The concentrations of HbAi and red-cell 2, 3 DPG were determined in 91 newly discovered and/or untreated diabetic subjects who were divided into 3 groups: 80 diabetics without ketonuria (group 1), 6 with ketonuria but without acidosis (group 2), and 5 with ketoacidosis (group 3). The results were compared with those obtained for a group of non-diabetic control subjects.
The HbAI level in group 1 was significantly higher than that in the controls (12.1 ± 2.8% versus 6.2± 0.7%, Mean ± SD, p<0.01). Group 2 and group 3 also showed very much higher levels than the control subjects (group 2: 16.6± 2.2%, group 3: 18.1 ± 1.9%).
The red-cell 2, 3 DPG concentration was significantly increased in group 1 as compared to the control group (4.45 ± 0.81 μmol/m/ RBC versus 4.10 ± 0.39 pmol/ml RBC, p<0.05), and was even higher in group 2 (4.62 ± 0.39 pmol/ml RBC). In the ketoacidotic diabetics (group 3), the average 2, 3 DPG concentration was markedly decreased (2.24± 0.91 μmol/ ml RBC).
A high and significant correlation existed between the red-cell 2, 3 DPG and pH in the patiets with ketonuria (n =11, r =0.92, p<0.001).
Two of five patients with ketoacidosis were treated by continuous intravenous infusion of insulin, and this treatment was changed to subcutaneous administration when the blood glucose decreased appropriately.
The levels of HbAI decreased partially during insulin infusion. On the other hand, the redcell 2, 3 DPG concentrations decreased at 1 or 2 hr after the initial administration of insulin, and subsequently increased gradually.

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The present study concerns the role of cAMP and ⁴⁵Ca²⁺ uptake in the decreased glucose induced insulin release from 14-day cultured islets maintained in 5.5 mM glucose (A-islets), 5.5 mM glucose containing 1 mM adenosine (B-islets) and 16.7 mM glucose (C-islets), and the recovery effect of adenosine on insulin release in B-islets.
Insulin secretion, cAMP release, cAMP content and ⁴⁵Ca²⁺ uptake were observed in freshly isolated islets (F-islets) and the cultured islets incubated for 5 to 30 min in 3.3 or 16.7 mM glucose media with or without ⁴⁵Ca²⁺ (5 μCi/ml).
The results obtained on short incubation with 16.7 mM glucose may be summarized as follows.
(1) Insulin secretion was adequately preserved in B-and C-islets, but decreased to about onethird that in F-islets.
(2) B-islets showed a rapid, strong ⁴⁵Ca²⁺ uptake of 1.64±0.25, 6.21±0.35 and 7.79±0.44 pmol/islet at 5, 15 and 30 min, respectively, as did C-and F-islets. On the other hand, the ⁴⁵Ca²⁺ uptake in A-islets was remarkably low compared to the other islets throughout all the incubation periods.
(3) None of the cultured islets revealed any enhancement of cAMP content, but F-islets indicated a maximum amount of cAMP at 15 min and maintained the same level until 30 min.
(4) All the cultured islets released cAMP at about 35 fmol/islet, which was not significantly different from that on incubation with 3.3 mM glucose, for the first 5 min and the B-and C-islets continued to release cAMP gradually until 30 min. On the other hand, F-islets secreted a significant amount of cAMP over the same periods.
(5) There were no differences among the B-, C-and F-islets in the sum total of the cAMP content and the release in each incubation period, but the sum total for A-islets was significantly low compared to that in each of the other islets.
The above findings suggest that addition of adenosine may be effective in improving the decreased insulin secretion and ⁴⁵Ca²⁺ uptake which occurred in A-islets, and that as well as failure in increase in cAMP content, certain other disturbances in the insulin release-cAMP system may account for the impaired insulin response to glucose in cultured islets.

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Several reports have indicated that a form of hyperglucagonemia, which reacts with antibody specific to pancreatic glucagon, occurs in pancreatectomized and eviscerated rats. The kidney is suspected to be one of the sites of origin of glucagon other than the pancreas and gastrointestinal tract.
To detect whether the kidney releases glucagon, rat kidneys were perfused in vitro with 20 mM arginine or 10 ng and 100 ng isoproterenol, which are sufficient to release glucagon from perfused rat pancreas. The perfusates were assayed for glucagon using 30 K, but no increase of glucagon was detected.
It was also found impossible to extract glucagon from the rat kidney tissue.

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In order to assess the effects of continuous subcutaneous insulin infusion (CSII) on the control of plasma glucose and on the plasma levels of other metabolites in diabetes mellitus, a portable, battery-driven infusion pump was used for 4 days in 6 insulin dependent diabetic patients (including one depancreatized, one brittle type and one with pregnancy in the 3rd trimester). The pump can deliver undiluted regular insulin at 32 speeds ranging from 1 μl/hr to 29.6 μl/hr, leaving wide choice for a given basal infusion rate. Manual operation of the pump is also possible for a bolus infusion of prescribed units before meals. In this study a bolus infusion with appropriate dosage was added before each meal in every patient.
The mean 24-hr plasma glucose level (± S.D.) of 123±28 mg/dl on CSII treatment was significantly smaller than the level of 180 ± 22 mg/dl on conventional treatment although a smaller dosage of insulin was required in the former. The M value was also significantly improved from 73± 23 to 28±9 by CSII treatment. In 3 patients whose diabetic controls were very difficult, the 24-hr plasma glucose profile and M value were almost normalized by CSII treatment with a lower frequency of hypoglycemic episodes.
The 24-hr plasma NEFA profile tended to be normalized by CSII treatment. Fasting blood ketone bodies also showed a tendency to decline towards normal levels (beta-OH butyrate: from 150± 152 μM to 85±36 μM, acetoacetate: from 66 ± 54 μM to 44±16 μM). The serum cholesterol, triglyceride and p-lipoprotein levels remained unchanged after CSII treatment. The blood alanine, pyruvate, lactate, and erythrocyte 2, 3-diphosphoglycerate concentrations were unchanged from those on conventional treatment.
In one patient possessing no insulin antibody, the 24-hr plasma IRI profile was determined, It revealed a lower level than that on conventional treatment. This may reflect a decrease in exogenous insulin used and a slightly reduced secretion of endogenous insulin (estimated from the plasma CPR profile) compared with those in conventional treatment. Even in this case, the plasma glucose control was improved by CSII treatment.
In conclusion, our easily usable CSII treatment is considered to be very effective from improving glucose metabolism in insulin dependent diabetics, especially unstable ones. It thus provides a promising means for long-term routine therapy in insulin dependent diabetics to prevent diabetic complications.

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Although it has been said that ischemic heart disease as cause of death is increasing among Japanese diabetics with the changing dietary habits of the Japanese people, there are few prospective studies dealing with the causes of death of Japanese diabetics visiting diabetes clinics. To assess the increase in ischemic heart disease as a cause of death in Japanese diabetics, we undertook a prospective follow-up study of 1, 629 diabetic patients (898 males, 731 females) who had visited our Diabetes Center in 1976. In the present paper, we describe the results of a two-year follow-up study, especially regarding the underlying causes of death in Japanese diabetics.
During this follow-up study, only one case dropped out within two years from the start. The deaths of 70 cases (52 males, 18 females) among the 1, 629 were confirmed at the end of the twoyear follow-up. We obtained death certificates for all the 70 deceased patients and decided the underlying causes of death according to the eighth revision of ICD.
The main underlying causes of death in the present study were malignant neoplasms (21), ischemic heart disease (17), diabetes mellitus (11), cerebrovascular disease (7) and other causes (14). The increase in rate of malignant neoplasms and ischemic heart disease as underlying causes of death among Japanese diabetics was confirmed.
Analysis by comparison of the observed number of deaths with that expected for the sex-and agespecific rates of the general population over the same period of time, showed a significant excess in deaths from diabetes mellitus and ischemic heart disease in the patients of the study sample. Although 0.8 deaths attributable to diabetes mellitus were expected among the patients of the study sample, 11 deaths actually occurred: 3.8 deaths from ischemic heart disease were expected, whereas 17 actually occurred. No significant differences between observed and expected numbers of death were found for malignant neoplasms, cerebrovascular disease and other causes of death.
Many deceased cases from ischemic heart disease were found in the group whose death was onfirmed from copies of the residence or census register. Autopsy was performed in only 24.3% of the deceased cases, and 74.3% of the 70 deceased cases died at hospitals. Mention of the diagnosis of diabetes mellitus was found in only 38.6% of the death certificates of the deceased diabetics.

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Twenty-five cases of diabetes with non-clostridial gas gangrene have been reported since 1893. In the present report, we describe two cases of diabetes with non-clostridial gas-producing infec tions. Both cases died, and the severity of these infections is emphasized. The clinical findings are discussed.
Case 1, a 45-year-old man, had been controlled on oral agents for 4 years. One day a fish bone became stuck in his anal region. He developed an egg-sized induration and redness in the left perianal region. Antibiotics and insulin were given. However, 10 days later, an ulcer was present with subcutaneous emphysema in the left perianal region. The subcutaneous emphysema extended to the scrotum, bilateral inguinal region, left abdomen, and left breast. He rapidly deteriorated, and died on the 11th hospital day. Aerobic and anaerobic cultures of specimens of pus obtained from the left perianal gangrenous tissue yielded a growth of E. coli. Clostridia were not isolated.
Case 2, a 41-year-old man, had suffered from thirst and emaciation for one year. One day some cutting pliers dropped and injured his right foot. Ten days later he developed fever and pain in the right foot. In spite of treatment with antibiotics and insulin, high fever continued. The right foot became swollen, and subcutaneous emphysema was palpable beneath the inflamed area, but there was no ulcer. Aerobic and anaerobic cultures from the foot, CSF, and blood yielded Klebsiella. Clostridia were not isolated. The patient died on the 8th hospital day.
It is important to distinguish between clostridial infections and non-clostridial infections. Differentiation is effected primarily on clinical grounds, but it may be helpful to undertake bacteriological and radiological examinations. The mortality rate from these infections is high. Multiple incisions and debriedments to free the tissues of gas and pus, and administration of antibiotics are the treatments of choice. However, the condition of these infectios can be such that prompt and extensive surgical treatment appears necessary.

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In a 28-yr-old woman with idiopathic hypoparathyroidism, the insulin and glucagon responses to an oral glucose tolerance test (O-GTT), intravenous glucose tolerance test (IV-GTT) and arginine tolerance test (ATT) were studied before (serum calcium concentration: 3.4 mEq/l) and after treatment (serum calcium concentration: 4.6 mEq/l).
In the case of O-GTT, impaired glucose tolerance was apparent before treatment, but a normal blood sugar response and improved insulin secretion were observed after treatment. In IV-GTT, the blood glucose and insulin responses were similar before and after treatment. Glucagon suppression in O-GTT and IV-GTT revealed a similar pattern before and after treatment. In ATT, decreased insulin release and increased glucagon secretion were observed before treatment, but they were normalized after treatment.
These results suggest that insulin releases to glucose and arginine are dependent on the serum calcium concentration, but glucagon secretion may be independent of serum calcium concentration in idiopathic hypoparathyroidism.

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