A survey was made of the causes of death in 385 patients with primary diabetes who diedduring the three-year period from 1977 to 1979 in Ehime Prefecture, based on questionnaires sent to the members of the Ehime Medical Association.
The mean age of death was 67.4 years and the average duration of illness was 8.7 years for the 385 cases reported (193 males and 192 females).
The most frequent cause of death was cerebrovascular disease (21.0%), followed, in order, by heart disease (20.3%), infection (15.6%), malignant neoplasm (13.5%), renal disease (12.2%), diseases of the digestive organs (6.2%), diabetic coma (5.5%), hypoglycemic coma (0.8%) and others (4.9%).
When analyzed according to the place where death occurred, the incidence of deaths showed high values for malignant neoplasms, heart diseases, cerebrovascular diseases and renal diseases at hospitals. At physician's offices and patient's homes, however, cerebrovascular diseases and heart diseases were the most frequent causes, whereas deaths from renal diseases and malignant neoplasms showed an extremely low incidence.

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The changes of HbAt and red-cell 2, 3 DPG on 100 g OGTT were studied in 9 diabetics and 10 non-diabetic control subjects.
The results obtained were as follows:
(1) The HbAi levels in the 9 diabetics increased gradually after glucose ingestion. The average level reached its highest point at 180 min, and there was a significant increase between the level before glucose ingestion and that after 180 min, based on the student pair t-test (p<0.01).
These findings suggested that HbAi was produced by the hyperglycemia for glucose load, and that fast glycosylation of HbAi is partially effected during 100 g OGTT.
(2) In the case of the diabetics, the serum inorganic phosphate concentrations after glucose ingestion decreased a little and at the same time the red-cell 2, 3 DPG levels increased in 7 of the 9 diabetics, but not significantly. In the non-diabetic control subjects, the average level of serum inorganic phosphate after glucose load reached its lowest point at 60 min and returned to the original level at 180 min. In this group, the redcell 2, 3 DPG levels decreased significantly on glucose load, both at 30 min and at 60 min. (p<0.05).
It can be hypothesized therefore that, because the IRI responses increased after glucose load, the serum inorganic phosphate decreased and led to a relative decrease of red-cell 2, 3 DPG concentration in the controls. On the other hand, such phenomena did not occur in the diabetics.

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The present investigation documents the alkaline phoshatase (ALP) isoenzyme fractions in a large number of diabetic patients, relates the findings for intestinal-type ALP isoenzyme (i-ALP) to the diabetic state, and assesses any changes in serum ALP isoenzyme patterns following treatment with diet and drug or insulin. Electrophoretic determinations were made on serum samples collected before breakfast from a group of 50 normal subjects and 286 diabetic patients, including 20 cases with ketone bodies in the urine. Samples were taken on the 2nd day and again on the 14th day following admission. Serial determinations of serum ALP isoenzymes were also carried out in a group of 9 patients with diabetic coma. The prevalence of significant amounts of i-ALP was higher in diabetics (26.2%) than in normals (10.0%). Of the 286 diabetics, 73.8% had no demonstrable i-ALP (group 1), whereas the others had significant amounts of i-ALP in the serum obtained on the 2nd admission day. However, i-ALP then disappeared from the serum in 17.1% of the total diabetics on the 14th day (group 2). In the remaining patients (9.1%, group 3), no significant changes were observed in the amounts of i-ALP between samples taken on days 2 and 14. Patients of group 3 were ABH secretors of blood group B or O.
The prevalence of i-ALP in ABH non-secretors of blood group A, AB, B or O and ABH secretors of blood group A or AB in diabetic patients was nearly the same as that in normal subiects. On the other hand, the prevalence of i-ALP in diabetic ABH secretors of blood group B or O was higher (63.9%) than that in normal subjects (20.0%). Most of the patients in group 2 were either untreated or under a poor state of control at the time of admission. i-ALP was significantly more frequent in diabetic patients with ketone bodies in the urine (35.0%) and diabetic coma (55.6%) than in those without ketones, and the incidence of i-ALP observed on electrophoresis increased in proportion to the aggravation of the diabetes mellitus. The i-ALP found in patients with diabetic coma disappeared on treatment and improvement of the diabetes mellitus. These results indicate that not only a genetic predisposition but also metabolic disorders of diabetes mellitus due to lack of insulin, appear to be concerned with the appearance of i-ALP in the serum.

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Serum LCAT activity was measured in 82 diabetics and 50 non-diabetic controls in order to examine the mechanisms of hyper HDL-cholesterolemia in diabetics treated with insulin. The serum HDL-cholesterol levels of diabetics treated with insulin were significantly higher and the serum triglyceride levels of female diabetics treated with insulin were significantly lower than those of the other groups (diabetics treated with oral agents, diet alone and controls).
However, the serum LCAT activity of diabetics treated with insulin was not significantly different from that of other groups.
The important role of hyper HDL-cholesterolemia in diabetics treated with insulin may be due not to serum LCAT activity, but rather to enhanced serum LPL activity by exogenous insulin.

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A diabetic patient (35 years old, male) complicated with acromegaly showed continuous diarrhea lasting for more than 1 year. He had severe diabetes and his blood sugar levels remained unstable despite insulin therapy. The diarrhea persisted after pituitary extirpation. Daily fecal fat excretion reached 28 g but he revealed no symptoms of malnutrition except for slight hypocholesterolemia. His exocrine pancreatic function and plasma VIP levels were normal.
The gastric emptying rate (acetaminophen absorption method) and transit in the upper digestive tract (lactulose-breath hydrogen method) were markedly accelerated. A shortening of the transit time in the total digestive tract (single stool-marker method) was also noted. Plasma motilin levels measured serially during fasting were strikingly elevated and showed fluctuations. The motilin levels tended to decrease after test meal ingestion.
Although the precise etiology of the diarrhea in the present case could not be elucidated, its mechanism appeared to be related to the marked increase in motility of the upper digestive tract. The increase in both gastrointestinal motility and plasma motilin was unusual. Its was not found in diabetic patients complicated with neuropathy and gastrointestinal dysfunction. Thus, the increased gastrointestinal motility probably causing diarrhea in the present patient may be based on the elevated motilin level or vice versa.

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A 42-year-old woman with diabetic ketoacidosis and fever was admitted to another hospital. She was treated by intravenous infusion of fluid, insulin and antibiotics. She was subsequently transferred to our hospital for further examination of a tender mass in the right upper quadrant in May, 1979.
Physical examinations revealed a wasted female with a temperature of 38.5°C, pulse of 78, and blood pressure of 112/70 mmHg. Initial laboratory studies gave a white blood cell count of 8, 900, fasting blood glucose of 304 mg/100 ml, blood urea nitrogen of 31 mg/100 ml, and creatinine of 2 mg/100 ml. Urinalysis showed glucose (+), acetone (-), protein (+), with numerous white blood cells per high power field. Urine culture yielded Micrococcus. A plain X-ray of the abdomen demonstrated unusual gas overlying the right renal bed. A drip infusion pyelogram revealed a normalappearing left kidney but non-functioning of the right kidney. A retrograde pyelogram indicated no ureteral obstruction. A diagnosis of gas-forming infection of the right kidney (so-called emphysematous pyelonephritis) was made. The patient did not improve despite intensive medical therapy and the right kidney was speculated to have suffered severe necrosis. Nephrectomy was therefore performed. Gas chromatographic analysis of the gas obtained from the kidney during the operation, demonstrated a significant content of carbon dioxide. Culture of pus obtained from the kidney yielded a heavy growth of E. coil. Pathologic examinations showed that the kidney parenchyma was almost totally destroyed by a yellow purulent abscess. Post-operatively, the patient recovered rapidly and her diabetes was controlled with 12 units of lente insulin daily.
A review of the 62 previously reported cases plus our own case of emphysematous pyelonephritis suggests that the majority of the patients are diabetic and emphasizes that from the viewpoint of treatment, surgical intervention tends to reduce the mortality of this lethal disea

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Gross hypertriglyceridemia induced by alcohol in a diabetic patient is reported. A 61-year-old female with a family history of diabetes mellitus and hyperlipidemia was admitted to our hospital due to general malaise. She had drunk a moderate amount of alcohol more or less every day for 30 years. Diabetes mellitus had been diagnosed 15 years previously and she had been treated for the previous 6 years. At the age of 59, poor control of blood glucose, alcoholic hepatitis and hypertriglyceridemia with lactescent serum were noted and she was first admitted to the Diabetes Center. After admission, she stopped ingestion of alcohol and began dietary treatment. During a 3-week hospitalization, serum triglyceride and liver tests returned to normal levels with a definite improvement in glucose intolerance, but hypercholesterolemia persisted. Six months later, the patient resumed drinking. Hyperlipemia recurred and gradually increased until the triglyceride and cholesterol levels were 2, 961 mg/dl and 736 mg/dl, respectively. On second admission, she had xanthoma, diabetic retinopathy (Scott II), cardiomegaly and hepatomegaly. With dietary treatment and abstinence from alcohol intake, the triglyceridemia, LCAT activity and HDL-CH returned to normal. Serum cholesterol and VLDL-CH improved but were not satisfactory. We noted a recurring phenomenon of endogenous hypertriglyceridemia followed by its disappearance during a brief hospitalization. The clinical course indicated that the ingestion of alcohol exaggerated the lipidemic response in this diabetic patient with familial hyperlipoproteinemia. These factors were considered to increase the endogenous triglyceride synthesis

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Type III hyperlipoproteinemia (HLP) is a disorder characterized by abnormal accumulation of intermediate density lipoprotein (IDL, remnant) and premature atherosclerosis. Only a few cases of type III HLP secondary to diabetes mellitus without ketoacidosis have been reported in Japan.
A 68-year-old male diabetic patient with type III HLP, femoral arterial occlusion and myocardial infarction is described in this paper. He was admitted to our hospital due to of intermittent claudication. He had suffered from myocardial infarction 8 years previously, and was then readmitted to our clinic several times complaining of dyspnea.
The patient had received acetohexamide (500 mg/day) until 6 months prior to admission, and was thereafter treated with insulin.
The plasma cholesterol and triglyceride levels on admission were 303 and 393 mg/dl, respectively. Agarose gel electrophoresis revealed broad beta bands. The values for the cholesterol in VLDL (d<1.006 g/ml), VLDL-cholesterol to VLDL triglyceride ratio, and VLDL-cholesterol to total triglyceride ratio were 113 mg/dl, 0.43, and 0.302, respectively, and were compatible with the laboratory diagnostic criteria of type 1ff HLP. The electrophoretic pattern changed from type III to type II b after treatment by diet and insulin. Both the postheparin lipoprotein lipase and hepatic lipase activities were normal.
Three phenotypes, ApoE-N, ApoE-ND, and ApoE-D (E-III deficiency pattern), were differentiated on the basis of the ApoE- II /ApoE-III ratios by isoelectric focusing of ApoVLDL. The ratio was 0.74 in the present case, which was compatible with ApoE-ND.Such an ApoE composition may contribute to the development of type III HLP secondary to diabetes mellitus. It is concluded that such abnormal lipoprotein metabolism may play an important role in the development of severe atherosclerotic vascular disease in diabetes mellitus.

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