OBJECTIVE— To investigate the usefulness of the homeostasis model assessment as an index of insulin resistance (HOMA-IR) for evaluating the clinical course of patients with type 2 diabetes. RESEARCH DESIGN AND METHODS— The usefulness of HOMA-IR and its relationship with insulin resistance assessed by the hyperinsulinemic-euglycemic clamp study (clamp IR) were evaluated in 55 Japanese patients with type 2 diabetes before and after treatment. The patients were subjected to diet (∼1,440-1,720 kcal/day) and exercise therapy (walking 10,000 steps daily) for 6 weeks during their hospitalization. RESULTS— Univariate regression analysis disclosed a significant correlation between log-transformed HOMA-IR and log-transformed clamp IR before (r = -0.613, P < 0.0001) and after (r = -0.734, P < 0.0001) treatment. Neither the slopes (-0.71 ± 0.12 vs. -0.79 ± 0.09, F = 0.25, P = 0.61) nor the intercepts (y-intercept = 1.67 vs. 1.70, x-intercept = 2.36 vs. 2.15, F = 0.02, P = 0.88) of the regression lines between HOMA-IR and clamp IR were significantly different before and after treatment. There was a significant correlation between the decrease in log-transformed HOMA-IR and the increase in clamp IR during treatment (r = -0.617, P < 0.0001). CONCLUSIONS— HOMA-IR may constitute a useful method not only for diagnosing insulin resistance, but also for follow-up during the treatment of patients with type 2 diabetes.

To investigate the direct relationship of oxidative stress with obesity and insulin resistance in men, we measured the plasma levels of 8-epi-prostaglandin F2α (PGF2α) in 14 obese and 17 nonobese men and evaluated their relationship with body mass index; body fat weight; visceral, sc, and total fat areas, measured by computed tomography; and glucose infusion rate during a euglycemic hyperinsulinemic clamp study. Obese men had significantly higher plasma concentrations of 8-epi-PGF2α than nonobese men (P < 0.05). The plasma levels of 8-epi-PGF2α were significantly correlated with body mass index (r = 0.408; P < 0.05), body fat weight (r = 0.467; P < 0.05), visceral (r = 0.387; P < 0.05) and total fat area (r = 0.359; P < 0.05) in all (obese and nonobese) men. There was also a significant correlation between the plasma levels of 8-epi-PGF2α and glucose infusion rate in obese men (r = −0.552; P < 0.05) and all men (r = −0.668; P < 0.01). In all subjects, the plasma levels of 8-epi-PGF2α were significantly correlated with fasting serum levels of insulin (r = 0.487; P < 0.01). In brief, these findings showed that the circulating levels of 8-epi-PGF2α are related to adiposity and insulin resistance in men. Although correlation does not prove causation, the results of this study suggest that obesity is an important factor for enhanced oxidative stress and that this oxidative stress triggers the development of insulin resistance in men.

Objective To determine the efficacy of a 23-valent pneumococcal polysaccharide vaccine in people at high risk of pneumococcal pneumonia. Design Prospective, randomised, placebo controlled double blind study. Setting Nursing homes in Japan. Participants 1006 nursing home residents. Interventions Participants were randomly allocated to either 23-valent pneumococcal polysaccharide vaccine (n=502) or placebo (n=504). Main outcome measures The primary end points were the incidence of all cause pneumonia and pneumococcal pneumonia. Secondary end points were deaths from pneumococcal pneumonia, all cause pneumonia, and other causes. Results Pneumonia occurred in 63 (12.5%) participants in the vaccine group and 104 (20.6%) in the placebo group. Pneumococcal pneumonia was diagnosed in 14 (2.8%) participants in the vaccine group and 37 (7.3%) in the placebo group (P<0.001). All cause pneumonia and pneumococcal pneumonia were significantly more frequent in the placebo group than in the vaccine group: incidence per 1000 person years 55 v 91 (P<0.0006) and 12 v 32 (P<0.001), respectively. Death from pneumococcal pneumonia was significantly higher in the placebo group than in the vaccine group (35.1% (13/37) v 0% (0/14), P<0.01). The death rate from all cause pneumonia (vaccine group 20.6% (13/63) v placebo group 25.0% (26/104), P=0.5) and from other causes (vaccine group 17.7% (89/502) v placebo group (80/504) 15.9%, P=0.4) did not differ between the two study groups. Conclusion The 23-valent pneumococcal polysaccharide vaccine prevented pneumococcal pneumonia and reduced mortality from pneumococcal pneumonia in nursing home residents. Trial registration Japan Medical Association Center for Clinical Trials JMA-IIA00024.

OBJECTIVE—The purpose of this study was to investigate the association between visceral adiposity or triglyceride (TG) metabolism and insulin resistance in metabolically obese, normal weight (MONW) Japanese individuals with normal glucose tolerance. RESEARCH DESIGN AND METHODS—We evaluated body fat areas, lipid profiles, and the glucose infusion rate (GIR) during a euglycemic-hyperinsulinemic clamp study in 20 MONW subjects (BMI <25 kg/m²and visceral fat areas 100 cm²) with normal glucose tolerance. Body fat areas were measured by computed tomography scans. Control data were obtained from 20 normal subjects (BMI <25 kg/m² and visceral fat areas <100 cm²). RESULTS—MONW subjects showed a significant increase in fasting serum levels of TG (P < 0.01) and a decrease in GIR (P < 0.01) compared with normal subjects. There were significant correlations between visceral fat areas (r = −0.563, P < 0.01) or serum levels of TG (r = −0.474, P < 0.05) and GIR in MONW subjects. Multiple regression analyses showed that visceral fat areas (F = 7.702, P < 0.02) and serum levels of TG (F = 7.114, P < 0.05) were significantly associated with GIR in all (MONW and normal) subjects. CONCLUSIONS—Increased visceral fat and serum levels of TG are associated with insulin resistance in Japanese MONW subjects with normal glucose tolerance. Excess visceral fat and elevated TG levels may play important roles in the development of insulin resistance in Japanese MONW subjects with normal glucose tolerance.

Some Bacteroidetes and other human colonic bacteria can degrade arabinoxylans, common polysaccharides found in dietary fiber. Previous work has identified gene clusters (polysaccharide-utilization loci, PULs) for degradation of simple arabinoxylans. However, the degradation of complex arabinoxylans (containing side chains such as ferulic acid, a phenolic compound) is poorly understood. Here, we identify a PUL that encodes multiple esterases for degradation of complex arabinoxylans inBacteroidesspecies. The PUL is specifically upregulated in the presence of complex arabinoxylans. We characterize some of the esterases biochemically and structurally, and show that they release ferulic acid from complex arabinoxylans. Growth of four different colonic Bacteroidetes members, includingBacteroides intestinalis, on complex arabinoxylans results in accumulation of ferulic acid, a compound known to have antioxidative and immunomodulatory properties.

We examined the expression of tissue factor (TF) and vascular endothelial growth factor (VEGF) and the microvessel density (MVD) in 100 patients with colorectal cancer, and we investigated the relationship of the expression of TF or VEGF with angiogenesis. TF antigen was positive in 57.0% of all specimens. Incidence of TF expression was 41.2%, 45.5%, 52.6%, 84.6%, and 81.3% in tumors from patients in clinical stages I, II, IIIA, IIIB, and IV, respectively. TF expression was correlated with the Dukes' classification (P = 0.01) and the clinical stage of colorectal cancer (P = 0.02). VEGF antigen was positive in 64.0% of all specimens. Incidence of VEGF expression was 41.2%, 57.6%, 73.7%, 84.6%, and 75.0% in tumors from patients in clinical stages I, II, IIIA, IIIB, and IV, respectively. VEGF expression was correlated with the Dukes' classification (P = 0.01) but showed a weak association with the clinical stage (P = 0.08). MVD was significantly associated with the depth of invasion (P = 0.01), lymph node metastasis (P = 0.001), and liver metastasis (P = 0.02). The mean values of MVD were 7.5 ± 2.8, 10.1 ± 5.7, 14.6 ± 5.8, 13.5 ± 3.9, and 15.9 ± 4.2 in tumors from patients in clinical stages I, II, IIIA, IIIB, and IV, respectively. A close relationship between VEGF and MVD (P < 0.001) and a significant correlation between TF expression and MVD were observed (P = 0.02). TF‐positive carcinomas presented high MVD and VEGF expression (P < 0.001) more frequently than did TF‐negative tumors. These results suggest that involvement of TF in the process of metastasis and progression of colorectal cancer may depend on increased angiogenesis. Am. J. Hematol. 69:247–254, 2002.