We applied continuous intravenous insulin infusion (CIVII) and continuous subcutaneous insulin infusion (CSII) for control of blood glucose in 151 surgical cases of glucose intolerance during and after the operation; 123 diabetic subjects (DM group) and 28 borderline cases (B group).
As a rule, conventional insulin injection and administration of oral hypoglycemic agents were omitted on the morning of the operation. During surgery, intravenous fluid-infusion was started with glucose-free fluids, which was changed to glucose-containing fluids about three hours after the start of the operation. The blood glucose levels were measured every 30-60 minutes. CIVII was started when the blood glucose levels rose to over 200mg/dl, and was continued overnight postoperatively in most cases.
CIVII was changed to CSII in 40 cases who were placed on hyperalimentation therapy. When only glucose-free solution was infused during surgery, insulin infusion was needed to control blood glucose in only 22 percent of the DM group and 7 percent of the B group, and the insulin requirement of the former was about twice as high as that of the latter.
During surgery, infusion of glucose-containing solution was performed in about 20 percent of cases in the DM and B groups, and insulin infusion was needed to control the blood glucose levels in 84 and 50 per cent of these cases, respectively. Insulin infusion rate and intraoperative mean blood glucose levels were about the same in the two groups.
In cases receiving both CIVII and CSII, the mean levels of infused glucose per unit of insulin were 3.4g/u and 10.1g/u, respectively. This result suggests that the effectiveness of insulin is improved in the early postoperative period.
In conclusion, the present method in which glucose solution is not administered intraoperatively in minor surgery, and glucose infusion and CIVII are performed intraoperatively and then changed to CSII postoperatively in major surgery, is a better, easier and safer treatment than the other conventional methods.

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Adipose tissue oxygen consumption in obese mice was investigated in order to estimate whether or not change in this parameter influenced the appearance of the adaptation phenomenon.
Ob/ob male mice (thermogenic obesity) and high-fat-diet obese DD mice (regulatory obesity) were used as experimental animals.
Whole body oxygen consumption was estimated by measuring the reduction in gas volume in a closed chamber where a mouse was confined and expired bicarbonate was absorbed to soda lime. Results were expressed as volume of oxygen consumption per body weight. White and brown adipose tissue oxygen consumption was measured with a biological oxygen monitor.
In ob/ob male mice, not only the whole body oxygen consumption per body weight under cold exposure but also white and brown adipose tissue oxygen consumption were smaller than those in high-fat-diet DD mice. In both whole body and adipose tissues, the oxygen consumption of high-fat-diet DD mice was larger than that of DD mice feeding normally.
High-fat-diet DD mice even with restricted feeding for 2 weeks became equally obese compared with mice on unrestricted feeding. However, the oxygen consumption of white adipose tissue in mice on restricted feeding was less than that in the unrestricted ones. Under restricted food intake, it seemed that energy tended to be stored in white adipose tissue.
Since the amount of white adipose tissue as a whole is larger than that of brown adipose tissue, it is considered that changes of oxygen consumption in white adipose tissue may be related with the appearance of adaptation phenomenon.

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The influence of insulin on cardiac function was studied in 35 patients with old anterior myocardial infarction. RI angiocardiography was used to determine the global ejection fraction (GEF), infarcted regional ejection fraction (IEF), non-infarcted ejection fraction (NEF) and enddiastolic volume (EDV). The 75g oral glucose tolerance test (OGTT) was performed to obtainΣBS and ΣIRI.
The results were as follows: 1.ΣBS and ΣBS/ΣIRI had no significant correlation with GEF, NEF, IEF or EDV.
2.ΣIRI correlated well with GEF, NEF, IEF and EDV:
GEF=-41.4×(logΣIRI) ²+440.6×logΣIRI-1124.6 (p<0.01)
NEF=-42.5×(logΣIRI) ²+448.3×logΣIRI-1122.3 (p<0.01)
IEF=-33.4×(logΣIRI) ²+356.0×logΣIRI-914.2 (p<0.01)
EDV=89.3×(logΣIRI) ²-950.0×logΣIRI+2623 (p<0.01)
3. The highest value of GEF, NEF and IEF with the lowest value of EDV was observed whenΣIRIwas in the area of 200μU/ml.
These results suggest that insulin has a protective effect on the myocardium when insulin response to 75g OGTT is in the normal range.

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To assess the intrinsic insulin secretion in patients with diabetes mellitus, the degree of renalreabsorption of C-peptide was estimated by determining urinary C-peptide clearance/creatinine clearance ratio (CCPR/Ccr), and the corrected value of 24-hour urinary C-peptide excretion (24h-UCPR) by CCPR/Ccr was evaluated.
In 51 diabetic patients (DM) and 6 non-diabetic controls, Ccr and CCPR/Ccr were determined in the early morning after fasting. A couple of days before or after these determinations, 24h-UCPR was also measured, and 24h-UCPR/(CCPR/Ccr-10) was employed as the corrected value of 24h-UCPR (c-24h-UCPR). The value of CCPR/Ccr was 0.10±0.04 (mean±SD) in controls, whereas in DM it showed a wide range from 0.07 to 0.88 (0.27±0.16). CCPR/Ccr was correlated significantly with fasting plasma glucose (r=0.36, p<0.002), but not with HbA₁ (r=0.18) or urinary N-acetyl-β-D-glucosaminidase (r=0.29). In DM with Ccr<70ml/min or with proteinuria, the levels of CCPR/Ccr tended to be slightly higher than those in DM with normal renal function, but with no significant difference. 24h-UCPR values in controls and DM were 56.6±26.4 μg/day and 62.2±35.8μg/day, and c-24h-UCPR values were 58.2±28.1μg/day and 27.9±17.3μg/day, respectively. In DM with Ccr>70ml/min, c-24h-UCPR was correlated more significantly with integrated serum insulin or C-peptide concentrations, compared to 24h-UCPR, before and one and two hours after breakfast. The linear regressions of the increments of serum C-peptide concentrations after breakfast and c-24h-UCPR values were similar in both groups of DM with Ccr>70 ml/min and those with Ccr<70ml/min: in the former it was Y=5.0X+8.4 (r=0.82) and in the latter Y=4.7X+5.5 (r=0.74).
It was revealed that the value of CCPR/Ccr in DM was affected by hyperglycemia and renal dysfunction resulting in higher values, which indicated there was considerable intra-and interpatient variability in urinary C-peptide excretion rates. However, c-24h-UCPR was found to reflect the intrinsic insulin secretion over the whole day more faithfully than 24h-UCPR. Furthermore, c-24h-UCPR was considered valid even in DM with renal dysfunction.

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Platelets contain platelet-derived growth factor (PDGF) and other growth factors capable of stimulating proliferation of vascular smooth muscle cells (VSMC). Over-proliferation of VSMC mayplay an important role in the pathogenesis of atherosclerosis, the morbidity of which is higher in diabetic patients than in the non-diabetic population.
In this study, growth-promoting activity (GPA) in platelet supernatant (PS) from insulindependent diabetic (IDDM) patients was measured by a bioassay using cultured VSMC from rat aorta. An incorporaion rate of 3H-thymidine into DNA was measured and results were expressed as the percent value of GPA in 10% calf serum in incubation medium.
GPA in PS from poorly controled IDDM (HbA₁ 12.3±2.5%, M±SD) was 33.1±2.5% significantly higher (p<0.001) than that from normal controls (16.5±1.5%). Meanwhile six other IDDM (HbA₁ 9.9±1.6) patients treated with insulin in the conventional way wer changed to intensive insulin therapy, that is, continuous subcutaneous insulin infusion (CSII) and Pen infuser, in that order, for 3 months each. GPA in PS from these six patients was 38.2±14.4% during conventional treatment, and decreased to 19.2±9.2 and to 15.7±4.5% during CSII and Pen infuser, respectively.
These results suggest GPA in PS from IDDM is increased and that this abnormality might lead such patients to atherosclerotic diseases. With respect to the possibility of preventing diabetic vascular complications, it is also important that an increased GPA could be normalized by intensive insulin treatments.

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Type-I diabetes was subdivided into three subclasses from a pathogenetic point of view. In order to investigate the pathogenesis of Type-I diabetes in Japanese, 176 patients with Type-I childhood diabetes were studied for islet-cell antibodies (ICA), complement-fixing islet-cell antibodies (CF-ICA), thyroid-microsomal antibodies (MCHA) and antinuclear antibodies (ANA). These autoantibodies were followed in 35 patients with Type-I childhood diabetes for three years.
The incidences of ICA and CF-ICA during a period of less than one year from the onset of Type-I diabetes was 66.7% and 45.5%, respectisely, and were the highest. This frequency gradually decreased with duration. None with a duration of more than ten years from the onset had ICA or CF-ICA. Five patients were positive for ICA for three years; however, titers of ICA gradually decreased in four of the patients. There was a tendency for ICA to disappear by 4 or 5 years from onset and for CF-ICA to disappear more rapidly. In three patients with MCHA at the first examination, MCHA persisted for three years; however, ICA tended to disappear.
From these results, it may be suspected that ICA in patients with Type-I childhood diabetes disappears by 4 or 5 years from onset and that the proportion of Type-I diabetic patients classifiable into “subclass a” may be much smaller in Japanese than in Caucasians.

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A 67-year-old female case of insulinomas associated with extreme obseity (approximately 100% overweight) and typical fatty liver cirrhosis is reported. The obesity had developed gradually after an oophorectomy for a cyst of the right ovary at the age of 41. No history of alcoholism, hepatitis or blood transfusion was obtained. She visited our clinic for the first time in 1976 with the chief complaints of loss of consciousness and weakness in the early morning after overnight fasting.
During her hospital course it was confirmed that at each episode of unconsciousness the serum immuno-reactive insulin (IRI) was at a high level and there was also a constant elevation of Turner's amended score over 200μU/mg, sometimes reaching a value of over 2000μU/mg. Serum C-peptide concentrations were also markedly elevated, ranging from 4.2 to 9.5ng/ml after overnight fasting. Insulinoma was suspected but all diagnostic techniques such as CT scanning, sonography and selective arteriography failed to demonstrate the pancreatic tumor. The patient had bouts of transient gastrointestinal hemorrhage due to peptic ulcer, but serum gastrin level was normal.
In addition, clinical and laboratory findings compatible with liver cirrhosis, such as hepatosplenomegaly, elevation of serum enzymes, and retarded elimination of ICG (over 50% during 15 min) were noted. After 1981, the serum ammonia increased and flapping tremor appeared aside from the hypoglycemic attacks. She died of hepatic coma in January, 1984.
At autopsy, there were two insulinomas, one in the body and the other in the head of the pancreas, measuring about 12×10×10mm and 10×10×8mm, respectively. Beta granules were proved by Gomori's aldehyde-fuchsin method. The liver showed a picture of typical fatty cirrhosis.
In the present case, it is of great interest to assume that long-standing hyperinsulinemia would have led to the development of extreme obesity and fatty liver cirrhosis, through caloric over-intake in an attempt to relieve the hypoglycemic symptoms.

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A 47-year-old male patients was studied since his first admission due to diabetic ketoacidoticcoma at the age of 40. He achieved his first remission one month later as a result of intensive insulin treatment, such as the use of an artificial pancreas, CSII and multiple insulin injection.
During this 7-year follow-up period, he experienced another two exacerbations of diabetes mellitus. ICSA was found to have become positive on the second and third admissions, but ICA and other autoantibodies remained negative. Also, there were no significant changes in the titers of antibody to various viruses.
He again entered into his second and third remissions within a relatively shorter period, by intensive treatment with insulin. His ICSA was again found to be negative on both occasions.
There was no clinically apparent microangiopathy after 7 years, although he showed impaired glucose tolerance during each remission period as indicated in sequential OGTTs.
This is the first case report in the world, as far as we have investigated, of such a patient successfully introduced into third remission.

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A 39-year-old male diabetic patient associated with painful diabetic neuropathy was treated with carbamazepine (CBZ) at 400 mg daily for nine days, but obtained no pain relief with this medication. After withdrawal of CBZ, symptoms such as general malaise and anorexia rapidly developed. Laboratory examination revealed hyponatremia (118 mEq/L) and hyposmolarity (244 mOsm/L), and successive water restriction (500 ml/day) for nine days restored these abnormalities to normal levels (140 mEq/L, 290 mOsm/L). These findings led us to suspect the coexistence of the syndrome of inappropriate secretion of anti-diuretic hormone (SIADH) and prompted us to elucidate its cause.
Furthr physical and laboratory examinations did not show any endocrinological and neurological disorders, nor the presence of malignancy in respiratory and digestive organs.
Water loading test (20ml/kg orally) was performed twice at the eraly stage after development of hyponatremia and at the late stage of admission when serum Na and plasma osmolarity levels were almost within normal ranges. Total urine volume over 4 hours reached only to the level of 25% and 35% of the loaded water volume, respectively. The free water clearance failed to rise and plasma ADH response was not suppressed. In a hypertonic saline loading test (2.5% NaCl 650 ml intravenously), which was performed twice, plasma ADH level did not start to rise until plasma osmolarity reached the level of 310 mOsm/L. Moreover, there was no correlation between plasma ADH and plasma osmolarity levels (r=0.1493).
Re-administration of CBZ 400 mg daily for nine days failed to produce recurrence of hyponatremia even though the serum concentration of CBZ was kept within the level of 8.6-9.4μg/ml. However, serum Na level was found to be 129 mEq/L on the fourth day after stopping CBZ administration and persisted at a similar level for seven days. The direct induction of SIADH could not be attained by re-administration of CBZ. However, when the process of recognition of hyponatremia was taken into consideration, it might not be deniable that CBZ played any role in occurrence of SIADH.
These results showed that in this case, there was no integrity in the regulation of water metabolism through the neurohypophysial ADH system, which ascending stimuli reach via osmoreceptors, and volume and/or baroreceptors. The cause of this disorder might be related to diabetic autonomicdysfunction. Moreover, it might also be possible that CBZ administration was instrumental in disclosing this potential abnormality to develop SIADH.

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