c-peptide and Growth-Disorders

Low-dose GH (LGH) therapy has been reported to improve insulin sensitivity in GH-deficient adults; however, the mechanism is unclear.. Effects of LGH therapy on insulin sensitivity are mediated through changes in cortisol metabolism and ectopic fat accumulation.. This was a double-blind, placebo-controlled, parallel, 3-month study.. Seventeen GH-deficient adults were randomized to receive either daily LGH or placebo injections. Fasting blood samples were collected at baseline, and months 1 and 3, whereas hyperinsulinemic-euglycemic clamps, magnetic resonance spectroscopy scans, 24-hour cortisol production rates (CPRs), and sc abdominal fat biopsies were performed at baseline and month 3.. Clamp glucose infusion rate, intramyocellular, extramyocellular, and intrahepatic lipid content, 24-hour CPRs, adipocyte size, and adipocyte 11β-hydroxysteroid dehydrogenase activity in adults with GH deficiency were evaluated.. At month 1, LGH did not alter fasting levels of glucose, insulin, C-peptide, free fatty acid, adiponectin, total IGF-1, IGF-1 bioactivity, IGF-2, IGF binding protein (IGFBP)-2, or IGF-1 to IGFBP-3 molar ratio. At month 3, LGH increased clamp glucose infusion rates (P < .01) and IGF-1 to IGFBP-3 molar ratio (P < .05), but fasting glucose, insulin, C-peptide, free fatty acid, adiponectin, IGF-1 bioactivity, IGF-2, IGFBP-2, 24-hour CPRs, adipocyte size, adipocyte 11β-hydroxysteroid dehydrogenase activity, intrahepatic lipid, extramyocellular, or intramyocellular were unchanged. In the placebo group, all within-group parameters from months 1 and 3 compared with baseline were unchanged.. Short-term LGH therapy improves insulin sensitivity without inducing basal lipolysis and had no effect on cortisol metabolism and ectopic fat accumulation in GH-deficient adults. This may reflect an LGH-induced increase in IGF-1 to IGFBP-3 molar ratio exerting insulin-like effects through the abundant muscle IGF-1 receptors, but this hypothesis requires confirmation with further studies.

Topics: 11-beta-Hydroxysteroid Dehydrogenase Type 1; Adipocytes; Adipose Tissue; Adult; Anthropometry; Blood Glucose; C-Peptide; Double-Blind Method; Female; Glucose Clamp Technique; Growth Disorders; Human Growth Hormone; Humans; Hydrocortisone; Insulin Resistance; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Male

To assess the effect of growth hormone (GH) treatment on body composition and insulin resistance, and the interdependence of these factors, in short children born small for gestational age (SGA) and children with growth hormone deficiency (GHD).. In this longitudinal study we describe the relationship between changes in fasting hormone levels, and forearm cross-sectional fat/muscle area in 54 short children with GHD and 37 short children born SGA during the first 12 months of GH treatment. Mean GH dose was 31.4 microg/kg/day for GHD and 53.2 microg/kg/day for SGA. HOMA2-IR was calculated as a steady-state fasting measure of insulin resistance.. At baseline the SGA group displayed higher fasting glucose, insulin, C-peptide serum levels and higher HOMA2-IR (p < 0.01) than GHD patients despite similar low muscle mass and less fat mass. Both groups had low muscle mass for height, and mean changes in muscle, fat, insulin, C-peptide and HOMA2-IR during GH treatment were also similar. HOMA2-IR correlated positively with IGF-1 changes in both groups. In the SGA group, but not in the GHD group, the increase in fasting serum insulin, C-peptide and HOMA2-IR correlated negatively with increase in muscle mass (R(2) = 0.32, p < 0.001) and decrease in fat mass (R(2) = 0.12, p = 0.034).. In SGA, unlike in GHD, the insulin resistance caused by GH treatment appears to be diminished by the GH-induced increase in muscle mass and decrease in fat mass.

Topics: Body Composition; C-Peptide; Child; Growth Disorders; Human Growth Hormone; Humans; Infant, Newborn; Infant, Small for Gestational Age; Insulin Resistance; Muscle, Skeletal

Digenic causes of human disease are rarely reported. Insulin via its receptor, which is encoded by INSR, plays a key role in both metabolic and growth signaling pathways. Heterozygous INSR mutations are the most common cause of monogenic insulin resistance. However, growth retardation is only reported with homozygous or compound heterozygous mutations. We describe a novel translocation [t(7,19)(p15.2;p13.2)] cosegregating with insulin resistance and pre- and postnatal growth deficiency. Chromosome translocations present a unique opportunity to identify modifying loci; therefore, our objective was to determine the mutational mechanism resulting in this complex phenotype.. Breakpoint mapping was performed by fluorescence in situ hybridization (FISH) on patient chromosomes. Sequencing and gene expression studies of disrupted and adjacent genes were performed on patient-derived tissues. RESULTS Affected individuals had increased insulin, C-peptide, insulin-to-C-peptide ratio, and adiponectin levels consistent with an insulin receptoropathy. FISH mapping established that the translocation breakpoints disrupt INSR on chromosome 19p15.2 and CHN2 on chromosome 7p13.2. Sequencing demonstrated INSR haploinsufficiency accounting for elevated insulin levels and dysglycemia. CHN2 encoding beta-2 chimerin was shown to be expressed in insulin-sensitive tissues, and its disruption was shown to result in decreased gene expression in patient-derived adipose tissue.. We present a likely digenic cause of insulin resistance and growth deficiency resulting from the combined heterozygous disruption of INSR and CHN2, implicating CHN2 for the first time as a key element of proximal insulin signaling in vivo.

Topics: Adult; Age of Onset; Antigens, CD; Biomarkers; Blood Glucose; C-Peptide; Chromosome Mapping; Chromosomes, Human, Pair 19; Chromosomes, Human, Pair 7; Diabetes Mellitus; DNA-Binding Proteins; Female; Fetal Growth Retardation; Gene Expression Regulation; Growth Disorders; Haplotypes; Humans; In Situ Hybridization, Fluorescence; Insulin; Insulin Resistance; Male; Pregnancy; Receptor, Insulin; Receptors, Steroid; Receptors, Thyroid Hormone; Sequence Analysis, DNA; Signal Transduction; Translocation, Genetic

Children with Cerebral Palsy (CP) are generally undernourished and growth retarded than normal children. The reasons of malnutrition are not only due to poor nutritional status but also nonnutritional factors including negative neurotrophic effects and indirect factor such as immobility, endocrinological abnormalities or spasticity that energy requirements might be contributing factors. Several studies indicated that leptin which is produced by adipocytes, might regulate energy intake and expenditure. The aim of this study is to determine serum leptin levels in children with CP and to investigate the relationship between nutritional status and anthropometric measurements.. Forty children with CP and 18 healthy controls were included in this study. The weight, height, body mass index (BMI), upper arm length (UAL) and triceps skinfold thickness (TST) was measured in all children. Serum leptin, growth hormone, C-peptide and cortisol levels were studied. Based on TST measurement CP patients were divided as DSF group (decreased subcutaneous fat) and non-DSF group (nondecreased subcutaneous fat).. UAL were shorter and TST measurements were thinner than control group (p<0.05, p<0.01). Group DSF had lower leptin concentrations compared to Group non-DSF and controls (p<0.001, p<0.001). On the other hand non DSF group had higher leptin levels than controls (p<0.05). There was a positive and significant correlation between leptin and anthropometric measurements, especially TST in children with CP. Serum leptin levels were also lower in non-ambulatory children than ambulatory children with CP (p<0.05).. This study has shown that triceps skinfold thickness is better index for the evaluation of nutritional status in children with CP. Serum leptin levels were lower in CP, especially in DSF group. The possible explanation of this finding may not only related with malnutrition, but also immobility related other factors such as bone metabolism and spasticity. We concluded that leptin which regulates energy intake might have a role of nutritional disorders in cerebral palsy. To better understand this relationship further studies are needed.

Topics: Adolescent; Anthropometry; C-Peptide; Cerebral Palsy; Child; Child Nutrition Disorders; Child, Preschool; Energy Metabolism; Female; Growth Disorders; Human Growth Hormone; Humans; Hydrocortisone; Leptin; Male; Nutritional Status

The pancreatic endocrine system normally guarantees a quick and efficient response to daily metabolic perturbations, but associated data for human immunodeficiency virus (HIV)-infected patients are lacking. A prospective study was performed to evaluate pancreatic endocrine secretion and its possible association with failure to thrive among HIV-infected children.. Fourteen well-nourished, prepubertal, HIV-infected children (6 boys and 8 girls; age range, 5-11 years), none of whom were receiving protease inhibitors, and 16 clinically healthy sex- and age-matched children formed the patient group and the control group, respectively. At yearly follow-up examinations, insulin, glucagon, C-peptide, and glucose levels were measured; the ratio of insulin to glucose, the ratio of insulin to glucagon, and the homeostasis model assessment (HOMA) index were calculated; the glucagon test was administered; and growth hormone, thyroid-stimulating hormone, adrenocorticotropic hormone, cortisol, and lipid patterns were evaluated.. Insulin, glucagon, C-peptide, glucose, and HOMA measurements were significantly higher among patients, compared with control subjects, at all 3 follow-ups performed to date. The glucagon test revealed a normal glycemic response in all the healthy control subjects and a significantly impaired response in 11 patients. A significant correlation emerged between the ratio of insulin to glucagon and the growth velocity of HIV-infected children.. To our knowledge, the present study provides the first evidence of altered pancreatic endocrine secretion and its association with growth failure among HIV-infected children.

Topics: Blood Glucose; C-Peptide; Child; Female; Glucagon; Growth Disorders; HIV Infections; Homeostasis; Hormones; Humans; Insulin; Lipids; Male; Pancreas; Prospective Studies

Growth hormone (GH) has well known effects on carbohydrate metabolism. We have evaluated the effects of long-term growth hormone (GH) therapy on carbohydrate metabolism in children with classical GH deficiency (GHD) or GH neurosecretory dysfunction (GHND).. Glucose, insulin and C-peptide concentrations at baseline and during oral glucose tolerance test (OGTT) were measured before and after 18 and 36 months of GH therapy (0.6-0.8 IU/Kg/week in 6 evening doses) in 13 GHD and 7 GHND children (15 boys and 5 girls, 15 prepubertal and 5 early pubertal; age at diagnosis 2.11-13.1 y).. Mean fasting insulin and C-peptide concentrations after 18 months were similar to the pretreatment values, while after 36 months they were significantly higher than before treatment. Fasting glucose concentrations were similar to pretreatment both after 18 and 36 months. The mean areas under the curve (AUC) during OGTT for glucose, insulin, and C-peptide were significantly increased after 18 and 36 months. There were no differences between GHD and GHND patients. During the treatment period 10 of the 15 prepubertal patients entered puberty. A significant increase of insulin and C-peptide concentrations occurred after 36 months of GH treatment in the patients that remained prepubertal during treatment as well as in those who were pubertal when treatment was started. In three of our patients GH treatment caused glucose intolerance, which resolved after 6-12 months of a normal calorie low-simple carbohydrate diet without requiring discontinuation of treatment.. Our data show that long-term GH treatment in GH deficient children causes hyperglycaemia and increased insulin secretion. These effects may in some patients induce glucose intolerance, which is reversible with appropriate dietary measures and does not require discontinuation of treatment.

Topics: Adolescent; Area Under Curve; Blood Glucose; C-Peptide; Carbohydrate Metabolism; Child; Child, Preschool; Female; Glucose Tolerance Test; Growth Disorders; Growth Hormone; Humans; Insulin; Male; Prospective Studies; Time Factors

To assess the effects of GH treatment on carbohydrate and protein metabolism, we studied eight patients with short stature before and after the commencement of GH treatment. The hyperglycemic clamp procedure was employed to produce a hyperglycemic stimulus of 50 mg/dL above fasting levels for 120 min. These patients were then treated with 0.3 mg/kg. week GH for 6 months, after which they were restudied. Patients were compared to eight healthy control children matched for age, sex, and Tanner stage. Fasting plasma glucose did not change significantly, but fasting plasma insulin levels were higher after GH therapy (P < 0.005). Despite identical glucose increments during the glucose clamp procedure, both first, and second phase insulin responses were markedly greater after instituting GH treatment. Even in the face of higher mean plasma insulin levels after GH treatment, the rate of insulin-stimulated glucose metabolism did not differ during the last 60 min of both studies. Hence, the rate of insulin-stimulated glucose metabolism/mean plasma insulin ratio (an index of insulin sensitivity) was sharply reduced after GH treatment (P < 0.01). During the clamp, the fall in circulating branched chain amino acid levels was significantly greater after GH therapy (P < 0.02). We conclude that glucose-stimulated insulin responses are increased in short children treated with GH and that such hyperinsulinemic responses compensate for reductions in insulin sensitivity. The compensatory hyperinsulinemic responses induced by GH therapy may serve a beneficial role by augmenting insulin's anabolic effects on protein metabolism.

Topics: Adaptation, Physiological; Adolescent; Amino Acids, Branched-Chain; Body Height; C-Peptide; Child; Female; Glucose Clamp Technique; Growth Disorders; Human Growth Hormone; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Male

A case of growth retardation in a bull is reported. Serum concentration of insulin-like-growth-factor-I, insulin-like-growth-factor-binding-protein-3, insulin, C-peptide, T3, T4, and fT4 were low compared with a normal growing bull in the same age. The causes of growth retardation are discussed.

Topics: Animals; C-Peptide; Cattle; Cattle Diseases; Growth Disorders; Insulin; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Male; Thyroid Hormones

It has been suggested that recombinant human IGF-I (rhIGF-I) is a potential therapeutic agent in diabetes mellitus. It is known to have glucose-lowering effects in normal individuals, in patients with non-insulin-dependent diabetes (NIDDM) and in extreme insulin-resistant states. IGF-binding proteins (IGFBPs) have the potential to affect the biological activity of rhIGF-I. We have studied the effect of infused rhIGF-I on IGFBP-1 and IGFBP-3 in a patient with Mendenhall's syndrome, a rare insulin-resistant state. During an infusion of 20 mg rhIGF-I, glucose concentrations fell from 44.1 +/- 7.2 to 31.5 +/- 7.2 (S.E.M.) mmol/l (P = 0.001), and insulin and C-peptide levels fell from 920 +/- 62 to 542 +/- 45 mU/l (P = 0.008) and 5466 +/- 633 to 3071 +/- 297 pmol/l (P = 0.02) respectively. Significant lowering of phosphate, magnesium and alkaline phosphatase concentrations was also noted. IGF-I levels rose from 48 +/- 10.2 to 410 +/- 50.1 micrograms/l (P = 0.001), and those of IGF-II fell from 279.8 +/- 8.3 to 104.3 +/- 7.9 micrograms/l (P = 0.001). IGFBP-1 concentrations did not significantly change during the infusion but those of IGFBP-3 increased from 1655 +/- 127 to 2197 +/- 334 micrograms/l (P = 0.002), despite a significant fall in GH concentrations from 10.7 +/- 2.6 to 4.1 +/- 1.1 mU/l (P = 0.007), suggesting that IGFBP-3 regulation is also IGF-I-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acanthosis Nigricans; Adolescent; Blood Glucose; C-Peptide; Carrier Proteins; Diabetes Mellitus; Growth Disorders; Humans; Insulin; Insulin Resistance; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Male; Syndrome

Cockayne syndrome is a rare autosomal recessive disorder of childhood characterized by cachectic dwarfism with senile-like appearance, mental retardation, photosensitive dermatitis, loss of adipose tissue, pigmentary degeneration of retina, microcephaly, deafness, skeletal and neurologic abnormalities. We describe here an 18 year old boy with Cockayne syndrome who had, in addition to the typical features of the disorder, fasting hyperinsulinemia and growth hormone deficiency.

Topics: Adolescent; C-Peptide; Cockayne Syndrome; Growth Disorders; Growth Hormone; Humans; Hyperinsulinism; Insulin; Male; Optic Atrophy; Retinal Degeneration