Skip to main content
Top
Published in: Acta Diabetologica 6/2016

Open Access 01-12-2016 | Original Article

Acute-phase proteins and incidence of diabetes: a population-based cohort study

Authors: Iram Faqir Muhammad, Yan Borné, Bo Hedblad, Peter M. Nilsson, Margaretha Persson, Gunnar Engström

Published in: Acta Diabetologica | Issue 6/2016

Login to get access

Abstract

Aims

To examine the relationship between plasma levels of the acute-phase proteins ceruloplasmin, alpha-1-antitrypsin, orosomucoid, haptoglobin and C-reactive protein (CRP), and incidence of diabetes in the population-based Malmö Diet and Cancer Study—Cardiovascular Cohort (MDCS-CC).

Methods

The study population consists of 4246 participants (aged 46–67 years, 60.8 % women) with no previous history of diabetes. Participants were followed, and incidence of diabetes was assessed by linkage with national registers and a clinical re-examination of the cohort. Cox proportional hazard regression analysis was used to compare incidence of diabetes in relation to sex-specific quartiles of the acute-phase proteins.

Results

During a mean follow-up period of 15.6 ± 3.4 years, a total of 390 participants were diagnosed with diabetes. Orosomucoid, haptoglobin, and CRP showed a significant increased risk of diabetes after adjustment for potential confounders. However, further adjustments for fasting glucose at baseline resulted in significant association only for CRP. The multivariable-adjusted hazard ratios (HR: 4th vs. 1st quartile) were 1.18 (95 % CI: 0.83–1.67; p = 0.51), 1.19 (CI: 0.85–1.62; p = 0.10), and 1.40 (CI: 1.01–1.95; p = 0.046) for orosomucoid, haptoglobin, and CRP respectively.

Conclusion

The study demonstrated that there are associations between orosomucoid, haptoglobin and CRP and the risk of incidence of diabetes. However, after additional adjustment for fasting glucose levels at baseline, the association stayed significant only for CRP.
Appendix
Available only for authorised users
Literature
3.
go back to reference Fletcher B, Gulanick M, Lamendola C (2002) Risk factors for type 2 diabetes mellitus. J Cardiovasc Nurs 16(2):17–23CrossRefPubMed Fletcher B, Gulanick M, Lamendola C (2002) Risk factors for type 2 diabetes mellitus. J Cardiovasc Nurs 16(2):17–23CrossRefPubMed
4.
go back to reference Pickup JC (2004) Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes. Diabetes Care 27(3):813–823CrossRefPubMed Pickup JC (2004) Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes. Diabetes Care 27(3):813–823CrossRefPubMed
5.
go back to reference Festa A, D’Agostino R Jr, Tracy RP, Haffner SM, Insulin Resistance Atherosclerosis Study (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(4):1131–1137CrossRefPubMed Festa A, D’Agostino R Jr, Tracy RP, Haffner SM, Insulin Resistance Atherosclerosis Study (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(4):1131–1137CrossRefPubMed
6.
go back to reference McMillan DE (1989) Increased levels of acute-phase serum proteins in diabetes. Metabolism 38(11):1042–1046CrossRefPubMed McMillan DE (1989) Increased levels of acute-phase serum proteins in diabetes. Metabolism 38(11):1042–1046CrossRefPubMed
7.
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(3):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(3):327–334CrossRefPubMed
8.
go back to reference Ford ES (2002) Leukocyte count, erythrocyte sedimentation rate, and diabetes incidence in a national sample of US adults. Am J Epidemiol 155(1):57–64CrossRefPubMed Ford ES (2002) Leukocyte count, erythrocyte sedimentation rate, and diabetes incidence in a national sample of US adults. Am J Epidemiol 155(1):57–64CrossRefPubMed
9.
go back to reference Ganrot PO, Gydell K, Ekelund H (1967) Serum concentration of alpha-2-macroglobulin, haptoglobin and alpha-1-antitrypsin in diabetes mellitus. Acta Endocrinol (Copenh) 55(3):537–544 Ganrot PO, Gydell K, Ekelund H (1967) Serum concentration of alpha-2-macroglobulin, haptoglobin and alpha-1-antitrypsin in diabetes mellitus. Acta Endocrinol (Copenh) 55(3):537–544
10.
go back to reference Fiorentino TV, Hribal ML, Perticone M et al (2015) Unfavorable inflammatory profile in adults at risk of type 2 diabetes identified by hemoglobin A1c levels according to the American Diabetes Association criteria. Acta Diabetol 52(2):349–356CrossRefPubMed Fiorentino TV, Hribal ML, Perticone M et al (2015) Unfavorable inflammatory profile in adults at risk of type 2 diabetes identified by hemoglobin A1c levels according to the American Diabetes Association criteria. Acta Diabetol 52(2):349–356CrossRefPubMed
11.
go back to reference Schmidt MI, Duncan BB, Sharrett AR et al (1999) Markers of inflammation and prediction of diabetes mellitus in adults (Atherosclerosis Risk in Communities study): a cohort study. Lancet 353(9165):1649–1652CrossRefPubMed Schmidt MI, Duncan BB, Sharrett AR et al (1999) Markers of inflammation and prediction of diabetes mellitus in adults (Atherosclerosis Risk in Communities study): a cohort study. Lancet 353(9165):1649–1652CrossRefPubMed
12.
go back to reference Engstrom G, Hedblad B, Stavenow L, Lind P, Janzon L, Lindgarde F (2003) Inflammation-sensitive plasma proteins are associated with future weight gain. Diabetes 52(8):2097–2101CrossRefPubMed Engstrom G, Hedblad B, Stavenow L, Lind P, Janzon L, Lindgarde F (2003) Inflammation-sensitive plasma proteins are associated with future weight gain. Diabetes 52(8):2097–2101CrossRefPubMed
13.
go back to reference Engstrom G, Stavenow L, Hedblad B et al (2003) Inflammation-sensitive plasma proteins, diabetes, and mortality and incidence of myocardial infarction and stroke: a population-based study. Diabetes 52(2):442–447CrossRefPubMed Engstrom G, Stavenow L, Hedblad B et al (2003) Inflammation-sensitive plasma proteins, diabetes, and mortality and incidence of myocardial infarction and stroke: a population-based study. Diabetes 52(2):442–447CrossRefPubMed
14.
go back to reference Manjer J, Carlsson S, Elmstahl S et al (2001) The Malmo Diet and Cancer Study: representativity, cancer incidence and mortality in participants and non-participants. Eur J Cancer Prev 10(6):489–499CrossRefPubMed Manjer J, Carlsson S, Elmstahl S et al (2001) The Malmo Diet and Cancer Study: representativity, cancer incidence and mortality in participants and non-participants. Eur J Cancer Prev 10(6):489–499CrossRefPubMed
15.
go back to reference Hedblad B, Nilsson P, Janzon L, Berglund G (2000) Relation between insulin resistance and carotid intima-media thickness and stenosis in non-diabetic subjects. Results from a cross-sectional study in Malmo, Sweden. Diabetes Med 17(4):299–307CrossRef Hedblad B, Nilsson P, Janzon L, Berglund G (2000) Relation between insulin resistance and carotid intima-media thickness and stenosis in non-diabetic subjects. Results from a cross-sectional study in Malmo, Sweden. Diabetes Med 17(4):299–307CrossRef
16.
go back to reference Berglund G, Elmstahl S, Janzon L, Larsson SA, The Malmo Diet and Cancer Study (1993) Design and feasibility. J Intern Med 233(1):45–51CrossRefPubMed Berglund G, Elmstahl S, Janzon L, Larsson SA, The Malmo Diet and Cancer Study (1993) Design and feasibility. J Intern Med 233(1):45–51CrossRefPubMed
17.
go back to reference Li C, Aronsson CA, Hedblad B, Gullberg B, Wirfalt E, Berglund G (2009) Ability of physical activity measurements to assess health-related risks. Eur J Clin Nutr 63(12):1448–1451CrossRefPubMed Li C, Aronsson CA, Hedblad B, Gullberg B, Wirfalt E, Berglund G (2009) Ability of physical activity measurements to assess health-related risks. Eur J Clin Nutr 63(12):1448–1451CrossRefPubMed
18.
go back to reference Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (2003) Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 26(Suppl 1):S5–S20 Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (2003) Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 26(Suppl 1):S5–S20
19.
go back to reference Konsensuswerte der Deutschen Gesellschaft für Laboratoriumsmedizin, der Deutschen Gesellschaft für Klinische Chemie und des Verbandes der Diagnostica-Industrie e.V. (VDGH) (1995) DG Klinische Chemie Mitteilungen 26:119–122 Konsensuswerte der Deutschen Gesellschaft für Laboratoriumsmedizin, der Deutschen Gesellschaft für Klinische Chemie und des Verbandes der Diagnostica-Industrie e.V. (VDGH) (1995) DG Klinische Chemie Mitteilungen 26:119–122
21.
go back to reference Melander O, Maisel AS, Almgren P et al (2012) Plasma proneurotensin and incidence of diabetes, cardiovascular disease, breast cancer, and mortality. JAMA 308(14):1469–1475CrossRefPubMed Melander O, Maisel AS, Almgren P et al (2012) Plasma proneurotensin and incidence of diabetes, cardiovascular disease, breast cancer, and mortality. JAMA 308(14):1469–1475CrossRefPubMed
22.
go back to reference Engstrom G, Hedblad B, Eriksson KF, Janzon L, Lindgarde F (2005) Complement C3 is a risk factor for the development of diabetes: a population-based cohort study. Diabetes 54(2):570–575CrossRefPubMed Engstrom G, Hedblad B, Eriksson KF, Janzon L, Lindgarde F (2005) Complement C3 is a risk factor for the development of diabetes: a population-based cohort study. Diabetes 54(2):570–575CrossRefPubMed
23.
go back to reference Lee CC, Adler AI, Sandhu MS et al (2009) Association of C-reactive protein with type 2 diabetes: prospective analysis and meta-analysis. Diabetologia 52(6):1040–1047CrossRefPubMed Lee CC, Adler AI, Sandhu MS et al (2009) Association of C-reactive protein with type 2 diabetes: prospective analysis and meta-analysis. Diabetologia 52(6):1040–1047CrossRefPubMed
24.
go back to reference Oda E (2015) High-sensitivity C-reactive protein, but not white blood cell count, independently predicted incident diabetes in a Japanese health screening population. Acta Diabetol 52(5):983–990CrossRefPubMed Oda E (2015) High-sensitivity C-reactive protein, but not white blood cell count, independently predicted incident diabetes in a Japanese health screening population. Acta Diabetol 52(5):983–990CrossRefPubMed
25.
go back to reference Bode JG, Albrecht U, Haussinger D, Heinrich PC, Schaper F (2012) Hepatic acute phase proteins—regulation by IL-6- and IL-1-type cytokines involving STAT3 and its crosstalk with NF-kappaB-dependent signaling. Eur J Cell Biol 91(6–7):496–505CrossRefPubMed Bode JG, Albrecht U, Haussinger D, Heinrich PC, Schaper F (2012) Hepatic acute phase proteins—regulation by IL-6- and IL-1-type cytokines involving STAT3 and its crosstalk with NF-kappaB-dependent signaling. Eur J Cell Biol 91(6–7):496–505CrossRefPubMed
26.
27.
go back to reference Dandona P, Aljada A, Bandyopadhyay A (2004) Inflammation: the link between insulin resistance, obesity and diabetes. Trends Immunol 25(1):4–7CrossRefPubMed Dandona P, Aljada A, Bandyopadhyay A (2004) Inflammation: the link between insulin resistance, obesity and diabetes. Trends Immunol 25(1):4–7CrossRefPubMed
28.
go back to reference Hotamisligil GS, Shargill NS, Spiegelman BM (1993) Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259(5091):87–91CrossRefPubMed Hotamisligil GS, Shargill NS, Spiegelman BM (1993) Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259(5091):87–91CrossRefPubMed
29.
go back to reference Hotamisligil GS, Peraldi P, Budavari A, Ellis R, White MF, Spiegelman BM (1996) IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance. Science 271(5249):665–668CrossRefPubMed Hotamisligil GS, Peraldi P, Budavari A, Ellis R, White MF, Spiegelman BM (1996) IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance. Science 271(5249):665–668CrossRefPubMed
30.
go back to reference Dandona P, Weinstock R, Thusu K, Abdel-Rahman E, Aljada A, Wadden T (1998) Tumor necrosis factor-alpha in sera of obese patients: fall with weight loss. J Clin Endocrinol Metab 83(8):2907–2910PubMed Dandona P, Weinstock R, Thusu K, Abdel-Rahman E, Aljada A, Wadden T (1998) Tumor necrosis factor-alpha in sera of obese patients: fall with weight loss. J Clin Endocrinol Metab 83(8):2907–2910PubMed
31.
go back to reference Ghanim H, Abuaysheh S, Sia CL et al (2009) Increase in plasma endotoxin concentrations and the expression of Toll-like receptors and suppressor of cytokine signaling-3 in mononuclear cells after a high-fat, high-carbohydrate meal: implications for insulin resistance. Diabetes Care 32(12):2281–2287CrossRefPubMedPubMedCentral Ghanim H, Abuaysheh S, Sia CL et al (2009) Increase in plasma endotoxin concentrations and the expression of Toll-like receptors and suppressor of cytokine signaling-3 in mononuclear cells after a high-fat, high-carbohydrate meal: implications for insulin resistance. Diabetes Care 32(12):2281–2287CrossRefPubMedPubMedCentral
32.
go back to reference Fogarty CL, Nieminen JK, Peraneva L et al (2015) High-fat meals induce systemic cytokine release without evidence of endotoxemia-mediated cytokine production from circulating monocytes or myeloid dendritic cells. Acta Diabetol 52(2):315–322CrossRefPubMed Fogarty CL, Nieminen JK, Peraneva L et al (2015) High-fat meals induce systemic cytokine release without evidence of endotoxemia-mediated cytokine production from circulating monocytes or myeloid dendritic cells. Acta Diabetol 52(2):315–322CrossRefPubMed
33.
go back to reference Hotamisligil GS (1999) The role of TNFalpha and TNF receptors in obesity and insulin resistance. J Intern Med 245(6):621–625CrossRefPubMed Hotamisligil GS (1999) The role of TNFalpha and TNF receptors in obesity and insulin resistance. J Intern Med 245(6):621–625CrossRefPubMed
34.
go back to reference Yudkin JS, Stehouwer CD, Emeis JJ, Coppack SW (1999) C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? Arterioscler Thromb Vasc Biol 19(4):972–978CrossRefPubMed Yudkin JS, Stehouwer CD, Emeis JJ, Coppack SW (1999) C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? Arterioscler Thromb Vasc Biol 19(4):972–978CrossRefPubMed
35.
go back to reference Brunner EJ, Kivimaki M, Witte DR et al (2008) Inflammation, insulin resistance, and diabetes–Mendelian randomization using CRP haplotypes points upstream. PLoS Med 5(8):e155CrossRefPubMedPubMedCentral Brunner EJ, Kivimaki M, Witte DR et al (2008) Inflammation, insulin resistance, and diabetes–Mendelian randomization using CRP haplotypes points upstream. PLoS Med 5(8):e155CrossRefPubMedPubMedCentral
36.
37.
go back to reference Maahs DM, West NA, Lawrence JM, Mayer-Davis EJ (2010) Epidemiology of type 1 diabetes. Endocrinol Metab Clin N Am 39(3):481–497CrossRef Maahs DM, West NA, Lawrence JM, Mayer-Davis EJ (2010) Epidemiology of type 1 diabetes. Endocrinol Metab Clin N Am 39(3):481–497CrossRef
Metadata
Title
Acute-phase proteins and incidence of diabetes: a population-based cohort study
Authors
Iram Faqir Muhammad
Yan Borné
Bo Hedblad
Peter M. Nilsson
Margaretha Persson
Gunnar Engström
Publication date
01-12-2016
Publisher
Springer Milan
Published in
Acta Diabetologica / Issue 6/2016
Print ISSN: 0940-5429
Electronic ISSN: 1432-5233
DOI
https://doi.org/10.1007/s00592-016-0903-8

Other articles of this Issue 6/2016

Acta Diabetologica 6/2016 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.