In patients with diabetes mellitus, the coefficient of variation (CV) of R-R interval in the electrocardiogram and the threshold of taste were determined and their clinical significance discussed. In 160 normal subjects and 112 diabetics, after a 15 min rest in a supine position, CV a was measured with an Autonomic R-100 (MEC, Tokyo, Japan). Also, in 109 normal subjects and 112 diabetics, the threshold of taste in the chorda tympani nerve area was measured with an electrogustometer (MEC, Tokyo, Japan).
In both groups of normal subjects and diabetics, CV decreased and the threshold of taste increased with aging. CV in diabetics more than 30 years old showed a significant decrease as compared with that in normal subjects of the same age. The threshold of taste in diabetics 30 to 60 years old showed a significant increase as compared with that in normal subjects of the same age. In diabetics, the longer the duration of diabetes mellitus, the greate the degree of CV decrease and the threshold of taste increase; further, in diabetics with poorer metabolic control, CV showed a lower level and the threshold of taste, a higher level. Patients with clinical symptoms suggestive of diabetic neuropathy showed a significant decrease of CV and a significant increase in the threshold of taste as compared with patients without such clinical symptoms. The threshold of taste was found to increase with the progress of diabetic retinopathy. CV in diabetics with proteinuria showed a significant decrease as compared with that in those without proteinuria. Furthermore, even in patients without diabetic retinopathy, proteinuria or clinical symptoms of diabetic neuropathy, CV showed a significant decrease and the threshold of taste showed a significant increase as compared with those of age-matched normal subjects, and CV and the threshold of taste showed a significant negative correlation. These findings indicate that disorders of autonomic nerves as well as gustation precede other diabetic complications, and that autonomic neuropathy parallels gustatory disorder, suggesting that these examinations in diabetics are useful for detecting complications in patients with diabetes mellitus.

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Recently, embolization of the hepatic artery has been widely used as a therapy for hepatoma. However, hyperglycemia experienced after such embolization has not been reported.
In this study nineteen cases of hepatoma and fourteen cases of liver cirrhosis (group C) were studied. In nine (group A) out of the nineteen hepatoma cases, embolization was performed, while in the remaining ten (group B) hepatoma cases, this procedure was not done. Changes in blood glucose before and after hepatic artery embolization were investigated retrospectively.
The increases in blood glucose were 52.9±17.2 mg/dl (mean±SEM), 4±4.4mg/dl, and-0.9±4.1mg/dl in groups A, B and C, respectively. In the nineteen subjects with hepatoma and the fourteen cases with liver cirrhosis, multivariate regression analysis was performed using the change in glucose as an objective variable and ICG, the degree of embolization, tumor size, and the use of steroid hormones as explaining variables.
An equation (change in glucose=-20.7+0.76×ICG+25.2×the degree of embolization) was cbtained. The equation explained the change of glucose in an external sample very well.
This indicated that the glucose change induced was mainly affected by the value of ICG and the degree of embolization. This suggested that the hepatic reserve and the hepatic injury caused by the blockage of the artery explained the glucose change.

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The relationship between body mass index (BMI) and percentage standard weight (PSW) was investigated in 50 male and 50 female Japanese patients with NIDDM in the Sanin. district. BMI was found to correlate highly with PSW. From the equation relating PSW and BMI, it could be calculated that BMI, at 120% PSW, was 25.39 in males and 25.49 in females. It appears that patients whose BMI is equal to or greater than 25 should be regarded as obese in Japanese NIDDM.

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1. Purpose: The purpose of this study was to evaluate the usefulness of a guide to diabetes in the home management of diabetes in childhood.
2. Subjects and Methods: The subjects of this study were 104 guardians of diabetic children who were registered members of the childhood diabetes association in three major districts in western Japan. Firstly, a survey of these subjects was made by contacting them by mailed questionnaire accompanied with multiple answers to each question among which the subjects were asked to choose. The questionnaire consisted of 10 questions about general knowledge of diabetes and 20 others pertaining to behavioral changes necessary for the successful home management of juvenile diabetes. Secondly, a guide to diabetes that meets pedagogical requirements was written and named “Textbook of Diabetes Education” by us. This booklet is comprehensible but sufficiently academic, contains a purposeful sequence of units and, moreover, allows the reader to check his or her knowledge of the disease and its management. Thirdly, the booklet was sent by mail to each subject with a request to read it through. Fourthly, the subjects were ontacted once again by the questionnaire sent by mail 8 weeks after they had received the booklet. The usefulness of the booklet was evaluated by comparing the number of correct answers to the questionnaire before and after reading the booklet.
3. Results: Valid responses were obtained from 91 subjects.
(1) The number of correct answers to questions about the general principles of diabetic regimen was significantly greater after (7.6±1.5) than before reading (6.9±1.6)(p<0.001). Frequency distribution of correct answers to questions about general understanding of diabetes mellitus moved to higher scores after presentation with “Textbook of Diabetes Education” (p< 0.10).
(2) The number of correct answers to questions about behavioral changes necessary for the successful home management of diabetes was also significantly greater after (14.2±2.5) than before reading (13.4±2.5)(p<0.01). Frequency distribution of correct answers to questions of special knowledge necessary for the successful home management of diabetes moved to higher scores after presentation of “Textbook of Diabetes Education” (p<0.02).
4. Conclusion: The booklet proved to be of pedagogic value and may be assumed to provide a useful means of giving instruction in diabetes.

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The relationship between pupil area in darkness (PA) and abnormality on R-R interval variation was studied in 45 patients with diabetes mellitus. The patients were divided into four groups according to the grade of somatic neuropathy. Group I consisted of patients clinically diagnosed as latent diabetes. Group II, III and IV consisted of diabetics without, with mild and with severe somatic neuropathy, respectively. PA was measured in complete darkness by infrared video-pupillography, and each was compared individually with sex-and age-matched controls. Mean PA was normal in Group I, but was significantly smaller in Groups II, III and IV. The degree of miosis (decrease in PA) correlated with the grade of somatic neuropathy. Mean coefficient of variation of R-R intervals on ECG during deep breathing (CV) showed no significant difference between controls and Groups I, II and III, but was decreased in Group IV. Although mean PA in patients with abnormal CV was smaller than in those with normal CV, there was no correlation between PA and CV. It is concluded that measurement of PA is a more sensitive and useful technique for detecting autonomic dysfunction in diabetes mellitus.

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To clarify the relationship between diabetic urinary bladder dysfunction (DUBD) and subjective symptoms related to DUBD, and also between DUBD and coefficient variation of R-R interval in ECG (CV_R-R), cystometry was carried out in 54 diabetics ranging in age from 29 to 65 years. The criteria for DUBD in this study were based on the result of cystometry in 8 healthy subjects.
Frequency of residual urine (RU), and abnormalities in first desire to void volume (FDVV) and maximum desire to void volume (MDVV) were 31.5, 61.1 and 72.2%, respectively. The prevalence of patients with one of these abnormalities was 81.1%. The cystometrograms of all of the dibetics with DUBD showed underactive detrusor function and detrusor areflexia. High incidence of DUBD was recognized even in patients without subjective symptoms and/or with a slight degree of symptoms related to DUBD. There were high incidence of RU and abnormal MDVV in diabetics with advanced retinopathy, proteinuria and orthostatic hypotension. CV_R-R of diabetics with RU was higher (p<0.001) than that of patients without RU. CVR_R was negatively correlated to both FDVV (r=-0.56) and MDVV (r=-0.62).
From these results, it is possible to conclude that there was a high prevalence of DUBD even in patients without subjective symptoms, and that complication with DUBD can be suspected by a decrease in CV_R-R without the patient having to undergo cystometry.

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A multi-center double-blind study was conducted on human monocomponent insulin (HMI) preparations enzymatically semisynthesized from porcine insulin for their safety, efficacy and immunological evaluation. Purified porcine insulin (PPI) preparations were employed as the control agents. Of a total of 190 diabetics participating in the study, 182 were finally included in the analysis of patient data (93 receiving HMI, 89 receiving PPI). Actrapid and Monotard prepartions of both HMI and PPI were employed. The compositions of the HMI and PPI groups were equivalent in term of the patients' backgrounds and compliance with the physicians' directions. In the final analysis, no statistically significant differences were observed between the two groups with regard to the global improvement rating, overall safety rating and global utility rating, in comparison with the initial stages. These data were subjected to further analysis in different stratified subgroups of patients. With regard to the type and frequency of adverse effects, also no significant differences were observed between the two groups. In addition, no abnormal finding which could be considered to be due to the effects of the test drugs were observed in the laboratory test results.

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A multi-center double-blind study was conducted on human monocomponent insulin (HMI) preparations, enzymatically semisynthesized from porcine insulin, for their safety, efficacy and immunological evaluation. Purified porcine insulin (PPI) preparations were employed as the control agents. The subjects of this study were 182 diabetics who had been under treatment with PPI exclusively. During the administration period, there were certain time point where the daily insulin requirement and the frequency of daily injectons were found to be significantly larger statistically in the HMI group in comparison with the PPI group.
With respect to fasting blood glucose level, the HMI group showed a statistically higher level than the PPI group at several time points, while no significant difference was observed between the two groups regarding the HbA, level. There were some time points where the anti-insulin IgG antibody level tended to be lower in the HMI group than in the PPI group and at some time points the insulin-specific IgE antibody level was statistically lower in the HMI group. Thus, HMI seems to be less immunogenic compared with PPI. On the basis of the above results, it can be concluded that HMI's clinical utility is equal to that of PPI as long as it is employed bearing in mind that there may be some differences between HMI and PPI with respect to drug absorption from the site of subcutaneous injection.

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We describe the characterization of the antigen (s) in human pancreatic β-cell line (JHPI-1) recognized by islet cell surface antibodies that have been found in the serum of insulin-dependent diabetes mellitus (IDDM). Briefly, NP-40 lysates of JHPI-1 cells were analyzed by SDS-PAGE on 7.5-10% uniform slab gels in a discontinuous buffer system of Laemmli. The proteins in the slabgel were electrophoretically transferred onto nitrocellulose membranes. The transferred nitrocellulose membranes were incubated with islet cell surface antibodies or normal healthy control serum as first antibodies, and stained using the Avidin-Biotin method. As a result, six bands, 120 K, 80 K, 64 K, 42 K, 34 K and 27 K proteins, were tentatively identified. On the other hand, control serum did not provide any ricognizable proteins. It is concluded that islet cell surface antibodies recognize a protein with Mr 64, 000 expressed in JHPI-1 cells as previously reported in human islet cells.

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Nocturnal penile tumescence (NPT) during sleep was measured in 28 impotent diabetics to differentiate the causes of the impotence. The subjects had no severe complications and had not taken drugs that induce impotence. Before the measurement of NPT, all drugs that could interfere with erection during the REM period had been cleared from the body.
Twelve patients showed the normal pattern of NPT, which was more than 20% increase of maximal NPT in penile circumference at the tip or base, and the remaining 16 patients showed abnormal NPT.
There were no significant differences in age, duration of diabetes, duration of impotence, libA, body weight and the methods of treatment of diabetes between the normal NPT and abnormal NPT groups. However, the Achilles tendon reflex and nerve conduction velocity of the leg were significantly decreased in the abnormal NPT patients. Among these patients, orthostatic hypotension and a tendency to depression were more frequent than in the group with normal NPT.
In conclusion about 40% of the diabetic patients who complained of impotence were functional and they had less peripheral neuropathy, orthostatic hypotension and depressive tendencies than those with abnormal NPT. We experienced three patients whose impotence improved after we showed and explained to them the results of their NPT measurements.

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We report a patient with severe diabetic diarrhea and atonic bladder, who was restored to health by continuous subcutaneous insulin infusion (CSII) and elemental diet (EI).
A 41 year-old woman was admitted to our hospital because of hyperglycemia and dysuria. Before admission, she had stopped insulin therapy on her own for two years, resulting in poor control of blood glucose and a decrease in body weight associated with severe diarrhea and steatorrhea.
We treated this patient with ED and CSII therapy for nutritional improvement and control of blood glucose. Thereafter, the frequency of diarrhea decreased remarkably and the steatorrhea disappeared. Five months later, she had gained about 12 kg, and serum albumin had recovered to the normal level. Four months after withdrawal of ED and CSII, spontaneous urination appeared, and she did not needs urethral catheter.
The present study suggests that the improvement of nutritional conditions, in addition to strict control of blood glucose, may be an important factor for the management of severe diarrhea and atonic bladder in patients with diabetes mellitus.

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Autoantibody to endogenous insulin was studied in a patient with rheumatoid arthritis (RA) and Sjögren's syndrome who was treated with tiopronin (α-mercaptopropionyl glycine: MPG). MPG has been used in patients with RA in recent years, because of its immunomoderating action. Although MPG has a good effect in some patients with RA, one patient was found to have autoantibody to endogenous insulin accidentally.
A 46-year-old female rheumatoid patient treated with MPG and with no history of previous exogenous insulin exposure, had frequent hypoglycemic episodes after 16 days of re-administration of MPG. The anti-insulin antibody was evaluated by the specific precipitation method, using radioisotope-labelled insulin. The antibodies to IgG. IgA, IgM, kappa and lambda were used in order to determine the immunoglobulin class and light chain type of anti-insulin antibody. The patient's serum showed 2, 974 μU/ml of total immunoreactive insulin (IRI), 22 μU/ml of free IRI and IgG (κ) type anti-insulin antibody. She was diagnosed as having insulin autoimmune syndrome (IAS). When MPG was stopped, her hypoglycemic attacks disappeared. She had a further mild hypoglycemic attack on the 11th day after challenge of MPG.
It was therefore concluded that MPG may produce autoantibody to endogenous insulin and induce IAS to patients with RA who have abnormalities of immune response.

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Multiple streptozotocin (STZ)-induced diabetes in mice and Bio-Breeding/Worcester (BB/W) rats has been employed as a model of human Type I diabetes and cyclosporin (CYA) was reported to prevent diabetes in the BB/W rat. We have investigated whether or not the effect of CYA on multiple STZ-induced diabetes is the same in mice.
Male CD-1 mice were given 4 successive daily doses of STZ 40 mg/kg and an additonal dose of 40 mg/kg one week later. CYA treatment at a dose of 10 mg/kg per day or more, was begun on the same day as the STZ treatment and continued for 14 days. Animals received CYA orally which was dissolved in alcohol and Tween 20. Intraperitoneal glucose tolerance tests were done 2, 4 and 8 weeks later. After the last glucose tolerance test, histological examination of pancreatic islets was performed.
The blood glucose level after STZ with/without CYA administration resulted in a stepwise increase with time. A significant enhancement of the blood glucose level by CYA was obtained in a dose-dependent manner. The fasting blood glucose levels 2 weeks after the administration of STZ, STZ with CYA (10 mg/kg) and STZ with CYA (30 mg/kg) were 128±39mg/dl, 134±43mg/dl and 325±93mg/dl, respectively. Histologically, at this stage, insulitis was observed in the STZ+CYA group as in the STZ only group. However, alcohol and Tween 20 without CYA caused no change in blood glucose level and histological findings. Pancreatic islets in STZ with/without CYA-treated mice 8 weeks after were small in size and reduced in number as compared with those in the control mice.
The present study indicates that CYA has a dose-dependent diabetogenic effect on multiple STZinduced diabetes in mice.

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