Download PDF
Exp Clin Endocrinol Diabetes 2004; 112(7): 378-382
DOI: 10.1055/s-2004-821023
Article

J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Low Grade Inflammation in Juvenile Obesity and Type 1 Diabetes Associated with Early Signs of Atherosclerosis

H. Mangge1 , K. Schauenstein2 , L. Stroedter3 , A. Griesl1 , W. Maerz1 , M. Borkenstein4
  • 1Clinical Institute of Medical and Chemical Laboratory Diagnosis, Medical University of Graz, Austria
  • 2Institute of Pathophysiology, Medical University of Graz, Austria
  • 3Department of Pediatric Surgery, Medical University of Graz, Austria
  • 4Department of Pediatrics, Medical University of Graz, Austria
Further Information

Publication History

Received: March 11, 2003 First decision: June 16, 2003

Accepted: December 8, 2003

Publication Date:
07 July 2004 (online)

Also available at
    Permissions and Reprints

Abstract

Background: Subclinical inflammation has been implicated in the initiation and/or progression of atherosclerosis. Diabetes mellitus and obesity are risk factors for atherosclerosis, and asymptomatic low grade inflammation occurs prior to overt vascular lesions in these patients. In contrast to adults, little information exists concerning low grade inflammation in young type 1 diabetes and juvenile obesity.

Aim: To investigate low grade inflammation and immune activation in juvenile diabetes mellitus and obesity.

Methods: hs-CRP, soluble interleukin-2 receptor (sIL-2R), C-peptide, insulin, cortisol, vitamin B12, folic acid, leptin, and homocysteine were determined in 148 patients with juvenile type 1 diabetes, 86 obese children and 142 normal weighted age-matched healthy controls. Intima-media thickness (IMT) and lumen diameter of both common carotid arteries (CCA) was measured by ultrasonography in 52 healthy pediatric controls, 10 diabetics, and 34 obese juveniles.

Results: Serum hs-CRP was significantly elevated in patients with type 1 diabetes (p < 0.0001), and obese children (p < 0.0001) as compared to the control group. The obese juveniles (p < 0.0001) and the diabetics (p < 0.0001) showed significantly increased values for IMT of CAAs. Levels of homocysteine, sIL-2R, insulin, cortisol, vitamin B12, and folic acid did not differ from the controls. The elevation of hs-CRP was more pronounced in obesity as compared to type 1 diabetes (p < 0.0001), and the hs-CRP values correlated significantly with body mass index standard deviation score (BMI-SDS) values. Furthermore, the IMT and the luminal diameter of CCAs showed significant correlations with BMI-SDS values.

Conclusion: A low grade inflammation as determined by serum hs-CRP is significantly increased in children with type 1 diabetes, and even more pronounced in apparently healthy juveniles with obesity. The increased IMT of CCAs strongly argues for an association between this low grade inflammation and early atherosclerotic vessel injury.

Key words

hs-CRP - juvenile obesity - juvenile type 1 diabetes

References

  • 1 Aso Y, Okumura K, Takebayashi K, Wakabayashi S, Inukai T. Relationships of plasma interleukin-18 concentrations to hyperhomocysteinemia and carotid intimal-media wall thickness in patients with type 2 diabetes.  Diabetes Care. 2003;  26 2622-2627
    PubMedSearch in Google Scholar
  • 2 Bhakdi S, Torzewski M, Klouche M, Hemmes M. Complement and atherogenesis: binding of CRP to degraded, nonoxidized LDL enhances complement activation.  Arterioscler Thromb Vasc Biol. 1999;  19 2348-2354
    PubMedSearch in Google Scholar
  • 3 Blankenberg S, Tiret L, Bickel C, Peetz D, Cambien F, Meyer J, Rupprecht H J. Interleukin-18 is a strong predictor of cardiovascular death in stable and unstable angina.  Circulation. 2002;  106 24-30
    CrossrefPubMedSearch in Google Scholar
  • 4 Danesh J, Whincup P, Walker M, Lennon L, Thomson A, Appleby P, Gallimore J R, Pepys M B. Low grade inflammation and coronary heart disease: prospective study and updated meta-analyses.  BMJ. 2000;  321 199-204
    CrossrefPubMedSearch in Google Scholar
  • 5 de Ferranti S, Rifai N. C-reactive protein and cardiovascular disease: a review of risk prediction and interventions.  Clin Chim Acta. 2002;  317 1-15
    CrossrefPubMedSearch in Google Scholar
  • 6 Dorchy H, Coulon Y, Willems D. Increased levels of ultra sensitive CRP in young type 1 diabetic patients with or without subclinical complications.  (abstract) J Pediatr Endocrinol Metab. 2002;  15 1063
    PubMedSearch in Google Scholar
  • 7 Erbagci A B, Tarakcioglu M, Coskun Y, Sivasli E, Sibel Namiduru E. Mediators of inflammation in children with type I diabetes mellitus: cytokines in type I diabetic children.  Clin Biochem. 2001;  34 645-650
    CrossrefPubMedSearch in Google Scholar
  • 8 Esposito K, Nappo F, Marfella R, Giugliano G, Giugliano F, Ciotola M, Quagliaro L, Ceriello A, Giugliano D. Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress.  Circulation. 2002;  106 2067-2072
    CrossrefPubMedSearch in Google Scholar
  • 9 Ford E S, Galuska D A, Gillespie C, Will J C, Giles W H, Dietz W H. C-reactive protein and body mass index in children: findings from the Third National Health and Nutrition Examination Survey, 1988 - 1994.  J Pediatr. 2001;  138 486-492
    CrossrefPubMedSearch in Google Scholar
  • 10 Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation.  N Engl J Med. 1999;  340 448-454
    CrossrefPubMedSearch in Google Scholar
  • 11 Glowinska B, Urban M, Koput A, Galar M. New atherosclerosis risk factors in obese, hypertensive and diabetic children and adolescents.  Atherosclerosis. 2003;  167 275-286
    CrossrefPubMedSearch in Google Scholar
  • 12 Hayaishi-Okano R, Yamasaki Y, Katakami N, Ohtoshi K, Gorogawa S, Kuroda A, Matsuhisa M, Kosugi K, Nishikawa N, Kajimoto Y, Hori M. Elevated C-reactive protein associates with early-stage carotid atherosclerosis in young subjects with type 1 diabetes.  Diabetes Care. 2002;  8 1432-1438
    PubMedSearch in Google Scholar
  • 13 Kiechl S, Willeit J. The natural course of atherosclerosis.  Arterioscler Thromb Vasc Biol. 1999;  19 1484-1498
    PubMedSearch in Google Scholar
  • 14 Kilpatrick E S, Keevil B G, Jagger C, Spooner R J, Small M. Determinants of raised C-reactive protein concentration in type 1 diabetes.  QJM. 2000;  93 231-236
    CrossrefPubMedSearch in Google Scholar
  • 15 Macy E M, Hayes T E, Tracy R P. Variability in the measurement of C-reactive protein in healthy subjects: implications for reference intervals and epidemiological applications.  Clin Chem. 1997;  43 52-58
    PubMedSearch in Google Scholar
  • 16 Magyar M T, Szikszai Z, Balla J, Valikovics A, Kappelmayer J, Imre S, Balla G, Jeney V, Csiba L, Bereczki D. Early-onset carotid atherosclerosis is associated with increased intima-media thickness and elevated serum levels of inflammatory markers.  Stroke. 2003;  34 58-63
    CrossrefPubMedSearch in Google Scholar
  • 17 Margaglione M, Cappucci G, Colaizzo D, Vecchione G, Grandone E, Di Minno G. C-reactive protein in offspring is associated with the occurrence of myocardial infarction in first-degree relatives.  Arterioscler Thromb Vasc Biol. 2000;  20 198-203
    PubMedSearch in Google Scholar
  • 18 Meier-Ewert H K, Ridker P M, Rifai N, Price N, Dinges D F, Mullington J M. Absence of diurnal variation of C-reactive protein concentrations in healthy human subjects.  Clin Chem. 2001;  47 426-430
    PubMedSearch in Google Scholar
  • 19 Muller S, Martin S, Koenig W, Hanifi-Moghaddam P, Rathmann W, Haastert B, Giani G, Illig T, Thorand B, Kolb H. Impaired glucose tolerance is associated with increased serum concentrations of interleukin 6 and co-regulated acute-phase proteins but not TNF-alpha or its receptors.  Diabetologica. 2002;  45 805-812
    CrossrefPubMedSearch in Google Scholar
  • 20 Ockene I S, Matthews C E, Rifai N, Ridker P M, Reed G, Stanek E. Variability and classification accuracy of serial high-sensitivity C-reactive protein measurements in healthy adults.  Clin Chem. 2001;  47 444-450
    PubMedSearch in Google Scholar
  • 21 Pasceri V, Willerson J T, Yeh E T. Direct proinflammatory effect of C-reactive protein on human endothelial cells.  Circulation. 2000;  102 2165-2168
    CrossrefPubMedSearch in Google Scholar
  • 22 Pickup J C, Chusney G D, Thomas S M, Burt D. Plasma interleukin-6, tumour necrosis factor alpha and blood cytokine production in type 2 diabetes.  Life Sci. 2000;  67 291-300
    CrossrefPubMedSearch in Google Scholar
  • 23 Pieroni L, Bastard J P, Piton A, Khalil L, Hainque B, Jardel C. Interpretation of circulating C-reactive protein levels in adults: body mass index and gender are a must.  Diabetes Metab. 2003;  29 133-138
    PubMedSearch in Google Scholar
  • 24 Pignoli P, Tremoli E, Poli A, Oreste P, Paoletti R. Intimal plus medial thickness of the arterial wall: a direct measurement with ultrasound imaging.  Circulation. 1986;  74 1399-1406
    CrossrefPubMedSearch in Google Scholar
  • 25 Ridker P M, Hennekens C H, Buring J E, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women.  N Engl J Med. 2000;  342 836-843
    CrossrefPubMedSearch in Google Scholar
  • 26 Saito I, Yonemasu K, Inami F. Association of body mass index, body fat, and weight gain with inflammation markers among rural residents in Japan.  Circ J. 2003;  67 323-329
    CrossrefPubMedSearch in Google Scholar
  • 27 Viikari J S, Raitakari O T, Simell O. Nutritional influences on lipids and future atherosclerosis beginning prenatally and during childhood.  Curr Opin Lipidol. 2002;  1 11-18
    PubMedSearch in Google Scholar
  • 28 Visser M, Bouter L M, McQuillan G M, Wener M H, Harris T B. Elevated C-reactive protein levels in overweight and obese adults.  JAMA. 1999;  282 2131-2135
    CrossrefPubMedSearch in Google Scholar
  • 29 Visser M, Bouter L M, McQuillan G M, Wener M H, Harris T B. Low-grade systemic inflammation in overweight children.  Pediatrics. 2001;  107 E13
    CrossrefPubMedSearch in Google Scholar
  • 30 Yu H, Rifai N. High-sensitivity C-reactive protein and atherosclerosis: from theory to therapy.  Clin Biochem. 2000;  33 601-610
    PubMedSearch in Google Scholar

Associate Professor M. D. Harald Mangge

Clinical Institute of Medical and Chemical Laboratory Diagnosis and Pediatric Rheumatology/Immunology
Medical University of Graz

Auenbruggerplatz 36

8036 Graz

Austria

Phone: + 4331638583340

Fax: + 43 31 63 85 26 19

Email: harald.mangge@uni-graz.at