Insulin response to paired oral and intravenous glucose loading were determined in 26 nonobese individuals classified as normal (nondiabetic control) subjects, mild to moderate diabetic subjects and borderline of these two categories. All these subjects were previously divided into one of the three groups by 50 gram oral glucose tolerance test. 8 cases with diabetes had diabetic glucose tolerance and were confirmed to have diabetic microangiopathy. Intravenous glucose tolerance test (IVGTT) was undertaken to determine eraly insulin response after intravenous glucose administration. Blood samples were collected from the antecubital vein before and 1, 2, 3, 5, 7, 10, 20, 30, 40, and 60 minutes after rapid glucose infusion of 0.33 g per kg of body weight. Blood glucose levels were determined by autoanalyser of Hoffman's method, and serum insulin levels were measured immunologically by modification of Hales and Randle's method. Results are summarized as follows. 1) Decreased insulin response during 50 g oral glucose tolerance test in diabetic group was confirmed. 2) All three groups had peak blood glucose levels during IVGTT between 2 and 3 minutes after the infusion. The highest blood glucose levels were seen in diabetic group, and its k-value was 0.68. Nondiabetic control group had lower blood glucose levels with k-value of 2.0. Peak blood glucose levels in borderline cases were seen between normal control group and diabetic group, and mean of their k-value was 1.84. 3) Impaired insulin responses among diabetic group in early phase of IVGTT were noted andthis was significantly (p<0.01) lower than normal subjects. But, peak insulin levels of borderline cases were not significantly higher than those of normal controls. From these data, biological significance of impaired insulin response in early phase of IVGTT was discussed.
The causes of death in diabetic patients were studied with regard to the age, known duration of diabetes, complication and treatment. During 10 years from 1961 to 1970, 510 patients with primary diabetes had been admitted to the First Department of Internal Medicine, Kanazawa University Hospital. Among them, 31 had died during their stay in the hospital, 15 of whom had been autopsied. The remaining 479 patients were followed up using the questionnaire, and 36 of them were known to be dead after they had been discharged from the hospital. Of these 67 patients who died, 50 were males and 17 females. The causes of the death were determined based on the autopsy finding, clinical evidence, or both. Sudden death without any evidence of involvements of other systems was judged to be the cardiac death. Results are summarized as follows: 1) The leading causes of death were cardiac disease (14 cases; 21%), neoplasm (12; 18%) and diabetic nephropathy (11; 16%), followed by liver disease (7; 10%) and cerebrovascular accident (5; 8%); of 5 cerebrovascular accident, 4 were cerebral thrombosis. Therefore, the deaths from the cardiovascular disease including cardiac disease, nephropathy and cerebrovascular accident made up about a half (45%) of deaths among the diabetics. 2) The deaths from cardiac disease and cerebrovascular accident occurred only in patients with adult type diabetes and none in those with juvenile type. 3) The death from diabetic nephropathy was more frequently observed among the diabetics with juvenile onset, compaired with those with adult onset. 4) The deaths from neoplasm occurred in patients after fifty were one years of age. These neoplasms included 4 gastric, 3 pulmonary, 2 pancreatic cancers and 1 each of hepatic, biliary and metastatic pleural cancer. 5) Most of the patients with long diabetic history died of neoplasm or cerebrovascular accident. 6) There was no significant difference in the frequency of complications, such as hypertension, diabetic nephropathy, retinopathy and neuropathy, between each group of the death cause. 7) The use of oral hypoglycemic agents or insulin did not appear to be related to the cause of death.
Since it has been revealed that 20 to 30 per cent of maltose administered was excreted in urine, the role of the kidney in the metabolism of maltose was investigated. When maltose was administered to nephrectomized rabbits, 14C-maltose disappeared from the blood stream very slowly and the increase in 14C-glucose was minimum. Maltase activities in the cortex of the kidney were ten times as high as in the medulla. In the isolated glomeruli, however, little maltase activities were observed. When maltose was injected to the rabbits pretreated with phloridzin, 14C-maltose decreased rapidly in blood and 14C-glucose did not increase. The difference between plasma maltose levels in the artery and vein across the kidney was increased after maltose was injected to the normal rabbits, whereas the plasma glucose concentrations in the renal vein exceeded those in the renal artery. In phloridzinized rabbits, the A-V difference of maltose was smaller as compared with normal rabbits and plasma glucose levels in the renal vein did not exceed those in the artery. The disappearance of 14C-maltose administered to the pancreatectomized rabbits was slightly delayed and urinary excretion of maltose and glucose increased. When the isolated kidney was perfused for 30 minutes with maltose solution, the levels of maltose and glucose in the renal vein rose and not only maltose but also glucose were excreted in urine. These results suggest that the kidney plays an important role in the metabolism of maltose administered intravenously. The mechanism as to urinary excretion of glucose after maltose injection was discussed.
Diabetic state was analysed on the assumption that a functional state in a living system would be explained by the state of some functional units composing the total function of a living system. The objects of this study were diabetic patients who newly visited the Second Department of Internal Medicine of Kobe University from 1965 to 1971. At first, some statistical analysises for 94 patients were carried out with general raw clinical data consisting of 25 items. Then, 25 items were transformed into 16 items expecting to reveal a hidden meaning in raw data or to represent a reasonable meaning from a viewpoint of a control theory. One hundred and twenty three patients who completed the 16 items were studied similarly. The 25 items used in these analysises were as follows. Sex, age, body height, body weight, systolic blood pressure, diastolic blood pressure, FBS, double loading 50 g oral glucose tolerance test with a 2-hours interval between the 2 loads (6 points), urinary glucose excretion during GTT (first 2 hrs and second 2 hrs), serum total protein, serum total bilirubin, serum alkaline phosphatase, serum cholesterol, GOT, GPT, cobalt reaction, urine sugar, urine protein and findings of eye fundus. Whereas, in 16 items analysis, urine protein, urine sugar and findings of eye fundus were excluded, sex, body weight and body height were transformed into one item i. e. obesity index, and 6 GTT points were transformed into 3 items i. e. GTT 30 min-FBS, GTT 2hr-FBS and GTT 4hr-FBS and total urinary glucose excretion during GTT (sum of first and second 2 hrs) was used. In both 25 items and 16 items, mean, standard deviation, coefficient of variation, simple, partial and multiple correlation coefficients were calculated, and factor analysis method was used. As the result of factor analysis, 7 factors were obtained. Next interpretations for each factor were available; factor which represents the state of 1) active carbohydrate metabolism, 2) passive carbohydrate metabolism, 3) vascular system, 4) liver cell function, 5) biliary passages function, 6) protein metabolism and 7) fat metabolism, respectively. The results obtained from these analysises were not so different from the general diabetic concept. According to the results, some substantial diabetic problems were discussed. It is expected that such statistical analysis will shed new light on the clinical medicine and the study of biological mechanism.
Diabetes mellitus and hypertriglyceridemia ferquently coexist and both have been known to be associated with the vascular disease. By analogy with the glucose tolerance test, fat tolerance tests have been used to detect latent abnormalities of lipid metabolism. In the present paper we have investigated an intravenous fat tolerance test utilizing the fat emulsion, 10% Intralipid, and reported its clinical application to the study of lipid metabolism in diabetes. Serial changes in the serum levels of triglyceride (TG), free fatty acid (FFA), blood sugar, IRI and in the lipoprotein metabolism after intravenous infusion of Intralipid in 12 diabetics without fasting hypertriglyceridemia. The results were compared with those obtained from control subjects. 1) Fat infusion caused significantly higer TG responses in diabetics immediately after (p<0.02), at 30 (p<0.01) and 60 (p<0.02) minutes. 2) FFA rose greatly immediately after the infusion of fat and gradually decreased, but no differences were apparent in the FFA response between diabetics and control subjects. 3) Serum IRI and blood glucose values after the fat infusion remained unchanged. 4) Chylomicron increased maximally immediately after the fat infusion, while pre-β lipoprotein showed the highest response at 30 minutes. These findings suggested a decreased fat tolerance in diabetics.
A case of young diabetic patient with familial type IV hyperlipoproteinemia is presented. A 28-year-old man was found to have a lactescent serum and glycosuria. He has no hepatosplenomegaly nor xanthoma. The diagnosis was established by measurement of fasting serum lipids, plasma postheparin lipolytic activity, determination of lipoprotein patterns by paper-electrophoresis and glucose tolerance test with concurrent assay of plasma IRI. Serum cholesterol, triglycerides and FFA were 515 mg/dl, 1200 mg/dl and 1.12 meq/l. On admission, his serum was lactescent and cream layer over turbid infranatant was found after overnight standing in the cold. Pre-β lipoprotein on paperelectrophoresis was increased. Glucose tolerance test showed diabetic curve and immunoreactive insulin response to glucose was imapired. After one week on a 90 per cent carbohydrate diet, serum triglyceride demonstrated an exaggerated rise. After one week on a 60 per cent fat diet, serum triglyceride decreased and no chylomicron appeared. Nine members in three generations of his family were also studied. A 35-year-old brother had the similar clinical features to the patient. As a dietary treatment, low calory and low carbohydrate diet was instituted. Two weeks later this regimen reduced the serum lipid levels with a definite improvement of carbohydrate intolerance, but was not satisfactory. The additive therapy with hypolipidemic agents and SU drug to the restricted diet controlled both derangements of lipids and carbohydrate metabolism in the patient.
The changes in small blood vessels of nailbed were examined with the vital capillaromicroscopy in 56 diabetics older than 40 years of age. We have proposed the grading system for the statistical analysis of pathological changes of the small blood vessels in this study. The abnormal morphological changes such as dilatations, wavings, tortuosities, branchings, nodular apical enlargements (NAE), tanglings, granularities and so called the fine capillaries were picked up in each photographic picture, and points were given according to their severity. Summation of points for NAE, granularities and fine capillaries was significantly high in diabetic patients compared with that of healthy control. Patients with nephropathy received higher points (37.6±4.2) than those who have retinopathy alone (26.5±2.4). The possibility for the usage of this useful method was discussed for the detection of peripheral microangiopathy in diabetic patients.
The principal component analysis was applied to assess the genesis of microangiopathy of the samll blood vessels of nailbed in diabetics. The scores of patients were calculated by the points given to abnormal findings in loops of nailbed vessels. Calculation for principal component analysis was carried out with the computer NEAC 2200. Abnormal findings of the small blood vessels in nailbed such as dilatations, wavings, tortuosities, branchings, nodular apical enlargements (NAE), tanglings, granularities and so called the fine capillaries were found to be separated into three groups. The first component includes dilatations and NAE findings and seems to indicate the changes due to dilatation of the vessels. The second one consists of granulalities and fine capillaries and seems to express sclerotic changes. The third one includes other four findings and indicates the changes in a vessel length. These results suggests the findings in small blood vessels of nailbed in adult diabetics to be classified at least three different kinds of pathological changes.