c-peptide and Fetal-Growth-Retardation

We aimed to identify critical periods and specific longitudinal growth patterns from fetal life onwards associated with childhood insulin and C-peptide levels.. In a prospective population-based cohort study of 4328 children, we repeatedly measured (femur) length and (estimated fetal) weight from the second trimester of fetal life until 6 years of age. BMI was calculated from 6 months onwards. Insulin and C-peptide levels were measured at 6 years of age.. Preterm birth and small or large size for gestational age at birth were not associated with childhood insulin levels. Conditional growth modelling showed that, independent of growth in other time intervals, weight growth in each time interval from birth onwards, length growth from 6 months onwards and BMI growth from 12 months onwards were positively associated with childhood insulin levels. The strongest associations were present for weight and BMI growth between 48 and 72 months of age. Repeated measurement analyses showed that, compared with children in the lowest quartile of childhood insulin, those in the highest quartile had a higher length from birth onwards and a higher weight and BMI from 24 months onwards. These differences increased with age. No associations were observed for fetal growth characteristics. Similar results were observed for C-peptide levels.. Our results suggest that rapid length, weight and BMI growth from birth onwards, but not during fetal life, is associated with higher insulin levels in childhood.

Topics: Adult; Body Mass Index; C-Peptide; Female; Fetal Development; Fetal Growth Retardation; Gestational Age; Humans; Insulin; Male; Pregnancy; Pregnancy Trimesters; Prospective Studies

Inadequate nutrition supply during the period of intrauterine growth and the first year of life leads to persistent metabolic changes and provokes development of various diseases.. Тo compare physical development, body composition, and hormonal status (insulin, insulin-like growth factor-1 (IGF-1), somatotropic hormone (STH), C-Peptide, cortisol) indices in premature infants born with intrauterine growth restriction (IUGR) at the term corrected age with the same indices in mature infants with IUGR and premature infants with weight appropriate for their gestational age (GA).. А crossover study of anthropometric measures, body composition and growth hormones changes assessment was carried out. It included 140 premature infants with weight appropriate for their GA, 58 premature infants with IUGR and 64 mature infants with IUGR. Anthropometric measures were assessed with Fenton and Anthro growth charts (WHO, 2009); body composition was studied with the air plethysmography method (РЕA POD, LMi, USA). Level of hormones in blood serum was assessed with biochemical methods.. It is found that anthropometric measures in premature infants with weight appropriate for their GA and premature infants with IUGR at the term corrected age did not have any significant differences while premature infants with IUGR tended to have lower weight. Studying body composition we found that both groups of premature infants had slightly higher level of fat mass in comparison with mature infants. High concentration of insulin, cortisol, IGF-1, and C-peptide was found in premature and mature infants with IUGR. Instead, lower levels of STH was found in infants with IUGR. Formula fed premature infants (comparing to breastfed ones) had higher levels of fat mass, insulin, IGF-1, and C-peptide. Mature infants with IUGR did not tend to have the correlation between levels of fat mass, insulin, IGF-1, C-peptide, and type of feeding.. Not only insufficient intrauterine growth but also nutrition pattern plays important role in development of body composition disbalance and hormonal shifts in premature infants.

Topics: Anthropometry; C-Peptide; Female; Fetal Growth Retardation; Gestational Age; Humans; Hydrocortisone; Infant, Newborn; Infant, Premature; Insulin; Insulin-Like Growth Factor I; Male; Nutritional Status; Statistics as Topic

Poor fetal growth, also known as intrauterine growth restriction (IUGR), is a worldwide health concern. IUGR is commonly associated with both an increased risk in perinatal mortality and a higher prevalence of developing chronic metabolic diseases later in life. Obesity, type 2 diabetes or metabolic syndrome could result from noxious "metabolic programming." In order to better understand early alterations involved in metabolic programming, we modeled IUGR rat pups through either prenatal exposure to synthetic glucocorticoid (dams infused with dexamethasone 100 µg/kg/day, DEX) or prenatal undernutrition (dams feeding restricted to 30% of ad libitum intake, UN). Physiological (glucose and insulin tolerance), morphometric (automated tissue image analysis) and transcriptomic (quantitative PCR) approaches were combined during early life of these IUGR pups with a special focus on their endocrine pancreas and adipose tissue development. In the absence of catch-up growth before weaning, DEX and UN IUGR pups both presented basal hyperglycaemia, decreased glucose tolerance, and pancreatic islet atrophy. Other early metabolic defects were model-specific: DEX pups presented decreased insulin sensitivity whereas UN pups exhibited lowered glucose-induced insulin secretion and more marked alterations in gene expression of pancreatic islet and adipose tissue development regulators. In conclusion, these results show that before any catch-up growth, IUGR rats present early physiologic, morphologic and transcriptomic defects, which can be considered as initial mechanistic basis of metabolic programming.

Topics: Adipose Tissue; Analysis of Variance; Animals; Blood Glucose; Blotting, Western; Body Weights and Measures; C-Peptide; Corticosterone; Dexamethasone; DNA Primers; Female; Fetal Growth Retardation; Gene Expression Profiling; Insulin; Insulin Resistance; Islets of Langerhans; Leptin; Malnutrition; Pregnancy; Prenatal Exposure Delayed Effects; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction

Obesity and its associated comorbidities are of major worldwide concern. It is now recognized that there are a number of metabolically distinct pathways of obesity development. The present paper investigates the effect of moderate daily exercise on the underlying mechanisms of one such pathway to obesity, through interrogation of metabolic flexibility. Pregnant Wistar rats were either fed chow ad libitum or undernourished throughout pregnancy, generating control or intrauterine growth restricted (IUGR) offspring, respectively. At 250 d of age, dual-emission x-ray absorptiometry scans and plasma analyses showed that moderate daily exercise, in the form of a measured amount of wheel running (56 m/d), prevented the development of obesity consistently observed in nonexercised IUGR offspring. Increased plasma C-peptide and hepatic atypical protein kinase Czeta levels explained increased glucose uptake and increased hepatic glycogen storage in IUGR offspring. Importantly, whereas circulating levels of retinol binding protein 4 were elevated in obese, nonexercised IUGR offspring, indicative of glucose sparing without exercise, retinol binding protein 4 levels were normalized in the exercised IUGR group. These data suggest that IUGR offspring have increased flexibility of energy storage and use and that moderate daily exercise prevents obesity development through activation of distinct pathways of energy use. Thus, despite a predisposition to develop obesity under sedentary conditions, obesity development was prevented in IUGR offspring when exercise was available. These results emphasize the importance of tailored lifestyle changes that activate distinct pathways of metabolic flexibility for obesity prevention.

Topics: Animal Feed; Animals; Blood Glucose; Body Composition; C-Peptide; Diet, Reducing; Energy Intake; Female; Fetal Growth Retardation; Insulin; Leptin; Lipids; Obesity; Physical Conditioning, Animal; Pregnancy; Rats; Rats, Wistar; Retinol-Binding Proteins, Plasma

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

Obesity and type 2 diabetes are worldwide health issues. The present paper investigates prenatal and postnatal pathways to obesity, identifying different metabolic outcomes with different effects on insulin sensitivity and different underlying mechanisms involving key components of insulin receptor signaling pathways. Pregnant Wistar rats either were fed chow ad libitum or were undernourished throughout pregnancy, generating either control or intrauterine growth restricted (IUGR) offspring. Male offspring were fed either standard chow or a high-fat diet from weaning. At 260 d of age, whole-body insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp, and other metabolic parameters were measured. As expected, high-fat feeding caused diet-induced obesity (DIO) and insulin resistance. Importantly, the insulin sensitivity of IUGR offspring was similar to that of control offspring, despite fasting insulin hypersecretion and increased adiposity, irrespective of postnatal nutrition. Real-time PCR and Western blot analyses of key markers of insulin sensitivity and metabolic regulation showed that IUGR offspring had increased hepatic levels of atypical protein kinase C zeta (PKC zeta) and increased expression of fatty acid synthase mRNA. In contrast, DIO led to decreased expression of fatty acid synthase mRNA and hepatic steatosis. The decrease in hepatic PKC zeta with DIO may explain, at least in part, the insulin resistance. Our data suggest that the mechanisms of obesity induced by prenatal events are fundamentally different from those of obesity induced by postnatal high-fat nutrition. The origin of insulin hypersecretion in IUGR offspring may be independent of the mechanistic events that trigger the insulin resistance commonly observed in DIO.

Topics: Animal Feed; Animals; Blood Glucose; C-Peptide; Caloric Restriction; Diabetes, Gestational; Dietary Fats; Female; Fetal Growth Retardation; Fetal Nutrition Disorders; Glucose Clamp Technique; Glycogen; Hyperinsulinism; Insulin; Insulin Resistance; Insulin Secretion; Lipid Metabolism; Liver; Male; Muscle, Skeletal; Obesity; Phosphoenolpyruvate Carboxykinase (GTP); Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar

Intrauterine growth retardation (IUGR) is a major cause of short stature in childhood. Most but not all children experience catch-up growth by 2 years of age.. We investigated the endocrine profile (thyroid function, prolactin, cortisol, C-peptide and insulin-like growth factor-I [IGF-IJ levels) of 57 children with IUGR, aged 2-10 years, and compared it with 30 controls whose birth weight was appropriate-for-gestational-age.. The hormonal profile for both groups was similar for thyroid hormones, prolactin, C-peptide and IGF-I. Cortisol levels were significantly lower in the IUGR group compared to controls (p <0,05). When the IUGR group was divided into 'catch-up' growth and 'non-catch-up' subgroups, the latter had significantly lower IGF-I levels (p <0.001).. Lower cortisol levels in children born with IUGR may reflect impaired function of the hypothalamic-pituitary-adrenal axis associated with this condition. The significantly lower IGF-I levels of the 'non-catch-up' subgroup may be involved in their failure to grow.

Topics: C-Peptide; Child; Child, Preschool; Female; Fetal Growth Retardation; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Insulin-Like Growth Factor I; Male; Pituitary-Adrenal System; Prolactin; Prospective Studies; Thyroid Hormones

To investigate different factors related to fetal growth restriction (FGR) and to find out the possible causes of FGR with unclear etiologies.. Sixty-three women who were suspected of FGR during pregnancy between March 2002 and March 2003 were included in this study. Their age, body mass index (BMI) before pregnancy, and gestational weeks were recorded at the time when they were first diagnosed. Haemoglobin levels, haematocrit (HCT), TORCH, anticardiolipin antibody (ACA), 50 gram glucose challenge test (50g GCT), 75 gram oral glucose tolerance test (75g OGTT), leptin levels, systolic/diastolic (S/D) ratio by color doppler monitor and chlamydia trachomatis (CT) were detected and urine culture was done in these groups during the same period. The gestational week, birth weight, body length and the gender were recorded at the delivery period. The FGR group was then divided into two subgroups according to the birth weights: study A group whose birth weights were lower than 10th% of the birth weights at the given gestational weeks (29 cases) and study B group whose birth weights were beyond 10th% (34 cases). The chromosome, leptin, C-peptide, insulin and TORCH of umbilical blood were measured at delivery. The other 25 normal pregnant women were included as control and the same tests were performed accordingly.. The fasting glucose and the third hour's glucose of 75 gram oral glucose tolerance test of study A were (3.8 +/- 0.6) mmol/L and (4.5 +/- 1.1) mmol/L. The fetal leptin, C-peptide, and insulin were (7.3 +/- 5.2) ng/ml, (0.5 +/- 0.3) nmol/L and (2.3 +/- 1.3) mU/L. The S/D ratio of umbilical artery, maternal and fetal infection rate of CMV, positive rate of ACA-IgM and the rate of asymptomatic bacteriuria were 3.06, 20.7%, 24.1%, 44.8% and 62.1% respectively. The fasting glucose and the third hour's glucose of 75 gram oral glucose tolerance test of study B were (4.4 +/- 0.7) mmol/L and (4.6 +/- 1.1) mmol/L. The fetal leptin, C-peptide, and insulin were (13.2 +/- 11.3) ng/ml, (0.7 +/- 0.4) nmol/L and (4.3 +/- 3.3) mU/L. The S/D ratio of umbilical artery, maternal and fetal infection rate of CMV, positive rate of ACA-IgM and the rate of asymptomatic bacteriuria were 2.63, 2.9%, 0%, 5.9% and 44.1% respectively. The fasting glucose and the third hour's glucose of 75 gram oral glucose tolerance test in control were (4.3 +/- 0.7) mmol/L and (5.3 +/- 1.2) mmol/L. The fetal leptin, C-peptide, and insulin were (20.5 +/- 12.0) ng/ml, (1.0 +/- 0.4) nmol/L and (6.3 +/- 4.0) mU/L. The S/D ratio of umbilical artery, maternal and fetal infection rate of CMV, positive rate of ACA-IgM and the rate of the asymptomatic bacteriuria were 2.80, 0, 0, 0 and 24.0% respectively. All these items were significantly higher in study A than those in the control (P < 0.05). There was no significant difference between the study B and the control in all the items.. Many factors may play a role in the pathogenesis of FGR, including the maternal blood glucose level, the ability for fetus to use the glucose, the infection of some microorganisms, insufficiency of the blood supply and the autoimmunity of the mother. Finding out the possible causes of FGR and managing them accordingly may improve the outcomes of the fetus.

Topics: Adult; Birth Weight; C-Peptide; Cytomegalovirus Infections; Female; Fetal Growth Retardation; Glucose Metabolism Disorders; Glucose Tolerance Test; Humans; Insulin; Leptin; Pregnancy; Pregnancy Outcome; Risk Factors

To study the insulin resistance in the pathogenesis of pregnancy induced hypertension (PIH), and its relationship to perinatal outcome.. In 111 PIH and 155 control group, the concentration of C peptide and insulin of maternal blood samples before and after 32 gestational weeks, and fetal blood samples just after delivery was determined. Fetal outcomes were assessed by the neonatal weight at delivery, Apgar scores and the quality and quantity of amniotic fluid.. The maternal concentration of C peptide and insulin in PIH was higher than that of control group (P < 0.05, or P < 0.01). In PIH group, the maternal concentration of C peptide and insulin in the subgroup of adverse perinatal outcomes tended to be higher than that in the subgroup of good perinatal outcomes; but in control group, there was no significantly difference between these two subgroups.. Insulin resistance may be one of the factors which couse PIH, and it has significant relationship with advese perinatal outcomes.

Topics: Adult; C-Peptide; Female; Fetal Growth Retardation; Humans; Insulin; Insulin Resistance; Pre-Eclampsia; Pregnancy; Pregnancy Outcome

Our purpose was to examine the regulation of fetal serum concentrations of insulin (C-peptide), insulin-like growth factor-I, insulin-like growth factor-II, and insulin-like growth factor binding protein-1, which are growth-regulating factors in the fetus, in monozygotic and dizygotic twin pairs.. Cord serum samples were collected from 110 twin pairs and compared with 178 nonsibling singleton pairs with the same gestational age. Five twin pairs were excluded from the statistical analyses because of severe intrauterine growth restriction and placental abnormalities in one. Zygosity was assigned by histologic examination of the placenta and by a questionnaire sent to the mother when the twins were > or = 6 months old. Analyses included the calculation of correlation coefficients, between-pair variation, and univariate genetic analysis.. Cord serum C-peptide concentrations were highly correlated in monozygotic (r = 0.94) and dizygotic twins (r = 0.79) but not in singleton pairs (r = -0.05); the between-pair variation was also smaller in twins than in singletons. Genetic analysis demonstrated a large contribution of the common environment to the variance in C-peptide concentrations (80%) and a smaller genetic contribution (12%). Insulin-like growth factor-I concentrations were better correlated in monozygotic (r = 0.82) than in dizygotic twins (r = 0.42), with a smaller between-pair variation in the former group (22% +/- 4% vs 51% +/- 5%). Univariate genetic analysis indicated that insulin-like growth factor-I levels were regulated predominantly by genetic mechanisms (93% in boys and 77% in girls). The regulation of insulin-like growth factor-II was more complex, with a gender-specific genetic contribution (50% for both sexes combined, 63% for girls but only 5% for boys). Insulin-like growth factor binding protein-1 was regulated by genetic mechanisms (41%) and the common environment (32%) but also by the specific or unique environment of each fetus (27%). In all five twins with intrauterine growth restriction of one member insulin-like growth factor binding protein-1 concentrations were markedly higher in the growth-restricted fetus.. Insulin secretion in twin fetuses is determined primarily by their common, probably maternal, environment, whereas insulin-like growth factor-I production is predominantly genetically regulated. Insulin-like growth factor-II and insulin-like growth factor binding protein-1 are regulated by both genetic and environmental factors. Of these growth-regulating factors, insulin-like growth factor binding protein-1 appears to be the best marker of intrauterine growth restriction in the individual case.

Topics: C-Peptide; Environment; Female; Fetal Blood; Fetal Growth Retardation; Genetics; Gestational Age; Humans; Infant, Newborn; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Male; Sex Factors; Twins

Topics: C-Peptide; Female; Fetal Growth Retardation; Humans; Infant, Newborn; Insulin; Islets of Langerhans; Male; Proinsulin; Radioimmunoassay; Retrospective Studies

Insulin, proinsulin and C-peptide responses to intravenous glucose (glucose infusion test, GIT) and insulin sensitivity were measured in women who previously and for unexplained reasons gave birth to small-for-gestational-age infants (SGA, n = 10) or appropriate-for-gestational-age infants (AGA, n = 11). Insulin sensitivity was evaluated by two different methods, somatostatin-, insulin- and glucose infusion test (SIGIT) and Bergman's minimal model method applied to the frequently samples intravenous glucose tolerance test. The two groups were comparable with regard to age, parity and body mass index. The SGA group exhibited significantly (p < 0.01) lower early (0-10 min) and late (10-60 min) insulin, C-peptide and proinsulin responses during GIT than were seen in the control AGA group. Insulin sensitivity evaluated by the two techniques was increased in the SGA group, significantly so only with the minimal model method. The insulin sensitivity index (Si) according to Bergman was 10.98 +/- 2.10 in the SGA as compared to 4.36 +/- 1.18 x 10(-4)min-1 x uU-1 in the AGA group (antilogged values +/- 95% confidence intervals). Early insulin response (GIT) and Si values were inversely correlated (r = -0.48, p < 0.05).

Topics: Adult; C-Peptide; Female; Fetal Growth Retardation; Glucose; Glucose Tolerance Test; Humans; Infant, Newborn; Infant, Small for Gestational Age; Insulin; Islets of Langerhans; Proinsulin; Somatostatin

The content of hormones that regulate carbohydrate metabolism was studied during the early neonatal period in 80 full-term neonates with intrauterine hypotrophy. Early application to the breast (2 to 6 hours after the birth) was shown to promote the normalization of the hormonal content. The levels of blood serum C-peptide in the newborn depend on the degree of the rise of the mother's body weight during pregnancy and the presence of toxicosis. The levels of cortisol, somatotropic hormone, immunoreactive insulin and C-peptide were determined by the degree of morphological immaturity of the tissues whereas the content of STH and cortisol by the intensity of hypotrophy as well. The moment of the birth and the early neonatal period of children with intrauterine hypotrophy is characterized by a decrease of the activity of lactate dehydrogenase, alpha-hydroxybutyrate dehydrogenase, creatine kinase and aspartate aminotransferase.

Topics: Blood Glucose; C-Peptide; Female; Fetal Growth Retardation; Growth Hormone-Releasing Hormone; Humans; Hydrocortisone; Hypoglycemia; Infant, Newborn; Infant, Newborn, Diseases; Insulin; Oxidoreductases; Pregnancy

The interrelationship between amniotic fluid (AF) concentration and content (AF X conc) of C-peptide and cortisol was studied in four groups of women comprising 10 gestational and 16 type-I diabetics, 11 women with intrauterine growth retarded fetuses (IUGR), and 17 healthy control women. Mean AF volume was significantly greater (P less than 0.05) in the type-I diabetic group than in the control group. Both concentration and content of AF C-peptide was significantly higher in the type-I diabetic group than in the control group (P less than 0.05 and P less than 0.01, respectively). The corresponding values were significantly lower in mothers with IUGR fetuses compared to controls (P less than 0.05). AF cortisol content was significantly higher (P less than 0.05) in the gestational diabetic group compared to the control group; there were no other significant differences between the groups regarding the cortisol concentration or content. Both cortisol and C-peptide contents were significantly interrelated in both control women (r = 0.68, P less than 0.01) and women with gestational (r = 0.68, P less than 0.05) and type-I diabetes (r = 0.63, P less than 0.01). The C-peptide/cortisol ratio was lowest in the IUGR group and highest in the type-I diabetic group. The same ratio was intermediate and almost equal in the control and gestational diabetic group. Both C-peptide and cortisol concentrations were unrelated to AF volume as well as infant birthweight. C-peptide content was significantly correlated to birthweight percentile in type-I diabetic women (r = 0.61, P less than 0.05). No such correlation was found in the three other groups.

Topics: Amniotic Fluid; Birth Weight; C-Peptide; Diabetes Mellitus, Type 1; Female; Fetal Growth Retardation; Fetus; Gestational Age; Humans; Hydrocortisone; Infant, Newborn; Pregnancy; Pregnancy in Diabetics

Topics: Amniotic Fluid; C-Peptide; Fatty Acids; Female; Fetal Growth Retardation; Gestational Age; Humans; Phosphatidylcholines; Pregnancy

Topics: Amniotic Fluid; Animals; Blood Circulation; C-Peptide; Disease Models, Animal; Female; Fetal Growth Retardation; Insulin; Insulin Secretion; Peptides; Placenta; Pregnancy; Rats; Uterus

Topics: Amniotic Fluid; C-Peptide; Female; Fetal Growth Retardation; Humans; Infant, Newborn; Peptides; Pregnancy; Pregnancy Trimester, Second; Pregnancy Trimester, Third