Prediction of childhood obesity by infancy weight gain: an individual-level meta-analysis.

To assess the predictive ability of infant weight gain on subsequent obesity we performed a meta-analysis of individual-level data on 47,661 participants from 10 cohort studies from the UK, France, Finland, Sweden, the US and Seychelles. For each individual, weight SD scores at birth and age 1 year were calculated using the same external reference (British 1990). Childhood obesity was defined by International Obesity Task Force criteria. Each +1 unit increase in weight SD scores between 0 and 1 year conferred a twofold higher risk of childhood obesity (odds ratio = 1.97 [95% confidence interval (CI) 1.83, 2.12]), and a 23% higher risk of adult obesity (odds ratio = 1.23 [1.16, 1.30]), adjusted for sex, age and birthweight. There was little heterogeneity between studies. A risk score for childhood obesity comprising weight gain 0-1 year, mother's body mass index, birthweight and sex was generated in a random 50% selection of individuals from general population cohorts with available information (n = 8236); this score showed moderate predictive ability in the remaining 50% sample (area under receiving operating curve = 77% [95% CI 74, 80%]). A separate risk score for childhood overweight showed similar predictive ability (area under receiving operating curve = 76% [73, 79%]). In conclusion, infant weight gain showed a consistent positive association with subsequent obesity. A risk score combining birthweight and infant weight gain (or simply infant weight), together with mother's body mass index and sex may allow early stratification of infants at risk of childhood obesity.

A truncation mutation in TBC1D4 in a family with acanthosis nigricans and postprandial hyperinsulinemia.

Tre-2, BUB2, CDC16, 1 domain family member 4 (TBC1D4) (AS160) is a Rab-GTPase activating protein implicated in insulin-stimulated glucose transporter 4 (GLUT4) translocation in adipocytes and myotubes. To determine whether loss-of-function mutations in TBC1D4 might impair GLUT4 translocation and cause insulin resistance in humans, we screened the coding regions of this gene in 156 severely insulin-resistant patients. A female presenting at age 11 years with acanthosis nigricans and extreme postprandial hyperinsulinemia was heterozygous for a premature stop mutation (R363X) in TBC1D4. After demonstrating reduced expression of wild-type TBC1D4 protein and expression of the truncated protein in lymphocytes from the proband, we further characterized the biological effects of the truncated protein in 3T3L1 adipocytes. Prematurely truncated TBC1D4 protein tended to increase basal cell membrane GLUT4 levels (P = 0.053) and significantly reduced insulin-stimulated GLUT4 cell membrane translocation (P < 0.05). When coexpressed with wild-type TBC1D4, the truncated protein dimerized with full-length TBC1D4, suggesting that the heterozygous truncated variant might interfere with its wild-type counterpart in a dominant negative fashion. Two overweight family members with the mutation also manifested normal fasting glucose and insulin levels but disproportionately elevated insulin levels following an oral glucose challenge. This family provides unique genetic evidence of TBC1D4 involvement in human insulin action.

Early childhood predictors of adult body composition.

Intra-uterine life has been identified as a possible critical period for the development of obesity risk in both adults and children; others have highlighted the importance of growth and nutrition in the first few years. It is suggested that fetal growth, as assessed by birth weight, may programme lean body mass later in life. Children who are born small for gestational age also have a predisposition to accumulating fat mass, particularly intra-abdominal fat. It is not yet clear whether this predisposition is due to their prenatal growth restraint, their rapid postnatal catch-up growth or a combination of both. Recently, genetic and heritable factors have been shown to contribute to both rapid postnatal growth and childhood obesity risk in children and adults. Future studies should explore their timing of action and potential interactions with markers of antenatal growth restraint.

Independent effect of visceral adipose tissue on metabolic syndrome in obese adolescents.

BACKGROUND/AIMS: Obesity is linked to metabolic complications, even in children, but the role of the distribution of adiposity is unclear. We aimed to assess which compartment of fat mass - total (TFM), visceral (VFM) or subcutaneous (SCFM)--is related to metabolic complications in overweight and obese children and adolescents. DESIGN: Analyses were conducted in 159 overweight or obese children and adolescents (median body mass index 4.0 SD). TFM was measured by dual-energy x-ray absorptiometry. Distribution of abdominal fat was assessed by MRI. Insulin resistance (IR) was determined using a homeostatic model assessment. The definition of metabolic syndrome (MS) was derived from National Cholesterol Education Program ATP III. RESULTS: A parental history of obesity was positively and significantly associated with fat content of the three compartments (TFM: beta = 2.22; VFM: beta = 0.17; SCFM: beta = 0.12, respectively). VFM was also associated with gender (beta = -0.29) and ethnicity (beta = -0.54). TFM was a significant and independent determinant of IR (beta = 0.02) whereas IR and VFM only were significantly related to MS (OR = 3.55 and 3.66 respectively). CONCLUSION: Our data indicate that even in overweight children VFM was influenced by several factors such as sex and ethnicity and that a relationship was evidenced between the amount of VFM and MS.

Characterization of insulin secretion and resistance in type 2 diabetes of adolescents.

CONTEXT: Type 2 diabetes (T2D) in obese children is an emerging problem, including in Europe. Its presentation at diagnosis very often differs from that in adults. OBJECTIVE: The objective of this study was to investigate the relative contributions of the two components of T2D, insulin resistance and insulin secretion, early in the history of the disease in adolescents. PATIENTS AND METHODS: Six obese adolescents with T2D were included 2 months to 4.3 yr after diagnosis (five girls and one boy; median age, 15.4 yr; median body mass index, 4.4 sd). Peripheral and hepatic insulin sensitivity was evaluated with euglycemic hyperinsulinemic (40 mU/m(2).min) clamp. First-phase insulin release was evaluated after iv glucose stimulation. A graded iv glucose infusion and an arginine test were performed to measure insulin secretion. RESULTS: All patients showed decreased peripheral glucose uptake to the same extent. Five patients showed hepatic insulin resistance. First-phase insulin release was very low in two patients. Three patients showed an exaggerated insulin response under graded glucose infusion and preserved secretion under arginine stimulation. Three other patients, with elevated fasting plasma glucose levels, demonstrated a very low insulin response under glucose stimulation and a low insulin response under arginine stimulation. CONCLUSIONS: These data emphasize that together with marked insulin resistance, the failure of beta-cell function is a major component in the course of T2D in childhood.

Diet in 45- to 74-year-old individuals with diagnosed diabetes: comparison to counterparts without diabetes in a nationally representative survey (Etude Nationale Nutrition Santé 2006-2007).

A healthy diet has been shown to prevent diabetes complications. However, the eating habits of individuals with diabetes who are aware of their glycemic condition have been poorly studied. This study's objective was to assess the dietary behavior overall and according to dietary recommendations in adults diagnosed with diabetes compared with those of a general population of the same age (45 to 74 years) in a nationally representative survey carried out in France in 2006-2007 (Etude Nationale Nutrition Santé) (n=1,476 including 101 patients with diabetes). Trained dietitians assessed diet using three 24-hour recalls and diabetes was self-declared. After weighting and using multiple adjustments, mean food and nutrient intakes were compared according to diabetes status. Interactions with age and sex were sought. Adults with diabetes had lower intakes of sweetened foods (40 g/day vs 125 g/day), alcohol (1.45 g/day vs 1.64 g/day), energy (1,790 kcal/day vs 1,986 kcal/day), and simple sugar (63.1 g/day vs 89.8 g/day) and higher intakes of meat (126 g/day vs 109 g/day), complex carbohydrates (26.3% energy intake vs 23.6% energy intake), and vitamins B and E (628 µg/day vs 541 µg/day). In addition, 45- to 59-year-old individuals with diabetes ate more fruits and vegetables, fiber, beta carotene, folate, vitamin C, and potassium than adults of the same age who did not have diabetes. Overall, 45- to 74-year-old adults with diabetes had a higher-quality diet than individuals without diabetes. However, compared with recommendations, a healthy diet continues to represent a public health challenge in terms of preventing diabetes complications.

[Type 2 diabetes in France: epidemiology, trends of medical care, social and economic burden]. / Le diabète de type 2 en France : épidémiologie, évolution de la qualité de la prise en charge, poids social et économique. Entred 2007.

Between 2001 and 2007, treatments for type 2 diabetes have increased and therapeutic choices have improved. However glycemic control remains insufficient. Cardiovascular risk control has widely increased. Statins, hypertensive and antithrombotic treatments are more often prescribed. Blood pressure and LDL cholesterol levels have decreased whatever age. However, progress remains possible, especially regarding blood pressure control. Obesity has increased between 2001 and 2007 to reach 41% whereas the frequency of dietetic visits has decreased. Insulin therapy (more than obesity) determines the frequency of dietetic visits: dietetic care happens too late. Important improvements of the quality of follow-up are observed. However, fundus exams and more specifically albuminuria measurement remain insufficiently performed and their progression is too slow, as well as the podiatric examination. Only 10% of people with type 2 diabetes have an endocrinology visit, which has been stable between 2001 and 2007. Information expectations of people with type 2 diabetes are strong, especially for diet. Education demand is lower but more important for people who have already benefited. This improvement of medical care leads to an increase in the cost of reimbursements. The consequences of diabetes, more than the disease itself, alter the quality of life.

Novel modeling of reference values of cardiovascular risk factors in children aged 7 to 20 years.

BACKGROUND AND OBJECTIVE: Most of the cardiovascular risk factors strongly associated with obesity and overweight vary with age and gender. However, few reference values are available for healthy European children. Our objective was to establish pediatric reference ranges for waist circumference, systolic and diastolic blood pressures, fasting lipid levels (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides), glucose, and insulin. METHODS: A representative sample of 1976 healthy French individuals (1004 female participants and 972 male participants) aged 7 to 20 years was used to obtain age- and gender-specific normal ranges for each of the above-listed cardiovascular risk factors, based on the Royston and Wright method. RESULTS: Mean waist circumference increased with age in both genders and was slightly higher in males than in females. Whereas systolic blood pressure increased gradually with age, with the increase being steeper in males than in females, no gender effect was found for diastolic blood pressure, which was therefore modeled after pooling males and females. Total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglyceride values varied little with age and gender. Glucose and insulin levels revealed pubertal peaks, which were sharper in females than in males, reflecting the normal insulin resistance during puberty. CONCLUSIONS: These ranges can be used as references for European children to monitor cardiovascular risk factors and to plan interventions and education programs.

Metabolic syndrome in children: comparison of the International Diabetes Federation 2007 consensus with an adapted National Cholesterol Education Program definition in 300 overweight and obese French children.

BACKGROUND/AIMS: Former definitions of metabolic syndrome (MS) in children have been adapted from adult MS definitions using age-related thresholds for each biochemical component, whereas the International Diabetes Federation (IDF) definition is based on absolute values. We compared the IDF childhood MS definition (IDF-MS) to the adapted National Cholesterol Education Program (adapted-NCEP) definition in overweight children. METHODS: 300 overweight and obese children were included with a median age of 11 years and BMI SDS of +4.7. RESULTS: Below 10 years of age, the frequency of MS according to the adapted-NCEP-MS definition was 18.6%, and 86.1% had abdominal obesity. In children aged 10 to <16 years (n = 214), the frequency of IDF-MS was 8.9% compared to 14.5% by adapted-NCEP. IDF-MS children had a larger waist circumference, and higher triglycerides, fasting insulin and tended to be older than the intermediate severity group of children with MS only according to adapted-NCEP. Children with MS only according to adapted-NCEP (IDF-MS negative), differed from non-MS children in systolic blood pressure, triglycerides and high-density lipoprotein cholesterol. CONCLUSIONS: The recent IDF-MS criterion in children represents a more severe definition and appears to identify a group of children with higher fasting insulin than the adapted-MS definition which uses age-related thresholds (90th percentile).

Insulin resistance in children: consensus, perspective, and future directions.

OBJECTIVE: Emerging data indicate that insulin resistance is common among children and adolescents and is related to cardiometabolic risk, therefore requiring consideration early in life. However, there is still confusion on how to define insulin resistance, how to measure it, what its risk factors are, and whether there are effective strategies to prevent and treat it. A consensus conference was organized in order to clarify these points. PARTICIPANTS: The consensus was internationally supported by all the major scientific societies in pediatric endocrinology and 37 participants. EVIDENCE: An independent and systematic search of the literature was conducted to identify key articles relating to insulin resistance in children. CONSENSUS PROCESS: The conference was divided into five themes and working groups: background and definition; methods of measurement and screening; risk factors and consequences; prevention; and treatment. Each group selected key issues, searched the literature, and developed a draft document. During a 3-d meeting, these papers were debated and finalized by each group before presenting them to the full forum for further discussion and agreement. CONCLUSIONS: Given the current childhood obesity epidemic, insulin resistance in children is an important issue confronting health care professionals. There are no clear criteria to define insulin resistance in children, and surrogate markers such as fasting insulin are poor measures of insulin sensitivity. Based on current screening criteria and methodology, there is no justification for screening children for insulin resistance. Lifestyle interventions including diet and exercise can improve insulin sensitivity, whereas drugs should be implemented only in selected cases.

Association between birth weight and visceral fat in adults.

BACKGROUND: Several studies reported inverse associations between birth weight and central adiposity in adults. However, few studies investigated the contributions of different abdominal fat compartments. OBJECTIVE: We examined associations between birth weight and adult visceral and subcutaneous abdominal fat in the population-based Fenland study. DESIGN: A total of 1092 adults (437 men and 655 women) aged 30-55 y had available data on reported birth weight, standard anthropometric measures, and visceral and subcutaneous abdominal fat estimated by ultrasound. In a subgroup (n = 766), dual-energy X-ray absorptiometry assessment of total abdominal fat was performed. Linear regression models were used to analyze relations between birth weight and the various fat variables adjusted for sex, age, education, smoking, and body mass index (BMI). RESULTS: After adjustment for adult BMI, there was an inverse association between birth weight and total abdominal fat [B (partial regression coefficient expressed as SD/1-kg change in birth weight) = -0.09, P = 0.002] and visceral fat (B = -0.07, P = 0.01) but not between birth weight and subcutaneous abdominal fat (B = -0.01, P = 0.3). Tests for interaction showed that adult BMI modified the association between birth weight and visceral fat (P for interaction = 0.01). In stratified analysis, the association between birth weight and visceral fat was apparent only in individuals with the highest BMI tertile (B = -0.08, P = 0.04). CONCLUSIONS: The inverse association between birth weight and adult abdominal fat appeared to be specific to visceral fat. However, associations with birth weight were apparent only after adjustment for adult BMI. Therefore, we suggest that rapid postnatal weight gain, rather than birth weight alone, leads to increased visceral fat.

Insulin resistance and the metabolic syndrome in obese French children.

OBJECTIVE: To estimate the frequency of the metabolic syndrome (MS) and of the insulin resistance syndrome (IRS) in overweight or obese French children and to determine the risk factors. DESIGN, PATIENTS AND METHODS: A total of 308 overweight and obese children [166 girls, 142 boys, aged 7-17 years; median body mass index (BMI) 4.7 standard deviation (SD) (Q1-Q3: 3.9-5.8) adjusted for age and sex] were included. The frequency of the MS was assessed with the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) criteria and the frequency of the IRS with World Health Organization (WHO) criteria. RESULTS: The overall frequency of MS and IRS was 15.9% and 42.5%, respectively. The most common component, after abdominal obesity (95.8%) and IR (71.8%), was elevated systolic blood pressure (28.6%). The frequency of glucose tolerance disorders was low (3.6%). The frequency of MS was independently influenced by homeostatic model assessment (HOMA) (P = 0.06) and waist-to-hip ratio (P = 0.09), whereas the frequency of IRS was influenced by adiposity (degree of obesity: P = 0.02; waist-to-hip ratio: P = 0.05), puberty (P = 0.05) and mother's BMI (P = 0.01). Ethnicity had no effect on either MS or IRS. CONCLUSIONS: Metabolic complications and IR are frequent in overweight and obese children whereas the frequency of glucose tolerance disorders is very low. IRS is more prevalent than MS, indicating a major role of IR, which could precede the other metabolic complications in obese children. IRS is a relevant marker for the risk of type 2 diabetes (T2D) and cardiovascular complications in obese European children.