Biomedical subjects

David B Dunger

Publications and source records attributed to David B Dunger.

At least 19 recordsLinked to original sources

PubMed2006

Association of weight gain in infancy and early childhood with metabolic risk in young adults.

CONTEXT: Early postnatal life has been suggested as an important window during which risks for long-term health may be influenced. OBJECTIVE: The aim of this study was to examine the independent associations between weight gain during infancy (0-6 months) and early childhood (3-6 yr) with components of the metabolic syndrome in young adults. DESIGN: This was a prospective cohort study (The Stockholm Weight Development Study). SETTING: The study was conducted in a general community. PARTICIPANTS: Subjects included 128 (54 males) singletons, followed from birth to 17 yr. MAIN OUTCOME MEASURE: None of these young adults met the full criteria for the metabolic syndrome. We therefore calculated a continuous clustered metabolic risk score by averaging the standardized values of the following components: waist circumference, blood pressure, fasting triglycerides, high-density lipoprotein cholesterol, glucose, and insulin level. RESULTS: Clustered metabolic risk at age 17 yr was predicted by weight gain during infancy (standardized beta = 0.16; P < 0.0001) but not during early childhood (standardized beta = 0.10; P = 0.23), adjusted for birth weight, gestational age, current height, maternal fat mass, and socioeconomic status at age 17 yr. Further adjustment for current fat mass and weight gain during childhood did not alter the significant association between infancy weight gain with the metabolic risk score (standardized beta = 0.20; P = 0.007). CONCLUSIONS: Rapid weight gain during infancy (0-6 months) but not during early childhood (3-6 yr) predicted clustered metabolic risk at age 17 yr. Early interventions to moderate rapid weight gain even at very young ages may help to reduce adult cardiovascular disease risks.

Adolescent↗

PubMed2006

Early and late weight gain and the timing of puberty.

Nutrition is an important regulator of the tempo of growth and obesity is usually associated with tall childhood stature and earlier pubertal development. Several longitudinal studies have demonstrated that timing of puberty is most closely linked to infancy weight gain: suggesting an early window for programming of growth and development. Earlier puberty in the UK MRC 1946 birth cohort was related to smaller size at birth and rapid growth between 0 and 2 years. Rapid early weight gain leads to taller childhood stature and higher insulin-like growth factor I (IGF-I) levels, possibly through early induction of growth hormone (GH) receptor numbers, and such children are also at risk of childhood obesity. In the Avon Longitudinal Study of Parents and Children, rapid infancy weight gain was associated with increased risk of obesity at 5 and 8 years, with evidence of insulin resistance, exaggerated adrenarche and reduced levels of sex hormone binding globulin (SHBG). Potentially the elevated IGF-I and adrenal androgen levels, increased aromatase activity and increased 'free' sex steroid levels consequent to lower SHBG levels could all promote activity of the GnRH pulse generator. In addition obese children have higher leptin levels, a proven permissive factor in initiating LH pulsatility. Obesity could also affect the rate of progression through puberty as nutrition and SHBG may act respectively as an accelerator and brake on peripheral sex steroid action. Early weight gain and early pubertal development might also be associated with loss of the pubertal growth spurt perhaps through obesity-related suppression of GH secretion. Trans-generational recurrence of low birth weight, early catch-up weight gain, earlier menarche, and shorter adult stature have been observed in women, and could contribute to the strong heritability in age at menarche.

Age Factors↗

PubMed2006

Lessons from large population studies on timing and tempo of puberty (secular trends and relation to body size): the European trend.

Ever since the publication of the first textbook on human growth by Johann Augustin Stoeller in 1729, temporal changes (or secular trends) in growth and pubertal maturation have been observed throughout the world. Data covering the longest time span are often reported from European populations. For example, in Norway and Denmark the age at menarche has fallen rapidly since the 19th century, by up to 12 months per decade. These changes have broadly paralleled increases in adult height in most European countries over the last century, with rates of around 10-30mm per decade. These secular trends are influenced by background ethnic, geographical and socio-economic factors, and clearly nutritional changes have an important role as reflected by positive correlations between age at puberty onset or age at menarche and childhood body size. Changes in height, pubertal maturation, and childhood body size have all also been related to rate of weight gain in infancy, and there is growing evidence to suggest that this early postnatal period may represent an early window of susceptibility to long-term 'programming' of various outcomes in humans. There is debate as to whether the secular trends in pubertal maturation are continuing or have reached their limit. Even where temporal changes are overall clearly significant, they are most marked in the more nutritionally deprived sub-groups. Whether over-nutrition and increasing childhood obesity will continue to lead earlier puberty is uncertain. The confirmation of an estimated advance in the age at menarche of 6-12 months per 100 years will require a long-term perspective on behalf of current investigators, and new consideration of methodological approaches in an age of increasing recognition of children's rights for privacy.

Adolescent↗

PubMed2006

A genome-wide association study of nonsynonymous SNPs identifies a type 1 diabetes locus in the interferon-induced helicase (IFIH1) region.

In this study we report convincing statistical support for a sixth type 1 diabetes (T1D) locus in the innate immunity viral RNA receptor gene region IFIH1 (also known as mda-5 or Helicard) on chromosome 2q24.3. We found the association in an interim analysis of a genome-wide nonsynonymous SNP (nsSNP) scan, and we validated it in a case-control collection and replicated it in an independent family collection. In 4,253 cases, 5,842 controls and 2,134 parent-child trio genotypes, the risk ratio for the minor allele of the nsSNP rs1990760 A --> G (A946T) was 0.86 (95% confidence interval = 0.82-0.90) at P = 1.42 x 10(-10).

Chromosomes, Human, Pair 2↗

PubMed2006

Metformin treatment to prevent early puberty in girls with precocious pubarche.

CONTEXT AND OBJECTIVE: Girls with precocious pubarche (PP, pubic hair at < 8 yr of age) are at high risk for early onset and rapid progression of puberty, in particular if their prenatal growth was restrained, i.e. low birth weight (LBW), and followed by rapid postnatal catch-up of weight gain. We postulated that insulin resistance contributes to early onset and rapid progression of puberty in LBW-PP girls and thus explored the puberty-delaying effects of insulin sensitization with metformin initiated shortly after PP diagnosis. SETTING, DESIGN, AND PATIENTS: The study population consisted of 38 prepubertal LBW girls with PP attributed to exaggerated adrenarche [mean body weight, 2.4 kg; age, 7.9 yr; body mass index (BMI), 18.4 kg/m(2)]. These girls were randomly assigned to remain untreated (n = 19) or to receive metformin (n = 19; 425 mg/d) for 2 yr. MAIN OUTCOME MEASURES: Pubertal staging, age at menarche, body composition by absorptiometry, fasting insulin, glucose, lipids, leptin, IGF-I, IGF-binding protein-1, testosterone, dehydroepiandrosterone sulfate, and SHBG were the main outcome measures. RESULTS: Metformin treatment was associated with a less adipose body composition (and lower serum leptin levels) and with a 0.4-yr delay in the clinical onset of puberty (Tanner B2; 9.5 vs. 9.1 yr; P < 0.01). These findings were corroborated by a delay of at least 1 yr in the puberty-associated rise of circulating IGF-I (P < 0.01). Available results also point to a metformin-associated delay of menarche (P < 0.02). Gain in height and lean mass was not divergent between study subgroups. CONCLUSION: The efficacy of early metformin treatment in PP girls is here extended to include not only a less adipose body composition after 2 yr but also a less advanced onset of puberty, whereas height gain is maintained. These findings open the perspective that, ultimately, metformin treatment may also prove to heighten the short adult stature of LBW-PP girls.

Adrenarche↗

PubMed2006

Impact of treatment with recombinant human GH and IGF-I on visceral adipose tissue and glucose homeostasis in adults.

Supraphysiological doses of growth hormone (GH) therapy are generally thought to antagonize the effects of insulin, whereas the insulin-like growth factor I (IGF-I) potentiates insulin-like actions. Paradoxically, adults with GH deficiency and patients with acromegaly are both predisposed to glucose intolerance and insulin resistance; however, one cannot extrapolate from these pathological conditions to determine the true metabolic roles of GH and IGF-I in glucose homeostasis. Growth hormone also promotes lipolysis, which has been shown to be the principal determinant of its insulin-antagonistic properties; on the other hand, IGF-I, which acts as an insulin sensitizer, does not exert any direct effect on lipolysis or lipogenesis. Under physiological conditions, the insulin-sensitizing effect of IGF-I is evident only after feeding, when the bioavailability of circulating IGF-I is increased. In contrast to supraphysiological GH doses, low doses of GH treatment have been shown to increase circulating IGF-I levels and IGF-I bioavailability and, thus, may theoretically enhance insulin sensitivity without inducing lipolysis. We have recently reported that a fixed administration of a very low GH dose (1.7 microg/kg/day or 0.1mg/day) improved insulin sensitivity in adults with GH deficiency and increased peripheral glucose uptake in subjects with impaired glucose tolerance and the metabolic syndrome. Our data raise the possibility that this very low GH dose may play a role in maintaining beta-cell function and possibly delay the progression to type 2 diabetes in these high-risk patients.

Adult↗

PubMed2006

The insulin gene variable number of tandem repeat: associations and interactions with childhood body fat mass and insulin secretion in normal children.

CONTEXT: Polymorphism at the insulin gene (INS) variable number of tandem repeat (VNTR) shows variable associations with childhood body mass index (BMI) in different populations. OBJECTIVE: The objective of this study was to observe INS VNTR associations with body composition and insulin secretion in children. DESIGN: The study was designed as a prospective birth cohort study. PARTICIPANTS: A total of 947 children genotyped for the INS VNTR participated. MAIN OUTCOME MEASURES: Main outcome measures were whole body dual x-ray emission absorptiometry at 9 yr to estimate height-corrected fat mass index (FMI), truncal FMI, and fat-free mass, and insulin secretion after oral glucose at 8 yr. RESULTS: Homozygous III/III children had higher BMI (P = 0.020), FMI (P = 0.015), and truncal FMI (P = 0.022) at 9 yr than class I bearers, but no difference in fat-free mass (P = 0.23). Gain in weight sd score between birth and 3 yr was associated positively with BMI, FMI, and truncal FMI in class I bearers, but not in III/III children (p-interaction with genotype = 0.009-0.066). INS VNTR genotype was not associated overall with insulin secretion at 8 yr (P = 0.64), but class I bearers showed a stronger positive correlation between insulin secretion and BMI at 8 yr (regression coefficient +/- se, 0.26 +/- 0.05; P < 0.0001) than III/III children (-0.10 +/- 0.07; P = 0.48) (p-interaction = 0.003). CONCLUSION: We clarified that the overall association between INS VNTR class III/III genotype and larger BMI in this population relates to fat mass, but not fat-free mass. In contrast, among the subgroup of children who showed rapid infancy weight gain, class I bearers tended to have larger BMI and fat mass than III/III children. This genetic interaction could relate to insulin secretion, which, in class I bearers, increased more rapidly with overweight and obesity.

Body Composition↗

PubMed2006

Hirsutism.

Explore the source record for details and available documents.

Androgen Antagonists↗

PubMed2006

Early development of adiposity and insulin resistance after catch-up weight gain in small-for-gestational-age children.

CONTEXT AND OBJECTIVE: Low birth weight followed by rapid postnatal weight gain is associated with long-term risks for central obesity and insulin resistance. However, the timing of these changes is unclear. SETTING, DESIGN, AND PATIENTS: This was a longitudinal cohort study in low birth weight (SGA; birth weight < -2 sd; n = 29) and normal birth weight (AGA; n = 22) children from Barcelona. MAIN OUTCOME MEASURES: Body composition, by dual-energy x-ray absorptiometry scan, and insulin sensitivity, assessed longitudinally at ages 2, 3, and 4 yr, were measured. RESULTS: Mean height, weight, and body mass index at ages 2, 3, and 4 yr were not different between SGA and AGA children. At age 2 yr, SGA children had similar body composition but were more insulin sensitive than AGA children and had lower serum IGF-I levels and lower neutrophil counts. Between ages 2 and 4 yr, despite similar gains in weight and body mass index, SGA children gained more abdominal fat and body adiposity and less lean mass than AGA children; by age 4 yr, SGA children had greater adiposity, insulin resistance, and higher neutrophil counts than AGA children (P = 0.01-0.0004). In SGA children, total and abdominal fat mass at 4 yr was more closely related to rate of weight gain between 0 and 2 yr (P = 0.002-0.0003) than between 2 and 4 yr (P = 0.04-0.1). CONCLUSION: Consequent to catch-up weight gain between birth and 2 yr, SGA children showed a dramatic transition toward central adiposity and insulin resistance between ages 2 and 4 yr. Understanding the mechanisms underlying this predisposition to adverse future health could lead to specific preventive interventions during early childhood.

Adiposity↗

PubMed2006

Metformin therapy during puberty delays menarche, prolongs pubertal growth, and augments adult height: a randomized study in low-birth-weight girls with early-normal onset of puberty.

CONTEXT AND OBJECTIVE: Low-birth-weight (LBW) girls who enter puberty earlier (around 8-9 yr) tend to have earlier menarche, earlier growth arrest, and a shorter adult stature. At present, there is no therapy for most of these girls. In LBW girls with early puberty, hyperinsulinemic insulin resistance could underpin their rapid transit through puberty and their loss of adult stature. We explored the effects of insulin sensitization with metformin during puberty. SETTING, DESIGN, AND PATIENTS: In an open-labeled, prospective study, 22 LBW girls (birth weight < -1.5 sd score for gestational age) with early-normal puberty (stage 2 breast development at age 8-9 yr) were randomized to remain untreated (n = 12) or to receive metformin (850 mg/d; n = 10) for 36 months (mean age at start, 9.0 yr). All girls remained untreated between 36 and 42 months. MAIN OUTCOME MEASURES: Pubertal growth, body composition by absorptiometry, uterine-ovarian size by ultrasound, fasting insulin, glucose, lipids, leptin, IGF-I, and IGF-binding protein-1 were assessed. RESULTS: Metformin treatment resulted in a longer duration from stage 2 breast development to menarche (P < 0.01; median difference, +1.0 yr), taller near-adult height (P < 0.01), and leaner body composition (P < 0.001). Metformin was also associated with lower insulin resistance and leptin and IGF-I levels and higher SHBG and IGF-binding protein-1 levels and with a more favorable lipid profile. Bone mineral density and uterine-ovarian growth were unaffected. CONCLUSION: Metformin treatment for 36 months in LBW girls with early-normal puberty normalized their pubertal progression to menarche and increased height gains up to adult stature. These data support the concept that insulin is a major codeterminant of the pubertal tempo and pubertal height gain in girls.

Body Composition↗

PubMed2006

Associations between common variation in the aromatase gene promoter region and testosterone concentrations in two young female populations.

We recently reported association between a coding-region single nucleotide polymorphism (SNP50) in the aromatase gene that encodes a key enzyme in testosterone metabolism, with risk for the development of precocious pubarche and circulating testosterone concentrations in two independent female populations. We have now explored further association with variation in the promoter-region of the aromatase gene. We genotyped six promoter-region haplotype-tag SNPs in young women from Oxford, UK (n = 109), and in girls with precocious pubarche (n = 186) and controls (n = 71) from Barcelona, Spain. Aromatase distal promoter-region variation was associated with plasma testosterone concentrations in both Oxford (r(2) = 18.3%, p = 0.01) and Barcelona (r(2) = 8.5%, p = 0.03) females. These associations were independent of SNP50, but appeared to be dependent on different SNPs in Oxford (r(2) = 13.7%, p = 0.006 with SNPs 11 (p = 0.009), 28 (p = 0.02) and 39 (p = 0.06)) and Barcelona (r(2) = 5.9%, p = 0.002 with SNP43 (p = 0.002)) populations. Aromatase distal promoter-region variation was also associated with PCOS symptom score in Oxford women (r(2) = 14.5%, p = 0.048), but, unlike SNP50, was not associated with precocious pubarche risk in Barcelona girls. In conclusion, aromatase distal promoter-region variation appears to have functional consequences for plasma testosterone concentrations in females. The variable associations with androgen-related clinical features could possibly reflect the tissue-specific promoters of the aromatase gene.

Adolescent↗

PubMed2006

Babies born small for gestational age: insulin sensitivity and growth hormone treatment.

Epidemiological studies have identified an association between size at birth and adult risk for type 2 diabetes mellitus and cardiovascular disease. In contemporary populations, children who are relatively small at birth and show rapid infancy weight gain are at greatest risk for the development of childhood obesity, increased visceral fat and insulin resistance: possible early markers of adult disease risk. Individuals presenting to growth clinics with short stature and a history of low birthweight will not have shown post-natal catch-up growth and may be a very heterogeneous group. Nevertheless, there are some data to suggest that as a group they are insulin resistant with decreased lean mass. Growth hormone treatment leads to reversible worsening of the insulin resistance, and short-term data do not indicate an increased risk for type 2 diabetes. However, further long-term follow-up is required, and particular care should be taken in monitoring children with a strong family history of type 2 diabetes and those from ethnic groups in which there is a high background prevalence of the disease.

Adult↗

PubMed2006

Insulin resistance is an intrinsic defect independent of fat mass in women with Turner's syndrome.

BACKGROUND/AIMS: Turner's syndrome (TS) is associated with increased insulin resistance and adiposity, which might be associated with type 2 diabetes in later life. We aimed to determine whether the defect in insulin sensitivity is a primary intrinsic defect in TS or dependent on variation in body composition. METHODS: Sixteen women with TS not on growth hormone replacement but receiving oestrogen replacement therapy [age (mean +/- SD): 30.2 +/- 8.5 years; height-corrected fat-free mass: 26.1 +/- 3.1 kg/height] and a control group of 16 normal healthy women (age: 30.1 +/- 8.2 years; height-corrected fat-free mass: 25.9 +/- 2.4 kg/height) were studied. Fasting blood samples were obtained for measurement of glucose, insulin, IGF-I, IGFBP-1, IGFBP-3 and lipid levels. The hyperinsulinaemic euglycaemic clamp was performed to assess peripheral insulin sensitivity (M value), and the Homeostasis Model Assessment (HOMA-S) was used to estimate fasting insulin sensitivity. Body composition was assessed using a dual-energy X-ray absorptiometry scan. RESULTS: Fasting insulin sensitivity (HOMA-S 103.2 +/- 78.6 vs. 193.9 +/- 93.5, p = 0.006) was lower in TS subjects compared to controls as was whole-body insulin sensitivity (M value 2.9 +/- 1.9 vs. 5.5 +/- 2.6 mg/kg/min, p = 0.003). In a multiple regression analysis the Turner karyotype was significantly related to insulin sensitivity (p = 0.008) independent of any differences in fat-free mass and percent whole-body fat mass. CONCLUSION: The increased insulin resistance in women with TS is independent of measures of body composition and may represent an intrinsic defect related to their chromosomal abnormality.

Adolescent↗

PubMed2006

Upward weight percentile crossing in infancy and early childhood independently predicts fat mass in young adults: the Stockholm Weight Development Study (SWEDES).

BACKGROUND: Rapid early postnatal weight gain predicts increased subsequent obesity and related disease risks. However, the exact timing of adverse rapid postnatal weight gain is unclear. OBJECTIVE: The objective was to examine the associations between rapid weight gain in infancy and in early childhood in relation to body composition at age 17 y. DESIGN: This prospective cohort study was conducted in 248 (103 males) singletons and their mothers. Height and weight were measured at birth, 6 mo, and 3 and 6 y. The rates of weight gain during infancy (0-6 mo) and early childhood (3-6 y) were calculated as changes in sex- and age-adjusted weight SD scores during these time periods. At 17 y, body composition was measured by air-displacement plethysmography. RESULTS: Increasing weight gain during infancy and early childhood were both independently associated with larger body mass index, fat mass, relative fat mass, fat-free mass, and waist circumference at 17 y (P < 0.005 for all; adjusted for sex, birth weight, gestational age, current height, maternal socioeconomic status, and maternal fat mass). Rapid weight gain in infancy, but not in early childhood, also predicted taller height at 17 y (P < 0.001). CONCLUSIONS: Rapid weight gain in both infancy and early childhood is a risk factor for adult adiposity and obesity. Rapid weight gain in infancy also predicted taller adult height. We hypothesize that rapid weight gains in infancy and early childhood are different processes and may allow separate opportunities for early intervention against obesity risk later in life.

Adipose Tissue↗

PubMed2006

Persisting effects on fasting glucose levels and insulin sensitivity after 6 months of discontinuation of a very low-dose GH therapy in adults with severe GH deficiency.

OBJECTIVE: We recently reported that, in contrast to the standard GH (SGH) replacement dose titrated to normalize serum IGF-I levels, 12-month treatment with a fixed low GH dose (LGH) (0.1 mg/day) decreased fasting glucose levels and improved insulin sensitivity with little effect on body composition in severely GH-deficient adults. In this study, we have subsequently examined the effects after 6 months of discontinuation of these variable GH doses (LGH: n = 8; fixed dose 0.10 mg/day and SGH: n = 8; mean dose 0.50 mg/day) on glucose metabolism, body composition and other surrogate cardiovascular risk markers. METHODS: Fasting insulin sensitivity using the homeostasis model assessment, and body composition using dual-energy X-ray absorptiometry scans were assessed at baseline, after 12 months of therapy (month 12) and after 6 months following discontinuation of therapy (month 18). RESULTS: At month 12, the LGH decreased fasting glucose levels and improved insulin sensitivity without altering body composition, whereas the SGH improved body composition without modifying insulin sensitivity. Six months after discontinuation of the LGH treatment (month 18), fasting glucose levels remained decreased and the enhanced insulin sensitivity persisted. In contrast, after discontinuation of SGH treatment (month 18), body composition reverted to baseline without changes in either fasting glucose levels or insulin sensitivity. CONCLUSION In contrast to the SGH, the LGH induces effects on fasting glucose levels and insulin sensitivity, which persist after 6 months of discontinuation of therapy. The exact molecular mechanisms are unclear but may involve the modulation of hepatic and muscle insulin sensitivity, possibly by altering insulin and IGF-I receptor responsiveness and/or density.

Adult↗

PubMed2006

Short-term suppression of elevated growth hormone concentrations following insulin-like growth factor 1 administration in young adults with type 1 diabetes does not alter glomerular filtration or albumin excretion rates.

OBJECTIVE: Young adults with type 1 diabetes mellitus (T1DM) have increased glomerular filtration rate (GFR), which may mediate progressive renal disease and microalbuminuria. This may be secondary to low concentrations of insulin-like growth factor (IGF)-I and GH hypersecretion. We tested the hypothesis that restoration of circulating IGF-I concentrations in young adults with T1DM might suppress GH secretion, GFR and urinary albumin excretion. DESIGN: In a randomized double blind crossover study six young adults with T1DM (three men, 19-24 years) received 7 days treatment with rhIGF-I/insulin-like growth factor binding protein (IGFBP)-3 complex (SomatoKine) 0.4 mg/kg/day and placebo. Subjects underwent overnight insulin infusion for euglycaemia, followed by determination of GFR and albumin excretion rate. RESULTS: Following IGF-I/IGFBP-3 complex, overnight insulin requirements (0.15 vs placebo 0.21 mU/kg/min, P < 0.04), plasma insulin (77 vs placebo 152 pmol/l, P < 0.01) and mean overnight GH (2.6 vs placebo 4.8 mU/l, P < 0.04) fell. IGF-I (492 vs placebo 218 ng/ml, P < 0.01) and IGFBP-3 (4.5 vs placebo 3.9 microg/ml, P < 0.05) increased. GFR did not change (145.5 (23.9) ml/min/1.73 m(2) post-IGF-I/IGFBP-3 complex vs 152.2 (19.8) post placebo). Albumin excretion rate did not change 9.5 (5.5-16.6)mg/24 h pre- vs 11.5 (9.9-20.2) post-IGF-I/IGFBP-3 complex and 10.7 (8.1-21.2) pre- vs 11.5 (8.7-29.9) post placebo. Plasma creatinine levels were lower following IGF-I/IGFBP-3 complex (mean +/- SD, 56.2 +/- 16.8 micromol/l) vs placebo (61.5, 45.0, P < 0.02). CONCLUSIONS: Seven days treatment with IGF-I/IGFBP-3 complex enhanced overnight insulin sensitivity and reduced GH levels, but there was no effect on glomerular hyperfiltration or albumin excretion rates.

Adult↗

PubMed2006

Conscious level in children with diabetic ketoacidosis is related to severity of acidosis and not to blood glucose concentration.

OBJECTIVE: To ascertain whether initial depression of conscious level in children with diabetic ketoacidosis (DKA) is related to hyperosmolality, acidosis or other factors. METHODS: In 225 episodes of DKA without evidence of cerebral edema, we examined the relationship between conscious level and initial biochemical variables. We contrasted these findings with those in 42 children who later developed cerebral oedema. RESULTS: On admission, 42/225 (19%) had mild (pH 7.26-7.35); 96 (44%) moderate (pH 7.11-7.25); and 80 (37%) severe DKA (pH <or= 7.10). Conscious level: alert and oriented (group 1, n=123), drowsy but oriented when woken (group 2, n=62), semi-conscious or confused/agitated (group 3, n=9), comatose (group 4, n=4). Glasgow Coma Score (GCS) was available in 65. pH varied significantly with conscious level; group 1, 7.20+/- 0.11(mean+/- SD); group 2, 7.10+/- 0.16; group 3, 6.96+/- 0.11; group 4, 6.88+/- 0.09 (anova, p<0.001). Blood glucose (BG) was not different between the groups. GCS was related to pH (r(s) = 0.49, p < 0.001), but not to BG or electrolyte levels. Age, sex, plasma sodium, corrected sodium and osmolality also varied with conscious level in a univariate model. Using multivariate analysis comparing groups 1 with groups 2-4, lower pH and younger age were the only independent determinants of impaired conscious level (p<0.001, p=0.036). Conscious level in the children with cerebral edema was also closely related to pH and not to other biochemical variables. pH was lower at each conscious level in the children with later cerebral edema. CONCLUSIONS: In children with DKA, initial conscious level is closely related to pH and weakly to age, but not to BG or plasma sodium level. Thus cerebral function in DKA is related to severity of acidosis even when there is no evidence of cerebral edema.

Adolescent↗

PubMed2006

Dietary energy intake at the age of 4 months predicts postnatal weight gain and childhood body mass index.

OBJECTIVE: Rapid infant weight gain has been shown to predict later obesity risk; however, it is unclear which factors influence infant diet and weight gain. The objective of this study was to determine whether different feeding patterns and energy intakes that are provided to infants affect body weight and BMI later in childhood. METHODS: This representative birth cohort study was conducted in the United Kingdom. Energy intake at age 4 months was estimated from 1-day unweighed dietary records in 881 infants and related to their childhood weight gain and BMI. RESULTS: Among formula- or mixed-fed infants (N = 582), energy intake was higher in first-born infants (mean +/- SE: 2730 +/- 29.4 kJ/day; n = 263) than in subsequent-born infants (2620.8 +/- 25.2 kJ/day; n = 296). Energy intake at 4 months was also higher in infants who were given solid foods earlier (1-2 months: 2805.6 +/- 50.4 kJ/day, n = 89; 2-3 months: 2658.6 +/- 25.2 kJ/day, n = 339; 4+ months: 2587.2 +/- 46.2 kJ/day, n = 111). Higher energy intake at 4 months predicted greater weight gain between birth to age 1, 2, or 3 years and larger body weight and BMI at ages 1 to 5 years. No significant associations were seen in breastfed infants (N = 299). CONCLUSIONS: Among formula- or mixed-fed infants, dietary energy intake at age 4 months predicted postnatal weight gain and childhood obesity risk. Both prenatal and postnatal factors may influence infant energy intake and postnatal weight gain.

Birth Weight↗