Comparison of breath gases, including acetone, with blood glucose and blood ketones in children and adolescents with type 1 diabetes.

Previous studies have suggested that breath gases may be related to simultaneous blood glucose and blood ketone levels in adults with type 2 and type 1 diabetes. The aims of this study were to investigate these relationships in children and young people with type 1 diabetes in order to assess the efficacy of a simple breath test as a non-invasive means of diabetes management. Gases were collected in breath bags and measurements were compared with capillary blood glucose and ketone levels taken at the same time on a single visit to a routine hospital clinic in 113 subjects (59 male, age 7 years 11 months-18 years 3 months) with type 1 diabetes. The patients were well-controlled with relatively low concentrations of the blood ketone measured (ß hydroxybutyrate, 0-0.4 mmol l(-1)). Breath acetone levels were found to increase with blood ß hydroxybutyrate levels and a significant relationship was found between the two (Spearman's rank correlation ρ = 0.364, p < 10(-4)). A weak positive relationship was found between blood glucose and breath acetone (ρ = 0.16, p = 0.1), but led to the conclusion that single breath measurements of acetone do not provide a good measure of blood glucose levels in this cohort. This result suggests a potential to develop breath gas analysis to provide an alternative to blood testing for ketone measurement, for example to assist with the management of type 1 diabetes.

How can cerebral edema during treatment of diabetic ketoacidosis be avoided?

Cerebral edema during diabetic ketoacidosis (DKA) is a rare complication but it can be devastating, with significant mortality and long-term morbidity. Certain risk factors have been teased out with some large case-control studies, but more research needs to be done to make management guidelines safer. This article will discuss how DKA might be prevented from occurring in the first instance, known risk factors for cerebral edema, fluid and insulin management, the importance of careful monitoring during DKA treatment, and the importance of recognizing and acting on the earliest symptoms to prevent long-term harm.

Analysis of transcription factors key for mouse pancreatic development establishes NKX2-2 and MNX1 mutations as causes of neonatal diabetes in man.

Understanding transcriptional regulation of pancreatic development is required to advance current efforts in developing beta cell replacement therapies for patients with diabetes. Current knowledge of key transcriptional regulators has predominantly come from mouse studies, with rare, naturally occurring mutations establishing their relevance in man. This study used a combination of homozygosity analysis and Sanger sequencing in 37 consanguineous patients with permanent neonatal diabetes to search for homozygous mutations in 29 transcription factor genes important for murine pancreatic development. We identified homozygous mutations in 7 different genes in 11 unrelated patients and show that NKX2-2 and MNX1 are etiological genes for neonatal diabetes, thus confirming their key role in development of the human pancreas. The similar phenotype of the patients with recessive mutations and mice with inactivation of a transcription factor gene support there being common steps critical for pancreatic development and validate the use of rodent models for beta cell development.

The fifth UK paediatric diabetes services survey: meeting guidelines and recommendations?

AIM: To assess the provision of UK paediatric and adolescent diabetes services and examine changes in service delivery since 2002. METHOD: Questionnaires were sent to the lead paediatric consultant from all paediatric and adolescent diabetes services (n=205). Questions were based on National Institute for Health and Clinical Excellence and Scottish Intercollegiate Guidelines recommendations for diabetes care in childhood. Results were analysed using parametric and non-parametric tests. RESULTS: 129 Services (63%) returned questionnaires involving 220 clinics. Staffing has improved and 98% of consultants have a special interest in diabetes (89%, 2002). In 88% of services, the diabetes specialist nurse worked solely in paediatric diabetes (53%, 2002). Only 21% of clinics have a psychological professional integrated within the diabetes team (20%, 2002). Over 94% of services offered support with intensive insulin regimens causing problems at school for 36% of services. Almost all services offer annual microvascular screening (98-100%) but transitional care was variable; only 76% of services have specific local protocols for transition and 21% organise transfer by letter only. CONCLUSION: Paediatric and adolescent diabetes services are rising to the challenge of providing high-quality care despite rising prevalence and increasingly complex insulin regimes. Services have improved in a number of key areas but serious deficiencies remain.

Sibling psychological adjustment to type 1 diabetes mellitus.

OBJECTIVE: Type 1 diabetes mellitus (T1DM) is a chronic condition whose management affects the whole family, and siblings of children with chronic conditions have been shown to be at higher risk of emotional and behavioural problems. The aims of this study were to investigate sibling adjustment to T1DM using a cross-sectional questionnaire survey design. METHODS: Forty-one families (48% of those eligible) were recruited from a children's diabetes clinic. From each family, one parent and one sibling of the child with T1DM participated. Parents completed questionnaires measuring sibling adjustment and measures of major life events, social support and parenting stress. Demographic and disease information was obtained from medical records. Siblings completed questionnaires assessing cognitive appraisals and coping strategies. A semi-structured interview was also administered to siblings. RESULTS: Siblings were found to be better adjusted than normative data (p < 0.01). Factors associated with poorer sibling adjustment were higher sibling age at diagnosis, higher levels of parenting stress, more difficult sibling temperament, poorer adjustment of the child with T1DM, higher levels of parental distress and more negative sibling perceptions of diabetes and its impact on the family. Results suggest that sibling perceptions of diabetes and parental distress are important predictors of sibling adjustment to T1DM. CONCLUSIONS: The findings from this study emphasize the relationships between the adjustment of the sibling and that of the child with T1DM and their parents. Many parents worry about how the siblings may cope with the diabetes, but the results of this study are generally reassuring.

Clinical and molecular genetic spectrum of congenital deficiency of the leptin receptor.

BACKGROUND: A single family has been described in which obesity results from a mutation in the leptin-receptor gene (LEPR), but the prevalence of such mutations in severe, early-onset obesity has not been systematically examined. METHODS: We sequenced LEPR in 300 subjects with hyperphagia and severe early-onset obesity, including 90 probands from consanguineous families, and investigated the extent to which mutations cosegregated with obesity and affected receptor function. We evaluated metabolic, endocrine, and immune function in probands and affected relatives. RESULTS: Of the 300 subjects, 8 (3%) had nonsense or missense LEPR mutations--7 were homozygotes, and 1 was a compound heterozygote. All missense mutations resulted in impaired receptor signaling. Affected subjects were characterized by hyperphagia, severe obesity, alterations in immune function, and delayed puberty due to hypogonadotropic hypogonadism. Serum leptin levels were within the range predicted by the elevated fat mass in these subjects. Their clinical features were less severe than those of subjects with congenital leptin deficiency. CONCLUSIONS: The prevalence of pathogenic LEPR mutations in a cohort of subjects with severe, early-onset obesity was 3%. Circulating levels of leptin were not disproportionately elevated, suggesting that serum leptin cannot be used as a marker for leptin-receptor deficiency. Congenital leptin-receptor deficiency should be considered in the differential diagnosis in any child with hyperphagia and severe obesity in the absence of developmental delay or dysmorphism.

Conscious level in children with diabetic ketoacidosis is related to severity of acidosis and not to blood glucose concentration.

OBJECTIVE: To ascertain whether initial depression of conscious level in children with diabetic ketoacidosis (DKA) is related to hyperosmolality, acidosis or other factors. METHODS: In 225 episodes of DKA without evidence of cerebral edema, we examined the relationship between conscious level and initial biochemical variables. We contrasted these findings with those in 42 children who later developed cerebral oedema. RESULTS: On admission, 42/225 (19%) had mild (pH 7.26-7.35); 96 (44%) moderate (pH 7.11-7.25); and 80 (37%) severe DKA (pH

Hypoglycemia prevalence in prepubertal children with type 1 diabetes on standard insulin regimen: use of continuous glucose monitoring system.

OBJECTIVE: To determine hypoglycemia prevalence in prepubertal children on thrice (TID) and twice (BID) daily insulin regimens, using the Medtronic Minimed Continuous Glucose Monitoring System. RESEARCH DESIGN AND METHODS: Twenty-eight children aged <12 years (median 9.8, range 6.9-11.8) wore the sensor for three consecutive days and nights. Hypoglycemia was defined as glucose <60 mg/dl for >15 min. Data are expressed as the percentage of time period spent hypoglycemic. RESULTS: Hypoglycemia prevalence was 10.1% (mean 2.6 h. subject(-1) x day(-1)). Hypoglycemia was more common at night compared with daytime (18.81 vs. 4.4%, P < 0.001); 78 and 43% of subjects showed hypoglycemia on at least one night and two or more nights, respectively. Nocturnal episodes were prolonged (median 3.3 h) and asymptomatic (91% of episodes). Prevalence was greater between 0400 and 0730 h than between 2200 and 0400 h (25.5 vs. 15.4%, P < 0.001). On a TID compared with a BID regimen, nocturnal hypoglycemia prevalence was reduced, particularly between 0400-0730 h (22.9 vs. 27.4%, P = 0.005), whereas hypoglycemia the following morning (0730-1200 h) was greater (7.8 vs. 2.8%, P < 0.001). Nocturnal hypoglycemia risk was associated with decreasing age (by a factor of 0.6 for a year less in age), increased insulin dose (by 1.6 for an increase of 0.1 units. kg(-1) x day(-1)), insulin regimen (by 0.2 on a BID compared with a TID regimen), and increased weight standard deviation score (SDS) (by 2.7 for a one SDS rise). CONCLUSIONS: Use of standard insulin regimens results in high prevalence and large intraindividual variation in hypoglycemia, particularly at night. Independent risk factors for nocturnal hypoglycemia were younger age, greater daily insulin dose, insulin regimen, and increasing weight.

Randomized cross-over trial of insulin glargine plus lispro or NPH insulin plus regular human insulin in adolescents with type 1 diabetes on intensive insulin regimens.

OBJECTIVE: To compare blood glucose control and incidence of nocturnal hypoglycemia in adolescents with type 1 diabetes on multiple injection regimens managed with either an insulin analog combination or NPH insulin plus regular human insulin. RESEARCH DESIGN AND METHODS: In a randomized cross-over study, 28 adolescents with type 1 diabetes on multiple injection therapy received either insulin glargine prebedtime plus lispro preprandially (LIS/GLAR) or NPH insulin prebedtime plus regular human insulin preprandially (R/NPH). During each 16-week treatment arm, subjects completed home blood glucose profiles, and at the end of each treatment arm, they were admitted for an overnight metabolic profile. A total of 25 subjects completed the study. RESULTS: Compared with R/NPH therapy, LIS/GLAR was associated with lower mean blood glucose levels (LIS/GLAR versus R/NPH): fasting (8.0 vs. 9.2 mmol/l, P < 0.0001), 2 h postbreakfast (8.1 vs. 10.7 mmol/l, P < 0.0005), prelunch (8.9 vs. 10.1 mmol/l, P < 0.01), and 2 h postlunch (8.0 vs. 9.5 mmol/l, P < 0.002). However, there was no difference in mean blood glucose levels before or after the evening meal. Incidence of nocturnal hypoglycemia on overnight profiles was 43% lower on LIS/GLAR compared with R/NPH therapy; however, there was no difference in rates of self-reported symptomatic hypoglycemia. Total insulin dose required to achieve target blood glucose control was lower on LIS/GLAR (1.16 IU/kg) compared with R/NPH therapy (1.26 IU/kg, P < 0.005), but there was no significant difference in HbA(1c) levels (LIS/GLAR versus R/NPH: 8.7 vs. 9.1%, P = 0.13). CONCLUSIONS: Combination therapy with insulin glargine plus lispro reduced the incidence of nocturnal hypoglycemia and was at least as effective as R/NPH insulin therapy in maintaining glycemic control in adolescents on multiple injection regimens.