Twelve patients with sulfonylurea-treated non-insulin-dependent diabetes mellitus (SU-NIDDM), six with insulin-treated NIDDM (I-NIDDM) and eleven with insulin-dependent diabetes mellitus (IDDM) were subjected to strict control (SC) using an artificial pancreas (Biostator®) for 24 hours, and serum ketone body and lipid levels were examined comparatively between conventional therapy and 24-hour SC.
As a result, significant increases in total serum ketone body (TKB)(90±18 vs 211±52 μmol/l, p<0.01) and free fatty acid (FFA)(410±86 vs 869±160 μEq/l, p<0.05) and a significant decrease in serum triglyceride (TG)(116±9 vs 92±7 mg/dl, p<0.05) with the strict control regime were noted for SU-NIDDM. These changes were not observed in I-NIDDM, although there was no difference between I-NIDDM and SU-NIDDM in plasma glucose, HbA₁c, FFA and TG levels before strict control. In IDDM, a significant decrease in TKB alone was observed. Addition of sulfonylurea during strict control in SU-NIDDM reduced elevated TKB levels significantly, while FFA remained unchanged. In light of these results it was supposed that the sequence of TKB change observed in SU-NIDDM was related mainly to sulfonylurea administration.
Moreover, additional administration of sulfonylurea in six patients with NIDDM on conventional insulin therapy decreased their TKB levels significantly (130±17 vs 78±8, p<0.05) in spite of unchanged plasma glucose and FFA.
These results suggest that sulfonylurea may inhibit hepatic ketogenesis in diabetic patients, a phenomenon previously shown in diabetic animals.

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The cytotoxic actions of cytokines and macrophages were studied using rat insulinoma cell line (RIN). The inhibition of growth of RIN cells by cytokines was evaluated using a dye-uptake method after 4 days incubation with IL-1, TNF, and interferon-γ. The cytotoxicity of macrophages against RIN or GH₃ cells was also studied by a ⁵¹Cr-release assay using peritoneal cells from BB/W rats, which are an animal model of type 1 diabetes mellitus. IL-1 inhibited RIN cell growth, whereas TNF had little effect. Combinations of various cytokines acted synergistically to inhibit the growth of RIN cells. On the other hand, peritoneal cells, which were mainly macrophages from acutely diabetic BB/W rats, showed specific cytotoxicity against RIN cells. These results suggest that cytokines and macrophages have a role in the development of diabetes in BB/W rats.

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The underlying diseases including the predisposing causes and clinical laboratory data of 53 inpatients with lactic acidosis (blood lactic acid>50 mg/dl and blood pH<7.35) were analyzed. The most common underlying disease accompanied by lactic acidosis was malignant neoplasm. Organ failure, cardiovascular disease and diabetes mellitus were also common. The prognosis of cases with malignant disease, organ failure, diabetes mellitus, infection and paraquat intoxication was grave. However, those cases with cardiovascular disease, surgical procedures, trauma and convulsions had a favorable prognosis. Twenty-nine of the 53 cases in this series died.
Clinical laboratory date (M ± SD) showed, blood lactic acid 162.8±90.4 mg/dl, blood pH7.141±0.141 and blood glucose 348.2±282.1 mg/dl Elevation of total bilirubin, GOT, GPT, LDH, CPK, BUN and creatinine and a decrease of total protein were observed. Those cases who die showed higher levels of blood lactic acid, and a bigger anion gap, and more severe organ failure. The above finidngs clearly indicate that most cases of lactic acidosis are assosiated with hyperglycemia and that the prognosis of lactic acidosis is grave in cases with organ failure.

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The effects of rat IAPP-amide (IAPP-NH2) on hepatic glycogen metabolism were investigated in the perfused rat liver.
Glycogenolysis and cyclic AMP production were distinctly stimulated by infusion of glucagon (6×10^-11M) for 5 min into the portal vein. When insulin (3×10^-10M) for 10 min was added 5 min before the beginning of glucagon infusion, glucagon-stimulated glycogenolysis and cyclic AMP production were suppressed b+C27y about 30%. On the other hand, infusion of IAPP-NH2 alone (1×10^-8M) increased cyclic AMP in the perfusate to a level similar to that with infusion of glucagon (6×10^-11M), but showed no glycogenolytic effects. When IAPP-N H₂ was added 5 min before the beginning of glucagon infusion, the effect of IAPP-NH₂ on cyclic AMP was additive to that of glucagon infusion, but IAPP-NH₂ did not influence glucagon-stimulated glycogenolysis. IAPP-NH₂ showed also no influence on insulin suppression of glucagon-stimulated glycogenolysis.
These findings suggest that IAPP-N H₂ may act on the liver in a way different from glucagon, and that the increased cyclic AMP induced by IAPP-NH₂ does not regulate glycogenolysis.

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The relationship between age at onset and type of diabetes was examined in 1293 Japanese patients under the age of 30 who were diagnosed as having diabetes and were registered at the Diabetes Center of Tokyo Women's Medical College betvVeen 1980 and 1988. Of the 1293 patients, 477 (36.9 %) had insulindependent diabetes mellitus (IDDM), 753 (58.2 %) had non-insulin-dependent diabetes mellitus (NIDDM) and 63 (4.9%) could not be classified into either type. The number of female IDDM patients (n= 290) was significantly higher than that of male IDDM patients (n=187)(p<0.01), whereas the number of female NIDDM patients (n=346) was slightly lower than that of male NIDDM patients (n=407). In addition, the number of patients under the age of 13 at onset was significantly higher (p<0.01) in IDDM than in NIDDM, wherase the incidence of NIDDM increased with age after the age of 14. There were no NIDDM patients under the age of 9 at onset.

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A self-learning system for children with diabetes based on computerassisted instruction (CAI), ISLAND, has been developed. In this paper, the educational goal-strategy-evaluation and system structure of ISLAND are presented, and the necessity of CAI and the importance of ISLAND in teaching children with diabetes are also discussed. The basic structure of ISLAND is composed of three programs, i.e., to represent pictures on graphic display, to control the sequence of pictures and to process data, and to supervise data files. The form of the computer programs consists of five tutorials and one simulation. Each program allows systematic learning to understand and control insulin-dependent diabetes mellitus for children with diabetes. ISLAND has the following features for teaching children with diabetes: It enables children with diabetes to achieve self-learning, individualized learning, repetition-learning, selt-management of several data and stimulation of learning.

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We investigated the role of the pituitary-adrenal axis in the development of hyperinsulinemia and obesity in rats with medial basal hypothalamic deafferentation.
Female Wistar rats each weighing about 200g were used. Medial basal hypothalamic deafferentation (DEAFF) and sham-operation (SHAM) were performed after adrenalectomy (ADX) or hypophysectomy (HYPDX). After DEAFF, body weight changes and postprandial serum insulin concentrations were determined.
ADX-DEAFF rats exhibited transient body weight gain for the 4 days immediately after DEAFF. However, body weight increments in these rats were not different from those in non ADX-nonDEAFF rats on the 4th day after DEAFF. DEAFF caused significant body weight gain in ADX-DEAFF rats in which the serum corticosterone level was greater than 10 ng/ml, but did not in ADX-DEAFF rats in which the serum corticosterone level was less than 10 ng/ml. In HYPDX rats DEAFF significantly increased body weight gain and adipose tissue weight. Adrenalectomy failed to induce the postprandial hyperinsulinemia induced by DEAFF, which was observed in HYPDX-DEAFF rats.
The results of the present experiment suggest that (1) a small amount of glucocorticoid is necessary for fat deposition in DEAFF rats in the later period after treatment, (2) postprandial hyperinsulinemia is also necessary for excessive fat deposition in HYPDX-DEAFF rats, (3) an increased response of body weight gain mechanisms to glucocorticoid was observed in DEAFF rats.

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We developed a new simple pupillographic method for measuring the dark-adpated pupillary area (DAPA, mm²), using a conventional camera with an infrared flash. In this study, an attempt was made to simplify previous pupillographic methods used in diabetic autonomic function testing and to confirm the effectiveness of this method in comparison with other neurological examinations.
The procedure was reproducible with a coefficient of variation of 4.4%. One hundred and four patients with diabetes mellitus were studied and the data was compared with that from 48 age-matched normal subjects. The DAPA in normal subjects decreased with age. The DAPA in diabetics was significantly smaller than that in age-matched normal subjects and decreased in proportion to the duration of diabetes. The incidence of abnormality of DAPA was 24% in patients with 2 to 5 year durations and 77% in patients with durations greater than 11 years. The extent of vibratory perception threshold, nerve conduction velocity, heart rate variation and cold recovery test became more severe in parallel with the decrease in DAPA, but the changes in DAPA tended to appear earlier than in other examinations. Our new DAPA measurement is simple, noninvasive and reproducible and is therefore very useful for routine clinical application to estimate diabetic autonomic neuropathy.

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A 47-year-old man with a 20 year history of obesity and hypertension was referred to us because of a 2 month history of pain in the left lateral thoracic area. His height was 162cm, weight 80kg. He had poorly controlled NIDDM (HbA_1c 8.7%) with retinopathy (Scott Illb), incipient nephropathy and a mild degree of peripheral and autonomic neuropathies. His blood sugar became well controlled by diet alone but his pain continued with a noctural exacerbation. Chest and abdominal examinations including coronary angiogram and myelogram didn't reveal any cause of his pain. 7 months after the onset, he noticed a bulge in his left hypochondrium compatible with the anterior distribution of the 8th thoracic spinal nerve, the same area where he had pain. An electromyogram and muscle biopsy from the swollen area revealed a neurogenic pattern of muscle degeneration. His cerebrospinal fluid showed a moderate increase in protein content. His pain and swelling spontaneously disappeared 13 months after onset.
Our case is compatible with diabetic truncal mononeuropathy (DTM) involving not only sensory, but also motor nerves. This is the first report of this type of DTM in Japan to our knowledge.

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