Epigenetic regulation of POMC; implications for nutritional programming, obesity and metabolic disease.

Proopiomelanocortin (POMC) is a key mediator of satiety. Epigenetic marks such as DNA methylation may modulate POMC expression and provide a biological link between early life exposures and later phenotype. Animal studies suggest epigenetic marks at POMC are influenced by maternal energy excess and restriction, prenatal stress and Triclosan exposure. Postnatal factors including energy excess, folate, vitamin A, conjugated linoleic acid and leptin may also affect POMC methylation. Recent human studies suggest POMC DNA methylation is influenced by maternal nutrition in early pregnancy and associated with childhood and adult obesity. Studies in children propose a link between POMC DNA methylation and elevated lipids and insulin, independent of body habitus. This review brings together evidence from animal and human studies and suggests that POMC is sensitive to nutritional programming and is associated with a wide range of weight-related and metabolic outcomes.

Continuing rise of Type 2 diabetes incidence in children and young people in the UK.

AIMS: To estimate the incidence of Type 2 diabetes in children aged <17 years, compare this with similar data 10 years ago, and characterize clinical features at diagnosis in the UK and Republic of Ireland. METHODS: Using the British Paediatric Surveillance Unit reporting framework, cases of Type 2 diabetes diagnosed in children aged <17 years between 1 April 2015 and 30 April 2016 were reported each month. RESULTS: A total of 106 cases were reported, giving a UK incidence of 0.72/100 000 (95% CI 0.58-0.88). Children from ethnic minorities had significantly higher incidence compared with white children (0.44/100 000) with rates of 2.92/100 000 and 1.67/100 000, in Asian and BACBB (black/African/Caribbean/black British) children respectively. Sixty-seven percent were girls and 81% had a family history of Type 2 diabetes. The mean BMI sd score at diagnosis was 2.89 (2.88, girls; 2.92, boys); 81% were obese. Children of Asian ethnicity had a significantly lower BMI sd score compared with white children (P<0.001). There was a trend in increased incidence from 2005 to 2015, with a rate ratio of 1.35 (95% CI 0.99-1.84), although this was not statistically significant (P=0.062). There was statistical evidence of increased incidence among girls (P=0.03) and children of South-Asian ethnicity (P=0.01) when comparing the 2005 and 2015 surveys. CONCLUSIONS: Type 2 diabetes remains far less common than Type 1 diabetes in childhood in the UK, but the number of cases continues to rise, with significantly increased incidence among girls and South-Asian children over a decade. Female gender, family history, non-white ethnicity and obesity were found to be strongly associated with the condition.

Hypercholesterolaemia screening in Type 1 diabetes: a difference of opinion.

AIM: To assess cholesterol screening of children with Type 1 diabetes by diabetes professionals using a survey of current practice, given that National Institute of Health and Care Excellence guidelines on childhood Type 1 diabetes do not recommend cholesterol screening, yet the National Paediatric Diabetes Audit has an annual cholesterol measure (> 12 years) as a key outcome indicator. METHODS: An online survey was sent to 280 members of the Association of Children's Diabetes Clinicians to assess cholesterol screening practice in children. RESULTS: A total of 87 diabetes professionals (31%) responded. The results showed that 94% of respondents measured cholesterol, 33% did this annually on all children, and 7% measured fasting cholesterol. A total of 63% used no guidelines to decide treatment or further investigation. The definition of 'high' cholesterol varied from > 4.5 to > 8 mmol/l, with 40% giving no response or specific level. Only 14% of clinicians had started statin therapy in their diabetes clinic in the previous 5 years. CONCLUSION: Whilst the majority of diabetes professionals measured cholesterol in children with Type 1 diabetes, there was marked variability in sampling, in children screened and in action taken if levels were considered abnormal. It is debatable whether cholesterol measures should be undertaken, certainly more than once, and whether cholesterol level should feature as a key outcome in the national audit in future.

The clinical significance of disturbed sleep and the use of hypnotics.

This article discusses the causes of sleeplessness and its long-term management. Sleep may be repeatedly disturbed by pain, dyspnoea, micturition, or restlessness. The sleep patterns of the diseases which produce these symptoms are given, with an explanation in physiological terms of why they disturb sleep. A knowledge of these sleep patterns provides a valuable aid to diagnosis. It is concluded that there is only one condition, senility leading to senile dementia, for which long-term night sedation is justified.