Sixteen cases of diabetic ketotic coma with gastrointestinal symptoms such as anorexia, nausea, vomiting, abdominal pain and diarrhoea, and one case of non-comatose diabetic ketosis accompanying such gastrointestinal symptoms, were observed in Hyogo Prefectural Kakogawa Hospital and Nishikawa Hospital, Himeji, between 1967 and 1976.
In all cases, the severity of both the gastrointestinal symptoms and alteration of the sensorium, was found to parallel closely the levels of blood ketone bodies as well as the levels of blood fat and fatty acids, while no clear relation to blood sugar levels was observed.
These clinical results indicate that the severe ketosis was the cause of the occurrence of gastrointestinal symptoms and alteration of the sensorium.
Except in a few cases, the alteration of the sensorium followed the gastrointestinal symptoms, among which vomiting was especially frequent.
The colorimetric salicylaldehyde method based on Frommer's reaction originally proposed by Behre, was employed to estimate the blood ketone bodies, due to its rapidity and reasonable accuracy as indicated by Takenaka.
It may be concluded from the present findings that the effect of insulin action was particularly strong on fat metabolism, but unstable on blood sugar regulation.

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In 1977, the clinical use of phenformin for treating diabetes mellitus was prohibited since this substance was found to cause lactic acidosis.
Due to the strong clinical toxicity of phenformin, we used 1, 1-dimethyl-biguanide (metformin) as a biguanide (BG) preparation. The present study was undertaken to determine the effects of longterm metformin administration on blood lactate levels, arterial pH and anion gap in diabetic patients.
Thirty-five subjects receiving oral administrations of metformin, 750mg/day, for more than 3yr (BG-group), 10 normal subjects, and 94 diabetics treated without using BG, were examined.
A significant increase in blood lactate levels and anion gap, and a significant decrease in arterial pH were observed in the BG-group when compared with the other groups not receiving BG. However, the extent of the observed increase in blood lactate level (21.0mg/dl), the minimum arterial pH (7.35), and the maximum anion gap (7.1mEq/l) in the BG-group were outside the limits of the criteria for the diagnosis of lactic acidosis: blood lactate>6mEq/l (≅54.2mg/dl), arterial pH <7.33, and anion gap> 20mEq/l.
It is concluded therefore that although no patient receiving metformin therapy appeared to develop lactic acidosis, blood lactate levels and arterial pH should be carefully and regularly monitored in patients during metformin therapy since their blood lactate could easily be enhanced through various causes and so result in lactic acidosis.

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The authors have reported diminished insulin response during OGTT in mothers of large babies and nondiabetic relatives of a juvenile diabetic patient. In the present study, one of a series on prediabetes, the insulin response to glucose in relatives of diabetic patients was evaluated using 4 indices established by the authors.
A total of 822 subjects who were admitted to the authors' institute for health check-ups, were studied. Of these subjects, 84 (10.2%) gave a family history of diabetes: 49 in first degree, 18 n second degree and 17 in third degree relatives. Among nonobese subjects, a diabetic type glucose tolerance test was found at a higher rate in relatives than in nonrelatives. Insulin secretion was definitely lower in the relatives, regardless the degree of glucose intolerance. Among obese subjects, however, no difference in rate of diabetic type glucose tolerance tests was found, although the ratio of those with glucose intolerance increased in the two groups as a whole.
In subjects with normal glucose tolerance, a marked decrease in the insulinogenic index and glucose-insulin coefficient was noted in nonobese relatives, suggesting decreased acute insulin secretion. The ratio of IRI area to glucose area was lower in relatives regardless obesity, indicating diminished total insulin secretion. The ratio of the IRI area during 30 min to the whole IRI area was also lower in nonobese relatives, and the insulin response was of a delayed type in this group.
It was concluded that both total and acute insulin secretion was diminished even in relatives of diabetic patients with normal glucose tolerance.

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Measurements of beta 2-microglobulin and total protein were made in 24-hr urinesamples from 32 diabetic subjects without clinical proteinuria and 20 non-diabetic controls. Twelve of the diabetics were found to excrete an abnormally high amount of beta 2-microglobulin in the urine. In these subjects the ratio of beta 2-microglobulin to total proteinwas significantly increased, although there was a quantitative correlation between the beta 2-microglobulin and total protein in their urine. These results suggest that some diabetic subjectshave tubular dysfunction despite an apparent absence of renal involvement. The mechanism and clinical importance of such beta 2-microglobulinuria are discussed.

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The variation in R-R interval in ECG has been reported to be decreased in diabetics. However, no definite parameter exists to express the degree of R-R interval variation. In the present study, the coefficient of variation (CV) was used to express the parasympathetic function. CV is considered to be a parameter of vagal function, since the R-R interval variation is abolished after blocking the vagal nerve with atropine. The relationships between CV and sympathetic function, somatic neuropathy, diabetic retinopathy, and duration of diabetes were investigated.
ECG's were taken before and after the intravenous injection of atropine in 12 juvenile-onset type diabetics aged less than 40 yr in the resting supine position. A total of 100 consecutive R-R intervals was analyzed by computer and the interval histogram, mean and variance were recorded. The increment in plasma renin activity (ΔPRA) by standing and intravenous injection of furosemide, serum dopamine-β-hydroxylase (DBH) activity, and postural fall in blood pressure were used as parameters of sympathetic function. Somatic neuropathy was judged from loss of the Achilles jerk, and disturbed vibration sensation. The patients were divided into 2 groups either by the degree of retinopathy (i.e. up to and including Ma, or more advanced than Ma on Scott's classification) or the duration of diabetes (i.e. less or more than 6 yr). The results obtained were as follows.
1) The correlation coefficient between CV and APRA was O.76 (p<0.02) and that between CV and DBH was O.79 (p<0.02), indicating a close correlation between the degrees of disturbance of sympathetic and parasympathetic function.
2) CV was found to be reduced in diabetics of longer duration (1.56%), advanced retinopathy (1.14%) and somatic neuropathy (1.86%), as compared to age-matched healthy individuals (5.82%). The differences were highly significant (p<0.001). The correlation coefficient between CV and the duration of diabetes was -0.84 (p<0.001). suggesting that the duration of diabetes influences the development of autonomic neuropathy.
3) The coefficient of variation (CV) of the R-R interval in ECG in the resting supine position was thus shown to be a useful parameter for determining the autonomic function by a noninvasive technique.

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Postheparin plasma triglyceride lipases, i.e. hepatic triglyceride lipase and lipoprotein lipase, were purified by heparin-sepharose affinity chromatography. In the guinea pig, hepatic triglyceride lipase was found to be almost completely absent, while lipoprotein lipase was well preserved. The deficiency of the former enzyme was further confirmed by an inability to demonstrate the presence of this enzyme in liver tissue extracts. It was also found that guinea pig plasma could not activate lipoprotein lipase, indicating a lack of activator in the plasma.
On the basis of the present findings, the guinea pig appears to represent a useful animal for studying lipid metabolism in close relation to enzyme functions.

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A 59-yr-old housewife was admitted to the Kanazawa Medical University Hospital in May, 1977 due to loss of consciousness with cyanosis. She had been administered trichlormethiazide and insulin for hypertension with diabetes mellitus since March, 1977. In April, she began to complain of episodic vertigo, nausea and anorexia, was therefore treated intermittently with sodium bicarbonate to reliv relieve these symptoms. On May 11, 1977, while she was talking with her family, she suddenly suffered an attack of loss of consciousness with convulsions and cyanosis of the lips and nails. On admission she was found to be cyanotic and her ventilatory rate decreased from 16 to 12 per min with shallow chest-cage movements. She was able to perform several deep breaths, upon request. Her condition was thus consistent with the definition of Ondine's curse.
Laboratory examinations on admission revealed hyperglycemia, hypersmorality, striking hypopotassemia, and hypochloremia. Spirometry indicated that her vital capacity and tidal volume were decreased to 1200ml, and 200ml, respectively, without obstructive pulmonarydisease. Arterial gas analyses revealed metabolic alkalosis and hypercapnia, with carbonate and carbon dioxide pressure values of 41.3mEq/l, and 53.3mmHg respectively. Administration of potassium and regular insulin led to progressive improvement of the metabolic alkalosis and alveolar hypoventilation.
The aim of the present study was to determine the effects of trichlormethiazide and sodium bicarbonate on the serum electrolytes, carbohydrate metabolism and pulmonary function.
A trichlormethiazide (10mg/day) and sodium bicarbonate (24g/day) loading test induced hypopotassemia, hypochloremia and decreased minute volume and tidal volume in spirometry. Blood gas analyses then revealed metabolic alkalosis and hypercapnia.
Our clinical examinations suggested that trichlormethiazide and sodium bicarbonate induced hypopotassemia, hypochloremia, azotemia and metabolic alkalosis, followed by compensatory alveolar hypoventilation with carbon dioxide retention.
The above findings indicate a need for routine examination of serum electrolytes and arterial blood gas analysis in all diabetics with disturbance of consciousness, in order to decide the most appropriate replacement therapy for such patients.

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Diabetes mellitus involves metabolic disturbances of whole organs. The liver, which plays a central role in energy metabolism, reflects various metabolic disorders in response to nutritional demands.
It is well known that hepatomegaly due to fat infiltration or glycogen accumulation develops in the course of diabetes mellitus. We observed a case of diabetes mellitus with acute hepatomegaly and hyperlactatemia. However, no report has yet discussed the etiology of hepatomegaly and hyperlactatemia in diabetes mellitus in correlation with factors observed during the course of treatment.
In our case, the hepatomegaly was due to both fat infiltration and glycogen deposition. These conditions could be attributed to an insufficiency of fat transportation from the liver due to hypoalbuminemia and hyperinsulinemia or hyperglycemia, respectively.
The etiologic factors involved in the hyperlactatemia in our case were as follows.
1) Decrease in hepatic uptake of lactate because of hepatomegaly
2) Increase in lactate release from peripheral tissues during overnight fasting
3) Lactate overproduction by hepatic glycogenolysis
4) Use of fructose and xylitol in treatment
Hepatomegaly disappeared by correction of the insulin dose and hypoalbuminemia. Hyperlacta temia was satisfactorily improved after continuous infusion of insulin and glucose at night. We observed no recurrence of hyperlactatemia after the diabetic state and hepatomegaly had been successfully treated. These results indicate that the diurnal profile of lactate levels may provide significant information about the pathogenesis and therapy of hyperlactatemia.

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Both plasma and pancreatic insulin concentrations were determined in hypothalamic obese female rats treated with monosodium glutamate (MSG). MSG (2 mg/g B.W.) was injected subcutaneously into newborn Wistar rats everyday for 5 days after birth. On the 145th day, blood samples were taken from the jugular (j), portal (p) and caval (c) veins of the rats. Their pancreases were extracted in 2M acetic acid. The mean Lee Index, as a marker of obesity, of the MSG-treated rats was significantly higher than that in the controls. The mean plasma glucose concentration in the MSG-treated rats (119±3mg/dl) was higher than that in the controls (91±5mg/dl). Also, the mean plasma immunoreactive insulin (IRI) concentration (j: 5.7±0.9ng/ml, p: 22.0±3.3ng/ml, c: 5.0±0.6ng/ml) and the mean pancreatic IRI concentration (P: 82.9±8.9ng/μg protein) in the MSG-treated rats were markedly higher than those in the controls (j: 1.2±0.3ng/ml, p: 3.4±0.5ng/m/, c: 3±0.0ng/ml; P: 42.8±2.2ng/μg protein). It is well known that MSG destroys not only the ventromedial nucleus of the hypothalamus but also the arcuate nucleus. The above data suggest that these nucleuses play an important role in the regulation of insulin secretion.

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