Insulin Resistance In Children Research Articles

Evidence of the influence of physical activity on the metabolic syndrome and/or on insulin resistance in pediatric populations: a systematic review

This study is aimed at updating the relationships between physical activity (PA) and the metabolic syndrome (MetS) and/or insulin resistance (IR) in youth. Cross-sectional, prospective cohort and intervention studies, which examined the effect of PA on MetS, its components and IR in children and adolescents (<18 yrs), were searched by applying a combination of criteria in the PubMed database. The electronic search of studies published from 2000-2010 yielded >150 references. Of these, 37 studies were included. Twenty-six studies (70%) were cross-sectional observation studies, and two studies (8%) were prospective cohort studies. The remaining eight studies (22%) were interventions, of which three (<10% of all included studies) were randomized controlled trials. Commonly, higher PA levels were consistently associated with an improved metabolic profile and a reduced risk for MetS and/or IR in these populations. The impact of PA on MetS and/or IR appeared to be either independent of other factors, or alternatively or simultaneously mediated by the physical fitness and adiposity of youth. However, more-robustly designed interventions (i.e., some mega-randomized controlled trials based on lifestyle interventions) and additional cohort studies are required to make definitive inference about the magnitude and role of PA as a single genuine preventive and treatment strategy for the metabolic and cardiovascular risk of youth in the current obesogenic context.

Low maternal B12 status is associated with offspring insulin resistance but B12 or folate supplementation does not alter that risk

There is concern that high maternal folate and low B12 status are associated with offspring insulin resistance (HOMA). We previously reported that maternal micronutrient supplementation had no effect on HOMA. Here, we report the association between maternal folate and B12 status and HOMA. In a substudy (n=1132) of a RCT of vitamin A alone (control) or with folic acid, folic acid-iron, folic acid-iron-zinc, or multiple micronutrient supplements, micronutrient status was assessed in early and late pregnancy (~10 and 36 wks gestation). In the offspring at 6–8 y, insulin resistance was estimated with the HOMA model using fasting insulin and glucose. Child HOMA was not associated with maternal plasma folate or B12 at early (folate β=0.05, p=0.48; B12 β=−0.05, p=0.42) or late (folate β=−0.02, p=0.77; B12 β=−0.09, p=0.21) pregnancy in continuous models. However, children whose mothers were B12 deficient (<148 pmol/L) at enrollment had a 26.7% increase in HOMA (p=0.02); this was not observed for low or high folate levels. Among B12 deficient women, micronutrient supplements containing folate with or without B12 among other nutrients did not affect HOMA (p>0.05 for all). Low B12 but not folate status during pregnancy is associated with insulin resistance in childhood, but maternal micronutrient supplementation that includes B12 does not alter that risk. Funded by the Gates Foundation and USAID.

P300 auditory event-related potentials in children with obesity: is childhood obesity related to impairment in cognitive functions?

To investigate alterations in P300 auditory event-related potentials in children with obesity to detect changes in cognitive functions. A total of 50 children with obesity and 23 age- and sex-matched healthy control subjects were included in the study. Laboratory tests were performed to detect dislipidemia and insulin resistance (IR). The latencies and amplitudes of P300 waves were measured in healthy and obese subjects with or without IR. The oddball paradigm was used in recordings of P300 auditory event-related potentials. A significant difference was observed between groups regarding latency and amplitude of P300 component obtained from central (Cz) electrode. The grand means of P300 latency were longer, and amplitude decreased significantly in obese group compared to that of healthy controls. When the obese group was divided into two different subgroups, those with IR and without IR, the grand means of P300 latency were longer and the amplitude decreased significantly in subjects with IR compared to those without IR. Both decreased amplitude and prolonged latency of P300 are associated with IR in children with obesity, which shows the impairment of neural activity associated with sensory and cognitive information processing in these children. Further studies are necessary to strengthen the current findings and to determine the exact mechanism of cognitive impairment in obese children.

Obesity and Insulin Resistance in Children

Obesity and Insulin Resistance in Children

Chronic Parenteral Nutrition Induces Hepatic Inflammation, Steatosis, and Insulin Resistance in Neonatal Pigs1–3

Prematurity and overfeeding in infants are associated with insulin resistance in childhood and may increase the risk of adult disease. Total parenteral nutrition (TPN) is a major source of infant nutritional support and may influence neonatal metabolic function. Our aim was to test the hypothesis that TPN induces increased adiposity and insulin resistance compared with enteral nutrition (EN) in neonatal pigs. Neonatal pigs were either fed enteral formula orally or i.v. administered a TPN mixture for 17 d; macronutrient intake was similar in both groups. During the 17-d period, we measured body composition by dual-energy X-ray absorptiometry scanning; fasting i.v. glucose tolerance tests (IVGTT) and hyperinsulinemic-euglycemic clamps (CLAMP) were performed to quantify insulin resistance. On d 17, tissue was collected after 1-h, low-dose CLAMP for tissue insulin signaling assays. TPN pigs gained less lean and more body fat and developed hepatic steatosis compared with EN pigs. After 7 and 13 d, IVGTT showed evidence of insulin resistance in the TPN compared with the EN group. Fasting plasma glucose and insulin also were higher in TPN pigs. CLAMP showed that insulin sensitivity was markedly lower in TPN pigs than in EN pigs. TPN also reduced the abundance of the insulin receptor, insulin receptor substrate 1, and phosphatidylinositol 3 kinase in skeletal muscle and liver and the proliferation of total pancreatic cells and β-cells. Hepatic proinflammatory genes as well as c-Jun-N-terminal kinase 1 phosphorylation, plasma interleukin 6, and tumor necrosis factor-α were all higher in TPN pigs than in EN pigs. The results demonstrate that chronic TPN induces a hepatic inflammatory response that is associated with significant insulin resistance, hepatic steatosis, and fat deposition compared with EN in neonatal pigs. Further studies are warranted to establish the mechanism of TPN-induced insulin resistance and hepatic metabolic dysfunction and whether there are persistent metabolic consequences of this lifesaving form of infant nutritional support.

Relationship between resistin and aPAI‐1 levels with insulin resistance in Saudi children

Association of resistin with insulin resistance (IR) in humans is still controversial and few studies have investigated the association of plasminogen activator inhibitor-1 (PAI-1) with IR in children. The purpose of the present study was therefore to evaluate serum levels of resistin and active PAI-1 (aPAI-1) in Saudi children and their association with the various obesity-related complications. In this cross-sectional study, 73 boys and 77 girls with varying body mass index (BMI) were recruited. They were assessed for anthropometric measures and fasting serum levels of glucose, insulin, lipid profile, resistin, angiotensin II (ANG II) and aPAI-1. Resistin was positively correlated with hips (r = 0.33, P < 0.01), waist (r = 0.23, P < 0.05) and BMI (r = 0.33, P < 0.01). The association of resistin with the markers of obesity was also significant in girls but lost significance in boys. aPAI-1 was positively correlated with total cholesterol (r = 0.24; P < 0.01), triglycerides (r = 0.2, P < 0.05), HOMA-IR (r = 0.26, P < 0.01) and insulin (r = 0.26, P < 0.01). The significant association of aPAI-1 with IR was also true in girls but lost significance in boys. Resistin is not correlated with IR and further studies are needed to explore the role of resistin especially in childhood obesity. In contrast, increased levels of PAI-1 may contribute to the risk of cardiovascular diseases related to obesity and insulin resistance in children. The observed gender-related differences in the association between resistin, aPAI-1 with obesity markers and IR could be attributed to sexual dimorphism in body fat distribution.

The early origins of chronic heart failure: impaired placental growth and initiation of insulin resistance in childhood.

Low birth weight and low placental weight predict later coronary heart disease and hypertension. This has led to the hypothesis that these diseases are initiated by foetal programming, the process by which foetal malnutrition leads to permanent changes in the body in ways that lead to chronic disease in later life. Here we examine the association between body and placental size at birth and later chronic heart failure. We identified 187 patients taking medications for chronic heart failure in a birth cohort of 13,345 people born in Helsinki, Finland during 1934-44. Chronic heart failure was associated with a small placental surface area. In people born with a placental area less than 225 cm(2), the odds ratio for chronic heart failure was 1.7 (1.1-2.5), compared with people born with a placental area greater than 295 cm(2). The risk of heart failure was further increased by rapid gain in body mass index after the age of 2 years, a path of growth known to be linked to insulin resistance in later life. In a simultaneous regression, low body mass index at 2 years and high body mass index at 11 years were each associated with chronic heart failure (P = 0.008 and 0.001, respectively). Chronic heart failure in adult life may be initiated by impaired placental growth which adversely affects cardiac development. People born with a vulnerable heart are more likely to develop chronic heart failure if they become insulin resistant.

Preliminary data on the association between waist circumference and insulin resistance in children without a previous diagnosis

The aim of the present work was to study the association between different anthropometric parameters and insulin resistance (IR) in Spanish schoolchildren without a previous diagnosis. A total of 443 Spanish schoolchildren (9-11 years of age) were studied in this cross-sectional study. The anthropometric measurements collected were weight, height, body circumferences and skinfolds. Body mass index (BMI), waist/hip ratio, percentage body fat and fat-free body mass were determined. Overnight-fasted blood lipids, insulin and glucose levels were analysed, and estimation of IR, taking into account the homeostasis model assessment (HOMA), was calculated. The children with IR had higher serum triglycerides and insulin levels, were heavier and taller, and had a higher BMI, a larger waist circumference, a larger hip circumference, a larger waist/hip ratio and thicker bicipital and tricipital skinfolds than those who did not have IR. Age, sex, BMI and waist circumference explained 32.0% of the variance in the HOMA values; only sex, triglycerides and waist circumference independently influenced this variable. A 1-cm increase in waist circumference was associated with approximately a 3.8% increase in the mean HOMA value. The children with a waist circumference of over the p90 for their age and sex were at greater risk of showing IR as measured by the HOMA: odds ratio = 6.94 (2.01-23.91; P < 0.001). In conclusion, according to these results, waist circumference is the best anthropometric parameter associated with IR in children, and those with a waist circumference of over the p90 for their age and sex would appear to be at particular risk.

Association of osteoprotegerin and rankl levels with insulin resistance in pubertal obese children

Abstract Osteoprotegerin (OPG)/“receptor activator of nuclear factor kappa B-ligand” (RANKL) system has an important role in the remodeling of bone through regulation of osteoclastogenesis. We aimed to detect OPG and RANKL levels, particularly in obese children in the pubertal period and to investigate whether these parameters correlate with insulin resistance in childhood. Our study included 66 obese children ranging in age from 9.1 to 16 years, and 22 non-obese children ranging in age from 10.5 to 16 years. Blood glucose, insulin, total cholesterol, HDL cholesterol, and LDL cholesterol levels were measured for all cases; HOMA-IR, Quicki index and atherogenic index were calculated. Serum OPG and RANKL levels were also measured. OPG and RANKL levels did not show any difference between obese and non-obese children (P&gt;.05). No difference in these 2 parameters were observed among the children with and without insulin resistance (P&gt;.05). No correlation could be established between the OPG, the HOMA-IR, Quick and atherogenic indices. Obesity and insulin resistance are believed to show their effect in the later period of life to become able to change some of the parameters.

Weight Gain and Insulin Resistance in Children Treated With Valproate: The Influence of Time

This study was undertaken in 2 parts to investigate the relationship between body size and insulin resistance during treatment with valproic acid in children. The cross-sectional part revealed differences in terms of body size and homeostasis model assessment of insulin resistance, which were higher in the group on medication. The longitudinal part showed a major increase in body size and insulin resistance during the first year of therapy. There was a subsequent decrease in insulin resistance in association with the rise of body size, however with a trend to level off. These results might be helpful to enhance the knowledge of valproic acid action on both insulin resistance and weight gain, allowing to plan appropriate approach for the prevention of the consequences of the treatment with valproic acid.

Serum glucocorticoids and adiponectin associate with insulin resistance in children born small for gestational age

Altered glucocorticoid activity is one possible mechanism linking fetal growth restriction with later insulin resistance (IR) and type 2 diabetes. We aimed to investigate whether serum glucocorticoid parameters are related to IR in children born small for gestational age (SGA). A total of 110 children (55 age- and gender-matched pairs born SGA or appropriate for gestational age (AGA) in a case-control setting) were studied at the mean age of 12.2 (s.d. 0.2) years. Serum cortisol, corticosteroid-binding globulin (CBG), free cortisol index (FCI=cortisol/CBG), and glucocorticoid bioactivity (GBA, transactivation assay) were analyzed and related to serum adiponectin and insulin-like growth factor-binding protein 1 (IGFBP1) concentrations and homeostasis model assessment for IR (HOMA-IR) and QUICKI indices. In the pooled study population, GBA correlated well with cortisol and FCI (r=0.681 and 0.586 respectively; P<0.001 for both). Serum cortisol, CBG, FCI, GBA, HOMA-IR, or QUICKI did not differ between the SGA and AGA subjects, but the SGA children had lower body mass index (P=0.005) and waist circumference (WC) (P=0.001). The mean GBA in the highest GBA quartile was higher among the SGA subjects than among the AGA subjects (138.6 vs 96.4 nmol/l cortisol equivalents, P<0.001). In the SGA children, GBA correlated positively with HOMA-IR (r=0.522, P<0.001) and inversely with adiponectin (r=-0.278, P=0.042) (WC/height ratio adjustments), and in logistic regression analysis, higher GBA (odds ratio (OR) 1.3; P=0.013), lower adiponectin (OR 1.4; P=0.038), and lower IGFBP1 (OR 1.9; P=0.010) associated independently with higher HOMA-IR. These findings suggest that increased glucocorticoid activity and low serum adiponectin concentrations associate with IR in SGA children.

The relationship between birth weight and insulin resistance in childhood

Chronic diseases that are typical of adulthood may originate in intra-uterine life through inadequate fetal development. The present epidemiological cohort study of 506 healthy children aged 5-8 years evaluated the relationship between birth weight and insulin resistance in an age group that has been assessed in few similar studies. Insulin concentration was determined by chemiluminescence and insulin resistance by the homeostasis model assessment (HOMA). Blood glucose, total cholesterol and fractions (LDL cholesterol and HDL cholesterol) and TAG concentrations were determined by automated enzymatic methods. Linear regression analysis investigated the relationship between birth weight (assessed as a continuous variable and in three categories: small for gestational age, SGA; adequate for gestational age and large for gestational age) and the HOMA index, using backward stepwise selection and biological models to explain the causal pathway of the relationship. There were negative associations between birth weight (P < 0.001), SGA (P = 0.027) and the HOMA index, and a positive association between waist circumference (P < 0.001) and the HOMA index. Considering the significant associations between birth weight and waist circumference (P < 0.001) and waist circumference and insulin resistance (P < 0.001), we can probably suspect that lower birth weight is a common cause of higher waist circumference and insulin resistance. In summary, the results of the present study showed increased insulin resistance in apparently healthy, young children, who had lower weight at birth and higher measurements of waist circumference. There is a need to develop public health policies that adopt preventive measures to promote adequate maternal-fetal and child development and enable early diagnosis of metabolic abnormalities.

Prevalence of metabolic markers of insulin resistance in offspring of gestational diabetes pregnancies

In utero hyperglycemia has been associated with insulin resistance (IR) in children; however, there are limited data in low-risk populations. The purpose of this study was to describe the prevalence of metabolic markers of IR in a primarily Caucasian cohort of gestational diabetes mellitus (GDM) offspring aged 7-11 yr (mean 9.1) and to correlate offspring with maternal indexes. Sixty-eight children were recruited through a follow-up study of women who participated in a randomized controlled trial of minimal intervention vs. tight glycemic control for GDM. All participants had a fasting plasma glucose (FPG), insulin, total cholesterol, high-density lipoprotein cholesterol (HDL-chol), triglyceride (TG) level, and a 2-h oral glucose tolerance test. We calculated homeostasis model assessment (HOMA) and recorded body mass index and waist circumference (WC). Criteria for metabolic syndrome for children included: FPG > 6.0 mmol/L, HDL-chol < 1.03 mmol/L, TG > 1.24 mmol/L, WC > 90% for age and gender, and 2-h glucose > 7.8 mmol/L. Among these children, 45 (66%), 17 (25%), 5 (7%), and 1 (1.5%) had zero, one, two, or three metabolic markers of IR, respectively. Hypertriglyceridemia (21%) was most prevalent, with no child having an elevated FPG. WC (p = 0.018) and TG (p = 0.005) were strong predictors of IR in the offspring after adjustment for age, gender, birthweight, family history, and maternal IR. Maternal and offspring HDL-chol, TG, WC, and HOMA but not fasting or 2-h glucose levels were significantly correlated. We conclude that metabolic markers of IR in children exposed to GDM may be present in the absence of abnormal fasting or 2-h glucose values. Screening strategies that focus on glucose levels may need to be reconsidered to institute early intervention with lifestyle changes for children at risk.

Metabolic programming of offspring by vitamin B12/folate imbalance during pregnancy

With two reports in the current issue of Diabetologia, C. S. Yajnik and his international cast of collaborators have created conceptual bridges between some of the most important global public health challenges of our time: obesity (or is it adiposity?), fetal or early life origins of adult disease, and prevalent and persisting micronutrient malnutrition [1, 2]. One study from the cohort within the Pune Maternal Nutrition Study allows analysis of the relationship between maternal nutritional status and midand late pregnancy and childhood outcomes at 6 years of age [1]. A striking finding was that two-thirds of the mothers had low circulating levels of vitamin B12; their offspring were short and thin, but had more body fat. This was associated with a high prevalence of insulin resistance, presumably presaging later entry into the epidemic of type 2 diabetes among adults in India. From this novel focus comes the observation that the combination or interaction of vitamin B12 deficiency and high erythrocyte folate in mothers is associated with the highest prevalence of insulin resistance according to homeostatic model assessment of insulin resistance. This provides confirmation of a previous study reporting childhood insulin resistance in association with higher adiposity and thinness (presumably with low lean mass) [3]. The observation of low vitamin B12 status in mothers [1] was not surprising, given the high prevalence of vegetarian dietary habits, but the relationship to later insulin resistance and adiposity in the offspring provides a powerful challenge for further work to explain this relationship and its persistence in the offspring. While the evidence presented by Yajnik et al. [1] does not distinguish between the positive relationship between adiposity and insulin resistance, as opposed to an inverse relationship between low lean or muscle mass and insulin resistance, these data call out for a mechanistic explanation of the relationship between micronutrient changes in the mother in late pregnancy and persisting metabolic/functional abnormalities in the offspring. Some suggestions are offered by the authors, although with no supporting data as yet. The concept of fetal or early infancy programming of later metabolic and disease outcomes is well described [4, 5], even though the mechanism by which programming in fetal life or infancy might be sustained remains unexplained. We know that the two micronutrients in this report are related metabolically, and that both folate and vitamin B12 are involved in DNA synthesis and methylation— actions at the core of what has been called epigenetics. Folate in particular is related to the efficiency of DNA methylation, which in turn has lasting effects on selected metabolic processes through the ability of strategic DNA methylation to promote or silence gene expression. One of the two known functions of vitamin B12 as a cofactor in the methionine synthase reaction (Fig. 1), which converts homocysteine into methionine, depends on methylfolate to provide the methyl group, and methionine is converted into S-adenosyl methionine, which is subsequently utilised in dozens of methylation reactions, including methylation of Diabetologia (2008) 51:6–7 DOI 10.1007/s00125-007-0869-8

Insulin resistance and body composition in preterm born children during prepubertal ages

Premature born children may show insulin resistance in childhood which may be due to intrauterine or postnatal adverse environmental factors. Aim of this study was to evaluate insulin resistance and body composition in preterm born children born appropriate for gestational age (AGA) or small for gestational age (SGA) and relations with IGF-I, IGFBP-3 axis. Ninety-three preterm born children grouped as premature SGA (n = 30) and premature AGA (n = 63) were evaluated at age 4.6 +/- 0.2 years and 4.7 +/- 0.1 years with respect to their glucose, insulin, IGF-I, IGFBP-3, IGFBP-1, leptin levels and body composition by dual-energy X-ray absorptiometry. Their data were compared to that of body mass index (BMI) matched term SGA (n = 42) and term AGA (n = 44) children of age 4.5 +/- 0.2 and 3.8 +/- 0.1 years. All children had height appropriate for their target height. Insulin resistance was evaluated by basal insulin and homeostasis model assessment for insulin resistance (HOMA-IR). Basal insulin level was similar in preterm AGA (4.3 +/- 1.4 pmol/l) and term AGA (7.9 +/- 6.4 pmol/l) children at similar and normal BMI levels. Preterm SGA children had insulin levels (5.0 +/- 3.6 pmol/l) similar to preterm AGA children but significantly lower than that in term SGA children (23.7 +/- 20.8 pmol/l) (P = 0.001). Similar results were obtained for HOMA-IR. Term SGA children had also significantly lower IGFBP-1 levels. Body composition, leptin and IGFBP-3 did not differ between the respective groups. IGF-I was lower in preterm AGA (5.0 +/- 0.6 nmol/l) than in term AGA (8.3 +/- 1.2 nmol/l) (P < 0.001) children. Premature born AGA and SGA children do not have insulin resistance when compared to term children if they have made a catch-up growth appropriate for their target height and have normal BMI. The similar insulin levels in preterm SGA and preterm AGA children together with increased insulin levels in term SGA children points to the fact that it is the intrauterine restriction in the third trimester that has an adverse effect on future adverse metabolic outcome.

Obesity and Insulin Resistance in Childhood

Obesity is a serious risk factor for insulin resistance leading to diabetes and other disorders. As it is also occurring at ever younger age groups the aim of this study was to compare average levels of the homeostatic indices HOMA and QUICKI in obese compared to healthy children in an effort to find convenient markers for insulin sensitivity in clinical pediatric practice. Twenty one obese and 29 healthy children were selected. The average level of HOMA in obese children was 3.6, in healthy children 1.7 while the average level of QUICKI in obese children was 0.33 and in healthy children 0.36. The results demonstrate the possibility of insulin sensitivity assessment using these indices in pediatric practice. QUICKI has a narrower confidence interval and thus lower variability.

Behavior of Insulin Resistance and Its Metabolic Correlates in Prepubertal Children

Secular trends in childhood obesity suggest that many children are gaining excess fat, thereby contributing to an emerging epidemic of type 2 diabetes in young people (1,2). However, it is normal for children to accumulate some fat in the years before puberty (3). These considerations highlight the difficulty in distinguishing pathological from physiological fat accumulation. Longitudinal data in healthy children are required in order to properly examine the relationships between adiposity and metabolic health. We prospectively studied a cohort of healthy prepubertal British school children and report here some unexpected temporal relationships between adiposity and insulin resistance. EarlyBird is a prospective nonintervention study investigating the emergence of insulin resistance in childhood. A cohort of 307 healthy children was recruited in 2000–2001 from randomly selected schools in Plymouth, U.K. Most are Caucasian, with a wide socioeconomic mix. Mean ± SD age at recruitment was 4.9 ± 0.25 years. The protocol has previously been described in detail (4). Results are reported for the first 4 study years, when the children were aged 5, 6, 7, and then 8 years. Only children who attended at all four time points (130 boys and 100 girls) were included for analysis. Those excluded (40 boys and 37 girls) did not differ anthropometrically or in metabolic measures at age 5 years ( t tests; all P > 0.05). The male preponderance resulted from random recruitment. Results are presented separately by sex. ### Annual measures Annual measures included height, weight, BMI standardized to 1990 U.K. reference data (SD scores), sum of five skinfolds (SSF) (skinfolds measured twice over biceps and triceps of the left arm and the subscapular, suprailiac, …

Childhood obesity and insulin resistance

Insulin resistance (IR) in childhood has importance to the understanding and prevention of the growing epidemic of insulin resistance syndrome (IRS) in adults with attendant obesity, type 2 diabetes (T2DM), atherosclerotic diseases, hypertension, gout, non-alcoholic, steato-hepatitis (NASH), gall bladder disease, nephropathy, polycystic ovarian disease (PCOS), infertility and premature senility. The severity of IR and its' complications in children unfortunately and usually progresses in their pubertal transition to adulthood; affected young children are more likely than adults to have underlying causal monogenic disorders; the sequence of natural history and events give insights into disease pathogeneses, and optimal life style choices that last are best made during the early formative years. Some features of IR in children discussed herein are: a strong tendency to low birth weight for gestational age, adverse effects of adrenarche and therapeutic steroid therapy, predisposition to premature pubarche, acanthosis nigricans, tall stature despite pituitary GH suppression, allergic diathesis, hyperandrogenism and PCOS, dyslipidemia and fatty liver disease, and diagnosis by clinical and biochemical markers of IR including insulin regulated hepatic hormonal binding proteins such as IGFBP-1. The national preoccupation with the "metabolic syndrome" T2DM and obesity, should be appropriately directed to an improved understanding of IR in children and their management, if the looming health crisis in affected adults is to be seriously addressed. The nation is facing its' first generation of children who will be less healthy and die younger than the previous generation (Marks (2005) Presentation to the American Association of Diabetes Educators 32nd Annual Meeting and Exhibition, August 10-13, Washington, DC).

Glucose Regulation in Young Adults with Very Low Birth Weight

The association between small size at birth and impaired glucose regulation later in life is well established in persons born at term. Preterm birth with very low birth weight (<1500 g) is also associated with insulin resistance in childhood. If insulin resistance persists into adulthood, preterm birth with very low birth weight also may be associated with an increased risk of disease in adulthood. We assessed glucose tolerance and insulin sensitivity and measured serum lipid levels and blood pressure in young adults with very low birth weight. We performed a standard 75-g oral glucose-tolerance test, measuring insulin and glucose concentrations at baseline and at 120 minutes in 163 young adults (age range, 18 to 27 years) with very low birth weight and in 169 subjects who had been born at term and were not small for gestational age. The two groups were similar with regard to age, sex, and birth hospital. We measured blood pressure and serum lipid levels, and in 150 very-low-birth-weight subjects and 136 subjects born at term, we also measured body composition by means of dual-energy x-ray absorptiometry. As compared with the subjects born at term, the very-low-birth-weight subjects had a 6.7% increase in the 2-hour glucose concentration (95% confidence interval [CI], 0.8 to 12.9), a 16.7% increase in the fasting insulin concentration (95% CI, 4.6 to 30.2), a 40.0% increase in the 2-hour insulin concentration (95% CI, 17.5 to 66.8), an 18.9% increase in the insulin-resistance index determined by homeostatic model assessment (95% CI, 5.7 to 33.7), and an increase of 4.8 mm Hg in systolic blood pressure (95% CI, 2.1 to 7.4). Adjustment for the lower lean body mass in the very-low-birth-weight subjects did not attenuate these relationships. Young adults with a very low birth weight have higher indexes of insulin resistance and glucose intolerance and higher blood pressure than those born at term.

Development of insulin resistance and its relation to diet in the obese child

The incidence rate of obesity in youth has continued to increase worldwide and about 30% of obese children display insulin resistance (IR) and other metabolic abnormalities. The present study reviews the mechanisms for development of IR in the obese child and possible links between IR and dietary factors in childhood and adolescence. Although increased concentrations of plasma free fatty acids (FFA) and their counter part at intracellular level, long-chain acyl-coenzyme A (LC acyl-CoA), have been related to the early onset of IR in childhood obesity, a new endocrine paradigm states that adipose tissue secretes a wide variety of hormones and cytokines that regulate lipid energy metabolism. These hormonal changes precede any changes in metabolites such as FFA and glucose and appear to be associated with early IR in childhood. Excessive caloric intake increases IR in children; opposite, substantial reduction of overweight achieved by a hypocaloric diet decreases it. Elevated consumption of animal protein, particularly in early life, as well as diets rich in saturated, trans, and n-6 polyunsaturated fatty acids, and diets with a high carbohydrate to fat ratio, besides a high glycaemic and low-fiber diet also appear to exacerbate adiposity and IR.