samples obtained simultaneously at 20-min intervals were assayed for growth hormone (GH). Ninety-one children, 5 to 16 y (Tanner stage 1 to 3) participated; group 1 were healthy children, group 2 were children with organic GH deficiency, and group 3 had idiopathic growth failure and normal GH stimulation tests. Serum pool GH concentrations in group 1 were similar to those in group 3 (3.3 +/- 0.3 versus 3.4 +/- 0.2 micrograms/L); group 2 had significantly lower GH concentrations (1.6 +/- 0.2 micrograms/L). Plasma IGF-I levels were significantly greater in groups 1 (14.2 +/- 2.6 nmol/L, p less than 0.001) than in groups 2 and 3 (2.6 +/- 0.5 and 5.5 +/- 0.7 nmol/L, respectively). Urinary GH (mean +/- SEM) standardized for body weight (micrograms/kg) in group 1 (0.31 +/- 0.02) was significantly greater than in group 2 (0.14 +/- 0.01) and group 3 (0.20 +/- 0.01). However, when expressed as microgram/mol creatinine, the output of GH was similar in group 1 (4.0 +/- 0.3) and group 3 (3.4 +/- 0.3); both groups had significantly greater output compared to group 2 (1.3 +/- 0.2). Urinary IGF-I (nmol/kg) in group 1 (0.22 +/- 0.02) was significantly greater than in group 2 (0.12 +/- 0.01) or group 3 (0.07 +/- 0.01). Urinary GH correlated with serum pool GH concentration (r = 0.64, p less than 0.001). Although urinary GH output reflects endogenous GH secretion, the overlap between groups 1 and 3 precludes using urinary GH measurements as a diagnostic test for GH deficiency in children with idiopathic growth failure.


Subject(s)
Growth Disorders/urine , Growth Hormone/urine , Adolescent , Child , Child, Preschool , Female , Growth Disorders/blood , Growth Disorders/diagnosis , Growth Hormone/blood , Growth Hormone/deficiency , Humans , Insulin-Like Growth Factor I/metabolism , Insulin-Like Growth Factor I/urine , Male
15.
J Endocrinol Invest ; 14(5): 375-81, 1991 May.
Article in English | MEDLINE | ID: mdl-1908492

ABSTRACT

Since premature thelarche (PT) can be a first sign of precocious puberty (PP), the aim of our study was to identify simple items in the course of the first 6 months of follow-up that could help predict if PT would evolve to PP. Thirty-two girls with PT were studied. First evaluation included bone age (BA), basal estradiol, FSH, LH and prolactin. GnRH was performed in 15 subjects and BA was checked at 6 month intervals in 30. Based on clinical outcome after a mean follow-up of 33.4 +/- 16.5 (SD) months, patients were divided into 2 groups: Group I (G-I) included subjects whose breast development either remained unchanged, increased or regressed; Group II (G-II) included subjects who progressed to PP. The multivariate combination of the items which was able to best discriminate between the two groups was chosen in predicting the evolution of PT. The items considered included four variables available at the time of diagnosis [chronological (CA) at onset less than 3 years, basal FSH, basal LH and BA/CA ratio] and two additional variables after a 6-month follow-up (delta BA/delta CA and growth velocity); 88% of G-I and 14% of G-II had CA less than 3 yr. Basal FSH levels were elevated in both G-I (7.6 +/- 3.0 mIU/ml) and G-II (12.1 +/- 4.1) with respect to controls (2.6 +/- 1.2); however, approximately 20% of G-I had low FSH levels. Basal LH levels were consistently higher in G-II (8.0 +/- 1.3 mIU/ml) than in G-I (2.9 +/- 1.5) or controls (2.8 +/- 1.2). Although initial BA was advanced (greater than 2SD) in 21% of G-I and in all of G-II, an acceleration of BA was seen only in G-II. The mean growth velocity of G-I (44.1 +/- 31.5%) was significantly less than G-II (92 +/- 32%; p less than 0.0025). With the help of the discriminant equations derived from data obtained at diagnosis and during the first 6 months of follow-up, all subjects with isolated premature thelarche could be sharply distinguished from those who subsequently progressed to precocious puberty.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Breast/growth & development , Puberty, Precocious/epidemiology , Adolescent , Child , Discriminant Analysis , Estradiol/blood , Female , Follicle Stimulating Hormone/blood , Follow-Up Studies , Humans , Luteinizing Hormone/blood , Multivariate Analysis , Prognosis , Prolactin/blood , Puberty, Precocious/blood , Puberty, Precocious/pathology
16.
J Pediatr Psychol ; 15(6): 699-709, 1990 Dec.
Article in English | MEDLINE | ID: mdl-2283575

ABSTRACT

Management of infants born with ambiguous sex organs requires the close collaboration of a team of professionals: pediatric endocrinologist, pediatric psychologist, gynecologist, and surgeon. The interdisciplinary teamwork of a group of professionals is described in the case of a patient announced at birth as a male but within days reannounced and reared as a female. Over the next 21 years, she became completely aware of her endocrine condition, including its medical classification (male pseudohermaphroditism), her chromosomal (46 XY) and gonadal (testes) status, and her early history of male sex assignment. The clinical management described herein helped this person deal effectively with her condition despite unsuccessful reconstructive vagal surgery. Substantiation of this is provided by the patient's personal comments.


Subject(s)
Disorders of Sex Development/therapy , Adolescent , Adult , Child , Disorders of Sex Development/psychology , Disorders of Sex Development/surgery , Family Therapy , Female , Gender Identity , Humans , Infant, Newborn , Patient Care Team
17.
Pediatr Res ; 28(3): 209-12, 1990 Sep.
Article in English | MEDLINE | ID: mdl-2235116

ABSTRACT

The output of urinary growth hormone (GH) and IGF-I were quantitated by RIA in 12-h urine collections obtained from infants who were preterm, small for gestational age (PT-SGA, n = 13); preterm, appropriate for gestational age (PT-AGA, n = 27); full term, small for gestational age (FT-SGA, n = 13); and full term, appropriate for gestational age (FT-AGA, n = 29); and from normal children (n = 33). The amounts of GH and IGF-I (mean +/- SEM) excreted by the PT-SGA and FT-SGA infants were not significantly lower than those excreted by the PT-AGA and FT-AGA groups, respectively [GH (micrograms/kg): PT-SGA 13.7 +/- 3.1 versus PT-AGA 14.0 +/- 2.2, FT-SGA 7.8 +/- 2.4 versus FT-AGA 6.6 +/- 1.8; IGF-I (nmol/kg): PT-SGA 0.52 +/- 0.09 versus PT-AGA 0.53 +/- 0.04, FT-SGA 0.31 +/- 0.05 versus FT-AGA 0.35 +/- 0.04]. All infant groups exhibited significantly greater outputs of urinary GH and IGF-I compared with the children (p less than 0.01). The plasma concentrations of GH in all infant groups were high, whereas the plasma IGF-I levels were low. Microalbumin and beta-2 microglobulin excretion did not correlate with urinary GH and IGF-I output. Despite the higher microalbumin output in FT babies, urinary GH and IGF-I excretion was lower in these groups.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Growth Hormone/urine , Infant, Premature/urine , Infant, Small for Gestational Age/urine , Insulin-Like Growth Factor I/urine , Adolescent , Child , Child, Preschool , Female , Humans , Infant, Newborn , Male , Reference Values
18.
J Clin Endocrinol Metab ; 66(4): 792-7, 1988 Apr.
Article in English | MEDLINE | ID: mdl-3346357

ABSTRACT

Urinary GH and somatomedin-C/insulin-like growth factor I (Sm-C/IGF-I) excretion were measured in 12-h urine collections obtained from 43 infants (27 stable preterm infants and 16 healthy fullterm infants) and 31 normal children, aged 3-17 yr. Urinary Sm-C/IGF-I was excreted as the free hormone, since no binding of radiolabeled Sm-C/IGF-I to any urine protein with a mol wt similar to those described for plasma Sm-C/IGF-I-binding proteins was found. The preterm infants excreted significantly more urinary GH [13.5 +/- 2.1 (+/- SE) ng/kg.12 h] than either the fullterm infants (5.3 +/- 1.6 ng/kg.12h) or the children (0.27 +/- 0.02 ng/kg.12 h; P less than 0.01). The mean urinary Sm-C/IGF-I excretion in the preterm infants (98.9 +/- 7.5 mU/kg.12 h) was comparable to that in fullterm infants (87.6 +/- 9.7 mU/kg.12 h); both groups excreted significantly more urinary Sm-C/IGF-I than children (28.4 +/- 2.1 mU/kg.12 h; P less than 0.01). The group differences were similar when the results were expressed in terms of creatinine excretion. Urinary GH excretion correlated positively with urinary Sm-C/IGF-I excretion (r = 0.68). The higher output of these peptides in rapidly growing infants and their positive correlation in urine provide additional support for the Sm hypothesis.


Subject(s)
Growth Hormone/urine , Infant, Premature/urine , Insulin-Like Growth Factor I/urine , Somatomedins/urine , Adolescent , Child , Child, Preschool , Growth Hormone/blood , Humans , Infant , Infant, Newborn , Infant, Premature/blood , Insulin-Like Growth Factor I/blood
19.
Pediatr Res ; 23(1): 89-92, 1988 Jan.
Article in English | MEDLINE | ID: mdl-3340452

ABSTRACT

Urinary growth hormone (GH) excretion was quantitated in 12-h overnight urine collections obtained from 31 control children, ages 3 to 17 yr (group 1); 21 children, ages 5 to 19 yr with GH deficiency (group 2), and 30 subjects, ages 10 to 18 yr with idiopathic growth failure and normal GH stimulation tests (group 3). The output of urinary GH was measured in one acromegalic woman. The authenticity of urinary GH, 22 kDa, was confirmed by high-performance liquid chromatography. The elution pattern of urinary GH was identical to that of biosynthetic and pituitary-derived GH. The immunoreactive profiles characterized by monoclonal immunoradiometric GH assay and standard GH radioimmunoassay were identical. The quantity of GH (mean +/- SEM per kg body weight) in group 1 (0.27 +/- 0.02 ng/kg) was significantly greater than group 2 (0.08 +/- 0.02 ng/kg) or group 3 (0.17 +/- 0.02 ng/kg, p less than 0.01). Approximately 50% of the subjects in group 3 had urinary GH measurements indistinguishable from those observed in the GH-deficient population. Twelve hypopituitary patients (group 2) excreted significantly greater amounts of urinary GH in the first 12 h after GH administration compared to the baseline period (0.41 +/- 0.07 versus 0.12 +/- 0.02 ng/kg, p less than 0.01). Markedly elevated output of urinary GH (2.0 ng/kg) was documented in one acromegalic patient. The data suggest that measurements of urinary GH may be a useful, simple, and noninvasive screening test for identifying patients with GH deficiency or excess.


Subject(s)
Growth Disorders/urine , Growth Hormone/urine , Adolescent , Child , Child, Preschool , Chromatography, High Pressure Liquid , Creatinine/urine , Female , Growth Hormone/deficiency , Humans , Male
20.
J Clin Endocrinol Metab ; 65(6): 1168-71, 1987 Dec.
Article in English | MEDLINE | ID: mdl-3680479

ABSTRACT

The renal excretion of radioimmunoassayable somatomedin-C/insulin-like growth factor I (Sm-C/IGF-I) was measured in 12-h overnight urine samples obtained from 88 subjects, aged 3-19 yr. The participants included 34 healthy children (group 1), 29 children with idiopathic growth failure and normal GH stimulation tests (group 2), and 25 GH-deficient subjects (group 3). The mean (+/- SEM) urinary Sm-C/IGF-I excretion in group 1 (28.4 +/- 2.1 mU/kg) was significantly greater than that in group 2 (8.1 +/- 1.6 mU/kg) or group 3 (8.6 +/- 1.3 mU/kg). Twenty-two of the 29 subjects in group 2 had urinary Sm-C/IGF-I values less than 8 mU/kg. After the administration of biosynthetic GH to 12 GH-deficient subjects, urinary Sm-C/IGF-I excretion rose from 10.3 +/- 2.3 to 21.4 +/- 4.2 mU/kg within 12 h (P less than 0.05), indicating that renal excretion of Sm-C/IGF-I is GH dependent. One woman with acromegaly had markedly elevated urinary Sm-C/IGF-I excretion (420 mU/kg). The authenticity of urinary Sm-C/IGF-I was confirmed by high pressure liquid chromatography (HPLC). Assay of serial dilutions of urinary Sm-C/IGF-I demonstrated a direct proportionality between concentration and dilution. Although it is not possible to identify whether urinary Sm-C/IGF-I reflects local or generalized synthesis of the peptide, we hypothesize that quantitation of Sm-C/IGF-I in timed urine collections will yield additional information about GH production and action in children with normal and abnormal growth.


Subject(s)
Growth Disorders/urine , Insulin-Like Growth Factor I/urine , Somatomedins/urine , Adolescent , Adult , Body Height , Child , Child, Preschool , Chromatography, High Pressure Liquid , Female , Humans , Male , Puberty
SELECTION OF CITATIONS
SEARCH DETAIL
...