Elevated C-Reactive Protein Is a Predictor of the Development of Diabetes in a General Japanese Population

Abstract

OBJECTIVE -We examined the association between high-sensitivity C-reactive protein (CRP) levels and the development of diabetes in a general Japanese population. RESEARCH DESIGN AND METHODS-A total of 1,759 Japanese subjects, aged 40 -79 years and without diabetes (according to American Diabetes Association fasting criteria), were stratified into three groups according to CRP tertiles by sex and followed up prospectively for a mean of 9.0 years.RESULTS -During the follow-up, 131 subjects (67 men and 64 women) developed diabetes. In both sexes, the age-adjusted cumulative incidence of diabetes increased significantly as the tertiles of CRP levels increased. In multivariate analyses, the risk of developing diabetes was significantly higher in the highest CRP tertile than in the lowest after adjustment for a number of confounding factors (odds ratio 2.63 [95% CI 1.23-5.65] for men and 2.25 [1.01-5.01] for women). In stratified analyses, this CRP-diabetes association was stronger in subjects without obesity or other risk factors related to insulin resistance and in nondrinking subjects.CONCLUSIONS -Our findings suggest that elevated CRP concentration is a significant predictor of diabetes in the general Japanese population, independent of obesity and insulin resistance. Diabetes Care 28:2497-2500, 2005I n some cohort and nested case-control studies in Western countries, an elevated C-reactive protein (CRP) level has been an independent predictor of diabetes (1-10). Recent cross-sectional studies have also demonstrated clear associations of elevated serum CRP levels with obesity and insulin resistance (11-13). These findings suggest that the inflammatory state illustrated by elevated CRP concentrations is associated with hyperglycemia and diabetes through obesity or increased insulin resistance. However, epidemiological findings concerning this issue are still controversial; several studies have reported a significant positive association between elevation in CRP levels and the future risk of diabetes even after adjustment for BMI (1,2,4,7,9,10), whereas in other studies (3,6) this association disappeared after adjustment for BMI.Japanese are characterized by low BMI levels and low CRP concentrations in blood compared with Westerners (14). Moreover, there have been no reports on the relationship between CRP levels and the development of diabetes among general populations in Japan. The aim of the present study is to examine the effects of serum CRP levels on the development of diabetes in a prospective study of a defined Japanese population, taking into account comprehensive risk factors. RESEARCH DESIGN AND METHODS Study population and follow-up surveyIn 1988, a screening survey for the present study was performed in the Town of Hisayama in Japan. A total of 2,587 residents aged 40 -79 years (80.2% of the total population of this age-group) participated in the baseline survey. The diabetes classification was based on the fasting criteria of the American Diabetes Association (15), i.e., subjects with fasting plasma gl...

Sex Differences in the Prediction of Type 2 Diabetes by Inflammatory Markers

“…In addition, recently published results from the cross-sectional Health, Aging and Body Composition Study demonstrated a significant sex interaction between levels of CRP and the presence of diabetes, impaired glucose tolerance, or impaired fasting glucose as determined by an oral glucose tolerance test in the age-, race-, and lifestyle-adjusted model and showed that CRP was not associated with diabetes or hyperglycemic status after further adjustment for physiologic risk factors in men but remained highly associated with the outcome in women (35). However, our results are in contrast with observations from the Hoorn Study, where CRP was only associated with diabetes in men but not in women (11) and with results from two Japanese populations, where an equally strong association between CRP and diabetes was seen in men and women (15,16). Furthermore, results of the present study are in contrast with those of the West of Scotland Coronary Prevention Study and the Kuopio Ischemic Heart Disease Risk Factor Study, both of which demonstrated an independent association between CRP and incident type 2 diabetes in men (7,14).…”

“…This hypothesis has recently been supported by several prospective studies showing that subjects who developed type 2 diabetes during the follow-up period had elevated levels of markers of inflammation such as C-reactive protein (CRP) or interleukin (IL)-6 at baseline compared with subjects who did not develop the disease (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). However, although various studies have examined these associations, few reported sexspecific results (5,11,15,16). This lack of data is surprising, since there is strong evidence for sex differences in associations between diabetes, obesity, endogenous sex hormones, and inflammation (17)(18)(19)(20)(21).…”

“…All four previous studies that separately analyzed men and women (5,11,15,16) were relatively small. The smallest study included only 54 incident cases (25 men and 29 women) (11), and even the largest included only 131 incident cases (67 men and 64 women) (15). Second, different degrees of adjustment might have affected the results.…”

“…While the Hoorn Study, conducted in the Netherlands, reported a significant association between CRP and incident diabetes in men but not in women (11), the opposite was seen in the Mexico City Diabetes Study (5). Finally, in two studies conducted in subjects of Japanese origin, CRP was significantly associated with incident type 2 diabetes in both sexes (15,16).…”

Association of C-reactive protein with type 2 diabetes: prospective analysis and meta-analysis

“…There is heterogeneity between studies, with some demonstrating an independently positive association of CRP with incident diabetes [3][4][5][6][7][8][9][10][11], while others show no association after adjustment for adiposity and insulin resistance [12][13][14][15]. Differences in the association between CRP and diabetes by sex have also been reported [16][17][18].…”