The intravenous glucose tolerance tests were performed in two cases of hyperinsulinism (ectopic colonization of pancreatic β-cells and insulinoma of the pancreas head) at pre-, intraand postoperative periods. Their plasma glucose and immunoreactive insulin (IRI) values were compared with those in five control cases. Although the glucose tolerance curve and plasma IRI showed different patterns from those of the controls, insulin/glucose ratios were decreased during surgery in these patients, as well as in the control cases.
Serial determinations of plasma glucose and IRI during and after surgery revealed the following results: after the removal of the tumor, plasma IRI disappeared rapidly and plasma glucose concentration rose continuously.
Relatively rapid recovery of insulin secretion after surgery suggested that exogenous administration of insulin should be abandoned or limited to minimal dose, even in severe cases.

View full abstract

Changes in the carbohydrate tolerance of 26 pregnant diabetics had been investigated.
Of the 26 diabetics, 16 cases showed improved carbohydrate tolerance or decreasing insulin requirement throughout pregnancy. Most of those cases were class C, D and F patients according to the White classification. Their serum insulin levels were low even during pregnancy and their urinary estriol excretion was within the distribution of the controls.
Another 10 cases showed decreasing or unchanged carbohydrate tolerance or increasing insulin requirement during pregnancy. All of them were class A and B patients. Their serum insulin levels during pregnancy were significantly higher than the former and their estriol excretion was higher than in the former and the controls during the third trimester.
Estriol seemed to have an insulin antagonistic effect directly or indirectly.
Changes in the carbohydrate tolerance of pregnant diabetics was suggested to be due to the levels of insulin antagonists and not to the serum insulin level.

View full abstract

The following studies were performed in an attempt to investigate carbohydrate metabolism in patients with liver diseases, including 36 cases of cirrhosis, 39 of chronic hepatitis of active type, 31 of chronic hepatitis of inactive type, 19 of acute hepatitis. 2 of toxic hepatitis, 1 of fatty liver and 5 of obstructive jaundice by cancer. The diagnoses of those liver diseases were confirmed in 127 cases by hepatic biopsy, in 5 cases by laparatomy and in one case by autopsy. Glucose tolerance tests (GTT) (50gm of glucose orally) were performed to estimate blood sugar and IRI levels in venous blood of fasting patients as well as after 60, 120, 180 minutes of glucose loading.
Results were as follows:
1) The diabetic type and borderline type of GTT were frequently found in patients with cirrhosis (78%), chronic hepatitis of active type (62%), chronic hepatitis of inactive type (39%) and acute hepatitis (58%), with the diabetic type showing significantly higher frequency with cirrhosis than in other liver diseases.
2) Hyperinsulinemia (the hyper-response of the IRI secretion to glucose loading) was present in all the patients with a liver disease, and most remarkably among those with cirrhosis, especially with the obese subjects.
3) An oxyhyperglycemic pattern in GTT was often found in cirrhosis and chronic hepatitis. while in acute hepatitis delayed pattern was observed.
4)ΔIRI/ΔBS at 60 minutes was 1.06 in the case of cirrhosis, 1.43 in that of chronic hepa. titis of activ.: type, 1.38 in that of chronic hepatitis of inactive type and 1.14 in that of acute hepatitis. Each of these reveals a greater numerical value than in the case of normal subjects, which was 0.87.
5) There was a marked correlation between the degree of impairment of GTT and liver function tests. Significant relation was detected in ZTT, γ-globulin or A/G values. And TTT t-cholesterol. GOT. GPT also proved to be worse as carbohydrate metabolism grew ingravescent.
6) In patients with severe jaundice (icterus index more than 100) regardless of the causes, nine of eleven showed impaired GTT (diabetic and borderline type) and the mean value of ΔRI/ΔBS was 0.65 at 60 minutes. In those with obstructive jaundice by cancer, the value was 0.48, which was lower than those with the cirrhosis and hepatitis (0.79).
7) In 29 patients, GTT was performed twice for three and a half months on average, in the course of hospitalization. Liver function tended to parallel GTT. Improvement was more often observed with acute hepatitis and toxic hepatitis than with other cases, and improvement of the liver function was generally seen to be a little earlier than that of GTT. The ratios of improvement were 69% in liver function and 52% in GTT.

View full abstract

As judged by hypoglycemic and immunological responses, insulin can be absorbed from the intestine in a biologically and immunologically active form. To enhance intestinal absorption of insulin, we have prepared an insulin derivative, β-naphthyl-azo-polystyrene insulin (β-NAS-I), which is not affected by digestive enzymes. In this preparation, the insulin was bound physically to diazopolystyrene quenched with β-naphthol. In the present experiments, changes in blood glucose and serum insulin levels in response to enteral administration of β-NAS-1 have been studied in rabbits.
1) When insulin suspension at a dose of 150U/kg was infused to the upper jejunum via an indwelling catherer, the mean serum insulin rose slightry to peak at 38μU/m/, followed by a slight fall in blood glucose. When β-NAS-1 was infused, on the other hand, a marked decrease in blood glucose, with a maximum decrease of 45% with 100U/kg and 65% with 150U/kg, was observed and the blood glucose remained low for the three hour experimental period. There was also a considerable increase in serum insulin concentrations. With doses of 100 and 150U/kg of β-NAS-I, the serum insulin increased to the peak of 71 and 99μU/ml, respectively.
2) Infusion of the insulin suspension, up to 150U/kg into the stomach, failed to produce a significant hypoglycemic response. A significant depression of the blood glucose was noted with doses of 100 and 150U/kg of & -NAS-I, when administered into the stomach. With doses of 100 and 150U/kg of & -NAS-I, insulin increased from the basal level of 10 to the peak of 25 and 40μU/m/, respectively.
Present experiments indicate the possible use of insulin adsorbed physically on & -NAS particles for oral administration of insulin. Oral administration, as well as jejunal administration of & -NAS-I to rabbits, resulted in a hypoglycemic response, possibly by protecting the insulin molecule from digestive destruction.

View full abstract

Weight reduction has been k nown to be effective in ameliorating glucose intolerance and elevated serum lipids in obese diabetics. However, uncertainty is still present concerning the change in fatty acid composition of serum lipids and the adipose tissue of diabetics during a weight reducing regimen.
This experiment was conducted on 5 mildly obese and 5 non-obese diabetics. The two groups of patients were placed on a total calorie diet of 25Cal per kg of their ideal body weight, corn. prising 20% protein, 28% fat and 52% carbohydrate. The patients did not received various types of insulin or oral hypoglycemic agents. Serum lipid levels, the fatty acid composition of adipose tissue and serum lipids, and the response of glucose, IRI and free fatty acids, to 100 g oral glucose tolerance tests were determined before and after treatment and the results corn pared between and within the two groups.
In the obese group, mean fasting blood sugar (FBS) decreased from 114mg% to 96mg%, mean serum cholesterol from 238mg% to 195mg%, and mean serum triglyceride (TG) from 124mg% to 65mg% and mean body weight decreased 13% from their initial body weight after dietary treatment. In the non-obese group, mean FBS decreased from 135mg% to 100mg%. but serum lipid level and body weight remained unchanged 3 months after dietary treatment.
There was a delay in the fall of FFA during GTT in both groups before treatment, and an improvemet of a delay in the obese group was obeserved after treatment. IRI response during GTT was improved after treatment in both groups.
In the obese group, palmitic acid of adipose tissue and linoleic acid of serum TG and cholesterol-ester fractions increased slightly, but the changes were not significant after dietary treatment. In the non-obese group, there was no remarkable changes of fatty acid composition after treatment.
These results indicate that the serum lipids tended to be esterified with linoleic acid which was abundant in obese diabetic adipose tissue after weight reduction and that high TG and cholesterol levels before treatment in obese diabetics were derived from overproduction of TG and cholesterol respectively.

View full abstract

The present study was carried out to see the life patterns of diabetic patients with more than three years duration of the disease. A questionnaire was sent to the patients by mail and the response was 64 per cent. The analysis contained 1022 cases.
Cases with a better prognosis, i.e., those working uneventfully, feeling fit, or not bed-ridden because of illness, were most frequently cases whose diabetes was discovered in their thirties and forties. On the contrary, cases with a worse prognosis, i.e., cases who were bed-ridden or who could not work for almost a year, were frequently in the cases whose diabetes was dia. gnosed in their twenties or younger. The longer duration of the disease, the more frequent the cases were who could not work, who had many symptoms suggesting the presence of chronic diabetic complications, or who were not feeling fit. The cases treated only with a diet regimen. had a relatively better prognosis and the cases receiving insulin injection had a worse prognosis This study revealed that the prognosis of the patient was quite different according to whether the disease occurred before or after 30 years of age.

View full abstract

Serum lipids, postheparin triacylglycerol lipase (PHTGL) and postheparin monoacylglycerol hydrolase (PHMGH) activities in rats with streptozotocin-induced diabetes (80mg/kg) were measured. Release of triacylglycerol lipase and n.cncacy: E, cerol 1.yc: Iclase in vArc frcrn slices of liver and adipose tissue in these rats were also measured.
Following results were obtained:
1) Serum triacylglycerol and free fatty acid (FFA) levels were significanty higher in the diabetic than the control rats. However, serum phospholipid and cholesterol levels were not significantly different between these two groups.
2) PHTGL and PHMGH activities were significantly lower in the diabetic than the control rats.
3) In vitro release of triacylglycerol lipase from the adipose tissue in diabetic rats was significantly smaller than in the control rats.
4) In vitro release of monoaylglycerol hydrolase from the liver was markedly decreased in diabetic rats.
5) The increase in serum triacylglycerol (TG) and FFA and the decrease in PHTGL and PH MGH activities in the diabetic rats were significantly inhibited by the administration of insulin.
These results suggest that the increase of the serum TG in diabetic rats was caused the reduced PHTGL activity of the adipose tissue probably due to the insulin deficiency.

View full abstract

Bone destruction secondary to soft-tissue necrosis are occasionally observed in the gangrenous toe of diabetics. Recently, diabetic osteopathy of the feet has been frequently reported in patients with severe neuropathy.
This paper presents five cases of bone destruction in the lower extremities of diabetics with gangrenous necrosis complicated by infection or without cutaneous lesions. Most of the cases have diabetes mellitus with poor control and a long-duration of over 10 years, complicated by severe peripheral neuropathy and retinopathy, except for one case. Clinical if anifestations in the feet were skin ulceration associated with infection or swelling with slight pain, redness and fever. Bone changes on X-ray consist of destruction secondary to osteomyelitis or to softtissue necrosis and osteopathy observed in pharanges, metatarsals and partly in tarsal bones in cases without cutaneous lesions. Osteolysis observed in osteopathy was also detected in different parts of necrotic lesions in a patient with gangrene. Follow-up studies revealed that a part of the bone lesions in osteomyelitis and diabetic osteopathy showed proliferative changes. Autopsy findings in a case with extensive gangrene showed the kidney abscess and the bone changes, char'cterized by atrophy of the osseous trabeculae and edematous fibrous stroma with a few osteoblast type giant cells and no cell infiltration.
The nature, pathogenesis and differentiation of these bone changes of the lower extremity in patients with diabetes mellitus were discussed together with a review of the literatures concerning diabetic osteopathy, including the diabetic Charcot's joint.

View full abstract

The purpose of this paper is to clarify the special clinical features of diabetic retinopathy with juvenile-onset diabetes in Japan.
The fundi of 96 cases with diabetes mellitus who acquired diabetes prior to 20 years of age were examined ophthalmoscopically and diabetic retinopathy was found in 35 cases (37%). The youngest patient with diabetic retinopathy was four years of age, and the average age was over 16 years when diabetic retinopathy was first observed in 71 per cent of all cases. The shortest duration of known diabetes when diabetic retinopathy was first observed was wthin a year. Sixty percent of thecasesexhibiteddiabetic retinopathy after a duration of between 6 and 9 years. Among the 17cases whose diabetic conditions had been observed five years ago, diabetic retinopathy was found in 35 per cent. Among the 20 cases whose diabetic conditions were noted ten years ago, diabetic retinopathy was found in 55 per cent. There were only 5 cases whose diabetes mellitus had been found 20 years ago and 3 (60 per cent) of them had diabetic retinopathy. In these cases, proliferative diabetic retinopathy was observed in 10 cases (10 per cent). The youngest patient with proliferative diabetic retinopathy was 19 years of age and the shortest duration of diabetes when proliferative diabetic retinopathy was first observed was 3 years. Among these cases, complications of diabetic retinopathy was correlated with the worsening of blood sugar level control. In the proliferative diabetic retinopathy complicated by the juvenile-onset diabetes, the same rule was observed, i.e., proliferative diabetic retinopathy was found in 17 per cent of the cases which were in the group with poor blood sugar level control.
The examination of fluorescence angiography carried out on 34 cases who were below 20 years of age, revealed pathological findings in 31 cases. The extravasation of fluorescein from the capillaries and microaneurysms, the tissue staining of the retina by fluorescein, the occluded part of the vascular bed or the avascular space of retina and the fluorescence dots of retina which appeared to be mostly microaneurysms were found, but the extravasation of fluorescein which came from the broad vessels and the wide avascular space of retina which were observed frequently in adult-onset diabetes was not found in their fundi.
It may be concluded, therefore, that diabetic retinopathy with juvenile-onset diabetes was first observed among patients over 16 years of age and with over 6 years of diabetic duration, proliferative diabetic retinopathy was first found in patients over 20 years of age. Serious pathological findings of the fluorescence angiography were not observed prior to 20 years ofage.

View full abstract

This is a clinical description of a 35-year-old male, non-obese diabetic, who developed generalized edema including clinical manifestations of cardiac failure, following the institution of insulin therapy.
The patient had been treated with glibenclamide (10 mg/day) but his fasting blood sugar remained as high as 235 mg/dl on admission. He showed slight dehydration but there were no findings of ketoacidosis.
The oral hypoglycemic agent was switched to actrapid insulin soon after admission. On the third day of insulin therapy, however, weight gain and pitting edema in the lower extremities began to develop, along with rapid improvement of abnormal carbohydrate metabolism. On the seventh day, generalized edema with orthopnea developed. The chest X-ray revealed manifestation of congestive heart failure, with cardiac enlargement and pleural effusion. The administration of furosemide and reduction of the insulin dosage produced a prompt amelioration of edema as well as cardiac failure. Throughout the course, no signs of the impaired renal function were demonstrated.
“Insulin edema”, which has been described in some textbooks, is fairly unusual condtion and a development of “anasarca” accompanied by cardiac failure is considered to be exetremely rare.
Pathogenesis of “insulin edema” has not been clearly understood. Some authors pointed out the presence of a close relationship between carbohydrate intake and Na retention, and others suggested that changes of the osmolarity between the tissue and the extracellular space following changes in the blood glucose levels play a significant role in the development of “insulin edema”. In our case, however, we could not demonstrate any causative factors for the generalized edema with the laboratory examinations except for slight hypoalbuminemia on admission.
It is finally emphasized that not only “insulin edema” but also congestive heart failure might be provoked by the rapid diabetic treatment, as shown in this patient.

View full abstract