LCAT is an enzyme catalyzing esterification of cholesterol in plasma by transferring fatty acid from beta-position of lecithin to 3-OH of cholesterol. The enzyme works mainly on plasma lipoproteins. There are several reports describing the plasma level of LCAT is low in the patients with hepatic parenchymal disorders. However, only a few papers have been published concerning the LCAT activities in other pathological conditions. We measured serum LCAT activities in diabetics by incubating 50 μl of the patient's serum with one ml heated D=1.063 infranatant serum fraction containing 14C cholesterol. After the extractionof lipids with chloroform: methanol, the esterified cholesterol was separated by thin-layer chromatography and the incorporation of radioactivities into the esterified cholesterol was determined, and the esterification was expressed in μg cholesterol estrified per ml per hr. The results were as follows: A) No significant correlation was found between the serum LCAT activities and the blood glucose levels. Also there was no significant difference in serum LCAT activities between diabetics and normal controls. B) Serum LCAT activities of non-treated diabetics had a significant positive correlation to serum cholesterol concentrations. C) There was a significant positive correlation between the degree of relative obesity and serum LCAT activity in the group of patients whose unesterified cholesterol levels were higher than 65 mg/100 ml, however no significant correlation was found when whole non-treated patients were included. D) The mean LCAT activities decreased significantly after insulin treatment in comparison with those of pre-treatment. It seems that the low level of LCAT after insulin therapy relates to the metabolic sequences which would be associated with the decrease of serum cholesterol level by insulin administration.
Although diet regulation is a basal therapeutic means for diabetes, little is known about its primary effect on diabetic metabolism, including insulin secretion. The purpose of this investigation is to throw a light on this problem. Twenty-two non-ketotic diabetics were selected for study, who were newly-diagnosed or had interrupted the treatment of diabetes for long time, having no other diseases which might affect carbohydrate metabolism. In these patients, blood glucose, FFA and IRI response to oral loading of 100 g glucose were compared before and after 4 week diet regulation. The diet which was indicated to them was composed of 60% carbohydrate, 15-20% protein and 20-25% fat. The total calorie was restricted in relation to their weight and physical activity. The patients were asked to weigh their daily food. 24h intake of carbohydrate, protein and fat, and total calorie were calculated as accurately as possible. According to this calculation, dietetic intakes of seven of these twenty-two patients were found not to be significantly changed between before and after the instruction of diet regulation. Therefore, we divided all patients studied into two groups, namely control group (7 cases) and diet treatment group (15 cases). After the diet regulation in the latter group, fasting glucose was decreased from 164.1±14.6 mg% to 121.7±7.1 mg%(p<0.01), glucose tolerance was significantly improved and insulin response estimated by measuring the area under the curve was increased from 6, 807±958 μU·min/m/ to 10, 392±1, 657 μU·Eminim/(p<0.01) in spite of lowered level of blood glucose. However, the sluggishness in early insulin response to glucose was not markedly changed. Insulinogenic index was also significantly increased at 180 minutes after oral glucose loading. Plasma FFA response to oral glucose was ameliorated at 120 minutes. On the other hand, the control group did not show any significant changes in blood glucose and IRI and FFA response to glucose loading before and after 4 week observation periods. Therefore, the metabolic effects of the diet regulation should be at least in part ascribed to the increased secretion of insulin. These results support the classical concept, “Resting the Pancreas”, brought about by caloric restriction.
In an attempt to evaluate the effects of treatments of diabetes on the occurrence and development of diabetic angiopathy with special reference to long-term oral antidiabetic therapy, the clinical features of vascular disorders in 373 patients attending our diabetic ambulance regularly for at least five years were analysed. The following results were obtained. 1) Among 373 diabetic patients, 136 patients had been treated with sulfonylurea, 17 patients with biguanide, 61 patients with the combination of sulfonylurea and biguanide, 73 patients with insulin, 46 patients diet alone and 40 patients receiving either oral drugs or insulin for less than five years. 2) There were many juvenile-onset diabetics in those receiving insulin treatment. The age, fasting blood sugar and glucose tolerance of combination group were almost equal to those of insulin group. The rate of incidence of cases poorly controlled was highest in insulin group, followed by combination group. 3) Appearance of retinopathy was significantly more frequent in the insulin and combination groups than in the other groups. 4) In the diet group, frequency of progression of proteinuria was significantly lower than in the other groups. 5) The rate of occurrence and development of ischemic myocardial damage was significantly higher in the combination treatment group than in any of the other treatment groups. Among the patients who were treated with oral hypoglycemic agents, the progression of ischemic myocardial damage was significantly more frequent in the poor controlled group than in the good controlled group, though in our general diabetic patients, there was no significant difference of frequency of ST, T abnormality between the ECG finding of good controlled and poor controlled groups. From these results, it should be stressed that oral antidiabetic therapy should be employed with more caution than in the past. Moreover these results suggest that sulfonylurea exerts its hypoglycemic action not only through the stimulatory effect on pancreatic islets, but also through some direct effects on extrapancreatic tissues.
The San-in Area is located in the western part of Japan and faces to the Japan Sea where the weather is cold and damp in winter. In this area, diabetic gangrene seems to be more frequent than in other parts of Japan. Since 1969, ten patients with diabetic gangrene have been treated at our clinic. The clinical findings of these ten patients are summarized as follows: 1) Among the 469 diabetic patients treated between October 1969 and April 1972, at the First Department of Internal Medicine of the Tottori University School of Medicine, 10 cases suffered from gangrene of the lower extremities. The incidence amounted to 2.13%. The ages ranged from 21 to 72 (average 52.9). 2) There was no significant difference in incidence between the sexes; six cases of diabetic gangrene were found among the 277 males (2.16%), and 4 cases among the 192 females (2.08%). 3) All of the patients with diabetic gangrene were suffering from diabetes unsatisfactorily treated over long periods. 4) In all cases, the pulses of the A. dorsalis pedis were palpable and these gangrenes appeared as “spotty” lesions. In all cases, the walls of the small vessels of the skin obtained by biopsy were positively stained with PAS. 5) Low temperatures, rubber shoes, and moxibustion tended to render diabetics in this area more prone to the development of gangrene of the lower extremities. 6) Diabetic retinopathy, neuropathy, and/or nephropathy were found in high incidence among the 10 patients with diabetic gangrene.
In diabetics, patients with diabetic amyotrophy might generally be rare in Japan. In fact, a few case reports had been presented previously. In San-in area the incidence of diabetic amyotrophy seems to be higher than in other areas. This area is located in the western part of Japan and faces to the Sea of Japan. Its weather is cold and moist in winter. In the period from October 1969 to January 1973, 511 diabetic patients were treated in our clinic. The results of our experience are as follows: Among them, 5 cases (0.98%) had diabetic amyotrophy, showing the syndrome described by Garland. There was no difference of incidence in both sexes. Among 299 males, diabetic amyotrophy was found in 3 (1.00%) and among 212 females in 2 (0.95%). The age of these 5 ranged from 48 to 70 (average 63.4). They all showed diabetic neuropathy and retinopathy.
A case of hypoglycemia with auto-antibody to insulin and characteristics of the antibody were reported. A 65-year-old female was admitted to our hospital because of unconciousness early in the morning. Her blood glucose values at the attacks were 16 to 19 mg/dl and the attacks were relieved by glucose injection. Her OGTT showed a delayed curve, but the IVGTT showed a normal K value (2.77). Despite of no history of insulin injection, insulin antibody was demonstrated in the serum by means of ethanol precipitation, paper chromatography, gel filtration and dextran-coated-charcoal procedure. Total immunoreactive insulin extracted from the serum was 22, 200μU/ml. As the celiac angiography suggested the presence of a tumor in the pancreas, the operation was performed under the diagnosis of insulinoma with insulin antibody. The laparotomy disclosed, however, no tumor in the pancreas and 95% distal resection of the pancreas was made. The histological examination showed a slight decrease of the Langerhans' islets, but no pathological changes were found.Insulin content of the pancreas was 1.11 U/g. 1251-porcine-insulin bound with the patient's serum was separated each other by acidification. The insulin binding protein was classified as IgG, and the light chain was K type. On the other hand, a control study showed that the insulin antibodies of the insulin treated patients were IgG, IgA and IgM, and the light chain was K and L type. Protein fraction, obtained by acidified gel filtration from the serum, reacted well with human and porcine insulin, but less with bovine insulin. A passive cutaneous allergic reaction was positive in a guinea pig and negative in other guinea pig. Precipitation reaction by the method of Ochterlony was not demonstrated. After the operation the insulin binding capacity of her antibody decreased gradually, but it was still recognized six months after operation. It was concluded that the insulin binding protein in the serum might be auto-antibody to the endogenous insulin, because she had never recieved any insulin injection.