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1.
Hum Reprod ; 35(4): 913-928, 2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-32325494

RESUMO

STUDY QUESTION: Are maternal serum phthalate metabolite, phenol and paraben concentrations measured at 10-17 weeks of gestation associated with male infant genital developmental outcomes, specifically cryptorchidism, anogenital distance (AGD), penile length and testicular descent distance, at birth and postnatally? SUMMARY ANSWER: Maternal serum bisphenol A (BPA) concentration at 10-17 weeks of gestation was positively associated with congenital or postnatally acquired cryptorchidism, and n-propyl paraben (n-PrP) concentration was associated with shorter AGD from birth to 24 months of age. WHAT IS KNOWN ALREADY: Male reproductive disorders are increasing in prevalence, which may reflect environmental influences on foetal testicular development. Animal studies have implicated phthalates, BPA and parabens, to which humans are ubiquitously exposed. However, epidemiological studies have generated conflicting results and have often been limited by small sample size and/or measurement of chemical exposures outside the most relevant developmental window. STUDY DESIGN, SIZE, DURATION: Case-control study of cryptorchidism nested within a prospective cohort study (Cambridge Baby Growth Study), with recruitment of pregnant women at 10-17 postmenstrual weeks of gestation from a single UK maternity unit between 2001 and 2009 and 24 months of infant follow-up. Of 2229 recruited women, 1640 continued with the infancy study after delivery, of whom 330 mothers of 334 male infants (30 with congenital cryptorchidism, 25 with postnatally acquired cryptorchidism and 279 unmatched controls) were included in the present analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Maternal blood was collected at enrolment, and serum levels of 16 phthalate metabolites, 9 phenols (including BPA) and 6 parabens were measured using liquid chromatography/tandem mass spectrometry. Logistic regression was used to model the association of cryptorchidism with serum chemical concentrations, adjusting for putative confounders. Additionally, offspring AGD, penile length and testicular descent distance were assessed at 0, 3, 12, 18 and 24 months of age, and age-specific Z scores were calculated. Associations between serum chemical levels and these outcomes were tested using linear mixed models. MAIN RESULTS AND THE ROLE OF CHANCE: Maternal serum BPA concentration was associated with offspring all-type cryptorchidism both when considered as a continuous exposure (adjusted odds ratio per log10 µg/l: 2.90, 95% CI 1.31-6.43, P = 0.009) and as quartiles (phet = 0.002). Detection of n-PrP in maternal serum was associated with shorter AGD (by 0.242 standard deviations, 95% CI 0.051-0.433, P = 0.01) from birth to 24 months of age; this reduction was independent of body size and other putative confounders. We did not find any consistent associations with offspring outcomes for the other phenols, parabens, and phthalate metabolites measured. LIMITATIONS, REASONS FOR CAUTION: We cannot discount confounding by other demographic factors or endocrine-disrupting chemicals. There may have been misclassification of chemical exposure due to use of single serum measurements. The cohort was not fully representative of pregnant women in the UK, particularly in terms of smoking prevalence and maternal ethnicity. WIDER IMPLICATIONS OF THE FINDINGS: Our observational findings support experimental evidence that intrauterine exposure to BPA and n-PrP during early gestation may adversely affect male reproductive development. More evidence is required before specific public health recommendations can be made. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a European Union Framework V programme, the World Cancer Research Fund International, the Medical Research Council (UK), Newlife the Charity for Disabled Children, the Mothercare Group Foundation, Mead Johnson Nutrition and the National Institute for Health Research Cambridge Comprehensive Biomedical Research Centre. Visiting Fellowship (J.M.): Regional Programme 'Jiménez de la Espada' for Research Mobility, Cooperation and Internationalization, Seneca Foundation-Science and Technology Agency for the Region of Murcia (No. 20136/EE/17). K.O. is supported by the Medical Research Council (UK) (Unit Programme number: MC_UU_12015/2). The authors declare no conflict of interest.


Assuntos
Parabenos , Fenóis , Compostos Benzidrílicos , Estudos de Casos e Controles , Criança , Feminino , Humanos , Lactente , Masculino , Fenóis/toxicidade , Gravidez , Estudos Prospectivos
2.
Ann Hum Biol ; 47(2): 142-149, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32429763

RESUMO

Background: Highly consistent positive associations are reported between infancy growth and later obesity risk. However, it is unclear whether infancy growth parameters beyond body weight add to the prediction of later obesity risk.Aim: To assess whether infancy length and skinfold thicknesses add to infancy weight in the prediction of childhood adiposity.Subjects and methods: This analysis included 254 children with available data on infant growth from birth to 24 months and childhood adiposity at age 6-11 years measured by DXA. Multilevel linear regression was used to examine the predictors of childhood percent body fat (%BF), with adjustment for sex and age at follow-up visit.Results: Birth weight and weight gain (modelled as changes in z-score) between 0-3 months and 3-24 months showed independent positive relationships with childhood %BF. The addition of gains in infant length and skinfolds between 0-3 months, but not 3-24 months, improved overall model prediction, from 18.7% to 20.7% of the variance in childhood %BF (likelihood ratio test, p < 0.0001), although their independent effect estimates were small (infant length gain: negative trend, partial R-square 0.6%, p = 0.2; skinfolds: positive trend, 1.3%, p = 0.09).Conclusion: Infancy length and skinfolds contribute significantly, but only modestly, to the prediction of childhood adiposity.


Assuntos
Adiposidade , Desenvolvimento Infantil , Obesidade Infantil/etiologia , Aumento de Peso , Peso ao Nascer , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino
3.
N Engl J Med ; 373(22): 2129-2140, 2015 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-26379095

RESUMO

BACKGROUND: The feasibility, safety, and efficacy of prolonged use of an artificial beta cell (closed-loop insulin-delivery system) in the home setting have not been established. METHODS: In two multicenter, crossover, randomized, controlled studies conducted under free-living home conditions, we compared closed-loop insulin delivery with sensor-augmented pump therapy in 58 patients with type 1 diabetes. The closed-loop system was used day and night by 33 adults and overnight by 25 children and adolescents. Participants used the closed-loop system for a 12-week period and sensor-augmented pump therapy (control) for a similar period. The primary end point was the proportion of time that the glucose level was between 70 mg and 180 mg per deciliter for adults and between 70 mg and 145 mg per deciliter for children and adolescents. RESULTS: Among adults, the proportion of time that the glucose level was in the target range was 11.0 percentage points (95% confidence interval [CI], 8.1 to 13.8) greater with the use of the closed-loop system day and night than with control therapy (P<0.001). The mean glucose level was lower during the closed-loop phase than during the control phase (difference, -11 mg per deciliter; 95% CI, -17 to -6; P<0.001), as were the area under the curve for the period when the glucose level was less than 63 mg per deciliter (39% lower; 95% CI, 24 to 51; P<0.001) and the mean glycated hemoglobin level (difference, -0.3%; 95% CI, -0.5 to -0.1; P=0.002). Among children and adolescents, the proportion of time with the nighttime glucose level in the target range was higher during the closed-loop phase than during the control phase (by 24.7 percentage points; 95% CI, 20.6 to 28.7; P<0.001), and the mean nighttime glucose level was lower (difference, -29 mg per deciliter; 95% CI, -39 to -20; P<0.001). The area under the curve for the period in which the day-and-night glucose levels were less than 63 mg per deciliter was lower by 42% (95% CI, 4 to 65; P=0.03). Three severe hypoglycemic episodes occurred during the closed-loop phase when the closed-loop system was not in use. CONCLUSIONS: Among patients with type 1 diabetes, 12-week use of a closed-loop system, as compared with sensor-augmented pump therapy, improved glucose control, reduced hypoglycemia, and, in adults, resulted in a lower glycated hemoglobin level. (Funded by the JDRF and others; AP@home04 and APCam08 ClinicalTrials.gov numbers, NCT01961622 and NCT01778348.).


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Sistemas de Infusão de Insulina , Insulina/efeitos adversos , Adolescente , Adulto , Algoritmos , Criança , Estudos Cross-Over , Diabetes Mellitus Tipo 1/sangue , Desenho de Equipamento , Feminino , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/administração & dosagem , Bombas de Infusão Implantáveis , Insulina/administração & dosagem , Sistemas de Infusão de Insulina/efeitos adversos , Masculino , Pessoa de Meia-Idade
4.
Diabet Med ; 35(10): 1425-1433, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29766563

RESUMO

AIM: Fetal exposure to gestational diabetes mellitus (GDM) is said to alter fetal growth and increase the risk of macrosomia. However, little research on GDM exists in African populations. This study aimed to assess longitudinal fetal growth and neonatal birth measures among Black African babies exposed to GDM. METHODS: Pregnant women (Soweto, South Africa) enrolled into a cohort study were followed up with repeated fetal ultrasounds. At 24-28 weeks' gestation a 2-h 75 g oral glucose tolerance test was performed and GDM was diagnosed using the World Health Organization's 2013 criteria. Neonatal birth measures were assessed. RESULTS: The study involved 741 women; 83 (11.2%) with GDM and 658 (88.8%) without. A total of 4040 fetal ultrasounds were performed. GDM exposure was associated with an increase in fetal growth measures, especially abdominal circumference, which was already seen at 16-18 weeks' gestation. Male fetuses in particular, showed a significant association between GDM exposure and increased abdominal circumference (P = 0.009). Most women with GDM (66.3%) received management; all received diet therapy and 32.7% were prescribed medication. There was no difference in birth measures between the GDM-exposed and unexposed neonates. CONCLUSION: Repeated ultrasound measures identified the effects of GDM as early as 16-18 weeks' gestation, well before a diagnosis of GDM would usually be made. Sex differences in fetal growth were observed, with GDM-exposed male fetuses being more affected with larger abdominal circumferences than females. A low rate of macrosomia was observed compared with historical GDM populations.


Assuntos
Peso ao Nascer/fisiologia , Diabetes Gestacional/epidemiologia , Desenvolvimento Fetal/fisiologia , Adulto , Pesos e Medidas Corporais , Estudos de Coortes , Diabetes Gestacional/sangue , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/fisiopatologia , Feminino , Macrossomia Fetal/diagnóstico , Macrossomia Fetal/epidemiologia , Teste de Tolerância a Glucose , Humanos , Recém-Nascido , Masculino , Gravidez , África do Sul/epidemiologia , Ultrassonografia Pré-Natal , Adulto Jovem
5.
Diabet Med ; 34(4): 460-466, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27973749

RESUMO

Adolescence is a challenging period of life for any young person, and for those with Type 1 diabetes, physiological and psychological factors can result in a deterioration in glycaemic control. In young people with Type 1 diabetes, puberty may be an additional risk factor impacting on the lifetime risk for renal and cardiovascular complications. Our longitudinal studies have identified that increases in urinary albumin excretion through childhood are associated with the development of microalbuminuria and a generalized endotheliopathy linked to cardiovascular risk. Screening of participants recruited to the Adolescent type 1 Diabetes cardio-renal Intervention Trial (AdDIT) confirms that these early changes in albumin excretion are related to both diabetic nephropathy and cardiovascular risk; in part, independent of glycaemic control. Thus, as well as current attempts to improve glycaemic control through enhanced targeted insulin delivery, pumps, sensors and closed loop, we have explored the role of angiotensin-converting enzyme inhibitors and statins in providing cardio-renal protection during adolescence.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Complicações do Diabetes/prevenção & controle , Diabetes Mellitus Tipo 1/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Adolescente , Glicemia/metabolismo , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Complicações do Diabetes/etiologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/metabolismo , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/prevenção & controle , Humanos , Sistemas de Infusão de Insulina , Comportamento de Redução do Risco
6.
Diabet Med ; 34(3): 419-425, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27151105

RESUMO

AIM: To examine the hypothesis that the quality, magnitude and breadth of helper T-lymphocyte responses to ß cells differ in Type 1 diabetes according to diagnosis in childhood or adulthood. METHODS: We studied helper T-lymphocyte reactivity against ß-cell autoantigens by measuring production of the pro-inflammatory cytokine interferon-γ and the anti-inflammatory cytokine interleukin-10, using enzyme-linked immunospot assays in 61 people with Type 1 diabetes (within 3 months of diagnosis, positive for HLA DRB1*0301 and/or *0401), of whom 33 were children/adolescents, and a further 91 were unaffected siblings. RESULTS: Interferon-γ responses were significantly more frequent in children with Type 1 diabetes compared with adults (85 vs 61%; P = 0.04). Insulin and proinsulin peptides were preferentially targeted in children (P = 0.0001 and P = 0.04, respectively) and the breadth of the interferon-γ response was also greater, with 70% of children having an interferon-γ response to three or more peptides compared with 14% of adults (P < 0.0001). Islet ß-cell antigen-specific interleukin-10 responses were similar in children and adults in terms of frequency, breadth and magnitude, with the exception of responses to glutamic acid decarboxylase 65, which were significantly less frequent in adults. CONCLUSIONS: At diagnosis of Type 1 diabetes, pro-inflammatory autoreactivity is significantly more prevalent, focuses on a wider range of targets, and is more focused on insulin/proinsulin in children than adults. We interpret this as indicating a more aggressive immunological response in the younger age group that is especially characterized by loss of tolerance to proinsulin. These findings highlight the existence of age-related heterogeneity in Type 1 diabetes pathogenesis that could have relevance to the development of immune-based therapies.


Assuntos
Envelhecimento , Autoimunidade , Linfócitos T CD4-Positivos/metabolismo , Diabetes Mellitus Tipo 1/imunologia , Células Secretoras de Insulina/imunologia , Modelos Imunológicos , Adolescente , Adulto , Autoanticorpos/análise , Autoantígenos/metabolismo , Linfócitos T CD4-Positivos/imunologia , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/metabolismo , Feminino , Humanos , Células Secretoras de Insulina/metabolismo , Testes de Liberação de Interferon-gama , Interleucina-10/metabolismo , Masculino , Irmãos , Adulto Jovem
7.
Hum Reprod ; 31(11): 2642-2650, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27609981

RESUMO

STUDY QUESTION: What is the relationship between maternal paracetamol intake during the masculinisation programming window (MPW, 8-14 weeks of gestation) and male infant anogenital distance (AGD), a biomarker for androgen action during the MPW? SUMMARY ANSWER: Intrauterine paracetamol exposure during 8-14 weeks of gestation is associated with shorter AGD from birth to 24 months of age. WHAT IS ALREADY KNOWN: The increasing prevalence of male reproductive disorders may reflect environmental influences on foetal testicular development during the MPW. Animal and human xenograft studies have demonstrated that paracetamol reduces foetal testicular testosterone production, consistent with reported epidemiological associations between prenatal paracetamol exposure and cryptorchidism. STUDY DESIGN, SIZE, DURATION: Prospective cohort study (Cambridge Baby Growth Study), with recruitment of pregnant women at ~12 post-menstrual weeks of gestation from a single UK maternity unit between 2001 and 2009, and 24 months of infant follow-up. Of 2229 recruited women, 1640 continued with the infancy study after delivery, of whom 676 delivered male infants and completed a medicine consumption questionnaire. PARTICIPANTS/MATERIALS, SETTING, METHOD: Mothers self-reported medicine consumption during pregnancy by a questionnaire administered during the perinatal period. Infant AGD (measured from 2006 onwards), penile length and testicular descent were assessed at 0, 3, 12, 18 and 24 months of age, and age-specific Z scores were calculated. Associations between paracetamol intake during three gestational periods (<8 weeks, 8-14 weeks and >14 weeks) and these outcomes were tested by linear mixed models. Two hundred and twenty-five (33%) of six hundred and eighty-one male infants were exposed to paracetamol during pregnancy, of whom sixty-eight were reported to be exposed during 8-14 weeks. AGD measurements were available for 434 male infants. MAIN RESULTS AND THE ROLE OF CHANCE: Paracetamol exposure during 8-14 weeks of gestation, but not any other period, was associated with shorter AGD (by 0.27 SD, 95% CI 0.06-0.48, P = 0.014) from birth to 24 months of age. This reduction was independent of body size. Paracetamol exposure was not related to penile length or testicular descent. LIMITATIONS, REASONS FOR CAUTION: Confounding by other drugs or endocrine-disrupting chemicals cannot be discounted. The cohort was not fully representative of pregnant women in the UK, particularly in terms of maternal ethnicity and smoking prevalence. There is likely to have been misclassification of paracetamol exposure due to recall error. WIDER IMPLICATIONS OF THE FINDINGS: Our observational findings support experimental evidence that intrauterine paracetamol exposure during the MPW may adversely affect male reproductive development. STUDY FUNDING/COMPETING INTERESTS: This work was supported by a European Union Framework V programme, the World Cancer Research Fund International, the Medical Research Council (UK), the Newlife Foundation for Disabled Children, the Evelyn Trust, the Mothercare Group Foundation, Mead Johnson Nutrition, and the National Institute for Health Research Cambridge Comprehensive Biomedical Research Centre. The authors declare no conflict of interest.


Assuntos
Acetaminofen/administração & dosagem , Canal Anal/anatomia & histologia , Efeitos Tardios da Exposição Pré-Natal , Testículo/anatomia & histologia , Canal Anal/efeitos dos fármacos , Biomarcadores , Pesos e Medidas Corporais , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Testículo/efeitos dos fármacos
8.
Int J Obes (Lond) ; 39(6): 939-44, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25771929

RESUMO

BACKGROUND: Early postnatal rapid 'catch-up' weight gain has been consistently associated with subsequent higher obesity risk and earlier pubertal development. In many low- and middle-income countries, infancy catch-up weight gain is transient and often followed by growth faltering. We explored the hypothesis that even transient catch-up weight gain during infancy is associated with later obesity risk and earlier puberty. METHODS: A total of 2352 (1151 male, 1201 female) black South African children in the birth to twenty prospective birth cohort study (Johannesburg-Soweto) underwent serial measurements of body size and composition from birth to 18 years of age. At the age of 18 years, whole-body fat mass and fat-free mass were determined using dual-energy X-ray absorptiometry. Pubertal development was assessed by the research team between ages 9 and 10 years, and it was recorded annually from the age of 11 years using a validated self-assessment protocol. RESULTS: Catch-up weight gain from birth to the age of 1 year, despite being followed by growth faltering between ages 1 and 2 years, was associated with greater mid-upper arm circumference (P=0.04) and skinfold thickness (P=0.048) at 8 years of age, and with higher weight (P<0.001) and body mass index (P=0.001) at 18 years of age after adjustment for sex, age, smoking during pregnancy, birth order, gestational age, formula-milk feeding and household socio-economic status. Infancy catch-up weight gain was also associated with younger age at menarche in girls (P<0.001). This association persisted after adjustment for smoking during pregnancy, birth order, gestational age, formula-milk feeding and household socio-economic status (P=0.005). CONCLUSION: Transient catch-up weight gain from birth to the age of 1 year among children born in a low-income area of South Africa was associated with earlier menarche and greater adiposity in early adulthood. This observation suggests that modifiable determinants of rapid infancy weight gain may be targeted in order to prevent later obesity and consequences of earlier puberty in girls.


Assuntos
Adiposidade , Peso ao Nascer , Menarca , Aumento de Peso , Absorciometria de Fóton , Adiposidade/fisiologia , Adolescente , Fatores Etários , Peso ao Nascer/fisiologia , Índice de Massa Corporal , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Menarca/fisiologia , Estudos Prospectivos , Fatores de Risco , Dobras Cutâneas , África do Sul/epidemiologia , Aumento de Peso/fisiologia
9.
Clin Endocrinol (Oxf) ; 82(6): 862-9, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25418044

RESUMO

OBJECTIVE: Progress through puberty involves a complex hormonal cascade, but the individual contributions of hormones, particularly IGF-1, are unknown. We reanalysed Chard growth study data to explore the tempo of puberty based on changes in both height and hormone levels, using a novel method of growth curve analysis. DESIGN AND SUBJECTS: Schoolboys (n = 54) and girls (n = 70) from Chard, Somerset, England, recruited in 1981 at age 8/9 and followed to age 16. MEASUREMENTS: Every 6 months, height and Tanner stages (genitalia, breast, pubic hair) were recorded, and in a subsample (24 boys, 27 girls), blood samples were taken. Serum IGF-1, testosterone (boys) and oestradiol (girls) were measured by radioimmunoassay. Individual growth curves for each outcome were analysed using variants of the super-imposition by translation and rotation (SITAR) method, which estimates a mean curve and subject-specific random effects corresponding to size, and age and magnitude of peak velocity. RESULTS: The SITAR models fitted the data well, explaining 99%, 65%, 86% and 47% of variance for height, IGF-1, testosterone and oestradiol, respectively, and 69-88% for the Tanner stages. During puberty, the variables all increased steeply in value in individuals, the ages at peak velocity for the different variables being highly correlated, particularly for IGF-1 vs height (r = 0·74 for girls, 0·92 for boys). CONCLUSIONS: IGF-1, like height, the sex steroids and Tanner stages, rises steeply in individuals during puberty, with the timings of the rises tightly synchronized within individuals. This suggests that IGF-1 may play an important role in determining the timing of puberty.


Assuntos
Desenvolvimento do Adolescente/fisiologia , Estradiol/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Puberdade/fisiologia , Testosterona/sangue , Adolescente , Estatura/fisiologia , Criança , Inglaterra , Feminino , Humanos , Estudos Longitudinais , Masculino , Maturidade Sexual/fisiologia
10.
Diabet Med ; 32(2): 250-6, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25186101

RESUMO

AIM: To explore adolescents' views and experiences of different treatments for Type 2 diabetes, in order to improve treatment concordance and consider how the current treatment pathway for adolescent Type 2 diabetes could be improved. METHODS: In-depth interviews were held with 12 adolescents who had been diagnosed with Type 2 diabetes. Adolescents were sampled from a UK cohort study. Data were analysed thematically. RESULTS: Interviewees struggled to maintain lifestyle changes. Insulin, metformin and liraglutide were described as effective but, in some cases, as resulting in side effects. Injected treatments were viewed less favourably than oral medications. Weight loss surgery was considered an acceptable treatment for obese adolescents who had tried other treatments for their diabetes. It was apparent that some adolescents had not been surprised by their diagnosis and did not fully appreciate the implications of having diabetes. It was also evident that some individuals had not told peers about their diagnosis due to fearing how they would react. Factors identified as improving treatment concordance included reminders and viewing treatment as effective and easy to take. CONCLUSIONS: Adolescents want treatments that are effective, discrete, easy to take and do not make them different from their peers. As liraglutide was described as effective, and surgery viewed as acceptable in certain circumstances, greater consideration should be given to their potential role in treating adolescent Type 2 diabetes. Practitioners need to ensure that adolescents appreciate the implications of having diabetes and may want to address adolescents' concerns regarding how others view this condition.


Assuntos
Atitude Frente a Saúde , Efeitos Psicossociais da Doença , Diabetes Mellitus Tipo 2/terapia , Estilo de Vida , Obesidade/complicações , Sobrepeso/complicações , Cooperação do Paciente , Adolescente , Cirurgia Bariátrica/efeitos adversos , Índice de Massa Corporal , Estudos de Coortes , Terapia Combinada/efeitos adversos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/dietoterapia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dieta para Diabéticos/efeitos adversos , Dieta Redutora/efeitos adversos , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Masculino , Atividade Motora , Obesidade/dietoterapia , Obesidade/cirurgia , Obesidade/terapia , Sobrepeso/dietoterapia , Sobrepeso/terapia , Reino Unido
11.
Diabetes Obes Metab ; 17(5): 452-8, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25492378

RESUMO

AIMS: To compare overnight closed-loop and sensor-augmented pump therapy in patients with type 1 diabetes by combining data collected during free-living unsupervised randomized crossover home studies. METHODS: A total of 40 participants with type 1 diabetes, of whom 24 were adults [mean ± standard deviation (s.d.) age 43 ± 12 years and glycated haemoglobin (HbA1c) 8.0 ± 0.9%] and 16 were adolescents (mean ± s.d. age 15.6 ± 3.6 years and HbA1c 8.1 ± 0.8%), underwent two periods of sensor-augmented pump therapy in the home setting, in combination with or without an overnight closed-loop insulin delivery system that uses a model predictive control algorithm to direct insulin delivery. The order of the two interventions was random; each period lasted 4 weeks in adults and 3 weeks in adolescents. The primary outcome was time during which sensor glucose readings were in the target range of 3.9-8.0 mmol/l. RESULTS: The proportion of time when sensor glucose was in the target range (3.9-8.0 mmol/l) overnight (between 24:00 and 08:00 hours) was 18.5% greater during closed-loop insulin delivery than during sensor-augmented therapy (p < 0.001). Closed-loop therapy significantly reduced mean overnight glucose levels by 0.9 mmol/l (p < 0.001), with no difference in glycaemic variability, as measured by the standard deviation of sensor glucose. Time spent above the target range was reduced (p = 0.001), as was time spent in hypoglycaemia (<3.9 mmol/l; p = 0.014) during closed-loop therapy. Lower mean overnight glucose levels during closed-loop therapy were brought about by increased overnight insulin delivery (p < 0.001) without changes to the total daily delivery (p = 0.84). CONCLUSION: Overnight closed-loop insulin therapy at home in adults and adolescents with type 1 diabetes is feasible, showing improvements in glucose control and reducing the risk of nocturnal hypoglycaemia.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Adolescente , Adulto , Algoritmos , Glicemia/metabolismo , Automonitorização da Glicemia/métodos , Estudos Cross-Over , Diabetes Mellitus Tipo 1/sangue , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemia/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento
12.
Diabetes Obes Metab ; 17(12): 1173-9, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26257323

RESUMO

AIMS: To evaluate safety, efficacy and glucose turnover during closed-loop with meal announcement using reduced prandial insulin boluses in adolescents with type 1 diabetes (T1D). METHODS: We conducted a randomized crossover study comparing closed-loop therapy with standard prandial insulin boluses versus closed-loop therapy with prandial boluses reduced by 25%. Eight adolescents with T1D [3 males; mean (standard deviation) age 15.9 (1.5) years, glycated haemoglobin 74 (17) mmol/mol; median (interquartile range) total daily dose 0.9 (0.7, 1.1) IU/kg/day] were studied on two 36-h-long visits. In random order, subjects received closed-loop therapy with either standard or reduced insulin boluses administered with main meals (50-80 g carbohydrates) but not with snacks (15-30 g carbohydrates). Stable-label tracer dilution methodology measured total glucose appearance (Ra_total) and glucose disposal (Rd). RESULTS: The median (interquartile range) time spent in target (3.9-10 mmol/l) was similar between the two interventions [74 (66, 84)% vs 80 (65, 96)%; p = 0.87] as was time spent above 10 mmol/l [21.8 (16.3, 33.5)% vs 18.0 (4.1, 34.2)%; p = 0.87] and below 3.9 mmol/l [0 (0, 1.5)% vs 0 (0, 1.8)%; p = 0.88]. Mean plasma glucose was identical during the two interventions [8.4 (0.9) mmol/l; p = 0.98]. Hypoglycaemia occurred once 1.5 h post-meal during closed-loop therapy with standard bolus. Overall insulin delivery was lower with reduced prandial boluses [61.9 (55.2, 75.0) vs 72.5 (63.6, 80.3) IU; p = 0.01] and resulted in lower mean plasma insulin concentration [186 (171, 260) vs 252 (198, 336) pmol/l; p = 0.002]. Lower plasma insulin was also documented overnight [160 (136, 192) vs 191 (133, 252) pmol/l; p = 0.01, pooled nights]. Ra_total was similar [26.3 (21.9, 28.0) vs 25.4 (21.0, 29.2) µmol/kg/min; p = 0.19] during the two interventions as was Rd [25.8 (21.0, 26.9) vs 25.2 (21.2, 28.8) µmol/kg/min; p = 0.46]. CONCLUSIONS: A 25% reduction in prandial boluses during closed-loop therapy maintains similar glucose control in adolescents with T1D whilst lowering overall plasma insulin levels. It remains unclear whether closed-loop therapy with a 25% reduction in prandial boluses would prevent postprandial hypoglycaemia.


Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemia/prevenção & controle , Hipoglicemiantes/administração & dosagem , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Monitorização Fisiológica , Adolescente , Algoritmos , Estudos Cross-Over , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/metabolismo , Esquema de Medicação , Inglaterra/epidemiologia , Feminino , Carga Glicêmica , Humanos , Hiperinsulinismo/induzido quimicamente , Hiperinsulinismo/epidemiologia , Hiperinsulinismo/prevenção & controle , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/sangue , Hipoglicemiantes/uso terapêutico , Injeções Subcutâneas , Insulina/efeitos adversos , Insulina/sangue , Insulina/uso terapêutico , Resistência à Insulina , Masculino , Refeições , Risco
13.
Clin Exp Immunol ; 177(3): 571-85, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24773525

RESUMO

The appearance of circulating islet-specific autoantibodies before disease diagnosis is a hallmark of human type 1 diabetes (T1D), and suggests a role for B cells in the pathogenesis of the disease. Alterations in the peripheral B cell compartment have been reported in T1D patients; however, to date, such studies have produced conflicting results and have been limited by sample size. In this study, we have performed a detailed characterization of the B cell compartment in T1D patients (n = 45) and healthy controls (n = 46), and assessed the secretion of the anti-inflammatory cytokine interleukin (IL)-10 in purified B cells from the same donors. Overall, we found no evidence for a profound alteration of the B cell compartment or in the production of IL-10 in peripheral blood of T1D patients. We also investigated age-related changes in peripheral B cell subsets and confirmed the sharp decrease with age of transitional CD19(+) CD27(-) CD24(hi) CD38(hi) B cells, a subset that has recently been ascribed a putative regulatory function. Genetic analysis of the B cell compartment revealed evidence for association of the IL2-IL21 T1D locus with IL-10 production by both memory B cells (P = 6·4 × 10(-4) ) and islet-specific CD4(+) T cells (P = 2·9 × 10(-3) ). In contrast to previous reports, we found no evidence for an alteration of the B cell compartment in healthy individuals homozygous for the non-synonymous PTPN22 Trp(620) T1D risk allele (rs2476601; Arg(620) Trp). The IL2-IL21 association we have identified, if confirmed, suggests a novel role for B cells in T1D pathogenesis through the production of IL-10, and reinforces the importance of IL-10 production by autoreactive CD4(+) T cells.


Assuntos
Subpopulações de Linfócitos B/imunologia , Subpopulações de Linfócitos B/metabolismo , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/imunologia , Adolescente , Adulto , Fatores Etários , Autoanticorpos/imunologia , Estudos de Casos e Controles , Criança , Citocinas/biossíntese , Diabetes Mellitus Tipo 1/metabolismo , Feminino , Citometria de Fluxo , Regulação da Expressão Gênica , Estudos de Associação Genética , Humanos , Imunofenotipagem , Masculino , Fenótipo , Proteína Tirosina Fosfatase não Receptora Tipo 22/genética , Transdução de Sinais , Adulto Jovem
14.
Diabetes Obes Metab ; 16(11): 1174-8, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24909206

RESUMO

We evaluated the safety and efficacy of closed-loop therapy with meal announcement during reduction and omission of meal insulin boluses in adolescents with type 1 diabetes (T1D). Twelve adolescents with T1D [six male; mean (s.d.) age 15.9 (1.8) years; mean (s.d.) glycated haemoglobin (HbA1c) 77 (27) mmol/mol] were studied in a randomized crossover study comparing closed-loop therapy with meal announcement with conventional pump therapy over two 24-h stays at a clinical research facility. Identical meals were given on both occasions. The evening meal insulin bolus was calculated to cover half of the carbohydrate content of the meal and no bolus was delivered for lunch. Plasma glucose levels were in the target range of 3.9-10 mmol/l for a median [interquartile range (IQR)] of 74 (55,86)% of the time during closed-loop therapy with meal announcement and for 62 (49,75)% of the time during conventional therapy (p = 0.26). Median (IQR) time spent with plasma glucose levels > 10 mmol/l [23 (13,39) vs. 27 (10,50)%; p = 0.88] or < 3.9 mmol/l [1(0,4) vs. 5 (1,10)%; p = 0.24] and mean [standard deviation (SD)] glucose levels [8.0 (7.6,9.3) vs. 7.7 (6.6,10.1) mmol/l, p = 0.79] were also similar. In conclusion, these results assist home testing of closed-loop delivery with meal announcement in adolescents with poorly controlled T1D who miscalculate or miss meal insulin boluses.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hemoglobinas Glicadas/metabolismo , Hipoglicemiantes/administração & dosagem , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Adolescente , Algoritmos , Estudos Cross-Over , Diabetes Mellitus Tipo 1/sangue , Feminino , Humanos , Masculino , Refeições , Resultado do Tratamento
15.
Diabetologia ; 56(5): 1108-17, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23435829

RESUMO

AIMS/HYPOTHESIS: Successful postprandial glycaemia management requires understanding of absorption patterns after meals containing variable complex carbohydrates. We studied eight young participants with type 1 diabetes to investigate a large low-glycaemic-load (LG) meal and another eight participants to investigate a high-glycaemic-load (HG) meal matched for carbohydrates (121 g). METHODS: On Visit 1, participants consumed an evening meal. On follow-up Visit 2, a variable-target glucose clamp was performed to reproduce glucose and insulin levels from Visit 1. Adopting stable-label tracer dilution methodology, we measured endogenous glucose production on Visit 2 and subtracted it from total glucose appearance measured on Visit 1 to obtain meal-attributable glucose appearance. RESULTS: After the LG meal, 25%, 50% and 75% of cumulative glucose appearance was at 88 ± 21, 175 ± 39 and 270 ± 54 min (mean ± SD), whereas glucose from the HG meal appeared significantly faster at 56 ± 12, 100 ± 25 and 153 ± 39 min (p < 0.001 to 0.003), and resulted in a 50% higher peak appearance (p < 0.001). Higher apparent bioavailability by 15% (p = 0.037) was observed after the LG meal. We documented a 20 min deceleration of dietary mixed carbohydrates compared with dietary glucose for the HG meal and a twofold deceleration for the LG meal. CONCLUSIONS/INTERPRETATION: Absorption patterns may be influenced by glycaemic load and/or meal composition, affecting optimum prandial insulin dosing in type 1 diabetes.


Assuntos
Diabetes Mellitus Tipo 1/metabolismo , Carboidratos da Dieta/metabolismo , Hiperglicemia/prevenção & controle , Absorção Intestinal , Refeições , Modelos Biológicos , Adolescente , Adulto , Glicemia/análise , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/dietoterapia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Carboidratos da Dieta/efeitos adversos , Carboidratos da Dieta/uso terapêutico , Feminino , Gluconeogênese , Técnica Clamp de Glucose , Índice Glicêmico , Humanos , Hiperglicemia/etiologia , Hipoglicemiantes/sangue , Hipoglicemiantes/uso terapêutico , Técnicas de Diluição do Indicador , Insulina/sangue , Insulina/uso terapêutico , Masculino , Período Pós-Prandial , Adulto Jovem
16.
Nat Genet ; 19(1): 98-100, 1998 May.
Artigo em Inglês | MEDLINE | ID: mdl-9590300

RESUMO

Size at birth is an important determinant of perinatal survival and has also been associated with the risk for cardiovascular disease and type 2 diabetes in adult life. Common genetic variation that regulates fetal growth could therefore influence perinatal survival and predispose to the development of adult disease. We have tested the insulin gene (INS) variable number of tandem repeats (VNTR) locus, which in Caucasians has two main allele sizes (class I and class III; ref. 3), as a functional candidate polymorphism for association with size at birth, as it has been shown to influence transcription of INS (refs 3-5). In a cohort of 758 term singletons (Avon Longitudinal Study of Pregnancy and Childhood; ALSPAC) followed longitudinally from birth to 2 years, we detected significant genetic associations with size at birth: class III homozygotes had larger mean head circumference (P=0.004) than class I homozygotes. These associations were amplified in babies who did not show postnatal realignment of growth (45%), and were also evident for length (P=0.015) and weight (P=0.009) at birth. The INS VNTR III/II genotype might have bestowed a perinatal survival during human history by conferring larger size at birth. Common genetic variation of this kind may contribute to reported associations between birth size and adult disease.


Assuntos
Peso ao Nascer/genética , Insulina/genética , Repetições Minissatélites , Pré-Escolar , Estudos de Coortes , Suscetibilidade a Doenças , Genótipo , Homozigoto , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais
17.
Diabetologia ; 55(2): 282-93, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22080230

RESUMO

AIMS/HYPOTHESIS: Although maternal hyperglycaemia is associated with increased risk of adverse pregnancy outcome, the mechanisms of postprandial hyperglycaemia during pregnancy are poorly understood. We aimed to describe glucose turnover in pregnant women with type 1 diabetes, according to stage of gestation (early vs late gestation). METHODS: The rates of systemic glucose appearance (R(a)) and glucose disposal (R(d)) were measured in ten pregnant women with type 1 diabetes during early (12-16 weeks) and late (28-32 weeks) gestation. Women ate standardised meals--a starch-rich 80 g carbohydrate dinner and a sugar-rich 60 g carbohydrate breakfast--and fasted between meals and overnight. Stable-label isotope tracers ([6,6-(2)H(2)]glucose and [U-(13)C]glucose) were used to determine R(a), R(d) and glucose bioavailability. Closed-loop insulin delivery maintained stable glycaemic conditions. RESULTS: There were no changes in fasting R(a) (10 ± 2 vs 11 ± 2 µmol kg(-1) min(-1); p = 0.32) or fasting R(d) (11 ± 2 vs 11 ± 1 µmol kg(-1) min(-1); p = 0.77) in early vs late gestation. There was increased hepatic insulin resistance (381 ± 237 vs 540 ± 242 µmol kg(-1) min(-1) × pmol/l; p = 0.04) and decreased peripheral insulin sensitivity (0.09 ± 0.04 vs 0.05 ± 0.02 µmol kg(-1) min(-1) per pmol/l dinner, 0.11 ± 0.05 vs 0.07 ± 0.03 µmol kg(-1) min(-1) per pmol/l breakfast; p = 0.002) in late gestation. It also took longer for insulin levels to reach maximal concentrations (49 [37-55] vs 71 [52-108] min; p = 0.004) with significantly delayed glucose disposal (108 [87-125] vs 135 [110-158] min; p = 0.005) in late gestation. CONCLUSIONS/INTERPRETATION: Postprandial glucose control is impaired by significantly slower glucose disposal in late gestation. Early prandial insulin dosing may help to accelerate glucose disposal and potentially ameliorate postprandial hyperglycaemia in late pregnancy. TRIAL REGISTRATION: ISRCTN 62568875 FUNDING: Diabetes UK Project Grant BDA 07/003551. H.R. Murphy is funded by a National Institute for Health Research (NIHR) research fellowship (PDF/08/01/036). Supported also by the Juvenile Diabetes Research Foundation (JDRF), Abbott Diabetes Care (Freestyle Navigator CGM and sensors free of charge), Medical Research Council Centre for Obesity and Related Metabolic Diseases and NIHR Cambridge Biomedical Research Centre.


Assuntos
Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Gestacional/fisiopatologia , Hiperglicemia/fisiopatologia , Complicações na Gravidez , Administração Oral , Adulto , Glicemia/metabolismo , Índice de Massa Corporal , Carboidratos/química , Diabetes Mellitus Tipo 1/complicações , Jejum , Feminino , Humanos , Resistência à Insulina , Período Pós-Prandial , Gravidez , Resultado da Gravidez , Risco , Fatores de Tempo
18.
Am J Physiol Endocrinol Metab ; 302(12): E1493-501, 2012 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-22454288

RESUMO

The triple-tracer (TT) dilution technique has been proposed to be the gold standard method to measure postprandial glucose appearance. However, validation against an independent standard has been missing. We addressed this issue and also validated the simpler dual-tracer (DT) technique. Sixteen young subjects with type 1 diabetes (age 19.5 ± 3.8 yr, BMI 23.4 ± 1.5 kg/m(2), HbA(1c) 8.7 ± 1.7%, diabetes duration 9.0 ± 6.9 yr, total daily insulin 0.9 ± 0.2 U·kg(-1)·day(-1), mean ± SD) received a variable intravenous 20% dextrose infusion enriched with [U-(13)C]glucose over 8 h to achieve postprandial-resembling glucose excursions while intravenous insulin was administered to achieve postprandial-resembling levels of plasma insulin. Primed [6,6-(2)H(2)]glucose was infused in a manner that mimicked the expected endogenous glucose production and [U-(13)C; 1,2,3,4,5,6,6-(2)H(7)]glucose was infused in a manner that mimicked the expected glucose appearance from a standard meal. Plasma glucose enrichment was measured by gas chromatography-mass spectrometry. The intravenous dextrose infusion served as an independent standard and was reconstructed using the TT and DT techniques with the two-compartment Radziuk/Mari model and an advanced stochastic computational method. The difference between the infused and reconstructed dextrose profile was similar for the two methods (root mean square error 6.6 ± 1.9 vs. 8.0 ± 3.5 µmol·kg(-1)·min(-1), TT vs. DT, P = NS, paired t-test). The TT technique was more accurate in recovering the overall dextrose infusion (100 ± 9 and 92 ± 12%; P = 0.02). The root mean square error associated with the mean dextrose infusion profile was 2.5 and 3.3 µmol·kg(-1)·min(-1) for the TT and DT techniques, respectively. We conclude that the TT and DT techniques combined with the advanced computational method can measure accurately exogenous glucose appearance. The TT technique tends to outperform slightly the DT technique, but the latter benefits from reduced experimental and computational complexity.


Assuntos
Glucose/metabolismo , Traçadores Radioativos , Técnica de Diluição de Radioisótopos , Adolescente , Algoritmos , Área Sob a Curva , Glicemia/metabolismo , Radioisótopos de Carbono/química , Interpretação Estatística de Dados , Deutério/química , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Glucose/farmacologia , Hemoglobinas Glicadas/análise , Humanos , Infusões Intravenosas , Insulina/sangue , Absorção Intestinal , Marcação por Isótopo , Análise dos Mínimos Quadrados , Masculino , Reprodutibilidade dos Testes , Processos Estocásticos , Adulto Jovem
19.
Diabet Med ; 29(10): 1297-302, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22416821

RESUMO

AIMS: Patients with the highest albumin:creatinine ratio within the normal range are at an increased risk for developing microalbuminuria. The mechanistic basis for this is unknown, but may be related to renal inflammation. Our goal was to characterize the urinary excretion of cytokines/chemokines in normoalbuminuric adolescents with Type 1 diabetes to determine whether higher range normoalbuminuria is associated with evidence of renal inflammation. METHODS: Forty-two urinary cytokines/chemokines were measured in subjects who were screened for the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial. Urinary cytokines/chemokines were compared across low (n = 50), middle (n = 50) or high (n = 50) albumin:creatinine ratio tertile groups. RESULTS: At baseline, participants in the upper tertile were younger and had shorter diabetes duration compared with the other groups. Other clinical characteristics were similar. Urinary levels of interleukin 6, interleukin 8, platelet-derived growth factor-AA and RANTES differed across albumin:creatinine ratio tertiles, with higher values in patients in the middle and high tertiles compared with the lower tertile (ANCOVA P ≤ 0.01). CONCLUSIONS: Within the normal albumin:creatinine ratio range, higher urinary albumin excretion is associated with elevated urinary levels of inflammatory markers. Ultimately, this may provide mechanistic insights into disease pathophysiology and stratify the risk of nephropathy in Type 1 diabetes.


Assuntos
Albuminúria/urina , Diabetes Mellitus Tipo 1/urina , Nefropatias Diabéticas/urina , Inflamação/urina , Adolescente , Albuminúria/patologia , Biomarcadores/urina , Quimiocinas/urina , Criança , Creatina/urina , Citocinas/urina , Diabetes Mellitus Tipo 1/patologia , Nefropatias Diabéticas/patologia , Progressão da Doença , Método Duplo-Cego , Feminino , Humanos , Masculino , Fatores de Risco
20.
Diabet Med ; 28(6): 685-91, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21294768

RESUMO

AIMS: Asymmetric dimethylarginine (ADMA) is an independent risk factor for cardiovascular disease and its concentrations are increased in several diseases, including diabetes. However, there is limited information on this plasma marker in young people, particularly in those with Type 1 diabetes. The aim of the present study was therefore to perform a longitudinal evaluation of plasma ADMA and of its determinants in young people with childhood-onset Type 1 diabetes. METHODS: For measurement of ADMA using mass spectrometry, 1018 longitudinal stored blood samples were available from 330 young people with Type 1 diabetes followed in the Oxford Regional Prospective Study. Additional data concerning annual assessments of HbA(1c) , height, weight, insulin dose and three early morning urine samples for measurement of the albumin/creatinine ratio were available. RESULTS: ADMA levels were significantly higher in males than in females (mean ± SD: 0.477 ± 0.090 vs. 0.460 ± 0.089 µmol/l, P=0.002) and declined with chronological age (estimate ± SE: -0.0106 ± 0.0008, P<0.001). A significant inverse association was detected between ADMA and HbA(1c) (estimate ± SE:-0.0113 ± 0.001, P<0.001). ADMA levels were lower in subjects developing microalbuminuria (mean ± SD: 0.455 ± 0.093 vs. 0.476 ± 0.087 µmol/l, P=0.001) than in subjects with normoalbuminuria, but this difference disappeared after adjusting for HbA(1c) . CONCLUSIONS: In this longitudinal study, ADMA concentrations decreased with age and were significantly higher in males and lower in subjects developing microalbuminuria. These associations were largely explained by a paradoxical negative association between HbA(1c) and ADMA. We suggest that chronic hyperglycaemia might down-regulate mechanisms implicated in ADMA production or stimulate its metabolism confounding short-term associations with complications risk.


Assuntos
Arginina/análogos & derivados , Doenças Cardiovasculares/metabolismo , Diabetes Mellitus Tipo 1/sangue , Adolescente , Albuminúria/metabolismo , Arginina/sangue , Biomarcadores/metabolismo , Glicemia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Criança , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/fisiopatologia , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/fisiopatologia , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Estudos Longitudinais , Masculino , Fatores de Risco
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