Misao Owada

Increased Incidence of Non-Insulin Dependent Diabetes Mellitus Among Japanese Schoolchildren Correlates with an Increased Intake of Animal Protein and Fat

Non-insulin dependent diabetes (NIDDM) was diagnosed in 188 of more than 7 million Tokyo schoolchildren tested between 1974 and 1994 for glycosuria followed by oral glucose tolerance testing. The incidence rate of NIDDM in youth has continued to increase since 1976. While the daily energy intake has not changed significantly, the consumption of animal protein and fat by the Japanese population has greatly increased during the past two decades, and this change in diet, with low levels of physical activity, may exacerbate insulin resistance and glucose intolerance. Clin Pediatr. 1998;37:111-116

Is there a mechanism for introducing acid hydrolases into liver lysosomes that is independent of mannose 6-phosphate recognition? Evidence from I-cell disease.

Abstract We have examined frozen liver tissue for N-acetylglucosamine-l-phosphotransferase, an enzyme required for the formation of the mannose 6-phosphate recognition marker of lysosomal enzymes. Using [β32P]-UDPGlcNAc and placental β-hexosaminidase B as N-acetylglucosamine l-phosphate donor and acceptor, respectively, we were unable to find activity of the transferase in 100,000 × g membranes prepared from livers of patients with I-cell disease, whereas activity was readily observed in membranes from control livers stored under the same conditions. Yet the activity of several lysosomal enzymes (β-N-acetylglucosaminidase, β-glucuronidase, α-mannosidase and α- L -iduronidase) was comparable in liver tissue of I-cell patients and controls, and only β-galactosidase activity showed a marked reduction. These results suggest that in contrast to cultured skin fibroblasts, liver may be able to introduce into lysosomes acid hydrolases that lack the mannose 6-phosphate recognition marker.

Epidemiology of type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus in Japanese children

The overall annual IDDM incidence rates by area in Japan for 1985-1989 for children 0-14 years of age at diagnosis were from 1.65 to 2.07 per 100,000. The incidence in males and females did not show any temporal trends during the period between 1980 and 1989. The prevalence of IDDM was about 1 per 10,000. The clinical features at diagnosis among Japanese IDDM children identified during the 2-year period between 1979 and 1980 were as follows. Fourteen percent of the cases were in coma and 12% of the cases were asymptomatic at diagnosis. There is a suggestion that slow onset IDDM is often seen in Japan. In these children, the decline of serum CPR levels and the prevalence of ICA (islet cell antibodies) over the course of diabetes was slower than in those with an abrupt onset classical IDDM. During the period from 1975 through 1990 the incidence rates of NIDDM in school children showed as much as an approximate 1.5-fold increase along with a similar increase in the prevalence of obesity. About eighty percent of these NIDDM children were obese. A predominance of female children developing diabetes was seen in both type of diabetes, IDDM and NIDDM, in Japan. Non-obese type NIDDM in children was more common in females than in males. It is interesting to note that the mean height of Japanese children with IDDM was not different from the national average, but children with NIDDM were significantly taller than the national average.

Urine Glucose Screening Program at Schools in Japan to Detect Children with Diabetes and Its Outcome-Incidence and Clinical Characteristics of Childhood Type 2 Diabetes in Japan

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.

I-cell disease: clinical studies of 21 Japanese cases

Clinical pictures of 21 cases with I‐cell disease patients, 12 males and 9 females, were analyzed. Characteristic coarse facial features and shortness of stature were observed in all cases. In general, the motor development was found to be more severely retarded than the mental development of the patients. Rather little involvement of the nervous system seemed to cause somewhat acceptable mental development in some cases, and also cause the absence of epileptic seizures in all cases. Involvement of the cardiovascular system, especially progressive hypertrophic cardiomyopathy, could be highly responsible for frequent sudden death of I‐cell disease patients.

Descriptive Epidemiology of Non-Insulin Dependent Diabetes Mellitus Detected by Urine Glucose Screening in School Children in Japan

During the period from 1974 through 1988, we annually examined approximately 225,000 to 386,400 school children residing in Tokyo for glycosuria to detect juvenile diabetes. If the first test was positive for glucose, glycosuria was confirmed by a second test. In children who gave a positive result in both the first and second tests 0‐GTT were performed. All 124 patients were diagnosed as NIDDM according to the criteria of the WHO Report on Diabetes of 1985. The incidence of NIDDM in children in Japan has increased in recent years and from 1984 to 1986 was approximately 3.8 per 100,000 per year. The frequency of NIDDM increases with age up to 14 years. In about 84% of cases, the body weight at diagnosis is more than 20% above the ideal weight and the height is often above average. There is a high frequency in families with a history of diabetes. Diet and exercise therapy in newly diagnosed patients irrespective of the presence or absence of obesity may result in remission, but some cases may require insulin therapy or oral administration of a hypogly cemic drug to obtain a better glycemic control. Children with NIDDM are more likely to be complicated by incipient retinopathy within two years after diagnosis than those with IDDM. Therefore, it is important to keep strict glycemic control to prevent diabetic complications in NIDDM children just as in juvenile onset IDDM.

Bone marrow transplantation for Niemann-Pick mice

The Niemann-Pick mice which received bone marrow transplants showed a decreased accumulation of sphingomyelin and cholesterol quantitatively in their spleen. The sphingomyelin deposit in the bone marrow was also reduced histochemically. However, the neurological manifestations were not improved by the bone marrow graft.

Serial Changes in the Prevalence of Islet Cell Antibodies and Islet Cell Antibody Titer in Children With IDDM of Abrupt or Slow Onset

OBJECTIVE To elucidate the significance of clinical and immunogenic heterogeneity in Japanese children with insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS Serial changes in the prevalence of islet cell antibodies (ICAs) and in ICA titer were monitored for 10 years after diagnosis in 34 IDDM children, 17 with abrupt onset and 17 with slow onset, whose durations of disease were > 5 years. RESULTS In slow-onset IDDM children, enough β-cell function was maintained in the early phase of the disease within 2 years after diagnosis. There was a high prevalence of ICAs in children with both forms of IDDM at the time of diagnosis (abrupt onset 94% slow onset 82%). However, the decline in the frequency of ICAs in slow-onset IDDM seemed less marked than in abrupt-onset IDDM after a duration of ≥ 1 year (47 vs. 82%, 1–3 years; 24 vs. 47%, 3–5 years; 24 vs. 47%, 5–7 years; 18 vs. 53%, 7–10 years, P < 0.05). In terms of changes in ICA titer, abrupt-onset IDDM children initially had high ICA levels of 160–320 Juvenile Diabetes Foundation units (JDF U), but these titers decreased rapidly after the 1st year. On the other hand, slow-onset IDDM children tended to continue to be ICA+ for a relatively long period with low titers of 20–40 JDF U. Among 12 children who remained ICA+ for > 5 years, slow onset was noted in 67% while abrupt onset was seen in only 33%. CONCLUSIONS From these results, we speculated that changes in ICA titer reflect the slow autoimmune destruction of pancreatic β-cells. It may be probable that immunogenic factors as well as environmental factors could affect the clinical features in the early phase of IDDM in children.

Usefulness of the addition of metformin to insulin in pediatric patients with type 1 diabetes mellitus

Background : 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.

Markers Associated with Inborn Errors of Metabolism of Branched-Chain Amino Acids and Their Relevance to Upper Levels of Intake in Healthy People: An Implication from Clinical and Molecular Investigations on Maple Syrup Urine Disease

Maple syrup urine disease (MSUD) is caused by a deficiency in the branched-chain alpha-ketoacid dehydrogenase complex. Accumulations of branched-chain amino acids (BCAAs) and branched-chain alpha-ketoacids (BCKAs) in patients with MSUD induce ketoacidosis, neurological disorders, and developmental disturbance. BCAAs and BCKAs influence on the nervous system can be estimated by analyzing these patients. According to clinical investigations on MSUD patients, leucine levels over 400 micromol/L apparently can cause any clinical problem derived from impaired function of the central nervous system. Damage to neuronal cells found in MSUD patients are presumably because of higher concentrations of both blood BCAAs or BCKAs, especially alpha-ketoisocapronic acids. These clinical data from MSUD patients provide a valuable basis on understanding leucine toxicity in the normal subject.