Body composition in children and adolescents born after in vitro fertilization or spontaneous conception

CONTEXT: Increasing evidence suggests that adverse conditions during prenatal life are associated with the development of chronic diseases in adult life. It is still unclear whether in vitro fertilization (IVF) conception could affect the vulnerable developmental processes in humans occurring during early prenatal development with long-term perturbations of developmental pathways. OBJECTIVE: Our objective was to examine body composition in 8- to 18-yr-old IVF singletons and spontaneously conceived controls born from subfertile parents. DESIGN AND SETTING: This follow-up study was conducted at the VU University Medical Center in Amsterdam, The Netherlands. PARTICIPANTS: Participants included 233 IVF children (139 pubertal children) and 233 age- and gender-matched control children (143 pubertal children). MAIN OUTCOME MEASURES: Body composition measures were assessed by anthropometry and dual-energy x-ray absorptiometry in the pubertal subpopulation. RESULTS: IVF children had a significantly lower subscapular-triceps skinfold ratio and a significantly higher sum of peripheral skinfolds, peripheral body mass, and percentage of peripheral body fat as compared with controls. Although not reaching statistical significance, both dual-energy x-ray absorptiometry and skinfold measurements suggested that total body fat in IVF children is increased. Neither current and early risk factors nor parental factors, such as subfertility cause, could explain the differences in peripheral fat assessed by anthropometry between IVF children and controls. No differences in bone mineral composition between IVF children and controls were found. CONCLUSIONS: Our observations indicate that body fat composition in IVF children is disturbed. Follow-up of IVF children to monitor body fat pattern and potentially related health problems from adolescence into adulthood is of great importance.     

In vitro fertilization improves childhood growth and metabolism

BACKGROUND: There is limited information regarding the long-term outcome of children born after in vitro fertilization (IVF), although an increase in rare imprinted gene disorders such as Beckwith-Wiedemann syndrome has been reported. METHODS: We recruited healthy, prepubertal children born at term after singleton pregnancy. The children in the study group were conceived using IVF with fresh embryo transfer, whereas controls were naturally conceived. Anthropometric measurements, bone age, dual-energy x-ray absorptiometry, fasting serum glucose, insulin, lipid profile, IGF-I and -II, and IGF-binding proteins 1, 2, and 3 were performed. RESULTS: There were 69 IVF children aged 5.9 +/- 0.2 yr and 71 control children aged 6.9 yr. IVF children were taller than controls when corrected for parents' heights (height sd score of 1.05 +/- 0.1 vs. 0.51 +/- 0.11, P = 0.001) with higher levels of serum IGF-II (850 +/- 24 vs. 773 +/- 24 microg/liter, P = 0.03), higher IGF-I to IGF-binding protein 3 ratio (P = 0.04), and a trend toward higher IGF-I (105 +/- 4 vs. 92 +/- 4 microg/liter, P = 0.06). IVF children had higher high-density lipoprotein (1.67 +/- 0.04 mmol/liter vs. 1.53 +/- 0.04 mmol/liter, P = 0.02), lower triglycerides (0.65 +/- 0.04 mmol/liter vs. 0.78 +/- 0.04 mmol/liter, P = 0.02), and a lower total to high-density lipoprotein cholesterol ratio (2.58 vs. 2.86, P = 0.01). There were no differences in body composition. CONCLUSIONS: IVF children are taller with higher IGF-I and IGF-II levels and have a slightly more favorable lipid profile. We speculate that IVF results in epigenetic change through altered methylation of genes involved in growth and metabolism. IVF programs should consider long-term longitudinal follow-up of IVF offspring.     

Period prevalence of abnormal glucose tolerance and cardiovascular risk factors among obese children attending an obesity centre in Italy

BACKGROUND AND AIM: Several reports have described an increasing prevalence and incidence of type 2 diabetes among children. Limited information is available about the prevalence of impaired glucose tolerance (IGT) and type 2 diabetes in obese children, particularly in Europe. The aim of this study was to examine the prevalence of glucose intolerance and other cardiovascular risk factors in obese children over a 24-year period. METHODS AND RESULTS: The study population consisted of 1376 consecutive subjects who attended a national centre for the study of obesity between 1979 and 2002. Subjects were divided into three successive 8-year cohorts: cohort 1 (period 1979-1986, n=453, male: 39%), cohort 2 (period 1987-1994, n=409, male: 46%), cohort 3 (period 1995-2002, n=514, male: 48%). All subjects underwent an oral glucose tolerance test. Lipids, blood pressure, uric acid, C-reactive protein (CRP), fasting insulin and birth weight were recorded. Insulin resistance was measured by homeostasis model assessment (HOMA-IR). The degree of obesity was higher in the more recent cohorts (standard deviation score of body mass index: 3.3+/-0.04 vs. 3.7+/-0.04 vs. 3.8+/-0.03, P<0.0001). The proportion of subjects with glucose intolerance was lower in the last two cohorts compared with the first one (11.2% vs. 3.9% vs. 6.0%, P<0.0001). This was predominantly due to changes in the frequency of IGT (9.1% vs. 3.2% vs. 5.4%, P<0.001 in cohorts 1, 2 and 3, respectively) while the prevalence of undiagnosed type 2 diabetes and impaired fasting glucose was similar in the three cohorts (0.9% vs. 0% vs. 0.2% and 1.3% vs. 0.7% vs. 0.4%, respectively). After adjustment for differences in age, sex, pubertal status and birth weight the levels of fasting insulin, HOMA-IR, total cholesterol, triglycerides and blood pressure, were significantly lower in cohorts 2 and 3 than in cohort 1 while CRP and uric acid were higher in the last two cohorts. CONCLUSION: Over a recent period spanning 24 years, the degree of obesity has risen but the prevalence of glucose intolerance has fallen in obese children admitted to an obesity centre. This was accompanied by an improvement in traditional but a worsening in non-traditional risk factors for cardiovascular disease.     

Blood glucose concentrations are reduced in children born small for gestational age (SGA), and thyroid-stimulating hormone levels are increased in SGA with blunted postnatal catch-up growth

Fetal growth restriction is associated with an increased risk of developing insulin resistance and type 2 diabetes in adulthood. In addition, 10-20% of children born small for gestational age (SGA) do not achieve a normal final height. The purpose of this study was to investigate insulin sensitivity and endocrine status in SGA children, compared with that in children born appropriate for gestational age (AGA). Furthermore, within the SGA group, we aimed to relate postnatal growth to anthropometric, biochemical, and endocrine parameters. Eighty-two SGA children (with a mean age of 8.6 +/- 3.5 yr) and 53 short-AGA children (with a mean age of 9.3 +/- 3.3 yr) were studied. A case-control study was carried out in 26 SGA and 26 short-AGA subjects. For each SGA subject, we selected a short-AGA child matched for sex, age (within 1 yr), pubertal status, body mass index (within 0.5 kg/m(2)), and height (within 0.25 z-score). Children's statures were corrected for their midparental height, and SGA children were subdivided into 2 groups: catch-up growth (CG) group (children with corrected height with at least 0 z-score); and non-CG (NCG) group (subjects with corrected height with less than 0 z-score). Comparing SGA with short-AGA subjects, no significant differences in fasting insulin, fasting glucose/insulin ratio, homeostasis assessment model for insulin resistance, and homeostasis assessment model-beta-cell values were observed. SGA children showed significantly reduced levels of glucose (4.4 +/- 0.6 vs. 4.9 +/- 0.6 mM, P < 0.0001), total cholesterol (160.1 +/- 28.8 vs. 171.8 +/- 28.5 mg/dl, P = 0.02), and high-density-lipoprotein cholesterol (53.3 +/- 12.1 vs. 58 +/- 11.4 mg/dl, P = 0.02). The analysis of the subjects selected for the case-control study confirmed that SGA children did not have significant differences in the indices of insulin sensitivity but showed significantly lower glucose levels (4.4 +/- 0.7 vs. 4.9 +/- 0.4 mM, P < 0.005). Subdividing the SGA group into CG (n = 25) and NCG (n = 57) children, we found that NCG children showed significantly higher levels of TSH (2.5 +/- 1.3 vs. 1.9 +/- 0.6 mU/liter, P = 0.002). Our data indicate that SGA children do not have altered insulin sensitivity when compared with auxologically identical AGA subjects but show a significant reduction of glucose concentrations. Whether the lower glucose levels are attributable to an early phase of augmented insulin sensitivity, as previously reported in animal models, has to be established. The finding of higher TSH concentrations in SGA children with blunted CG suggests that intrauterine reprogramming might involve thyroid function, which, in turn, might affect postnatal growth and cholesterol metabolism, eventually increasing the risk of cardiovascular disease.     

Serum adiponectin and leptin levels and insulin resistance in children born large for gestational age are affected by the degree of overweight

OBJECTIVE: Children born large for gestational age (LGA) are prone to develop insulin resistance later in life. One factor that affects insulin sensitivity is the hormone adiponectin. The aim of this study was to determine whether being LGA has an impact on serum adiponectin and leptin levels and insulin resistance parameters during childhood, taking into account the severity of overweight. STUDY DESIGN: Serum levels of adiponectin, leptin, fasting glucose and insulin, homeostasis model assessment insulin resistance index (HOMA-IR), and anthropometric indices were evaluated in groups of non-obese children aged 6.5-8 years, born appropriate for gestational age (AGA, n = 40) or LGA (n = 41), matched for age, gender, height, weight and body mass index. The LGA group was divided in two subgroups according to the degree of overweight: (a) LGA with birthweight 90th-97th percentile (n = 25); and (b) LGA with birthweight > 97th percentile (n = 16). RESULTS: LGA children had a higher mean serum adiponectin level than AGA children: 17.0 +/- 9 vs. 11.1 +/- 5 (microg/ml) (P < 0.01). LGA children had also higher insulin 6.2 +/- 2.8 vs. 4.8 +/- 2.4 (microU/ml) (P < 0.05) and HOMA-IR 1.32 +/- 0.66 vs. 1.02 +/- 0.55 (P < 0.01) than AGA children. Children born LGA > 97th percentile had a significantly higher mean serum leptin level than both AGA and LGA 90th-97th percentile children (17 +/- 13, 9.6 +/- 9.5, 7.8 +/- 7.9 ng/ml, respectively, P < 0.05), and more severely affected insulin resistance indices than LGA 90th-97th percentile children. In the regression analysis, birthweight was found to be an independent predictor of adiponectin serum levels. CONCLUSION: Prepubertal LGA-born children had a higher mean serum adiponectin levels than matched AGA controls despite the fact that they were more insulin resistant. The degree of excess in utero weight gain appears to influence the metabolic profile in LGA-born prepubertal children. Further studies are needed to delineate the role of adiponectin in the risk of development of insulin resistance in children born LGA.     

Hypertension in obese children: fasting serum insulin levels are closely correlated with blood pressure

The relationship between blood pressure and anthropometric or metabolic factors was studied in 324 obese children aged 9.5 +/- 1.8 years (mean +/- standard deviation). Obese children had a significantly higher blood pressure than non-obese children (systolic blood pressure: 121 +/- 14 mmHg in obese children vs 112 +/- 11 mmHg in non-obese children, P less than 0.001; diastolic blood pressure: 72 +/- 9 mmHg in obese children vs 66 +/- 7 mmHg in non-obese children, P less than 0.001). When the obese children were divided into hypertensive and normotensive groups, there was a significant difference in fasting serum insulin levels between the two groups (19.3 +/- 9.3 microU/ml in the hypertensive group vs 13.0 +/- 6.1 microU/ml in the normotensive group), and a close correlation between fasting serum insulin levels and systolic blood pressure was demonstrated (r = 0.63, P less than 0.001). However, there was no significant correlation between blood pressure and the degree of obesity itself or the waist-to-hip ratio in the obese children. There was no significant correlation between blood pressure and fasting plasma glucose, serum total cholesterol, or triglycerides levels in the obese children. Moreover, the correlation between fasting insulin levels and blood pressure was shown to be independent of the degree of obesity or waist-to-hip ratio and age by multiple regression analysis. These results indicate that hyperinsulinemia itself may play an important role in the pathogenesis of hypertension in obese children.     

Attenuation of fructose-induced hypertension in rats by exercise training

This study was initiated to see if the insulin resistance, hyperinsulinemia, and hypertension that follow feeding normotensive Sprague-Dawley rats a fructose-rich diet could be prevented by letting rats run spontaneously in exercise wheel cages. Blood pressure in sedentary rats increased from (mean +/- SEM) 125 +/- 2 to 148 +/- 3 mm Hg in response to 2 weeks of a high fructose diet, and this increment was significantly (p less than 0.001) attenuated in exercising rats (from 121 +/- 1 to 131 +/- 2 mm Hg). In addition, mean (+/- SEM) plasma insulin concentration was lower in fructose-fed rats allowed to run spontaneously (44 +/- 2 vs 62 +/- 5 microU/ml; p less than 0.01). Finally, resistance to insulin-stimulated glucose uptake was assessed by determining the steady state plasma glucose response to a continuous glucose and exogenous insulin infusion during a period in which endogenous insulin secretion was suppressed. The results of these studies indicated that the mean (+/- SEM) steady state plasma glucose concentration was significantly lower in the exercise-trained rats (127 +/- 5 vs 168 +/- 6 mg/dl; p less than 0.001), despite the fact that the steady state plasma insulin levels were also lower in rats allowed to run spontaneously (75 +/- 4 vs 90 +/- 5 microU/ml; p less than 0.05). Thus, the ability of exercise-trained rats to stimulate glucose disposal was enhanced as compared with that of sedentary rats fed the same fructose-rich diet. These data demonstrate that the insulin resistance, hyperinsulinemia, and hypertension produced in normotensive rats by feeding them a high fructose diet can be attenuated if rats are allowed to run spontaneously.(ABSTRACT TRUNCATED AT 250 WORDS)     

Glucose tolerance,insulin sensitivity,and insulin secretion in children born small for gestational age

Intrauterine growth retardation is associated with an increased risk of developing adult diseases, such as noninsulin-dependent diabetes mellitus (NIDDM). NIDDM could result from a decreased insulin sensitivity or a reduced insulin secretion or a combination of both. Glucose tolerance, insulin sensitivity, and insulin secretion were studied in prepubertal children born small for gestational age (SGA). Twenty-nine SGA children with a mean age of 9.1 +/- 1.1 yr and 24 children born appropriate for gestational age (AGA), with a mean age of 9.0 +/- 1.1 yr, were studied. All children were born at term and were prepubertal. Children were studied on two separate days after 12 h of overnight fasting. Day 1: Glucose tolerance was studied with an oral glucose tolerance test. AUC(ins0-120 min)/AUC(gluc0-120 min) was used to estimate beta-cell function in the two groups. Day 2: A hyperinsulinemic euglycemic clamp study was performed to determine insulin sensitivity (M-value). Glucose tolerance and beta-cell function were not different between the two groups. M-value in SGA children was significantly lower than M-value in AGA children: 12.9 +/- 4.0 mg/kg.min vs. 15.6 +/- 2.3 mg/kg.min [P = 0.009; after adjustment for appropriate gestational age body mass index (BMI), P = 0.001]. The M-value tended to be higher in SGA children without catch-up growth compared with SGA children with catch-up growth (15.8 +/- 4.3 vs. 12.3 +/- 3.8 mg/kg.min; P = 0.079) and was comparable to AGA controls (15.6 +/- 2.3 mg/kg.min). The M-value in SGA children who had shown catch-up growth was comparable to AGA children (13.4 +/- 3.4 vs. 15.6 +/- 2.3 mg/kg.min; P = 0.06), provided they had a BMI of 17 kg/m(2) or less. However, the SGA children with catch-up growth and a BMI greater than 17 kg/m(2) were those having the lowest M-values (9.3 +/- 3.4 mg/kg.min). In conclusion, during oral glucose tolerance tests, no differences were found in glucose tolerance and beta-cell function between the SGA and AGA groups. However, the hyperinsulinemic clamp showed a reduced insulin sensitivity in SGA children, which may contribute to the enhanced risk of developing NIDDM in adult life, especially in SGA children with catch-up growth and a high BMI. The implications of our findings in relation to height are unclear, but might be of potential importance when considering GH treatment. In addition, interventions to improve fetal growth and to control obesity in childhood seem to be important factors in the prevention of NIDDM.     

Persistent improvement of cardiovascular risk factors in spontaneously hypertensive rats following early short-term captopril treatment

This study was designed to determine whether an improvement in cardiovascular risk factors persists in spontaneously hypertensive rats (SHR) following withdrawal of angiotensin converting enzyme inhibitor (ACE-I) treatment. SHR were given deionized drinking water or captopril solution from four to sixteen weeks of age. At twelve weeks of age, rats from each group were instrumented with radiotelemetry devices for continuous monitoring of blood pressure. Mean arterial blood pressure was significantly lower in captopril-treated SHR during treatment (92+/-2 vs 147+/-1 mm Hg), and at twelve weeks after treatment withdrawal (131+/-2 vs 158+/-2 mm Hg). In addition, proteinuria, renal vascular resistance, plasma triglyceride levels, fasting glucose levels, post-prandial insulin levels, and heart weights were significantly reduced in the treated SHR compared to control SHR, at time-points between three to seven months after captopril withdrawal. Our findings indicate that short-term administration of an ACE-I during the developmental phase of hypertension in the SHR results in a long-term overall improvement of cardiovascular risk factors.     

Low-grade inflammation independently associates with cardiometabolic risk in children with overweight/obesity

Background and aimsPediatric obesity associates with both low-grade inflammation and cardiometabolic risk on the population level. Yet on an individual patient level, overweight/obesity does not always equal increased cardiometabolic risk. In this study, we examine whether low-grade inflammation associates with cardiometabolic risk in Danish children, independent of degree of adiposity. We further assess the value of integrating multiple inflammation markers to identify children with very-high cardiometabolic risk profiles.Method and resultsWe studied 2192 children and adolescents aged 6–18 years from an obesity clinic cohort and a population-based cohort, in a cross-sectional study design. Anthropometry, blood pressure, pubertal stage and body composition by dual-energy X-ray absorptiometry were assessed, and biomarkers including fasting serum high sensitivity C-reactive protein (hsCRP), white blood cells (WBC), resistin, lipid profile and glucose metabolism were measured. Adjusted correlation analysis and odds ratios were calculated. We found that, independent of degree of adiposity, having high-normal inflammation marker concentrations associated with increased cardiometabolic risk: for girls, hsCRP >0.57–9.98 mg/L (mid/upper tertile) associated with ~2-fold higher odds of dyslipidemia and hepatic steatosis (vs. lower tertile). For both sexes, WBC >7.0–12.4 10⁹/L (upper tertile) associated with 2.5-fold higher odds of insulin resistance. Lastly, children with multiple inflammation markers in the high-normal range exhibited the most severe cardiometabolic risk profile.ConclusionLow-grade inflammation associates with cardiometabolic risk in children independent of degree of adiposity. The associations vary with sex and inflammation marker measured. Finally, integrating multiple low-grade inflammation markers identifies a very-high-risk subgroup of children with overweight/obesity and may have clinical value.     

Insulin, glucagon and growth hormone responses during glucose, arginine and insulin tolerance tests in children with hyperthyroidism

There are many reports of glucose intolerance in adult patients with hyperthyroidism but few reports of glucose intolerance in hyperthyroid children. In this study, we measured plasma levels of glucose, insulin, glucagon and growth hormone in hyperthyroid children and control subjects by the use of three kinds of tolerance tests: an oral glucose tolerance test, an arginine tolerance test and an insulin tolerance test. In the oral glucose tolerance test, mean fasting glucose levels (79.6 +/- 1.4 mg/dl) rose to maximum levels (157.3 +/- 4.3 mg/dl) at 30 min in hyperthyroid children which were significantly higher than the levels in control subjects (p less than 0.01). The maximum levels of glucose fell slowly and returned to fasting levels at 180 min. In this test, plasma insulin levels increased from basal levels (12.7 +/- 1.9 microU/ml) to maximum levels (120.8 +/- 22.1 microU/ml) at 30 min in the prepubertal age group of hyperthyroidism. On the other hand, in the pubertal age group of hyperthyroidism, maximum levels of insulin were observed at 60 min, but not at 30 min. These maximum levels of insulin of both hyperthyroid age groups were significantly higher than those in the control subjects (p less than 0.05, p less than 0.01 respectively). There was no difference in insulin-glucose ratio at 30 min (delta IRI/delta BG) and insulinogenic index (I.I.) at 0 to 60 min between these two groups of hyperthyroid children and control subjects. However, I.I. at 0 to 120 min and 0 to 180 min decreased significantly in the pubertal age group of hyperthyroidism as compared with those in the control group (p less than 0.05, p less than 0.02 respectively). In the oral glucose tolerance test, plasma glucagon levels decreased from basal levels (74.1 +/- 4.3 pg/ml) to minimum levels (36.4 +/- 4.7 pg/ml) at 90 min in hyperthyroidism, which were significantly lower than those in the controls (p less than 0.05). However, there was no difference in -epsilon delta IRG/epsilon delta BG (cumulative glucagon response/cumulative glucose response) between the subjects with hyperthyroidism and the controls. On the other hand, lower responses of blood glucose, insulin, glucagon and growth hormone to arginine were observed in subjects with hyperthyroidism than in the controls. Moreover in the insulin tolerance test, there was no difference in glucagon and growth hormone response between the subjects with hyperthyroidism and the controls. Thus our conclusions are as follows: A marked increase in blood glucose after oral glucose load was observed in spite of normal insulin-glucose ratio in hyperthyroid children, suggesting the existence of peripheral insulin resistance.(ABSTRACT TRUNCATED AT 400 WORDS)     

Serum levels of adiponectin and IGFBP-1 in short children born small for gestational age

OBJECTIVE: The aim of this study was to quantify serum adiponectin concentrations in short children born small for gestational age (SGA) compared with those in children born appropriate for gestational age (AGA), and to assess the relationship between the serum levels of adiponectin and insulin-like growth factor binding protein-1 (IGFBP-1) known as a predictor of the development of type 2 diabetes mellitus and cardiovascular disease. SUBJECTS AND METHODS: Sixteen prepubertal short children born SGA and 20 short children born AGA, matched for age, body mass index, height, pubertal status, gestational age, bone age and midparental height, were included in the study. The serum levels of adiponectin, IGFBP-1, insulin and insulin-like growth factor-I (IGF-I) were measured in the fasting state. RESULTS: The levels of serum adiponectin were significantly lower in the SGA than in AGA children (10.5 +/- 4.2 vs. 13.9 +/- 5.1 micro g/ml, P < 0.05). The levels of serum IGFBP-1, insulin and IGF-I were all similar in both groups. Overall, there was a significant positive correlation between adiponectin and IGFBP-1 (r = 0.40, P < 0.05). CONCLUSIONS: Our results suggest that hypoadiponectinaemia in short SGA children without catch-up growth may reflect insulin resistance and imply a higher risk of developing type 2 diabetes mellitus. Additionally, adiponectin may be a more sensitive indicator for latent insulin resistance than IGFBP-1 in short SGA children.     

IGFs and binding proteins in short children with intrauterine growth retardation.

The aim of this study was to examine the relationship between the IGF-IGF binding protein (IGFBP) axis and insulin secretion in short intrauterine growth retardation (IUGR) children. Fifteen IUGR and 12 normal short prepubertal subjects had a 90-min frequently sampled iv glucose tolerance test performed to measure plasma glucose, insulin, IGF-I, IGF-II, IGFBP-3, and IGFBP-1. In addition, 29 nonobese prepubertal subjects of normal height had fasting plasma IGF-I and IGFBP-3 levels measured. In comparison to short normal subjects, IUGR subjects had higher plasma values for IGF-I (42 +/- 10 vs. 77 +/- 31 microg/liter; P < 0.0001), IGF-II (291 +/- 76 vs. 370 +/- 66 microg/liter; P < 0.008), IGFBP-3 (1.66 +/- 0.28 vs. 2.07 +/- 0.48 mg/liter; P < 0.0005), fasting insulin (2 +/- 1 vs. 4 +/- 2 mU/liter; P < 0.004), and acute insulin response (AIR; 215 +/- 36 vs. 504 +/- 90 mU/liter; P = 0.008). Nonobese subjects of normal height had higher plasma IGF-I (117 +/- 9 microg/liter; P < 0.0001) and IGFBP-3 (2.34 +/- 0.12 mg/liter) values than the IUGR group (P < 0.0005). During the frequently sampled iv glucose tolerance test, the magnitude of the AIR in short normal subjects was related to the fall in IGFBP-1 levels (P = 0.03); however, no relationship was seen between AIR and fall in IGFBP-1 in IUGR subjects (P = 0.24). In conclusion, short IUGR children have higher plasma IGF-I, IGF-II, and IGFBP-3, when compared with normal children matched for height, weight, and pubertal status. We speculate that hyperinsulinism secondary to insulin resistance may have led to these changes to the IGF-IGFBP axis in the IUGR group.     

Glucose and insulin levels in young subjects with different maternal histories of hypertension: The Hypertension in Pregnancy Offspring Study

Objective: To analyse whether hypertension during pregnancy is associated with early signs of impaired glucose metabolism in the offspring.
Design: Longitudinal study with a 5-year follow-up.
Setting: University Hospital, Göteborg, Sweden.
Main outcome measures: Fasting levels of glucose, insulin and C-peptide.
Subjects: Thirty-six children were born to mothers with hypertension in pregnancy. The children were divided into two groups according to their mothers' blood pressure at follow-up 7–12 years after pregnancy. Nineteen children had hypertensive mothers (HT), while 17 children had normotensive mothers at follow-up (NT). A control group (C) comprised 16 children, who were born after normotensive pregnancies to mothers who remained normotensive.
Results: Fasting plasma glucose was significantly higher in HT than in NT (5.2 vs. 4.9 mmol L⁻¹; P < 0.05). In C fasting glucose was 5.1 mmol L⁻¹. The same trend was seen for fasting insulin in HT, NT and C, respectively (6.7 vs. 4.7 vs. 5.3 μU mL⁻¹). The C-peptide level was 1.61, 155 and 1.64 ng mL⁻¹, respectively. Calculated insulin resistance was 1.5 in HT, 1.0 in NT and 1.2 in C.
Conclusions: It is suggested that hypertension during pregnancy may be associated with impaired glucose metabolism and elevated fasting glucose levels in the offspring during adolescence.     

The risk of metabolic derangements is higher in children and adolescents with overweight or obesity born small for gestational age

Background and aimsBirth weight (BW) has been associated with the risk of obesity and metabolic derangements in children and adults. The aims of this study were: i. to evaluate the distribution of BW in a sample of overweight and obese children and adolescents compared with the general reference population; ii. to explore the relationship between the BW and insulin resistance and other cardiometabolic derangements in a population of children and adolescents with overweight and obesity.Methods and results710 overweight and obese children and adolescents were recruited and categorized into small (SGA), appropriate (AGA), and large (LGA) for gestational age, according to the BW percentile. Arterial blood pressure, lipid profile, glucose metabolism and hepatic steatosis were evaluated to assess cardiometabolic obesity-related derangements. The distribution of BW categories in our population was significantly different compared with the general population (SGA 6.9% vs. 8.6%, AGA 74.6% vs. 81.4%, LGA 18.5% vs. 10%; p < 0.0001). We found a higher frequency of prediabetes conditions (21.7% vs 8.9%, OR 2.97, 95% CI 1.38–6.38, p = 0.005) and borderline/high low-density lipoprotein cholesterol (31.8% vs 18.6%, OR 2.13, 95% CI 1.09–4.18, p = 0.033) in overweight and obese children born SGA compared to those born non-SGA, independently of age, sex, and BMI.ConclusionsBW is a risk factor of cardiometabolic derangements in a population of children and adolescents with overweight and obesity. Therefore, adequate obesity prevention strategies should be planned for children born SGA to minimize their risk to become obese and to reduce their short- and long-term cardiometabolic risks.     

国产比索洛尔对高血压2型糖尿病患者糖代谢的影响

目的观察国产比索洛尔对高血压合并2型糖尿病患者糖代谢及血压的影响情况。方法将符合纳入标准的高血压合并2型糖尿病患者随机分组。观察治疗前后患者糖化血红蛋白(HbA1c)、空腹血糖、糖耐量和血压等的变化。结果共有92例患者完成研究,其中比索洛尔组47例,卡托普利组45例。治疗前和经12周治疗后两组HbA1c、空腹血糖、餐后2h血糖、收缩压和舒张压差异均无统计学意义(P=0.05)。结论本研究表明比索洛尔作为高选择性β1受体阻滞剂,对于原发性高血压合并2型糖尿病患者糖代谢无明显不良影响,同时具有良好的降压效果。     

Fat distribution in non-obese girls with and without precocious pubarche: central adiposity related to insulinaemia and androgenaemia from prepuberty to postmenarche

OBJECTIVE: Precocious pubarche (PP) in girls is associated with hyperinsulinaemia and dyslipidaemia of prepubertal onset, and with ovarian hyperandrogenism and ovulatory dysfunction in adolescence, particularly if they also had prenatal growth restraint and postnatal growth acceleration. Hyperinsulinaemia may be the pathogenic key factor, possibly amplified by hyperandrogenaemia. While such PP girls do not have increased body mass index (BMI), we hypothesized that body fat mass and fat distribution may differ between PP girls and matched controls, and may relate to insulin and androgen levels. PATIENTS AND DESIGN: Sixty-seven PP girls (age range 6.0-18.0 years) and 65 control girls matched for age and pubertal stage (5.9-18.0 years) had height, weight, waist and hip circumferences measured, and dual-energy X-ray absorptiometry (DXA) assessment of total body fat mass, and fat mass in abdominal and truncal regions. All girls had fasting plasma glucose, serum insulin, lipids, testosterone and SHBG levels measured; PP girls also had a standard 2-h oral glucose tolerance test (oGTT). RESULTS: Despite no differences in BMI, PP girls had significantly larger waist circumference, waist-to-hip ratio, total fat mass, percentage fat mass, abdominal fat mass, and truncal fat mass vs. controls in each pubertal stage. Overall, fasting insulin levels, free androgen index (FAI) and blood lipid levels were more closely related to central fat than to total body fat mass. In a multiple regression analysis, truncal fat mass was independently related to both fasting insulin (P = 0.009) and FAI (P < 0.0001). Abdominal fat mass was inversely related to birthweight (r = -0.25, P = 0.001). In PP girls, central fat mass was positively related to insulin levels after oGTT (truncal fat vs. 30 min insulin; r = 0.46, P < 0.0005). CONCLUSIONS: Precocious pubarche girls had excess total body and central fat mass throughout all pubertal stages, and increased central fat was related to hyperinsulinaemia and hyperandrogenaemia. It remains to be verified whether body composition in PP girls can be normalized by insulin-sensitization and/or antiandrogen therapy.     

Polycystic ovary syndrome: lack of hypertension despite profound insulin resistance.

It has been hypothesized that insulin resistance and hyperinsulinemia contribute to the development of arterial hypertension. To further investigate this relationship, we compared arterial blood pressure in controls and women with polycystic ovary syndrome (PCO), an insulin-resistant state. Fourteen PCO women and 18 normal control women of similar age, body mass index, and race were studied. Plasma glucose and insulin levels were determined in an oral glucose tolerance test. The insulin sensitivity (SI) index was determined by the minimal model method. Systolic and diastolic blood pressure were measured by 24-h ambulatory monitoring. Left ventricular mass was assessed by echocardiography. The two groups had comparable fasting glucose levels, but the 2-h postload glucose was higher in PCO (8.0 +/- 0.5 vs. 5.6 +/- 0.3 mmol/L; P less than 0.001). Compared to controls, PCO women were significantly more insulin resistant by fasting insulin, 2-h insulin concentrations, and SI (28.3 +/- 6.7 vs. 68.3 +/- 10.0 min-1/nmol.mL; P less than 0.01). Average ambulatory systolic (121 +/- 2 vs. 118 +/- 2 mm Hg) and diastolic (76 +/- 2 vs. 73 +/- 2 mm Hg) blood pressures were similar for PCO and control women. No difference was found in left ventricular mass. Therefore, despite profound insulin resistance and hyperinsulinemia, women with PCO do not have increased arterial pressure or left ventricular mass.     

IGFBP-1 levels in adult women born small for gestational age suggest insulin resistance in spite of normal BMI

OBJECTIVE: Impaired fetal development may contribute to decreased insulin sensitivity. This study was designed to characterize serum markers of insulin resistance in adults born small for date or born prematurely. STUDY DESIGN: Fifty subjects, all women, were evaluated at a mean age +/- SD of 26 +/- 2 years (range: 23-30 years). They were allocated to three groups: (i) born fullterm with birth weight <2600 g (n = 18) (small for gestational age, SGA), (ii) born before gestational week 32 (n = 15) (ex-preterm), and (iii) controls, born fullterm with appropriate birth weight (n = 17). Anthropometric data as well as fasting serum samples of plasma B-glucose, serum lipids, insulin, insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-1 (IGFBP-1) levels were determined. RESULTS: In the SGA group final height was lower and they weighed less compared with the controls. Fasting insulin and glucose levels did not differ amongst the groups. Triglycerides were lower in the SGA group and in the ex-preterm group compared with the controls (P < 0.05). The SGA group showed lower IGFBP-1 levels compared with the controls median 17 (range 3-121) vs. 26 (7-67) microg L-1; P < 0.05]. The IGF-I levels in the SGA, ex-preterm and control groups were 212 +/- 58, 259 +/- 37 and 216 +/- 32 microg L-1, respectively, corresponding to a mean SD score of -0.8 +/- 1.0, 0.1 +/- 0.6 and -0.6 +/- 0.6. CONCLUSION: As IGFBP-1 is a marker of insulin sensitivity, the low levels observed in adult women with normal BMI, born small for date, suggest relative insulin resistance in spite of normal BMI.     

Increased oxidative stress in prepubertal children born small for gestational age

CONTEXT: Low birth weight is associated with an increased risk of metabolic and cardiovascular diseases in adulthood. The development of insulin resistance (IR) seems to play a pivotal role; no data on the oxidant-antioxidant status are available in this risk group. OBJECTIVE: This study is an assessment of oxidant-antioxidant status in prepubertal children born small for gestational age (SGA) in comparison to healthy controls and the relationship to IR. DESIGN: This cross-sectional study compares indexes of IR and oxidant-antioxidant status in three different groups (SGA+, SGA-, controls), with analysis by post hoc and Pearson correlation. SETTING: The study was conducted in the Academic Department of Pediatrics. PARTICIPANTS: A total of 19 SGA+ and 16 SGA- children were compared with 13 controls. INTERVENTION: No intervention was used. MAIN OUTCOME MEASURES: Indexes of IR (glucose to insulin ratio, homeostasis model assessment of IR) were evaluated, and markers of oxidative stress (lag phase, malonildialdehyde, vitamin E) were measured. RESULTS: Homeostasis model assessment of IR was significantly higher in SGA+ than SGA- children (1.32+/-0.9 vs. 0.69+/-0.47; P=0.03) and controls (0.71+/-0.37; P=0.04). Glucose to insulin ratio was significantly lower in SGA+ than SGA- children (12.41+/-5.01 vs. 26.54+/-17.18; P=0.02) and controls (26.96+/-20.70; P=0.04). Lag phase was significantly shorter in SGA+ than SGA- children (24.3+/-4.38 vs. 35.59+/-11.29 min; P=0.003) and controls (45.28+/-7.69 min; P=0.0001) and in SGA- than controls (P=0.01). Malonildialdehyde was significantly higher in SGA+ than SGA- children (0.79+/-0.3 vs. 0.6+/-0.1 nmol/mg; P=0.03) and controls (0.36+/-0.04 nmol/mg; P=0.0001) and in SGA- children than controls (P=0.02). Vitamin E was significantly reduced in SGA+ children than controls (27.54+/-7.9 vs. 43.23+/-11.32 micromol/liter; P=0.002). CONCLUSION: Oxidative stress is present in both SGA+ and SGA- children, with a continuous alteration in relation to IR. Therefore, catch-up growth might exert the greatest influence in the development of future diseases.