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Published in: Diabetologia 8/2004

01-08-2004 | Article

C-reactive protein and the development of the metabolic syndrome and diabetes in middle-aged men

Authors: D. E. Laaksonen, L. Niskanen, K. Nyyssönen, K. Punnonen, T.-P. Tuomainen, V.-P. Valkonen, R. Salonen, J. T. Salonen

Published in: Diabetologia | Issue 8/2004

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Abstract

Aims/hypothesis

Low-grade inflammation has been implicated in the development of Type 2 diabetes and cardiovascular disease, but its role in the pathogenesis of the metabolic syndrome is unclear. We investigated the association between C-reactive protein (CRP) levels and the development of the metabolic syndrome and diabetes in men.

Methods

Serum CRP concentrations and factors related to insulin resistance were determined in middle-aged Finnish men who participated in a population-based cohort study and were free of diabetes at baseline.

Results

At the 11-year follow-up, 143 of 680 men had developed the metabolic syndrome as defined by the National Cholesterol Education Program (NCEP) and 103 of 598 men had developed the metabolic syndrome as defined by the World Health Organization (WHO). Our analyses excluded men with the metabolic syndrome by the respective definition at baseline. In all, 78 of 762 men developed diabetes over the same period. Men with CRP concentrations ≥3 mg/l had a several-fold higher age-adjusted risk of developing the metabolic syndrome (NCEP definition: odds ratio [OR]=3.2, 95% CI 1.9–5.5; WHO definition: OR=3.4, 95% CI 2.0–6.1) or diabetes (OR=4.1, 95% CI 2.1–8.0) than men whose CRP levels were <1.0 mg/l. Even after further adjustment for potentially confounding lifestyle factors and factors related to insulin resistance, the risk of diabetes (OR=2.3, 95% CI 1.0–5.1) was still increased in men with CRP concentrations ≥3 mg/l, but the association with the metabolic syndrome was no longer significant.

Conclusions/interpretation

Low-grade inflammation may increase the risk of the metabolic syndrome and diabetes in middle-aged men, but some of the risk is mediated through obesity and factors related to insulin resistance.
Literature
1.
go back to reference Yudkin JS, Kumari M, Humphries SE, Mohamed-Ali V (1999) Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link? Atherosclerosis 148:209–214CrossRef Yudkin JS, Kumari M, Humphries SE, Mohamed-Ali V (1999) Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link? Atherosclerosis 148:209–214CrossRef
2.
go back to reference Pradhan AD, Ridker PM (2002) Do atherosclerosis and type 2 diabetes share a common inflammatory basis? Eur Heart J 23:831–834CrossRefPubMed Pradhan AD, Ridker PM (2002) Do atherosclerosis and type 2 diabetes share a common inflammatory basis? Eur Heart J 23:831–834CrossRefPubMed
3.
go back to reference Blake GJ, Ridker PM (2003) C-reactive protein: a surrogate risk marker or mediator of atherothrombosis? Am J Physiol Regul Integr Comp Physiol 285:R1250–R1252PubMed Blake GJ, Ridker PM (2003) C-reactive protein: a surrogate risk marker or mediator of atherothrombosis? Am J Physiol Regul Integr Comp Physiol 285:R1250–R1252PubMed
4.
go back to reference Fernandez-Real JM, Ricart W (2003) Insulin resistance and chronic cardiovascular inflammatory syndrome. Endocr Rev 24:278–301CrossRefPubMed Fernandez-Real JM, Ricart W (2003) Insulin resistance and chronic cardiovascular inflammatory syndrome. Endocr Rev 24:278–301CrossRefPubMed
5.
go back to reference Verma S, Yeh ET (2003) C-reactive protein and atherothrombosis—beyond a biomarker: an actual partaker of lesion formation. Am J Physiol Regul Integr Comp Physiol 285:R1253–R1256PubMed Verma S, Yeh ET (2003) C-reactive protein and atherothrombosis—beyond a biomarker: an actual partaker of lesion formation. Am J Physiol Regul Integr Comp Physiol 285:R1253–R1256PubMed
6.
go back to reference 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 107:499–511CrossRefPubMed 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 107:499–511CrossRefPubMed
7.
go back to reference Laaksonen DE, Niskanen L, Punnonen K et al. (2003) Sex hormones, inflammation and the metabolic syndrome: a population-based study. Eur J Endocrinol 149:601–608PubMed Laaksonen DE, Niskanen L, Punnonen K et al. (2003) Sex hormones, inflammation and the metabolic syndrome: a population-based study. Eur J Endocrinol 149:601–608PubMed
8.
go back to reference Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH (1997) Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 336:973–979CrossRefPubMed Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH (1997) Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 336:973–979CrossRefPubMed
9.
go back to reference Ridker PM, Buring JE, Shih J, Matias M, Hennekens CH (1998) Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women. Circulation 98:731–733PubMed Ridker PM, Buring JE, Shih J, Matias M, Hennekens CH (1998) Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women. Circulation 98:731–733PubMed
10.
go back to reference 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 286:327–334CrossRefPubMed 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 286:327–334CrossRefPubMed
11.
go back to reference Festa A, D’Agostino R Jr, Tracy RP, Haffner SM (2002) Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of type 2 diabetes: the insulin resistance atherosclerosis study. Diabetes 51:1131–1137PubMed Festa A, D’Agostino R Jr, Tracy RP, Haffner SM (2002) Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of type 2 diabetes: the insulin resistance atherosclerosis study. Diabetes 51:1131–1137PubMed
12.
go back to reference Nakanishi S, Yamane K, Kamei N, Okubo M, Kohno N (2003) Elevated C-reactive protein is a risk factor for the development of type 2 diabetes in Japanese Americans. Diabetes Care 26:2754–2757PubMed Nakanishi S, Yamane K, Kamei N, Okubo M, Kohno N (2003) Elevated C-reactive protein is a risk factor for the development of type 2 diabetes in Japanese Americans. Diabetes Care 26:2754–2757PubMed
13.
go back to reference Tan KC, Wat NM, Tam SC, Janus ED, Lam TH, Lam KS (2003) C-reactive protein predicts the deterioration of glycemia in Chinese subjects with impaired glucose tolerance. Diabetes Care 26:2323–2328PubMed Tan KC, Wat NM, Tam SC, Janus ED, Lam TH, Lam KS (2003) C-reactive protein predicts the deterioration of glycemia in Chinese subjects with impaired glucose tolerance. Diabetes Care 26:2323–2328PubMed
14.
go back to reference Thorand B, Lowel H, Schneider A et al. (2003) C-reactive protein as a predictor for incident diabetes mellitus among middle-aged men: results from the MONICA Augsburg cohort study, 1984–1998. Arch Intern Med 163:93–99CrossRefPubMed Thorand B, Lowel H, Schneider A et al. (2003) C-reactive protein as a predictor for incident diabetes mellitus among middle-aged men: results from the MONICA Augsburg cohort study, 1984–1998. Arch Intern Med 163:93–99CrossRefPubMed
15.
go back to reference Senn JJ, Klover PJ, Nowak IA et al. (2003) Suppressor of cytokine signaling-3 (SOCS-3), a potential mediator of interleukin-6-dependent insulin resistance in hepatocytes. J Biol Chem 278:13740–13746CrossRefPubMed Senn JJ, Klover PJ, Nowak IA et al. (2003) Suppressor of cytokine signaling-3 (SOCS-3), a potential mediator of interleukin-6-dependent insulin resistance in hepatocytes. J Biol Chem 278:13740–13746CrossRefPubMed
16.
go back to reference Fernandez-Real J-M, Pugeat M, Grasa M et al. (2002) Serum corticosteroid-binding globulin concentration and insulin resistance syndrome: A population study. J Clin Endocrinol Metab 87:4686–4690CrossRefPubMed Fernandez-Real J-M, Pugeat M, Grasa M et al. (2002) Serum corticosteroid-binding globulin concentration and insulin resistance syndrome: A population study. J Clin Endocrinol Metab 87:4686–4690CrossRefPubMed
17.
go back to reference Rask-Madsen C, Dominguez H, Ihlemann N, Hermann T, Kober L, Torp-Pedersen C (2003) Tumor necrosis factor-alpha inhibits insulin’s stimulating effect on glucose uptake and endothelium-dependent vasodilation in humans. Circulation 108:1815–1821CrossRefPubMed Rask-Madsen C, Dominguez H, Ihlemann N, Hermann T, Kober L, Torp-Pedersen C (2003) Tumor necrosis factor-alpha inhibits insulin’s stimulating effect on glucose uptake and endothelium-dependent vasodilation in humans. Circulation 108:1815–1821CrossRefPubMed
18.
go back to reference Festa A, Hanley AJ, Tracy RP, D’Agostino R Jr, Haffner SM (2003) Inflammation in the prediabetic state is related to increased insulin resistance rather than decreased insulin secretion. Circulation 108:1822–1830CrossRefPubMed Festa A, Hanley AJ, Tracy RP, D’Agostino R Jr, Haffner SM (2003) Inflammation in the prediabetic state is related to increased insulin resistance rather than decreased insulin secretion. Circulation 108:1822–1830CrossRefPubMed
19.
go back to reference Spranger J, Kroke A, Mohlig M et al. (2003) Inflammatory cytokines and the risk to develop type 2 diabetes: results of the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Diabetes 52:812–817PubMed Spranger J, Kroke A, Mohlig M et al. (2003) Inflammatory cytokines and the risk to develop type 2 diabetes: results of the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Diabetes 52:812–817PubMed
20.
go back to reference 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 51:1596–1600PubMed 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 51:1596–1600PubMed
21.
go back to reference National Cholesterol Education Program (2001) Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 285:2486–2497PubMed National Cholesterol Education Program (2001) Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 285:2486–2497PubMed
22.
go back to reference World Health Organization—International Society of Hypertension (1999) 1999 World Health Organization—International Society of Hypertension Guidelines for the Management of Hypertension. Guidelines Subcommittee. J Hypertens 17:151–183CrossRefPubMed World Health Organization—International Society of Hypertension (1999) 1999 World Health Organization—International Society of Hypertension Guidelines for the Management of Hypertension. Guidelines Subcommittee. J Hypertens 17:151–183CrossRefPubMed
23.
go back to reference Laaksonen DE, Lakka HM, Niskanen LK, Kaplan GA, Salonen JT, Lakka TA (2002) Metabolic syndrome and development of diabetes mellitus: application and validation of recently suggested definitions of the metabolic syndrome in a prospective cohort study. Am J Epidemiol 156:1070–1077CrossRefPubMed Laaksonen DE, Lakka HM, Niskanen LK, Kaplan GA, Salonen JT, Lakka TA (2002) Metabolic syndrome and development of diabetes mellitus: application and validation of recently suggested definitions of the metabolic syndrome in a prospective cohort study. Am J Epidemiol 156:1070–1077CrossRefPubMed
24.
go back to reference Lakka HM, Laaksonen DE, Lakka TA et al. (2002) The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 288:2709–2716CrossRefPubMed Lakka HM, Laaksonen DE, Lakka TA et al. (2002) The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 288:2709–2716CrossRefPubMed
25.
go back to reference Han TS, Sattar N, Williams K, Gonzalez-Villalpando C, Lean ME, 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 25:2016–2021PubMed Han TS, Sattar N, Williams K, Gonzalez-Villalpando C, Lean ME, 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 25:2016–2021PubMed
26.
go back to reference Salonen JT (1988) Is there a continuing need for longitudinal epidemiologic research? The Kuopio Ischaemic Heart Disease Risk Factor Study. Ann Clin Res 20:46–50PubMed Salonen JT (1988) Is there a continuing need for longitudinal epidemiologic research? The Kuopio Ischaemic Heart Disease Risk Factor Study. Ann Clin Res 20:46–50PubMed
27.
go back to reference Alberti KG, Zimmet PZ (1998) Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus. Provisional report of a WHO consultation. Diabet Med 15:539–553CrossRefPubMed Alberti KG, Zimmet PZ (1998) Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus. Provisional report of a WHO consultation. Diabet Med 15:539–553CrossRefPubMed
28.
go back to reference Lakka TA, Venäläinen JM, Rauramaa R, Salonen R, Tuomilehto J, Salonen JT (1994) Relation of leisure-time physical activity and cardiorespiratory fitness to the risk of acute myocardial infarction. N Engl J Med 330:1549–1554CrossRefPubMed Lakka TA, Venäläinen JM, Rauramaa R, Salonen R, Tuomilehto J, Salonen JT (1994) Relation of leisure-time physical activity and cardiorespiratory fitness to the risk of acute myocardial infarction. N Engl J Med 330:1549–1554CrossRefPubMed
29.
go back to reference Lynch JW, Kaplan GA, Cohen RD et al. (1994) Childhood and adult socioeconomic status as predictors of mortality in Finland. Lancet 343:524–527CrossRefPubMed Lynch JW, Kaplan GA, Cohen RD et al. (1994) Childhood and adult socioeconomic status as predictors of mortality in Finland. Lancet 343:524–527CrossRefPubMed
30.
go back to reference Laaksonen DE, Lakka HM, Salonen JT, Niskanen LK, Rauramaa R, Lakka TA (2002) Low levels of leisure-time physical activity and cardiorespiratory fitness predict development of the metabolic syndrome. Diabetes Care 25:1612–1618PubMed Laaksonen DE, Lakka HM, Salonen JT, Niskanen LK, Rauramaa R, Lakka TA (2002) Low levels of leisure-time physical activity and cardiorespiratory fitness predict development of the metabolic syndrome. Diabetes Care 25:1612–1618PubMed
31.
go back to reference Duncan BB, Schmidt MI, Chambless LE, Folsom AR, Carpenter M, Heiss G (2000) Fibrinogen, other putative markers of inflammation, and weight gain in middle-aged adults—the ARIC study. Atherosclerosis Risk in Communities. Obes Res 8:279–286PubMed Duncan BB, Schmidt MI, Chambless LE, Folsom AR, Carpenter M, Heiss G (2000) Fibrinogen, other putative markers of inflammation, and weight gain in middle-aged adults—the ARIC study. Atherosclerosis Risk in Communities. Obes Res 8:279–286PubMed
32.
go back to reference Kopp HP, Kopp CW, Festa A et al. (2003) Impact of weight loss on inflammatory proteins and their association with the insulin resistance syndrome in morbidly obese patients. Arterioscler Thromb Vasc Biol 23:1042–1047CrossRefPubMed Kopp HP, Kopp CW, Festa A et al. (2003) Impact of weight loss on inflammatory proteins and their association with the insulin resistance syndrome in morbidly obese patients. Arterioscler Thromb Vasc Biol 23:1042–1047CrossRefPubMed
33.
go back to reference Sesso HD, Buring JE, Rifai N, Blake GJ, Gaziano JM, Ridker PM (2003) C-reactive protein and the risk of developing hypertension. JAMA 290:2945–2951CrossRefPubMed Sesso HD, Buring JE, Rifai N, Blake GJ, Gaziano JM, Ridker PM (2003) C-reactive protein and the risk of developing hypertension. JAMA 290:2945–2951CrossRefPubMed
34.
go back to reference Seppala-Lindroos A, Vehkavaara S, Hakkinen AM et al. (2002) Fat accumulation in the liver is associated with defects in insulin suppression of glucose production and serum free fatty acids independent of obesity in normal men. J Clin Endocrinol Metab 87:3023–3028CrossRefPubMed Seppala-Lindroos A, Vehkavaara S, Hakkinen AM et al. (2002) Fat accumulation in the liver is associated with defects in insulin suppression of glucose production and serum free fatty acids independent of obesity in normal men. J Clin Endocrinol Metab 87:3023–3028CrossRefPubMed
35.
go back to reference Hundal RS, Petersen KF, Mayerson AB et al. (2002) Mechanism by which high-dose aspirin improves glucose metabolism in type 2 diabetes. J Clin Invest 109:1321–1326CrossRefPubMed Hundal RS, Petersen KF, Mayerson AB et al. (2002) Mechanism by which high-dose aspirin improves glucose metabolism in type 2 diabetes. J Clin Invest 109:1321–1326CrossRefPubMed
36.
go back to reference Yuan M, Konstantopoulos N, Lee J et al. (2001) Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta. Science 293:1673–1677CrossRefPubMed Yuan M, Konstantopoulos N, Lee J et al. (2001) Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta. Science 293:1673–1677CrossRefPubMed
37.
go back to reference Plutzky J (2003) The potential role of peroxisome proliferator-activated receptors on inflammation in type 2 diabetes mellitus and atherosclerosis. Am J Cardiol 92:34J–41JCrossRefPubMed Plutzky J (2003) The potential role of peroxisome proliferator-activated receptors on inflammation in type 2 diabetes mellitus and atherosclerosis. Am J Cardiol 92:34J–41JCrossRefPubMed
38.
go back to reference Laaksonen DE, Niskanen L, Lakka H-M, Lakka TA, Uusitupa M (2004) Epidemiology and treatment of the metabolic syndrome. Ann Med (in press) Laaksonen DE, Niskanen L, Lakka H-M, Lakka TA, Uusitupa M (2004) Epidemiology and treatment of the metabolic syndrome. Ann Med (in press)
39.
go back to reference Tuomilehto J, Lindström J, Eriksson JG et al. (2001) Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 344:1343–1350CrossRefPubMed Tuomilehto J, Lindström J, Eriksson JG et al. (2001) Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 344:1343–1350CrossRefPubMed
40.
go back to reference Knowler WC, Barrett-Connor E, Fowler SE et al. (2002) Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 346:393–403CrossRefPubMed Knowler WC, Barrett-Connor E, Fowler SE et al. (2002) Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 346:393–403CrossRefPubMed
41.
go back to reference Pischon T, Hankinson SE, Hotamisligil GS, Rifai N, Willett WC, Rimm EB (2003) Habitual dietary intake of n-3 and n-6 fatty acids in relation to inflammatory markers among US men and women. Circulation 108:155–160CrossRefPubMed Pischon T, Hankinson SE, Hotamisligil GS, Rifai N, Willett WC, Rimm EB (2003) Habitual dietary intake of n-3 and n-6 fatty acids in relation to inflammatory markers among US men and women. Circulation 108:155–160CrossRefPubMed
42.
go back to reference Esposito K, Pontillo A, Di Palo C et al. (2003) Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. JAMA 289:1799–1804CrossRefPubMed Esposito K, Pontillo A, Di Palo C et al. (2003) Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. JAMA 289:1799–1804CrossRefPubMed
43.
go back to reference Liu S, Manson JE, Buring JE, Stampfer MJ, Willett WC, Ridker PM (2002) Relation between a diet with a high glycemic load and plasma concentrations of high-sensitivity C-reactive protein in middle-aged women. Am J Clin Nutr 75:492–498PubMed Liu S, Manson JE, Buring JE, Stampfer MJ, Willett WC, Ridker PM (2002) Relation between a diet with a high glycemic load and plasma concentrations of high-sensitivity C-reactive protein in middle-aged women. Am J Clin Nutr 75:492–498PubMed
44.
go back to reference Lakka TA, Laaksonen DE, Lakka H-M et al. (2003) Sedentary lifestyle, poor cardiorespiratory fitness and the metabolic syndrome. Med Sci Sports Exerc 35:1279–1286PubMed Lakka TA, Laaksonen DE, Lakka H-M et al. (2003) Sedentary lifestyle, poor cardiorespiratory fitness and the metabolic syndrome. Med Sci Sports Exerc 35:1279–1286PubMed
45.
go back to reference Church TS, Barlow CE, Earnest CP, Kampert JB, Priest EL, Blair SN (2002) Associations between cardiorespiratory fitness and C-reactive protein in men. Arterioscler Thromb Vasc Biol 22:1869–1876CrossRefPubMed Church TS, Barlow CE, Earnest CP, Kampert JB, Priest EL, Blair SN (2002) Associations between cardiorespiratory fitness and C-reactive protein in men. Arterioscler Thromb Vasc Biol 22:1869–1876CrossRefPubMed
46.
go back to reference Crook MA, Scott DA, Stapleton JA, Palmer RM, Wilson RF, Sutherland G (2000) Circulating concentrations of C-reactive protein and total sialic acid in tobacco smokers remain unchanged following one year of validated smoking cessation. Eur J Clin Invest 30:861–865CrossRefPubMed Crook MA, Scott DA, Stapleton JA, Palmer RM, Wilson RF, Sutherland G (2000) Circulating concentrations of C-reactive protein and total sialic acid in tobacco smokers remain unchanged following one year of validated smoking cessation. Eur J Clin Invest 30:861–865CrossRefPubMed
Metadata
Title
C-reactive protein and the development of the metabolic syndrome and diabetes in middle-aged men
Authors
D. E. Laaksonen
L. Niskanen
K. Nyyssönen
K. Punnonen
T.-P. Tuomainen
V.-P. Valkonen
R. Salonen
J. T. Salonen
Publication date
01-08-2004
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 8/2004
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-004-1472-x

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