Delayed-onset paraparesis in Lassa fever: A case report.

Lassa fever (LF) is an endemic viral hemorrhagic fever in West Africa. Among the serious complications of the disease are neurological manifestations whose spectrum is incompletely known. Here we report the case of a 61-year-old man who developed a delayed-onset paraparesis a few weeks after getting infected with Lassa virus, thereby suggesting a possible association between LF and spinal cord disorders.

European survey on national training activities in clinical research.

BACKGROUND: Investigator-initiated clinical studies (IITs) are crucial to generate reliable evidence that answers questions of day-to-day clinical practice. Many challenges make IITs a complex endeavour, for example, IITs often need to be multinational in order to recruit a sufficient number of patients. Recent studies highlighted that well-trained study personnel are a major factor to conduct such complex IITs successfully. As of today, however, no overview of the European training activities, requirements and career options for clinical study personnel exists. METHODS: To fill this knowledge gap, a survey was performed in all 11 member and observer countries of the European Clinical Research Infrastructure Network (ECRIN), using a standardised questionnaire. Three rounds of data collection were performed to maximize completeness and comparability of the received answers. The survey aimed to describe the landscape of academic training opportunities, to facilitate the exchange of expertise and experience among countries and to identify new fields of action. RESULTS: The survey found that training for Good Clinical Practice (GCP) and investigator training is offered in all but one country. A specific training for study nurses or study coordinators is also either provided or planned in ten out of eleven countries. A majority of countries train in monitoring and clinical pharmacovigilance and offer specific training for principal investigators but only few countries also train operators of clinical research organisations (CRO) or provide training for methodology and quality management systems (QMS). Minimal requirements for study-specific functions cover GCP in ten countries. Only three countries issued no requirements or recommendations regarding the continuous training of study personnel. Yet, only four countries developed a national strategy for training in clinical research and the career options for clinical researchers are still limited in the majority of countries. CONCLUSIONS: There is a substantial and impressive investment in training and education of clinical research in the individual ECRIN countries. But so far, a systematic approach for (top-down) strategic and overarching considerations and cross-network exchange is missing. Exchange of available curricula and sets of core competencies between countries could be a starting point for improving the situation.

[Well-being in adulthood of patients with chronic conditions in childhood: The GEDEPAC-2 questionnaire]. / Bien-être à l'âge adulte des enfants atteints de maladies chroniques : le questionnaire GEDEPAC-2.

BACKGROUND: In France, chronic diseases affect 3 million children. In children with chronic conditions, long-term somatic outcome has been well described, but little is known about the psychosocial aspects of well-being. METHODS: Our aim was to build a self-administered questionnaire of global well-being in adults who had a chronic disease since or during childhood using a multidimensional and nonspecific approach. The questionnaire was constructed by a multidisciplinary group (epidemiologists, clinicians, sociologist, statistician). Items were built in compliance with reference data from the French general population (national surveys, free access) to allow comparative analysis adjusted for age and sex (and eventually other confounding factors) by indirect standardization (qualitative variables) or Z-scores (quantitative variables). RESULTS: The GEDEPAC-2 includes 108 items exploring 11 domains: education, employment, housing, material security, social links, civic engagement, leisure, environment, physical health/risky behavior, health-related quality of life and sex life. Factual questions and satisfaction scales jointly explore social well-being. Quality of life is analyzed in terms of physical quality of life, mental quality of life, fatigue and burden of treatment by 3 questionnaires validated in French (SF-12; MFI-20; Burden of Treatment Questionnaire). Experience of transition from pediatric to adult healthcare is described in 21 items. Paper and electronic versions were developed. CONCLUSION: Built in a multidimensional approach to well-being and in line with the available reference data, GEDEPAC-2 will facilitate the implementation of future studies on impact in adulthood of chronic disease in childhood.

Long-term impact of childhood-onset type 1 diabetes on social life, quality of life and sexuality.

AIM: This study describes the socio-professional outcomes, health-related quality of life (HRQOL) and sexuality of adults with childhood-onset type 1 diabetes (T1D). METHODS: The study participants (n=388), recruited from a nationwide registry (age: 28.5 ± 3.1 years; T1D duration: 17.0 ± 2.7 years), completed a questionnaire (198 items); the results were compared with the French general population using standardized incidence ratios (SIRs) and Z scores matched for age, gender and period with/without education levels and patterns of family life. Linear regression models also investigated correlates of SF-36 Physical (PCS) and Mental Composite Scores (MCS). RESULTS: Compared with the French general population, education levels of people with T1D were similar, with 68.6% having at least a high-school diploma or higher (SIR: 1.06, 95% CI: 0.93; 1.20), as were also their patterns of family life. Unemployment was higher in T1D women (15.3%, SIR: 1.50, 1.00; 2.05), but not in T1D men (8.6%, SIR: 0.96, 0.51; 1.57). Social discrimination was more common (SIR: 5.64, 4.64; 6.62), and frequency of daily alcohol consumption was higher (SIR: men, 3.34, 2.38; 4.54; women, 6.53, 4.57; 12.99). PCS and MCS were decreased moderately (mean ± SD: 52.0 ± 7.5; mean Z score: -0.2, 95% CI: -0.3; -0.1) and substantially (mean ± SD: 42.1 ± 12.4; mean Z score: -0.7, -0.8; -0.6), respectively. Fatigue and abandoning sports were predictive of a lower HRQOL. Both men and women were more frequently dissatisfied with their sex life. Prevalence of sexual problems was higher in women (SIR for: dysorgasmia, 1.91, 1.21-2.88; decreased/loss of desire: 2.11, 1.35-3.08), but similar in men. Participants with T1D-related complications had preserved social outcomes, but altered HRQOL. CONCLUSION: Young adults with T1D have satisfactory social participation. However, their higher alcohol consumption, lower MCS and frequent dissatisfaction with sexuality suggest a heavy impact of the disease on morale, especially in women. Improving the everyday well-being of these young adults represents a key challenge for diabetes healthcare.

[Ketoacidosis at time of diagnosis of type 1 diabetes in children and adolescents: effect of a national prevention campaign]. / Effet à un an de la campagne nationale de prévention de l'acidocétose au moment du diagnostic de diabète de type 1 chez l'enfant et l'adolescent.

The aim of the study was to evaluate, after the first year of a national information campaign, the effect on the frequency and severity of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes (T1D) in children and adolescents in France. The following data were collected during a 2-year period in people younger than 15 years of age at diagnosis of T1D, in 146 pediatric centers: age, sex, duration of symptoms, patient's previous care, clinical and biological signs, and family history of T1D. DKA was defined as pH<7.30 or bicarbonate<15mmol/L, severe DKA as pH<7.10 or bicarbonate <5mmol/L. During the 2nd year, an information campaign targeting health professionals and families was launched with the objective of reducing the time to diagnosis. Data were compared between the year before the campaign (year 0) and the first year of the campaign (year 1). The number of new cases of T1D was 1299 for year 0 and 1247 for year 1. Between year 0 and year 1, the rate of DKA decreased from 43.9% to 40.5% (P=0.08), exclusively due to the decrease of severe DKA from 14.8 to 11.4% (P=0.01). In the 0- to 5-year-old and 5- to 10-year-old age groups, the relative decrease in the rate of DKA was 13% and 15%, and 23% and 41% for severe DKA, respectively. In patients referred to the hospital by a pediatrician or who came at the family's initiative, the decrease was 34% and 7%, and 39% and 32% for severe DKA, respectively. No change was observed in the 10- to 15-year-old group or in those children who were referred by a general practitioner. In multivariate analyses, a higher DKA rate was associated with the young age of the child (<5 years), being hospitalized at the parents' initiative rather than being referred by a doctor, and the absence of a family history of T1D. A higher rate of severe DKA was associated with these last two factors but not with the child's age. The frequency of DKA at diagnosis of type 1 diabetes remains high in children and adolescents, but the first year of an information campaign decreased it. The results have also helped better define the strategy and targets of the continuing prevention campaign, to more efficiently reduce the morbidity and mortality of T1D at diagnosis in children and adolescents in France.

Ketoacidosis at diagnosis of type 1 diabetes in French children and adolescents.

OBJECTIVES: This study aimed to evaluate the frequency of diabetic ketoacidosis (DKA) and its associated factors at the diagnosis of type 1 diabetes (T1D) in French children and adolescents prior to launching a public-health campaign of information to prevent DKA. PATIENTS AND METHODS: Over a 1-year period, 1299 youngsters (aged < 15 years) were diagnosed with T1D at 146 paediatric centres in all regions of France. Age, gender, duration of symptoms, patient's pathway to diagnosis, clinical and biological signs, and family history of T1D were collected for each newly diagnosed patient. DKA was defined as pH < 7.30 or bicarbonate < 15 mmol/L, and severe DKA as pH < 7.10 or bicarbonate < 5 mmol/L. RESULTS: At the time of diagnosis, 26% of the children were aged 0-5 years, 34% were 5-10 years and 40% were 10-15 years. The overall prevalence of DKA was 43.9% (0-5 years: 54.2%; 5-10 years: 43.4%; and 10-15 years: 37.1%) and 14.8% for severe DKA (0-5 years: 16.6%; 5-10 years: 14.4%; and 10-15 years: 13.9%; < 2 years: 25.3%). Severe DKA was more frequent when the child was hospitalized at the family's behest (26.6%) than when referred by a general practitioner (7.6%) or paediatrician (5.1%; 30.6%, 53.7% and 9.2%, respectively, by patients' age group). The frequency of DKA decreased to 20.1% (severe DKA: 4.4%) in families with a history of T1D. Multivariate analysis showed that age, pathway to diagnosis, duration of polyuria/polydipsia (< 1 week) and family history of T1D were associated with the presence of DKA, while pathway to diagnosis and family history of T1D were associated with severe DKA. CONCLUSION: DKA at the time of T1D diagnosis in children and adolescents is frequent and often severe. Patients' age, pathway to hospitalization and family history of diabetes were the main factors associated with DKA. These data suggest that a public-health campaign to prevent DKA at diagnosis can help reduce the frequency of DKA and also provide baseline data for evaluating the efficacy of such a campaign.

[Epidemiology of diabetes mellitus in childhood]. / Épidémiologie des diabètes sucrés chez l'enfant.

Diabetes mellitus in childhood may correspond to different pathophysiological entities but type 1 diabetes is by far the most common form of diabetes in children. Its incidence has been increasing steadily over the past two decades. This trend is particularly important among younger children, leading to a youngest median age at the discovery of diabetes. Thus, approximately 25% of diagnoses of type 1 diabetes are in children under 5 years. In France, the type 2 diabetes in children is rare despite the rise in obesity. Investigations for the diagnosis are recommended in obese adolescents with a family history of type 2 diabetes. Monogenic diabetes are more common than type 2 diabetes in Europe. Their research depends on the analysis of family history and may lead to a specific therapeutic approach.

Plasminogen activator inhibitor type-1 is an independent marker of metabolic disorders in young adults born small for gestational age.

BACKGROUND: Metabolic syndrome (MS) has been associated with being born small for gestational age (SGA). In epidemiological studies plasminogen activator inhibitor type-1 (PAI-1) levels have been associated with MS. Few studies have examined this association in subjects born SGA. PATIENTS AND METHODS: Five hundred and fifty-seven SGA adults (birth weight < 10th percentile) were compared with 671 subjects with a birth weight between the 25th and 75th percentiles (control group). MS was defined using the World Health Organization (WHO) definition. Active PAI-1 was measured on citrated plasma with bio-immunoassay. RESULTS: MS was more prevalent in the SGA group (8.7%) than in the control group (5.5%; P = 0.03). In both groups, PAI-1 concentrations were significantly correlated with waist circumference, plasma triglycerides, homeostatic model assessment-insulin resistance (HOMA-IR) and associated with male sex and MS. PAI-1 concentrations were significantly increased in the SGA group (12.2 ± 21.2 vs. 10.0 ± 13.5 IU mL⁻¹, P = 0.03) and this remained after adjustment of metabolic variables (P = 0.009). PAI-1 concentrations above 4.9 IU mL⁻¹ (= median of PAI-1 concentration in the control group) were present in 94% of the subjects with MS. Moreover, the adjusted odds ratio (OR) for having elevated PAI-1 was 1.48 (1.08; 1.95) in the SGA group in comparison with the control group (P = 0.005). CONCLUSIONS: PAI-1 plasma concentrations were significantly increased in SGA subjects independently of MS. These data suggest that elevation of PAI-1 concentrations might be an indication of an abnormal secretion at the level of the adipose tissue, endothelial cells or liver and implicated in metabolic disorders reported in SGA subjects.

Fertility is not altered in young adults born small for gestational age.

BACKGROUND: The intrauterine environment may have a lifelong impact on individuals' health. However, results on the relationship between birth size and gonadal function are conflicting, and it remains unknown whether reproductive function is altered in adults born small for gestational age (SGA). The aim of the present study was to compare the fertility of young adults from the general population, born either SGA or appropriate for gestational age (AGA). METHODS: There were 579 adults born SGA (birthweight under the 10th percentile) who were compared with 703 subjects of the same age (age 29.4 +/- 4.1 years) born AGA (birthweight between 25th and 75th percentiles). They fulfilled a questionnaire focusing on the first attempt to give birth, to have a measure of the time to pregnancy and an estimation of the fecundability (the monthly pregnancy probability), two relevant indicators of fertility at the couple level. Ratios of fecundability between AGA and SGA subjects were adjusted for known fertility factors (age, smoking, reproductive history) and for socioeconomic status. RESULTS: Time to pregnancy was comparable in the two groups: 5.7 +/- 8.0 versus 6.6 +/- 10.5 months in AGA and SGA, respectively (P = 0.31), in women and 5.1 +/- 7 versus 6.0 +/- 9 months in AGA and SGA, respectively, in men (P = 0.53). The adjusted ratios of fecundability comparing SGA to AGA subjects were not significant: HR = 0.91 [0.68;1.21] (P = 0.5) in women and HR = 0.95 [0.67;1.74] (P = 0.82) in men. CONCLUSION: When studied in young adults from the general population, fertility is not reduced in those born SGA.

11beta-hydroxysteroid dehydrogenase type 1 of the subcutaneous adipose tissue is dysregulated but not associated with metabolic disorders in adults born small for gestational age.

INTRODUCTION: The mechanisms relating being born small for gestational age (SGA) and the later risk of metabolic disorders are not yet fully understood. Adipose 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) activity and expression have been positively associated with metabolic syndrome. In humans, no in vivo studies have explored 11beta-HSD1 activity and gene expression in sc adipose tissue of SGA subjects. SUBJECTS AND METHODS: Thirty-nine subjects SGA (birth weight<10th percentile) were matched on gender and age with 36 subjects born appropriate for gestational age (AGA) (25th percentile

Independent effects of weight gain and fetal programming on metabolic complications in adults born small for gestational age.

AIMS/HYPOTHESIS: Insulin resistance (IR) and the metabolic syndrome (MS) have been reported in adults as a consequence of being born small for gestational age (SGA). The process seems to be initiated early in life; however, little is known about the progression of MS and IR in young adults. We hypothesised that being born SGA would promote a greater progression over time of IR and MS, reflecting not only the gain in weight and fat mass but also the extension of the fetal programming process. METHODS: Participants were selected from a community-based cohort and born full-term either SGA (birthweight <10th percentile) or appropriate for gestational age (25th < birthweight < 75th percentile). A total of 1,308 individuals were prospectively followed between the ages of 22 and 30 years. RESULTS: At both ages, individuals born SGA were more insulin-resistant and showed a significantly higher prevalence of MS. Over the 8 year follow-up, the risk of developing MS was twofold higher in those SGA, after adjustment for gain in BMI, whereas the progression of IR was not significantly affected by the birth status. CONCLUSIONS/INTERPRETATION: Our data suggest that metabolic disorders in SGA individuals are amplified by the weight gain with time when adults, both probably resulting from fetal programming. Moreover, the modest increase in IR contrasts with the constant and much higher prevalence of MS.

The growing incidence of type 1 diabetes in children: the 17-year French experience in Aquitaine.

BACKGROUND: While the incidence of type 1 diabetes in children has increased in various parts of the world, in France, no actual figures have been available since 1997. OBJECTIVE: The aim of this study was to determine whether or not the pattern of increase in the incidence of type 1 diabetes in children aged less than 15 years varies with age at onset in Aquitaine (France) over a 17-year period. PATIENTS AND METHODS: From 1988 to 1997, all newly diagnosed cases of type 1 diabetes were confirmed by registration into the French Registry of Incidence of Diabetes. Subsequently, all cases registered from 1998 to 2004 were collected within paediatric centres in Aquitaine as part of their hospital-based prospective records. RESULTS: In the overall population, the age- and gender-adjusted incidence rate increased from 8.86 per 100,000 per year (95% CI: 6.27-11.45) in 1988 to 13.47 per 100,000 per year (95% CI: 10.29-16.65) in 2004, indicating an annual increase in incidence of 3.34% (95% CI: 3.33-3.34). Median age at diabetes onset for cases in the first registration period (1988-1996) was significantly higher than that in the second registration period (1997-2004): 10.04 years (range: 6.64-12.53) versus 8.83 years (range: 5.48-11.73), respectively (P=0.01). The annual increase in incidence rate was highest in the youngest children and varied significantly with age (0-4 years: 7.59%; 5-9 years: 4.06%; 10-14 years: 1.28%). CONCLUSION: These results indicate a doubling of the incidence of type 1 diabetes in children every 30 years in Aquitaine, with an even steeper increase among younger children, thus underscoring the need for appropriate adaptation of the system of healthcare provision.

Impact of fetal growth restriction on body composition and hormonal status at birth in infants of small and appropriate weight for gestational age.

BACKGROUND: Fetal growth restriction (FGR) has been related to several health risks, which have been generally identified in small-for-gestational age (SGA) individuals. OBJECTIVE: To evaluate the impact of FGR on body composition and hormonal status in infants born either small- or appropriate-for-gestational age (AGA). METHODS: Fetal growth was assessed by ultrasound every 4 weeks from mid-gestation to birth in 248 high-risk pregnancies for SGA. Fetal growth velocity was calculated as change in the estimated fetal weight percentiles and FGR defined as its reduction by more than 20 percentiles from 22 gestational weeks to birth. Impact of FGR on body composition, cord insulin, IGF-I, IGF binding protein-3 (IGFBP-3), and cortisol concentrations was assessed in SGA and AGA newborns. RESULTS: Growth-retarded AGA infants showed significantly reduced birth weight, ponderal index, percentage of fat mass, and bone mineral density when compared with AGA newborns with stable intrauterine growth. Cord IGF-I and IGFBP-3 concentrations were significantly decreased in growth-retarded infants in both SGA and AGA groups. Cord insulin concentration was significantly lower and cord cortisol significantly higher in AGA infants with FGR versus AGA newborns with stable intrauterine growth. After adjustment for gestational age and gender, birth weight was directly related to fetal growth velocity and cord IGF-I concentration. The variation in infant's adiposity was best explained by fetal growth velocity and cord insulin concentration. CONCLUSIONS: FGR affects body composition and hormonal parameters in newborns with birth weight within the normal range, suggesting these individuals could be at similar metabolic risks as SGA. .

Prevalence and clinical features of celiac disease in 950 children with type 1 diabetes in France.

UNLABELLED: The prevalence of celiac disease is higher in children with type 1 diabetes mellitus (DM) than in the general pediatric population, but may vary widely across countries. Sensitive and specific antibody tests are available for detecting celiac disease. AIMS: To evaluate the prevalence in France of histologically documented celiac disease in a vast cohort of children with type 1 DM, and to describe the features of celiac disease and treatment response. METHODS: Retrospective cohort study of 950 children with type 1 diabetes seen between 1994 and 2001. Antibodies to gliadin, reticulin, endomysium and transglutaminase were looked for one to seven times in each patient. RESULTS: Fifteen patients (1.6%) had biopsy-confirmed celiac disease. Symptoms led to the diagnosis in six patients (mean age, 7 years) and screening tests in nine patients (mean age, 11 years). Anti-endomysium antibodies were consistently positive. Tests for HLA-DQB1 0201 and/or 0302 were positive. Anti-endomysium antibody seroconversion was seen in two patients, 2 and 6 years, respectively, after the diagnosis of diabetes. In another patient, the biopsy became abnormal 6 years after the first positive anti-endomysium antibody test (latent form). After a mean of 3 years on a gluten-free diet, significant increases were noted in body weight (P=0.04) and insulin dose (P=0.05); clinical symptoms completely resolved in five of the six symptomatic patients. CONCLUSIONS: The prevalence of celiac disease is higher in children with type 1 DM than in the general pediatric population. Serological screening is useful for diagnosing asymptomatic celiac disease, detecting seroconversion and monitoring latent forms of disease.

Single nucleotide polymorphisms in the neuropeptide Y2 receptor (NPY2R) gene and association with severe obesity in French white subjects.

AIMS/HYPOTHESIS: Genetic variants of genes for peptide YY (PYY), neuropeptide Y2 receptor (NPY2R) and pancreatic polypeptide (PPY) were investigated for association with severe obesity. SUBJECTS AND METHODS: The initial screening of the genes for variants was performed by sequencing in a group of severely obese subjects (n=161). Case-control analysis of the common variants was then carried out in 557 severely obese adults, 515 severely obese children and 1,163 non-obese/non-diabetic control subjects. Rare variants were genotyped in 700 obese children and the non-obese/non-diabetic control subjects (n=1,163). RESULTS: Significant association was found for a 5' variant (rs6857715) in the NPY2R gene with both severe adult obesity (p=0.002) and childhood obesity (p=0.02). This significant association was further supported by a pooled allelic analysis of all obese cases (adults and children, n=928) vs the control subjects (n=938) (p=0.0004, odds ratio=1.3, 95% CI 1.1-1.5). Quantitative trait analysis of BMI and WHR was performed and significant association was observed for SNP rs1047214 in NPY2R with an increase in WHR in the severely obese children (co-dominant model p=0.005, recessive model p=0.001). Association was also observed for an intron 3 variant (rs162430) in the PYY gene with childhood obesity (p=0.04). No significant associations were observed for PPY variants. Only one rare variant in the NPY2R gene (C-5641T) was not found in lean individuals and this was found to co-segregate with obesity in one family. CONCLUSIONS/INTERPRETATION: These results provide evidence of association for NPY2R and PYY gene variants with obesity and none for PPY variants. A rare variant of the NPY2R gene showed evidence of co-segregation with obesity and its contribution to obesity should be investigated further.

Small for gestational age and the metabolic syndrome: which mechanism is suggested by epidemiological and clinical studies?

The metabolic and cardiovascular complications associated with in-utero undernutrition have been identified during the past 10 years. Reduced fetal growth is independently associated with an increased risk of development of cardiovascular diseases, the insulin-resistance syndrome or one of its components (i.e., hypertension, dyslipidaemia, impaired glucose tolerance and type 2 diabetes). Insulin resistance appears to be a key component underlying these metabolic complications. Although the mechanism remains unclear, several pieces of evidence support an active role of adipose tissue in the emergence of insulin resistance (an abnormal growth pattern and repartition, hypersensitivity to catecholamines, regulation of leptin and adiponectin secretion and modulation of peroxisome proliferator-activated receptor gamma). Among individuals born SGA, those who are more at risk of gaining excess adiposity are those who are thin at birth following a period of fetal growth restriction. This period of undernutrition is followed by a neonatal period of catch-up growth and renutrition. This pattern induces important modifications in adipose tissue, with long-term consequences, among which is a high risk of early development of insulin resistance. Not all individuals born SGA will show such modifications in adipose tissue, meaning that not all of those born SGA are at risk of insulin resistance and diabetes. From a broader point of view, several hypotheses have been proposed over the past 10 years to explain this unexpected association between being born SGA and the later development of disease. Each of them points to a detrimental fetal environment, to a genetic susceptibility or to interactions between these two components playing a critical role in this context. Although not confirmed, the hypothesis suggesting that this association could be the consequence of genetic/environmental interactions remains the most attractive.

Low serum adiponectin levels in subjects born small for gestational age: impact on insulin sensitivity.

OBJECTIVE: Increasing evidence point to the role of the adipose tissue on the insulin resistance associated with reduced fetal growth. Since adiponectin, exclusively produced by the adipose tissue, exerts an important insulin-sensitizing activity, it appears critical to investigate the effect of being born small for gestational age (SGA) on adiponectin production in adulthood and its relationship with insulin sensitivity. SUBJECTS AND METHODS: Serum adiponectin concentrations were measured in 486 young adults born SGA, precisely selected on birth data, who were compared to 573 age-matched subjects born appropriate for gestational age (AGA). The relationship between serum adiponectin levels and insulin-resistance indices measured under OGTT were tested and compared between the two groups. RESULTS: The SGA group demonstrated significantly reduced serum adiponectin levels than controls (12.6 +/- 6.9 vs 13.2 +/- 6.4 microg/ml, P = 0.02) and the difference remained significant when the key regulatory factors were taken into account (P = 0.008). In the AGA group, fasting I/G taken as an insulin-resistance index negatively correlated with serum adiponectin concentrations (P = 0.02), while the relationship followed a U-shape with increased fasting I/G ratio despite high concentrations of serum adiponectin in the SGA group (P = 0.12). CONCLUSION: Subjects born SGA demonstrated significantly reduced serum adiponectin levels, which were not related to insulin-resistance indices in comparison to what observed in age-matched subjects born AGA. Although this defect in adiponectin production and in its insulin-sensitizing action remains to be elucidated at the molecular level, it strengthens the critical contribution of the adipose tissue in the metabolic complications associated with reduced fetal growth.

Smallness for gestational age is associated with persistent change in insulin-like growth factor I (IGF-I) and the ratio of IGF-I/IGF-binding protein-3 in adulthood.

CONTEXT: Implication of the IGF-IGF-binding protein (IGFBP) axis in the development of metabolic and cardiovascular diseases has been well documented. It has also been shown that an adverse intrauterine environment alters the IGF-IGFBP axis during childhood. OBJECTIVE: The objective of this study was to investigate whether these alterations persist into adulthood. DESIGN AND METHODS: Fasting serum IGF-I, IGFBP-3, and insulin concentrations were measured, and their determinants were analyzed in a cohort of young adult subjects (22 yr of age) born either small (SGA; n = 461) or appropriate (AGA; n = 568) for gestational age. RESULTS: In adulthood, subjects born SGA had significantly lower mean serum IGF-I (320 +/- 137 vs. 348 +/- 143 microg/liter; P = 0.0015), IGFBP-3 (4700 +/- 700 vs. 4800 +/- 800 microg/liter; P = 0.04), and IGF-I/IGFBP-3 ratio (0.067 +/- 0.026 vs. 0.072 +/- 0.025; P = 0.01) than those born AGA. The fasting IGF-I concentration and the IGF-I/IGFBP-3 ratio were significantly inversely associated with age, body mass index, smoking, and oral contraception and were positively related to birth weight and fasting insulin levels. The IGFBP-3 concentration was significantly negatively correlated to age and smoking and was positively related to insulin concentration and oral contraception. After adjustment for age, height, body mass index, gender, smoking, and oral contraception, the mean IGF-I concentration and the mean IGF-I/IGFBP-3 ratio remained significantly lower in the SGA compared with the AGA group (P = 0.003 and P = 0.01, respectively). CONCLUSIONS: Serum IGF-I concentrations and the IGF-I/IGFBP-3 ratio are lower in adult subjects born SGA. Although the origin of this persisting alteration of the IGF-IGFBP axis in adulthood needs to be elucidated, its potential contribution to the long-term metabolic and cardiovascular complications associated with fetal growth restriction is important to consider in the future.