To make clear the pathogenesis of microangiopathy such as retinal microaneurysms and nephropathy found in carbon disulfide workers, that is, to elucidate whether or not these microvascular alterations due to carbon disulfide are closely related to those seen in diabetics, prednisolone glucose tolerance test and fluorescein fundus angiography were carried out in 113 carbon disulfide and 45 control workers.
Both one-and two-hour blood glucose levels during prednisolone GTT in carbon disulfide workers were significantly different from those in control workers (p<0.01, p<0.05, respectively) while the difference in fasting blood glucose between carbon disulfide and control workers was not significant. The blood glucose responces following prednisolone GTT increased with lengthening of duration of exposure to carbon disulfide.
Abnormal prednisolone GTT was found in 23% of the carbon disulfide workers and in 4.4% of controls. Retinal microaneurysms were found in 37.7% of the former, and in 15.4% of the latter. A clear trend toward higher incidence of microaneurysms with increasing duration of exposure to carbon disulfide was observed. In 23 cases out of 101 carbon disulfide workers with retinal microaneurysms abnormal prednisolone GTT was fuond (28.9%), and in controls with retinal microaneurysms no cases with abnormal prednisolone GTT was found.
The facts that carbon disulfide influences the blood glucose responces following prednisolone GTT, and carbohydrate metabolism in carbon disulfide workers with retinal microaneurysms particularly is disturbed subclinically, permit the statement that carbon disulfide inhaled would have a mild diabetogenic action, and retinal microaneurysms may be induced by the same possible factors responsiblefor the microvascular changes seen in diabetes mellitus.

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In order to compare influence of various diabetic treatments on the development of vascular complications, fasting blood sugar, serum lipids, body weight and the occurrence of vascular complications were studied in 429 diabetic patients during the periods of treatment which extended one year to ten years. Causes of death were also analysed in 99 deceased cases among 821 diabetic patients including those who had been treated for less than one year. Among 429 diabetic patients, 87 patients had been treated with diet alone, 206 patients with sulfonylurea, 17 patients with biguanide, 103 patients with insulin and 16 patients with the combination of the oral drugs and insulin. The average fasting blood sugar of these treatment groups showed a significant decrease in 2 years after the initiation of treatment, followed by a gradual increase both in insulin group and in sulfonylurea group. The rate of incidence of cases poorly controlled was highest in those receiving insulin treatment, followed by those treated with sulfonylurea. The incidence of hypercholesterolemia and albuminuria both in sulfonylurea group and in insulin group decreased significantly during the first 2 years after the treatment and increased thereafter. Albuminuria was more frequent in insulin group (20-40%) than in sulfonylurea group (10-20%). No significant difference was found among the groups in the rate of appearance of diabetic retinopathy (10-20%) as well as in the incidence of hypertension (10-30%). The increase in body weight (over 5kg/year) was observed more often in insulin group (15-30%) than in diet group (8-10%). The rate of appearance of ECG abnormality was 10-30% in all groups. Ketonuria and hypoglycemic episode were frequnet (17-30%) in insulin group.
Cancer was the most frequent cause of death in all groups. Diabetic nephropathy was the most common among the vascular complications which led the patients to death. Comparatively speaking, more patients in insulin group (5.8%) died from diabetic nephropathy than those in sulfonylurea group (0.4%) and in diet group (1.3%), while more patients in insulin group (2.1%) and in diet group (1.9%) died from cerebrovascular accidents than those in sulfonylurea group (0.7%). The rate of death from coronary heart disease was 0.7% in diet group, 0.4% in sulfonylurea group and 1.6% in insulin group and these figures were much lower than those reported by the University Group Diabetes Program (UGDP) in U. S. A. The present results, consisted with those from other investigators in Japan, suggest that the death from myocardial infarction in Japan is rare in diabetics receiving sulfonylurea treatment as well as those receiving other treatments. Though the method employed in this study is retrospective one and is different from that of UGDP in several points, it seems that our results did not support the current emphasis on the relationship between sulfonylurea treatment and death form myocardial infarction, as postulated by UGDP.

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The antibody against exogenous insulin is formed after a few months of insulin injection in the diabetic patients who are treated with insulin. Till recently it was not possible to determine serum insulin level by the usual radioimmunoassay. In this study the method to determine the serum insulin level in the patients whose sera contain insulin antibody due to insulin injection was examined and the serum insulin response during oral glucose tolerance test and the daily change of serum insulin after insulin injection in insulin-treated diabetics were investigated.
Sixty-one diabetic patients who were injected insulin every morning were studied. Blood sugar and serum FFA were determined. The serum total insulin was extracted with acid alcohol, the supernatant was added to ten times volume of acetone-ether mixture (2: 1) and the IRI in the precipitate was determined by the radioimmunoassay. For the determination of free insulin, the serum was added to ethanol (final conc. 77%) and the supernatant was treated as mentioned. As the titer of insulin antibody, 6μU¹³¹I insulin and 25μU unlabelled insulin were added to 0.05 ml of serum, the free and bound insulin were separated by dextran-coated charcoal and the percentage of radioactivity of bound insulin was calculated.
The results are as follows.
1) The recovery of total and free insulin after extraction was approximately 90 % and 70 %, respectively.
2) No insulin antibody was found in the supernatant of alcohol-treated serum.
3) The total insulin in 18% of the patients was undetectable (under 75μEU/ml) and the free insulin in 20 %(under 30μU/ml)
4) The level of serum total and free insulin increased moderately during the oral glucose tolerance test in good control group (8 subjects), but no increase was observed in poor control group (4 subjects). The insulin antibody titer did not change in both groups.
5) Generally high fasting levels of total and free insulin were observed in both groups. In good control group, both insulin level and insulin antibody titer were a little high compared with those in poor control group, but they were not significant.
6) The change of free and total insulin levels during 24 hours was investigated in 6 insulintreated patients who were injected insulin subcutaneously before breakfast. The increase of both insulin was found already at 2 hours after breakfast, and got to the maximum level at 2 hours after lunch, returning to the fasting level on the next morning. The titer of insulin antibody decreased significantly after insulin injection and got back gradually to the fasting level on the next morning.
7) The significant correlation was found between the level of total and free insulin, or between the total insulin level and the insulin antibody titer in the fasting serum.
8) The fasting levels of both insulin and insulin antibody increased in parallel with the dose of exogenous insulin and duration of insulin treatment.

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A simple method for separation of plasma chylomicron and colorimetric determination of its triglyceride content was described.
Chylomicron in plasma, diluted appropriately, was collected by ultra-filtration using cellulose nitrate membrane filter with pore size of 100mμ. Chylomicron in residue was extracted with chloroform and triglyceride-glycerol was measured. The mean recovery rate of chylomicron-triglyceride was 88.6%. The mean relative error was 7.6% and there was no loss of accuracy for plasma from patients with gross hyperchylomicronemia.
An analysis using paper electrophoresis revealed validity of chylomicron separation by the filtration method.
The mean value of fasting chylomicron-triglyceride was 4.8±1.1 mg/100 ml (± SE) in 15 normal subjects, 12.2±2.0 mg/100 ml in 18 moderate diabetics and 30.9±5.0 mg/100 ml in 13 severe diabetics.

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This report deals with the second case with insulin-autoimmune syndrome ; spontaneous hypoglycemia, reduced glucose tolerance, hyperplasia of pancreatic islets and the existence of insulin-binding antibodies in the serum.
In this case attacks of mild hypoglycemia appeared from 1968 and severe hypoglycemic coma and convulsions occurred from August 14, 1969, when he was 61-year-old.
The partial resection of the pancreas was carried out in September 24, 1969, and no islet cell tumor was able to be found in his pancreas.
After the operation the hypoglycemic attacks disappeared, insulin-binding capacity of the serum dereased and the blood sugar responce in the glucose tolerance test changed from a diabetic pattern to an oxyhyperglycemic pattern.
Previously we have reported another case who showed the same syndrome of this case. It is suggested that there may be a new syndrome produced by insulin-autoimmunity. This synddrome consists of some characteristic signs and findings as follows:
1) Spontaneous hypoglycemia.
2) Reduced gloucose tolerance.
3) Existence of insuiln-binding antibodies in the serum.
4) Increased serum insulin.
5) Generalized islet hypertrophy in the pancreas.

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