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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. [ABSTRACT FROM AUTHOR]

Aims/hypothesis. It has been postulated that hypoglycaemia-related cardiac dysrhythmia and, in particular, prolonged cardiac repolarisation, may contribute to increased mortality rates in children and adolescents with type 1 diabetes. Methods. We examined the prevalence of prolonged QT interval on ECG during spontaneous hypoglycaemia in 44 type 1 diabetic subjects (aged 7-18 years), and explored the relationships between serial overnight measurements of QT interval corrected for heart rate (QTc) and serum glucose, potassium and epinephrine levels. Each subject underwent two overnight profiles; blood was sampled every 15 mm for glucose measurements and hourly for potassium and epinephrine. Serial ECGs recorded half-hourly between 23.00 and 07.00 hours were available on 74 nights: 29 with spontaneous hypoglycaemia (defined as blood glucose <3.5 mmol/l) and 45 without hypoglycaemia. Results. Mean overnight QTc was longer in females than in males (412 vs 400 ms, p=0.02), but was not related to age, diabetes duration or HbA1c. Prolonged QTc (>440 ms) occurred on 20 out of 74 (27%) nights, with no significant differences between male and female subjects, and was more prevalent on nights with hypoglycaemia (13/29, 44%) than on nights without (7/45, 15%, p=0.0008). Potassium levels were lower on nights when hypoglycaemia occurred (minimum potassium 3.4 vs 3.7 mmol/I, p=0.0003) and were inversely correlated with maximum QTc (r=-0.40, p=0.03). In contrast, epinephrine levels were not higher on nights with hypoglycaemia and were not related to QTc. Conclusions/interpretation. In young type 1 diabetic subjects, prolonged QTc occurred frequently with spontaneous overnight hypoglycaemia and may be related to insulin-induced hypokalaemia. [ABSTRACT FROM AUTHOR]

Susceptibility to diabetic nephropathy has not yet been causally linked to any genetic factors. We investigated in nuclear families whether parental ambulatory blood pressure, lipids and urine albumin excretion were early markers of risk of microalbuminuria in young adults with Type 1 diabetes. A subset of 98 young adults from the Oxford Regional Prospective Study were followed from diagnosis until aged ≥ 16 years and duration of diabetes ≥ 5 years (probands). Of these subjects, 24 developed microalbuminuria (males ≥ 3.5 mg/mmol; females ≥ 4 mg/mmol) and were designated cases, whereas 74 were controls. Family medical history, 24-h ambulatory blood pressure, urine albumin to creatinine ratio (ACR), non-fasting lipid profile and apolipoproteins (A1 and B) were measured in mothers and fathers. The prevalence of a parental hypertension (taking anti-hypertensive medication or daytime blood pressure > 140/90 mmHg), was similar in cases and controls (29% vs. 35%; χ2 test, P = 0.3). The systolic blood pressure night to day ratio and also ACR were higher in the fathers of cases when compared with the fathers of controls [systolic 0.88 (0.08), n = 14 vs. 0.85 (0.12), n = 53, P = 0.041]; [ACR median (IQ range) 0.6 mg/mmol (0.2–16.9) vs. 0.47 mg/mmol (0.3–3.7), P = 0.049]. Paternal night-time systolic blood pressure, night to day systolic blood pressure ratio and ACR were correlated with an index of susceptibility to albuminuria ( r = 0.25, P = 0.042, n = 69 and r = 0.28, P = 0.022, n = 0.67 and r = 0.24, P = 0.029, n = 0.85, respectively). Higher paternal ACR and night to day ratio of ambulatory blood pressure, but not parental hypertension or maternal factors, are associated with microalbuminuria in young adults with Type 1 diabetes. Diabet. Med. 21, 246–251 (2004) [ABSTRACT FROM AUTHOR]

We have previously demonstrated that insulin sensitivity and secretion at age 1 year was in part related to variation in weight and height gain during infancy. In order to determine whether genetic variation at the insulin gene could also influence these associations, we have studied the relationship between insulin gene variable number of tandem repeat ( INS VNTR) genotypes, insulin secretion and early postnatal growth. We assessed fasting and dynamic insulin secretion in 99 healthy infants at age 1 year, using a short intravenous glucose tolerance test (sIVGTT). Infants were genotyped at the – 23 HphI locus, as a surrogate marker for INS VNTR allele classes I and III. Anthropometric data were recorded at birth and at 1 year. Data are shown as median (interquartile range). Fasting insulin levels were higher in III/III infants ( n = 9) than in I/I infants [ n = 55; 27·4 (17·6–75·6) pmol/l vs. 18·1 (10·3–25·2) pmol/l; P < 0·05]. Insulin secretion during the sIVGTT, as estimated by the serum insulin area under the curve, was also higher in III/III infants [2417 (891–4041) pmol min/l vs. 1208 (592–2284) pmol min/l; P < 0·05]. Fasting and postload plasma glucose levels were similar in both groups. Analysis of covariance showed that genotype differences in fasting insulin sensitivity and insulin secretion were independent of size at birth, postnatal growth velocity and current body mass index. Significant associations between INS VNTR genotype and both insulin sensitivity and secretion were apparent in infancy; these might interact with childhood appetite and nutrition to impact the development of childhood obesity and insulin resistance. [ABSTRACT FROM AUTHOR]

A cross-sectional observational study was used to investigate the reported association between polycystic ovarian syndrome and bulimia nervosa in a group of young, post-menarcheal women in the normal population. Volunteers aged 18–25 years were recruited from two universities and two general practice surgeries in Oxford. A total of 230 women completed an interviewer-based eating disorder examination, which was used to diagnose bulimia nervosa and its variants, and to assess eating behaviour. Transabdominal ultrasound was used to diagnose the presence or absence of polycystic ovaries. Symptoms of polycystic ovarian syndrome were assessed using menstrual history, anthropometric measurements, clinical observation of acne and hirsutism, and biochemical analysis of a fasting blood sample. A total of 30% of all participants described episodes of overeating and 4% had used extreme methods of weight control. Two women were diagnosed with bulimia nervosa, and five women with binge-eating disorder; however, these diagnoses were not associated with polycystic ovaries. Scores for dieting and overall eating disorder symptoms in the polycystic ovary groups were not significantly higher than those for women with normal ovaries, and therefore the suggestion that polycystic ovaries predispose towards the development of eating disorders is not supported by this study. [ABSTRACT FROM PUBLISHER]

Objective: The early detection of a rise in albumin excretion within the normal range could permit early intervention to prevent the development of microalbuminuria (MA) in genetically susceptible subjects with type 1 diabetes. In the Oxford Regional Prospective Study we prospectively examined urine albumin excretion during the first years after diagnosis of childhood type 1 diabetes.Research Design and Methods: Between 1986 and 1995, 511 subjects aged < 16 years were recruited at diagnosis and followed for a median of 6 years (range 1-14). In 78 subjects (designated cases), an annual assessment of the albumin-to-creatinine ratio (ACR) in three morning first-void urine samples detected MA (males: ACR > or =3.5 mg/mmol, females: ACR > or =4.0 mg/mmol in two of three urine samples). In 63 of these subjects and 396 normoalbuminuric diabetic control subjects, rates of change of the ACR were calculated as the slope of the ACR over diabetes duration.Results: The baseline ACR (median [interquartile (IQ) range]), as measured at 1-2.5 years' duration of diabetes, was higher in microalbuminuric subjects than in the normoalbuminuric subjects (1.0 mg/mmol [0.6-2.1], n = 52, vs. 0.8 mg/mmol [0.6-1.2], n = 303; P = 0.02). The rate of increase of the ACR in the years before the onset of MA was higher in the microalbuminuric subjects than in the normoalbuminuric subjects (70% per year [37-149], n = 63, vs. 1% per year [-9 to 13], n = 396; P < 0.001). The mean HbA1c level after the onset of puberty was weakly correlated with the rate of change of the ACR (r = 0.11, P = 0.024, n = 418).Conclusions: Higher levels of ACR within the first 2 years after diagnosis and a significantly higher rate of increase of the ACR within the first 5 years from diagnosis can be detected in subjects who subsequently develop MA. HbA1c is a determinant of risk for MA, but pubertal factors have a greater effect on rates of progression of urine albumin excretion during adolescence in this cohort. [ABSTRACT FROM AUTHOR]

Discusses the markers of microvascular complications in insulin dependent diabetes. Microalbuminuria; Glycemic control; Blood pressure; Family phenotypes and genetic risk for diabetic complications; Endocrine and gender differences.

Responds to comment on the article "ALSPAC study team (2004) Insulin sensitivity and secretion in normal children related to size at birth, postnatal growth, and plasma insulin-like growth factor-I levels," published in a 2004 issue of the periodical "Diabetologia." Need for the confirmation of the risk of adolescent type 2 diabetes and glucose intolerance.