This study investigated the etiology of ischemic heart disease in diabetics. The frequency and potential risk factors for ischemic change on the ECG at the initial visit were evaluated in 1, 159 non-insulin dependent diabetics. These risk factors were compared to those for the microvascular complications retinopathy, nephropathy and neuropathy.
Evidence of ischemic change was present on the ECG in 133 cases (11% of all subjects), and its prevalence increased according to age. Ischemic change was associated with increasing age, earlier initial visit, higher blood pressure, and higher cholesterol levels. Regression analysis showed that the correlations with age and blood pressure were statistically significant with respect to ischemic change. Neither gender, duration of diabetes, obesity, hyperglycemia, or cholesterol were correlated ischemic change. These findings were similar to the risk factors for proteinuria, but quite different from those for retinopathy and neuropathy.
The results suggest that ischemic heart disease in diabetics is promoted by aging and hypertension and that its etiology is similar to that of diabetic nephropathy.

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The present study was conducted to examine whether urinary glutathione S-transferase (GST) activity is correlated with the degree of progression of diabetic nephropathy (study1) and whether the renal tissue distribution of GST reflects the renal damage in rats with streptozotocin (STZ)-induced diabetes (STZ rats)(study 2). Concentrating urine samples by freeze-drying enabled us to quantitate urinary GST activity. In study 1, urinary GST activity was significantly higher in the diabetic patients than in the healthy controls and was significantly correlated with the urinary albumin excretion index, and the N-acetyl-β-D-glucosaminidase and β₂-microglobulin levels. In study 2, immunochemical staining using anti-GST Ya antibody revealed that basic GST (GST Ya) was uniformly distributed in the proximal tubules, but it was not detected in either the glomerular region or the distal tubules. Basic GST was also detected in the proximal tubules of the STZ rats, however its intensity was clearly heterogeneous. Insulin treatment normalized the tissue distribution of basic GST in the kidneys of STZ rats. Acidic GST (GST Yp) stained positive in the outer medulla and there were no differences among the three groups.
Thus, elevated urinary GST activity in diabetic patients may reflect increased excretion of GST due to increased permeability of the proximal tubular cell membrane.

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We examined the usefulness of morphometric analysis of immunostained nerve fibers in biopsied skin specimens using both light microscopy and confocal laser scanning microscopy to evaluate diabetic neuropathy. In controls, PGP 9.5 immunoreactive (IR) nerve fiber length (NFL) in the epidermis showed a negative correlation with age on confocal laser scanning microscopic analysis. Diabetic patients showed significantly shorter NFL in the epidermis than age-matched control subjects, although NFL in the dermis revealed no difference between the two groups. NFL in the epidermis was significantly shorter in diabetic patients with than in those without sensory symptoms (p<0.05). NFL also showed a significant correlation with sural nerve conduction velocity among diabetic subjects (r=0.48, p<0.05), based on light microscopic analysis. These results suggest that the nerve degenerates from the nerve terminal in the epidermis in diabetic patients. Although these changes were also observed in elderly control subjects, the process seemed to be accelerated in diabetic patients. Taken together, these results suggest that quantitative analysis of PGP 9.5IR NFL, using biopsied skin samples, is potentially useful for the evaluation of DN.

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We compared the effects of two kinds of commercial diets, termed MM3 for “long term rearing” (high fiber diet) and MB3 for “special breeding” (low fiber diet) on the development of spontaneously occurring diabetes in NOD mice. Female NOD mice were fed MM3 or MB3 after weaning. Although there were no significant differences in body weight and the cumulative incidence of diabetes development at 28 weeks of age between the two groups, the onset age of diabetes in the MB3-fed group (22.7±4.7weeks) was slightly earlier than that in the MM3-fed group (24.6±5.7 weeks). At 28 weeks of age, although there was no significant difference in caloric intake between the two groups, a remarkable difference in dietary fiber intake was observed. The pancreatic insulin content of the MB3-fed group was significantly lower than that of the MM3 fed group. There was no difference in the severity of insulitis, histopathologically, between the two groups.
These data suggest that the increase in dietary fiber intake sustained the insulin content of the pancreas but did not affect the development of diabetes mellitus in NOD mice.

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The present study was conducted to detect the early stage of entdothelial dysfuntction in NIDDM subjects.Venostasis and hand grip stress tests were performed to so as achieve mild and severe hypoxia, respectively, in NIDDM patients and healthy controls. After an overnight fast, plasma fibrinogen (Fbg), soluble fibrin monomer complexes (SFMC), factor VIII related antigen (VIII-Rag) and type IV collagen (IV-C) were measured in 37 patients and 10 healthy controls before and after 5min of arm venous occlusion with a sphygmomanometer at mean blood pressure (venostasis test, Study I). The hand grip stress test was performed in 36 patients and 13 healthy controls using a hand grip exercise in addition to the venous occlusion (Study II). NIDDM patients were divided into three subgroups according to their urinary albumin excretion index (UAEI);<20mg/g·creatinine (mg/g·Cr)(group 1), 20≤UAEI<200mg/g·Cr (group 2), ≥200mg/g·Cr (group 3), and relationships between the four parameters and UAEI were examined.In Study I, SFMC, VIII-Rag and IV-C were significantly increased only in group 3. In Study II, SFMC, VIII-Rag and IV-C were significantly increased in group 2 as well as group 3.
From these results, it is suggested that endothelial and subendothelial damage is present even in the early stage of diabetic nephropathy and that the hand grip stress test is a potentially useful method for the early detection of endothelial and subendothelial dysfunction.

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We report a case of scleromyxedema complicating diabetic nephropathy treated by hemodialysis. A 32-year-old woman with a 4-year history of non-insulin-dependent diabetes mellitus was admitted to our hospital because of nephrosis. She was azotemic, had round injection scars on a lateral femoral lesion and sclerosis on bilateral crural lesions. Biopsy was performed on these lesions. The collagen fibers were separated and appeared to be rupturing in the edematuos dermis with much deposition of mucin (hyaluronic acid). A diagnosis of scleromyxedema was made, and the patient was treated with steroid therapy and hemodialysis. Her scleromyxedema improved slightly, this was a rare case and required careful follow-up.

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