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.

Efficacy, safety and immunogenicity of RIX4414 in Japanese infants during the first two years of life.

A phase III, randomized, double-blind study evaluated the efficacy, reactogenicity, safety and immunogenicity of a human rotavirus vaccine, RIX4414 in Japanese infants aged 6-14 weeks when administered as two doses (0, 1-month schedule). Efficacy against any and severe rotavirus gastroenteritis leading to medical intervention caused by circulating wild-type rotavirus from two weeks post-Dose 2 until two years of age was 79.3% (95% CI: 60.5-89.8%) and 91.6% (95% CI: 62.4-99.1%), respectively. Solicited, unsolicited symptoms and serious adverse events were reported at a similar frequency in both groups. Serum anti-rotavirus antibody seroconversion rate one-month post-Dose 2 was 85.3% (95% CI: 68.9-95%) in RIXX4414 group. RIX4414 was efficacious, well-tolerated and immunogenic in Japanese infants and introduction of vaccination could help in reducing the disease burden.

Single cytomegalovirus strain associated with fetal loss and then congenital infection of a subsequent child born to the same mother.

BACKGROUND: Intrauterine transmission of cytomegalovirus (CMV) can occur even in CMV-seropositive mothers. Previous studies demonstrated re-infection with a newly acquired CMV strain during pregnancy had a major role in such transmission. Although reactivation of latently infected CMV is another plausible cause, no direct evidence has been documented. OBJECTIVES: We sought to identify the route(s) and maternal risk factor of CMV infection that occurred in consecutive pregnancies and resulted in symptomatic congenital infections. STUDY DESIGN: A newborn identified with congenital CMV infection in our newborn screening program developed hearing loss and subsequent nystagmus. The mother had a history of an elective abortion due to a severe fetal CMV infection 32 months prior to delivery of this newborn. We analyzed maternal serological changes and compared CMV genomic sequences in specimens obtained from the aborted fetus and the present case. We also analyzed immunological functions of the mother. RESULTS: Our major findings were as follows: (1) the aborted fetus and the present case were infected with the same strain. (2) The congenital infection that resulted in the abortion was due to a primary infection. (3) CMV DNA was undetectable in the mother's blood from 3 months after the abortion. These results strongly suggested that maternal viral reactivation caused the congenital infection in the present case. However, we could not find impairment of immunological functions in the mother. CONCLUSIONS: Viral reactivation in an apparently immunocompetent mother can cause symptomatic congenital CMV infection.