Effectiveness of the Kids in Control of Food (KICk-OFF) structured education course for 11-16 year olds with Type 1 diabetes.

AIM: To assess the effect of a 5-day structured education course (Kids in Control of Food; KICk-OFF) on biomedical and psychological outcomes in young people with Type 1 diabetes. METHODS: This was a cluster-randomized trial involving 31 UK paediatric centres. Participants were recruited prior to stratified centre randomization. Intervention centres delivered KICk-OFF courses, whereas control centres delivered usual care. Participants were 11-16 years of age and had Type 1 diabetes for at least one year. The KICk-OFF course was delivered by trained educators to eight participants per course. Glycaemic control and quality of life were measured at baseline, 6, 12 and 24 months. Secondary outcomes were hypoglycaemia, ketoacidosis, fear of hypoglycaemia and diabetes self-efficacy. RESULTS: Three hundred and ninety-six participants provided baseline data (199 intervention and 197 control). At 6 and 12 months the intervention group showed significantly improved total generic quality of life scores compared with controls (baseline: 80 vs. 82; 6 months: 82 vs. 82; P = 0.04). Across the whole intervention group mean HbA1c levels were not significantly different from controls; baseline HbA1c mean (95% confidence interval), 78 mmol/mol (75-81) vs. 76 mmol/mol (74-79) [9.3% (9-9.6%) vs. 9.1% (8.9-9.4%); 24 months: 77 mmol/mol (74-79) vs. 78 mmol/mol (75-81) (9.2% (8.9-9.4%) vs. 9.3% (9-9.6%)], adjusted mean difference, -2.0 mmol/mol (6.5-2.5) [2.3% (-2.7% to 2.4%)], P = 0.38. CONCLUSIONS: Attending a KICk-OFF course was associated with significantly improved total quality of life scores within 6 months. Glycaemic control, as measured by HbA1c , was no different at 24 months. (Clinical Trial Registry No: ISRCTN3704268).

Expanding the Clinical Spectrum Associated With GLIS3 Mutations.

CONTEXT: GLIS3 (GLI-similar 3) is a member of the GLI-similar zinc finger protein family encoding for a nuclear protein with 5 C2H2-type zinc finger domains. The protein is expressed early in embryogenesis and plays a critical role as both a repressor and activator of transcription. Human GLIS3 mutations are extremely rare. OBJECTIVE: The purpose of this article was determine the phenotypic presentation of 12 patients with a variety of GLIS3 mutations. METHODS: GLIS3 gene mutations were sought by PCR amplification and sequence analysis of exons 1 to 11. Clinical information was provided by the referring clinicians and subsequently using a questionnaire circulated to gain further information. RESULTS: We report the first case of a patient with a compound heterozygous mutation in GLIS3 who did not present with congenital hypothyroidism. All patients presented with neonatal diabetes with a range of insulin sensitivities. Thyroid disease varied among patients. Hepatic and renal disease was common with liver dysfunction ranging from hepatitis to cirrhosis; cystic dysplasia was the most common renal manifestation. We describe new presenting features in patients with GLIS3 mutations, including craniosynostosis, hiatus hernia, atrial septal defect, splenic cyst, and choanal atresia and confirm further cases with sensorineural deafness and exocrine pancreatic insufficiency. CONCLUSION: We report new findings within the GLIS3 phenotype, further extending the spectrum of abnormalities associated with GLIS3 mutations and providing novel insights into the role of GLIS3 in human physiological development. All but 2 of the patients within our cohort are still alive, and we describe the first patient to live to adulthood with a GLIS3 mutation, suggesting that even patients with a severe GLIS3 phenotype may have a longer life expectancy than originally described.

Very low birth weight survivors have reduced peak bone mass and reduced insulin sensitivity.

CONTEXT: Increasing numbers of very low birth weight (VLBW) infants are surviving into adulthood because of improvements in neonatal intensive care. Adverse events in early life can have long-term effects through reprogramming of metabolic systems. OBJECTIVE: To determine whether young adult VLBW survivors have abnormalities of skeletal development or endocrine function. DESIGN: Cross-sectional, observational, case-control study. PARTICIPANTS: Thirty-seven VLBW subjects and 27 healthy controls at peak bone mass (mean age 23). MEASUREMENTS: Differences between cases and controls in body size, body composition, bone mass and bone geometry [assessed by dual-energy X-ray absorptiometry (DXA), hip structure analysis and peripheral quantitative computed tomography (pQCT)], bone turnover [urine N-terminal telopeptide of type I collagen (NTX), serum C-terminal telopeptide of type I collagen (CTX)], aminoterminal propeptide of type I procollagen (PINP) and bone alkaline phosphatase), hormones (sex steroids, IGF-1, PTH and 25-OH vitamin D) and insulin sensitivity (HOMA-IR and oral glucose tolerance testing). RESULTS: VLBW subjects had lower bone density at the lumbar spine (5.7%) and femoral neck (8.6%), which persisted after correction for bone size by the estimation of volumetric density (bone mineral apparent density). Urine NTX was higher in VLBW subjects than in controls, but there were no significant differences in other bone turnover markers. VLBW survivors had lower insulin sensitivity (mean INS-30 controls = 57.0, VLBW subjects = 94.3, P < 0.01), but there were no differences in whole body fat mass or truncal fat mass between VLBW subjects and controls. CONCLUSIONS: Young adult VLBW survivors have reduced bone density for their bone size and reduced insulin sensitivity, which may have significant implications for their risk of fracture and diabetes in later life.

Growth and the premature baby.

There is considerable evidence to show that babies born prematurely have poor postnatal growth, and the more premature the baby, the greater the impairment is likely to be and the longer it will persist. Nutrition has been shown to play an important part in this, but adequate nutrition is difficult, if not impossible, to achieve in these infants. In the most immature infants, growth retardation may continue for many months and catch-up may be delayed and incomplete. Evidence from long-term studies suggests that preterm infants will be shorter and lighter than term controls and that reduced stature and head size may be linked with lower intelligence. Although there is evidence linking better growth to better neurodevelopmental outcome, with reports suggesting that this can be achieved with dietary manipulation, there are also data that suggest that there could be a link between increased postnatal growth and increased morbidity and mortality in later childhood and adult life. Here, we provide an overview of current understanding of growth impairment in infants born prematurely and the effects in later life.

An unusal case of hermaphroditism--a 46,XX/69,XXY chimera.

A diploid/triploid karyotype is an uncommon but important cause of true hermaphroditism and ambiguous genitalia. Individuals have a recognisable phenotype and characteristic hydatidiform placental changes. We report a 46,XX/69,XXY chimeric hermaphrodite. This case highlights the typical features (large placenta, intrauterine growth retardation, asymmetric growth, cranio-facial anomalies, syndactyly and pigmentary dysplasia). It illustrates the importance of obtaining skin and gonadal karyotypes in the case of genital ambiguity, as the venous lymphocytic karyotype is usually diploid.

IGF-I and IGF-binding protein-3 measurements on filter paper blood spots in children and adolescents on GH treatment: use in monitoring and as markers of growth performance.

BACKGROUND/AIM: In childhood an appropriate response to GH treatment is achieved by titration of growth response against dose administered, with careful observation for side-effects. In order to evaluate the potential use of IGF monitoring in children treated with GH, a cross-sectional study has been carried in 215 children and adolescents (134 with GH deficiency (GHD), 54 with Turner syndrome (TS) and 27 with non-GHD growth disorders) treated with GH for 0.2-13.7 years. METHODS: IGF-I and IGF-binding protein-3 (IGFBP-3) were measured in ELISAs, using dried capillary blood collected onto filter papers. Results were expressed as the mean S.D. range (SDS). Values of either analyte < -2 or > +2 SDS were considered abnormal. RESULTS: IGF-I and IGFBP-3 SDS were higher in the TS and non-GHD groups (mean +0.01 and +0.1 respectively) than in those with GHD (mean value -0.6). Nineteen per cent of the IGF-I values (13% low, 6% high) and 12% of IGFBP-3 values were abnormal (10% low, 2% high). Abnormalities, either low or high, were most common in the GHD group. There was a weak but significant relationship between change in height SDS over the Year up to the time of sampling in the whole group and IGF-I SDS. Satisfactory growth performance (+0.5>change in height SDS> -0.5) was found in those with high (7.2%), normal (60%) and low (9.3%) IGF-I levels. Overall, it was estimated that 26% of the tests would indicate that an adjustment to GH dose (up in 18% and down in 8%) could be considered. CONCLUSIONS: From this cross-sectional study of IGF monitoring across a broad range of diagnoses and ages, it can be concluded that the majority of children on GH have normal levels of IGF-I and IGFBP-3, but 26% of tests could suggest that a change of GH dose should be considered. Regular monitoring of IGF-I and IGFBP-3 should be considered in any child on GH treatment.

The incidence of hypoglycaemia in children with type 1 diabetes and treated asthma.

AIMS: To investigate whether treatment of coexisting asthma has any effect on the incidence of hypoglycaemia and on glycaemic control in children with type 1 diabetes. METHODS: An observational study of children attending the paediatric diabetes clinics of five hospitals in the North Trent Region. Information on the frequency of hypoglycaemia in the preceding three months, treatment for asthma, and the individual's latest HbA1c, was recorded when they attended for review. RESULTS: Data were collected on 226 children, of whom 27 (12%) had treated asthma. Only 11/27 children with asthma were taking their prescribed inhaled steroids. All used beta agonists at least once a week. There was a reduction of 20% in the incidence of hypoglycaemia in the diabetic children with treated asthma. Of the children with diabetes and treated asthma, 52% reported an episode of hypoglycaemia in the previous three months compared to 72% of those with only diabetes. There was no difference in the proportion of children experiencing nocturnal or severe hypoglycaemia. Although not significant, those with asthma and diabetes also had better overall control (HbA1c 8.8%) compared to those with diabetes alone (HbA1c 9.3%). CONCLUSIONS: Diabetic children with treated asthma have significantly fewer episodes of hypoglycaemia and better glycaemic control compared to children with diabetes alone. This observation needs further investigation but raises an interesting question. Do the drugs used to treat asthma, in particular beta agonists, have the therapeutic potential to reduce hypoglycaemia and facilitate an improvement in glycaemic control?

Serum leptin and leptin binding activity in children and adolescents with hypothalamic dysfunction.

Marked disturbance in eating behaviour and obesity are common sequelae of hypothalamic damage. To investigate whether these were associated with dysfunctional leptin central feedback, we evaluated serum leptin and leptin binding activity in 37 patients (age 3.5-21 yr) with tumour or trauma involving the hypothalamic-pituitary axis compared with 138 healthy children (age 5.0-18.2 yr). Patients were subdivided by BMI <2 SDS or > or = 2 SDS and healthy children and children with simple obesity of comparable age and pubertal status served as controls. Patients had higher BMI (mean 1.9 vs 0.2 SDS; p <0.001), a greater proportion had BMI > or = 2 SDS (54% vs 8%; p <0.001) and higher serum leptin (mean 2.1 vs 0.04 SDS; p <0.001) than healthy children. Serum leptin (mean 1.1 vs -0.1 SDS; p = 0.004) and values adjusted for BMI (median 0.42 vs 0.23 microg/l:kg/m2; p = 0.02) were higher in patients with BMI <2 SDS. However, serum leptin adjusted for BMI was similar in patients with BMI > or = 2 SDS compared to corresponding controls (1.08 vs 0.95; p = 0.6). Log serum leptin correlated with BMI SDS in all subject groups but the relationship in patients with BMI <2 SDS was of higher magnitude (r = 0.65, slope = 0.29, p =0.05 for difference between slopes) than in healthy controls (r = 0.42, slope = 0.19). Serum leptin binding activity (median 7.5 vs 9.3%; p = 0.02) and values adjusted for BMI (median 0.28 vs 0.48 % x m2/kg; p <0.001) were lower in patients than in healthy children. The markedly elevated leptin levels with increasing BMI in non-obese patients with hypothalamic-pituitary damage are suggestive of an unrestrained pattern of leptin secretion. This along with low leptin binding activity and hence higher free leptin levels would be consistent with central leptin insensitivity.