Fifteen-minute consultation: Management of albuminuria in children and young people with diabetes.

Albuminuria is a marker of diabetic kidney disease. Raised albuminuria in children and young people with diabetes is associated with an increased risk of microvascular and macrovascular complications. This review provides guidance for paediatricians caring for children and young people with type 1 and type 2 diabetes on screening, investigations and treatments for albuminuria in line with relevant national and international recommendations.

Maternal Paracetamol Intake During Pregnancy-Impacts on Offspring Reproductive Development.

Paracetamol (acetaminophen) is the preferred antipyretic/analgesic for pregnant women as it is believed there are no adverse fetal effects at the recommended dose. However, emerging evidence suggests that intrauterine paracetamol exposure may be associated with certain urogenital/reproductive disorders in the offspring. In this mini-review, we describe human fetal sex development and possible pharmacological mechanisms by which paracetamol may disrupt this process, including reduced testicular production of testosterone and/or insulin-like peptide 3. We then review the available epidemiological literature on associations between maternal paracetamol exposure and offspring sexual development. Three epidemiological studies have reported associations between maternal paracetamol intake and increased risk of cryptorchidism, although five others have not. None have found associations with hypospadias or penile length. Two out of three studies have reported a shorter anogenital distance (a marker of androgen action during the masculinisation programming window, ∼8-14 weeks of gestation) in male infants antenatally exposed to paracetamol. One study has described a dose-dependent relationship between maternal paracetamol consumption and earlier female (but not male) attainment of puberty. Such epidemiological analyses are complicated by various factors, including method of paracetamol exposure assessment (usually retrospective self-report), variation in diagnostic accuracy, selection bias, confounding by clinical indication, and demographic/genetic differences between geographically separated populations. There is an urgent need for stronger evidence in this area, from both relevant experimental studies and large, carefully-designed prospective studies. In the meantime, a precautionary attitude to gestational paracetamol usage should be considered as the evidence for clinically significant reproductive effects in humans is limited.

Temporal trends without seasonal effects on gestational diabetes incidence relate to reductions in indices of insulin secretion: the Cambridge Baby Growth Study.

AIMS: The incidence of gestational diabetes has been reported to have risen over the first decade of this century. Some studies have also found it to vary with seasons of the year. We investigated temporal and seasonal trends on gestational diabetes incidence in a single-centre cohort study from Cambridge, UK, and attempted to explain trends using associated risk factors. METHODS: Using a cosinor model, we tested both temporal and seasonal trends in gestational diabetes incidence in 1074 women recruited to the Cambridge Baby Growth Study in 2001-2009 who underwent oral glucose tolerance tests around week 28 of pregnancy. RESULTS: There was a temporal increase in gestational diabetes incidence over the course of recruitment to this study [0.014 (0.005, 0.022) proportional increase per year, p = 2.1 × 10-3], but no seasonal effect (p = 0.7). HOMA B [- 0.015 (- 0.025, - 0.005) per year, p = 3.0 × 10-3] and the insulin disposition index [- 0.036 (- 0.060, - 0.013) per year, p = 3.0 × 10-3], unlike HOMA S, showed negative temporal trends. Risk factor analyses showed a concomitant temporal slight increase in the index of multiple deprivation [0.191 (0.138, 0.257) units per year, p = 4.6 × 10-10]. This index was positively associated with HOMA B (p = 6.1 × 10-5) but not directly with gestational diabetes (p = 0.6), HOMA S (p = 0.2) or the insulin disposition index (p = 0.4). CONCLUSIONS: In this cohort, there were temporal, but not seasonal, increases in gestational diabetes incidence between the years 2001 and 2009, which appeared to be related more to reductions in insulin secretion than sensitivity. Possible mediators of this link include confounding factors related to deprivation.

Serum Phthalate and Triclosan Levels Have Opposing Associations With Risk Factors for Gestational Diabetes Mellitus.

Certain phthalates and bisphenol A (BPA) have been associated with insulin resistance and type 2 diabetes in non-pregnant adults, but studies of gestational diabetes mellitus (GDM) have reported conflicting results for phthalates and no associations with BPA. Our aim was to investigate the relationship between maternal serum levels of phthalate metabolites and phenols at 10-17 weeks of gestation and glucose homeostasis at 28 weeks of gestation. 232 women aged ≥16 years without type 1 or 2 diabetes with singleton male pregnancies were recruited from a single UK maternity centre between 2001 and 2009 as part of a prospective observational study (Cambridge Baby Growth Study). Serum levels of 16 phthalate metabolites and 9 phenols (including BPA) were measured using liquid chromatography/tandem mass spectrometry. Oral glucose tolerance tests were performed at 28 weeks. 47/232 (20.3%) women had GDM. First-trimester triclosan (TCS) was inversely associated with incident GDM (adjusted odds ratio per log increase in concentration 0.54, 95% confidence interval 0.34-0.86, p = 0.010). Amongst women without GDM, first-trimester mono-(2-ethylhexyl) phthalate and mono(carboxyisooctyl) phthalate levels were positively associated with 120-min plasma glucose (adjusted ß 0.268 and 0.183, p = 0.0002 and 0.010, respectively) in mid-pregnancy. No other monotonic associations were detected between phthalate or phenol levels and fasting or stimulated plasma glucose, ß-cell function, insulin resistance, or 60-min disposition index. Our results support a glycaemia-raising effect of phthalates during pregnancy, consistent with findings in non-pregnant populations and suggest a possible protective effect of exposure to TCS against GDM.

Understanding the growth hormone therapy adherence paradigm: a systematic review.

INTRODUCTION: Growth hormone (GH) therapy is used to treat a variety of growth disorders in childhood/adolescence. Its efficacy is thought to be dependent on patients' adherence to their treatment regimen. METHODS: PubMed was searched using the keywords 'growth hormone', 'child'[Mesh], 'adolescent'[Mesh], and 'patient compliance'[Mesh]. RESULTS: Most studies of adherence to paediatric GH therapy have used either issued/encashed GH prescriptions or questionnaires. Estimates of prevalence of non-adherence vary from 5-82%, depending on the methods and definitions used. Different studies have variously demonstrated an association (or lack thereof) between adherence and age, socioeconomic status, treatment duration, injection device used and injection-giver. A number of interventions have been proposed to improve adherence, including offering a choice of injection device, but none are supported by trials. Poor adherence is associated with reduced height velocity and likely increased economic costs; evidence for other effects is circumstantial. CONCLUSION: Adherence to paediatric GH therapy is suboptimal, which may partially explain why the mean final height attained is below that of the general population. Analysis of the causes of non-adherence is complicated by conflicting evidence from different studies. Multifactorial interventions are most likely to be successful in improving adherence. We make recommendations for further research.

Record-based, stepwise screening for type 2 diabetes integrated into an annual cardiovascular care review system: Findings from a UK general practice.

AIMS: Screening high-risk individuals for type 2 diabetes (T2DM) is recommended by many organisations. We report results from a pragmatic stepwise T2DM screening programme integrated into an annual review system in a UK general practice. METHODS: Patients with hypertension, cardiovascular disease or chronic kidney disease attending an annual review were screened for dysglycaemia by random blood glucose (RBG) measurement. At the discretion of the usual doctor, individuals with an RBG≥6.1 mmol/l were invited to return for fasting blood glucose (FBG) or HbA(1C) measurement, allowing diagnosis of T2DM. RESULTS: 786 eligible patients were invited for T2DM screening as part of their annual review. 544 attended screening, of whom 120 had an RBG≥6.1 mmol/l. 40 individuals attended FBG measurement and 8 individuals attended HbA(1C) measurement, leading to 9 T2DM diagnoses. The positive predictive value of the test for T2DM was 19% and the laboratory cost was £91 per patient diagnosed with T2DM. CONCLUSIONS: It is feasible to integrate a simple T2DM screening programme within an annual review system in a UK general practice. Different strategies may be required to increase initial attendance and ensure completion of the screening programme.