Elevated C-Reactive Protein Is a Risk Factor for the Development of Type 2 Diabetes in Japanese Americans

Abstract

OBJECTIVE -Increasing evidence from a cohort of Caucasians recently suggests that an elevated level of C-reactive protein (CRP) is associated with an increased risk of developing type 2 diabetes. However, Japanese subjects are skewed to lower CRP concentrations than westerners. Therefore, the effect of CRP on the development of type 2 diabetes among Japanese is unclear.RESEARCH DESIGN AND METHODS -We examined 396 male and 551 female nondiabetic Japanese Americans who underwent a 75-g oral glucose tolerance test (GTT) and were then followed for an average of 6.5 years. We investigated whether elevated serum CRP level is a risk factor in the development of type 2 diabetes among these subjects.RESULTS -Subjects with a high CRP level showed a significantly higher incidence of type 2 diabetes compared with subjects with a low level among both men (P ϭ 0.028) and women (P ϭ 0.004) in a log-rank test. In a Cox proportional hazards model dividing quartiles of CRP, the hazard ratios for diabetes development in the highest versus lowest quartile of CRP levels were 2.84 (95% CI 1.09 -7.39) among men and 3.11 (1.25-7.75) among women after adjustment for age, smoking, family history of diabetes, classification of a 75-g GTT, hormone replacement therapy (among women), BMI, and homeostasis model assessment.CONCLUSIONS -Among Japanese Americans, CRP may be a risk factor for development of type 2 diabetes independent of either obesity or insulin resistance. Our results suggest that inflammation may be closely related to the mechanism of type 2 diabetes among Japanese Americans. Diabetes Care 26:2754 -2757, 2003C omplications of diabetes reduce patients' quality of life. Therefore, it is necessary to identify individuals with glucose intolerance as early as possible to prevent its progression into diabetes. Thus, it may be more efficient to intervene when high-risk factors in subjects can be readily identified.C-reactive protein (CRP) is a marker of acute inflammation and is generally used as a measure of inflammatory disease. Recently, CRP increases have been reported in obesity (1,2) and type 2 diabetes (1). Thus, there is increasing evidence to suggest that insulin resistance is a chronic low-grade inflammatory state (3). In prospective case-control studies (4 -9), elevated levels of CRP predict the development of type 2 diabetes, supporting a possible role for inflammation in diabetogenesis (4, 6 -8).According to the literature on Japanese populations (10), Japanese subjects are skewed to lower CRP concentrations than westerners. Therefore, the acutephase response may vary due to racial differences. However, there have been no published reports investigating the relationship between CRP and the development of type 2 diabetes among Japanese. Although Americans of Japanese descent share a virtually identical genetic makeup with native Japanese currently living in Japan, Japanese Americans have approximately twice the incidence of type 2 diabetes compared with Japanese living in Japan, primarily because of a westernized lifestyl...

C-reactive protein and the risk of developing type 2 diabetes in Aboriginal Australians

“…A study in Mexico City showed that the association was strong and significant in women but not in men [17]. An independent association was observed in women aged 45-year or older in the United States [7], in middle-aged men in Eastern Finland [10] and in Japanese American men and women [9]. In a matched case-control study in a high risk population of Pima Indians, no association between CRP and diabetes was found [20], possibly due to the lack of power due to the small sample size.…”

“…The association between inflammatory markers and incident diabetes has been examined in a few prospective studies in other populations [7], [8], [9], [10], [17], [18] and [19]. A study in Mexico City showed that the association was strong and significant in women but not in men [17].…”

“…Most previous prospective studies of Caucasian populations examined either men [8] and [10] or women alone [7]. Studies in Mexicans [17] and Japanese Americans [9] examined and compared the associations between CRP and incident diabetes in both sexes. In both studies the association tended to be higher in women than in men.…”

“…Inflammation has also been postulated to play a role in the pathogenesis of type 2 diabetes. Recent prospective studies have suggested that an elevated level of CRP is associated with an increased risk of developing type 2 diabetes [7], [8], [9] and [10]. Some of the risk may be mediated through obesity and factors related to insulin resistance [10].…”

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].…”