Serum high-density lipoprotein (HDL)-cholesterol concentrations were measured in 79 diabetics and 84 non-diabetic controls using the Heparin-Mn2+precipitation method. The platelet adhesivenessand aggregation in the diabetics were also measured.
The mean (±SEM) HDL-cholesterol concentrations of the diabetics (52.8±1.9 mg/dl) were significantly lower than those of the controls (60.6±1.3 mg/dl; p<0.001). There were no significant differences in HDL-cholesterol concentrations by age and sex except in the case of over 70-yr-old control women. The HDL-cholesterol concentrations were significantly reduced in obese controls compared to non-obese controls (42.8±2.6 vs. 60.6±1.3 mg/dl; p<0.001). Among the non-obese subjects, the HDL-cholesterol concentrations were significantly lower in the group on sulphonylureas compared to the controls (p<0.01). The HDL-cholesterol in diabetic patients on insulin and on diet therapy alone was not significantly different from that in the controls. The ratios of HDLcholesterol to total cholesterol were decreased in the diabetics on insulin (p<0.05) and on diet therapy alone (p<0.01), but these ratios were not significantly different in the three groups. The mean HDL-cholesterol concentrations were significantly lower in diabetics with angiopathy (including macroangiopathy and microangiopathy) than in those without (p<0.001).
Platelet hyperaggregability tended to be associated with decreasing HDL-cholesterol concentration. It was concluded that a low HDL-cholesterol/total cholesterol ratio as well as a low level of HDLcholesterol may play an important role in the occurrence and progression of angiopathy in diabetics.

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The concentration of vitamin E (Vit. E) in very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) was determined by the fluorometric method in 34 diabetic patients to elucidate the role of Vit. E in diabetic angiopathy. Each value for the diabetics was compared statistically with data for 19 age-matched controls.
The total plasma concentration of Vit. E (Tot.-Vit. E) was 1.58±0.10 mg/dl (mean±SE) in the diabetics. This was significantly higher than the value of 1.30±0.07 mg/dl in the controls (p<0.05).
The percent distribution of Vit. E into VLDL (% VLDL-Vit. E), LDL (% LDL-Vit. E) and HDL (% HDL-Vit. E) was calculated.% VLDL-Vit. E in the diabetics was significantly higher than that in the controls. On the other hand, % HDL-Vit. E in the diabetics (25.6±1.5%) was significantly lower than that in the controls (34. 8±2.1%) (p <O.01). There was no significantdifference in % LDL-Vit. E between the two groups.
Since it has been reported that Tot-Vit. E tends to be higher in cases of hyperlipemia, subjects without hyperlipemia should be studied. As regards Tot.-Vit. E, there was no significant diffei ence between diabetics and controls, but % HDL-Vit. E in the diabetics (28.4±2.0) was again significantly lower than in the controls (35.3±2.4).
In diabetics with diabetic retinopathy or ischemic heart disease, % HDL-Vit. E and the concentration of vit. E in HDL (HDL-Vit. E) were significantly lower than those in diabetics without angiopathy (p <0.05).
The above results indicate that the Vit. E in plasma-lipoprotein fractions, especially HDL-Vit. E, has a close relationship to diabetic angiopathy.

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The relationship between the HbAic and blood glucose levels of untreated diabetics, and the changes in HbAic after one month's treatment, were studied.
The results obtained were as follows.
1) The HbAic concentrations in untreated diabetics (11.18±2.27, mean±SD, percent of total hemoglobin) were significantly higher than those of normal subjects (5.32±0.63%, p<0.001).
2) The concentrations of HbAic in untreated diabetics were correlated with the fasting blood glucose levels measured on the same samples (r=0.51, p<0.001).
3) HbAic concentrations were closely associated with blood glucose levels at 1 hr and 2 hr of oral glucose tolerance tests (r=0.39, p<0.05; r=0.42, p<0.02, respectively).
The HbAic levels before and after diabetic treatment were compared in 19 diabetics (taken from a group of 43 untreated diabetics) who were measured for HbAic after 1 month's treatment, and in 6 patients who were changed to an alternative treatment due to poor control.
The results obtained were as follows.
1) After 1 month's treatment, the decrease in HbAic was similar in all cases where the blood glucose level had dropped to the same extent, whether treated with diet alone, sulfonylurea or insulin.
2) After 1 month's treatment, the decrease in HbAic was slower in patients with retinopathy than in those without retinopathy.
These findings indicated that the concentrations of HbAic in the untreated diabetics fully reflected the degree of hyperglycemia at that time.
The decrement of HbAic levels after 1 month's treatment was similar among the three kinds of therapy, but was slower in the diabetics with retinopathy than in those without.

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In recent years, dietary fibers (unabsorbable plant polysaccharides) have been used successfully in the treatment of diabetics and have also been shown to exert a hypocholesterolemic action. We therefore investigated the influence of glucomannan (prepared from tubers of Amorphophallus Konjac) on the glucose and lipid metabolism of diabetics, and the effects on glucose tolerance of two dietary fibers (glucomannan and guar gum) were compared.
During 50 g oral glucose tolerance tests (OGTT), the peaks in the blood glucose and serum insulin concentrations were slightly delayed and reduced by the addition of 2.6 g glucomannan, both in 5 healthy men and in 10 diabetics. This suggested that the action of glucomannan may delay the absorption of glucose from the small intestinal lumen as do other dietary fibers.
On addition of 2.6 g guar gum, the OGTT results improved in 5 normal subjects, but there was no improvement in 4 diabetics.
The plasma glucagon levels were unchanged during the OGTT on addition of either glucomannan or guar gum, while the plasma gut glucagon levels were slightly suppressed during the OGTT on addition of glucomannan.
When 13 diabetics patients (adult type) had their metabolic ward diets supplemented with 3.9 or 7.8 g glucomannan daily for 90 days, their mean serum cholesterol at 20 days fell by 11.2%(P<0.1) and their mean fasting glucose fell by 29%(P<0.025) for 30 days. The dose of insulin or hypoglycemic agents was therefore reduced or, in some case, withdrawn.
The serum total bile levels were reduced during the OGTT on addition of 2.6 g glucomannan.
It is suggested that the hypocholesterolemic activity of glucomannan may be due to impairment of cholesterol and bile acid absorption from the small intestinal lumen.
We conclude that glucomannan may be a useful agent for the treatment of diabetic patients as well as guar gum and pectin.

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The purpose of the present study was to investigate the pancreatic polypeptide (PP) binding antibodies and their immunological properties in the sera of insulin-treated diabetics. The amount of contaminating immunoreactive PP in commercial insulin preparations was measured by radioimmunoassay, and the PP binding antibodies were determined by three methods, i.e. with polyethylene glycol (PEG), gel filtration, and specific radioimmuno-precipitation (SRIP). The results were obtained were as follows.
1) Significant amounts of immunoreactive PP (2.5-1, 700 pg/unit insulin) were detected in some commercial insulin preparations, but not in a highly purified new insulin preparation.
2) Although no specific binding of ¹²⁵I-bovine PP with sera was found in 30 healthy subjects and 75 non-insulintreated diabetics, PP binding antibodies were found in 24 out of 106sera (22.4%) from insulin-treated diabetics.
3) The immunoglobulin class of these PP binding antibodies was uniformly classified as IgG. Their types of light chains showed variety, including bitypic patterns (both the K-and λ-type) and monotypic patterns (the K-or λ-type).
In 10 out of 13 cases, the PP binding antibodies showed a significantly high affinity for bovine PP as compared to human PP. However, in the other 3 cases, they showed almost the same affinities for bovine and human PP.
It is concluded that the PP binding antibodies which can be demonstrated in insulin-treated diabetics might to induced by the administration of commercial insulin containing small amounts of PP (porcine or bovine).

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To determine whether or not the pancreatic A cell dysfunction observed in diabetics is reversible, plasma glucagon responses to an oral glucose load, arginine infusion and insulin-induced hypoglycemia were investigated before and after diabetic treatment in 15 adult onset diabetic patients consisting of 10 men and 5 women. Along with the plasma glucagon (GI), the responses of plasma C-peptide (CPR) and blood glucose were also studied under the same circumstances.
The fasting blood glucose concentration was decreased from 219±14 mg/dl (the value before treatment) to 120±5 mg/dl after treatment, and the peak value of the blood glucose during OGTT prior to treatment, 400±18 mg/dl, fell significantly after treatment reaching a corresponding value of 282±14 mg/dl. A significant difference was observed in the plasma CPR concentrations at 90 min (p<0.05) and 120 min (p<0.01) during OGTT before and after treatment.ΣCPR, the incremental area of the plasma CPR, was significantly increased from 130±34 ng·min/dl. (the value before treatment) to 276±56 ng·min/dl after treatment (p<0.05). The plasma GI level was not suppressed during OGTT either before or after treatment in the diabetics. Thus, the pancreatic B cell response to hyperglycemia was significantly improved, but the A cell function to the same stimulus revealed no remarkable change after treatment. The exaggerated response of plaima glucagon to i.v. arginine was reduced following appropriate treatment.ΣGI, the incremental area of the plasma GI, was decreased from 9901±1567 pg·min/ml (the value before treatment) to 7366±1224 pg·min/m/ after treatment, but the difference between these values was not statistically significant. After treatment, the plasma CPR response to i.v. arginine was increased and consequently a significant augmentation of ΣCPR resulted.
The patients revealed a minimal level of blood glucose at 45 to 60 min after insulin injection. The blood glucose before and after the treatment during ITT showed nadirs of 46±4 mg/dl and 36±4 mg/dl, respectively. The latter value was significantly lower than the former (p<0.05), though both fall into the hypoglycemic range. The rate of blood glucose fall was similar in both situations. No significant change in plasma GI level was observed during ITT before the treatment, but it was significantly elevated after the treatment from an initial level of 130±11 pg/ml to a peak of 176±14 pg/m/ at 90 min. Also, the plasma GI values at 45, 60, 90 and 120 min were significantly higher than the initial level in the controlled patients. Likewise, ΣGI was significantly increased after the treatment, showing values of 1158±556 pg·min/ml before treatment and 3318±795 pg·min/ml after treatment (p<0.05). These results indicate that not only the B cell but also the A cell dysfunctions encountered in uncontrolled diabetics are reversible in part after treatment.

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Diabetic patients with ketoacidosis (1 case) and ketosis (3 cases) were treated with an artificial pancreatic beta cell system, comprising a closed-loop control system.
The results of such treatment were very satisfactory. The initial insulin infusion rates ranged from 24.2 to 140.6 mU/min, as calculated according to the glucose concentration and the rate of change in blood glucose concentration in each patient. By 5 to 8 hr after treatment, the blood glucose had decreased to levels of 100 to 170 mg/100 ml with a mean rate of decrease in blood glucose oncentration of 96±8 mg/100 ml·hr. The amounts of insulin infusion were26 to 40 U/8 hr. In 3 out of the 4 patients, plasma 3-hydroxybutyrate levels decreased rapidly andreturned to normal levels within 8 hr. In one patient, the 3-hydroxybutyrate levels decreased gradually to normal levels by 4 days after lente-insulin treatment (20 to 28 U/day) following artificial pancreatic beta cell application, even though the blood glucose concentrations were controlled at near170 to 200 ml/100 ml.
The present artificial pancreatic beta cell system is considered useful for clinical application, such as in the treatment of diabetic ketoacidosis or ketosis. By changing the parameters of the insulin infusion algorithm, it should be possible to regulate the diabetic conditions more effectively, and to provide optimal as well as adaptive control of blood glucose.

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Observations on ¹²⁵I-insulin degradation by human placental membranes obtained from mature and immature placentae of normal pregnant women, have shown that such degradationdepends on the incubation time, temperature and membrane concentration.
This paper compares the ¹²⁵I-insulin degradation by placental membranes of pregnant diabetics with that of normal pregnant women.
Placentae from 12 pregnant diabetics were obtained from deliveries at 38-40 weeksof gestation. One diabetic was treated by diet alone and the others with insulin throughout pregnancy. Control during pregnancy was good.
Placental membranes of 100, 000 g pellets were prepared by Posner's method, and membranes washed twice were used. The degradation experiments were carried out according tothe previously described method, using rebinding, TCA precipitability, immunoreactivity and gel-chromatography.
Placental membranes from normal pregnant women, and incubation of ¹²⁵I-insulin without membranes, were utilized as controls.
The 125I-insulin degradation by diabetic placental membranes was found to be muchgreater than that by non-diabetic membranes. In diabetics, the mean ¹²⁵I-insulin degradation rate was 21.7% at 5 min incubation, 53% at 40 min and 70% at 90 min, whereas in normal pregnant women, it was 8.7% at 5 min, 34.3% at 40 min and 48. 2% at 90 min. Significant differences were apparent at each incubation time between the membranes of normal pregnant women and those of pregnant diabetics. No significant differences in degradation were found between normal pregnant women and one diabetic with an intrauterine death.
It is suggested therefore that degradation systems may play a role in the regulation of insulin concentration in placental tissues.
It remains unknown, however, why the degradation in diabetics should be larger than that in non-diabetics. Further studies along these lines are clearly required.

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Hypophosphatemia has been known to develop during the treatment of diabetic ketoacidosis, but its clinical and pathological features have received little attention. Recently, several workers have suggested that the management of diabetic ketoacidosis should include phosphate replacement.
We present here two cases of diabetic coma associated with severe hypophosphatemia which developed during the treatment of diabetic ketoacidosis.
Case 1: A 19-yr-old man was admitted to our hospital with diabetic coma associated with mild acidosis. His laboratory data were: pH 7.34, HCO₃-13 mEq/l, blood sugar 425 mg/dl, urinary ketone bodies 2+. The diabetic ketoacidosis was treated with physiological saline and regular insulin. Urinary ketone bodies disappeared at 5 hr after the treatment but his level of consciousness did not change. The plasma phosphorus level on admission was very low, 0.7 mg/dl. On the second hospital day, he was given 9 mEq of sodium acid phosphate intravenously. At 32 br aftder the treatment, he became alert, when his plasma phosphorus level increased to 1.3 mg/dl and he complained of myalgia and muscular weakness of the bilateral upper extremities. On the 6th hospital day, he was suspected of cerebral hypofunction based on the results of electroencephalography, but the findings became normal on the 38th hospital day.
Case 2: A 38-yr-old woman was admitted to our hospital with diabetic coma. Her laboratory data on admission showed the following values: pH 7.06, HCO₃-5.6 mEq/l, blood sugar 522 mg/dl, urinary ketone bodies 2+, plasma phosphorus level 3.3 mg/dl. She received physiological saline, 5% xylitol and regular insulin treatment. At 4.5 hr after the treatment, her blood sugar level decreased to 230 mg/dl and her plasma phosphorus level to 1.2 mg/dl. On the morning of the second hospital day, her consciousness improved and urinary ketone bodies were negative. However, at noon on the same day, a shock state which was thought to be due to sepsis, developed and her level of consciousness progressively decreased. On the 8th hospital day, she diedof acute renal failure. The plasma phosphorus level on the 3rd hospital day was markedly low, 0.4 mg/dl. On the 6th hospital day, Jackson's epileptic seizures had developed and were thoughtto have been precipitated by severe hypophosphatemia. Autopsy findings included chronic pancreatitis with mild decrement of the numbers of islets of Langerhans, acute renal tubular necrosis, fatty degeneration of the liver, subarachnoidal hemorrhage of the r-temporal lobe, and degeneration of both cerebral and cerebellar nerve cells. However, findings compatible with sepsis were not revealed by the autopsy.
In diabetic ketoacidosis associated with shock, prolonged deep coma or other complications, phosphate replacement therapy should be given consideration.

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In diabetic patients, orthostatic hypotension is often found as one expression ofautonomic dysfunction. We therefore studied the impairment of the autoregulation of the cerebral circulation in diabetics with orthostatic hypotension.
The subjects consisted of 20 controls and 7 patients with diabetic orthostatic hypotension. Rheoencephalography was used to estimate the cerebrovascular resistance (CVR). That is to say, we measured the anacrotic section of the rheoencephalograrn from its initial rising point to its top, and then calculated its relative part towards the single cardiac cycle. This parameter provides information on vascular tone and cerebral resistance. The cerebral blood flow (CBF) was calculated by dividing the mean arterial blood pressure (MABP) by the CVR. The changes in CVR and CBF between the supine and tilting positions were analyzed quantitatively by using the following dysautoregulation indices (DAI):
DAI_CVR=-Change in CVR (%)/Change in MABP (mmHg)
DAI_CBF=-Change in CBF (%)/Change in MABP (mmHg)
The DAI_CVR was +0.60±0.73 in diabetics and -0.63±0.73 in controls, suggesting a significant increase in CVR in diabetics (p<0.01). On the other hand, the DAI_CBF was-1.34±0.32 in diabetics and-0.40±0.75 in controls, suggesting a significant decrease in CBF in diabetics (p<0.01).
The above results indicate that the autoregulation of the cerebral circulation may be impaired in diabetic orthostatic hypotension.

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