M Owada

Kagawa Nutrition University, Saitama, Saitama, Japan

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Publications (55)167.88 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The most appropriate time for screening for Fabry disease (FD) is school age. For this reason, we developed non-invasive methods for measuring urinary alpha-galactosidase A (alpha-gal A) protein, using enzyme-linked immunosorbent assay (ELISA), and for globotriaosylceramide (GL-3), using tandem mass spectrometry (MS/MS). We measured these two biomarkers in the urine of previously diagnosed FD hemizygotes and heterozygotes, and in controls. All the classic FD hemizygotes were clearly distinguished from controls by either method alone, and combining the two assays produced 96% sensitivity for detecting heterozygotes. To assess the utility of these methods for screening school children and adults at high risk of FD, a pilot study was conducted. To distinguish FD from 432 controls, cut-off values for alpha-gal A protein and GL-3 were set at the 5th and 95th centile values of the controls, respectively. Among the high-risk patients, the measurements exceeded the cut-off values for both biomarkers in male and female subjects and were strong indicators for Fabry hemizygotes and heterozygotes. However, we recommend that if the results of the first measurements exceed the cut-off values for only one of these biomarkers, another urine sample should be requested for re-assay to confirm the result.
    Pediatric Nephrology 10/2008; 23(9):1461-71. · 2.94 Impact Factor
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    ABSTRACT: Abstract Data collected in our institution, in which approximately one-fourth of the prenatal diagnoses for inborn errors of metabolism in Japan are performed, suggest somewhat higher prevalences of Gaucher disease and mucolipidoses in Japan than in the United States, European countries and Australia. Hunter disease seems to be more frequent than Hurler disease in Japan while the reverse is true in Europe and Australia. In contrast, family histories of Pompe disease or cystinosis were much less frequent indications for prenatal diagnosis in Japanese than in Caucasian populations. The results of a recent multicenter survey conducted in Japan on the indications for and reliability of prenatal diagnoses for inherited metabolic disease support the conclusions drown from our data. The relative frequencies of each of the lysosomal storage diseases, with the exception of the mucopolysaccharidoses, obtained from our prenatal diagnosis surveys were quite similar to those derived from an epidemiological study of lysosomal storage diseases in Japan. We conclude that prenatal diagnosis can be used an indicator of the prevalences of lysosomal storage diseases in Japan.
    Congenital Anomalies 05/2008; 32(2):135 - 141.
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    ABSTRACT: A large number of children with type 2 diabetes have been detected by a urine glucose screening program conducted at schools in Japan since 1975. The incidence of type 2 diabetes in children has increased over the last three decades, and the incidence is estimated to be approximately 3.0/100,000/y during 1975-2000. The incidence of type 2 diabetes in junior high school children is three to six times higher than that in primary school children. More than 80% of children with type 2 diabetes are obese, and boys are more likely to be obese than girls. It is speculated that the increase in the incidence of childhood type 2 diabetes over the years may be a consequence of the increase in the frequency of obesity in school children. However, this trend of increasing incidence of childhood obesity has recently become weaker, and perhaps as a consequence, the incidence of type 2 diabetes has also decreased after the year 2000 in some cities of Japan. Improved attention to physical activity and eating habits among young people may be responsible at least in part to the decrease in the incidence of type 2 diabetes noted in recent years in big cities of Japan.
    Pediatric Research 03/2007; 61(2):141-5. · 2.67 Impact Factor
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    ABSTRACT: This study evaluated recent changes in the annual incidence of childhood type 2 diabetes in the Tokyo metropolitan area. From 1974 to 2004, a total of 236 students were diagnosed as having type 2 diabetes by the urine glucose screening program at school. The overall incidence of type 2 diabetes was 2.55/100,000. Overall, 83.9% of students with diabetes were obese; junior high school students had a significantly higher incidence than primary school students (0.75 vs. 6.27/100,000). The annual incidences over the 5-yr periods from 1974-2004 were 1.73, 3.23, 3.05, 2.90, 2.70 and 1.41/100,000, respectively. The incidences in 1974-1980 and 2001-2004 were significantly lower than those in 1981-1985, 1986-1990 and 1991-1995, because primary school students in 1974-1980 had a significantly lower incidence (0.27/100,000), and junior high school students in 2001-2004 had a somewhat lower incidence (3.66/100,000) than during 1981-2000. In recent years, Japanese children's lifestyle and eating habits have gradually improved, and this may have contributed to the trend toward decrease in the incidence of type 2 diabetes in 2001-2004 in the Tokyo metropolitan area.
    Clinical Pediatric Endocrinology 01/2007; 16(2):53-58.
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    Diabetes Care 10/2006; 29(9):2176-7. · 7.74 Impact Factor
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    ABSTRACT: This study investigates the annual incidence and clinical characteristics of type 2 diabetes among school-aged children as detected by urine glucose screening from 1974 to 2002 in the Tokyo metropolitan area. In total, 8,812,356 school children were examined for glucosuria. Morning urine was used for the analysis. When the urine was positive for glucose, an oral glucose tolerance test was carried out to confirm diabetes. In all, 232 students were identified to have type 2 diabetes. The overall annual incidence of type 2 diabetes was 2.63/100,000. The annual incidence after 1981 was significantly higher than that before 1980 (1.73 vs. 2.76/100,000, P < 0.0001). The annual incidence was significantly higher for junior high school students compared with primary school students (0.78 vs. 6.43/100,000, P < 0.0001). The overall male-to-female ratio of students with type 2 diabetes was 1.0:1.19 (P = 0.296), but it was 1.0:1.56 (P = 0.278) for primary school students. Overall, 83.4% of children with diabetes were obese (> or = 20% overweight). However, nonobese girls (<20% overweight) with diabetes accounted for 23.0% of the patients, whereas markedly obese boys (> or = 40% overweight) accounted for 61.5% of the patients. The frequency of a family history of type 2 diabetes in second- and first-degree relatives was 56.5%. We confirmed that the incidence of young people with type 2 diabetes increased after 1981 in the Tokyo metropolitan area. The increase in the frequency of this disorder seemed to be strongly related to an increasing prevalence of obesity. Age and genetic susceptibility may be associated with the occurrence of type 2 diabetes.
    Diabetes Care 08/2005; 28(8):1876-81. · 7.74 Impact Factor
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    ABSTRACT: Fabry disease is an X-linked sphingolipidosis due to a deficiency of alpha-galactosidase A, which leads to the accumulation of globotriaosylceramide (GL-3) in several organs. When recombinant human alpha-galactosidase A is intravenously administered repeatedly before the patient develops permanent tissue damage, there is evidence that the accumulation of GL-3 is decreased in some organs and that the clinical symptoms are alleviated in some patients. However, Fabry disease is rare and many patients are not diagnosed until adulthood after irreversible tissue damage has occurred. Our group has developed a simple and non-invasive screening method for Fabry disease that measures total GL-3 in whole urine samples by tandem mass spectrometry. Using this method, we found that the concentration of GL-3 in whole urine sample from hemizygous patients, including pre-symptomatic young children with classic type Fabry disease, was significantly higher than that in controls. The mean concentration of GL-3 in urine from heterozygotes with symptoms was significantly higher than control concentrations, but GL-3 levels in the urine from 2 out of 8 heterozygotes of classic type Fabry disease were within control levels. An asymptomatic 14-year old hemizygote in the family of a cardiac variant did not have elevated urinary GL-3. Therefore, screening for the classic type and probably renal variant of Fabry disease is possible by measuring urinary GL-3, using our method. The early diagnosis of cardiac variant hemizygotes and some heterozygotes with all types of Fabry disease will not be possible using our method. We propose that this procedure can be used as a reliable, non-invasive, simple method for general and high-risk population screening for hemizygotic patients with the classic type and probably renal variant of Fabry disease.
    Molecular Genetics and Metabolism 08/2005; 85(3):196-202. · 2.83 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate the effect of metformin in addition to insulin therapy in adolescents and young adults with type 1 diabetes mellitus. Nine patients, two males and seven females, aged 18.1 +/- 3.0 years, with type 1 diabetes mellitus were studied. They were relatively overweight with a body mass index (BMI) of 24.2 +/- 1.8 and had high levels of HbA1c at 9.5 +/- 1.2% despite high doses of insulin of 74.0 +/- 31.2 U/day. Metformin at the dose of 500-750 mg daily was administered to the patients in addition to insulin therapy for 1 year. HbA1c, BMI and insulin dose were compared before 1 year without metformin therapy, at baseline, and at 3, 6 and 12 months during the use of metformin in addition to insulin therapy. HbA1c lowered (8.6 +/- 1.4**, 8.4 +/- 1.3**, 8.4 +/- 1.2*%), BMI was reduced (23.9 +/- 1.7*, 23.8 +/- 1.8, 23.5 +/- 1.8*), and insulin requirement decreased (69.8 +/- 29.7*, 68.7 +/- 29.8**, 67.3 +/- 29.1**U/d) significantly after the start of metformin therapy (*P < 0.05, **P < 0.01 vs at baseline). There were no adverse events, not even lactic acidosis, during the study period. Metformin is safe and may represent a useful adjunct to the management of type 1 diabetes mellitus in adolescents and young adults who have poor glycemic control despite a large amount of insulin.
    Pediatrics International 08/2005; 47(4):430-3. · 0.88 Impact Factor
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    ABSTRACT: The aim of the study was to examine the optimal use of quick-acting insulin analogue (Q) switching from regular insulin (R) in combination with basal insulin and its long-term effects in 40 Japanese children and adolescents with type 1 diabetes. Insulin regimens after administration of Q were increased to twice daily injections of basal insulin and modified use of Q or R as bolus insulin depending on the blood glucose profile and lifestyles. The mean dose of total insulin remained unchanged during treatment with using Q, but that of basal insulin increased 12 months after the use of Q (baseline: 25.8 +/- 12.2, after 12 months: 27.1 +/- 12.6 U/day). After switching to Q, the mean HbA1c value decreased in all patients (baseline: 7.6 +/- 1.0, after 12 months: 7.3 +/- 0.8%), which reflected improvement of HbA1c in patients with HbA1c > or = 8% at baseline. These results indicated that insulin regimens after switching from R to Q varied with increases of the number and the dosage of basal insulin. Use of Q seems to be useful to improve hyperglycemia in patients with a poor glucose profile under conventional insulin treatment with using R. The choice of insulin regimens with using Q in consideration of the blood glucose profile as well as lifestyles may lead to better glycemic control.
    Diabetes Research and Clinical Practice 06/2005; 68(2):96-103. · 2.74 Impact Factor
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    ABSTRACT: Fabry Disease (alpha-galactosidase A deficiency) is an X-linked hereditary disorder leading to the pathological accumulation of globotriaosylceramide (GL-3) in lysosomes, particularly in the vascular endothelium of the kidney, heart and brain. We report the results of an open-label phase 2 study that was undertaken to evaluate whether ethnic differences exist that would affect agalsidase beta (Fabrazyme) treatment of Fabry patients in the Japanese population, relative to safety and efficacy. The study design mirrored the design of the completed phase 3 clinical trial that led to approval of the product agalsidase beta. The 13 Japanese, male Fabry patients enrolled in the study received the enzyme replacement therapy over a period of 20 weeks as biweekly infusions. All selected efficacy end points showed improvements that were comparable with findings from the phase 3 study. These improvements included reductions of GL-3 accumulation in both kidney and skin capillary endothelial cells to (near) normal levels (92% of patients). Kidney and plasma GL-3 levels decreased by 51.9% and 100%, respectively, by ELISA. Renal function remained normal. Fabry-associated pain, and quality of life, showed improvement over baseline in multiple categories. Related adverse events were mild or moderate in intensity and mostly infusion-associated (fever and rigors). As expected, IgG antibody formation was observed in 85% of the patients, but had no effect on treatment response. These results suggest that treatment with agalsidase beta is safe and effective in Japanese patients with Fabry disease. With regard to safety and efficacy, no differences were observed as compared to the caucasian population.
    Journal of Inherited Metabolic Disease 02/2005; 28(4):575-83. · 4.07 Impact Factor
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    Diabetes Care 01/2003; 25(12):2353-4. · 7.74 Impact Factor
  • Pediatrics International 07/2002; 44(3):333-4. · 0.88 Impact Factor
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    ABSTRACT: We conducted a mass-screening method to detect presymptomatic Wilson's disease in children by measuring urinary holoceruloplasmin. Two cases of Wilson's disease were found by testing urine samples from 48,819 children. The diagnosis was confirmed by clinical laboratory tests and the detection of a mutated ATP 7B gene.
    Journal of Pediatrics 06/2002; 140(5):614-6. · 4.04 Impact Factor
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    ABSTRACT: To clarify the characteristics of idiopathic type 1 (type 1B) diabetes mellitus (DM), we compared the clinical features of immune-mediated type 1 (type 1A) DM and type 1B DM in 85 Japanese children and adolescents with DM. The prevalence of type 1B DM was 16.5%. The patients with type 1B DM were significantly younger at diagnosis and had a higher frequency of preceding viral infection before onset, compared to those with type 1A DM. They displayed more severe metabolic decompensation with a higher frequency of ketoacidosis at diagnosis than patients with type 1A DM. They had strong, HLA-defined genetic susceptibility, similar to that in type 1A DM. Some patients with type 1B DM exhibited a remarkably abrupt onset and rapid loss of beta-cell capacity. From these findings, it is considered that type 1B DM differs from type 1A DM with respect to age at onset and the trigger event, such as viral infection, leading to rapid destruction of beta-cells without autoimmunity in the etiology of the disease.
    Journal of pediatric endocrinology & metabolism: JPEM 04/2002; 15(3):283-8. · 0.75 Impact Factor
  • Clinical Pediatric Endocrinology. 01/2002; 11(1):43-47.
  • M Owada, T Kitagawa
    Nippon rinsho. Japanese journal of clinical medicine 01/2002; 59 Suppl 8:317-27.
  • M Owada
    Ryōikibetsu shōkōgun shirīzu. 02/2001;
  • M Owada, K Aoki, T Kitagawa
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    ABSTRACT: Low-phenylalanine formula for phenylketonuria (PKU) made from free amino acids as a protein source (AAM formula) has a poor taste and smell. We developed a more palatable formula using low-phenylalanine peptide (LPP) as a protein source. Palatability tests performed by 41 healthy adults confirmed that the palatability of LPP formula was significantly better than that of AAM formula. A group of 48 patients with PKU who had been administered AAM formula since the newborn period were assessed for their preference between the AAM and LPP formulae and their feeding behaviour was compared to that in healthy children. Of patients, 90.9% and 66.6% of healthy infants less than 18 months of age took both formulae without apparent preference, suggesting that sensitivity to taste and smell is more immature in infancy than in later life. Of patients with PKU aged between 18 months and 11 years, 29.1% liked AAM formula rather than the LPP formula, while 66.7% took both formulae without apparent preference. Most healthy children in the same age group who had never previously tasted therapeutic formulae disliked it, although they tended to prefer the LPP formula. Of patients aged between 11 and 17 years, 84.6% preferred the LPP formula while 15.4% preferred the AAM formula. In the controls of this age group, 33% disliked therapeutic formulae, but they tended to prefer the LPP formula. CONCLUSION: In some young children with phenylketonuria the characteristic taste of amino acid mixture formula encountered in early life is considered to be imprinted and remains as a preference for a long time. Since school children with phenylketonuria usually obtain about 50% of their energy intake from natural food containing small amounts of protein, these patients are considered to have come to have similar preferences as healthy people which result from a waning of the imprinted taste of amino acid mixture formula.
    European Journal of Pediatrics 12/2000; 159(11):846-50. · 1.91 Impact Factor
  • M Owada
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    ABSTRACT: I-cell disease (ML II) and pseudo-Hurler poly-dystrophy (ML-III) are lysosomal storage diseases caused by abnormal lysosomal enzyme phosphorylation and localization. In both diseases, newly synthesized lysosomal enzymes are secreted into the extra-cellular medium instead of being targeted correctly to lysosomes. All cells and tissues of affected medium instead of being targeted correctly to lysosomes. All cells and tissues of affected patients are deficient in UDP-N-acetylglucosamine: lysosomal enzyme N-acetylglucosamine-1-phosphotransferase activity. However, we have demonstrated that liver cells from ML II patients have normal lysosomal enzyme contents. In Japan, ML II is a relatively common disorder whereas ML III is very rare as compared to Western Countries. The natural history of 21 cases with ML II, as well as 5 prenatally diagnosed cases of ML II, have been reported by our research group.
    Nippon rinsho. Japanese journal of clinical medicine 02/2000;
  • Clinical Pediatric Endocrinology. 01/2000; 9(2):69-74.

Publication Stats

654 Citations
167.88 Total Impact Points

Institutions

  • 2005–2008
    • Kagawa Nutrition University
      Saitama, Saitama, Japan
  • 1983–2008
    • Nihon University
      • Department of Pediatrics
      Tokyo, Tokyo-to, Japan
  • 1997
    • Yokohama City University
      • Department of Psychiatry
      Yokohama, Kanagawa, Japan
  • 1982
    • Nippon Bunri University
      Edo, Tōkyō, Japan
    • Hiroshima University
      • Department of Pediatrics
      Hiroshima-shi, Hiroshima-ken, Japan
    • Tokyo Metropolitan Institute of Medical Science
      Edo, Tōkyō, Japan