Urinary tract infections in diabetics are commonly treated by the same curative means as usual to similar infections in non-diabetic patients. Also, there have been few reports on the relation between urinary tract infections and the metabolic disturbance in diabetes. The purpose of the present study was to investigate the chemoprophylactic effect of long-term therapy with a low dose of sulfamethoxazole-trimethoprim (ST) in recurrent urinary tract infections and to discuss the results with some reference to the control of diabetes.
Ninety-six patients (38 with symptoms and 58 with asymptomatic bacteriuria) were treated with one tablet (containing 400 mg sulfamethoxazole and 80 mg trimethoprim) every night before sleeping for two months to one year or more, and were followed up for six months to one year. Among 93 patients examined roentgenologically, 36 revealed residual urine (including 5 with diabetic neurogenic bladder, 16 with prostatic hypertrophy, 2 with renal stone and 1 with hydronephrosis) and there were no detectable causes of recurrence or persistence of urinary tract infections in the remaining 57 cases.
The incidence of urinary tract infections per year was 1.15 times before, and 0.28 times during the ST treatment. Also, the fasting blood sugar levels during chemoprophylaxis were decreased in 25 cases, and 16 of these cases did not undergo alteration of their doses of insulin or oral agent for diabetes. The incidence of urinary tract infections was decreased during the follow-up period after treatment.
Eleven cases were interrupted due to side effects (7 with nausea, 2 with skin rash, 1 with diarrhea and 1 with fatigue). Two cases of mild leucopenia before treatment (less than 4000/mm³) showed a fall in leucocyte count during the treatment, and 3 patients with a history of hepatic dysfunction showed rising serum transaminase.
In conclusion, ST is considered to represent a useful drug for chemoprophylaxis, but it should be administered with caution due to the side effects. The long-term chemoprophylaxis of urinary tract infections in diabetes is very important for the control of glucose metabolism.

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The circadian blood glucose profile of 15 unstable diabetics (4 IDDM, 11 NIDDM, 14-53 yrs.) was continuously monitored by the artificial endocrine pancreas (AEP, Biostator ®) with the conventional insulin therapy on the first day. On the next day, feedback control of 24-32 hours with the AEP was performed on each subject. Based on the data obtained, the patients received a new insulin regimen from the third day, consisting of two daily injections of a mixture of short-acting insulin (s.a.-I) and intermediate acting insulin (i.m.a.-I), 45-60 min. before meals. The dose of new insulin regimen was matched to about 60% of infused insulin dose with the AEP. The diurnal blood glucose profile of 6 subjects (2 IDDM, 4 NIDDM) was monitored again one month later.
1) The mean amplitude of glycemic excursions (MAGE) of 5 highly unstable (HU) diabetics was 187±14 mg/dl (mean±SD) and that of 10 moderately unstable (MU) diabetics was 138±13 mg/dl. There was a negative correlation between the sum of serum CPR during 50 gOGTT (ECPR) and the MAGE (r=-0.61, p<0.05).
2) The M-values before, during feedback control, and one month later were 66.6±26.6, 10.8± 4.1, 23.1±5.5 respectively. Each of the mean blood glucose concentrations (MBG) was 208±33mg/dl, 108±13 mg/dl, 122±27 mg/dl and the MAGE was 154±26 mg/dl, 65±16 mg/dl, 105±21 mg/dl respectively. The M-values, MBG and MAGE decreased significantly during feedback control and one month later, compared with those values obtained before feedback control. (p<0.001). However, the MAGE of 4 of 6 subjects did not remain in a stable range (<80 mg/dl), after 1 month. In those values obtained at each period, there was no significant difference between HU and MU subjects.
3) HbAt was 12.5±2.0% before feedback control, 11.2±1.8% one month later, 9.3±1.3% two months later and 9.2 + 1.2% four months later. The change of insulin dosage and the timing of injection caused a noticeable decrease in HbAI levels 1-4 months after feedback control (p<0.001).
4) The new insulin regimen was characterized by an increased proportion of s.a.-I in the daily dose from 26.4±12.1% to 40.3±11.5% after feedback control. (p<0.02). The rate of daily insulin dosage to the body weight increased from 0.56±0.18 U/kg (before) to 0.73±0.17 U/kg (after)(p<0.02). The new insulin regimen decreased hypoglycemic episodes.
Thus, we concluded that the AEP (Biostator ®) could be useful in the clinical management of unstable diabetics by providing a more precise estimate of the patient's insulin requirements, especially those of s. a.-I, leading to a better long-term control of blood glucose.

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The 2nd Department of Internal Medicine, Tohoku University School of Medicine, Sendai, JapanThe contents of cholesterol and hydroxyproline in the aortic wall, and of hydroxyproline in the glomeruli were compared among normal, diabetic, and insulin-treated diabetic rats. The content of cholesterol in the aorta of diabetic rats at 56 days after streptozotocin injection was 12.8±2.7 mg/g dry weight, which was significantly higher than that in normal and insulin-treated diabetic rats (8.5± 0.8 and 8.3±0.9 mg/g day weight, respectively). The hydroxyproline content of the aorta of normal rats increased from 248 μmoles/g dry weight on the 13th day to 321 μmoles/g dry weight on the 56th day, which was significantly higher than that in diabetic and insulintreated diabetic rats.
The hydroxyproline content in the glomeruli of normal rats also increased significantly with age. That of diabetic rats was lower than that of insulin-treated diabetic rats on the 27th and 56th days after streptozotocin injection.
These results suggest that one of the early changes in the aorta and glomeruli of diabetic rats is an increase in cholesterol content in the aorta and a decrease in hydroxyproline content in the glomeruli, which can be reversed by controlling the blood glucose by insulin injection.

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In 1976, Uchida et al. developed a malignant insulinoma by injecting BK virus (human papopa virus) into the brain of newborn golden hamsters. It can be transplanted subcutaneously and some can still continue to have functional hypoglycemic activity even after successive transplantation, but the others lose the activity and become nonfunctional.
In this study, gel filtration of the acid alcohol extract using Sephadex G-50 superfine was carried out, the IRI in the malignant insulinoma, transplanted functional tumor and normal pancreas was assayed and the insulin fraction and proinsulin-like componets (PLC) were calculated. In the nonfunctional tumor, the IRI was assayed directly. The results obtained were as follows.
1) There was no difference in gel filtration pattern of the tissue extract between the normal pancreas, malignant insulinoma and functional tumor, and there were no special findings suggestive of an increase in PLC.
2) The average insulin content calculated from the insulin fraction area in the normal pancreas was 2.73+0.40U/g (mean±SE), and the PLC over total IRI was 3.18±0.52%. In 2 cases of original malignant insulinoma, the insulin contents were 3.70U/g and 2.32U/g, respectively, and the average percentage of PLC was 3.37%. In 3 cases of functional tumor, the insulin content was 3.63±0.60U/g and the percentage of PLC was. 2.70±0.45%. On the other hand, in 3 cases of nonfunctional tumor, the insulin content was very low, close to zero. (0.0031-0.0015U/g).
3) Even after successive transplantations, the functional tumors were rich in insulin, causing hypoglycemia, while the nonfunctional ones were poor in it.

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Cardiac function in patients with myocardial infarction is associated with the severity of the obstructive lesions, the number of involved vessels, and the size of the infarcts. In patients with impaired glucose tolerance, cardiac function predictably deteriorates due to diabetic microangiopathy in the myocardium. In this paper, the effect of impaired glucose tolerance is discussed based on an analysis of the left ventricular function in patients with myocardial infarction.
1) Eighty-three patients with myocardial infarction and 15 with angina pectoris (total 98) were selected from coronary arteriograms in which significant obstructive lesions had been proved. The left ventricular function was evaluated from the end-diastolic prssure and volume, ejection fraction, stroke index, contractility index, total peripheral vascular resistance, and asynergic score.
2) The patients were divided into 3 groups according to the number of involved vessels, and each group was divided into 3 subgroups according to GTT type. The cardiac function was compared among the 3 subgroups. No significant differences in left ventricular function were found in these subgroups.
3) In patients with multiple vessel involvement, the group classified as type D of GTT frequently had accompanying high left ventricular end-diastolic pressure despite the small left ventricular enddiastolic volume. Such diastolic disturbance of the left ventricle suggested the participation of diabetic microangiopathy of the myocardium in this disease state, since there was no difference in the severity of coronary atherosclerosis or size of infarct from others. A significant difference could not be demonstrated even in this patient group, probably due to the fact that the investigated diabetes mellitus was mild and of short period from onset in most patients.

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Not only patients with diabetes mellitus but also patients with renal failure demonstrate high hemoglobin Ai (HbAI) levels. We therefore investigated the degree of elevation of HbAI values in patients with renal failure using high-performance liquid chromatography, the microcolumn method, and the thiobarbituric acid (TBA) colorimetric test. Among non-hemodialyzed uremics, those with a BUN level of 100mg/dl or above or those with a serum creatinine level of 10 mg/dl or above were selected for study. In addition, uremics satisfying the following criteria were selected as subjects: FBS <100 mg/dl and 1 hour postprandial blood glucose<140mg/dl.
Correlations between HbAI, on the one hand, and BUN and serum creatinine, on the other, were found in the patients with renal failure. High-performance liquid chromatographic quantification of the components of the HbAI fraction revealed that in diabetic patients, the increase in HbAI levels was due mainly to increased HbAic component, while patients with renal failure showed increases not only in HbAic but also in HbAia + b components. Thus, the fractional pattern of HbAI in the patients with renal failure was similar not to that seen in dabetic patients but to that seen in normal subjects.
We also measured the HbAI levels in diabetic patients, patients with renal failure and normal subjects by the colorimetric TBA method, and compared the results with data obtained by the microcolumn techique. In diabetic patients, there was a postive correlation between the HbAI values obtained by the two methods. In patients with renal failure, however, no correlation was noted between the data obtained by the two methods.
These findings strongly suggest that the HbAI in patients with renal failure might be formed by the binding of something other than glucose to hemoglobin rather than by Schiff base linkage or Amadori rearrangement of the glucose-hemoglobin adduct.

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The relationship between the ability for insulin secretion before treatment and the mode of treatment required for gaining good diabetic control, was studied in moderate or severe diabetic subjects who were nonobese.
The resul is obtained were as follows.
1) There were no differences in ability for insulin secretion among the three groups treated with diet only, oral hypoglycemic agents or insulin.
2) There was no difference in the percentage of subjects treated with diet only, between diabetics with and those without ability for insulin secretion. No patient who had shown insulin secretion was treated with insulin.
3) The percentage of subjects treated with diet only was larger in diabetics whose duration of diabetes was below one year than in those whose duration of diabetes was over one year.
For the purpose of assessing whether a patient could be well controlled with diet only, his duration of diabetes is thought to be a more useful criterion than his ability for insulin secretion before treatment.

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The prevalence of arteriosclerosis obliterans (ASO) of the lower extremities was studied in 1426 diabetic patients (781 men, 645 women) attending Jichi Medical School Hospital between April, 1979 and March, 1981. Twenty-two cases (1.8%), 17 men and 5 women, were diagnosed as having ASO on the basis of local arterial pulse deficit accompanied by clinical signs such as intermittent claudication, gangrene, or hypothermia of the skin. The age at diagnosis of ASO was 67±9 years.
ASO was not seen before the age of 50 years, and the prevalence increased with age: 5 (1.5%) in their 50s, 10 (3.0%) in their 60s, and 7 (5.1%) above their 70s. Intermittent claudication was observed in 11 (0.8%), ischemic gangrene in 11 (0.8%), and 5 cases had other symptoms. Amputation was performed in 7 cases (0.5%). The distribution of arterial occlusion was as follows:
arterial pulses were absent in 10 cases at the A. dorsalis pedis, in 9 at the A. poplitea, and in 3 at the A. femoralis. Eighteen cases showed bilateral loss of arterial pulses. Between patients with ASO and age-and sex-matched ASO-free diabetics, no definite differences were observed in fasting plasma glucose at the first visit, the degree of obesity, mode of treatment of diabetes, prevalence of hypertension or history of smoking. The percentage of untreated or poorly-controlled patients was higher in the group with ASO. In older patients with ASO (71 years or older), a history of smoking, obesity and hypertension were less frequent. The incidence of other macrovascular complications such as myocardial infarction, calcification of the aorta, ischemic ECG changes and cerebral vascular disease, was higher in patients with ASO but the incidence of microvascular complications was the same between the groups with and without ASO.
The pedal arterial pulses were examined in detail in 306 diabetic cases. Complete loss of pulsation of the A. dorsalis pedis was recorded in 15 cases (4.9%). This prevalence increased with age and was higher in men than in women, whereas such a tendency was not observed in the pulse of the A. tibialis posterior.
The present data indicate a much lower frequency of peripheral vascular disease of the lower extremities than that found in similar studies in Western countries. Loss of pulse of the A. dorsalis pedis may represent a good index of peripheral vascular disease.

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The effects of long-term physical training on 1251-insulin binding to erythrocytes were studied in 18 normals and 12 non-insulin-dependent obese diabetics. The specific insulin binding in 10 well-trained athletes (5.33±0.51) was significantly higher than that in 8 sedentary subjects (4.08±0.54)(p<0.05). The binding variation was due mainly to an increase in insulin receptor concentation rather than a change in receptor affinity. The fasting plasma insulin levels were comparable in the sedentary subjects and well-trained athletes. These results suggest that increased insulin binding to insulin receptor may contribute, at least in part, to enhanced insulin sensitivity in well-trained athletes. On the other hand, no significant changes in receptor affinity or receptor number were observed between 7 trained diabetics (VO₂ max 40%, 6 months) and 5 sedentary diabetics. Studies are now in progress to clarify the reasons for this discrepancy in results between the normal and diabetic groups.

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To clarify the efficacy of home blood glucose monitoring in the management of diabetic pregnancy, 11 patients (IDDM 1, NIDDM 9, gestational diabetes 1) began home monitoring at 3-25 weeks of gestation. Seven of the 11 were B and 4 were C by White's classification. The protocol to be followed was: 1) FBG daily, 2) full profile weekly, 3) spot checks. According to the data obtained, the diet schedule was reconsidered and the insulin prescriptions were adjusted on an insulin sliding scale.
After starting home monitoring, the FBG and HbAi levels improved from 115±23 mg/dl to 99±27 mg/dl and from 8.6±0.6% to 7.2±0.8%, respectively. During home monitoring, 8 insulin-treated patients increased their insulin dosage from 13±5 U/day to 30±13 U/day at delivery. Three cases treated by diet alone had to begin insulin at 25-35 weeks of gestation and their maximum dosage was 8-28 U/day. They returned to diet therapy after delivery. The pregnancy was uneventful except in one case. 5 delivered vaginal and 5 by cesarean section at 37-38 weeks of gestation. They gained weight by 6.8+3.0 kg during pregnancy. The mean body weight of the infants was 3100±267 g, which was not large for date. Neonatal hypoglycemia was observed in 6. No remarkable retinal changes were detected.
The results obtained suggest that home monitoring si highly effective in controlling diabetic pregnancy.

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It is well known that glycosylated hemoglobin, designated as hemoglobin AI (HbAI), and glucosylated albumin can provide useful information regarding long-term blood glucose control in diabetic patients.
The present study was undertaken to determine whether the values of HbAi and glucosylated albumin might increase in dialyzed uremic patients without diabetes mellitus. In 16 subjects among 37 dialyzed uremic patients, the chromatographically determined HbAi values (8.23±1.54%, mean ±SD) were more than 2 SD above the mean for normals (7.70±0.41%). On the other hand, the glucosylated albumin values obtained by the thiobarbituric acid method indicated no significant increase in the dialyzed uremic patients (6.84±1.06%) as compared of normals (6.29±0.98%).
In vitro studies of the HbAt values in red blood cells from normals showed significant increases at 5 days after incubation with a high concentration, of urea. When compared to the HbAI values without urea. However, in the dialyzed uremic patients, there were no significant correlation between HbAI values and serum urea (r=-0.14) and serum creatinine (r=0.22).
Further studies are required to clarify the reasons for the increase in HbAi values in renal failure.

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