It is believed that the pathogenesis of diabetic peripheral neuropathy involves a variety of factors including vascular disturbance and metabolic disorder.In the present study, we investigated the therapeutic effect of prostaglandin E1 (PGE₁) on diabetic peripheral neuropathy, since PGE₁ is known to exert blood flow increasing and anti-platelet aggregatory activities as well as a potent peripheral vasodilator activity.Fifty-three patients were given PGE₁ once daily by intravenous drip infusion in a dose ranging from 20 to 80μg.The treatment lasted for a period of 4 weeks as a rule.An improvement rate of over 80% was obtained in the subjective symptoms of diabetic peripheral neuropathy including spontaneous pain in the legs, hypesthesia and numbness.The motor nerve conduction velocity of the ulnar nerve was significantly improved at 4 weeks after treatment. A significant improvement in vibration sense was also observed at both 2 weeks and 4 weeks after treatment.However, no appreciable effect on the Achilles tendon reflex and patellar reflex was observed.The overall improvement rating, which was assessed on the basis of improvement of the subjective symptoms and nerve function tests, indicated an efficacy rate of 55% or 29 out of 53 cases.An assessment of usefulness rating demonstrated that PGE₁ was useful in 33 cases or 62%. The fasting blood sugar and HbA₁ levels slightly declined during the study, but this did not affect the therapeutic effect of PGE1.The above results suggest that PGE₁ is a useful drug for improvement of the subjective and objective symptoms of diabetic peripheral neuropathy.

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In the recovery stage of 8 patients with diabetic ketoacidosis, the oxygen transport system of erythrocyte hemoglobin was studied by measuring the oxyhemoglobin dissociation curve (ODC), red cell2, 3-diphosphoglycerate (2, 3-DPG), hemoglobin A₁ (Hb A₁) and plasma inorganic phosphate (Pi) Administration of insulin was carried out by a continuous intravenous infusion method of low-dose, and ODC was determined with an AMINCO HEM-O-SCANTM analyzer. The following results were obtained.
1) The venous pH was definitely decreased on admission (7.07±0.03, mean±SE), but increased to the normal range within 24 hours after treatment in all patients.
2) The average of the P₅₀in vivo pH was increased before the insulin infusion (31.0±0.9 mmHg), but gradually decreased to within normal limits during24hours following the insulin infusion in7patients and after treatment for 3 days in the other patient.
3) 2, 3-DPG was low in concentration before the treatment (2.4±0.3μmol/ml RBC), and it took 24 hours to return to normal in 3 of 8 patients, 3 days in another 3 patients, and one week in one patient.The remaining patient always maintained a normal level throughout the entire course of recovery.
4) Pi which was normal or a little higher on admission showed a precipitous fall24 hours after the insulin therapy.It took 3 days to return normal in 5 patients an one week in 3 patients.
5) Throughout the course of recovery from diabetic ketoacidosis, there was a highly significant inverse correlation between the P₅₀in vivo pH and venous pH or Pi.Pi was correlated with pH significantly and P₅₀pH7.4 was closely correlated with 2, 3-DPG.
Accordingly, during the continuous intravenous infusion therapy with low-dose insulin for ketoacidotic diabetics, no striking fall in the P₅₀in vivo pH was noted, and it is suggested that no impairment of oxygen transport occurred because of the rapid recovery of 2, 3-DPG and probably of Pi in this study.

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The genetic marker for diabetes is useful not only for analysis of the molecular mechanism of its pathogenesis but also for detection of high risk subjects, analysis of the clinical course and estimation of prognosis.
The blood types ABO, MN, P, Lewis, Kidd, and Rh were examined as the genetic marker in patients with adult-onset NIDDM (32), adult-onset patients on insulin<20U/day (14), adult-onset patients on insulin≥20 U/day (26), and patients with juvenile-onset IDDM (76): total148 cases. The frequency of P (+) blood type in adult-onset patients on insulin and Lewis Le (a+) and Le (a-, b+) of juvenile IDDM patients was significantly lower than that of other types of diabetics and also of the nornal population in the Tokyo area.There was no difference in prevalence of any of the other blood types in these patients.
These results indicate that there is some association between blood type and certain types of diabetes.However, it still remains to be clarified whether this association is really the linkage of these two genes or not.

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In order to determine the effect of diabetes mellitus on the metabolism of calcium and bone, the plasma, urinary and bone mineral content, and the bone weight, length and cortical thickness of the Chinese hamsters in the Asahikawa colony were measured.The animals were divided into two groups: diabetic hamstcrs (malen=11, 9.9±0.8months, body weight39.4±1.1g, FBS430±24mg/dl, 7.4±0.6months sincc onsct of glycosuria) and non-diabctic hamstcrs (male, n=17, 10.0±0.2months, 44.7±0.9g, 67.5±5mg/dl).
The plasma calcium concentration in diabetic hamsters (9.86±0.21mg/dl) was lower than that in non-diabetic hamsters (10.25±0.21 mg/dl) but not significantly. The diabetic hamsters had hypoinsulinemia, hyperglycosuria and hypercalciuria. Urinary cyclic AMP and hydroxyproline in diabetic hamsters were significantly lower than in non-diabetic hamsters. The dry and ashed weights of the femur in diabetic hamsters (52.4±1.6, 27.6±0.9g, respectively) were significantly lower than in non-diabetic hamsters (64.2±1.8, 36.8±0.9g, respectively). The ashed per dry weight ratio and femur calcium and magnesium content per dry weight in diabetic hamsters were significantly lower than in non-diabetic hamsters, which might indicate that the bone weight loss was due mainly to mineral (calcium and magnesium) loss.
The femur in diabetic hamsters (19.2±0.1mm) was significantly shorter than that in nondiabetic hamsters (20.1±0.1mm), which means that there was disturbed bone growth in diabetic hamsters.Furthermore diabetic hamsters had cortical bone thinning.
The present data suggest that spontaneously diabetic Chinese hamsters have altered calcium and bone metabolism.Further studies will be required to elucidate the pathogenesis of this altered metabolism.

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In an attempt to determine if there is a relationship that influences the development of diabetic retinopathy, the sialic acid levels in both platelets and plasma, and the sialidase activity in platelets in 60 patients with diabetes mellitus and 7 normal subjects were measured. Simultaneously the plasma acute phase proteins (APRs) which generally contain sialic acid as a terminal component at the non-reducing end of carbohydrate chains of glycoproteins, were determined. Sialic acid was determined by our fully enzymatic method and sialidase activity with a highly sensitive fluorogenic substrate. Plasma APRs were determined by single radial immunodiffusion with commercially available kits.
In the 60 diabetic patients there was a significant increase in plasma sialic acid (SA) and α 2-macroglobulin (α 2-M) as compared with those in the normal subjects. In contrast, α 1-acid glycoprotein (α 1-AG), liaptoglobin (Hp), and transferrin (Tf) were decreased in the diabetic group. The plasma SA content varied according to the blood glucose level and the degree of retinopathy. In 12 selected diabetic patients who were under good control with dietary treatment and who had no retinopathy, only α 2-M and platelet SA levels were elevated significantly as compared with those of normal subjects. Other parameters including SA in the plasma remained at the same levels as in normal subjects. In nine selected diabetic patients under poor control and who had retinopathy (Scott I-IV), significant ipereases in plasma SA, α 2-M, a 1-antitrypsin (α 1-AT) and platelet SA were observed. a 1-AC; and platelet sialidase were decreased significantly. The average SA content of normal platelets was 12.8 mg/g of protein, whereas that of platelets of nine diabetics was 43.8. The average sialidase activity of normal platelets was 4.3 n mol/mg of protein/h, while in those severe diabetics it was 1. 6. Platelet SA was positively correlated with plasma SA (r=0.31) and α 2-M (r=0.46) and negatively with a 1-AG (r= 0.55). Platelet sialidase was correlated negatively with plasma SA (r= 0.39), α 2-M (r= 0.31) and α 1-AT (r=-0.59), and positively with α 1-AG (r 0.19).
From these observations, it was concluded that the determination of platelet SA might provide useful information on the potential for development of retinal complications in diabetic patients. The significant correlation between platelet SA and plasma APRs suggests that the plasma sialoglycoprotein (s) may enhance platelet activity in diabetic patients

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Based on long-term follow-up, the incidence of cardiovascular complications of diabetes, i. e. coronary heart disease (CHD) and cerebrovascular accident (CVA), and their risk factors were investigated. The subjects studied comprised 1, 850 diabetic patients who were traced until the end of 1981, with a mean observation period of 7.1 years
Among them, 68 patients had a previous history of heart disease, and 24 of cerebrovascular lisease, and were excluded from the study. In the patients with no previous evidence of CHD or CVA, the incidence rates of CHD (death due to heart disease or heart attack) were 7.4 ° for males and 4.3 ° for females, while those of CVA (death due to CVA or stroke) were 6.0 % and 4. 2 °for males and females, respectively. There was a distinct male preponderance as well as a; harp increase with aging in the incidence rates of both CHD and CVA.
The symptoms presented at entry to the study were also closely associated with the incidence of CHD and CVA. There was a higher incidence of CHD with chest pain, and shortness of breath by excercise; and a higher incidence of CVA with difficulty in walking or speech, and abnormality of the peripheral sensory nerves.
Multiple logistic analysis was undertaken to elucidate the relationship between the incidence and other risk factors. It was found that aging, male sex, ischemic changes in ECG and elevated serum cholesterol levels were risk factors for CHD, while aging, male sex, elevated systolic blood pressure and fasting glucose levels, and albnminuria were risk factors for CVA.

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Among 196 active and retired sumo-wrestlers examined by means of a 100 g glucose tolerance test (GTT) in 1968-1969, follow-up data on fasting blood glucose (FBG) were obtained in 40 cases. The types of GTT were divided into 4 categories according to the new criteria of the Japan Diabetic Society as follows: normal, FBG <140 and 2-hr blood glucose (BG)<130 mg/d1: borderline, FBG <140 and 2 hr BG 130-159 mg/dl; IGT, FBG <140 and 2-hr BG 160-239 mg/dl; and diabetic, FBG >140 and/or 2-hr BG >240 mg/dl. Seven were already diabetic at the initial survey. Sixteen subjects in the normal type (6/19), borderline type (4/8), and IGT (6/6) groups became newly diabetic. The ratio of increment of serum insulin (pU/m/) to that of glucose (mg/d/) 30 minutes after a 100-g glucose load (Δ IRI/Δ BG) was 0.86 ± 0.67 (Mean ± SD) in subjects who later developed diabetes, while it was 1.39± O.97 in those who did not (p<O.1). Eleven out of 17 subjects (65%) in the normal-IGT groups with an initial Δ IRI/Δ BG lower than I.0 became diabetic, and 5 out of 16 subjects (31%) of those with an initial Δ IRI/ΔBG higher than 1.0 (p<O.1) became diabetic. There was no difference between groups of subjects who became diabetic and those who did not become diabetic in the initial and post-follow-up ages, the status of activity (active or retired), and the initial and subsequent weight index.
In conclusion, diabetes occurred more frequently in those who had more impaired initial glucose tolerance and lower Δ IRI/Δ BG. However, a considerable number of subjects with Δ IRI/Δ BG higher than 1.0 at the initial GTT became diabetic. Acquired diabetogenic factors such as obesity, if they are strong, may induce diabetes even in subjects with normal insulin response.

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C-peptide immunoreactivity in 24 hour-urine specimens from diabetic patients was assayed, and insulin dependent and non-insulin dependent diabetes were compared.
The mean±SD of urinary C-peptide (UCPR pg/day) was 74.7±26.3 in healthy subjects, 72.7±28.1in diet-treated diabetics and 61.8±28.3 in sulfonylurea (SU)-treated patients.UCPR was almost always more than 30μg/day in diet-and SU-treated patients.In insulin-treated patients, the mean±SD of urinary CPR was 30.3±27.5, which was significantlyless than in the SU-treated group (p<0.01), but UCPR values were widely scattered from undetectable levels to the normal range.
Insulin-treated patients were subdivided according to the reasons for starting insulin treatment. In group A, the probable IDDM group, with a history of abrupt onset of diabetes or ketoacidosis, UCPR was definitely low (9.2±8.8), and the individual value was less than 20μg in almost all patients with duration of diabetes of more than one year.In group B, in which insulin treatment was started because of co-existing liver disease, severe diabeticcomplications or surgery, UCPR did not differ significantly from that in the SU-treated group.In group C, in which insulin was initiated because of onset of diabetes at a young age, severe emaciation orunresponsiveness to SU drugs, UCPR was intermediate between group A and group B.
In conclusion, urinary C-peptide seems to provide a good and convenient parameter for determining the degree of insulin dependency in diabetic patients.

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The presence and the volume of residual urine (RU) were determined by postvoid bladder ultrasonography in 116 diabetic patients and 56 normal controls with no evidence of organic urological disease.The possible relationship between abnormal RU and the clinical features of diabetes mellitus was also investigated.
A significant correlation was found between the bladder area from ultrasound pictures in the middle sagittal plane and the actual volume of RU obtained by catheterization (r=0.917, p<0.001). As compared to the controls, some imaging of RU was more frequently found in diabetics regardless of age, and 20 (17.2%) showed abnormal RU with a bladder area of over 10 cm².Most of the cases were poorly-controlled, long duration of diabetes and revealed some neurological abnormalities including autonomic neuropathy as judged from the coefficient ofvariation of the R-R interval in resting ECGs.Furthermore, asymptomatic and significant bacteriuria (>10⁵/ml) was observed in about half of the diabetics with abnormal RU.Of these cases, somepoorly-controlled diabetics showed a definite decrease in RU after improvement of diabetic control only for a few months.
These results confirm that ultrasonography represents a reliabletechnique for detecting RU and suggest that RU in diabetics may have some relationship with notonly neurological abnormalities, but also metabolic disturbance, and plays a role in the increasedprevalence of urinary tract infection.

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A case of hyperparathyroidism complicated by pancreatic stones and diabetes mellitus is reported.
At the age of 28, the patient began to have epigastralgia frequently and pancreatic stones were pointed out at a local hospital.At the age of 30, he was first admitted to our hospital because of repeated attacks of epigastralgia.The diagnosis was hyperparathyroidism, pancreatic stones and hypopituitarism.He underwent parathyroidectomy.Microscopic examination showed hyperplasia of the parathyroid.Therefore his disease was diagnosed as multiple endocrine adenomatosis (MEA) Type 1.Six months before his second admission, thirst and weightloss started and diabetes was diagnosed.
On the second admission, hemoglobin A₁ was 15.4%, postprandial blood glucose showed hyperglycemia, and the insulin level was low.He had no diabetic microangiopathy.Pancreatic exocrine function and plasma PTH level were normal.In a pituitary function test, GH was low but ACTH, prolactin, TSH, LH and FSH were within normal range.On an X-ray of the skull, the pituitary fossa showed slight enlargement and X-ray of the abdomen clearlyshowed numerous pancreatic stones.The hyperglycemia was controlled by diet and insulin therapy (Monotard insulin 6 units).

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