Familial predisposition of type 1 diabetes mellitus in Japan, a country with low incidence. Japan Diabetes Society Data Committee for Childhood Diabetes.

The study group of the Japan Diabetes Society (JDS) carried out nationwide hospital-based and population-based surveys of childhood type 1 diabetes mellitus (DM) in Japan. According to the nationwide population-based survey, the incidence of childhood type 1 DM in Japan was 1.5 (1.4-1.6)/10(5), which did not differ for the 5 years from 1986-1990. Predisposition for DM and autoimmunity were studied in the first-degree relatives of the patients, including older and later cohorts. The prevalence of type 1 DM was 3.3% (12/369) among siblings and 2.2% (8/369) among parents, while the prevalence of type 2 DM was 0% among siblings and 4.3% (16/369) among parents. The risk of type 1 DM among siblings of the patients was 330 times higher than that among the general population in the Japanese population. The rate of positivity for autoantibodies, including ICA, IAA, GAD and IA-2, was 1.4-2.9% in parents (n=140) and 2.0-3.9% in siblings (n=203). The genetic susceptibility for type 1 DM is far lower in Japanese children than in Caucasian children, but predisposition to the disease and positive autoimmunity are almost the same in Japanese families of patients as in Caucasian families. The quality of life of Japanese parents of children with type 1 DM was less satisfactory that that of the Caucasian parents previously reported, which might be a result of the low incidence of type 1 DM in Japan.

Incidence of Type 1 diabetes mellitus in children aged 0-14 in Japan, 1986-1990, including an analysis for seasonality of onset and month of birth: JDS study. The Data Committee for Childhood Diabetes of the Japan Diabetes Society (JDS).

AIMS: To detect the incidence of childhood Type 1 diabetes mellitus (DM) (0-14 years) in Japan and to find out whether there is a seasonal pattern in the onset of disease and month of birth of children with diabetes. METHODS: Ascertained data for the period 1986-1990 could be collected in 35 out of 47 local government areas representing 69.4% of the childhood population (aged 0-14 years) of Japan. RESULTS: A total of 1,260 children with Type 1 DM were identified (738 girls, 522 boys). With age there was a progressive increase in incidence from 0.7 to 2.1/10(5) in boys and from 0.6 to 3.5/10(5) in girls. With the exception of 1987, when a coxsackie B3 virus epidemic was registered, no seasonal variation in the month of onset was observed, nor was a seasonal pattern of the month of birth registered in this cohort. CONCLUSIONS: Compared to European countries, the USA and Israel, the Japanese cohort of children with diabetes presents the following differences: the incidence is much lower, there is a preponderance of girls and there is (with one exception) no seasonal pattern.

Fish intake and cardiovascular risk among middle-aged Japanese in Japan and Brazil.

BACKGROUND: Studies of immigrant populations are useful for analysis of the effects of environmental factors on cardiovascular disease. We have examined the association between dietary habit of fish intake and cardiovascular risk. METHODS: Population-based samples of 433 middle-aged Japanese men and women in Japan (Shimane (group JS) and Okinawa (group JO)) and 269 Japanese immigrants in Brazil (Sâo Paulo (group BS) and Campo Grande (group BC)), who had originally moved to Brazil mainly from Shimane and Okinawa, were recruited to the study. They underwent blood pressure measurement, 24-h urine collection, blood tests and electrocardiographic examination, and completed a dietary questionnaire. RESULTS: There was a significant gradient through the groups, from JS to JO, BS and BC with respect to the prevalence of obesity, hypertension, increased glycohaemoglobin concentrations and ST-T segment change on the electrocardiogram (prevalences for men and women combined: group JS 2.0%, group JO 3.8%, group BS 3.9% and group BC 9.0%; P < 0.025). The prevalence of hypercholesterolaemia was noted more frequently in groups BS and BC. Twenty-four-hour urinary taurine excretion in both sexes and n-3 polyunsaturated fatty acids (n-3 PUFA) in plasma phospholipids in men were significantly higher in groups JS and JO than in groups BS and BC. A striking negative gradient in the frequency of fish intake per week was found from group JS (men/women, 4.7/4.8) to groups JO (3.8/3.6), BS (1.9/1.6) and BC (0.5/0.5). CONCLUSIONS: This study suggests a possible association between fish intake and reduced cardiovascular risk, through the beneficial effects of taurine and n-3 PUFA and a habitual low intake of calories and fat.

Effect of troglitazone, a new oral antidiabetic agent, on fructose-induced insulin resistance.

Troglitazone, a newly developed oral antidiabetic agent, improves hyperglycemia, and has been reported to improve insulin resistance and to decrease hepatic glucose production in diabetic animals. However, the exact mechanism of Troglitazone on the improvement of insulin resistance is not known. Chronic administration of fructose to normal rats leads to hyperglycemia, and hyperinsulinemia; it induces insulin resistance. To reveal the mechanism of Troglitazone, we studied the effect of Troglitazone on serum glucose and insulin in the fructose-induced, insulin-resistant rats. Male Sprague-Dawley (SD) rats were fed either on standard chow or one containing fructose. Troglitazone was administrated as a food admixture (150 mg/kg/day) for 8 weeks. The rats were fed on (1) standard chow, (2) standard chow and Troglitazone, (3) fructose-enriched chow, or (4) fructose-enriched chow and Troglitazone. Blood samples were obtained every two weeks, and the levels of serum glucose and insulin were measured. Fructose-enriched chow increased serum glucose and insulin levels and insulin-to-glucose ratios. Troglitazone improved the fructose-induced increases in serum glucose, insulin levels, and insulin/glucose ratios. In conclusion, Troglitazone improved the fructose-induced insulin resistance.

Summer camp.

The first summer camp in Japan was held at a site near Tokyo in 1963. The guide book was edited by Japan Diabetes Society in 1984. In 1992, 1012 children with diabetes participated at 36 sites all across Japan. The programme is characterized by the smooth combination between education for the children and their experience of recreation. The term of the camp, staff member issues, camp operating fund are discussed. A pan-pacific international diabetes summer camp was successfully held at the Ehime prefecture site in 1989 with 56 patients from eight countries. The summer camp is evaluated for the achievement of good psycho-physical growth of the participating children and the maintenance of good control of diabetes. The problems include the term length of the camp, finding a camp site and the national and local governmental subsidy. Finally, a more effective operation with a minimum number of educators should be another concern in the future.

A multicenter study on HLA and autoimmunity in Japanese patients with early-onset insulin-dependent diabetes mellitus (IDDM): the JDS Study.

The Japan Diabetes Society (JDS) conducted a multicenter study on HLA and autoimmunity in Japanese patients with early-onset insulin-dependent diabetes mellitus (IDDM). HLA, immunoglobulin heavy-chain complex (Gm), properdin factor B (BF), and glyoxalase of erythrocytes (GLO) were typed, and organ-specific autoantibodies including islet cell antibodies (ICA) were assayed in 159 IDDM patients and their relatives and in 258 healthy Japanese subjects. The HLA-DRw9 phenotype and HLA-Bw61/DRw9 haplotype were significantly increased among the patients with autoantibodies other than ICA, whereas the DR4 phenotype and Bw54/DR4 haplotype were significantly increased in those without the autoantibodies. The DR4 phenotype was significantly increased in the patients with autoimmune thyroid diseases. The relative risk of the HLA-DRw9/DR4 genotype was highest among all DR genotypes. The Gm phenotype of g and gft were significantly increased in the patients with the autoantibodies. The BF-F phenotype was significantly decreased in the patients either with or without the autoantibodies. There was no association of GLO types with IDDM. The prevalence of ICA among IDDM patients was decreased with duration of IDDM. No significant association was found between the prevalence of ICA and sex, age at onset, or HLA type. On the other hand, the prevalence of the autoantibodies was not significantly changed with duration of the disease, and was significantly higher in females than in males.

Chronic gliclazide treatment affects basal and post-ischemic cardiac function in diabetic rats.

1. A 6-week gliclazide treatment improved left ventricular developed pressure and left ventricular end-diastolic pressure, left ventricular pressure-rate products in isolated working hearts from streptozotocin-induced diabetic rats. 2. Post-ischemic recovery in heart rate, left ventricular developed pressure, left ventricular end-diastolic pressure, left ventricular pressure-rate products and cardiac work were also shown in gliclazide-treated diabetic rats. 3. Gliclazide treatment did not modify the degree of insulinopenia and hyperglycemia, nor the myocardial energy metabolism during ischemia-reperfusion. 4. The results suggest that the gliclazide treatment has a cardioprotective effect on basal and post-ischemic cardiac functions of chronic diabetes.

ICA and organ-specific autoantibodies among Japanese patients with early-onset insulin-dependent diabetes mellitus--the JDS study.

The Japan Diabetes Society (JDS) conducted a multicenter study on the immunogenetics of insulin-dependent diabetes mellitus (IDDM) among Japanese. The previous report of the JDS study described HLA types and other immunogenetic markers in Japanese patients with IDDM. In the present report, the autoimmunity of Japanese patients was studied by measuring ICA and other organ-specific autoantibodies in patients with different durations of IDDM. The prevalences of ICA were the highest in the first year after diagnosis (73.1%) and decreased to 58.0%, 18.3% and 2.8% in 1-5 years, 5-10 years and 10 years or more after diagnosis, respectively (P < 0.01), while the prevalences of the other organ specific autoantibodies increased gradually with duration of IDDM from 20% in the first year to 35% in 10 years or more after diagnosis (P < 0.05). There were no sex differences in the prevalences of ICA but those of other organ-specific autoantibodies were significantly higher in female patients than in male patients (P < 0.01). The prevalence of ICA was not correlated with sex, age at onset or HLA types. In one of the subjects, a girl, the titers of ICA increased in parallel with a decrease in insulin secretion before the development of overt IDDM and declined thereafter. These findings suggest that IDDM might develop when the autoimmunity specific to pancreatic islets is triggered in people with underlying autoimmunity as shown by the presence of organ-specific autoantibodies other than ICA.

Effect of FK506 on the development of diabetes in BB rats in comparison with that of cyclosporin.

FK506, a agent extracted from a streptomyces, has more potent immunosuppressive properties compared with cyclosporin in vitro. We compared the preventive effect of FK506 on the development of diabetes mellitus with that of cyclosporin in BB rats, which are regarded as a useful model of insulin-dependent diabetes mellitus. BB rats aged 30 days were treated intramuscularly with FK506 (0.1 mg/kg/day and 0.32 mg/kg/day) or with cyclosporin (10 mg/kg, alternate days) until 150 days of age. Diabetes developed in 2 (10.5%) of 19 rats treated with the lower dose of FK506 and none of 20 rats with the higher dose of FK506; on the other hand, 1 (5.3%) of 19 rats treated with cyclosporin developed diabetes. In contrast, 9 (36.0%) of 25 control rats became diabetic. The cumulative incidence of diabetes mellitus in the group treated with FK506 (0.32 mg/kg) showed a decrease similar to or more than that of the cyclosporin-treated group. Histological examination showed that FK506 and cyclosporin prevented the reduction in the average size of islets and in the area of beta cells. The analysis of lymphocyte subsets proved the decrease of W3/25: OX8 ratio in both FK506- and cyclosporin-treated groups. These data suggest that the administration of FK506 might be a more useful tool for preventing the development of insulin-dependent diabetes mellitus.

Diurnal variation and increase of disaccharidase activity in diabetic rats.

The small intestinal disaccharidase activity and its daily variation in the diabetic rat have not been well described. Therefore, the small intestinal disaccharidase (maltase, lactase and sucrase) activity and its daily profile were studied in streptozotocin-induced diabetic rats under physiological conditions. In diabetic rats, a similar pattern of diurnal variation of disaccharidase activity to control rats was observed, while the relationships between daily change of disaccharidase activity and that of food consumption suggested that there was a different mechanism of diurnal variation in diabetic rats. On the other hand, a significant increase of mean 24-h lactase and sucrase activities was noted in diabetic rats, while that of maltase was not significant. Using the in vitro incubation method, a significant correlation between glucose concentration and lactase or sucrase activity but not maltase activity was observed. However, insulin showed no effect on disaccharidase activity. Thus we clarified the presence of a diurnal variation of disaccharidase activity and an increase in its activity in diabetic rats. This change was suggested to be derived from high plasma glucose level.

Immune responses and serum levels of cytokines in adult T-cell leukemia patients and human T-cell leukemia virus type-I carriers.

To find predictive parameters for development and progression of adult T-cell leukemia (ATL) in human T-cell leukemia virus type-I (HTLV-I) carriers, we investigated cellular immune responses such as mitogenic responses and natural killer activity of the peripheral blood mononuclear cells (PBMC). And serum or plasma levels of cytokines, including tumor-necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and immunosuppressive acidic protein (IAP), were also measured in patients with ATL, healthy HTLV-I carriers and healthy HTLV-I non-carriers as controls. Results are as follows: (1) increased spontaneous proliferation and decreased mitogenic responses of PBMC already existed in HTLV-I carriers; (2) IAP was significantly higher in patients with acute/lymphoma type ATL than in those with chronic/smoldering type, HTLV-I carriers and HTLV-I non-carriers. These results suggest that spontaneous proliferation or mitogenic responses and IAP may be useful parameters for the development and progression of ATL from the carriers. Since HTLV-I carriers already have various grades of immunosuppression, we should seriously try to prevent further HTLV-I transmission.

Nutritional factors for longevity in Okinawa--present and future.

Several factors, such as environment and heredity, are presumed to be related to longevity. Of these nutrition is believed to function as a regulatory factor. Okinawa prefecture is well known as the leading area for longevity in the world. We therefore examined present and past nutrition records together with the background of all the 88 centenarians (18 male, 70 female) who are living in Okinawa in 1991. Their leading occupation was agriculture, and they were in work until the 8th decade. They took rice or potato as carbohydrate with abundant vegetables and vegetable protein or fish protein. Although they did not take a rich diet it was well balanced, and was assumed to be related to longevity because of the decreased incidence of atherosclerosis; together with a good genetic background, suggested by the accumulation of longevity in their siblings.

[An elderly case of idiopathic retroperitoneal fibrosis].

An elderly case of idiopathic retroperitoneal fibrosis (IRPF) with bilateral ureteral obstruction was reported. A 74-year-old man was admitted with complaints of general fatigue and loss of appetite. An elastic hard mass with a smooth surface was palpated in the left upper quadrant of the abdomen. Abnormal ESR and CRP were noticed. Abdominal ultrasonography showed both a homoechoic mass which surrounded the aorta in the retroperitoneal space and bilateral hydronephrosis. Computed tomography revealed a retroperitoneal mass involving bilateral ureters. Magnetic resonance imaging demonstrated a mass with a sharp image and signal intensity. Furthermore the morphological relationship between the mass and the ureters and major vessels clearly indicated the characteristics of benign retroperitoneal fibrosis. Based upon the above findings, a diagnosis of IRPF was made. After confirming the histological diagnosis by biopsy, treatment consisting of bilateral ureterolysis, intra-abdominal transposition of ureters and oral administration of prednisolone was performed, resulting in a normalization of laboratory findings. Analysis of 86 previously cases of IRPF reported up to 1990 in Japan, revealed the peak age to be in the 7th decade with predominance in males (males: females = 57:29).

Comparison of the acute hemodynamic and coronary vasodilating effects between nicorandil and glyceryl trinitrate.

Acute hemodynamic and coronary vasodilating effects of nicorandol (SG-75, Sigmat; CAS 65141-46-0) and glyceryl trinitrate (GTN, nitroglycerin) were examined in 20 subjects under cardiac catheterization and coronary arteriography. Nicorandil 4 mg i.v. produced significant increases in heart rate, cardiac index and stroke volume index and significant decreases in systolic, diastolic and mean blood pressure, pulmonary capillary wedge pressure, left ventricular enddiastolic pressure, systemic vascular resistance and total pulmonary resistance. Degree of percent changes in these parameters by nicorandil were similar to that by GTN 0.3 mg i.v. Coronary vasodilating effects of both drugs were also at the same degree. Results indicate that nicorandil has cardiovascular and coronary vasodilating effects similar to those of GTN when administered intravenously.

Chronic effects of tolbutamide on myocardial tension during ischemia and reperfusion in perfused hearts isolated from insulin dependent and non insulin dependent diabetic rats.

The chronic effects of tolbutamide on myocardial contractility of the diabetic heart during ischemia and reperfusion were evaluated in perfused, isolated rat hearts. Five experimental groups were used: (1) control rats (C), (2) insulin dependent diabetic rats (IDDM, single intravenous injection of 60 mg/kg streptozotocin (STZ) in male Sprague-Dawley rats), (3) non insulin dependent diabetic rats (NIDDM; single subcutaneous injection of 90 mg/kg STZ in 5 day neonates), (4) tolbutamide-treated IDDM and (5) NIDDM (T-IDDM, T-NIDDM; giving tolbutamide 100 mg/kg/day for 6 weeks via an orogastric tube every day, respectively). At 14 weeks of age, experiments were performed using a Langendorff perfused heart preparation. After equilibration, T (myocardial developed tension), +dT/dt (contraction velocity), -dT/dt (relaxation velocity) and RT (resting tension) were measured during a 15 min period of global ischemia, followed by reperfusion for 20 min. Basal values of T increased in both T-IDDM and T-NIDDM, compared to IDDM and NIDDM, respectively. The percent recovery rate of +dT/dt in T-IDDM increased significantly during both ischemia and reperfusion, but the change in T-NIDDM was not significant. The recovery rates of -dT/dt in T-IDDM and T-NIDDM were significantly higher throughout reperfusion than in IDDM and NIDDM, respectively. On the other hand, that of T in T-IDDM and T-NIDDM were significantly higher than IDDM and NIDDM throughout ischemia and reperfusion, respectively. The RT was significantly higher in IDDM than in C and NIDDM throughout ischemia and reperfusion. The RT was significantly lower during ischemia in IDDM, but it did not differ significantly from IDDM during reperfusion. These results indicate that chronic oral administration of tolbutamide directly improved myocardial contractility throughout ischemia and reperfusion regardless of the improvement of glycemia. The improvement was also greater in IDDM than in NIDDM.