The cholesterol contents of the thoracic aorta, the renal artery and the coronary artery were determined in 6 nondiabetic and 21 diabetic autopsy subjects. The average ages of the nondiabetic and diabetic groups were 59.0 and 64.5 years, respectively. The mean duration of diabetes was 12.9 years.
The dry weight of the aorta per area and of the arteries per length was greater in the diabetics than in the nondiabetics, suggesting that atherosclerosis was more advanced in the diabetics. The increase in cholesterol concentration in the arota with dry weight of the aorta per area, and in the renal artery with dry weight of the artery per length could be represented by the regression equations: y=-2.81+0.16x (r=0.718, p<0.001), and y=0.63+0.69x (r=0.478, p<0.05), respectively. The contents of cholesterol in the aorta, renal artery and coronary artery of the nondiabetics were 2.0±0.5%, 0.9±0.1% and 5.4 ± 3.1%, respectively, and a statistically significant difference was noted among them. The contents of cholesterol in these arteries in the diabetics were 4.9 ± 2.6, 2.7 ± 2.7%, and 5.4±3.7%, respectively. The content of cholesterol in the diabetics was greater in the groups with hypertension, ECG-abnormalities and long duration of diabetes, and that in the renal artery of the diabetics was markedly greater in the groups with proteinuria, long duration of diabetes and ECG-abnormalities.

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In order to study renal changes at the early stage in patients with diabetes mellitus, changes in urine albumin, urinary excretion and blood levels of N-acetyl-β-D-glucosaminidase (NAG), and urinary excretion of β-D-galactosidase (GAL) were determined before, during, and after exercise test by means of an ergometer in 16 patients with diabetes (15 NIDDM diabetics, one IDDM diabetic) and 10 normal subjects (controls). The following results were obtained.
1) In normal subjects, the urine albumin did not increase. Taking the level in normal subjects, X+2SD, as the normal range, it increased to a level in excess of the normal range in 6 patients with diabetes during and after the exercise test, and it increased slightly in 3 patients before or only after the test.
2) The serum NAG increased more significantly in the patients who showed an increase in urine albumin than in the patients who showed no increase in urine albumin.
3) There were no differences in urine NAG or GAL before, during, or after the exercise test. The urine NAG in patients with diabetes increased more significantly than that in the normal subjects before and during the exercise test.
4) The urinary excretion of albumin was significantly correlated to the urinary excretion of NAG, and to the urinary excretion of GAL, in patients with diabetes during and after the exercise test. Based on the above results, the urine NAG and urine GAL were considered to be involved in the occurrence of renal changes at the early stage of diabetes and to represent good indices for the early detection of diabetes mellitus.

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The present study was conducted to determine the clinical features of diabetic patients which might lead to myocardial necrosis. Autopsies on 141 diabetics (age: 43-85) with onset after the age of 40 years performed between 1967 and 1980, were reviewed. The subjects were divided into 3 groups according to the presence of myocardial necrosis. Group I included 45 cases with massive myocardial necrosis; Group II, 33 cases with patchy necrosis; and Group III, 63 cases without necrosis. There was no sex predominance in the incidence among each group. The autopsy findings indicated that coronary atherosclerosis and diabetic glomerulosclerosis were significantly more common in Groups I and II than in Group III (p<0.01). The clinical data showed that diabetics with elevated triglyceride levels were seen more often in Group I than in Group III (p<0.05). The duration of diabetes and the period between onset and initial treatment were also longer in Group I (p<0.01). However, the development of either massive or patchy necrosis was not significantly associated with the following parameters: modality, blood sugar, persistent proteinuria, diabetic retinopathy, blood cholesterol level, smoking history, blood pressure or body weight. On the other hand, combinations of any two factors among the three major risk factors (blood pressure, cholesterol and smoking) were seen more often in Group I than in Group III (p<0.05).
The results of this study indicated that the presence of severe coronary atherosclerosis and diabetic glomerulosclerosis were closely associated with the development of myocardial necrosis. No apparent difference in coronary atherosclerosis could be found between the group with massive necrosis and the group with patchy necrosis. Hypertriglyceridemia, a duration of diabetes of at least 10 years and a period between onset and initial treatment of at least 1 year seemed to be associated with myocardial necrosis. No significant relationship could be found between the development of myocardial infarction and any individual risk factor for coronary disease. However, the combined effects of three major risk factors may be related to the development of myocardial infarction in diabetics.

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The amounts of insulin and pancreatic polypeptide (PP) in the human pancreas within 6 hours after death were determined in 26 diabetic and 19 nondiabetic autopsy cases. The relations to the stability of fasting serum glucose based on the standard deviation of 15 determinations, and to renal or hepatic insufficiency were also investigated. The following results were obtained.
1) Gel filtration of acid ethanol extracts with a Sephadex G50 column revealed single insulin, PP and C-peptide peaks.
2) The PP contents at the tail of the pancreas in the diabetic and nondiabetic subjects were 9.55±2.41 μg/g and 7.71±1.52 μg/g wet weight of pancreas, respectively. Those at the head of the pancreas were 16.86±5.51 μg/g and 15.82±5.38 μg/g, respectively. No significant differences were found between the diabetic and nondiabetic values or between those at the tail and at the head of the pancreas. The PP contents at the head of the pancreas including both the diabetic and nondiabetic subjects were significantly higher than those at the tail (p<0.02).
3) The insulin content at the tail of the diabetic pancreas was lower than that in the nondiabeticpancreas (p<0.01). The values were 1.26±0.19 U/g and 2.55±0.35 U/g, respectively. The content at the head of the diabetic pancreas was not significantly different from that in the nondiabetic pancreas. The values were 1.14±0.27 U/g and 1.60±0.23 U/g, respectively.
4) In cases containing less than 0.5 U/g of insulin at the tail of the diabetic pancreas, the stability of the fasting serum glucose was very poor, indicating an unstable type of diabetes. However, the PP contents of the pancreas revealed no relation with the stability of the fasting serum glucose.
5) Renal insufficiency in the diabetics exerted no aggravating effect on the stability of the fasting serum glucose, and revealed no relation with the pancreatic contents of insulin or PP. In cases with hepatic insufficiency among the diabetics, the stability of the fasting serum glucose was somewhat poor, suggesting some contribution by liver insufficiency in the control of the blood sugar level.

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In order to study the insulin receptor kinetics under normal and pathophysiological conditions in humans with a small amount of blood, we assayed the insulin binding to erythrocytes from normal subjects (cord blood, 8 subjects; 6 mo to 6 yr old, 13; 7 to 19 yr old, 13; 20 to 59 yr old, 30; over 60 yr old, 12), 8 borderline diabetics by 50 g OGTT and 34 untreated Type II NIDDM patients. We also tested the insulin sensitivity of diabetic subjects by the method using somatostatin.
Cord blood showed the highest insulin binding with an increased number of binding sites on the erythrocytes (R₀). The other 4 groups of normals demonstrated increasing binding with age due to increased binding affinity (Ke) without changes in R₀.
The insulin binding was inversely correlated with the degree of impaired glucose tolerance. A broad distribution of insulin binding was observed in the diabetic patients due to the differences in Ke. Type H (diabetics with tracer bindings above the mean of those of diabetics: 4.86%, n=18). demonstrated higher FPG, lower insulin secretion and more insulin resistant as judged by the insulin sensitivity test than Type L (below 4.86%, n=16). The increased Ke observed in Type H failed to compensate the insulin resistance, suggesting that the changes in Ke did not contribute to amelioration of the insulin resistance.

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In order to examine whether the decrease of insulin receptor number (R₀) is genetically predetermined, or induced by metabolic derangement in Type II diabetes mellitus, we assayed the insulin binding to erythrocytes from untreated Type II NIDDM patients before and after treatment. None of these diabetics showed hyperinsulinemia.
Insulin binding was decreased in 5 patients of Type H (high insulin binders) after 1 to 2 weeks of short-term insulin treatment, and this was due to a decrease of binding affinity (Ke) with no changes in R₀. After 16 to 29 months of long-term treatment (diet only; oral hypoglycemic agent; insulin), 11 Type II diabetics demonstrated increased insulin binding with an increase of R₀. The Ke of their binding curves tended to decrease after treatment, although the difference was not significant. Furthermore, a significant negative relationship was observed between the levels of Hb Ai and R₀.
These results suggest that metabolic effects, rather than genetic factors, may play an important role in regulating the insulin receptor number in Type 11 diabetics, and indicate the possible existence of a potent metabolic factor to decrease R₀ besides the well-known mechanism, i. e., downregulation, in Type II NIDDM.

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The present report concerns a pregnant diabetic whose pregnancy was continued by treating her worsening retinopathy by photocoagulation. The diabetes of this 25-yr-old housewife was first diagnosed when she was 17 years old and insulin therapy was begun. Blood glucose control with 36 to 42 units of lente insulin was quite good. She married at 22. Although she did not attend hospital during the next two years, insulin therapy was continued. She came to the Diabetes Center in January 1980 in the 8th week of her first pregnancy. The previous condition of her ocular fundi is unknown. Her fasting blood glucose was 274mg/dl and the ocular fundi were rt. Scott I_a, It. Scott III _a. The patient was immediately admitted to the Center and, after an increased insulin dosage, her blood glucose was brought under control. Her diabetic retinopathy gradually worsened, however, to proliferative retinopathy, Scott III _b, in the 18th week of pregnancy.
Xenon photocoagulation for the retinopathy in her right eye in the 20th week of pregnancy and for that in her left eye in the 22nd week, decreased the retinal edema, bleeding, and white patches. Photocoagulation was performed twice more for the right eye, in the 27th and 30th weeks of pregnancy.
Since the patient's retinopathy did not worsen after photocoagulation, the pregnancy was continued. A female infant weighing 3080g was delivered by Caesarean section in the 37th week of pregnancy due to weakened fetal sounds and decreased fetal function. The baby's respiratory distress syndrome and hypoglycemia improved satisfactorily with therapy. A week after delivery, the mother's ocular fundi were Scott II. This case thus illustrates the efficacy of attempting photocoagulation, rather than therapeutic abortion, when treating worsened retinopathy during pregnancy in diabetics.

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A 23-year-old male student with insulin-dependent diabetes exhibited signs of severe emotional inadaptability, such as morbid fear and enervation, and also developed metabolic instability associated with hyperglycemia and hypoglycemic attacks. These two conditions could not be improved by ordinary therapeutic measures for diabetes. However, psychotherapy with counselling based on a proper understanding of the patient's psychology, when combined with medical treatment of his diabetes, proved to be effective in correcting the emotional inadaptability and metabolic instability as well as in restoring social adaptability to the patient.
The experience in this case indicates that a close relationship exists between good emotional adaptability and adequate control of diabetes in young dtabetic patients. It is concluded that counselling may be very useful both in improving emotional inadaptability and in correcting metabolic instability in such patients.

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Urinary N-acetyl-β-D-glucosaminidase (NAG) was measured in 108 diabetic patients with or without clinical diabetic nephropathy, and the correlation between urinary NAG activity and proteinuria, serum creatinine, and HbAI level were studied.
The results obtained were as follows.
1) The urinary NAG activity levels of non-diabetic controls, diabetics without proteinuria, diabetics with intermittent proteinuria and diabetics with persistent proteinuria were 2.74±1.41 (n=48), 7.70±4.62 (n=48), 12.26±6.35 (n=35) and 19.63±13.07 U/g creatinine (n=25), respectively. Such a marked and stepwise increment of urinary NAG activity suggests that the enzyme may represent a useful indicator of early diabetic renal involvement.
2) No correlation was noted between urinary NAG activity and serum creatinine level.
3) A significant positive correlation was observed between urinary NAG activity and HbAI level (r=0.28, n=75, p<0.02). However, further investigations are required to evaluate the relation between the state of metabolic control and the urinary NAG activity, since insulin-dependent poor control patients were more common among diabetics with persistent proteinuria who formed the high urinary NAG activity group.

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Recently, it has been found that the HbAI level tends to be high in renal failure without diabetes. In the present study, we investigated whether HbAI could be used as an indicator of control in patients with renal failure as well as in diabetic patients.
The correlations between HbAI and BUN, or serum creatinine for a duration of 8 weeks prior to blood collection were investigated. The best correlation was found between HbAI and BUN, or serum creatinine also at 1 to 2 weeks before blood collection. It was found that a better correlation existed between HbAI and BUN (r=0.59, n=32, p<0.001) than between HbAI and serum creatinine (r=0.42, n=31, p<0.02) at 1 to 2 weeks before.
It appeared, therefore, that HbAI was produced by carbamylation of urea, and HbAI could be used as an indicator of the state of renal failure of 1 to 2 weeks before in patients with renal failure without impaired glucose tolerance.

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