The purpose of this study was to analyze the incidence and precipitating factors of diabetic nephropathy, and the mutual relations among the precipitating factors in terms of clinico-laboratory variables.
Canonical correlation analysis was applied to the clinico-laboratory and patho-histological variables in 40 cases whose patho-histological changes were already known from biopsy or autopsy.
Testing of the accuracy of estimation was carried out in the 40 cases and resulted in a 90.0% coincidence between the estimated patho-histological changes of renal glomeruli based on the clinicolaboratory data and the patho-histological changes.
An investigation of the rates of coincidence in the 40 cases was carried out with the following criteria.
A: only slight “diffuse” changes
B: moderate diffuse changes
C: slight “nodular” changes with moderate or marked diffuse changes
D: marked diffuse changes with moderate or marked nodular changes
In an attempt to reevaluate the present treatment of diabetic nephropathy, the influence of correcting the 5 clinically controllable variables out of the 11 variables adopted for patho-histological changes of the renal glomeruli, was studied by the Marcov process in 220 diabetic outpatients.
The results of this analysis in patients remaining in poorly controlled states for years revealed a tendency for devastating lesions of the nodular type.
With the Marcov process control of blood glucose, blood pressure and the obesity index showed some relation to the development and/or progress of the glomerular changes.
It is concluded that correction of these factors, especially those which can be readily controlled by daily clinical practice, should be attempted to prevent and/or stop development of the diabetic nephropathy.

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Insulin-like activity (NSILA-s) in human blood which is not suppressed by insulin antibody was recently extracted and purified from human serum, and a radioreceptor assay (RRA) was developed to measure the insulin-like activity instead of bioassay. Based on the finding that somatomedine-c, like NSILA-s is a competitive inhibitor of ¹²⁵I-insulin binding to its receptor prepared from human placenta cell menbranes, RRA using insulin receptors solubilized from human placenta cell membranes was developed to measure NSILA-s.
The biological activity of the partially purified NSILA-s obtained was 6.3 to 8. 6 mU/mg, and the average was 7.1 mU/mg, as assayed by the isolated rat epididymal adipose cell method. NSILA-s was finally purified to the extent of 3550 times compared to the starting material. The activity as assayed by RRA was 8.8 mU/mg, which was closely almost similar to that estimated by bioassay.

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The validity of the new criteria proposed by Keen et al. was assessed on the basis of longterm prognosis, using subjects who were found in an epidemiologic survey. The 10-year relative survival rates (RSR) were examined in relation to the OGTT categories by the new criteria at the base line. The prognosis of normal subjects (fasting glucose value (F)<140 mg/dl and 2-hour glucose value (2 HR)<140 mg/dl) and IGT 1 (F<140 mg/dl and 2 HR between 140 and 200 mg /dl, originally defined as IGT) did not differ from that of the general population in Japan. Diabetics, however, revealed a significant decrease in RSR (59.5 ±11.0%), demonstrating an excess mortality in this group. Since the definition of OGTT by Keen et al. was not exhaustive, the following two groups were added and also assigned to IGT in the present study: IGT 2 (F<140 mg/dl and 2 HR>200 mg/dl) and IGT 3 (F>140 mg/dl and 2 HR <200 mg/dl), These two groups behaved quite differently: the RSR was 106.8±11.1% for IGT 2 and 50. 3 ± 23.7% for IGT 3. In addition, if a single value was employed for the distinction between normal and abnormal subjects, the RSR was 84.3 ± 8.3% for those with 2 HR>200 mg/dl and 66.2 ± 10.1% for those with F>140 mg/dl, suggesting that the fasting value was an effective parameter for the diagnosis of diabetes.
It is concluded that the new criteria, where the separation point was set at a much higher level, were broadly acceptable when examining the long-term prognosis of the subjects.

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Amino acid analysis was carried out on acid hydrolyzates of glomeruli isolated from kidneys obtained at autopsy from 19 nondiabetic and 21 diabetic subjects.
In the nondiabetic group, no differences in amino acid composition of the glomeruli were observed on the basis of the presence of albuminuria or hypertension. The contents of hydroxyproline, glycine and hydroxylysine in the glomeruli were significantly higher in the diabetic group than the nondiabetic group, especially in cases which showed nodular lesions in the glomeruli.
A linear relationship was obtained between the contents of hydroxyproline and hydroxylysine in the glomeruli isolated from all 40 subjects studied (Y =-8.11+ 6.31 x, r =0.918, p <0.001). The values for diabetics showing diffuse lesions and nodular lesions were scattered along the line.
The contents of basement membrane and fibrous collagen in the glomeruli were estimated from the glomerular contents of hydroxyproline and hydroxylysine. The ratio of basement membrane to fibrous collagen was about 2 in the non-diabetics and the sum of the basement membrane and fibrous collagen represented about 30% of the total protein in the glomeruli. The sum was about 50% of the total protein in glomeruli isolated from diabetic subjects showing no histological changes or diffuse lesions, and about 90% in glomeruli from diabetic subjects showing nodular lesions. The ratio of basement membrane to collagen was about 1 in the diabetic group regardless of the type of glomerular lesions.
These results suggest that the collagenous proteins in glomeruli obtained from diabetics are almost the same in character in diffuse lesions and nodular lesions.

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Morphological methods have mainly been used to quantify the diabetic glomerular basement membrane thickness. However, the small sampling of glomeruli especially by electron microscopy and the tedious measurement of basement membrane width limit these approaches.
In the present study, substantial numbers of glomruli were isolated from formaldehyde fixed kidneys of 30 nondiabetics and 41 diabetics, obtained at autopsy, and the glomerular hydroxyproline (expressed per glomerulus) was measured as an index of the glomerular basement membrane collagen in order to quantify the diabetic renovascular changes and to study the effect of diabetes on it.
1) The amount of hydroxyproline in glomeruli obtained from formaldehyde fixed kidneys was essentially the same as that in glomeruli obtained from fresh unfixed kidneys.
2) Using gas chromatography/mass spectrometry, the two isomers of hydroxyproline, 3-hydroxyproline and 4-hydroxyproline, were quantified in glomerular hydrolysates of 12 nondiabetics and 24 diabetics. The resultant ratios (3-hydroxyproline/4-hydroxyproline) were 0.089 ± 0.032 (mean ± SD) in nondiabetics and 0.079 ± 0.019 in diabetics. This indicates that 77-88% of the glomerular hydroxyproline was derived from basement membrane collagen. Thus, glomerular hydroxyproline can be utilized as a simple index of the amount of glomerular basement membrane collagen.
3) The glomeruli obtained from nondiabetics, between 33 and 85 years of age, showed no significant change in glomerular diameter and hydroxyproline content. In contrast, the diabetic glomerulibecame larger and contained 3.5 times more hydroxyproline than the nondiabetic glomeruli.
4) The hydroxyproline content of the diabetic glomeruli was significantly correlated with the severity of diabetic nephropathy, related to the blood, sugar levels and the intensity of various therapeutic regimens.
5) Since the glomerualr hydroxyproline content was significantly correlated with the degree of diffuse and nodular glomerular sclerosis, it could be used as a measure of the degree of diffuse glomerular sclerosis and could predict the presence of nodular changes in diabetic glomeruli.
The present method thus represents a simple and adequate, chemical means of estimation of glomerular basement membrane material in diabetic renovascular diseases and may be applicable in retrospective studies using autopsy materials and prospective investigations using renal biopsy specimens.

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A typical case of diabetic osteoarthropathy (Charcot's joint) is reported. The patient was a 53-year-old male, who was known to have had diabetes for 11 years. Destructive changes of the bones were initially found in the right navicular bone and the cuneiform bones, and subsequently invaded bones distal to the right foot joint. During 10 consecutive months, almost all bones distal to the ankle joint were destroyed without pain.
Electrophysiological studies revealed marked retardation of the maximal nerve conduction velocity. Sensory nerve conduction of the lower limb could not be evoked.
Pathological studies of nerves of the lower limb revealed a marked decrease in fiber density in both myelinated and unmyelinated fibers.
Based on teased nerve fiber studies, segmental demyelination and findings suggestive of axonal degeneration were found in all myelinated nerve fibers observed. Electronmicroscopic observations also revealed severe axonal degeneration and Schwann cell changes.
The pathogenesis of osteoarthropathy and the course and progress of the disease are discussed.

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