This study was intended to determine the cut off level of urinary transferrin and its different-day variation, and to compare the sensitivity of microtransferrinuria with microalbuminuria in NIDDM.
Mean transferrin index (TfI) in 431 healthy subjects is 0.55+0.20 mg/gCr (mean+SD) and the cut off level of TfI is determined as 0.95 mg/gCr (mean+2SD).Coefficient of variation in TfI and albumin index (AI) determined in 5 consecutive days in 10 normal subjects (43.7±21.3 vs 52.1+20.8%) and in 10 patients with NIDDM (50.6±53.1vs71.4+42.7%) were comparable.
One hundred seventy-five patients with NIDDM were devided into 4 groups according to Al (A: 0-9.9, B: 10.0-19.9, C: 20.0-49.9, D: 50.0-199.9mg/gCr). The urinary albumin and transferrin were measured by nephelometry, and Al and TfI were determined by deviding albumin and transferrin by creatinine content. Between 4 groups of AI, TfI increased significantly and in all groups AI and TfI were significantly correlated each other. Six of 91 subjects in group A and 12 of 30 subjects in group B had exceeded TfI despite normal Al.
These results indicate that microtransferrinuria may be as sensitive as microalbuminuria as a marker of diabetic nephropathy in NIDDM.

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The effect of physical training on serum lipid levels in relation to insulin sensitivity was studied in 18 patients with NIDDM. The 8-week physical training consisted of jogging and stretching exercises for one hour, in addition to diet therapy. Insulin sensitivity was determined using the insulin clamp technique. The following results were obtained:
(1) After the 8-wk training period, the rate pressure product (heart rate systolic blood pressure) decreased by 13.0% at rest, 15.2% at stage 1, and 13.2% at stage 2 during treadmill testing (p<0.05).
(2) Glucose metabolic clearance rate (MCR) under euglycemic insulin clamp increased significantly during the training program (p< 0.01).
(3) Serum triglyceride (TG) decreased and HDL-cholesterol (HDL-C) increased significantly (TG: p<0.01, HDL-C: p<0.01).
(4) The increase in MCR correlated significantly with the decrease in TG (r=0.46, p<0.05) and the increase in HDL-C (r=0.74, p<0.01) during the training programs.
In conclusion, these data suggested that the decrease in serum triglyceride and the increase in HDL-cholesterol levels induced by physical training are related to improved insulin sensitivity in patients with NIDDM.

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Albumin concentration of the first morning urine, with and without creatinine correction, was compared with overnight and 24-hour albumin excretion rates, in hospitalized patients in whom urine collection could be timed precisely. Subjects were 24 patients with IDDM who had no proteinuria by Albustix. Albumin concentration on the first morning correlated closely with the overnight albumin excretion rate (r=0.84) and the 24-hour albumin excretion rate (r=0.79). Albumin per creatinine ratio of the first urine in the morning correlated closely with the overnight albumin excretion rate (r=0.93) and the 24-hour albumin excretion rate (r=0.68). These findings suggest that creatinine correction is not needed for the first morning urine to express microalbuminuria. Since the albumin concentration of the first urine in the morning is not subject to water dilution and exercise load, we conclude that this concentration is useful for the follow-up of microalbuminuria.

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Prognosis and the relationship between risk factors present at baseline and causes of death were studied using 1939 non-insulin-dependent diabetic patients (NIDDM) who were followed up for a mean period of 9.4 years. A total of 503 deceased cases were observed during the follow-up period. Risk factors present at baseline which markedly influenced the patients' prognoses included male gender, age at onset, hypertension, ischemic ECG changes, diabetic retinopathy, albuminuria, elevated fasting glucose level. Insulin treatment and GOT 60 were related to an increased mortality rate. These factors were also related to the causes of death among the deceased patients. Malignant neoplasms were relatively increased in patients with negative albuminuria, fasting glucose level<140mg/dl, and diet treatment at baseline, that is, in patients with diabetes or diabetic complications of mild degree.On the other hand, heart disease increased in patients with ischemic ECG changes, and serum cholesterol levels 260mg/dl. Renal disease markedly increased in those with diabetic retinopathy or persistent albuminuria, and cirrhosis of the liver in patients with GOT R 60. No remarkable influence of the baseline risk factors was observed in terms of cerebrovascular disease.Observation based on the O/E ratio revealed largely the same results.

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The role of complement activation in the pathogenesis and the pathophysiology of diabetic nephropathy was examined in 55 patients with non-insulin-dependent diabetes mellitus (NIDDM). Plasma and/or urinary concentrations of complement components, complement breakdown products and complement regulatory protein were measured using SRID and ELISA techniques.
Serum levels of complement components and plasma levels of complement breakdown products were significantly increased in NIDDM patients. The level of plasma vitronectin, the regulatory protein of the complement system, was significantly decreased in NIDDM patients with renal dysfunction. These data revealed in vivo activation of the complement system in NIDDM. Urinary complement breakdown products were detected in NIDDM patients with renal dysfunction. Their unique behaviour was highly suggestive of complement-induced glomerular injury.
In conclusion, complement activation may take part in the development and progression of glomerular injury in diabetes mellitus.

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This study was disigned to reevaluate the effect of long-term CSII treatment on the progression of diabetic complications. Seven IDDM patients treated with multiple insulin injection therapy before CSII began, have been followed-up for 76.3±20.1 (M±SD) months.
The HbA₁c value, averaged per year for each patient (10.1±2.7%at entry), fell significantly to 7.1±1.7%(p<0.01) during the first year and showed a sustained significant decrease over the succeeding seven years of CSII treatment. The progression of diabetic complications was reevaluated. Retinopathy: improved in 2, unchanged in 3 (including 2 subjects with transient deterioration during the 6 months after CSII initiation) and slight progression in 2. Nephropathy: 2 of 3 patients with microalbuminuria (MA) improved to normoalbuminuria (NA) and in one low range persisted MA. Three of 4 patients with NA remained stable and one progressed to low range MA. Neuropathy: mean value of motor nerve conduction velocity improved significantly;from 46.9±2.6 m/s at entry to 54.4±0.8 m/s at the end of the follow-up period.
We conclude that long-term CSII therapy is well accepted by IDDM patients and can result in significant improvement of metabolic control. Furthermore, it may delay or prevent the early stage of diabetic complications.

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The study compared the mortality of IDDM patients with onset age of less than 18 years due to diabetic renal disease between Japan and Allegheny County, PA, the U. S. In Japan, 16 of 1394 died due to this condition, in contrast to only 2 of 986 in the U. S., a ten-fold increased risk of dying in Japanese cohort.(Age-adjusted mortality rate for renal disease: Japan vs. the U. S., 276.7 vs.22.8/100, 000 person-years). There was geographic variation in Japan, with the total and renal disease mortality associated inversely with socioeconomic status of the area, estimated by an average yearly income per person.
The reasons for the extremely high renal disease mortality in Japan are unclear. Hypotheses include differences in the incidence of renal disease, differences in the genetic susceptibility for renal disease and differences in the delivery of diabetes care between the two populations. There are a number of research avenues scientists could pursue at this time to explain the mortality differential observed. Collaboration within established multinational studies, such as the WHO DIAMOND study, ensures the application of standardized techniques and methods which can uncover important clues regarding renal disease mortality among IDDM cohorts: a potent, and possibly preventable, killer.

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We describe a 47-year-old diabetic female with slowly progressive distal limb weakness and sensory impairment since age 45. Sural nerve biopsy showed severe loss of myelinated fibers with occasional fibers with thin myelin and onion bulb formations. Detailed motor nerve conduction studies revealed considerable slowing in conduction velocity with multifocal conduction block localized to sharply circumscribed areas. These results were compatible with acquired multifocal demyelinating neuropathy and seemed to be extremely exceptional in a case of diabetic polyneuropathy. Concurrence of chronic inflammatory demyelinating polyneuropathy (CIDP) was, thus, strongly suspected in this case.Corticosteroids and plasma exchange may be effective for CIDP, nevertheless no specific treatment was employed because of severely degenerative retinopathy in this case.Early diagnosis is essential to prevent the progression of axonal degeneration in CIDP. Concurrence of CIDP and diabetes may exaggerate degenerative processes in nerve fibers.

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To investigate selective protein permeability in early diabetic glomerulopathy, urinary total IgG and IgG4 excretion and urinary albumin excretion were compared in patients with non insulin-dependent diabetes mellitus (NIDDM).
Sixty one NIDDM patients were classified according to their albumin excretion rate (AER) determined on the basis of overnight urine collections (22: AER<20μg/min, normoalbuminuria; 21: AER 20 to 200μg/min, microalbuminurla; 18: AER>200 μg/mnin, macroalbuminuria) NIDDM patients and 36 normal controls were analyzed for urinary total IgG, IgG4 and urinary NAG excretion. Urinary total IgG was detected by novel non-immunological competitive assay (biotin-avidin method), and IgG4 was detected using a newly developed ELISA employing anti-IgG4 monoclonal antibody.
U-Total IgG levels were significantly higher in both microalbuminuria and macroalbuminuria in comparison with normoalbuminuria or controls (p<0.01 and p<0.05, respectively). U-IgG4 levels were significantly increased in both macroalbuminuria and microalbuminuria, compared with normoalbuminuria and the controls (p<0.05). U-total IgG levels were clearly elevated in normoalbuminuria compared with the controls (p<0.01), whereas U-IgG4 levels for normoalbuminuria were within the normal range. Urinary NAG excretion was similar in the controls and the other groups.
These data indicate that selective urinary excretion of different IgG subclasses appears to provide a method of assessing besement membrane impairment in early diabetic nephropathy and may serve as an additional parameter to precisely characterize incipient diabetic nephropathy.

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