In order to study on amino acid metabolism in diabetes mellitus, the free plasma amino acids were examined with KLA-2 type Hitachi amino acid autoanalyzer in 34 patients with diabetes mellitus and 12 healthy subjects.
The difference of the free plasma amino acid pattern between diabetics and healthy subjects was observed and the changes in the free plasma amino acid reflecting the various clinical types of diabetes mellitus were analyzed.
Influence of treatments such as diet only, oral hypoglycemic agents or insulin on the plasma free amino acids was studied.
Effect of test meals which contain high, medium or low protein on the free plasma amino acids was also observed.
The results obtained were as follow:
1) Asparatic acid, threonine, glycine and alanine were significantly lower in patients than those in healthy normal subjects.
2) Histidine and arginine were significantly lower in the patients above 50 years of age than those in patients below 49 years old.
3) In the plasma amino acid levels of diabetic patients with FBS above 140mg/dl, arginine, histidine and phenylalanine decreased significantly, compared with those in patients with FBS below 139mg/dl. A tendency of inverse correlation was noted between these amino acids and FBS.
4) In diabetic patients with proteinuria, arginine was significantly decreased but serine was increased.
5) In the patients suffering from diabetes mellitus for one year or more, the plasma level of serine was significantly higher than that in those suffering for 12 months or less.
6) The free plasma amino acid of diabetic patients seemed to have no characteristic pattern in relation to the body types, total serum cholesterol, serum A/G retio or retinal abnormalities.
7) When the patients were controlled on both diet and oral hypoglycemic agents, only cysteine decreased significantly. On the other hand on insulin therapy, serine decreased, but cysteine increased significantly.
8) The free plasma amino acid levels in diabetics seemed to change depending on the protein content of the test meals.
The high protein meal caused increase in the level of arginine, proline, isoleucine and tyrosine. The low protein meal caused increase in the level of aspartic acid. The medium protein meal caused increase in valine, isoleucine, leucine, tyrosine and glycine significantly. A decrease of cysteine was seen by either of these three test meals.

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Cholesterol, phospholipid and bile acid in the gallbladder bile were analyzed in 13 diabetic patients, 8 obese non-diabetic subjects and 8 healthy persons and the relative molar concentration of cholesterol (RMCC) was calculated.
A significantly higher RMCC was observed in the diabetic group as compared with the normal group, but differences in RMCC between diabetic group or between obese group and normal group was not statistically significant.
We concluded that diabetic state was accompanied with the supersaturated bile with cholesterol.

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In order to determine the causes of human diabetic angiopathy, we have been studying renal lesions in KK mice and have made the following observations:
1) Abnormal glucose tolerance in KK mice was recognized when they were 4 months old, and was most remarkable at 6 months. The glucose tolerance, however, was inclined to be normalized at 16 months of age.
2) In two-month-old KK mice, glomerular lesions such as the segmental thickening of the basement membrane, similiar to those observed in diabetic patients, could be found with an electron microscope. The increase of mesangium matrix in six-month-old mice and the glomerular lesions in sixteen-month-old mice were also recognized with a light microscope.
3) The glomerular lesions of KK mice developed as they grew older, which could be clearly proved by the G. L. I. (glomerular lesion index).
4) It is expected that by observing the growth of glomerular lesions in KK mice we can appreciate better the causes of human diabetic angiopathy.
It is concluded that the development of glomerular lesions in KK mice is affected not only by a basic disturbance of glucose metabolism, but also by the advancing age.

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Serum lipids (total phospholipids, triglyceride, cholesterol) and serum phospholipids fractions were determined in 7 normal young subjects (mean age: 29.3), 6 normal aged subjects (mean age: 60.6) and 4 young diabetics (mean age: 28.5), 25 aged diabetics (mean age: 63.4).
1. The average serum total phospholipids concentration was much higher in normal aged subjects (216.7 mg/dl) than that of young subjects (167.6 mg/dl). In serum phospholipids fractions, serum lysolecithin was quantitatively elevated in normal aged subjects as compared with that of normal young subjects.
2. The increase of total phospholipids concentration was prominent in young diabetics (225.3mg/dl). In percentage, there was decrease of sphingomyelin, but quantitatively there was increase of phosphatidylethanolamine and lecithin.
3. There was no significant difference in serum total phospholipids between aged diabetics (230.4mg/dl) and normal aged subjects. In percentage, there was decrease of lysolecithin in aged diabetics (p<0.05).
4. Serum total phospholipids concentration was higher in aged diabetics (260.1 mg/dl, mean age: 59. 6) with hyperglyceridemia (>150 mg/dl) or hypercholesterolemia (>270 mg/dl) than in normal aged subjects, but the difference was not statistically significant. In serum phospholipids fractions, it was revealed that the increase of lecithin and decrease of lysolecithin in aged diabetics.
5. There was no significant change in serum total phospholipids and its fractions with regard to microangiopathy and control of blood glucose.
6. The diabetics on sulfonilurea or insulin therapy had higher levels of serum total phospholipids than those who were on diet alone. No statistical significance was observed in the levels of serum phosphatidylethanolamine between these three groups.
It was tentatively concluded that the changes of serum phospholipids concentration and its fractions observed in diabetics would be the manifestations of abnormal lipid profiles associated with diabetes mellitus. It remained to be elucidated whether these changes play fundamental role in the pathogenesis of vascular complications associated with diabetes mellitus.

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Ophthalmological examination of 148 Japanese diabetic patients, ranging from 19 to 78 years of age, showed that 45 cases had cataracts (30.4%), the incidence of cataracts for males and females being 13/73 (17.8%), and 32/75 (42.7%), respectively. The difference of the incidence between male and female patients is statistically significant (p<0.005). In young diabetic patients under the age of 29 the difference of the incidence of diabetic cataracts between both sexes is remarkable. All of the 6 males had no cataracts and 7 of 11 females had cataracts (p<0.05). Three of these 7 females were found to have had cataracts already when they were diagnosed as having diabetes and, in the other 4, lens opacities appeared within two years after the diagnosis of diabetes. Therefore, diabetic cataracts seem to occur in a short duration of diabetes and to develop rapidly in young female diabetic patients. As to the severity of diabetes (FBS before treatment), state of metabolic control, method for the treatment of diabetes and grade of diabetic retinopathy, no marked difference were observed between young diabetics with and without cataracts. The facts deserve, however, special mention that all of the 7 patients with cataracts developed diabetes after their ages of adolescence, while half of those without cataracts had been suffering from diabetes since childhood, and that the most of those with cataracts complain of disturbances of menstruation such as amenorrhea or oligomenorrhea. These facts suggest that endocrine environment including sex hormones may play a role for the pathogenesis of diabetic cataracts, possibly through the sorbitol pathway activity, the permeability of the capsule or the regenerative capacity of the lens.

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Two groups of patients who were well controlled with insulin or with sulfonylurea were selected retrospectively, and their clinical and laboratory findings were analysed to compose discriminant function with the best separation.
Age of onset, duration of diabetes mellitus, obesity index, fasting blood sugar level, urinary sugar for twenty-four hours, serum total cholesterol level, systolic and diastolic blood pressure, PSP (15 min.), and retinal findings before treatment were adopted for the study.
The composed discriminant function formula was
Y=-0.484×age of onset +0.176×duration of diabetes
-0.454×obesity index +0.586×fasting blood sugar
-0.047×urine sugar +0.066×cholesterol
+0.173×systolic blood pressure -0.037×diastolic blood pressure
-0.160×retinal findings +0.191×PSP
Data for each variable were standardized before used in the formula.
Negative score with this linear function suggest an indication for the treatment with sulfonylurea, and positive score with insulin.
The four most effective variables were used for the simplified discriminant function for the clinical usage as followings;
Y=-0.394×age of onset -0, 471×obesity index
+0.684×fasting blood sugar +0.005×urine sugar
Predata processings for diabetic patients complicated with nephropathy and/or liver cirrhosis are under study for the application of discriminant function.

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Experiments have been carried out to determine whether a stimulatory effect of glucose administerd orally on the secretion of gut glucagon was associated with the absorption process of glucose from the intestine. For this purpose, oral and intravenous glucose tolerance tests were performed in gastrectomized subjects treated 60 minutes previously with phenformin (DBI) which has been reported to cause an impairment of intestinal absorption of glucose, and changes in blood sugar, IRI, total IRG and pancreatic glucagon levels were compared with those obtained during the control experiment in which no DBI was administered previously.
DBI pretreatment flattened the blood sugar and IRI responses to oral glucose significantly but did not alter the response to the intravenous glucose. The drug produced no significant changes in basal plasma pancreatic glucagon and total IRG levels. Thirty minutes after the oral glucose alone, the total IRG level rose to a peak of 1.55±0.17ng/ml, a value being not different from the maximum level of 1.67±0.18ng/ml observed during the test pretreated with DBI. However, the mean total IRG levels obtained 120 and 180 minutes after the oral glucose with DBI were significantly higher than the corresponding values without DBI which seemed to be attributed to glucose retention in the gut caused by the drug. No significant changes in mean plasma levels of pancreatic glucagon were noted after the oral glucose with and without DBI. The intravenous injection of glucose caused a slight decline in total IRG concentration to the same extent in the both occasions.
These results suggest that gut glucagon is released in response to contact of glucose with the intestinal mucosal surface rather than the intestinal absorption of glucose.

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A case of maturity-onset diabetes with right femoral mononeuropathy was reported. The patient was a 64 year old male who had suffered from diabetes mellitus for 6 years and poorly controlled. Severe pain developed suddenly on the inner side of the right thigh after walking of fairly long distance. The pain occurred intermittently thereafter and became more severe, associated with hyperesthesia during absence of pain. Also he noticed weakness of the right hip and knee areas.
On examination, the significant abnormality was confined to the neuromuscular status in the right leg. There was moderate weakness and atrophy of the right thigh muscle. Right knee jerk diminished moderately and ankle jerk was absent. There was hyperesthesia on the inner side of the right leg but no diminution of vibratory sensation in the right foot. Roentogenological study of the lumbar spine revealed slight spondylosis deformans. Las-gue's sign was not demonstrated. Fundoscopic examination showed considerable microaneurysms.
Lumbar puncture was performed and results of C. S. F. examinations were normal except for a spinal fluid protein of 75 mg and sugar of 96 mg per 100 ml. Electromyogram revealed reduced pattern. Conduction velocity of the right femoral nerve was 20.0 m/sec to show a remarkable slowing Biopsy of the right thigh muscle revealed a marked denervation atrophy.The patient obtained a good control of blood sugar by receiving glibenclamide 2.5 mg daily. But attacks of the severe pain of the right leg were not subsided by almost all of analgetics and daily dose of 0.2 g of diphenylhydantoin. However, the severe pain, especially nocturnal pain was dramatically reduced by increased daily dose of diphenylhydantoin up to 0.3 g.

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Diabetic patients often have a history of life with excessive dietary intake besides insufficient physical exercise before the onset of diabetes mellitus. Among 600 diabetics, about 90% of the patients were of occupations those require less than usual amount of physical movement. The diabetic persons become to feel fit after having an effective exercise more than that of their usual life, because of reduction in weight and establishing good control with normal fasting blood sugar level. A group of diabetics having had walking exercise daily for more than thirty minutes during the period of three to five years was found to have less frequency in developing retinal arteriolosclerosis of Sheie's grade II, III or IV than the other group with insufficient exercise.
The amount of physical exercise must be appropriate according to diabetic individuals, and optimum amount of exercise is to be determined with gradual increase of physical movement. The diabetic patients must include the hours of exercise as a daily schedule, because it is tremendously beneficial on improvement of diabetic condition when performed every day. It was found with physical exercise that blood glucose decrease without elevation of serum immunoreactive insulin. It suggests that glucose have been utilized in the skeletal muscles.
In order to evaluate the effect of exercise, the symptoms of diabetes, body weight, blood sugar, serum lipids components are to be followed up, trying to make the above mentioned data approach to the normal ranges. Excessive physical exercise is warned to diabetics with insulin or with oral hypoglycemic agents because of developing hypoglycemic episodes. Physical exercise is of course contraindicated for a patients with complications which need bedrest.

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