Age-Adjusted Glycated Albumin at Diagnosis is more Correlated with the Product of Age and Plasma Glucose than Plasma Glucose Alone in Patients with Neonatal Diabetes Mellitus.

BACKGROUND: We previously showed that glycated albumin (GA) is a useful glycemic control indicator in patients with neonatal diabetes mellitus (NDM), and that age-adjusted GA (Aa-GA) can reflect more accurately glycemic control status. Here, we investigated whether the age at diagnosis influences Aa-GA at diagnosis of NDM. METHODS: Eight patients with NDM whose GA was measured at diagnosis (age at diagnosis: 39 ± 18 days; GA: 31.3 ± 7.6%; Aa-GA: 47.1 ± 10.3%; plasma glucose: 525 ± 194 mg/dl) were included. Aa-GA was calculated as follows: Aa-GA = GA × 14.0/[1.77 × log-age (days) + 6.65]. Correlations of GA or Aa-GA at diagnosis with its logarithmically transformed age in days (log-age), plasma glucose, and their product were investigated. RESULTS: GA at diagnosis was not significantly correlated with log-age or plasma glucose. On the other hand, Aa-GA at diagnosis was significantly positively correlated with plasma glucose (R = 0.75, P = 0.031) and was more strongly positively correlated with the product of plasma glucose and log-age (R = 0.82, P = 0.012) although it was not correlated with log-age. CONCLUSION: Aa-GA at diagnosis is influenced by both age in days and plasma glucose. This finding is likely to show the aspect that age in days is almost equal to diabetes duration because glycemic control indicators including GA reflect the weighted mean of plasma glucose.

Age-adjusted glycated albumin accurately reflects blood glucose in patients with neonatal diabetes mellitus: comparison with calculated glycated albumin determined by past blood glucose concentrations.

BACKGROUND: Glycated albumin is a useful glycaemic control indicator for neonatal diabetes mellitus. However, glycated albumin concentrations in infants are lower than those in adults and increase in an age-dependent manner. Based on our investigation of non-diabetic subjects, we proposed the possibility that the reference range for adults may be used regardless of age, provided that age-adjusted glycated albumin is employed. In the present study, we evaluate the usefulness of age-adjusted glycated albumin in neonatal diabetes mellitus patients. METHODS: Six neonatal diabetes mellitus patients (four patients with permanent neonatal diabetes mellitus and two patients with transient neonatal diabetes mellitus) were included. Measured glycated albumin or age-adjusted glycated albumin was compared to calculated glycated albumin, which was determined using calculation formulae we had reported based on past blood glucose over the 50 days before measurement of glycated albumin. RESULTS: Measured glycated albumin was significantly lower than calculated glycated albumin (20.5 ± 4.9% versus 28.2 ± 6.1%; p < 0.0001), whereas age-adjusted glycated albumin was equivalent to calculated glycated albumin, showing no significant difference (27.5 ± 6.8% versus 28.2 ± 6.1%). Measured glycated albumin concentrations in patients with transient neonatal diabetes mellitus in remission were lower than the reference range for adults, whereas age-adjusted glycated albumin concentrations were within the reference range for adults. CONCLUSION: We demonstrated that age-adjusted glycated albumin concentrations were consistent with calculated glycated albumin. Age-adjusted glycated albumin is therefore a useful glycaemic control indicator for neonatal diabetes mellitus patients.

Glycemic control and motor development in a patient with intermediate DEND.

The most common cause of neonatal diabetes, KCNJ11 gene mutation, can manifest as a neurological disorder. The most severe form consists of a constellation of developmental delay, epilepsy, and neonatal diabetes (DEND). Intermediate DEND (iDEND) refers to a milder presentation without epilepsy. We present a child with iDEND, for whom insulin injections were replaced with glibenclamide therapy at 17 months of age because of poor glycemic control and delayed motor development. Three months after initiation of glibenclamide, HbA1c decreased from 10.2% to 5.6%. Continuous glucose monitoring indicated that blood glucose fluctuations were suppressed while on glibenclamide. Furthermore, after initiating glibenclamide therapy, the developmental quotient (DQ) for motor ability markedly improved from 60 to 91, whereas the DQ for language and adoptive ability remained as they had been before the sulfonylurea treatment. Sulfonylurea treatment improved glycemic control and motor development in the present patient.

HbA1c can be a useful glycemic control marker for patients with neonatal diabetes mellitus older than 20 weeks of age.

BACKGROUND: The accuracy of most HbA1c analysis methods is affected by the presence of increased fetal hemoglobin (HbF). The objective of this study was to investigate the age at which HbA1c measurements become useful for monitoring glycemic control in patients with neonatal diabetes mellitus (NDM). METHODS: We retrospectively analyzed the data of 5 NDM patients diagnosed at 38±20 days of age, who each had several available HbA1c measurements during the first year of life, with a control group of HbA1c values over the course of 1 year for 13 patients with type 1 diabetes mellitus (T1DM). Mean blood glucose (MBG) levels derived from premeal or premeal plus bedtime blood glucose measurements prior to HbA1c measurements were compared to HbA1c values. RESULTS: The NDM patients' age at which the difference in the HbA1c/MBG ratios became not significant between the NDM patients and the T1DM patients was 21 weeks of age and over. Even after the HbA1c was adjusted for HbF, this ratio was significantly lower in the NDM patients at <21 weeks of age than in the T1DM patients. CONCLUSIONS: HbA1c can be a useful glycemic control marker for NDM patients >20 weeks of age.

Effect of neonatal hypoxia on the development of intraspinal serotonergic fibers in relation to spinal motoneurons.

Serotonin (5-hydroxytryptamine; 5-HT)-containing neurons trophically affect target neurons and modulate central nervous system neuronal activity. We studied effects of neonatal hypoxia on postnatal development of intraspinal 5-HT fibers in spinal motoneuron pools. Postnatal day (PND) 0 Sprague-Dawley rats received a hypoxic load and survivors were used for histological analyzes on PNDs 1, 7, and 14. Spinal motoneurons were labeled using choleratoxin B subunit as a retrograde neurotracer, and 5-HT fibers were detected immunohistochemically. On PND 1, 5-HT fibers were present in the lateral portion of the ventral horn at the cervical level, but were sparsely distributed at the lumbar level. On PND 14, cervical and lumbar level distributions were nearly identical. The 5-HT fibers and varicosities in close apposition to motoneurons increased from PNDs 1-14, however, the close apposition of cervical motoneurons was significantly different from lumbar motoneurons only on PND 1. Density of 5-HT fibers in control and hypoxic rats was not different on PND 1, while those in hypoxic rats were significantly reduced on PND 14. Close appositions of lumbar motoneurons were reduced more than cervical MNs after neonatal hypoxia. Neurodevelopmental deficit after neonatal hypoxia with a rostro-caudal gradient is associated with significant changes in the 5-HT system.

[Questionnaire survey on sleep habit of 3-year-old children in Asahikawa City].

The present study surveyed the sleep habits of 3-year-old children in Asahikawa city using questionnaires completed by a parent during children's medical check-ups. Questionnaires were collected from the parents of 404 children (209 males, 195 females; mean age, 3.1 years) enrolled in this survey. Among these children, the mean bedtime was 9.6 PM with 145 children (36%) going to bed after 10 PM. On the other hand, the mean wake-up time was 7.5 AM, with 123 children (30%) waking up after 8 AM. The mean nocturnal sleep duration was 10.1 hours. Nocturnal sleep durations in children that went to bed after 10 PM were significantly shorter than in children who went to bed earlier (p < 0.01). Seventy-three percent of the children had a daily afternoon nap. Twelve percent of these children usually awoke from their nap after 5 PM, and the mean bedtime for these children was 10.1 PM. A late bedtime was significantly correlated with parental complaints such as short-temper and poor appetite (p < 0.05). Although parents were concerned about night-time sleep conditions, they were not concerned about the daytime conditions which regulate children's sleep-wake rhythm, such as daylight exposure, daytime activity, and naps. While 24% of parents had complains regarding their children's sleep, only 3% had consulted with a doctor. Similar to the previous reports, the present findings demonstrate that children in Asahikawa city go to bed late and have decreased sleep duration. Since the establishment of a normal sleep-wake rhythm is essential for both physical and mental development in children, it is necessary to educate parents regarding the importance of children's sleep.

Molecular analysis and anticonvulsant therapy in two patients with glucose transporter 1 deficiency syndrome: a successful use of zonisamide for controlling the seizures.

Glucose transporter 1 (GLUT1) deficiency syndrome is caused by a deficit in glucose transport to the brain during the pre- and postnatal periods. Here, we report two cases of GLUT1 deficiency syndrome diagnosed on the basis of clinical features, reduced GLUT1 activities, and mutations in the GLUT1 gene. Patient 1 had a novel heterozygous 1bp insertion in exon 7 that resulted in a shift of the reading frame and the introduction of a premature stop codon at amino acid position 380. His clinical phenotype appeared to be more severe than that of Patient 2 who had a missense mutation in exon 8 resulting in an arginine-to-tryptophan substitution at amino acid position 333. Patient 1 had no meaningful words and could not walk unassisted, while Patient 2 could speak and walk unassisted. Both the patients developed seizures of various types that have been successfully treated with zonisamide. Although several antiepileptic drugs, including barbiturates, diazepam, chloralhydrate, and valproic acid, have been shown to inhibit GLUT1 function, the present study demonstrated no inhibitory effect of zonisamide on GLUT1-mediated glucose transport. Our data suggested that zonisamide might be preferable if add-on anticonvulsant therapy is required to control the seizures in patients with this disorder.

Postnatal development of brainstem serotonin-containing neurons projecting to lumbar spinal cord in rats.

We quantified postnatal changes in brainstem serotonin (5-hydroxytryptamine, 5-HT)-containing neurons projecting to lumbar spinal cord. The medulla-spinal cord descending neurons were identified by a retrograde neurotracer, choleratoxin B subunit (CTb), and 5-HT neurons were stained by immunohistochemistry. Double-labeled neurons were assumed to be 5-HT neurons projecting to the lumbar spinal cord, and were quantitatively analyzed in each raphe nucleus in the medulla. The following results were obtained: (1) At PND 3, numerous CTb-labeled neurons (CTLN) were already present in the raphe pallidus (B1), while few CTLN were seen in raphe obscurus (B2) and raphe magnus (B3). CTLN then rapidly increased in number and were separately distributed after PND 7 in B3 and after PND 14 in B2. (2) At PND 3, numerous 5-HT-containing neurons were already present in B1-B3, with 23.4% and 14.0% of them labeled with CTb in B1 and B2, respectively, while there were few double-labeled neurons in B3. From PND 3 to 28, although the proportion of double-labeled to 5-HT neurons remained unchanged in B1 and B2, that in B3 rapidly increased from 5.8% at PND 7 to 28.8% at PND 14. Previous studies have shown that the 5-HT neurons in B3 send fibers mainly to the dorsal horn, while those in B1 and B2 send fibers mainly to the ventral horn at all spinal cord levels. Taken together, the present findings suggest that the brainstem 5-HT systems influence the ventral horn of the spinal cord, where spinal motoneurons exist earlier than in the dorsal horn. The functional significance of these early 5-HT systems in motor development and/or disabilities is discussed.