RESUMEN
AIMS/HYPOTHESIS: The association between lower birthweight and metabolic syndrome may result from fetal undernutrition (fetal programming hypothesis) and/or genes causing both low birthweight and insulin resistance (fetal insulin hypothesis). We studied associations between the birthweight of parents and metabolic syndrome in the offspring. METHODS: We identified men and women (aged 35-68 years), who had been born in Holdsworth Memorial Hospital, Mysore, India. We also identified the offspring (20-46 years) of these men and women. In total, 283 offspring of 193 mothers and 223 offspring of 144 fathers were studied. Investigations included anthropometry, oral glucose tolerance, plasma insulin and lipid concentrations and blood pressure. The metabolic syndrome was defined using WHO criteria. RESULTS: Among the offspring, lower birthweight was associated with an increased risk of glucose intolerance (impaired glucose tolerance, impaired fasting glucose or type 2 diabetes) and higher cholesterol and triacylglycerol concentrations (p < 0.05 for all adjusted for sex and age). Most outcomes in the offspring, including most individual components of the metabolic syndrome, were unrelated to parental birthweight. However, both maternal and paternal birthweight were inversely related to offspring metabolic syndrome (odds ratio [OR] 0.36 [95% CI: 0.13-1.01] per kg, p = 0.053 for mother-offspring pairs; OR 0.26 [0.07-0.93], p = 0.04 for father-offspring pairs, adjusted for offspring age, sex, BMI and socioeconomic status). Maternal birthweight was inversely related to offspring systolic blood pressure (beta = -2.5 mmHg [-5.00 to 0.03] per kg maternal birthweight; p = 0.052). CONCLUSIONS/INTERPRETATION: Factors in both parents may influence the risk of metabolic syndrome in their offspring. There are several possible explanations, but the findings are consistent with the fetal insulin (genetic) hypothesis.
Asunto(s)
Peso al Nacer/fisiología , Síndrome Metabólico/epidemiología , Adulto , Hijos Adultos , Anciano , Peso al Nacer/genética , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/fisiopatología , Ambiente , Epigénesis Genética , Padre , Femenino , Intolerancia a la Glucosa/epidemiología , Humanos , India , Recién Nacido de Bajo Peso/fisiología , Recién Nacido , Resistencia a la Insulina/genética , Resistencia a la Insulina/fisiología , Masculino , Síndrome Metabólico/etnología , Síndrome Metabólico/fisiopatología , Persona de Mediana Edad , Madres , Estudios Retrospectivos , Factores de RiesgoRESUMEN
OBJECTIVES: To describe the use of disease-modifying anti-rheumatic drugs (DMARDs) in the treatment of rheumatoid arthritis (RA) and changing trends in their use. METHODS: We used the General Practice Research Database (GPRD) to describe DMARD use by patients with RA identified using ICD-9 codes. The GPRD is a UK national database containing records of more than 7 million individuals from 683 general practices. Subjects were studied between 1987 and 2002. The prevalence and duration of individual DMARD use and changing trends in DMARD use were investigated. RESULTS: Thirty-four thousand three hundred and sixty-four patients with RA were identified. Only 17,115 (50%) individuals were prescribed at least one DMARD during the study period. The most commonly prescribed DMARD over the study period was sulphasalazine (46.3%) and then methotrexate (31.4%). Use of methotrexate has increased 17-fold (1.8% of all DMARD prescriptions in 1988 to 30% in 2002) whereas use of gold has fallen (13.2% to 2.3%). Analysis of DMARD persistence using Kaplan-Meier survival curves showed the methotrexate use persisted significantly longer than other DMARDs with an estimated median of 8.1 yr. Prednisolone was used in up to 50% of RA patients in any one year and has remained fairly constant throughout the study period. CONCLUSIONS: Large numbers of individuals with a clinical diagnosis of RA identified from a large primary care database are not receiving DMARDs. This work suggests that many individuals with RA have not been treated appropriately and this may have major long-term consequences on joint damage and general health.
Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Anciano , Artritis Reumatoide/epidemiología , Bases de Datos Factuales , Utilización de Medicamentos/estadística & datos numéricos , Utilización de Medicamentos/tendencias , Medicina Familiar y Comunitaria/estadística & datos numéricos , Femenino , Humanos , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Sulfasalazina/uso terapéutico , Análisis de Supervivencia , Reino Unido/epidemiologíaRESUMEN
OBJECTIVES: Muscle-thin but adipose ('thin-fat') body composition of south Asian adults contributes to their high risk of type 2 diabetes. Studies in Pune, India showed that this phenotype is present at birth. We aimed to determine if south Indian babies have a 'thin-fat' phenotype and if this persists in childhood. DESIGN: Prospective cohort study. SETTING: Holdsworth Memorial Hospital, Mysore, India. SUBJECTS: Children (n = 663) whose mothers were recruited from the antenatal clinics. METHODS: Weight, length, head, mid-upper-arm, abdominal circumferences; triceps and subscapular skinfolds were measured at birth, one and four years, and compared with white Caucasian babies born in Southampton, UK (birth), and UK and Dutch growth standards (one and four years). RESULTS: Mysore babies were lighter (2983 g vs 3472 g; -1.10 SD, CI -1.16, -1.02) and smaller in all body measurements than UK neonates (P < 0.001). The deficit was greatest for mid-upper-arm (-1.07 SD), head (-0.89 SD) and abdominal circumferences (-0.73 SD), and least for length (-0.25 SD) and subscapular skinfold thickness (-0.19 SD). Predictors of skinfold thickness were maternal body mass index (P < 0.001) and socio-economic status (P = 0.05). At four years, subscapular skinfold thickness was larger than UK (+0.18 SD, CI +0.11, +0.25; P < 0.001) and Dutch standards (+0.61 SD, CI +0.51, +0.71; P < 0.001), despite all other body measurements remaining smaller. Predictors of 4-year skinfold thickness were neonatal skinfold thickness (P = 0.001) and maternal insulin concentrations (P = 0.05). CONCLUSIONS: Mysore newborns have a 'thin-fat' phenotype. This may reflect the action of genes and/or the 'maternal environment'. The phenotype persists in childhood, and may be the forerunner of a diabetogenic adult phenotype.