Kei Miyamura

Serum Type IV Collagen Concentrations in Diabetic Patients With Microangiopathy as Determined by Enzyme Immunoassay With Monoclonal Antibodies

In long-term diabetes mellitus, thickening of basement membrane in capillaries and small vessels is a characteristic lesion and plays an important role in the progression of diabetic microangiopathy. We have developed a sandwich enzyme immunoassay for human serum type IV collagen peptide with monoclonal antibodies. Previous studies suggested that collagen levels reflect the activity of fibrogenesis in basement membrane. Serum type IV collagen levels were measured in 137 non-insulin-dependent diabetic patients (aged 50–75 yr) with or without clinical signs of retinopathy, nephropathy, and/or neuropathy and 110 healthy subjects (aged 50–75 yr) without serological abnormality. Serum concentrations of type IV collagen were significantly higher (P < 0.01) in diabetic patients (mean ± SE 124.1 ± 4.1 ng/ml) than in healthy subjects (73.9 ± 2.2 ng/ml) and were increased with the prevalence or incidence of diabetic complications. In the patients with diabetic microangiopathy, serum type IV collagen levels became higher as clinical signs worsened. Especially in the patients with diabetic nephropathy, serum type IV collagen levels became higher with elevation of blood urea nitrogen, serum creatinine, and serum β2-microglobulin but not urinary excretion of β2- microglobulin and N-acetyl-β-glucosaminidase. These observations indicated that elevation of serum type IV collagen in diabetic nephropathy was related to glomerular filtration dysfunction rather than renal tubular dysfunction. However, the antigen, which can be detected by our assay system, did not exist in urine specimens of healthy subjects, and an intimate relationship was not observed between serum type IV collagen level and serum creatinine level. These results implied that the serum type IV collagen level reflects its increased synthetic activity in basement membrane rather than its reduced clearance rate. The concentration of serum type IV collagen peptide seems to be a useful, noninvasive, reproducible marker for assessment of the activity or progression of diabetic microangiopathy and for evaluation of therapeutic effects.

Diabetic neuropathy as a heterogeneous syndrome: multivariate analysis of clinical and neurological findings

We quantitatively assessed peripheral and autonomic nerve function in diabetic patients and compared them with various parameters of their diabetic status. Motor and sensory nerve conduction velocity (MCV, SCV), vibratory perception threshold (VPT) and the coefficient of variation of the ECG R-R interval (CV R-R) were measured in 85 diabetic patients aged 20-59 years. These values were compared with those of age-matched healthy subjects. Moreover, in 53 patients, MCV, SCV, VPT and CV R-R were investigated by multivariate analysis in relation to clinical parameters. In diabetics, MCV, SCV and CV R-R were significantly lower and VPT was higher than in age-matched healthy controls. The prevalence of impaired values in diabetics was 70% for VPT in the toe, 60% for SCV, and 55% for MCV, CV R-R and VPT in the finger. Impairments of MCV, SCV, CV R-R and VPT were closely correlated with diabetic retinopathy, proteinuria and duration of disease. Categorical regression analysis (multivariate analysis) revealed that the impairment of conduction velocity was closely related to diabetic retinopathy and to hypo- or areflexia, that the impairment of the vibratory perception threshold was related to ischemic changes in ECG and to hypo- or areflexia, and that the reduction of CV R-R was related to orthostatic hypotension and to proteinuria. These findings suggest that diabetic neuropathy progresses in parallel with other complications, and that it is a heterogeneous syndrome rather than a single entity.

Effect of calcium antagonists on reactive hypoglycemia associated with hyperinsulinemia

The clinical usefulness of calcium antagonists was studied in four patients with reactive hypoglycemia including two with alimentary and two with idiopathic. All patients had hyperresponses of plasma insulin (IRI) and C-peptide (CPR) during an oral glucose tolerance test (OGTT). A calcium antagonist (diltiazem 90 mg/d, or nifedipine 30 mg/d, or nicardipine 60 mg/d) was administered orally for about two months. After two months of treatment, plasma IRI and CPR responses during the OGTT were clearly suppressed in all patients and symptomatic reactive hypoglycemia disappeared. One month after the discontinuation of the treatment in two patients, plasma IRI and CPR responses during the OGTT became higher again and symptomatic reactive hypoglycemia recurred. In addition, an intravenous glucose tolerance test was performed before and after two months of the treatment with calcium antagonists in the two patients with reactive hypoglycemia and seven patients with hypertension, who were free from glucose intolerance and were also treated with a calcium antagonist. In these patients, plasma IRI and CPR responses were also reduced after the treatment compared with those before the treatment. These results suggest that calcium antagonists are useful as therapeutic agents for the treatment of reactive hypoglycemia associated with hyperinsulinemia, and that one of the main mechanisms of action of calcium antagonists is a direct action on the pancreatic B-cell to inhibit glucose-induced insulin release.

Properdin Factor B Frequencies in Four Asian Populations

The distribution of Properdin factor B (Bf) phenotypes and their gene frequencies were investigated in four Asian populations (Chinese, Filipino, Thai and Japanese). The frequency of the BfS phenotype in Filipinos (0.717) was significantly lower than that in Chinese (0.900) and Thai (0.889) (p less than 0.01), but not different from the Japanese (0.840). One variant, BfF 0.65 S, was identified in a Japanese subject. Thus, in the Asian populations studied, Bfs frequencies were high and the frequency of variants other than F and S were low.

Fructosamine concentration in serum and plasma of hemodialyzed patients with chronic renal failure

糖尿病性腎症23名を含む慢性腎不全透析症例48例より透析前後に採血し, 血清 (S) および血漿 (P) フルクトサミン値 (Fr) を測定し以下の成績を得た. 1) 透析前後とも, S-Frに比しEDTA-2Na採血後測定されたP-Frは有意の低値を示したが, 両者の間に有意の正相関が認められた. 2) S-Fr, P-Frとも透析前後の値に差異は認められなかった. その一因に, 透析前に比し除水により高値となった透析後のFrが, 透析中に添加されたheparinの影響により, 測定法上, 低下をきたしたことが考えられる. また, 透析前のS-Frにおいて, 3) 糖尿病性腎症のS-Frは非糖尿病性腎不全症例に比し高値を示した. 4) S-Frは, 同時測定された血糖値よりも過去2週間の平均透析前血糖値 (PG) との方が相関性が強く, affinity chromatography法によるglycated albumin and Hb値やHbA1and HbA1c値とも有意の正相関を示した. しかし, 尿素窒素, 尿酸クレアチニン, アセト酢酸, 3ヒドロキシ酪酸などの各値とは相関性を示さなかった. 5) PGは, S-Fr/総蛋白のA/G ratio>S-Fr/アルブミン値>S-Fr>S-Fr/総蛋白値, の順に強い有意の正相関を示した. 従って, Frの測定は糖尿病を含む慢性腎不全透析症例における過去2週間の長期的な血糖コントロール状態の指標として有用であることが実証された. また, S-Frを総蛋白のA/G ratioにより除すことにより, S-Frのみ, またはアルブミン値により除すFr補正値に比し, PGとの相関がより一層強くなることが示唆された. さらに, 一回の血液透析過程がFrに及ぼす影響としては, 主として透析中に添加されるheparinが, 測定法上, 透析後のFrの低下をきたすことも分かった.