The levels of alpha lipoprotein (HDL) cholesterol and beta lipoprotein (VLDL and LDL) cholesterol in diabetics were studied in relation to various pathological conditions. Each lipoprotein cholesterol was determined by the gas chromatography of extracts of fractions separated by agarose gel electrophoresis.
Results. The levels of alpha lipoprotein cholesterol (α-cho) were 55.2±16.1 mg/dl in controls (n=103) and 45. 9±15. 5 mg/dl in diabetics (n = 199). The ratio of α-cho to β-cho (α-cho/β-cho) was 0.46±0.20 in controls and 0.35±0.16 in diabetics. The incidence of high α-cho (exceeding 70 mg/dl) was significantly less in diabetics. In addition to substantial metabolic disorders of glucose, factors which may have led to a reduction of α-cho included poorly controlled hyperglycemia, obesity, advanced retinopathy and nephropathy which was recognized from proteinuria. Low levels of α-cho or α-cho/β-cho may be one of the causes of macroangiopathy (atherosclerosis), butwhether this might be a cause of microangiopathy (retinopathy, nephropathy, etc.) remains to be determined.

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Recurrent fibrinocoagulopathy such as chronic intravascular coagulation often occurs dominantly in the proliferative stage of diabetic retinopathy, and the advance of the disease is considered to be partly due to such microthrombus formation.
The plasm factors which react directly with thrombin in the final stage of blood coagulation are mainly fibrinogen, antithrombin (AT-III), and factor-XIII which is a fibrin crosslinking enzyme essentially required for fibroblast proliferation. In this respect, studies on the patterns of variation in the concentration of these three factors in the blood according to stage of retinopathy and their correlations are considered indispensable.
Blood samples were collected 4 times at 4-week intervals from 5 patients each of Scott degree Ia, IIa, III, IV-V_b, and control patients without retinopathy.
In Scott III, i.e. the early proliferative stage, a high fibrinogen concentration, both high and low factor-XIII concentrations and a good correlation (r=+0.78) between the factor-XIII and ATIII concentrations were observed.
In Scott IV'-V_b, i.e. the progressive stage of proliferation, the fibrinogen concentration was high, but the factor-XIII and AT-III concentrations were low.
The concentration of these factors in the peripheral blood should depend on the equilibrium between consumption and supply. A decrease in factor-XIII and AT-III was suggestive of thrombin generation, while an increase in fibrinogen was possibly due to an excess reaction in the biosynthetic response in relation to the consumption.
Based on these observations, the proliferative retinopathy appeared to represent a pathological state quite similar to the chronic DIC described by Ulutin et al., and participation of factor-XIII was recognized.

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Reliable preoperative localization of insulinoma is necessary to avoid reoperation. Arteriography has been considered the most valuable method for the preoperative localization of an insulinoma in the pancreas. However, the accuracy of localization is only 50 or 60%.
A patient was repeatedly subjected to selective angiography of the celiac and superior mesenteric artery, but no tumor could be demonstrated by this method, and the symptoms did not respond to medical therapy. Percutaneous transhepatic catheterization of the pancreatic vein was carried out and the levels of plasma insulin and C-peptide from the head of the pancreas were found to be 540μU / ml and 18.0 ng/ml, respectively. We confirmed a small tumor in the head of the pancreas on operation. Following surgery, the symptoms of hypoglycemia completely disappeared.
If no tumor is found at operation, and medical treatment has already failed, distal partial pancreatectomy would be indicated. However, this may be unsatisfactory since it removes only 25 to 55% of insulinomas. Therefore, if no tumor is found on arteriography, selective catheterization of the panceatic veins via a transhepatic route should be tried.

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A quantitative method for measuring the extravasation area of fluorescent dye from retinal vessels was established with a flying spot scanner (F.S.S.) equipped with a mini-computer. This method was applied to predict the development of malignant retinopathy in diabetic patients.
Fluorescein fundus angiography was performed in 49 diabetic patients. Forty-four of them had stage III diabetic retinopathy based on Scott's criteria (1957) and the remainder had new vessel formation. The fluorescein photograph was processed with the F.S.S. and mini-computer, and the extravasation area of fluorescein was computed for each photograph. Furthermore, extravasation curves were prepared by plotting the time after fluorescein injection (abscissa) against the extravasation area (ordinate) using serially photographed pictures.
Statistical analysis was performed in cases with stage III retinopathy in order to determine the relation between the degree of extravasation, expressed as the extravasation area at 120 sec afterfluorescein injection, and 13 clinical and laboratory findings, i.e., age of the patient, duration of diabetes mellitus, obesity index, systolic blood pressure, diastolic blood pressure, fasting blood sugar, urinary sugar, serum cholesterol, serum triglyceride, urinary protein, blood urea-N, phenolsulfonphthalein excretion test (15 min value) and insulinogenic index (30 min value of 50 g OGIT). The degree of extravasation was significantly correlated with fasting blood sugar, duration of diabetes mellitus, urinary protein, and insulinogenic index.
Extravasation curves of patients with new vessel formation revealed a sigmoid curve with a steep slope (N type) after fluorescein injection. The curves for stage III retinopathy were divided to three groups: sigmoid curves with a steep slope (A type) similar to the N type, a flat slope (Ctype) or intermediate (B type).
During three to six years observation, the extravasation curves of the A types became elevated in most cases, and one case developed to malignant retinopathy, whereas the extravasation curves of the B and C types remained relatively stable.
It was concluded that the extravasation phenomenon was closely related to aggravation of diabetic retinopathy, and that analysis of the extravasation phenomenon with the F.S.S. and minicomputer was useful for predicting the prognosis of diabetic retinopathy.

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The present study was carried out to determine the relation between control of diabetic state and glycosylated hemoglobin (HbA₁) in maturity onset diabetes.
The mean HbA₁ value in normal subjects was 8.4 ±1.1%(M± SD), while that in diabetics was 13.1 ± 3.4%(p<0.001).
In 70 patients, a significant correlation was found between HbA₁ and fasting blood glucose (FBS) measured on specimens obtained during the same day (r=0.57, p<0.001). A significant correlation was also found between HbA₁ and FBS measured 1 month or 3 months before (r=0.66, p<0.001; p=0.60, p<0.001). However, the relation between HbA₁ and FBS measured 5 months before was not remarkable (r = 0.49, p<0.02)
In 31 non-treated diabetics, strong cor relation was found between HbA₁ and the sum of the blood glucose values measured before and 1 hr after breakfast, lunch, dinner, and at night (r=0.86, p<0.001).
A strong correlation was found between HbA₁ and sum of the blood glucose values measured at 5 points during 50 g O-GTT (r=0.87, p<0.001). The relation between HbA₁ and the peak value of 50 g O-GTT was also highly significant (r=0.88, p<0.001). An even stronger negative correlation was found between HbA₁ and the sum of the serum IRI levels during 50 g O-GTT (r=-0. 59, p<0.01). The relation between HbA₁ and the basal IRI was not remarkable (r= -0.38, p<0.05).
The above results indicate that HbA₁ is useful as an indicator of diabetic controland degree of glucose intolerance.

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Microangiopathy and vaso-occlusive disease are recognized complications of diabetes mellitus, and platelets are probably involved in the pathogenesis of these disorders.
Increased platelet adhesiveness, an increased tendency to undergo spontaneous aggregation, and a heightened sensitivity to aggregating agents such as ADP., adrenaline and collagen, have been demonstrated in diabetic patients with vascular complications. However, there are considerable vari ations in these parameters and individual values for both control and diabetic subjects are so dispa rate that it is generally not possible to make distinctions between them on an individual basis.
β-Thromboglobulin represents a recently isolated platele-tspecific protein that is released during platelet aggregation. The sensitivity and precision of the j3-thromboglobulin radioimmunoassay have been proved satisfactory. Plasma β-thromboglobulin levels were therefore measured in blood samples from healthy control subjects and from diabetic patients with and without microangiopathic complications. The mean level of plasma β-thromboglobulin in the healthy controls was 24 ng/ml (n =36). The patients with retinopathy had significantly elevated β-thromboglobulin levels (56.2 33.5ng/ml, n=18), although no correlation was found between the plasma β-thromboglobulin and the extent or activity of the diabetic complications. There was no significant difference between the diabetic group without vascular complications and the healthy controls.
Diabetic patients in the stroke process of cerebral thrombosis at the time of examination had markedly elevated β-thromboglobulin levels, while diabetic patients in an established thrombotic state showed normal blood levels of β-thromboglobulin.
The above results are considered to provide additional evidence that platelet function in dia betes mellitus is abnormal. If elevation of the thromboglobulin concentration proves to be an early change associated with the development of widespread vascular lesions, use of this parameter in the assessment of the risk of developing vascular change may become possible.

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A 31-yr-old juvenile diabetic woman with 6 episodes of cardiorespiratory arrest is described. She had been treated irregularly with insulin for 14 yr before admission. Her history revealed ketoacidotic coma at 21 yr of age and brittle diabetes during these years. Physical examinations revealed severe diabetic complications including cataract, retinopathy to blindness, and anasarca due to nephropathy. In addition to the presence of sensory polyneuropathy, there were varied clinical symptoms associated with autonomic involvement. These consisted of orthostatic fainting, intractable vomiting, intermittent diarrhea, hypotonic bladder, etc.
The first cardiorespiratory arrest occurred following an injection of 5 mg diazepam used for alleviating recurrent vomiting one month after admission. External cardiac massage and assisted respiration under oxygen inhalation succeeded ineffecting rapid resuscitation. Six similar attacks have occurred in total without signs and symptoms of hypoglycemia or dysrhythmia. It was considered that continuous oral administration of diazepam might be one of the predisposing factors responsible for the repeated cardiorespiratory arrests.
Variations in beat-to-beat interval recorded with a cardiotachometer were examined on Valsalva's maneuver, deep breathing, standing, and with autonomic blocking agents such as propranolol and atropine sulfate. However, no significant changes in beat-to-beat variation were found in any of these tests. A fall in systolic blood pressure over 40 mmHg (diastolic over 20 mmHg) was observed after standing up, combined with a marked decrease in cardiac index.
It appears therefore that the cardiac autonomic innervation has been seriously impeded in this patient, and moreover, regulation of the cardiovascular reflex has been lacking. It is concluded that the principal cause of the repeated cardiorespiratory arrests may be closely associated with the cardiac denervated state.
Cardiorespiratory arrest due to diabetic autonomic neuropathy is rather rare. In fact, the present report may represent the first detailed description of such a case in Japan.

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Hand changes in juvenile diabetics are not so rare as is usually supposed. A longterm case of juvenile diabetic cheiroarthropathy, characterized by marked involvement of the interphalangeal joints of both hands, flexion of the fingers, and stunted growth, was observed.
The patient was a 22-year--old woman 141 cm tall. At the age of 6 she experienced a diabetic coma and was diagnosed as having diabetes mellitus. Since then she had been receiving insulin. Control of blood glucose was poor, and her diabetes was complicated by diabetic neuropathy, retinopathy, and nephropathy. At the age of 24 she died of renal insufficiency caused by diabetic nephropathy.
Her liver was palpable 1 finger breadth below the right costal margin. Only the interphalangeal joints of her hands showed articular involvement, other joints showing no abnormalities. Dupuytren's contracture was not present.
An X-ray film of her hands revealed slight atrophic changes but no articular changes. There was no family history of diabetes mellitus or stunted growth.

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Increased activities of intestinal alkaline phosphatase (ALP) have been found in the sera of blood group 0 or B secretors and this is augmented by fatty meals. The frequency of demonstration of high intestinal ALP activities is greatest in liver cirrhosis and significantly high in diabetes mellitus. It is not known, however, whether the increased activity in diabetics is due to the diabetes mellitus per se or to hepatic injury associated with it. We experienced a case of juvenile-onset diabetes mellitus with markedly elevated intestinal ALP. Detailed studies were made on this case with respect to the above point. The patient was a 21-year-old male of blood group B secretor. the initial fasting blood glucose level was 240 mg/dl with strongly positive urine glucose and weakly positive urine ketone bodies. Serum ALP was markedly elevated to 17.2 B-L u with slightly increased GOT (88 u) and GPT (100 u). The ALP was mostly of the β-migrating intestinal type upon agar-gel electrophoresis with more than 50 % inhibition by 5 mM L-phenylalanine. The increase in intestinal ALP was enhanced after a fatty meal. The ALP level decreased following insulin treatment and rose after its cessation, indicating the presence of a close correlation between them. No such relation was found with the blood glucose level, GOT or GPT activities. Involvement of liver injury was discounted by peritoneoscopy and liver biopsy. The above results suggest that a direct relationship may exist between elevation of intestinal ALP and insulin insufficiency.

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The cause of insulin lipoatrophy has remained unknown. The highly purified insulin preparation, Monocomponent Insulin (MC Insulin), has been reported by some investigators to be useful for the treatment of insulin lipoatrophy. However, we encountered a diabetic woman treated only with MC Insulin who demonstrated insulin lipoatrophy. She had been treated for 5 years with the MC Insulin and produced insulin antibody in her serum. The insulin antibody and a-component antibody in her serum were frequently examined from the commencement of the MC Insulin therapy. Slight subcutaneous fat atrophy was demonstrated in the regions of insulin injection in the extremities after treatment for 2 years, when the level of insulin antibody was maximal. The level of insulin antibody decreased gradually after that time. On the other hand, the subcutaneous fat atrophy became increasingly clear. A-component antibody was not demonstrated during the first 4 years, but was produced after 4 years.
The results for this case suggested the possibility that insulin lipoatrophy could even be induced by MC Insulin injections, and the insulin lipoatrophy might be due to insulin impurities such as a-component.

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A 34-yr-old female patient with juvenile onset diabetes developed atony and dilatation of both the bulb and loop of the duodenum, i.e. megaduodenum. She showed various symptoms of diabetic gastroenteropathy including constipation, nocturnal diarrhea and recurrent attacks of nausea and vomiting. Neurological examinations revealed diminished or absent reflexes and a sense of vibration of the extremities. The evoked EMG requision showed a low voltage and low duration. The ECG R-R interval requision revealed cardiac denervation. These findings suggested that she had peripheral diabetic neuropathy and autonomic neuropathy. X-ray examination of the upper gastrointestinal (GI) tract on her first admission revealed gastric atony, gastric retention, and disturbance of expulsion of the gastric contents without evidence of organic obstruction, i.e. functional pylorus stenosis. After 18 months, the upper GI series showed atony and dilatation of the duodenal bulb. Further, 5 years later, the X-ray findings for the duodenum revealed atony and dilatation of the duodenal loop in addition to the above findings. The patient was given ambenonium chloride (10 mg per day) as treatment for the atony and dilatation of the stomach and duodenum. An improvement of subjective symptoms was obtained, but no change was noted in the X-ray findings of the upper GI tract. Although no clear explanation of the pathogenesis of diabetic gastroenteropathy has yet been made, it seems likely that a close relation exists between gastrointestinal atony and diabetic neuropathy. It was thought of interest to report the present diabetic case with atony and dilatation of the duodenal loop, due to the rarity of this condition.

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A case of lactic acidosis in diabetes presumably induced by a large intake: of alcoholic beverage (whisky) and concomitant pneumonia is reported.
A 41-yr-old female was admitted to hospital due to disturbance of consciousness. She has had insulin dependent type diabetes for 5 years, following its detection by ketoacidosis coma.
On the day before admission, she had injected her usual dose of insulin and taken a bus trip. On the way, she drank a large amount of whisky. Nausea, vomiting, lethargy and general muscular pain ensued and she was taken to a local doctor's office. At that time her blood glucose was 676 mg/dl and her urine ketone was negative. In spite of an additional injection of insulin, her consciousness gradually deteriorated. She fell into an agitated state and was transferred to our ward. On admission, she was in a delirious condition. High fever and moist rales over the entire lungs were recognized. Her blood glucose was 340 mg/dl and blood gas analysis revealed the presence of hypoxia and metabolic acidosis, paO₂ 56.8, pCO₂ 14.2 mmHg, base excess -21.9 mEq/L, blood pH 7.182 and anion gap 26.6 mEq/L. Urine ketone was negative. Blood lactate was 5.27 mM, pyruvate O. 124 mM and the lactate/pyruvate ratio 42.6, indicating abnormal accumulation of lactate in the blood. In spite of oxygen supply, she rapidly fell into deep coma. Chest X-P revealed severe extensive pneumonia. Insulin, sodium bicarbonate, Tris buffer and antibiotics were administered and respiration was controlled with a respirator by the continuous positive pressure method. The patient recovered from the deep coma in 4 days. Abnormal elevation of blood urea nitrogen and creatinine persisted for 3 weeks, but finally normalized. LDH and amylase levels in the blood were elevated during the acute phase. After improvement, there was no impairment of renal and hepatic functions. Following the acute phase, her diabetes was found to be of the brittle type. There was virtually no response of blood C-peptide during the oral glucose tolerance test and the 24-hr urine C-peptide was almost undetectable.
Lactic acidosis in diabetes occurs mainly in patients treated with biguanide drugs. However, our patient did not take any biguanide. Her large intake of ethanol is thus considered likely as the precipitating cause of the lactic acidosis, and hypoxia due to severe pneumonia appears to have aggravated lactate accumulation.

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