Serum levels of total and free C-peptide immunoreactivity (CPR) as well as tota land free immunoreactive insulin (IRI) were determined in 28 insulin-treated diabetics before and after removing antibody bound human proinsulin-like components (PLC) and insulin during a 50 g oral glucose tolerance test (OGTT). The polyethylene glycol method for free CPR determination resulted in complete separation of antibody bound PLC and insulin from free forms of these peptides.
Fasting serum levels of free CPR and total CPR in 28 insulin-treated diabetics with circulating insulin antibodies were 1.5±0.9 and 3.6±4.4ng/ml, respectively (M±SD). The fasting serum level of free CPR was signi cantly lower than that of total CPR in these insulin-treated diabetics. The fasting serum level of total CPR in 16 healthy subjects was 2.0±0.4 ng/ml (M±SD) and this level was higher than the fasting serum level of free CPR (statistically significant) and was lower than that of total CPR in insulin-treated diabetics (statistically not significant).
Responses of almost the same magnitude of free CPR and free IRI to the oral glucose load were revealed in insulin-treated diabetics. Free and total CPR peaked at 120 min and free IRI peaked at 90 min after the oral glucose load. The free CPR and free IRI responses to glucose in insulin-treated subjects were significantly lower and more delayed than those seen in healthy subjects.
Percentage changes in the free CPR/total CPR ratio in 28 insulin-treated diabetics were 57.8 ±23.8%(fasting) reaching a maximum level of 72.8±26.0% at 90 min following glucose ingestion.
Positive correlation was observed between actual increments in free CPR and free IRI in insulin-treated diabetics after the glucose load.
Fasting sera of insulin-treated diabetics were extracted in acid-ethanol, gel-filtered and each fraction was assayed for its IRI and CPR. Elevated PLC concentrations were revealed invariably in elution diagrams of the sera obtained from 6 insulin-treated diabetics. The fasting serum level of total CPR was significantly higher in patients with higher serum concentration of PLC. Thus increased circulating PLC-insulin antibody complexes resulted in elevated total CPR levels in insulin-treated diabetics. And also the impairment in endogenous insulin secretion in insulintreated diabetics was suggested by the apparently diminished free CPR responses to glucose load in these subjects

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In order to examine a possible diabetic disturbance in the buffer mechanism in the liver for the caloric supply, different amounts of glucose (30 and 100g) were given orally and the plasma IRI, glucose, lactate, pyruvate, FFA, glycerol and the respiratory quotient were compared between healthy subjects and with diabetic subjects with categorized glucose intolerlance. In healthy subjects, the time course changes in these plasma levels except for IRI were not significantly different between the 30 g glucose loading test and 100 g glucose loading test, while an increase in IRI after 100 g glucose was markedly greater (P<0.01) than after 30 g glucose. These facts suggest that in healthy subjects the liver can buffer the fuel supply against varying amounts ingested.
In diabetic subjects, significanthy greater changes in plasma glucose were noted after 100g of glucose than after 30 g of glucose. Furthermore, the differences in the plasma glucose, lactate, pyruvate, FFA and glycerole levels between the 30g glucose test and 100g glucose test became quite apparent when the severity of diabetes mellitus was classified according to the fasting and post-glucose plasma glucose levels; i. e., the differences in the changes in these parameters between the two tests were much greater in the severe diabetics than in the less severe diabetics. These facts suggest that the liver of diabetics, in contrast to that in healthy subjects, cannot buffer the fuel supply against varying amounts ingested.

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The effect on blood sugar and endogeneous insulin secretion was studied in maturity-onset diabetic patients who had been treated with sulfonylureas for over eighteen months.
A 100g oral glucose tolerance test (OGTT) was given to thirty diabetic patients (twenty male and ten female) who had been on sulfonylureas (glibenclamide, acetohexamide, tolbutamide and others) before and one month after the discontinuation of treatment.
After discontinuation, the fasting blood sugar levels were found to be elevated in twentythree patients, and in OGTT bloodsugar and immunoreactive insulin (IRI) responses were impaired in twenty-five and twenty-three patients, respectively. It was shown that the changes after discontinuation had no relationship to the kind or dose of drugs.
To evaluate whether or not the control of blood sugar is dependent on sulfonylureas, the integrated blood sugar area (BS area) and IRI area were calculated. The BS area increased by more than twenty-five percent in eleven patients one month after discontinuation (highdependency group; HD group), and a marked decrease in IRI area was observed in ten patients of the HD group; one patient showed no change. Nineteen patients with less than twenty-five percent increase in BS area were designated as a low-dependency group (LD group).The IRI area after discontinuation was 73±6%(mean±SEM) of the previous value in theHD group and 85±5% in the LD group. The reduction of the ratio, IRI area/BS area, after the discontinuation of sulfonylureas was more remarkable in the HD group (from 0.126±0.017 to 0.062±0.009) than in the LD group (from 0.139±0.022 to 0.109±0.018). It was thus clearly demonstrated that the decrease in insulin secretion was more serious in the HD group, in which impairment of glucose tolerance was more marked, than in the LD group after the discontinuation of sulfonylureas.
We have therefore concluded that even after the long-term treatment with sulfonylureas for more than eighteen months, the acceleration of endogeneous insulin secretion is a major factor responsible for the control of blood sugar in maturity-onset diabetic patients.

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Cardiovascular disease represents the commonest cause of death in diabetic patients, especially congestive heart failure and myocardial infarction. The present study was designed to follow the development of left ventricular function in conjunction with diabetic controls, emphasizing the effect of sulfonylurea drugs (SU-drugs) on cardiac function.
Using the noninvasive method, the left ventricular systolic time interval was determined in 94 cases of diabetic patients (age range, 30 to 75 years) without other systemic heart disease. These patients were classified into three groups: a dietary cure group (D-G), a group treated with SU-drugs (SU-G), and a group receiving insulin injections (I-G).
The left ventricular ejection time (ET)/preejection period (PEP) ratio (ET/PEP) and corrected ET (ETc) were found to be significantly lower in I-G than in the other two groups. This result suggested that the insulin-treated patients may have some future possibility for the development of congestive heart failure.
Each of the three groups was subdivided into two further groups according to amount of fasting blood sugar (FBS): “A”, FBS≤140mg/dl; “B”, FBS>140 mg/dl. In group “A” of both D-G and I-G, ET/PEP was greater and ICT less than in group “B”. In D-G, there was a negative correlation between FBS and ET/PEP, and in I-G, a positive correlation between FBS and ICT. This suggested improvement of cardiac function by the diabetic controls.
In group “A” of SU-G, however, ET/PEP was significantly less (P<0.001) and ICT greater (P<0.02) than in group “B”. FBS was closely correlated with ET/PEP (r=0.5837, P<0.001) and ICT (r=-0.5287, P<0.01). Also in patients treated with SU-drugs for more than one year, a negative correlation between ET/PEP and period of medication was recognized (r=-0.5475, P<0.05).
In this group, therefore, cardiac function decreased with diabetic control.
A positive inotropic effect of SU-drugs was suggested since the results for ET/PEP, ETc and ICT in group “B” of SU-G were the same as those in group “A” of D-G.
Based on these findings, it appears that there was effective improvement of cardiac function in the first period of treatment with SU-drugs, but decreasing cardiac function was also recognized on longterm administration of SU-drugs.

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In spite of the widely recognized observation that atherosclerotic vascular lesions are frequently seen in diabetics, the nature of this correlation is poorly understood.
The purpose of the present study was to clarify the interrelationship between impaired glucose tolerance and atherosclerotic vascular lesions in aged subjects (over 60 years) by the use of analysis of variance.
The role of risk factors (age, sex, osteoporosis, Ht, serum triglyceride, total cholesterol, uric acid, fibrinogen, hypertension, and impaired glucose tolerance) in the development of atheroscle rotic lesions was analyzed by categorical regression analysis in approximately 200 subjects each with cerebral thrombosis, myocardial infarction, or calcification of the thoracic, abdominal aorta or femoral artery.
Impaired glucose tolerance was found to be intimately correlated with cerebral thrombosis, and calcification of the abdominal aorta and femoral artery, respectively. Attempts were then made to characterize the specific atherosclerotic vascular changes, if any, in the aged diabetics. Ninety-four aged subjects with diabetic glucose tolerance curves were subjected to categorical principal analysis to determine whether there were any vascular changes characteristic to aged diabetics. It was found that cerebral thrombosis and calcified femoral artery were characteristic, but not specific, to the diabetics. Furthermore, the analysis revealed that aged diabetics may be classified into 2 different clinical entities according to the pattern of vascular complications: DM1, which is free from the complications of cerebral thrombosis, but is usually accompanied by calcified femoral artery; and DM2, which is usually complicated by cerebral thrombosis, but is without calcified femoral artery.

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For several years diabetic screening among university students such as urinalysis and a glucose tolerance test has been commonly performed as well as a test for proteinuria. A study was made to summarize the incidence of glycosuria and abnormal glucose tolerance and to determine statistically the practical screening level for the oral 50 g glucose tolerance test (50 g GTT) among university students.
From 1971 through 1976 315 cases of glycosuria were detected out of 36, 408 Hiroshima University students and the 50 g GTT was carried out on 261students. Diabetic and borderline abnormalities were observed in 28 and 7 students, respectively.
The serum glucose content of 225 students was analysed by a graphic method using logarhythmic probability paper and by a computing method. The 97.5 and 84.0 percentile values and mean and standard deviation were obtained, and then screening levels were determined.
From the point of view of health administration, the critical serum glucose levels for diabetic screening among univesity students or young people recommended by this study were 100 mg/dl, 180 mg/dl and 125 mg/dl at the three time points of oral 50 g GTT, fasting, one hour and two hours after glucose loading, respectively.
These values were similar to the diagnostic criteria for diabetes with serum glucose suggested by the Japan Diabetic Society in 1970.

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Many methods have been developed for predicting standard weight from height. Broca, Jones, and others have provided equations for such prediction. In Japan, the modified equation of Broca's is the one generally used. However, as indicated by several investigators, this equation, while being simple, is at variance with reality.
We recently investigated the heights and weights of inhabitants of Yao, Japan, and compared the results with past data. Despite the fact that the general physique of the Japanese has recently improved, the average weight of young people of the same height remained un changed by generation and locality. We therefore conclude that standard weight is represented by the average weight of people of the same height in the age range from 20 to 39, and propose the following equation for its calculation:
Standard Weight (kg) = Height (cm)-50/2

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A 44-yr-old man was admitted to Kagoshima University Hospital in April, 1975, due to episodes of unconsciousness and irrational behavior in the early morning. A chest X-ray taken 15 years previously showed an abnormal round shadow at the middle base of the left lung. However, the patient had been active and well until 4 months prior to his admission when he experienced his first episode.
A chest X-ray on admission revealed a huge intrathoracic tumor, which occupied most of the space of the left thoracic cage. After admission, he developed frequent episodes of hypoglycemia. His blood sugar levels at the time of the attacks were below 50 mg/d/, reaching 15 mg/d/ at minimum, and his levels of serum IRI were also low (3-10μU/m/). Suppressed secretion of endogenous glucagon was also observed. Tolbutamide and leucine exerted no apparent effect on IRI release. Celiac arteriography revealed no abnormal findings. Based on these results, insulinoma was ruled out. Pituitary and adrenocortical functions were normal, as was liver function. The possibility of hypoglycemia resulting from the presence of the huge intrathoracic tumor was thus indicated. In June, 1975, extirpation of the tumor was successfully carried out, and was followed by a complete disappearance of the hypoglycemic attacks.
The tumor originated in the left interlobular pleura, weighed 3, 020 g, was lobulated and encapsulated with a smooth surface. Histological examination revealed fibrosarcoma of low grade malignancy. The contents of glycogen, lactate and IRI in the tumor tissue were not elevated. The levels of ILA in acid-ethanol extracts of the tumor tissue and serum were so low as to be virtually undetectable. The activities of glycolytic enzymes, especially those of the key enzymes, hexokinase and pyruvate kinase, were higher in the tumor tissue than in normalred blood cells.
Over-consumption of blood glucose by the tumor tissue thus appears to represent one of the most probable mechanisms of the hypoglycemia observed in the present case. However, there is no definite evidence to show that such over-consumption resulted from high activities of glycolytic enzymes in the tumor tissue. The suppressed secretion of endogenous glucagon also appears to be one of the possible contributory factors to the hypoglycemic attacks.

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The incidence and pathogenesis of type III hyperlipoproteinemia in diabetes mellitus are not known. A higher incidence of atherosclerotic vascular complications in type hyperlipoproteinemia and in diabetes mellitus has been reported. A case of diabetes mellitus having type II hyperlipoproteinemia, acute myocardial infarction and a history of cerebral infarction, is described here, and the relationships between diabetes mellitus, type la hyperlipoproteinemia and atherosclerotic vascular disease are discussed. The 55-yr-old male diabetic patient suffered cerebral infarction with r-hemiparesis and speech disturbance five years ago but recovered almost completely. He later complained of chest oppression and pain on Oct. 31, 1976. ECG showed a QS pattern and ST elevation in a V L, V₁ and V₂, ST depression in TI, 1ff and aVF, and negative T in V_{4, 5, 6}. He was diagnosed as having acute lateral and old anteroseptal myocardial infarction. Coronary angiography revealed marked atherosclerotic changes in all three main coronary arteries and their branches. Diabetes mellitus had been pointed out five years previously and the patient had received acetohexamide (500 mg/day) for a year. His blood glucose levels after 50 g glucose ingestion on Nov. 11, 1976 were 191 (0'), 295 (60') and 229 (120') mg/dl. His insulin responses to 50 g glucose ingestion, intravenous injection of tolbutamide (1 g) and glucagon (1 mg) were very weak. Eye fundus showed Scott 11 a and Scheie Si, H1 changes. Persistent proteinuria was found (0.51 g/day) and nodular diabetic glomerulosclerosis was observed in the kidney. However, no mesangial foam cells in the renal glomeruli, as reported by Amatruda, J.M., were noticed. Renal function was normal. The levels of plasma cholesterol and triglycerides on Nov. 16, 1976 were 318 and 441 mg/dl, respectively. Agarose gel electrophoresis showed floating β(broad β) lipoproteins. The values of cholesterol in VLDL (d<1.006 g/dl), VLDL cholesterol/VLDL triglycerides and VLDL cholesterol/plasma triglycerides were 107 mg/dl, O.38 and O.243, respectively. This abnormal lipoprotein pattern was considered to represent type III hyperlipoproteinemia, fulfilling the chemical indices of Vessby, Mishkel and Albers et al. The type III hyperlipoproteinemia changed to a type 11 a pattern after combined treatment by diet, clofibrate (2.0 g/day) and acetohexamide (250 mg/day). The hepatic and extrahepatic triglyceride lipase activities after intravenous injection of heparin (100 U/kg) were decreased to about half the activities of control subjects. All endocrinological tests including those of pituitary and thyroid function were normal. The patient had no xanthomas such as palmar, tendinous, tuberous, eruptive xanthomas or xanthelasma. No hepatosplenomegaly was observed. Stern. M.P. has described transient type hyperlipoproteinemia in a patient with diabetic ketoacidosis, but the present case is the first known report of transient type hyperlipoproteinemia associated with diabetes mellitus without ketoacidosis. It is considered that abnormal lipoprotein metabolism in the present diabetic patient may have played a significant etiological role in the development of atherosclerotic vascular disease.

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