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Erschienen in: Diabetologia 6/2009

01.06.2009 | Article

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

verfasst von: C. C. Lee, A. I. Adler, M. S. Sandhu, S. J. Sharp, N. G. Forouhi, S. Erqou, R. Luben, S. Bingham, K. T. Khaw, N. J. Wareham

Erschienen in: Diabetologia | Ausgabe 6/2009

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Abstract

Aims/hypothesis

We examined the association between serum C-reactive protein (CRP) and incident diabetes in a prospective study, and added these data to a literature-based meta-analysis to explore potential sources of heterogeneity between studies.

Methods

We analysed a case–control study nested within the European Prospective Investigation of Cancer (EPIC)-Norfolk cohort, including 293 incident diabetes cases and 708 controls. We combined 16 published studies on CRP and incident diabetes in a random-effect meta-analysis.

Results

In the EPIC-Norfolk cohort, serum CRP was associated with a higher risk of diabetes after adjusting for age, sex, BMI, family history of diabetes, smoking and physical activity (OR 1.49, comparing the extreme thirds of CRP distribution [95% CI 1.03–2.15], p = 0.03). However, the association was completely attenuated after further adjustment for WHR, serum γ-glutamyltransferase and serum adiponectin (OR 1.00; 95% CI 0.66–1.51, p = 1.0). In a meta-analysis of 16 published studies with 3,920 incident diabetes cases and 24,914 controls, the RR was 1.72 (95% CI 1.54–1.92), comparing the extreme thirds of CRP distribution, with substantial heterogeneity between studies (I 2 = 52.8%, p = 0.007).

Conclusions/interpretation

Initial evidence of association between CRP and incident diabetes was confounded by central adiposity, markers of liver dysfunction and adiponectin in the primary analysis. Despite an overall positive association in the meta-analysis, considerable heterogeneity existed between studies. The degree of adjustment for central adiposity and baseline glycaemia explained some of this heterogeneity and suggests that CRP may not be an independent risk factor for type 2 diabetes.
Literatur
1.
Zurück zum Zitat Pickup JC, Crook MA (1998) Is type II diabetes mellitus a disease of the innate immune system? Diabetologia 41:1241–1248PubMedCrossRef Pickup JC, Crook MA (1998) Is type II diabetes mellitus a disease of the innate immune system? Diabetologia 41:1241–1248PubMedCrossRef
2.
Zurück zum Zitat Pearson TA, Mensah GA, Alexander RW et al (2003) Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 107:499–511PubMedCrossRef Pearson TA, Mensah GA, Alexander RW et al (2003) Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 107:499–511PubMedCrossRef
3.
Zurück zum Zitat Dehghan A, Kardys I, de Matt MPM et al (2007) Genetic variation, C-reactive protein levels, and incidence of diabetes. Diabetes 56:872–878PubMedCrossRef Dehghan A, Kardys I, de Matt MPM et al (2007) Genetic variation, C-reactive protein levels, and incidence of diabetes. Diabetes 56:872–878PubMedCrossRef
4.
Zurück zum Zitat Doi Y, Kiyohara Y, Kubo M et al (2005) Elevated C-reactive protein is a predictor of the development of diabetes in a general Japanese population. Diabetes Care 28:2497–2500PubMedCrossRef Doi Y, Kiyohara Y, Kubo M et al (2005) Elevated C-reactive protein is a predictor of the development of diabetes in a general Japanese population. Diabetes Care 28:2497–2500PubMedCrossRef
5.
Zurück zum Zitat Laaksonen DE, Niskanen L, Nyyssonen K et al (2004) C-reactive protein and the development of the metabolic syndrome and diabetes in middle-aged men. Diabetologia 47:1403–1410PubMedCrossRef Laaksonen DE, Niskanen L, Nyyssonen K et al (2004) C-reactive protein and the development of the metabolic syndrome and diabetes in middle-aged men. Diabetologia 47:1403–1410PubMedCrossRef
6.
Zurück zum Zitat Hu FB, Meigs JB, Li TY, Rifai N, Manson JE (2004) Inflammatory markers and risk of developing type 2 diabetes in women. Diabetes 53:693–700PubMedCrossRef Hu FB, Meigs JB, Li TY, Rifai N, Manson JE (2004) Inflammatory markers and risk of developing type 2 diabetes in women. Diabetes 53:693–700PubMedCrossRef
7.
Zurück zum Zitat Nakanishi S, Yamane K, Kamei N, Okubo M, Kohno N (2003) Elevated C-reactive protein is risk factor for the development of type 2 diabetes in Japanese American. Diabetes Care 26:2754–2757PubMedCrossRef Nakanishi S, Yamane K, Kamei N, Okubo M, Kohno N (2003) Elevated C-reactive protein is risk factor for the development of type 2 diabetes in Japanese American. Diabetes Care 26:2754–2757PubMedCrossRef
8.
Zurück zum Zitat Spranger J, Kroke A, Mohlig M et al (2003) Inflammatory cytokines and the risk to develop type 2 diabetes. Diabetes 52:812–817PubMedCrossRef Spranger J, Kroke A, Mohlig M et al (2003) Inflammatory cytokines and the risk to develop type 2 diabetes. Diabetes 52:812–817PubMedCrossRef
9.
Zurück zum Zitat Freeman DJ, Norrie J, Caslake MJ et al (2002) C-reactive protein is an independent predictor of risk for the development of diabetes in the West of Scotland Coronary Prevention Study. Diabetes 51:1596–1600PubMedCrossRef Freeman DJ, Norrie J, Caslake MJ et al (2002) C-reactive protein is an independent predictor of risk for the development of diabetes in the West of Scotland Coronary Prevention Study. Diabetes 51:1596–1600PubMedCrossRef
10.
Zurück zum Zitat Barzilay JI, Abraham L, Heckbert SR et al (2001) The relation of markers of inflammation to the development of glucose disorders in the elderly. The Cardiovascular Health Study. Diabetes 50:2384–2389PubMedCrossRef Barzilay JI, Abraham L, Heckbert SR et al (2001) The relation of markers of inflammation to the development of glucose disorders in the elderly. The Cardiovascular Health Study. Diabetes 50:2384–2389PubMedCrossRef
11.
Zurück zum Zitat Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM (2001) C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 286:327–334PubMedCrossRef Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM (2001) C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 286:327–334PubMedCrossRef
12.
Zurück zum Zitat Thorand B, Lowel H, Schneider A et al (2003) C-reactive protein as a predictor for incident diabetes mellitus among middle-aged men. Arch Intern Med 163:93–99PubMedCrossRef Thorand B, Lowel H, Schneider A et al (2003) C-reactive protein as a predictor for incident diabetes mellitus among middle-aged men. Arch Intern Med 163:93–99PubMedCrossRef
13.
Zurück zum Zitat Duncan BB, Schmidt MI, Pankow JS et al (2003) Low-grade systemic inflammation and the development of type 2 diabetes. The Atherosclerosis Risk in Communities Study. Diabetes 52:1799–1805PubMedCrossRef Duncan BB, Schmidt MI, Pankow JS et al (2003) Low-grade systemic inflammation and the development of type 2 diabetes. The Atherosclerosis Risk in Communities Study. Diabetes 52:1799–1805PubMedCrossRef
14.
Zurück zum Zitat Festa A, D’Agostino R, Tracy RP, Haffner SM (2002) Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of type 2 diabetes. Diabetes 51:1131–1137PubMedCrossRef Festa A, D’Agostino R, Tracy RP, Haffner SM (2002) Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of type 2 diabetes. Diabetes 51:1131–1137PubMedCrossRef
15.
Zurück zum Zitat Krakoff J, Funahashi T, Stehouwer CDA et al (2003) Inflammatory markers, adiponectin and risk of type 2 diabetes in the Pima Indian. Diabetes Care 26:1745–1751PubMedCrossRef Krakoff J, Funahashi T, Stehouwer CDA et al (2003) Inflammatory markers, adiponectin and risk of type 2 diabetes in the Pima Indian. Diabetes Care 26:1745–1751PubMedCrossRef
16.
Zurück zum Zitat Han TS, Sattar N, Williams K, Gonzalez-Villalpando C, Lean MEJ, Haffner SM (2002) Prospective study of C-reactive protein in relation to the development of diabetes and metabolic syndrome in the Mexico City Diabetes Study. Diabetes Care 25:2016–2021PubMedCrossRef Han TS, Sattar N, Williams K, Gonzalez-Villalpando C, Lean MEJ, Haffner SM (2002) Prospective study of C-reactive protein in relation to the development of diabetes and metabolic syndrome in the Mexico City Diabetes Study. Diabetes Care 25:2016–2021PubMedCrossRef
17.
Zurück zum Zitat Snijder M, Dekker JM, Visser M et al (2003) Prospective relation of C-reactive protein with type 2 diabetes. Diabetes Care 26:1656–1657PubMedCrossRef Snijder M, Dekker JM, Visser M et al (2003) Prospective relation of C-reactive protein with type 2 diabetes. Diabetes Care 26:1656–1657PubMedCrossRef
18.
Zurück zum Zitat Thorand B, Baumert J, Kolb H et al (2007) Sex differences in the prediction of type 2 diabetes by inflammatory markers. Result from the MONICA/KORA Augsburg case–cohort study, 1984–2002. Diabetes Care 30:854–860PubMedCrossRef Thorand B, Baumert J, Kolb H et al (2007) Sex differences in the prediction of type 2 diabetes by inflammatory markers. Result from the MONICA/KORA Augsburg case–cohort study, 1984–2002. Diabetes Care 30:854–860PubMedCrossRef
19.
Zurück zum Zitat Lindsay RS, Funahashi T, Hanson RL et al (2002) Adiponectin and development of type 2 diabetes in the Pima Indian population. Lancet 360:57–58PubMedCrossRef Lindsay RS, Funahashi T, Hanson RL et al (2002) Adiponectin and development of type 2 diabetes in the Pima Indian population. Lancet 360:57–58PubMedCrossRef
20.
Zurück zum Zitat Spranger J, Kroke A, Mohlig M et al (2003) Adiponectin and protection against type 2 diabetes mellitus. Lancet 361:226–228PubMedCrossRef Spranger J, Kroke A, Mohlig M et al (2003) Adiponectin and protection against type 2 diabetes mellitus. Lancet 361:226–228PubMedCrossRef
21.
Zurück zum Zitat Duncan BB, Schmidt MI, Pankow JS et al (2004) Adiponectin and the development of type 2 diabetes. Diabetes 53:2473–2478PubMedCrossRef Duncan BB, Schmidt MI, Pankow JS et al (2004) Adiponectin and the development of type 2 diabetes. Diabetes 53:2473–2478PubMedCrossRef
22.
Zurück zum Zitat Lee DH, Silventoinen K, Jacobs DR Jr, Jousilahti P, Tuomileto J (2004) Gamma-glutamyltransferase, obesity, and the risk of type 2 diabetes: observational cohort study among 20,158 middle-aged men and women. J Clin Endocrinol Metab 89:5410–5414PubMedCrossRef Lee DH, Silventoinen K, Jacobs DR Jr, Jousilahti P, Tuomileto J (2004) Gamma-glutamyltransferase, obesity, and the risk of type 2 diabetes: observational cohort study among 20,158 middle-aged men and women. J Clin Endocrinol Metab 89:5410–5414PubMedCrossRef
23.
Zurück zum Zitat Nannipieri M, Gonzales C, Baldi S et al (2005) Liver enzymes, the metabolic syndrome and incident diabetes: the Mexico City Diabetes Study. Diabetes Care 28:1757–1762PubMedCrossRef Nannipieri M, Gonzales C, Baldi S et al (2005) Liver enzymes, the metabolic syndrome and incident diabetes: the Mexico City Diabetes Study. Diabetes Care 28:1757–1762PubMedCrossRef
24.
Zurück zum Zitat Andre P, Balkau B, Born C, Charles MA, Eschwege E (2006) Three-year increase of gamma-glutamyltransferase level and development of type 2 diabetes in middle-aged men and women: the DESIR cohort. Diabetologia 49:2599–2603PubMedCrossRef Andre P, Balkau B, Born C, Charles MA, Eschwege E (2006) Three-year increase of gamma-glutamyltransferase level and development of type 2 diabetes in middle-aged men and women: the DESIR cohort. Diabetologia 49:2599–2603PubMedCrossRef
25.
Zurück zum Zitat Schulze MB, Rimm EB, Shai I, Rifai N, Hu FB (2004) Relationship between adiponectin and glycemic control, blood lipids, and inflammatory markers in men with type 2 diabetes. Diabetes Care 27:1680–1687PubMedCrossRef Schulze MB, Rimm EB, Shai I, Rifai N, Hu FB (2004) Relationship between adiponectin and glycemic control, blood lipids, and inflammatory markers in men with type 2 diabetes. Diabetes Care 27:1680–1687PubMedCrossRef
26.
Zurück zum Zitat Lee DH, Jacobs DR Jr (2005) Association between serum gamma-glutamyltransferase and C-reactive protein. Atherosclerosis 178:327–330PubMedCrossRef Lee DH, Jacobs DR Jr (2005) Association between serum gamma-glutamyltransferase and C-reactive protein. Atherosclerosis 178:327–330PubMedCrossRef
27.
Zurück zum Zitat Day N, Oakes S, Luben R et al (1999) EPIC-Norfolk: study design, characteristics of the cohort. European Prospective Investigation of Cancer. Br J Cancer 80(Suppl 1):95–103PubMed Day N, Oakes S, Luben R et al (1999) EPIC-Norfolk: study design, characteristics of the cohort. European Prospective Investigation of Cancer. Br J Cancer 80(Suppl 1):95–103PubMed
28.
Zurück zum Zitat Harding AH, Day NE, Khaw KT et al (2004) Dietary fat and the risk of clinical type 2 diabetes: the European Prospective of Cancer—Norfolk Study. Am J Epidemiol 159:73–82PubMedCrossRef Harding AH, Day NE, Khaw KT et al (2004) Dietary fat and the risk of clinical type 2 diabetes: the European Prospective of Cancer—Norfolk Study. Am J Epidemiol 159:73–82PubMedCrossRef
29.
Zurück zum Zitat Forouhi NG, Harding AH, Allison M et al (2007) Elevated serum ferritin levels predict new-onset type 2 diabetes: results from the EPIC-Norfolk prospective study. Diabetologia 50:949–956PubMedCrossRef Forouhi NG, Harding AH, Allison M et al (2007) Elevated serum ferritin levels predict new-onset type 2 diabetes: results from the EPIC-Norfolk prospective study. Diabetologia 50:949–956PubMedCrossRef
30.
Zurück zum Zitat Danesh J, Collins R, Appleby P, Peto R (1998) Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analysis of prospective studies. JAMA 279:1477–1482PubMedCrossRef Danesh J, Collins R, Appleby P, Peto R (1998) Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analysis of prospective studies. JAMA 279:1477–1482PubMedCrossRef
31.
Zurück zum Zitat Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analysis. BMJ 327:557–560PubMedCrossRef Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analysis. BMJ 327:557–560PubMedCrossRef
32.
Zurück zum Zitat Yoneda M, Mawatari H, Fujita K et al (2007) High-sensitivity C-reactive protein is an independent clinical feature of nonalcoholic steatohepatitis (NASH) and also of the severity of fibrosis in NASH. J Gastroenterol 42:573–582PubMedCrossRef Yoneda M, Mawatari H, Fujita K et al (2007) High-sensitivity C-reactive protein is an independent clinical feature of nonalcoholic steatohepatitis (NASH) and also of the severity of fibrosis in NASH. J Gastroenterol 42:573–582PubMedCrossRef
33.
Zurück zum Zitat Rantala AO, Lilja M, Kauma H, Savolainen MJ, Reunanen A, Kesaniemi YA (2000) Gamma-glutamyl transpeptidase and the metabolic syndrome. J Intern Med 248:230–238PubMedCrossRef Rantala AO, Lilja M, Kauma H, Savolainen MJ, Reunanen A, Kesaniemi YA (2000) Gamma-glutamyl transpeptidase and the metabolic syndrome. J Intern Med 248:230–238PubMedCrossRef
34.
Zurück zum Zitat Kang YH, Min HK, Son SM, Kim IJ, Kim YK (2007) The association of serum gamma glutamyltransferase with components of the metabolic syndrome in the Korean adults. Diabetes Res Clin Pract 77:306–313PubMedCrossRef Kang YH, Min HK, Son SM, Kim IJ, Kim YK (2007) The association of serum gamma glutamyltransferase with components of the metabolic syndrome in the Korean adults. Diabetes Res Clin Pract 77:306–313PubMedCrossRef
35.
Zurück zum Zitat Sakugawa H, Nakayoshi T, Kobashigawa K et al (2004) Metabolic syndrome is directly associated with gamma glutamyl transpeptidase elevation in Japanese women. World J Gastroenterol 10:1052–1055PubMed Sakugawa H, Nakayoshi T, Kobashigawa K et al (2004) Metabolic syndrome is directly associated with gamma glutamyl transpeptidase elevation in Japanese women. World J Gastroenterol 10:1052–1055PubMed
36.
Zurück zum Zitat Yuan G, Chen X, Ma Q et al (2007) C-reactive protein inhibits adiponectin gene expression and secretion in 3T3-L1 adipocytes. J Endocrinol 194:275–281PubMedCrossRef Yuan G, Chen X, Ma Q et al (2007) C-reactive protein inhibits adiponectin gene expression and secretion in 3T3-L1 adipocytes. J Endocrinol 194:275–281PubMedCrossRef
37.
Zurück zum Zitat Hamdy O, Porramatikul S, Al-Ozairi E (2006) Metabolic obesity: the paradox between visceral and subcutaneous fat. Curr Diabetes Rev 2:367–373PubMed Hamdy O, Porramatikul S, Al-Ozairi E (2006) Metabolic obesity: the paradox between visceral and subcutaneous fat. Curr Diabetes Rev 2:367–373PubMed
38.
Zurück zum Zitat Greenfield JR, Samaras K, Jenkins AB et al (2004) Obesity is an important determinant of baseline serum C-reactive protein concentration in monozygotic twins, independent of genetic influences. Circulation 109:3022–3028PubMedCrossRef Greenfield JR, Samaras K, Jenkins AB et al (2004) Obesity is an important determinant of baseline serum C-reactive protein concentration in monozygotic twins, independent of genetic influences. Circulation 109:3022–3028PubMedCrossRef
39.
Zurück zum Zitat Manning PJ, Sutherland WH, Allum AR, de Jong SA, Jones SD (2002) Effect of hormone replacement therapy on inflammation-sensitive proteins in post-menopausal women with type 2 diabetes. Diabet Med 19:847–852PubMedCrossRef Manning PJ, Sutherland WH, Allum AR, de Jong SA, Jones SD (2002) Effect of hormone replacement therapy on inflammation-sensitive proteins in post-menopausal women with type 2 diabetes. Diabet Med 19:847–852PubMedCrossRef
40.
Zurück zum Zitat Meier-Ewert HK, Ridker PM, Rifai N et al (2001) Absence of diurnal variation of C-reactive protein concentrations in healthy human subjects. Clin Chem 47:426–430PubMed Meier-Ewert HK, Ridker PM, Rifai N et al (2001) Absence of diurnal variation of C-reactive protein concentrations in healthy human subjects. Clin Chem 47:426–430PubMed
41.
Zurück zum Zitat Danesh J, Wheeler JG, Hirschfield GM et al (2004) C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. N Engl J Med 350:1387–1397PubMedCrossRef Danesh J, Wheeler JG, Hirschfield GM et al (2004) C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. N Engl J Med 350:1387–1397PubMedCrossRef
Metadaten
Titel
Association of C-reactive protein with type 2 diabetes: prospective analysis and meta-analysis
verfasst von
C. C. Lee
A. I. Adler
M. S. Sandhu
S. J. Sharp
N. G. Forouhi
S. Erqou
R. Luben
S. Bingham
K. T. Khaw
N. J. Wareham
Publikationsdatum
01.06.2009
Verlag
Springer-Verlag
Erschienen in
Diabetologia / Ausgabe 6/2009
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-009-1338-3

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