Krystyna Matyka

Cognitive function and mood after profound nocturnal hypoglycaemia in prepubertal children with conventional insulin treatment for diabetes

OBJECTIVES To examine the frequency of nocturnal hypoglycaemia, and the effects on cognitive function and mood, in children with insulin dependent diabetes mellitus (IDDM). DESIGN Two overnight glucose profiles, in the home environment, and assessments of cognitive function and mood the following day. Twenty nine prepubertal patients with IDDM (median age, 9.4 years; range, 5.3–12.9) and 15 healthy controls (single overnight profile), median age 9.5 (range, 5.6–12.1) years were studied. RESULTS Asymptomatic hypoglycaemia (glucose < 3.5 mmol/l) was observed in 13 of 29 patients studied on night 1: four of these and seven others were hypoglycaemic on night 2. The median glucose nadir was 1.9 (range, 1.1–3.3) mmol/l and the median duration of hypoglycaemia was 270 (range, 30–630) minutes. Hypoglycaemia was related to insulin dose, but not glycosylated haemoglobin (HbA1c) values, and was partially predicted by a midnight glucose of < 7.2 mmol/l. Cognitive performance was not altered after hypoglycaemia but a lowering of mood was observed. CONCLUSIONS Young children on conventional insulin regimens are at high risk for profound, asymptomatic nocturnal hypoglycaemia, which is difficult to predict. There was no short term effect on cognitive function but mood change was detected.

Setting research priorities for Type 1 diabetes.

Diabet. Med. 29, 1321–1326 (2012)

Recessive SLC19A2 mutations are a cause of neonatal diabetes mellitus in thiamine-responsive megaloblastic anaemia

Permanent neonatal diabetes mellitus (PNDM) is diagnosed within the first 6 months of life, and is usually monogenic in origin. Heterozygous mutations in ABCC8, KCNJ11, and INS genes account for around half of cases of PNDM; mutations in 10 further genes account for a further 10%, and the remaining 40% of cases are currently without a molecular genetic diagnosis. Thiamine‐responsive megaloblastic anaemia (TRMA), due to mutations in the thiamine transporter SLC19A2, is associated with the classical clinical triad of diabetes, deafness, and megaloblastic anaemia. Diabetes in this condition is well described in infancy but has only very rarely been reported in association with neonatal diabetes. We used a combination of homozygosity mapping and evaluation of clinical information to identify cases of TRMA from our cohort of patients with PNDM. Homozygous mutations in SLC19A2 were identified in three cases in which diabetes presented in the first 6 months of life, and a further two cases in which diabetes presented between 6 and 12 months of age. We noted the presence of a significant neurological disorder in four of the five cases in our series, prompting us to examine the incidence of these and other non‐classical clinical features in TRMA. From 30 cases reported in the literature, we found significant neurological deficit (stroke, focal, or generalized epilepsy) in 27%, visual system disturbance in 43%, and cardiac abnormalities in 27% of cases. TRMA should be considered in the differential diagnosis of diabetes presenting in the neonatal period.

Managing childhood obesity: when lifestyle change is not enough

The management of childhood obesity is a clinical dilemma. Paediatricians will see those children whose weight is at the severe end of the spectrum with obesity‐related co‐morbidities and for whom more intensive weight loss therapies may be appropriate. A literature review was performed (January 1995–January 2010) of the roles of pharmacotherapy or bariatric surgery in the management of childhood obesity. Three hundred and eighty‐three abstracts were reviewed and 76 full‐text articles were requested. Of these, 34 were excluded and a total of 21 pharmacotherapy papers and 22 papers on surgery were reviewed in detail. All studies involved adolescents. Pharmacotherapy: Most studies were small and of short duration, the notable exceptions being two large RCTs of sibutramine and orlistat. Sibutramine led to a mean estimated change in BMI from baseline of −3.1 kg/m2 vs. −0.3 kg/m2 for placebo over 12 months. Orlistat was also beneficial with a mean reduction in BMI of 0.55 vs. an increase of 0.31 kg/m2 in the placebo group at 12 months. Bariatric surgery: Most papers presented clinical observations and there were no randomised controlled trials (RCTs). Robust selection criteria were not used and ideal candidate selection remains unclear. Most papers showed a significant benefit of surgery in severely obese adolescents in the short term but long‐term data were sparse. There were a surprisingly large number of papers examining the benefits of intensive weight management in obese adolescents. The study design of many was inadequate and the role of pharmacotherapy or surgery in childhood obesity remains unclear.

The concerns of school staff in caring for children with diabetes in primary school

Boden S, Lloyd CE, Gosden C, Macdougall C, Brown N, Matyka K. The concerns of school staff in caring for children with diabetes in primary school.

Genetic testing for maturity onset diabetes of the young in childhood hyperglycaemia

Mild hyperglycaemia is a common finding during minor illness in children. The differential diagnosis includes maturity onset diabetes of the young (MODY), which can be a difficult diagnosis to make clinically. As most genes resulting in MODY have been identified, it is possible to make a firm diagnosis using mutation detection. A case is reported of a 4 year old girl in whom a diagnosis of MODY2 was established by the finding of a heterozygous missense mutation in exon 7 of the glucokinase gene, resulting in the substitution at codon 259 of alanine by threonine (A259T). Observations from other glucokinase families suggest that hyperglycaemia in this child is likely to be stable and will not require intensive medical follow up, whereas other forms of MODY (1, 3, and 4) might carry a different prognosis. Key messages Maturity onset diabetes of the young is an important diagnosis to consider in a child with incidental hyperglycaemia. If considered, parents’ fasting blood glucose should be measured. If raised, molecular genetic testing may be useful. Molecular genetic testing has defined four different phenotypes of MODY with different clinical courses and prognoses. MODY2, resulting in defects of the glucokinase gene, carries a good prognosis.

Hypoglycaemia and Counterregulation during Childhood

Hypoglycaemia is particularly common in young children with type 1 diabetes mellitus yet the normal protective counterregulatory responses have been little studied in this age group. The studies reported have shown conflicting results, in part related to prior glycaemic control and also to the method of investigation used. Counterregulatory hormone responses during both spontaneous and experimentally induced episodes of nocturnal hypoglycaemia do appear to be blunted, which may be a function of sleep itself. Although studies of cognitive function have consistently shown defects in certain areas of neurocognitive performance, particularly in those children with early-onset diabetes or a prior history of severe hypoglycaemia, the contribution of nocturnal hypoglycaemia to the development of these impairments has not been evaluated. In young adults and adolescents, nocturnal hypoglycaemia has been linked to cardiac arrhythmia and the risk of sudden death. The development of new techniques for continuous subcutaneous glucose monitoring may allow detailed study of counterregulatory responses and symptom recognition in young children. Effective intensification of insulin therapy without an increased risk of hypoglycaemia may be possible using new insulin analogues or continued subcutaneous intravenous infusion (CSII), thus improving patient compliance and overall quality of clinical care.

Ethnicity and long-term heart rate variability in children

Background Low heart rate variability (HRV) is associated with increased cardiovascular disease risk. South Asians are at increased risk of cardiovascular disease. Methods This cross-sectional, observational study compared long-term HRV between South Asian and White European (EU) children. 155 children (92 White EU, 63 South Asian) aged 8±1 years wore a combined heart rate and activity monitor for 7 days. From 24-h beat-to-beat heart rate recordings, long-term HRV was calculated as the SD of the average RR intervals in each 5 min period (SDANN). Physical activity, daily energy expenditure, percentage body fat and maximal oxygen consumption (VO2max) were calculated using published or commercial algorithms. Results SDANN was significantly lower during the 24-h period in South Asian compared with White EU children (113±27 vs 130±28 ms, p<0.01, mean±SD) and during sleep (44±12 vs 54±16 ms, p<0.01, mean±SD). Ethnic differences in HRV were associated with lower levels of physical activity, daily energy expenditure, VO2max, and higher percentage body fat and resting heart rate, in South Asian children. Ethnic differences in HRV persisted despite statistical adjustment for these factors. SDANN was significantly lower in girls, but sex differences were no longer apparent when VO2max, physical activity and energy expenditure were statistically controlled for. Conclusions Our data confirm that South Asian children have lower HRV and reveal the novel information that the reduction is partially independent of physical activity and aerobic fitness.

The risk management of childhood diabetes by primary school teachers

This article explores the attitudes of primary school staff in relation to managing children with diabetes. It reports the findings of a qualitatively orientated study in which we conducted in-depth, semi-structured face-to-face interviews with 22 staff that held a variety of positions in primary schools and had a range of experience of caring for children with diabetes. We consider the anxieties and apprehensions expressed to us by our interviewees (covering topics such as injecting/blood testing, and the reactions of parents to school decisions), in both their capacities as educators and, increasingly, frontline care-givers to other peoples children. The expansion and formalisation of healthcare responsibilities within the primary school is shown to have impacted upon the risk assessments made of children with diabetes. Analysis of the data therefore focuses on health related risk anxieties as they are played out in adult/child relations and in the specific context of the primary school.