Eighty-one autopsy cases examined during the 1960 s and 209 autopsy cases examined during the 1970 s were studied. The severity of diabetic glomerulosclerosis and its relation to the duration of diabetes, age at death and causes of death were investigated. The following criteria were used for the severity fo renal changes: I: minimal change, II: arteriolosclerosis only, III: mesangial thickening, IV: nodular lesion and V: end-stage kidney. 1) Renal lesions were seen in 92% and 91% in of cases from the 1960 s and 1970 s, respectively. 2) The severity of diabetic glomerulosclerosis was well correlated with the duration of diabetes in the cases from the 1970 s, but such a relationship was not remarkable in the cases from the 1960 s. This was mainly due to the fact that only a few cases had had a disease duration of more than 16 years. In the cases from the 1970 s mesangial thickening mostly developed in cases having a disease duration of less than 15 years. Nodular lesions were mostly seen in cases having a disease duration of 16 to 25 years. 3) Cases dying in their 2nd or 3rd decade and having no glomerular change were seen in the 1960 s but not in the 1970 s. The number of cases showing mesangial thickening or nodular lesion, and dying in their 6th or 7th decade increased remarkably in the 1970 s. This was probably due to an increase in the number of long-term survivors. 4) As causes of death, infectious diseases were less frequent in the cases from the 1970 s than in those form the 1960 s. Deaths from malignancy increased during that period, although the death rate from malignancy was similar to that of autopsied cases from the general population. Coronary heart disease, cerebrovascular disease and renal disease were common in both decade3. As long-term survivors of diabetes increased, renal disease became more important as a cause of death.

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The purpose of this study was to investigate the psychological features of diabetics with severe complications (retinopathy). The subjects were 37 diabetics with proliferative retinopathy (severe diabetics). The control subjects were 25 diabetics without retinopathy (mild diabetics), whose ages and durations of diabetes were matched with the subjects. The Yatabe-Guilford personality test (YG) and State-Trait Anxiety Inventory (STAI) were applied to investigate psychological factors. An interview method was used to examine the durations of not attending medical checkups and not observing diet therapy from the onset of diabetes.
The results of the YG test revealed that severe diabetics were emotionally and socially better adjusted than mild diabetics. The STAI showed that severe diabetics were less anxious than mild diabetics. The interview method revealed that the severe diabetics had neglected medical checkups as well as diet longer than the mild diabetics. These results suggested that the severe diabetics, who were less anxious and better adjusted to society, tended to neglect the therapies. Therefore, it is very important for therapists to educate such patients thoroughly in accordance with their psychological status, so that they will observe diet therapy and attend regular medical checkups.

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Selective coronary angiography and 75-gram oral glucose tolerance test were carried out in 123 subjects to clarify the pathogenesis of the increased incidence of coronary heart disease (CHD) in diabetics.
The coronary score was defined on the basis of angiographic results. The subjects were divided into four groups according to the coronary score: N group, coronary score 0; L group, coronary score 1-7; M group, coronary score 8-12; H group, coronary score 13-. No obstruction was detected in subject in the N group. Subjects in the H group had severe coronary arterial lesions. Age, obesity index, plasma total cholesterol level and plasma triglyceride level were matched among the four groups.
1) The percentage of diabetics in each group was as follows: 5% for the N group, 14% for the L group, 30% for the M group, and 29% for the H group.
2) The plasma glucose and insulin levels before glucose ingestion and 30, 60 and 120 minutes after glucose ingestion were compared among the four groups. The severer were the coronary arterial lesions, the higher were the plasma glucose levels before and after glucose loading. The plasma insulinlevels before and after glucose loading were higher in the H group than those in the M group. The results suggest that hyperinsulinemia plays an important role in the development of CHD.
3) The coronary scores of the DM group and the non-DM group (N group) in men were compared. The coronary score in the DM group was significantly higher than that in the N group (p<0.05). Age, obesity index, blood pressure, daily consumption of tobacco, plasma total cholesterol level and plasma triglyceride level were matched in the DM group and the N group. These results suggest taat the diabetic state is an independent risk factor for CHD, and that the increased incidence of CHD in diabetics is not attributable of age, obesity, hypertension, tobacco, or hyperlipidemia.

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Although recent studies have revealed that biochemical changes caused by hyperglycemia in diabetic nerves might play an important role in the development of diabetic neuropathy, the exact relationship between these changes and acute or chronic electrophysiologic changes of peripheral nerves has not been definitely established.
In this study, the importance of sorbitol accumulation in the nerve tissue in relation to the development of nerve dysfunction was investigated using a newly developed inhibitor of aldose reductase, a rate-limiting enzyme of the polyol pathway. The sorbitol content of the nervous tissue increased significantly when hyperglycemia developed in streptozotocin diabetic rats. The impairment of motor nerve conduction velocity (MNCV) appeared when the sorbitol content reached a certain threshold level.
The administrtion of aldose reductase inhibitor (ARI) immediately after streptozotocin injection prevented the reduction of MNCV, whereas the sorbitol content of nerve tissue increased above normal range, which suggested that neurophysiological function might be preserved if the accumulation of sorbitol remained less than a threshold level.
ARI tretment restored the decreased MNCV in streptozotocin diabetic rats and significantly reduced the sorbitol content of nerve tissue.
These results suggested that the sorbitol content of nerve tissue contributes to the development of nerve dysfunction in the acute diabetic state, and that ARI, by reducing sorbitol accumulation, is beneficial in the treatment of diabetic neuropathy.

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1)[U-¹⁴C] glucose incorporations into hepatocytes, glycogen and nucleotide fractions were stimulated by insulin (200ng/ml): this effect seemed apparent as early as at two to four hours and most prominent at 24 hours after insulin addition.
2) At four hours, [U-¹⁴C] glucose incorporations into hepatocytes (100%), glycogen (8% of [U-¹⁴C] glucose incorporation into hepatocytes), lipid (9%), nucleotide fractions (29%) and medium lactate (340%) were all stimulated with insulin (200 ng/ml) by 28-54% over control. At 24 hours, [U-¹⁴C] glucose incorporations into hepatocytes (100%), glycogen (15% of [U-¹⁴C] glucose incorporation into hepatocytes), lipid (11%), nucleotide fractions (39%) and medium lactate (530%) increased in proportion to the glucose concentration up to 800 mg/dl and were further significantly stimulated by 21-112% over control with insulin supplementation.
3) Addition of cycloheximide (1μg/ml) totally abolished the effect of insulin on [U-¹⁴C] glucose incorporation into hepatocytes at 24 hours, while no significant suppressive effect was observed at four hours.
4) As for key enzyme activities, at four hours after the addition of insulin, activation of glycogen synthase (increase of % I activity) and pyruvate kinase (increased at 0.2 mM phosphoenol pyruvate) was noted, while at 24 housr, these two enzymes increased in the total activity. Regarding glucokinase and glucose 6-phosphate dehydrogenase, both enzyme activities increased by 30-35% and 65-93% at four and 24 hours, respectively.
5) Glucose utilization was increased in a dose-response manner in the presence of insulin (5-200ng/ml).
It is suggested that insulin stimulates several pathways of glucose metabolism in hepatocytes mainly through activation of glycogen synthase and glycolytic key enzymes as an early effect and probably through induction of these enzyme levels as a delayed effect.

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The effects of insulin on insulin-sensitive phosphodiesterase were investigated in fat cells from control (Eight weeks old) and obese (32 weeks old) rats. Isolated fat cells were incubated at 37° for 10 minutes with and without insulin. A crude microsomal fraction prepared by differential centrifugation was assayed for phosphodiesterase activity. The enzyme activities in obese rats were lower at 0.1-30 nM insulin concentrations than in control rats (p<0.001). The dose-response curve of insulin was biphasic and of the convex type in both groups. In obese rats, the curve shifted tothe right, and half-maximum stimulation was obtained at 0.7 nM in obese rats compared to 0.17 nM in control rats (p<0.001), indicating a decrease of insulin sensitivity. Insulin responsiveness, expressed as percent of basal enzyme activity, was also markedly reduced in obese rats. Specific binding of insulin in fat cells from control and obese rats was 4.8% and 13.0%/2×10⁵ cells, respectively, at 24° for 60 minutes of incubation. Scatchard analysis indicated that overall insulin receptor in fat cells from obese rats was greater than in fat cells from control rats. These results suggest that the insulin effector system related to the phosphodiesterase activation is affected in fat cells from spontaneously obese rats and that the inpairment of the phosphodiesterase activation system is predominantly due to postreceptor defects.

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A human pancreatic B-cell clone (JHPI-1) was used as a target of islet cell surface antibodies (ICSA) in comparison with rat and/or mouse islet cells by indirect immunofluorescence and ¹²⁵Iprotein A binding assay. ICSA was detected in the sera of patients with insuline-dependent diabetes mellitus (IDDM) and normal healthy controls. All the sera that were positive for ICSA against rat and/or mouse islet cells were also positive for ICSA against JHPI-1 cells as expected, while in healthy normal controls all the sera that were negative for ICSA against rat and/or mouse islet cells were also negative for anti JHPI-1 cell ICSA. The percentage of positively stained living JHPI-1 cells correlated with that of living rat islet cells (r=0.81, p<0.01). Conversely, some IDDM pa, -tients sera that were negative for ICSA against rat and/or mouse islet cells reacted with JHPI-1 cells. Furthermore, the binding of ¹²⁵I-protein A to JHPI-1 cells exposed to sera from IDDM patients correlated with the binding to rat and/or i slet cells, and the ability of JHPI-1 cells to bind ¹²⁵I wasgreater than that of the rat and/or mouse islet cells.
In conclusion, it was possible to use not only rat and mouse islet cells, but also a human pancreatic B-cell clone derived from human fetal pancreas as target cells in these assays. Our data also indicate that JHPI-1 cells express relatively species-specific antigens on their surfaces and that there might be human-specific ICSA against human islet cells in the sera of IDDM patients.

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This is a report of a 20-year-old man with diabetes mellitus developing a month after chicken pox. Thirst, loss of appetite, and weight reduction appeared approximately one month after the chicken pox was cured. Three months later, elevations in serum antibody titer against chicken pox, fasting blood glucose (304 mg/dl), hemoglobin A₁ (14.9%) and hemoglobin A_1c (11.6%) were observed. A 75 g glucose tolerance test showed a typical pattern for diabetes mellitus with low levels of immunoreactive insulin.
Human leucocyte antigen haplotypes wer Bw 54-DR 4 and MT 3, which are frequently found in patients with diabetes in this country. Antibody for islet cell surface was not detected.
Strict diet therapy improved the patient's fasting blood sugar levels and insulin secretion within three months.

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We studied the relationship between diabetes mellitus and renal arterial calcification in five diabetic patients and also observed the influences of calcification upon enal function.The results were as follows:
1) In all patients, renal arterial calcifications appeared as patches or spots in X-ray films, suggesting calcifications of atherosclerosis.
2) In all patients, renal arterial calcifications were observed bilaterally. At the same time, calcifications of the aorta, splenic artery, iliac arteries, nd femoral arteries were found in five, three, five, nd two of the five patients, respectively.
3) Renal dysfunction was seen in one of the five patients. But no atient seemed to have occlusions of the renal artery.
4) Control of diabetes mellitus of the five patients was poor. Fasting blood glucose was 210.2±41.0 mg/dl (mean±SEM) and the HbA₁ level was 7.0 ± 0.6%. Duration of diabetes mellitus of the five patients was 16.0±3.8 years, which was twice as long s that of the diabetes group without arterial calcification (n=210).
5) The age of the five patients was 69.2±2.2 years, and that of the diabetes group ithout arterial calcification was 50.9±0.9 (p<0.01).
6) Systolic blood pressure of the five patients was 168.4±8.5 mmHg, and that of diabetes group without arterial calcification was 134.4±1.8 mmHg. (p<0.01).
7) One of the five patients was accompanied by ST-T change in ECG. Retinopathy and roteinuria were seen in three and four of the five patients, respectively.
These results suggested the necessity of a study exploring microangiopathy and alcification of arteries including the renal artery in elderly patients with along duration of diabetes mellitus and hypertension.

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