Recent studies have demonstrated that triphenyltin compounds, widely used as agricultural chemicals and a marine antifoulant, induce diabetes in rabbits and hamsters. The present experiments were conducted to elucidate the mechanisms of the inhibition of insulin release from the hamster pancreatic islets by triphenyltin chloride (TPTC1). The oral administration of TPTC1 (60 mg/kg body weight) to hamsters inhibited the release of insulin from the isolated islets in response to 200 or 500mg/dl glucose (p<O.01) or 10^-7 M 4β-phorbol 12β-myristate 13α-acetate (PMA)(p<0.05). The exposure to TPTC1, diphenyltin dichloride or phenyltin trichloride in vitro had no effect on the release of insulin from the isolated islets in response to 500 mg/dl of glucose.
These results suggest that diabetes induced in hamster by TPTC1 is due to inhibition of insulin release from pancreatic islets. Since insulin release was not affected by addition of TPTC1 and other phenyltins in vitro, some metabolites of these compounds seem to be related to the inhibition of insulin release from pancreatic islets.

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The prevalence of abnormal glucose tolerance and diabetic complications was assessed in 27 acromegalic patients. By the Japan Diabetes Society (JDS) criteria of 1970, and 1979 of the 21 patients were defined as diabetic and 8 were borderline types according to glucose tolerance tests. By the JDS criteria of 1982, 3 of 4 were borderline types. In addition to these cases, one had already received treatment of diabetes and in the other case, the oral glucose tolerance test was omitted because of the elevated fasting plasma glucose level (128 mg/dl). Thus, 22 patients (88%) were abnormal with regard to glucose tolerance.
Between the diabetic and non-diabetic acromegalics, there was no significant difference in age, sex, duration of acromegaly, body weight, serum growth hormone (GH) level, or thyroid or adrenal function. In the non-diabetic cases, the plasma glucose levels in 50 g oral glucose tolerance tests (OGTT) were well correlated with the serum GH level. In the borderline cases, the insulin response to glucose load showed large variations, including hypersecretion, delayed peak and low response. However, in all the diabetic cases, the insulin response in the 50 g OGTT and insulinogenic index were very low. After the treatment of acromegaly with sufficient decrease of GH level, 6 of 9 diabetic cases continued to need treatment for diabetes.
Diabetic retinopathy was found in 1 of 10 diabetic patients and developing retinopathy appeared in another case after the acromegaly treatment. In this case, the retinopathy rapidly worsened to a proliferative type and was complicated by impaired renal function.

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The effect of the new carnitine analog (Emeriamine) on the plasma levels of ketone bodies, glucose and free fatty acid were investigated in experimentally induced severe diabetic ketoacidotic rats.
The diabetic rats showing glycosuria and ketonuria were divided into the following 4 experimental groups; group 1, saline infusion (3ml/2 hrs) for controls; group 2, β-aminobetaine (Emeriamine) 20-30mg/kg/2 hrs; group 3, regular insulin (human rapid-acting insulin) 0.4-0.5 U/kg/2 hrs; group 4, combined β-aminobetaine (Emeriamine) 20-30 mg and regular insulin (human rapid-acting insulin) 0.4-0.5 U/kg/2 hrs.
The levels of both acetoacetate (AcAc) and 3-hydroxybutyrate (3 OHBA) were rapidly reduced to 50% of the basal by analog infusion and to 30% by combined analog and insulin infusion.
The rise of glucose observed in the control saline group was abolished by analog infusion.
The small dose of insulin infusion alone caused no great improvement in ketone bodies or plasma glucose.
The level of free fatty acid did not change significantly with analog infusion.
It is suggested that the new analog is efficient and useful for the rapid reversal of diabetic ketoacidosis when infused alone or combined with insulin.

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Plasma concentraions of fructosamine, an indicator of glycosylated plasma proteins, were measured in diabetic patients using the Fructosamine Test (Roche). Samples were incubated with nitroblue tetrazolium at pH 10.35. (1) There was no difference in plasma fructosamine between the normal subjects and those with impaired glucose tolerance (IGT) diagnosed with the 75 g glucose tolerance test. Diabetic patients whose fasting plasma glucose (FPG) level was less than 140mg/dl showed significantly higher plasma fructosamine than normal or IGT subjects, as did patients of FPG level of 140 mg/dl or more. (2) Plasma fructosamine concentration in 298 diabetic patients was 3.25±0.92 (mmol/l, mean± SD), higher than that of normal subjects (2.32± 0.32, n=48). Correlatons were seen between fructosamine and FPG (r=0.450), HbA₁ (r=0.621) and HbA_1c (r=0.585) in these patients. (3) The relationship was studied between plasma fructosamine and preceding FPG levels measured weekly. The levels of FPG that were determined two weeks earlier showed the highest correlation.
Fructosamine assay is a simple and rapid procedure that can be fully automated. Our results suggest that fructosamine measurement may be helpful in screening for diabetes mellitus and useful in monitoring short-term control of plasma glucose in diabetic patients.

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A cross-section study of diabetic osteopenia was performed in 231 institutions throughout Japan on 10, 569 randomly selected patients with diabetes mellitus and 646 healthy control subjects. Based on six indices obtained by microdensitometry, the prevalence of osteopenia in diabetics was 20.1% throughout Japan, which was significantly higher than 7.9% in healthy control subjects. The prevalance of osteopenia in female patients was significantly higher than in males and than it was in age-and sex-matched controls. Prevalences of osteopenia in patients treated with insulin, oral anti diabetic agents and diet alone were 22.8, 20.3 and 16.0%, respectively, being higher in patients with insulin therapy and oral agents, compared to patients on diet alone. There were no significant difference in the prevalence of osteopenia between IDDM and NIDDM. The presence or absence of obesity had no significant effect. The prevalence of osteopenia increased during the first 5 years after the onset of diabetes, but remained almost constant thereafter. Patients with osteopenia had slightly but significantly higher prevalences of neuropathy, retinopathy and nephropathy.

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To determine whether there is a geographic difference in the prevalence of diabetic osteopenia, 5939 diabetic patients aged 50 to 69 throughout Japan were included in a multi-institutional survey using microdensitometric analysis of X-ray films of bones. The prevalence was higher in both male and female patients in northern Japan (Hokkaido and Tohoku District) than in southern Japan (Kyushu and Chu-Shikoku District). The prevalence on Japan Sea side was significantly higher than on Pacific Ocean side. The prevalence of osteopenia at inland was also significantly higher than at sea-side. When we compare the mean daily sunlight energy and the prevalence of osteopenia in seven districts of Japan, there was a negative correlation between them, indicating that sunshine is an important determinant in causing diabetic osteopenia.

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Insulin treated diabetic in-patients under caloric restriction (about 25 to 30 keal/kg standaid body weight/day) and 30 to 60 minutes of walking daily were divided into the three groups of non insulin dependent diabetics (NIDDM, n=21), NIDDM with chronic hepatitis (DM with CH, n=8) and insulin dependent diabetics (IDDM, n=7). 24 hour urinary C-peptide excretion (24 h U-CPR, μg/day) was 48±6 (mean±SEM) in NIDDM, 75±8 in DM with CH and ≤5.0 in all IDDM. Under 140mg/dl of fasting blood glucose, insulin dosage (U/kg body weight/day) was 0.36±0.03 in NIDDM, 0.43±0.05 in DM with CH and 0.51±0.04 in IDDM. CH, especially alcoholic CH, seemed to be a cause to an increase of insulin requirement in diabetic patients.
There was a good negative correlation between insulin dosage and 24 h U-CPR (r=-0.718, p<0.0005), fasting serum C-peptide (r=0.692, p<0.01) or 2 hour postprandial serum C-peptide (r=-0.532, p<0.025).
These results indicate that 24 h U-CPR and fasting or postprandial serum C-peptide are good and convenient parameters to assume the suitable insulin dosage in diabetic patients.

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A 35-year-old male was admitted to the Akita City Hospital because of polydipsia, polyuria, weight loss and palpitation, in February 1986. He had periodic episodes of paralysis due to hyperthyroidism at the age of 19 and took medicine for two years. Glycosuria was detected 3 months before admission. Physical examination revealed an enlarged thyroid gland with an irregular surface. Temperature was 37.3°C and pulse rate was 110/min. The laboratory data were as follows: PPBG 461mg/dl, urine sugar (+++), ketone body (++), TSH<2.0 U/ml, TBG 8.4mg/l, T₃ 1.3ng/ml, free-T₃ 4.1 pg/ml, T₄ 17.2 μg/dl, free T₄ 5.3 ng/dl and BMR.+30%. Thyroid scintigram demonstrated multiple hot nodules. Open biopsy of the thyroid gland enabled the diagnosis of adenomatous goiter to be made from the findings of various-sized follicles with mostly atrophic, and partially papillary hypertrophic epithelium. It was surmised that T₄ toxicosis was evoked by the inhibition of T₄ to T₃ due to hyperglycemia. T₄, free T₄ and BMR became normal only with insulin therapy.

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A male noninsulin-dependent diabetic patient, aged 38 years, was complicated by anorexia nervosa during the course of diabetes mellitus. He was first diagnosed as having diabetes mellitus at 33 years of age, when he noticed thirst, polyuria and weight loss (60→53kg). His diabetic state has been controlled initially by insulin and later only by diet and exercise therapy. However, his body weight continued to decrease from 45 kg at 35 years of age to 40 kg at 37 years. Because of additional complication by anemia and liver dysfunction, he was admitted to our University Hospital in January, 1986. On admission, his body weight was 36 kg (45% less than ideal body weight). Organic lesions which may induce excessive loss of body weight, such as hypopituitarism, malabsorption syndrome, malignancies, etc. were ruled out. During admission, a diet of 2, 000 kcal/day was served, but he was too strict about dietary treatment and too nervous about increasing plasma glucose levels to gain weight. So his body weight remained around 36 kg. The blood glucose level and HbA₁ were well controlled. Insulin secretion was very low, as assessed by urinary daily excretion of CPR as were responses of plasma IRI and CPR to oral and intravenous administration of glucose, glucagon and tolbutamide. A euglycemic glucose clamp study disclosed that sensitivity to insulin in the patient was increased to twice as much as the control. No differences were found in characteristics of the insulin recpetors on erythrocytes prepared from the patient and control subjects. Basal plasma concentrations of GH, LH and cortisol were increased and T₃ was decreased. Radiological examination did not show any abnormalities in the area of the hypothalamus and pituitary gland. Psychological tests indicated a tendency of neurosis in his character. It is postulated that the patient's strict adherence to the diet in the treatment of diabetes mellitus may have accelerated the manifestation of anorexia nervosa.

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A 39-year-old man was admitted to our hospital because of diabetic ketoacidosis and pneumonia. He had been diabetic for five years, and was not on treatment. The blood glucose value on admission was 602 mg/dl, and HbA₁ was 16.4%. His fundi showed only a few dot hemorrhages. He was treated by continuous intravenous insulin infusion, followed by subcutaneous injection of intermediate insulin. On about the 8th hospital day, pretibial edema, visual distrubance and pleural effusion developed, then disappeared until the 25th hopsital day. After the disappearance of insulin edema, many linear hemorrhages and soft exudates developed over the radial peripapillary capillary area. Since fluoresein angiography showed many non-perfusion areas in the midperipheral area, photocoagulation therapy was administerd. Paresthesia of the lower limbs, orthostatic hypotension and tachycardia also appeared, and the mean difference between maximal and minimal heart rate during deep breathing was small. Furthermore, he began to complain of diarrhea, impotence and hyperhydrosis in the upper trunk. Ten months later, his fundi showed neovascularization on the peripapillary area, but remained rather stable. Symptons of diarrhea and orthostatic hypotension slightly improved, but the autonomic function was still markedly impaired.
This is a case in which rapid tight control of blood glucose led to insulin edema, followed by rapid development of proliferative diabetic retinopathy and peripheral and autonomic neuropathy.

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A 52-year-old nurse came to our clinic because of hypoglycemic attacks. At 45 years of age she had been diagnosed as having bronchial asthma, and was subsequently treated with subcutaneous injections of insulin and aurothioglucose for eight months.
About two years after the injections ended, she begun to experience episodic hyoglycemic attacks. The blood glucose levels during the attacks ranged from 30 to 50mg/dl. A 75g oral glucose tolerance test revealed border-line conditions. Echographic and radiological examinations revealed nothing remarkable. The levels of immunoreactive insulin (IRI) and C-peptide immunoreactivity (CPR) extracted from the serum by the acid-ethanol method were enormously elevated, as was also the percentage of 1251-insulin binding. The elevated CPR was mainly due to increased proinsulin, which was confirmed by gel-filtration. Reverse-flow high-speed liquid chromatography revealed that the extracted insulin was normal human insulin. Bw62, Cw4, and DR4 were found in the typing of HLA. These results indicated that the hypoglycemia might be explained by the antibodies binding secreted insulin.
Corticosteroid treatment for three months reduced the frequency and severity of the hypoglycemic attacks concomitantly with decrease in the serum levels of insulin and proinsulin, and in the percentage of ¹²⁵I-insulin binding of the serum.

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We report the case of a 23-year-old diabetic man who was admitted to hospital with ketoacidosis. His electrocardiogram (ECG) showed sequential changes of acute pericarditis without pericardial effusion. These changes were transient: after 120 hours the ECG returned to normal.
A 23-year-old man without a history of diabetes, who had had increasing thirst, polyuria, nausea and vomiting of two weeks'duration, was admitted to the hospital with severe retrosternal chest pain and general fatigue. On examination, he was obviously dehydrated and slightly drowsy. Initial investigations showed urine ketone body (3+), urine sugar (4+), blood ketone body 7.7 mmol/l, arterial blood pH 7.29, BE-10.8 mmol/l, and blood glucose 498mg/dl. The ECG taken at admission showed definite ST elevation in leads I, II, III, _aV_F, and V_1-6, suggestive of acute pericarditis. However the echocardiograms did not show any pericardial effusion. The ECG abnormalities and clinical symptoms were largely resolved after initiation of treatment with intravenous fluid and continuous Actrapid insulin infusion.

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A workshop on ICSA determination was organized to study whether ICSA data from different institutions were consistent. or not. Forty-two serum samples were distributed to 11 institutions where ICSA of human samples is frequently assayed. The majority of samples were asseyed by at least five different institutions. The results for each sample from the different institutions were highly inconsistent. Relatively similar results were obtained in the institutions using cultured pancreatic endocrine cells as an antigen. Species differences in pancreatic endocrine cells (antigen) seemed not to have any effect on the results. Small differences in methods and techniques between institutions may have had a large effect on the results. We are not able to solve the problem of this inconsistency at present. However, during the course of the discussion, many of us agreed that easily obtainable cultured pancreatic endocrine cells (i. e., RINr cells) might be a preferable antigen for ICSA determination in view of the inter-institutional differences.

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