Skin blood flow (Periflux blood flow: PBF) was measured in the finger tips of diabetic patients by Periflux Laser Doppler Flowmeter (PLDF). PLDF is a new instrument for the direct, continuo us and noninvasive measurement of blood flow in skin capillaries. As a light source, a 2 mW He-Ne laser was used. The subjects consisted of 120 normal adults and 85 diabetic patients. The results obtained were as follows.
1) PBF value was 49.2± 7.1%(n=120) in normal subjects and 40.5 ± 10.7%(n=85) in diabetic patients; thus a significant decrease (p<0.001) in PBF was observed. in diabetic patients.
2) A negatively significant correlation (r=-0.340, p<0.005) was observed between PBF and the duration of diabetes mellitus.
3) In diabetic patients, PBF decreased according to the progression of diabetic retinopathy.
4) A significant correlation was found between PBF and the creatinine clearance ratio in patients with diabetic nephropathy (r=0.505, p<0.001).
5) Significant correlations were also found between PBF and motor conduction velocity (r=0.467, p<0.005) or sensory conduction velocity (r=0.432, p<0.005) in patients with diabetic neuropathy.
As a result, it is suggested that PBF could be used for the evaluation of diabetic complications.

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Fasting serum pancreatic secretory trypsin inhibitor (PSTI) levels were examined in patients with diabetes mellitus (DM) in relation to exocrine pancreatic function.
Nine patients with type I DM, 77 with type II DM and 136 healthy subjects with no family history of DM were studied. Those patients with renal or hepatic dysfunction on blood chemistry were excluded. Serum PSTI levels were measured using a PSTI RIA Kit (Shionogi & Co., Osaka, Japan). The oral N-benzoyl-L-tyrosyl-p-aminobenzoic acid load test [kPancreatic Function Diagnostant (PFD)] l was carried out in 71 of the diabetics, and the oral p-aminobenzoic acid load test (PABA) was also performed on a separate day in order to set off the potential factors that affect the absorption, metabolism, and urinary excretion of p-aminobenzoic acid. The ratio of recovery of p-aminobenzoic acid in six-hour urine after respective loading (PFD/PABA ratio) was used for the index of exocrine pancreatic function.
Serum PSTI levels in healthy subjects tended to increase with aging and showed increasedlevels in patients with renal dysfunction. PSTI levels of both the type I and II DM groups were significantly lower than those of the age-matched healthy group. In type II diabetics, lower serum PSTI levels in those with higher levels of fasting plasma glucose or those with lowered pancreatic B-cell function were observed. In 71 diabetics, fasting serum PSTI leves had a significant positive correlation with the PFD/PABA ratio (r=0.24, p< 0.05), and in 86 diabetics, these also had a significant positive correlation with fasting serum immunoreactive trypsin levels (r=0.42, p< 0.001).
These findings indicate that fasting serum PSTI levels are one of the useful indices for ascertaining the exocrine pancreatic function in diabetics.

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We suggested in a previous report that heart rate (HR) variations during supine resting position were predominantly affected by parasympathetic function and that HR response to stading was predominantly affected by sympathetic function. To compare cardiac parasympathetic and sympathetic function, 95 diabetics and 38 controls were examined using these two tests. All subjects were between 40 and 59 years old. HR variations were measured by Goto's instantaneous-HR-change continuous recorder. As indicies of autonomic function, the mean difference between maximal and minimal HR during deep breathing (I-E difference) and the HR increase on standing (HRmax) were determined.
The mean I-E difference and HRmax in diabetics were 9.4 beats/min and 15.1 beats/min, respectively. These values were significantly lower than those in controls (I-E difference 14.4, ΔHRmnax 20.5 beats/min). I-E difference correlated negatively to duration of diabetes and mean fasting blood glucose during the previous 6 months in diabetics, but HRmax did not correlate to them at all. Diminished I-E difference was found in patients with insulin treatment, retinopathy or persistent proteinuria. Diminished HRmax, however, was found only in patients with longstanding complicated diabetes.
The present studies, therefore, showed that both cardiac parasympathetic and sympathetic functionN were significantly impaired in diabetics as compared with controls and that parasympathetic damage occurred early whereas sympathetic innervation was preserved. Critical points in HR variation tests, at which diabetics aged 40 to 59 years had autonomic symptoms, were about 5.0 beats/min in I-E difference and about 10.0 beats/min in HRmax.

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Clinical features of mild type II diabetes mellitus complicated by proliferative retinopathy were compared to those without proliferative retinopathy. One hundred and twenty-two mild type II diabetics who were under good control with diet alone were divided into three groups according to the severity of their retinopathy: those without retinopathy (group 1, 63 patients), those with simple retinopathy (group 2, 47 patients) and those with proliferative retinopathy (group 3, 12 patients). Patients with proliferative retinopathy were found to have a significantly long history of diabetes and significantly heavy maximal body weight index in the past compared to the other two groups. Since it has already been established that the severity of diabetic retinopathy is correlated with the duration of diabetes, various clinical aspects were compared between 12 diabetics suffering from proliferative retinopathy (group 3) and 14 diabetics without retinopathy who were selected from group 1 by matching not only their age and sex, but also the duration of diabetes to their counterparts in goup 3, and the following results were obtained.
1) Patients with proliferative retinopathy and a longer untreated period for their diabetes and heavier maximal body weight index in the past than those without retinopathy.
2) In 10 out of the 12 diabetic patients with proliferative retinopathy, the condition had already developed before the initiation of treatment for diabetes.
3) Although both glucose tolerance and plasma insulin response to 50 g oral glucose had been significantly impaired in patients with proliferative retinopathy compared to those without retinopathy before the start of the treatment for diabetes, the impaired glucose tolerance and decreased insulin response in patients with proliferative retinopathy improved significantly, and there were no significant differences of glucose tolerance and insulin responses to 75 g oral glucose between patients with and without retinopathy after the good control had been obtained by diet therapy alone.
4) Hypertension more frequently complicated patients with proliferative retinopathy than those without.
Thus, it should be emphasized that even mild type II diabetics have the possibility of developing proliferative retinopathy when they have a long untreated period of diabetes with high blood glucose and increased body weight.

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We studied platelet sensitivity to prostacyclin (PGI₂) using ADP-induced platelet aggregation in diabetics having complications with varying degrees of severity. Namley, we evaluated an inhibitory effect of PG 12 on platelet aggregation and PG I₂ concentration indicatings 50 % inhibitory effect of platelet aggregation (IC₅₀). And these parameters were compared with several metabolic indicators. Our conclusions are as follows.
(1) In diabetic patients, mean fasting blood sugar was significantly higher than in controls (p< 0.001), and mean triglycerides were higher than in controls.
(2) All diabetic patients had varing degrees of severity of retinopathy and peripheral neuropathy diagnosed by motor and sensory nerve conduction velocities. Almost all patients had nephropathy by renal biopsy findings and/or persistent proteinuria.
(3) Maximal aggregation in ADP-induced platelet aggregation (6 μ M) indicated no significant difference between these two groups. Maximal aggregation of PG I₂ (0.5 ng/ml) was higher in diabetics than in controls (P < 0.001).
(4) IC₅₀ was significantly higher in diabetics (2.15 ng/ml) than in controls (0.30ng/ml, p< 0.001).
(5) There was a significant positive correlation between fasting blood sugar and IC₅₀ (r=0.79, P < 0.001).
(6) These results indicate that a reduced sensitivity of platelets to PG I₂ is an important factor of platelet hyperfunction and these abnormalities may contribute to the etiology and/or development of diabetic microangiopathy.

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KK mice known to be spontaneously diabetic animals, develop various morphologic changes, but little work has been done to study relationships between those changes and the diabetic state. In this study, an attempt to control the diabetic state of KK mice was made by diet limitation, and morphologic changes in the controlled KK mice were compared with those in diabetic animals.
Male mice of the KK strain were divided into two groups: one group was given a daily amount of food limited to 3-4.5 g/body so as to weigh 30-35 g (controlled group), and the other was permitted free access to food (non-controlled group). They all were examined for diabetic symptoms from 4 to 10-16 months of age and observed histologically for changes in the organs.
In the controlled group, the diet limitation successfully restored blood glucose and glucose tolerance to normal and abolished glycosuria. When examined histologically, such changes characteristic to the KK strain as increased cells in the islets of Langerhans, an irregularly thickened glomerular basement membrane and increased mesangial matrix in renal glomeruli were apparently improved; improvement of the former change in particular had a close relationship with the period of recovery from the diabetic state. On the one hand, these controlled animals, like the non-controlled animals, showed calcification mainly in small and medium-sized arteries in the heart, lung, and kidney.
These findings suggest that progress of the changes in the islets of Langerhans and the renal glomeruli is related to the diabetic state of KK mice and that calcification noted in the heart, lung, and kidney may be a change attributable to some other factor.

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Autoimmunity and an antecendant viral infection may play important roles in the occurrence of insulin-dependent diabetes mellitus (IDDM). Although there have been many immunological studies of adult IDDM, no such report on a sufficient number of children with this disorder has been made in Japan.
One hundred and forty children in Hokkaido with IDDM of which the onset was at less than 15 years of age were studied for their HLA antigens and the presence or absence of islet cell antibody (ICA), antimicrosomal antibody (AMA) and of antithyroglobulin antibody (ATA).
Among the HLA antigens studied, Bw 54, DR 4 and MT 3 were significantly higher in frequency in patients than in controls while the frequencies of B 5 and DR 2 in patients were lower than in controls. In particular, MT 3 was most often found in patients (97.1%). These findings suggest the positive linkage of a HLA haplotype Bw 54-DR 4-MT 3 and the negative linkage of B 5 and DR 2 antigens to IDDM.
Twenty-two (44.0 %) of 50 patients studied had ICA within 12 months from the onset of diabetes, but the ICA-positive patients tended to decrease in number thereafter.
AMA/ATA was positive in 23 (26.7%) of 86 patients. However, there was no difference as to the frequencies of HLA antigens and the AMA/ATA positive rate between the patients having ICA persistently for five or more years and those whose ICA had disappeared by the fourth year from the onset.
The findings in the present study indicate that (1) MT 3 antigen would be associated with IDDM, (2) autoimmunity is not the only etiological mechanism for the disease, and (3) the persistent presence of ICA does not mainly correlate to autoimmunity

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Impotence is a well-known complication in diabetic men, though there have been only a few studies concerning the problem in Japan. Most previous studies are noncomparative. This paper reports results from a comparative study of 100 impotent diabetics and 100 age-matched nonimpotent diabetics. Data collected included medical histories, physical examinations, HbA₁, variations of RR intervals, residual urine volume estimated by postvoiding pyelography, Self-rating Depression Scale (SDS) test and a questionnaire about the level of libido.
In the results, diabetics with impotence had a longer duration of diabetes mellitus, lower grade of obesity and a higher percentage of insulin treated patients than the diabetics without impotence. There was no difference in the level of HbA₁ between the two groups. The incidences of peripheral neuropathy, retinopathy and nephropathy were increased significantly in the group of impotent diabetics. Autonomic neuropathies disclosed by determination of RR intervals and of residual urine volume were much more frequent in the impotent than the nonimpotent group. SDS of the diabetics with impotence was 41 ± 9.8 (M ± S.D.) and that of diabetics without impotence was 32 ± 7.8, the difference being significant by a t-test comparison. About 80 % of the impotent diabetics at any age complained of loss of libido.
In conclusion, diabetic impotence is strongly correlated with retinopathy and nephropathy as well as neuropathy and the patients with impotence have a greater depressive tendency and recognize less libido than those without impotence.

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Urinary sulfosalicylic acid-soluble mucoprotein (U-SSMP) concentrations were measured in 67 diabetic patients with or without clinical diabetic nephropathy and their correlation with urinary N-acetyl-beta-D-glucosaminidase (NAG) activities, serum creatinine and HbA_1c levels, was studied.
The diabetic group showed a significant increase in U-SSMP levels compared to non-diabetic controls (17.27 ± 1.34 vs 6.51 ± 0.62 mg/dl, p< 0.001) The U-SSMP concentrations in diabetics without proteinuria, with intermittent proteinuria and with persistent proteinuria were 15.24 ± 1.38 (n=48), 24.20 ± 5.85 (n=10) and 20.40 ± 3.08 mg/dl (n=9), respectively. All these values were significantly higher than those in non-diabetics. In addition, diabetics with intermittent proteinuria showed significantly higher levels of U-SSMP than those without proteinuria (p< 0.05).
A significantly positive correlation was observed between U-SSMP concentrations and urinary NAG activities (r=0.80, n=67, p< 0.001). A positive correlaion was also found between U-SSMP concentrations and HbA_1c levels.
U-SSMP concentrations were abnormally high in 20 %(10/48) of the diabetics without proteinuria whose urinary NAG activities were normal. In contrast, only 6 %(3/48) of the diabetics without proteinuria demonstrated elevated urinary NAG activities despite normal U-SSMP levels.
These results suggest that the increased U-SSMP levels seen in diabetics might be associated with early diabetic renal involvement, although many additional studies will be needed to confirm this.

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