Nine hundred and thirty three diabetic autopsy cases were collected from the Annual Reports of autopsy cases which were published by the Japanese Pathological Society for the year 1958-1965 and statistical analyses were made for the cases. The most frequent cause of death in 811 primarydiabetes cases was vascular complications. Nephropathy was a cause of death in 17.7 per cent, whereas cerebral vascular accidents were the cause of death in 8.8 per cent and ischemic heart disease in 6.0 per cent of the cases, respectively. The next ranking cause of death was infections. Pulmonary tuberculosis was seen in 8.1 per cent, purulent lung infections in 5.5 per cent, urinary tract infections in 3.4 per cent, biliary tract infections in 1.3 per cent and sepsis in 1.3 per cent of the cases. Malignant neoplasms were a cause of death in 15.6 per cent of the cases. Cancer of the stomach was thought as a cause in 3.2 per cent and lung cancer in 3.3 per cent. Diabetic coma was a cause of death in 6.2 per cent and it was a major cause in juvenile diabetics. One hundred and twenty-two of the 933 cases were classified as secondary-diabetes. The secondarydiabetes group consisted of 51 cases of liver cirrhosis, 27 cases of cancer of the pancreas, 22 cases of steroid diabetes, 7 cases of hemochromatosis, 7 cases of acromegaly and 3 cases of Cushing disease. There was no case of hyperthyroidism and of hyperfunction of the adrenal glands. The presence of diabetic glomerulosclerosis was described in 10.6 per cent of the secondary-diabetes cases.
A new carbohydrate solution, SDT-25 was administered orally to experimental subjects in doses corresponding to 100g of glucose in order to investigate change in blood sugar level and the presence of side effects. Results obtained were as follows: 1) The oral administration of 100g of glucose produced gastric symptoms such as nausea and vomiting in 27% of the experimental subjects, whereas, the administration of SDT-25 did not produce any such side effect. 2) There was no significant difference between the change in blood sugar level after administration of 100g of glucose and that of SDT-25. 3) From the foregoing it is thought that SDT-25 is a promising new carbohydrate solution which may be used, safely without side effects, for glucose tolerance tests.
A widespread attention has been focused on the close association between diabetes mellitus and obesity. Although obesity is frequently expressed as the increased weight-height ratio, a more accurate definition of obesity is the abnormal increase of the total body fat. The measurement of the subcutaneous fat depot (skinfolds thickness) is therefore used for the purpose of indicating the state of body fat. Since the normal range of the skinfolds thickness among the aged subjects has scarcely been known, our study was first intended to establish the normal range of the skinfolds thickness of the “normal” aged and to see the correlations between these values and their body builds. Secondly the distribution of skinfolds thickness was compared between normal and diabetic subjects. [Mlaterials] Out of the apparently healthy persons with normal daily activity over the age ot sixty years, 41 males and 94 females were selected after conducting the complete medical examination. The diabetic subjects consisted of 39 males and 28 females selected from the ambulant patients at the outpatient clinic of the Department of Geriatrics, University of Tokyo Hospital and Eiju Hospital Clinic. [Method] The measurement of the skinfolds thickness was done by the skinfold caliper of the Eiken-type at the commonly measured points of the body-the upper arm (midway on the posterior line), below the scapula, the abdomen (beside the navel) and above the iliac crest (in the midaxillary line). [Results] 1) After the logarithmic conversion of the skewed distributions, the correlation between the values of skinfolds of the abdomen and the mean values of the skinfolds of the upper arm and below the scapula were figured with 5% critical ellipse. According to the result, the values of the upper arm and below the scapula were relatively well held even if in the persons with thinner skinfolds. 2) The values of the skinfolds of the diabetics were dotted upon this ellipse. Especially in the male diabetics, the values of the skinfolds were generally large and remarkably deviated. 3) Of the “normal” aged, the regression lines of the various points of the body on the somatic index (Ponderal Index; height cm/3 (aweight kg) were calculated with 95% confidence interval. 4) When the values of the skinfolds of the diabetics were plotted with the regression line, most of them were situated above this line and some of them beyond the 95% standard error range. This finding seems to indicate that the diabetics, even if the same body build as the non-diabetics, have more subcutaneous fat depot than the “normal” ones. 5) There appeared to be no relationship between the abnormal values of the diabetic and the findings of the blood glucose level at the first visit or the time of measurement, the duration, serum cholesterol and electrocardiogram. Further studies are being conducted on these points.
Glucose-6-Phosphate dehydrogenase activities were measured in erythrocyte of healthy individuals and diabetic patients, and in order to elucidate relation between erythrocyte G6PD activity and diabetes, effects of insulin on erythrocytes and their hemolysates of diabetes in vitro were examined. Following results were obtained: 1) The erythrocyte G6PD activity of an untreated diabetic patient was significantly lower than that of a healthy individual. But after treatment with insulin or sulfonylurea, the value of activity of this enzyme was restored to that of a healthy individual. 2) When erythrocyte of untreated diabetic patients, added with 0.2 unit of insulin, was incubated for 6 hours in vitro, significant rise of G6PD activity was observed. 3) When G6P was added to erythrocytes or hemolysates, a significant rise in the activity of this enzyme was noticed, but when insulin was furthermore added to either of them, no rise in the activity was noticed. Considering results above mentioned, the mechanism of the rise in the activity of this enzyme was discussed.
In the previous study of author, the relation between erythrocyte G6PD activity and insulin was examined. Consideration of various possibilities suggested that the relation between the G6PD activity of the erythrocytes of a diabetic patient and the “activating factor” of this enzyme in the stroma would be an interesting subject of study. In the present study, effects of the stroma obtained from a erythrocytes of a healthy individual and effects of that from a diabetic patient on the hemolysates G6PD of untreated diabetic patient, and the relation between the effects and insulin were examined. Following results were obtained: 1) In the case when hemolysate of an untreated diabetic patient was incubated together with stroma from an untreated diabetic patient, no effects were observed in G6PD activity, but when the former was incubated together with stroma from a healthy individual, significant rise in G6PD activity was noticed. 2) In the case when hemolysate of a healthy individual was incubated with stroma obtained from another healthy individual and/or from an untreated diabetic patient, G6PD activity did not change. 3) No rise in G6PD activity in the hemolysate of an untreated diabetic patient was noticed when insulin was added to stroma from untreated diabetic patient. Judging from above results, it may be supposed that in the stroma of a healthy individual there exists an “activating factor”( “stroma factor”) of G6PD activity and that G6PD in his hemolysate is of active type. On the other hand, it may be supposed that in a diabetic patient there is some defficiency of the “stroma factor” and that a considerable amount of G6PD as an inactive type is contained in his hemolysate.
Liver and retinae of rats fed with high fat diet for 100-400 days were compared with those of rats fed with normal diet. The following results were obtained. 1) Gluconeogenesis was increased, glycolysis was impaired in liver slices of high fat diet group in concomitant with disturbed carbohydrate tolerance, while normal diet group had no changes. 2) The incorporation of glucose-U-C14 into CO, in retinae of high fat fed rats were significantly lowerd than those of normally fed rats. 3) In retinae of high fat fed rats for 400 days, dilatations of blood vessels, degenerations of the ganglion cells and retinal bleedings were observed. 4) In tryptic digestes of retinae of high fat fed rats, microaneurysm was not demonstrated, but decreases in pericytes were observed. However, in retinae of the controll rats, no significant retinal changes were observed. 5) These changes observed in high fat fed rats were discussed in relation to the increased oxidation of fatty acid and pathogenesis of diabetic retinopathy.
Aromatic amino acids and amines which is precursors of adrenaline, were injected subcutaneously in rabbits to study the effect on bloods ugar. L-phenylalanine, L-tyrosine and tyramine had no hyper-glycemic action. The administration of DL-2·4-DOPA caused hyperglycemia, and a more remarkable hyperglycemia occurred following DL-3·4-DOPA and L-3·4-DOPA administration. The administration of dopamine caused a most marked hyperglycemia increasing 2-3 times of the normal level after 3 hours in all experiments. Thus, the hyperglycemic action became more remarkable from the stage of dihydroxyphenyl in the main pathway of adrenaline synthesis. The effects of various drugs on DOPA and dopamine hyperglycemia were studied. DOPA hyperglycemia was completely inhibited by the intravenous administration of L-α-methyl-DOPA. Dopamine hyperglycemia was not so markedly influenced by the intravenous injection of nialamide (MAOI), and the administration of phentolamine (α-blocker) have slightly inhibited dopamine hyperglycemia, but propranolol (β-blocker) have given no effect. The relationship between dopamine hyperglycemia and adrenergic receptor was not so clear. DOPA hyperglycemia was not influenced by the intravenous injection of tolbutamide, but was completely inhibited by insulin. Dopamine hyperglycemia was not influenced by the intravenous injection of tolbutamide.
When the Liver slices were incubated with glucose, the tissue glucose content and the output of glucose from tissue were increased in the diabetes more than that of the normal. The addition of xylitol or insulin to the diabetes caused a decrease of glucose output. The incorporation of glucose-U-14C into glycogen in the diabetes was simulated by the addition of xylitol. During the incubation for 1.5 hours, glucose-6-phosphate content increased twice, and uridinediphosphate glucose decreased to about a third by the addition of xylitol. The glycolytic intermediates were also determined by the enzymatic micoromethod. In the diabetic tissue, the concentration of glycolytic intermediates, and ATP, ADP and NAD were lower than those in the normal. The addition of xylitol to the diabetes caused the increases of the intermediates ofglycolysis, and particularly, the intermediates from triose-phosphate to pyruvate. The free energy change between glucose and pyruvate were -15.7 kcal/mole in the normal and -17.8 kcal/mole in the diabetes. With addition of xylitol to the diabetic liver slices, free energy change in glycolysis was -16.6 kcal/mole, and free energy change from glyceraldehyde phosphate to pyruvate became to small (-6.49→4.92 kcal/mole) Xylitol would be penetrated into the tissue without any relation to insulin and exert the positive feedback on glycolysis via Pentose Phosphate Cycle.