We previously demonstrated that hyperglycemia-induced embryopathy is mediated by myo-inositol depletion in the embryo during early organogenesis. The present experiment was performed to defermine whether myo-inositol depletion contributes to the pathogenesis of streptozotocin-induced diabetic embryopathy. Rats were made diabetic by streptozotocin injection prior to conception, and diabetic rats were treated with a diet supplemented with myo-inositol between gestational days 6 and 11. In each group, on gestational day 11.7th the incidence of malformations was recorded and the myo-inositol content of the embryos measured. The embryos of the diabetic rats had a lower myo-inositol content and an higher incidence of neural lesions. Restoration of embryo myo-inositol content by oral myo-inositol supplementation of the dams resulted in partial improvement in the incidence of neural lesions. These findings indicate that myo-inositol depletion of embryos during organogenesis may be one of the factors responsible for diabetic embryopathy.

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Mutations in the insulin receptor gene can lead to insulin resistance and cause diabetes mellitus in certain patients. We evaluated a 35-year-old diabetic man with Type-A insulin resistance and acanthosis nigricans. Insulin binding to the patient's erythrocytes, transformed lymphocytes, and fibroblasts was reduced. The dose-response curve for insulin-stimulated [¹⁴C]-glucose incorporation was shifted to the right, but the molecular weight of the α-subunit of the insulin receptor in this patient was normal according to the results of an affinity cross-linking study. Determination of the nucleotide sequence of the patient's insulin receptor genomic DNA by direct sequencing revealed a mis-sense mutation encoding the substitution of leucine for proline at position 193 in the cysteine-rich domain of the receptor. This mutation was homozygous in the patient and heterozygous in the patient's mother. These results suggest that the Pro¹⁹³→Leu¹⁹³ mutation causes markedly decreased insulin binding in patients with extreme insulin resistance.

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We investigated cardiac sympathetic nerve abnormalities in streptozocin-induced diabetic rats using ¹²⁵I-metaiodobenzylguanidine (MIBG). The radioactivity ratio of cardiac tissue to 1ml blood (H/B) was used as an index of cardiac MIBG uptake. 1) Cardiac ¹²⁵I-MIBG uptake (H/B) in 4-, 8-and 20-wk diabetic rats was 48% lower than that in control rats. Similar results were obtained even when the data were corrected forgwet tissue weight. 2) Although there was no improvement in H/B following 2-wk insulin treatment, the H/B ratio increased significantly, to 85% of control levels, following 4wk insulin treatment indicating the reveribility of impaired MIBG uptake in diabetic rats. 3) In vivo reserpine treatment resulted in a 50% reduction in the H/B value in control rats. However, the treatment did not sginificantly suppress uptake in diabetic rats. 4) Cardiac norepinephrine content in both 4-and 8-wk diabetic rats was significantly (p<0.05, P<0.01) higher than in the age matched controls. These results demonstrate that cardiac ventricular uptake of ¹²⁵I-MIBG in diabetic rats is significantly impaired due to cardiac sympathetic nerve abnormalities. These abnormalities are reversible, however, dependent on the diabetic state.

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A 24-year-old male was admitted in June 1990 for treatment of fever. On admission, he did not have clinical signs of pancreatitis but elevated levels of serum amylase (568IU/l), urine amylase (5550 IU/l), elastase 1 (4800 ng/dl) and lipase (636 IU/l) indicated pancreatitis and approriate treatment was initiated. Serum glucose level was low, 65 and 56 mg/dl on days 2 and 3, respectively. On day 4, it increased suddenly, and insulin treatment was required. All pancreatic enzymes had returned to normal levels around 12 weeks after admission, and ICA/ICSA were negative at that time. The HLA type was DR4/9, the most common type in Japanese IDDM.
In this case, IDDM developed after elevation of serum amylasemia and decrease in plasma glucose, indicating the possibility of simultaneous destruction of both endocrine and exocrine pancreatic functions in this case.
Elevation of serum amylase is often seen in the initial phase of IDDM and has been considered to be closely connected with the causative mechanism of IDDM.
This patient was a rare and informative case in whom the entire course of development of IDDM from its earliest stage could be observed during hospitalization.

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A 42-year-old man with uncontrolled NIDDM of 10years duration was admitted to our hospital. His presenting complaints were fatiguability and micturitional disturbance. Biochemical examination revealed elevated levels of fasting plasma glucose and HbA_1c. Fundoscopy showed Scott IIIa retinopathy. Findings of decreased deep tendon reflexes, reduced nerve conduction velocity and a small R-R coefficient of variation intervals on ECG indicated progression of both peripheral and autonomic neuropathy. In the urodynamic study, although the volume of residual urine was 25ml, cystometry showed a hypotonic hypoactive bladder. Uroflowmetry revealed a low flow rate of urine. Thus, diabetic neurogenic bladder was thought to be the cause of his micturitional disturbance. An α₁-adrenergic blocking agent, bunazocin hydrochloride, was administered at a daily dose of 3mg. During the α₁-adrenergic blocker treatment, his micturitional disturbance disappeared completely. Furthermore, uroflowmetry showed a marked improvement in the urinary flow rate. In conclusion, α₁-adrenergic blocker was demonstrated to be a useful agent for treatment of diabetic neurogenic bladder.

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[Purpose] The following experiment was conducted to examine the usefulness of percutaneous dialysis.
[Method] Four normal individuals and two diabetic patients were selected and placed in a bathtub filled with 200 l of hypertonic dialysis fluid which is similar to peritoneal dialysis fluid and consists of the following substances: C₆H₁₂O₆·H₂O, 2.5%: NaCl, 0.538%; C₃H₅Na 0.448%: CaCl₂·2H₂O 0.025%; MgCl₂·6H₂O, 0.00508%. Before bathing and 30, 60, and 120 minutes later, the following parameters were examined: weight reduction, VitB₁₂, Creatinine and Urea clearances, amount of protein transudation, blood pressure, pulse rate and electrocardiographic changes. Then, one normal subject and one diabetic patient were selected, and placed in the same bathtub for one hour a day for fourteen consecutive days.
[Result] Weight reductions and clearances examined are listed below:
As a result of bathing for one hour every day for a week, clearances of various substances were 15-90% of those obtained with peritoneal dialysis or hemodialysis.
[Conclusion] Percutaneous dialysis may be a feasible option in the early treatment of patients with renal failure due to diabetic nephropathy.

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1) The Epidemiology Data Committee started in 1988 to compile information from the literature regarding the prevalence and incidence of diabetes among Japanese people.Information was collected from on-line searches of the Japanese Medical Literature and by various other methods. Main sources of data included original articles in medical journals, proceedings from meetings, andofficial publications from the Ministry of Health and Welfare. Each article was evaluated by two members of the Committee. Approximately 60 articles were finally adoped and the principal data are summarized in 13 tables.
2) Community-based studies on adult diabetes gave only prevalnce data. In early studies, people were first screened by urine glucose tests at arbitrary times of 1-2 hours after a meal or glucose loading. Subjects who were positive for glucosuria were further evaluated by glucose tolerance tests (GTTs). Recent studies used 75g GTTs without prior urine screening. but 50g GTTs were more popular in earlier studies. Before 1984, most reports used the criteria advocated by the Japan Diabetes Society (1970), in which the blood glucose levels defining diabetic type were lower than in the present WHO criteria (1980). After 1985 WHO criteria were used widely, Before 1984, the prevalence of diabetes in subjects aged 40 years of older was 1.3-4.7% by urine glucose screening followed byGTTs. After 1985, the prevalence of diabetes in subjects older than 40 years was 2.1-5.4% when first screened by urine glucose tests, and 4-11%when all participants were tested using GTTs. The prevalence was as high as 10% in several studies carried out in 1988-1990, despite that WHO criteria being more stringent in defining diabetes than those from the Japan Diabetes Societ (1970). The prevalence of diabetes was higher in men than in women. The men: women ratio ranged 2: 1 to1: 1.
3) The incidence of diabetes in people younger than 18 years was 0.8-2.3 per 100, 000 per year. The peak incidence was observed among 10-14 year-old age group.There was no clear increasing temporal trend in IDDM incidence, nor were there any significant differences between northern and southern parts of Japan.The prevalence of IDDM in young people (<18years) was0.5-1.5 per 10, 000 when both types of diabetes were included.
4) Approximately 100, 000 atomic bomb survivors have been prospectively followed up for health evaluations since 1960's. As the exposure to the atomic bomb did not affect the development of diabetes, the data are regarded as equivalent to the community-based survey. These people are now older than 43 years. and the prevalence of diabetes was recently estimated to be 9.9%in men and 8.0%in women. There was an increase in prevalence of diabetes during the follow-up period.
5) Diabetes is more prevalent in the first and second generations of Japanese immigrants into Hawaii, Los Angelos and Seattle, in the USA. Recent studies in Seattle revealed that the prevalence of diabetes in the second generation immigrants older than 45 years of age was 21.5%in men and 16.1% in women.
6) Some publications from the Ministry of Health and Welfare in the government of Japan included the data on diabetes. These data were based on information on the known diabetic patients who were visiting medical clinics or hospitals. Naturally, the estimated prevalence was much lower than that obtained by the community surveys. However, this is a good source of information regarding long-term trends in the number of diabetic patients, because the data were collected nationwide using the same methods since 1950's or 1960's. The estimated prevalence of diabetes was 1.7% from the 1987 Patient Survey, and 1.1%from the 1989 Comprehensive Survey of Living Conditions of the People on Health and Welfare.This represented a 30-fold increase in the number of diabetic patients compared to early surveys. However, this increasing trend may be overestimated.

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