The purpose of this study is to clarify the role of pancreatic and gut glucagon in diabetic ketoacidosis through treatment with continuous insulin infusion for diabetic ketoacidosis.
Five diabetic ketoacidosis patients and one case of non-ketotic hyperosmolar coma were treated with continuous insulin infusion (CII) using regular or actrapid insulin (5 U/hr-10 U/hr). During the infusion period, blood glucose, plasma insulin (IRI), pancreatic glucagon (GI) and gut glucagon (GLI) levels were measured.
Although blood glucose levels upon admission showed 333 mg/100 ml-1, 045 mg/100 ml, by CII treatment (the mean decreasing rate of blood glucose was 49.7 mg/100 ml/hr-105.0 mg/100 ml/hr), blood glucose levels reached normal values and ketone bodies in the urine disappeared.
The range of plasma glucagon upon admission was 87.8 pg/ml-660 pg/m/ and plasma gut GLI was 20 pg/ml-1, 300 pg/ml. The high levels of GI and GLI upon admission gradually decreased during the CII period. However, the relatively low levels of plasma GI and GLI were not affected. Plasma IRI concentrations at two hours after CII wre 53.6 μU/ml-291.1 μU/ml, and this concentration of serum insulin seemed to be enough to improve hyperglycemia. These results indicated that CII was an effective treatment for diabetic ketoacidosis and without distinction of plasma GI or GLI, ketone bodies in the urine of all patients disappeared after insulin infusion.
These results suggest that the main cause of ketoacidosis is not due to glucagon, but to insulin deficiency. The role of GI and gut GLI in causing diabetic ketoacidosis is not fully understood. Thus, further study is needed.

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It cannot be said that between two characters a specific relationship exists between linkage disequilibrium and linkage and between linkage equilibrium and linkage. In particular, the presence of a correlationship between two characters and the presence of linkage between two characters should not be confused.
The authors reported previously (1982) that in estimating the coefficient of linkage disequilibrium between juvenile onset type diabetes mellitus (IDDM) and HLA-Bw 54, DYT, and DRw 4 a statistically significant level could not be reached. In the present study, using the same data the authors estimated the recombination value (θ) by the method of Hastings (1981). The results all showed the relationship of θ>0.5. As far as these data are concerned, a tendency was observed for the locus governing IDDM to exist at sites other than chromosome 6, which governs HLA.
However, it cannot be said that the method of Hastings employed in the present study is faultless. It may be that this method is not very effective when the coefficient of linkage disequilibrium is small. At any rate, further study is required.

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With the purpose of performing a genetic analysis on the interaction between the genotype responsible for fasting blood sugar (FBS) value and environment, the data of Kitazawa et al. (1979) were used to estimate mean FBS, variance, distribution of minimum and maximum values and +gene frequency responsible for FBS by age and year.
Regression analysis of these estimated values by aging and year was performed, and the following was found. (1) The regression coefficients by aging that were statistically significant were mean value and variance. In this case, a trend for linear regression is shown. Hardly any significant relationship could be found in the distribution of minimum and maximum value and +gene frequency. However, of these distributions, the observed maximum value showed a significant difference from the expected value and this is not compatible with the linear or quadratic regression. However, the values showed a trend to increase with age. (2) Of the regression coefficients by year, those that reached a statistically significant level were the mean value and variance in only the 40-to-49-year age group. The maximum value of variance and distribution showed poor correlation with the regression coefficients. Further, in hardly any did the +gene frequency reach a significant level.
In view of the above-mentioned series of trends, the increase in the hyperglycemic group due to aging and changes with year was already expected to occur in accordance with the increase of gene effects caused by aging and changes with year on the basis of the model reported by Furusho (1982). However, it is difficult to estimate the effects of aging by year alone from the results of this study. The reason for this is that changes in life-style after the termination of World War IIwere remarkable. For example, as the living environment of those in their 20s and those in their lOs differ greatly, the effects of the environment are included in the effects of aging. A model to analyze this point was also devised, but as there are not any data available at present for such an analysis, it will have to be deferred as problem for the future.

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To elucidate the effects of dietary fat saturation levels on serum cholesterol and apoprotein A-I (ApoA-I) in humans with impaired glucose tolerance (IGT), six healthy controls and four subjects with IGT participated in this study. Three diets were designed for each subject. The polyunsaturated/ saturated fat ratio was 1.00 in study 1 (diet R), 3.10 in study II (diet P) and 0.25 in study III (diet S). Diet R was given for the first two weeks, diet P for the second two weeks and diet S for the third two weeks. Overnight fasting venous blood samples were collected at the end of each period. Changes in body weight were controlled to within ±0.3 kg during the study.
In the subjects with IGT, both total cholesterol and LDL-cholesterol levels were lower in study II than in study I and higher in study III than in study II. The alterations of these levels in the healthy controls were similar to those of the subjects with IGT. Although HDL-cholesterol levels did not change in the healthy controls, those of the subjects with IGT decreased in study II from the levels in study I and no changes were seen between those of study II and III. ApoA-I levels increased only in study III from the levels in study II and I in healthy controls, However, there were no changes in the subjects with IGT throughout the study.
The response of total cholesterol and LDL-cholesterol to the changes of dietary fat saturation was rapid while the response of HDL-cholesterol and ApoA-I was slow. Therefore, in humans with both IGT and hypercholesterolemia. A high P/S diet should be maintained continuously.

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The variation in heart rate during deep breathing (JHR) was measured in 57 diabetic patients (7 insulin-dependent and 50 non insulin-dependent) and was evaluated as an index of autonomic neuropathy of diabetes. The value of ZIHR was consistently higher than 10 beats/min in all 78 nondiabetic controls and it was significantly correlated inversely with age. In diabetic patients, however, it was not correlated with age.Δ HR of less than 10 beats/min (low JHR) was observed in 41% of the patients with diabetes of less than 5 years duration and its frequency was higher than that of other diabetic complications; retinopathy (14 %), proteinuria (18 %), absent Achilles tendon reflex (22 %), and decreased vibratory sense (22 %). The incidence of patients with low JHR was 71 % in the group with diabetes of longer duration and was still higher than that any other complication. These results suggest that this abnormality can occur earlier than other diabetic complications and is a common finding in diabetic patients.
Decrease in systolic blood pressure in the orthostatic position and ΔHR were studied in selected cases. A significant negative correlation was observed between them and there weresome patients with low ΔHR without significant fall in blood pressure after standing. The decrease in ΔHR was found to precede orthostatic hypotension.
These results suggest that autonomic neuropathy is an early and common subclinical diabetic complication and the measurement of IFIR iq a noninvasive and useful method for its evaluation.

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The effect of 1α-hydroxyvitamin D₃ (1αOHD₃), a synthetic analog of 1α, 25 dihydroxyvitamin D3, on insulin secretion was investigated in rats in vivo and in vitro.
In the perfusion study of isolated rat pancreas, the addition of 1αOHD₃ (10 ng/ml) in the absence or presence of bovine parathyroid hormone (1 ng/ml) had no effect on insulin release. The in vivo injection of 1αOHD₃ (250 ng) did not directly influence blood sugar and serum insulin responses, and the blood sugar response and serum insulin secretion in the intravenous glucose tolerance test was not changed by the previous administration of 1αOHD₃.
These results indicate that 1αOHD₃ has no acute effect on blood sugar and insulin responses in rats in vivo and in vitro.

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To determine the factors that may contribute to the development of hypertriglyceridemia, we measured insulin binding to erythrocytes and postheparin plasma lipase activities in obese children and investigated whether these and other parameters were related with the serum triglyceride level. Insulin receptor binding to erythrocytes was assayed according to the method described by Gambhir et al. Activities of postheparin plasma lipoprotein lipase (LPL) and hepatic triglyceride lipase (HT GL) were measured by an immunochemical method utilizing an antiserum raised against HTGL. Postheparin plasma was obtained five minutes after administration of heparin at a dosage of 10 unit/ kg body weight or at a corrected dose that was calculated to compensate for the disproportion between body mass and plasma volume in obesity. Thirty-five obese children without fasting hyperglycemia (24 males and 11 females; ages ranging from five to 16 years) were studied. Thirty non-obese children served as controls for the serum lipid levels and two lipase activities.
Hypertriglyceridemia was common (57%) in obese children. Insulin binding to erythrocytes was inversely correlated with the logarithmic values of fasting serum insulin concentration (n=18), of the insulin area under the O-GTT insulin response curve (n=18) and of the serum triglyceride level (n=20). The LPL activity in obese children both at 10 unit/kg body weight of heparin (n=13) and at a corrected heparin dose (n=12) was similar to that in controls, suggesting that hypertriglyceridemia in these children was not due to the impairment of triglyceride removal. The serum triglyceride level was correlated with the fasting serum insulin concentration (n=29) and insulin area (n=20). Percent ideal body weight was also correlated with the latter two variables, while it was correlated with neither insulin binding nor the serum triglyceride level.
It was concluded that insulin resistance and hyperinsulinemia in obese children may be the major contributing factors in the development of hypertriglyceridemia, which is idependent of the degree of obesity and postheparin plasma LPL activity.

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Truncal titubation occurs due to a disturbance of the spinal cord or peripheral nerves as well as cerebellar disorders. The purpose of this study is to find unrecognized (occult) titubation in diabetics and to estimate it quantitatively by examining the patient's equilibrium function with the eyes open and closed.
The subjects consisted of 10 healthy controls and 13 diabetics with or without neuropathy. Truncal titubation was recorded on an X-Y recorder using a gravicorder. The patient stood on the gravicorder with the eyes open and then with the eyes closed for one minute each. The changing area of gravity was recorded by the gravicorder with the eyes open (Ao) and closed (Ac). The ratio of Ac to Ao (Ac/Ao) was calculated. The Ao, Ac and Ac/Ao were compared between healthy controls and diabetics. In diabetics, the relationship between these components and diabetic neuropathy was investigated.
The results were as follows. 1) In diabetics, Ao, Ac, and Ac/Ao were greater than in healthy controls. 2) In diabetics with neuropathy (loss of Achilles tendon reflex and disturbed vibratory sensation), Ao and Ac were significantly (p<0.05) greater than in healthy controls. 3) Ac/Ao in diabetics with vibratory disorder was significantly (p<0.02) greater than in healthy controls and diabetics without vibratory disorder. However, no influence of the presence or absence of Achilles tendon reflex on Ac/Ao was found.
The conclusions are as follows. 1) In diabetics with neuropathy, the degree of truncal titubation with the eyes open was greater than that in healthy controls and diabetics without neuropathy. 2) In diabetics with vibratory disorder, truncal titubation increased remarkably with the eyes closed. 3) Disorder (s) of the spinal cord and/or the peripheral nerves might be responsible for the truncal titubation in diabetic neuropathy. 4) From the above results, the Lterm “truncal ataxia” could be applied to truncal titubation in diabetics with neuropathy. 5) Truncal ataxia in diabetic neuropathy was recognized for the first time by our examination using a gravicorder.

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It has been said that “the longer the belt, the shorter the life.” On the other hand, in the experience of Joslin Clinic, the presence of obesity at the onset of diabetes resulted in good prognosis. To clarify the prognosis of Japanese diabetics, we undertook a prospective follow-up study of 1, 629 diabetic patients (898 males, 731 females) who visited our Diabetes Center located in Tokyo in 1976. In the present paper, we describe the results of a four-year follow-up study, especially regarding the effects of body weight on mortality and cause of death among Japanese diabetics.
During this follow-up study, only three cases dropped out within four years from the start. The deaths of 140 cases (98 males, 42 females) among the 1, 629 were confirmed at the end of the four year follow-up. The follow-up rate, therefore, was 99.8%. We obtained death certificates mentioning the causes of death for all the 140 deceased patients.
The cumulative death rate for four years among the 263 diabetics with a relative body weight at the registration of less than 90% was the highest at 11.8% and the greater the relative body weight, the higher the mortality rate. The cumulative death rates among the 812 patients with a relative body weight ranging from 90% to 109%, those among 471 patients with 110% through 129%, and those among 83 patients with 130% and more were 8.7%, 7.4% and 3.6%, respectively.
On the other hand, the cumulative death rate among the patients with a maximum relative body weight before entry less than 90% was as high as 18.2% and those among 364 patients with a maximum body weight range of 90% through 109%, among 662 patients with 110% through 129% and among 570 patients with 130% and more were 6.0%, 7.4% and 11.1%, respectively.
The most frequent cause of death among the groups with relative body weights at the registra tion of less than 90%, 90% through 109% and 110% through 129% was malignant neoplasms. The greater the relative body weight at the registration, the higher the rate of deaths from ischemic heart disease and cerebrovascular disease and the lower the rate of deaths from diabetic nephropathy, infections and cirrhosis of the liver. However, there was no significant relationship between the maximum relative body weight before entry and the distribution of causes of death.

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A case of recurrent ophthalmoplegia and headache in a 50-year-old male insulin-dependent diabetic patient was reported. He had nine-year a history of diabetes mellitus. His fasting blood glucose was 130 to 170 mg per cent. A palsy of a combination of the third, fourth and sixth cranial nerves at the left side occured. After four months, the palsy was improved. After two weeks, right oculomotor palsy occured, but three months later it was improved.
In 12 cases (10 males and two females) of cranial nerve palsy among 2597 diabetics hospitalized in our medical center from 1953 to 1980, the affected nerves at the first onset were the oculomotor (six cases), abducens (one case), a combination of oculomotor, trochlear and abducens (one case), facial (three cases) and vagal (one case). The pupils were intact. The recurrence of cranial nerve palsy was noted in Case 1 and Case 3 in Table 1 (Case 1 corresponds to Case 3 and Case 3 corresponds to Case 4 in Table 2). The average age was 65 years (range: 50-75) and the mean duration of the diabetes was 12 years (range: 5-30). the control of blood glucose was poor in three out of the 12 patients. The ophthalmoplegia disappeared in one to four months. Retinopathy (five cases), nephropathy (five cases) and neuropathy (six cases) were (complications).
In 12 cases (Seven males and four females) of recurrent ophthalmoplegia in Japanese diabetics reported in the literature, the mean age was 61 years (range: 50-67) and the mean duration of the diabetes was 12 years (range: 6-20). Oculomotor (eight cases), a combnation of oculomotor, trochlear and abducens (two cases), a combination of trochlear and facial (one case) and a combinatino of abducens and facial nerves (one case) were affected at the first onset. Ophthalmoplegia recurred in the same side (seven cases) or in the opposite side (four cases). In two cases, the pupils were involved. Ophthalmoplegia recoverd in one to four months. In 10 cases, the diabetes was under poor control at the onset of the palsy. The intervals between the first and the second ophthalmoplegia were 0.5 to 27 months. Retinopathy (5/8 cases), nephropathy (4/8 cases), and neuropathy (5/7 cases) were (complications).

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We have experienced two patients with diabetic ketosis and insulin edema that developed following insulin treatment.
A 35-year-old female was admitted to our hospital with diabetic ketosis. She was given sebcutaneous injection of 30 units of regular insulin and 1, 000 ml of intravenous fluid daily. After three days, she noticed edema on the legs and the face. After 10 days, there was definite edema not only of the legs and the face, but also of other parts of the body. Her chest x-ray showed effusion in the left lower lung field and left interlobar space. Her weght increased by 17.5kg in 10 days of treatment. Edema, however, disappeared rapidly when 1 mg of bumetanide was given for two days.
A 49-year-old female was admitted with diabetic ketosis. She was given subcutaneous injection of 30 units of regular insulin and 500 ml of intravenous fluid daily. After six days, she noticed edema on the legs and the face. The edema became generalized in 10 days, and her chest x-ray showed effusion in the right lower lung field. Her weight increased by 7 kg in 10 days of treatment. Her diabetes was well controlled on 30 units of regular insulin daily, and edema disappeared as the insulin dose was reduced. Twelve days after discontinuing insulin treatment, her weight was down to 50 kg which was almost the same as her weight on admission (49kg).
In the two cases presented herein, renal function so far as PSP is concerned was normal, and edema disappeared when insulin dose was reduced and diuretics were administered. Such great retention of fluid is usually observed in type 1 diabetic patients and may result from a sudden reduction of the larger quantities of blood glucose using insulin.
In our two cases, hypoproteinemia which was also regarded as one of the possible causes, was present.

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The cholesterol contents of the a. posterior cerebral, a. subclavia sinistra, a. common carotid sinistra, a. coronar, and a. renal 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 dry weight of the arteries per length in the diabetic group was 1.40 to 2.96 times greater than that in the nondiabetic group. The contents of cholesterol in the arteries of the diabetic group were also 1.07 to 4.10 times greater than those of the nondiabetic group.
The dry weight of the arteries per length in the nondiabetic group and the contents of cholesterol in the arteries could be expressed by the following regression equation: y=0.645 + 0.903x (r=-0.785, p<0.05) for the nondiabetic group, and y=2.470 +1.344x (r=0.917, p<0.001) for the diabetic group. The cholesterol content in the arteries between the diabetic group and the nondiabetic group could be expressed by the following regression equation: y=4.303-0.558x (r=-0.843, p<0.002).
These results suggest that arteriosclerosis is enhanced in diabetics, especially in arteries where the cholesterol content is low.

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