Prospective Study of C-Reactive Protein in Relation to the Development of Diabetes and Metabolic Syndrome in the Mexico City Diabetes Study

Abstract

OBJECTIVE -Recent evidence suggests that C-reactive protein (CRP) may predict development of diabetes in Caucasian populations. We evaluated CRP as a possible risk factor of the development of diabetes and metabolic syndrome in a 6-year study of 515 men and 729 women from the Mexico City Diabetes Study.RESEARCH DESIGN AND METHODS -Baseline CRP, indexes of adiposity, and insulin resistance (homeostasis model assessment [HOMA-IR]) were used to predict development of the metabolic syndrome, defined as including two or more of the following: 1) dyslipidemia (triglyceride Ն2.26 mmol/l or HDL cholesterol Յ0.91 mmol/l in men and Յ1.17 mmol/l in women; Ͻ35 and 40 mg/dl for men and women); 2) hypertension (blood pressure Ͼ140/90 mmHg or on hypertensive medication); or 3) diabetes (1999 World Health Organization criteria).RESULTS -At baseline, CRP correlated significantly (P Ͻ 0.001) with all metabolic indexes in women, but less so in men. After 6 years, 14.2% of men and 16.0% of women developed the metabolic syndrome. Compared with tertile 1, women with CRP in the highest tertile had an increased relative risk of developing the metabolic syndrome by 4.0 (95% CI 2.0 -7.9) and diabetes by 5.5 (2.2-13.5); these risks changed minimally after adjusting for BMI or HOMA-IR. The area under receiver-operating characteristic (ROC) curve for the prediction of the development of the syndrome was 0.684 for CRP, increasing to 0.706 when combined with BMI and to 0.710 for a complex model of CRP, BMI, and HOMA-IR.CONCLUSIONS -CRP was not a significant predictor of the development of the metabolic syndrome in men. Our data strongly support the notion that inflammation is important in the pathogenesis of diabetes and metabolic disorders in women. Diabetes Care 25:2016 -2021, 2002C -reactive protein (CRP) is an acutephase reactant that is a marker of inflammation in the body. Mild chronic elevations of CRP concentrations, even when within the clinically "normal" range, are independently predictive of future cardiovascular events (1,2). Recent cross-sectional studies show that elevated CRP levels correlate significantly with features of the metabolic syndrome (insulin resistance syndrome), including adiposity, hyperinsulinemia, insulin resistance, hypertriglyceridemia, and low HDL cholesterol (3,4). A recent study has also demonstrated that high levels of CRP are related to increased accumulation of visceral and subcutaneous fat depots measured by computerized tomography scan (5). Two studies have reported that CRP predicts development of diabetes in postmenopausal women (6) and the elderly (7). These studies require confirmation in other populations and extension to other features of the metabolic syndrome.Therefore, we assessed the 6-year development of diabetes and the metabolic syndrome in relation to baseline CRP levels in 515 men and 729 women from the Mexico City Diabetes Study. The metabolic syndrome was defined as subjects developing two or more of the metabolic disorders (dyslipidemia, hypertension, or diabetes) (8). We also compa...

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

“…Our data also show heterogeneity by sex, which is consistent with previous reports [16][17][18]. Whether this represents a fundamental biological process between sexes or more probably is a reflection of a different pattern of confounding between men and women is uncertain.…”

“…Mexico City Diabetes Study [16] central adiposity (p=0.004) and whether or not the analyses were adjusted for baseline glycaemia (p=0.05), as shown in Fig. 2.…”

“…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].…”

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].…”

“…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].…”