Miyuki Ishikawa

The metabolic syndrome is associated with elevated circulating C-reactive protein in healthy reference range, a systemic low-grade inflammatory state.

OBJECTIVE: To elucidate the underlying mechanisms between C-reactive protein (CRP) and cardiovascular disease, we exa-mined the association of circulating CRP in healthy reference range (≤1.0 mg/dl) measured by high-sensitive CRP assay with the metabolic syndrome (MS).DESIGN: Cross-sectional study of circulating CRP in adult men.SUBJECTS: A total of 3692 Japanese men aged 34–69 y.MEASUREMENTS: Serum CRP, total cholesterol, triglycerides, LDL-cholesterol, fasting glucose, fasting insulin, uric acid, systolic blood pressure, diastolic blood pressure, and body mass index (BMI).RESULTS: There was a statistically significant positive correlation between CRP and BMI (r=0.25), total cholesterol (r=0.096), triglycerides (r=0.22), LDL-cholesterol (r=0.12), fasting glucose (r=0.088), fasting insulin (r=0.17), uric acid (r=0.13), systolic blood pressure (r=0.12), and diastolic blood pressure (r=0.11), and a significant negative correlation of CRP with HDL-cholesterol (r=0.24). After adjusting for age, smoking, and all other components of MS, obesity, hypertriglyceridemia, hyper-LDL-cholesterolemia, diabetes, hyperinsulinemia, and hyperuricemia were significantly associated with both mildly (≥0.06 mg/dl) and moderately (≥0.11 mg/dl) elevated CRP. Compared with men who had no such components of the MS, those who had one, two, three, four, and five or more components were, respectively, 1.48, 1.84, 1.92, 3.42, and 4.17 times more likely to have mildly elevated CRP levels (trend P<0.001). As for moderately elevated CRP, the same association was observed.CONCLUSIONS: These results indicate that a variety of components of the MS are associated with elevated CRP levels in a systemic low-grade inflammatory state.

Long-term body weight variability is associated with elevated C-reactive protein independent of current body mass index among Japanese men

OBJECTIVE: To elucidate the effect of long-term weight variability on C-reactive protein (CRP) levels.DESIGN: Cross-sectional study of the circulating CRP.SUBJECTS: A total of 637 Japanese men aged 40–49 y in1997.MEASUREMENTS: Serum CRP levels, body mass index in 1997 (current BMI), the slope of weight on age (weight-slope) representing an individuals weight trend of direction and magnitude, and the root mean square error around the slope of weight on age (weight-RMSE) representing the weight fluctuation magnitude, as calculated by a simple linear regression model in which each value of the subjects five actual weights (aged 20, 25, 30 y, five years ago, and current) was a dependent variable and the subjects ages independent variables.RESULTS: After adjustment for age and confounders, including smoking and health status, the odds ratios of elevated CRP (≥0.06 mg/dl) were 1.83 (95% CI: 1.25–2.69), 2.63 (1.69–4.11), and 10.31 (2.17–48.98) for upper normal-weight (BMI: 22–<25 kg/m2), overweight (25–<30), and obese (≥30) persons, respectively, compared with lower normal-weight persons (18.5–<22). Adjusting for age, confounders, and current BMI, weight-slope was positively associated with CRP level especially among subjects with BMI≥25 kg/m2 (trend P<0.01), and weight-RMSE was positively associated with CRP level particularly among subjects with BMI <25 kg/m2 (trend P<0.05).CONCLUSION: Our results suggest a state of low-grade systemic inflammation not only in overweight and obese persons, but also in normal-weight persons with large weight fluctuation, possibly explaining in part the positive association between weight fluctuation and CVD.

Stereocontrolled syntheses of α-C-mannosyltryptophan and its analogues

The total synthesis of α-C-mannosyltryptophan (C-Man-Trp), a naturally occurring C-glycosylamino acid, was achieved from a commercially available α-methyl-D-mannoside in 10 steps including the following key steps: the C-glycosidation of a mannose derivative with a stannylacetylene, Castro indole synthesis, and Sc(ClO4)3-promoted coupling with L-serine-derived aziridine carboxylate. The glucose- and galactose-analogues of C-Man-Trp were also synthesized in a similar manner. Conformational analyses of the synthesized C-glycosyltryptophan and its synthetic intermediate are briefly discussed.

Association between weight fluctuation and fasting insulin concentration in Japanese men

OBJECTIVE: To investigate whether long-term weight fluctuation is associated with the fasting serum insulin concentration.DESIGN AND SUBJECTS: Weight histories of 1932 male Japanese workers aged 40–59 y were analyzed in relation to their current fasting serum insulin concentration. MEASUREMENTS:Individual weight fluctuation was calculated by root mean square error (RMSE) along the linear regression line of weight measured at five to six different ages.RESULTS: The mean RMSE and fasting insulin concentration were 1.22 kg and 4.5 μU/ml, respectively. The multivariate adjusted insulin level became higher with the increase in weight fluctuation. Subanalysis stratified by current body mass index (BMI) showed that the multivariate adjusted insulin level in individuals in the top quartile of fluctuation was 4.3 μU/ml, against 3.9 μU/ml in those in the bottom quartile (P=0.018, analysis of covariance (ANCOVA)) in the normal weight subgroup with current BMI below 25 kg/m2. In the overweight subgroup with BMI 25 kg/m2 or above, the level was 6.9 μU/ml in individuals in the top quartile and 6.2 μU/ml in those in the bottom quartile (P=0.054, ANCOVA).CONCLUSION: The results suggest that weight fluctuation increases the risk of developing hyperinsulinemia. Prospective observations together with measurement of changes in adiposity are needed for confirmation.

Association between serum leptin concentration and white blood cell count in middle-aged Japanese men and women

Leptins hematopoietic or proinflammatory role has been experimentally reported. We investigated whether serum leptin concentrations are associated with white blood cell (WBC) counts in humans.