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1.
Contemp Clin Trials ; 94: 106024, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32389808

RESUMO

INTRODUCTION: Maternal obesity increases neonatal risk for obesity and metabolic syndrome later in life. Prior attempts to break this intergenerational obesity cycle by limiting excessive gestational weight gain have failed to reduce neonatal adiposity. Alternatively, pre-conception lifestyle interventions may improve the in utero metabolic milieu during early pregnancy leading to improved fetal outcomes. This randomized controlled trial (RCT) is evaluating whether a lifestyle intervention to reduce weight and improve maternal metabolism in preparation for pregnancy (LIPP) attenuates neonatal adiposity, compared to standard medical advice. MATERIAL AND METHODS: Overweight/class 1 obese women after a previous pregnancy, ~12 weeks postpartum, preparing for a subsequent pregnancy, will be block randomized (1:1) to either LIPP or standard of care in a parallel design. Randomization is stratified by lactation status and overweight vs. class 1 obesity. The LIPP program consists of intensive short-term weight loss followed by weight maintenance until conception using supervised exercise and a low glycemic Mediterranean diet. PRIMARY OUTCOMES: Group differences in neonatal adiposity at birth assessed by PEA POD and placental mitochondrial lipid metabolism. SECONDARY OUTCOMES: Group differences in maternal pregravid and gestational body composition, insulin sensitivity, ß-cell function, fasting metabolic and inflammatory biomarkers, and overall quality of life. Exploratory outcomes include umbilical cord blood insulin resistance, lipid profile and inflammation. DISCUSSION: This RCT will determine the efficacy of maternal weight loss prior to pregnancy on reducing neonatal adiposity. Findings may change standard obstetrical care by providing Level 1 evidence on lifestyle interventions improving neonatal outcomes for women planning for pregnancy. CLINICAL TRIAL REGISTRATION: NCT03146156.


Assuntos
Ganho de Peso na Gestação , Complicações na Gravidez , Feminino , Humanos , Estilo de Vida , Sobrepeso/terapia , Gravidez , Complicações na Gravidez/prevenção & controle , Cuidado Pré-Natal , Aumento de Peso
2.
Pediatr Obes ; 13(8): 485-491, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29573242

RESUMO

BACKGROUND: Cord blood adiponectin and leptin concentrations are associated with birth weight and adiposity. Birth size and rate of infant weight gain are associated with future obesity risk. However, it is unclear whether biomarkers reflecting the intrauterine environment are predictive of infant prospective body composition change. OBJECTIVES: To examine whether cord blood adiponectin and leptin are predictive of neonatal adiposity and fat mass (FM) accrual to 3 months of age. METHODS: Participants (n = 36) were healthy African American infants. Leptin and adiponectin concentrations were measured in umbilical cord blood. At 2 weeks and 3 months, infant body composition was assessed via air displacement plethysmography. Weight-for-length z-scores (WLZ) were calculated using World Health Organization standards. Multiple linear regression was used to examine associations of cord blood adiponectin and leptin with birth WLZ; WLZ, FM and fat-free mass at 2 weeks, and the conditional change in these variables from 2 weeks to 3 months (body composition at 3 months adjusted for body composition at 2 weeks). RESULTS: Adiponectin was positively associated with FM at 2 weeks (r = 0.45, P < 0.01), but inversely associated with conditional FM change from 2 weeks to 3 months of age (r = -0.38, P < 0.05). Leptin was not significantly associated with infant body composition. CONCLUSIONS: Adiponectin may be a marker for FM accrual in African American infants, a relatively understudied population with a high long-term obesity risk. Mechanistic studies are needed to determine whether adiponectin directly influences infant growth or is simply a maker reflective of other ongoing biological changes after birth.


Assuntos
Adiponectina/sangue , Tecido Adiposo/fisiologia , Adiposidade/fisiologia , Negro ou Afro-Americano/estatística & dados numéricos , Composição Corporal/fisiologia , Leptina/sangue , Biomarcadores/sangue , Peso ao Nascer , Feminino , Sangue Fetal , Humanos , Lactente , Recém-Nascido , Masculino , Pletismografia , Aumento de Peso
3.
Am J Obstet Gynecol ; 217(4): 445.e1-445.e6, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28599895

RESUMO

BACKGROUND: There are significant variations in gestational weight gain, with many women gaining in excess of the Institute of Medicine guidelines. Unfortunately, efforts to improve appropriate gestational weight gain have had only limited success. To date, interventions have focused primarily on decreasing energy intake and/or increasing physical activity. Maternal resting energy expenditure, which comprises ∼60% of total energy expenditure compared with the ∼20% that comes from physical activity, may be an important consideration in understanding variations in gestational weight gain. OBJECTIVE: Our objective was to quantify the changes in resting energy expenditure during pregnancy and their relationship to gestational weight gain and body composition changes among healthy women. We hypothesized that greater gestational weight gain, and fat mass accrual in particular, are inversely related to variations in resting energy expenditure. STUDY DESIGN: We conducted a secondary analysis of a prospective cohort studied before conception and late pregnancy (34-36 weeks). Body composition (estimated using hydrodensitometry) and resting energy expenditure (estimated using indirect calorimetry) were measured. The relationship between the changes in resting energy expenditure and gestational weight gain and the change in fat mass and fat-free mass were quantified. Resting energy expenditure was expressed as kilocalories per kilogram of fat-free mass per day (kilocalories per kilogram of fat-free mass-1/day-1) and kilocalories per day. Correlations are reported as r. RESULTS: Among 51 women, preconception body mass index was 23.0 (4.7) kg/m2; gestational weight gain was 12.8 (4.7) kg. Preconception and late pregnancy resting energy expenditure (kilocalories per day) correlated positively with the change in fat-free mass (r = 0.37, P = .008; r = 0.51, P = .001). Late-pregnancy resting energy expenditure (kilocalories per kilogram of fat-free mass-1/day-1) was inversely associated with the change in fat mass (r = -0.34, P = .02) and gestational weight gain (r = -0.29, P = .04). From before pregnancy through late gestation, the increase in resting energy expenditure (kilocalories per day) correlated positively with the change in fat-free mass (r = 0.44, P = .002) and negatively with the change in fat mass (r = -0.27, P = .06). CONCLUSION: The change in resting energy expenditure from before conception through late gestation correlated positively with changes in fat-free mass but negatively with fat mass accrual. Women with smaller increases in resting energy expenditure across pregnancy had greater gestational weight gain, specifically more adipose tissue. These data suggest that resting energy expenditure is an important factor in gestational weight gain, particularly excess fat mass accrual. Future lifestyle intervention studies need to consider clinically feasible means of estimating resting energy expenditure and, in response, tailor nutrient intake and composition recommendations. Implementing and testing such interventions would be a novel approach to improve compliance with gestational weight gain guidelines.


Assuntos
Metabolismo Energético , Descanso , Aumento de Peso , Adulto , Composição Corporal , Índice de Massa Corporal , Estudos de Coortes , Feminino , Humanos , Gravidez
4.
Int J Obes (Lond) ; 40(3): 538-42, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26388350

RESUMO

BACKGROUND: Excessive fat accumulation characterizes the over-nourished fetus in maternal diabetes and obesity with fetal insulin regarded as a primary driver. This study tested whether fetal insulin is related to subcutaneous adipose tissue (SAT) thickness at different body sites in neonates, and whether sites respond differentially to insulin. In addition, sex differences were assessed. METHODS: Cord blood insulin was measured for 414 neonates. After birth, SAT thickness was measured at 15 body sites using a validated device, a lipometer, that measures back-scattered light intensities corresponding to SAT. Associations between fetal insulin and SAT were assessed in linear regression models, adjusted for gestational age and birth weight, for males and females separately. RESULTS: No sex differences in insulin levels or total SAT thickness were found. In males, SAT thickness at most body sites was significantly correlated with insulin, with strongest associations between insulin and SAT on neck (beta 0.23, 95% CI 0.05; 0.41; P=0.01) and upper abdomen (beta 0.18, 95% CI 0.01; 0.36; P=0.04). In females, insulin was only associated with hip SAT thickness (beta 0.22, 95% CI 0.06; 0.39; P=0.01). Total SAT thickness was correlated with insulin in males (beta 0.03, 95% CI 0.01; 0.04; P=0.003), but not in females (beta 0.01, 95% CI -0.01; 0.02; P=0.38). CONCLUSIONS: Fat deposition in female neonates seems less affected by insulin as compared to males. This may reflect lower insulin sensitivity in females, or may be accounted for by other metabolic/endocrine factors overriding the association.


Assuntos
Sangue Fetal/metabolismo , Hiperglicemia/fisiopatologia , Insulina/sangue , Mães , Complicações na Gravidez/sangue , Efeitos Tardios da Exposição Pré-Natal/sangue , Gordura Subcutânea/metabolismo , Áustria/epidemiologia , Composição Corporal , Feminino , Humanos , Hiperglicemia/sangue , Recém-Nascido , Masculino , Gravidez , Complicações na Gravidez/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Fatores Sexuais
5.
J Matern Fetal Neonatal Med ; 28(10): 1113-5, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25012807

RESUMO

CONTEXT: There are many causes of impaired glucose tolerance in pregnant women. It is unclear whether genetic etiologies are a source of impaired glucose tolerance in pregnant women. OBJECTIVE: To prospectively determine the prevalence of maturity onset diabetes of the young (MODY) due to glucokinase (GCK) mutations in an American population of women with recent onset diabetes mellitus and gestational diabetes. We hypothesized that based on America's higher prevalence of gestational diabetes mellitus (GDM) and Type 2 diabetes, there may be an increased prevalence of GK mutations in our population than in previously reported studies from European studies. DESIGN: Over a three-year period, 72 pregnant women with recently diagnosed diabetes mellitus were prospectively assessed for presence of the most common pathogenic GCK mutations. SETTING: This study was performed in a gestational diabetes clinic in Urban America and a high-risk pregnancy clinic that served the military and their families on an American military base in Germany. PATIENTS: Seventy-two women; 65 with diagnosis of diabetes mellitus in this pregnancy (GDM/overt diabetes) and 7 with diagnosis in the last nine years prior to pregnancy were recruited during pregnancy and blood samples were obtained. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Each study participant's blood sample was analyzed with restriction fragment length polymorphism to assess for mutations in the GCK gene. RESULTS: There were 38 female and 34 male neonates born at 38 weeks gestation ± 1.2 weeks. Mean birth weight was 3351 g ± 450 g. There were no patients with GCK mutations found in our population 0/72. This prevalence is not greater than that seen in previous a similar study in European women with gestational diabetes, but in fact significantly less (p = 0.03). CONCLUSION: American women with recently diagnosed diabetes mellitus likely have no higher prevalence of MODY than in previously studied European women with diabetes mellitus and may have a lower prevalence.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Gestacional/genética , Glucoquinase/genética , Mutação , Adulto , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Polimorfismo de Fragmento de Restrição , Gravidez , Gravidez de Alto Risco , Prevalência , Estudos Prospectivos , Estados Unidos/epidemiologia , População Branca/genética , Adulto Jovem
6.
Pediatr Obes ; 9(6): e141-4, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25267097

RESUMO

BACKGROUND: Rapid weight gain in infancy has been established as a risk factor for the development of later obesity. OBJECTIVE: We aimed to investigate the role of changes in infant body composition (assessed via total body electrical conductivity) on the development of overweight/obesity in mid-childhood. METHODS: Fifty-three term infants were evaluated at birth, three times during infancy and in mid-childhood. Logistic regression was used to determine associations between rates of total weight gain, fat mass gain and lean mass gain during infancy and later overweight/obesity (defined as body mass index [BMI] ≥85th percentile), adjusted for birth weight and parent education. RESULTS: At follow-up (age 9.0 ± 1.8 years), 30% were overweight/obese. More rapid total weight gain from 0 to 4 months was associated with twofold odds (odds ratio [OR] 1.98, 95% confidence interval [CI] 1.05-3.74, P = 0.04) of overweight/obesity in mid-childhood. From 0 to 8 months, more rapid weight gain was associated with nearly fivefold odds (OR 4.76, 95% CI 1.05-21.5, P = 0.04), and more rapid fat mass gain was associated with eightfold odds (OR 8.03, 95% CI 1.11-58.2, P = 0.04) of later overweight/obesity. CONCLUSION: This exploratory study suggests that rapid weight gain, especially fat mass gain, in earlier infancy predisposes to mid-childhood overweight/obesity.


Assuntos
Composição Corporal , Obesidade Infantil/epidemiologia , Aumento de Peso , Peso ao Nascer , Índice de Massa Corporal , Causalidade , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Estudos Longitudinais , Masculino , Mães , Razão de Chances , Obesidade Infantil/prevenção & controle , Valor Preditivo dos Testes , Gravidez , Estudos Prospectivos , Fatores de Risco
7.
Int J Obes (Lond) ; 38(7): 887-905, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24662696

RESUMO

The 2013 Pennington Biomedical Research Center's Scientific Symposium focused on the treatment and management of pediatric obesity and was designed to (i) review recent scientific advances in the prevention, clinical treatment and management of pediatric obesity, (ii) integrate the latest published and unpublished findings and (iii) explore how these advances can be integrated into clinical and public health approaches. The symposium provided an overview of important new advances in the field, which led to several recommendations for incorporating the scientific evidence into practice. The science presented covered a range of topics related to pediatric obesity, including the role of genetic differences, epigenetic events influenced by in utero development, pre-pregnancy maternal obesity status, maternal nutrition and maternal weight gain on developmental programming of adiposity in offspring. Finally, the relative merits of a range of various behavioral approaches targeted at pediatric obesity were covered, together with the specific roles of pharmacotherapy and bariatric surgery in pediatric populations. In summary, pediatric obesity is a very challenging problem that is unprecedented in evolutionary terms; one which has the capacity to negate many of the health benefits that have contributed to the increased longevity observed in the developed world.


Assuntos
Adiposidade , Pesquisa Biomédica , Obesidade Infantil/prevenção & controle , Saúde Pública , Aumento de Peso , Adolescente , Adulto , Criança , Pré-Escolar , Dieta , Epigenômica , Medicina Baseada em Evidências , Exercício Físico , Conhecimentos, Atitudes e Prática em Saúde , Promoção da Saúde , Humanos , Obesidade Infantil/epidemiologia , Obesidade Infantil/genética , Vigilância da População , Prevalência , Fatores de Risco , Aumento de Peso/genética
8.
Diabet Med ; 31(3): 273-81, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24341419

RESUMO

Women with normal glucose tolerance pre-gravid and developing gestational diabetes in late gestation have subclinical metabolic dysfunction prior to conception compared with women with normal glucose tolerance. Because of the 60% decrease in insulin sensitivity with normal pregnancy, these women develop clinical hyperglycaemia/gestational diabetes in late gestation. The metabolic dysfunction includes impaired insulin response, decreased hepatic suppression of glucose production during insulin infusion and decreased insulin-stimulated glucose uptake in skeletal muscle, i.e. peripheral insulin resistance. The insulin resistance in normal glucose tolerance pregnancy is related to a decrease in the post-receptor insulin signalling cascade, specifically decreased insulin receptor substrate 1 tyrosine phosphorylation. In women with normal glucose tolerance this is reversed post-partum. In contrast, in gestational diabetes, in addition to the decrease in insulin receptor substrate 1 tyrosine phosphorylation, there is an additional decrease in tyrosine phosphorylation of the intracellular portion of the insulin receptor that is not related to the insulin receptor protein content. Post-partum women with gestational diabetes, who had retention of gestational weight gain, had no significant improvement in insulin sensitivity and increased inflammation expressed as increased plasma and skeletal muscle tumour necrosis factor alpha. The increased inflammation or meta-inflammation is a hallmark of obesity and during pregnancy develops in both white adipose tissue and placenta. Last gene array studies of placenta were associated with alterations in gene expression relating primarily to lipid in contrast to glucose metabolic pathways in gestational diabetes compared with Type 1 diabetes. Future studies are directed at decreasing inflammation prior to and during pregnancy using various lifestyle and nutritional interventions.


Assuntos
Diabetes Gestacional/fisiopatologia , Hiperglicemia/fisiopatologia , Inflamação/fisiopatologia , Resistência à Insulina , Músculo Esquelético/metabolismo , Obesidade/fisiopatologia , Transporte Biológico , Diabetes Gestacional/metabolismo , Feminino , Glucose/metabolismo , Humanos , Hiperglicemia/metabolismo , Recém-Nascido , Inflamação/metabolismo , Insulina/metabolismo , Obesidade/complicações , Fosforilação , Período Pós-Parto , Gravidez , Cuidado Pré-Natal , Receptores Proteína Tirosina Quinases/metabolismo , Receptor de Insulina/metabolismo , Comportamento de Redução do Risco , Transdução de Sinais
9.
J Perinatol ; 33(12): 934-8, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24030674

RESUMO

OBJECTIVE: To examine changes in skinfolds in late gestation in healthy women. STUDY DESIGN: Skinfold measures were performed in 39 women at 30.8 (mean) and 37.7 weeks gestation. Fat mass (kg) and sum of three skinfolds were calculated. RESULTS: A decrease in skinfold thickness was observed in 21 women (-3.1±2.1 mm) in late gestation, whereas 18 women had an increase (4.3±3.2 mm), P<0.001. The group of women who lost body fat (decrease in skinfold thickness) had a trend toward greater pregravid body mass index (BMI, 25 vs 22 kg/m(2), P=0.06), and gained less weight in late gestation (3.0 vs 4.3 kg, P=0.042). On multiple regression, maternal age and gestational weight gain were positively correlated with fat mass accrual, whereas pregravid BMI and dietary fiber were negative determinants of late gestational fat mass. CONCLUSION: Increases in maternal fat mass in late gestation were related to maternal age and gestational weight gain, whereas decreases were related to increased pregravid BMI and dietary fiber.


Assuntos
Tecido Adiposo/fisiologia , Terceiro Trimestre da Gravidez/fisiologia , Dobras Cutâneas , Adulto , Índice de Massa Corporal , Fibras na Dieta , Feminino , Humanos , Idade Materna , Gravidez , Análise de Regressão , Aumento de Peso
10.
Ultrasound Obstet Gynecol ; 39(5): 558-62, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-21898636

RESUMO

OBJECTIVE: Increased subcutaneous adipose tissue is a well known characteristic of diabetic fetopathy. Prenatal estimation of adipose tissue can be performed by ultrasound, while postnatally skinfold measurements are performed using a Holtain caliper. The aim of this study was to compare these methods in the same patients. METHODS: This was a prospective study of 172 pregnant patients (142 controls and 30 with gestational diabetes) at ≥ 37 gestational weeks. In addition to fetal weight estimation, fetal subcutaneous tissue was measured at the anterior abdomen lateral to the umbilicus (SonoSfAbd) and at the middle of the femur (SonoSfFem). Within 72 h after delivery, a Holtain caliper was used to measure neonatal skinfold thickness at the left anterior iliac spine (SfAbd), at the lower angle of the left scapula (SfSca), at the middle of the femur, above the left quadriceps femoris (SfFem) and at the middle of the left triceps (SfHum). Ultrasound and mechanical measurements were correlated. RESULTS: The sonographic and mechanical methods showed good correlation with each other. Linear regression analysis gave the following equations: SfAbd (mm) = SonoSfAbd (mm) × 0.489 + 1.988 (r(2) = 0.34, P < 0.001); SfSca (mm) = SonoSfAbd (mm) 0.457 + 2.043 (r(2) = 0.40, P < 0.001); SfFem (mm) = SonoSfFem (mm) × 0.714 + 1.763 (r(2) = 0.41, P < 0.001); SfHum (mm) = SonoSfFem (mm) 0.564 + 2.09 (r(2) = 0.39, P < 0.001). CONCLUSIONS: Ultrasound examination is a reliable method for non-invasive intrauterine measurement of fetal subcutaneous tissue and can be used to predict mechanical neonatal skinfold thickness measurements.


Assuntos
Diabetes Gestacional , Macrossomia Fetal/diagnóstico por imagem , Macrossomia Fetal/patologia , Feto/patologia , Dobras Cutâneas , Gordura Subcutânea/diagnóstico por imagem , Gordura Subcutânea/patologia , Ultrassonografia Pré-Natal , Adulto , Antropometria/instrumentação , Antropometria/métodos , Feminino , Humanos , Recém-Nascido , Masculino , Exame Físico , Valor Preditivo dos Testes , Gravidez , Estudos Prospectivos , Reprodutibilidade dos Testes , Gordura Subcutânea/embriologia
11.
J Dev Orig Health Dis ; 1(4): 208-15, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25141869

RESUMO

The in utero maternal metabolic environment is important relative to both short and long term development of the offspring. Although poor fetal growth remains a significant factor relative to long-term outcome, fetal overgrowth is assuming greater importance because of the increase in obesity in the world's populations. Maternal obesity and gestational diabetes are the most common metabolic complications of pregnancy related to fetal overgrowth and more specifically adiposity. Women with gestational diabetes have increased insulin resistance and inadequate insulin response compared with weight-matched controls. Gestational diabetes increases the risk of maternal hypertensive disease (preeclampsia) as well as cesarean delivery. At birth the neonate has increased adiposity and is at risk for birth injury. Multiple studies have reported that children of women with gestational diabetes have a greater prevalence childhood obesity and glucose intolerance; even at glucose concentrations less than currently used to define gestational diabetes, compared with normoglycemic women. Obese women also have increased insulin resistance, insulin response and inflammatory cytokines compared with average weight women both before and during pregnancy. They too are at increased risk for the metabolic syndrome-like disorders during pregnancy that is hypertension, hyperlipidemia, glucose intolerance and coagulation disorders. Analogous to women with gestational diabetes, neonates of obese women are heavier at delivery because of increased fat and not lean body mass. Similarly, these children have an increased risk of childhood adiposity and metabolic dysregulation. Hence, the preconceptional and perinatal period offers a unique opportunity to modify both short and long term risks for both the woman and her offspring.

12.
Diabetologia ; 53(3): 446-51, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20013109

RESUMO

AIMS/HYPOTHESIS: The aim of the study was to analyse the insulin requirements of women with type 1 diabetes mellitus throughout pregnancy. METHODS: We have examined the weekly mean blood glucose (mmol/l), insulin requirements (U kg(-1) day(-1)) and total insulin requirements (U/day) in 65 women with type 1 diabetes mellitus and tight metabolic control since before pregnancy (HbA(1c) < or =6.0%). RESULTS: Both insulin requirement and total insulin requirement displayed a peak in week 9, a nadir in week 16 and a second peak in week 37. For the change in insulin requirement (4.08% per week) and in total insulin requirement (5.19% per week), the sharpest slope was observed from week 16 to week 37. However, two changes of direction took place in the first 11 weeks and eight out of nine episodes of severe hypoglycaemia requiring treatment with glucagon or i.v. glucose took place in the first 16 weeks. CONCLUSIONS/INTERPRETATION: Pregnant women with type 1 diabetes mellitus and tight metabolic control since before pregnancy displayed changes in insulin requirement and total insulin requirement with successive changes of direction. The sharpest slope was observed between 16 and 37 weeks, but insulin requirements were more unstable in the first 16 weeks. This information could help patients and physicians to react to changes in glycaemic pattern in a prompt and adequate way.


Assuntos
Diabetes Mellitus Tipo 1/sangue , Insulina/metabolismo , Complicações na Gravidez/patologia , Adulto , Glicemia/metabolismo , Proteína C-Reativa/metabolismo , Estudos de Coortes , Complicações do Diabetes/patologia , Diabetes Mellitus Tipo 1/metabolismo , Feminino , Idade Gestacional , Humanos , Gravidez , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
13.
J Clin Endocrinol Metab ; 93(7): 2885-90, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18445668

RESUMO

CONTEXT: High plasma adiponectin concentrations in human fetuses and neonates are unique features of early developmental stages. Yet, the origins of the high adiponectin concentrations in the perinatal period remain elusive. OBJECTIVE: This study was undertaken to identify the sources and functional properties of adiponectin in utero. DESIGN AND METHODS: Tissue specimens were obtained at autopsy from 21- to 39-wk-old stillborn human fetuses. Adipose tissue and placenta were obtained at term elective cesarean section. Adiponectin complexes and expression were measured by immunodetection and real-time PCR. RESULTS: Adiponectin mRNA transcripts were detected in fetal sc and omental adipose depots at lower concentrations than in maternal adipose tissue. Immunoreactive adiponectin was also observed in vascular endothelial cells of fetal organs, including skeletal muscle, kidney, and brain. The absence of adiponectin in all placental cell types and lack of correlation between maternal and umbilical adiponectin indicate that umbilical adiponectin reflects its exclusive production by fetal tissues. The most prominent forms of adiponectin in fetal plasma were high and low molecular mass (HMW and LMW) multimers of 340 and 160 kDa, respectively. The proportion of the HMW complexes was 5-fold (P < 0.001) higher in umbilical plasma than in adult. The high HMW and total adiponectin levels were associated with lower insulin concentration and lower homeostasis model of assessment of insulin resistance indices in umbilical plasma, reflecting higher insulin sensitivity of the fetus compared with adult. CONCLUSIONS: The abundance of HMW adiponectin and its vascular expression are characteristics of human fetal adiponectin. Combined with high insulin sensitivity, fetal adiponectin may be a critical determinant of in utero growth.


Assuntos
Adiponectina/análise , Células Endoteliais/química , Feto/química , Adiponectina/genética , Feto/metabolismo , Humanos , Recém-Nascido , Resistência à Insulina , Peso Molecular , RNA Mensageiro/análise
14.
Placenta ; 29(3): 274-81, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18262644

RESUMO

Obesity and pregnancy are associated with a combination of insulin resistance and inflammatory changes which exacerbate in combination. Based on the similarity between the inflammatory transcriptomes of adipose tissue and placenta, we hypothesized that the placenta develops exaggerated inflammation in response to obesity. The aim of this study was to characterize placental inflammatory mediators and macrophage accumulation in relation to peripheral inflammation in obesity. Placental macrophages and maternal peripheral blood mononuclear cells (PBMC) from 20 obese and 15 lean women were functionally and phenotypically characterized using immunohistochemistry, flow cytometry and expression for macrophage markers and inflammatory cytokines. The number of resident CD68+ and CD14+ cells was increased 2-3 fold in the placenta of obese as compared to lean women. The macrophage population was characterized by a marked phenotypic heterogeneity with complex subsets of CD14+, CD68+ and CD11b+ (mac-1) cells and by an increased expression of the pro-inflammatory cytokines IL-1, TNF-alpha, IL-6. Placental inflammation was associated with an activation of PBMC gene expression with an increase in the monocyte differentiation and maturation markers CD14 and CD68 in maternal but not fetal PBMC. The inflammatory changes were associated with higher plasma concentrations of C-reactive protein and IL-6 in obese compared to lean women. In conclusion, the chronic inflammation state of pre-gravid obesity is extending to in utero life with accumulation of a heterogeneous macrophage population and pro-inflammatory mediators in the placenta. The resulting inflammatory milieu in which the fetus develops may have critical consequences for short and long term programming of obesity.


Assuntos
Macrófagos/citologia , Obesidade/complicações , Placenta/patologia , Complicações na Gravidez , Adulto , Antígenos CD/genética , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/genética , Antígenos de Diferenciação Mielomonocítica/metabolismo , Proteínas de Ligação ao Cálcio , Contagem de Células , Células Cultivadas , Feminino , Sangue Fetal/metabolismo , Humanos , Inflamação/complicações , Inflamação/patologia , Interleucina-6/genética , Interleucina-6/metabolismo , Leucócitos Mononucleares/metabolismo , Receptores de Lipopolissacarídeos/genética , Receptores de Lipopolissacarídeos/metabolismo , Macrófagos/metabolismo , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Mucinas/genética , Mucinas/metabolismo , Obesidade/sangue , Obesidade/imunologia , Obesidade/metabolismo , Placenta/citologia , Placenta/imunologia , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/imunologia , Complicações na Gravidez/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
15.
BJOG ; 113(10): 1126-33, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16827826

RESUMO

Obesity's increasing prevalence has reached epidemic proportions in the USA, with close to one-third of the adult population affected in 2000. Additionally, there is increasing prevalence of obesity in other industrialised areas of the world such as Europe. Of potentially more concern is the potential risks associated with obesity and related metabolic complications in the developing world. The maternal, fetal, peripartum and neonatal complications of obesity in pregnancy have far-reaching implications for both mother and offspring. Of alarming interest is the increasing rate of obesity among adolescents and the cycle of obesity in future generations it portends. The purpose in this review is to briefly review the maternal perinatal morbidities associated with maternal pregravid obesity. Additionally, we will review evidence of both short- and long-term effect of maternal obesity on the in utero environment as it relates to fetal growth, neonatal body composition and adolescent obesity.


Assuntos
Obesidade/complicações , Complicações na Gravidez/etiologia , Peso ao Nascer , Composição Corporal , Feminino , Desenvolvimento Fetal , Humanos , Gravidez , Resultado da Gravidez , Efeitos Tardios da Exposição Pré-Natal , Fatores de Risco
16.
Diabetologia ; 49(7): 1677-85, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16752186

RESUMO

AIMS/HYPOTHESIS: Adiponectin is upregulated during adipogenesis and downregulated in insulin-resistant states. The mechanism(s) governing the re-arrangements from adipogenesis to facilitated lipolysis during pregnancy are unknown. Our purpose was to analyse the role of adiponectin relative to the metabolic changes in human pregnancy. SUBJECTS, MATERIALS AND METHODS: Lean women (BMI <25 kg/m(2)) were evaluated longitudinally before conception, and in early (12-14 weeks) and late (34-36 weeks) pregnancy. Insulin sensitivity was measured using the glucose clamp technique. Venous blood and subcutaneous adipose tissue biopsies were obtained at each time point. RESULTS: Adiponectin concentrations were lower in the third trimester than in the pregravid condition (9.9+/-1.4 vs 13.5+/-1.8 microg/ml). The hypoadiponectinaemia was reflected by a 2.5-fold decrease in white adipose tissue adiponectin mRNA. These changes were associated with a 25% increase in fat mass (23.7+/-2.9 vs 18.9+/-2.9 kg). Insulin infusion decreased high molecular weight adiponectin complexes in pregravid women (9.9+/-0.6 vs 6.2+/-0.06) and the suppressive effect of insulin was lost during pregnancy. The pregnancy-mediated changes in adiponectin were strongly correlated with basal insulin levels and insulin sensitivity (p<0.0001). The relationship between adiponectin and insulin sensitivity was related to the decreased insulin regulation of glucose utilisation (r=0.55, p<0.001) but not of endogenous hepatic glucose production. CONCLUSIONS/INTERPRETATION: These data demonstrate that pregnancy is associated with adiponectin changes in lean women. Hypoadiponectinaemia is reflected by a lower amount of high molecular weight adiponectin and by the ratio of high to low molecular weight multimers. The adiponectin changes relate to decreased insulin sensitivity of glucose disposal rather than alterations of lipid metabolism.


Assuntos
Adiponectina/fisiologia , Glucose/metabolismo , Metabolismo dos Lipídeos , Gravidez/metabolismo , Adiponectina/sangue , Glicemia/análise , Metabolismo Energético , Feminino , Idade Gestacional , Técnica Clamp de Glucose , Humanos , Insulina/sangue , Insulina/farmacologia , Gravidez/sangue
17.
Diabetes Metab ; 28(4 Pt 1): 323-8, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12442070

RESUMO

BACKGROUND: To calculate an adjusted maternal weight gain during pregnancy including infant and placental weights to the actual weight gain and secondarily examine its influence on the occurrence of fetal macrosomia. METHODS: The corrected weight gain was calculated as follows: maternal body weight at the last prenatal visit - (pregravid body weight + birth weight + placental weight) in 259 women (65 with type 1 diabetes, 69 with gestational diabetes mellitus, and 125 controls). RESULTS: Although weight gain was greater in non obese normal glucose tolerant and type 1 diabetic mothers of macrosomic infants, the difference was no longer significant when using corrected maternal weight gain. The correlation between birth weight and maternal weight gain decreased when using this index. CONCLUSION: The corrected weight gain is a better estimate of true accretion of maternal weight. Our results suggest that recommendations for weight gain during pregnancy should take this index into account.


Assuntos
Diabetes Gestacional/fisiopatologia , Macrossomia Fetal/epidemiologia , Gravidez/fisiologia , Aumento de Peso/fisiologia , Adulto , Peso ao Nascer , Glicemia/metabolismo , Peso Corporal , Diabetes Mellitus Tipo 1/fisiopatologia , Feminino , Teste de Tolerância a Glucose , Hemoglobinas Glicadas/análise , Humanos , Recém-Nascido , Tamanho do Órgão , Paridade , Placenta/anatomia & histologia , Gravidez em Diabéticas/fisiopatologia , Fatores de Risco
18.
J Matern Fetal Neonatal Med ; 12(6): 396-401, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12683650

RESUMO

OBJECTIVE: To determine whether neonatal fat mass, which may be a better estimate of fetal overgrowth, is correlated with maternal fasting, preprandial and/or postprandial glucose values in women with gestational diabetes mellitus (GDM). STUDY DESIGN: Women with GDM and no other medical or obstetric problems, and their infants, were the subjects of this study. Portable reflectance meters were used by all participants for self-monitoring of blood glucose levels. Average fasting, preprandial, 2-h postprandial and bedtime glucose values were determined for each subject. Neonatal body composition was obtained by total body electric conductivity and/or anthropometric measurements within 48 h after delivery. RESULTS: Eighteen women with their infants participated in this study. The age (mean +/- SD) of the mothers was 28.0 +/- 5.7 years. Nine were treated with diet and nine with diet and insulin. An average of 40 fasting (84 +/- 13 mg/dl), 50 preprandial (87 +/- 14 mg/dl), 80 2-h postprandial (106 +/- 19 mg/dl) and 17 bedtime (104 +/- 19 mg/dl) glucose values were obtained from each subject. The average gestational age of the infants at birth was 38.3 +/- 1.3 weeks with a mean weight of 3,356 +/- 526 g. Three infants were > 4 kg and seven infants were > 90th centile for gestational age. The strongest correlation with neonatal fat mass was maternal fasting glucose level (r = 0.71, p < 0.01). Neonatal fat mass was not found to be significantly correlated with any other mean glucose value. Additionally, the infant's per cent body fat (r = 0.71, p < 0.01), sum of skinfold thicknesses (r = 0.70, p < 0.01), fat-free mass (r = 0.50, p < 0.05), and weight (r = 0.61, p < 0.01) were also found to be correlated with maternal fasting glucose level. No other maternal glucose measurements were correlated with either birth weight or estimates of fat free mass. CONCLUSION: Maternal fasting glucose levels correlated best with neonatal fat mass and other estimates of neonatal body composition.


Assuntos
Peso ao Nascer/fisiologia , Automonitorização da Glicemia , Composição Corporal/fisiologia , Diabetes Gestacional/sangue , Recém-Nascido/crescimento & desenvolvimento , Adulto , Diabetes Gestacional/fisiopatologia , Diabetes Gestacional/terapia , Dieta para Diabéticos , Jejum , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Modelos Lineares , Período Pós-Prandial , Gravidez , Resultado da Gravidez , Análise de Regressão , Fatores de Tempo
19.
Am J Obstet Gynecol ; 185(3): 660-7, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11568795

RESUMO

OBJECTIVE: Ethnic differences in birth outcomes are well established, but it is not clear whether differences in nutrition may partly explain unaccounted differences in birth outcomes. Our purpose was to evaluate the relationship of nutrition to ethnic differences in birth outcomes. STUDY DESIGN: This was a multicenter, prospective study of 4589 healthy nulliparous women who were enrolled in the Calcium for Preeclampsia Prevention trial conducted from 1992 to 1995. Main outcome measures were birth weight, gestational age at delivery, preterm birth, and small for gestational age birth after the data were controlled for maternal characteristics and intake of total calories, protein, carbohydrate, fat, and 13 vitamin and mineral constituents that were obtained from a 24-hour recall at 13 to 21 weeks' gestation. RESULTS: Black and non-Hispanic white women differed significantly in birth outcomes, with odds ratios of 2.06 (95% confidence interval, 1.48-2.86) for small for gestational age and 1.38 (95% confidence interval, 0.98-1.95) for preterm birth, after adjustment for maternal characteristics. These odds ratios were hardly changed by the further adjustment for all nutritional variables, even though there were substantial nutritional differences between black and white women. Differences in birth outcomes between Hispanic and non-Hispanic white women were small. Hispanic women who spoke only Spanish were better nourished than those Hispanic women who spoke English, but this had only a modest effect on birth outcomes. CONCLUSION: Nutritional variation among women in the United States does not appear to have a significant role in the explanation of ethnic differences in birth outcomes.


Assuntos
Negro ou Afro-Americano , Fenômenos Fisiológicos da Nutrição , Paridade , Resultado da Gravidez , População Branca , Adulto , Peso ao Nascer , Parto Obstétrico , Dieta , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Trabalho de Parto Prematuro , Gravidez , Estudos Prospectivos , Estados Unidos
20.
Diabetes Care ; 24(9): 1602-7, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11522706

RESUMO

OBJECTIVE: We examined whether selected indexes of insulin sensitivity derived from an oral glucose tolerance test (IS(OGTT)) or fasting glucose/insulin levels (IS(QUICKI) and IS(HOMA)) can be used to predict insulin sensitivity in women before and during pregnancy. RESEARCH DESIGN AND METHODS: A 2-h euglycemic-hyperinsulinemic clamp (5 mmol/l glucose, 40 mU. m(-2). min(-1) insulin) and a 120-min oral glucose tolerance test (75 g load pregravid, 100 g pregnant) were repeated on 15 women (10 with normal glucose tolerance [NGT] and 5 with gestational diabetes mellitus [GDM]) pregravid and during both early (12-14 weeks) and late (34-36 weeks) pregnancy. An index of insulin sensitivity derived from the clamp (IS(CLAMP)) was obtained from glucose infusion rates adjusted for change in fat-free mass and endogenous glucose production measured using [6,6(-2)H(2)]glucose. RESULTS: Univariate analysis using combined groups and periods of pregnancy resulted in significant correlations between IS(CLAMP) and IS(OGTT) (r(2) = 0.74, P < 0.0001), IS(QUICKI) (r(2) = 0.64, P < 0.0001), and IS(HOMA) (r(2) = 0.53, P < 0.0001). The IS(OGTT) provided a significantly better correlation (P < 0.0001) than either IS(QUICKI) or IS(HOMA.) Multivariate analysis showed a significant group effect (P < 0.0003) on the prediction model, and separate equations were developed for the NGT (r(2) = 0.64, P < 0.0001) and GDM (r(2) = 0.85, P < 0.0001) groups. When subdivided by period of pregnancy, the correlation between IS(CLAMP) and IS(OGTT) pregravid was r(2) = 0.63 (P = 0.0002), during early pregnancy was r(2) = 0.80 (P < 0.0001), and during late pregnancy was r(2) = 0.64 (P = 0.0002). CONCLUSIONS: Estimates of insulin sensitivity from the IS(OGTT) during pregnancy were significantly better than from fasting glucose and insulin values. However, separate prediction equations are necessary for pregnant women with NGT and women with GDM.


Assuntos
Glicemia/metabolismo , Diabetes Gestacional/sangue , Teste de Tolerância a Glucose , Insulina/sangue , Gravidez/sangue , Análise de Variância , Composição Corporal , Jejum , Feminino , Humanos , Hiperinsulinismo , Infusões Intravenosas , Insulina/administração & dosagem , Insulina/farmacologia , Gravidez/fisiologia , Primeiro Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Valores de Referência , Análise de Regressão , Reprodutibilidade dos Testes
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