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P a t h o p h y s i o l o g y / C o m p l i c a t i o n s
Early Signs of Cardiovascular Disease in
Youth With Obesity and Type 2 Diabetes

equivalent, Kruskal-Wallis. Bivariate rela- IM SUTTON-TYRRELL, PHD
tionships were examined with Spear-man’s correlation analysis because IMTand aPWV were not normally distributed.
Data are presented as means Ϯ SE. Statis- Atherosclerotic cardiovascular dis- byTannercriteria(10)(Table1).Type2 ticalsignificancewassetatPՅ0.05.As
formin with insulin (5), insulin alone (1), be used to establish risk of CVD, the val- atherosclerosis is early in childhood with progression toward clinically significant tion to lifestyle modification. None of the subjects had a family history of hereditary cluded from statistical analysis (14). Data from type 2 diabetic patients taking insu- lin (n ϭ 6) were excluded from fasting (aPWV), a measure of arterial stiffness, are tiple linear regression was used to evalu- erosclerosis that have been used as surro- gate measures of cardiovascular events in various adult studies (4 –9). Data regard- ing IMT and arterial stiffness in children for glucose, insulin, C-peptide, adiponec- are limited despite the increasing tide of tin, lipid profile, high-sensitivity C-reac- RESULTS — Clinical, biochemical, and
obesity and type 2 diabetes. Therefore, in this pilot study, we aimed 1) to evaluate was not different among the three groups.
type 2 diabetes and 2) to investigate the ponectin level were used as surrogate es- timates of insulin sensitivity (11–12).
was highest in the type 2 diabetic subjects RESEARCH DESIGN AND
jects (496.9 Ϯ 15.2) (Table 1). In the total METHODS — We studied 20 adoles-
group, after controlling for systolic blood pressure (because increased arterial stiff- ness is directly related to pulsatile blood cantly with BMI (r ϭ 0.50), fasting insulin (r ϭ 0.46), fasting glucose (r ϭ 0.38), age, sex, ethnicity, and puberty assessed HOMA-IS (r ϭ Ϫ0.52), HbA1c (r ϭ0.28), triglycerides (r ϭ 0.27), and hs- ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● CRP (r ϭ 0.47) (P Ͻ 0.001– 0.042). A From the 1Division of Pediatric Endocrinology Metabolism and Diabetes Mellitus, Children’s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; the 2Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania; and the3 Division of Biostatistics, Department of Family Medicine and Clinical Epidemiology, University of Pitts- burgh, School of Medicine, Pittsburgh, Pennsylvania.
Address correspondence and reprint requests to Silva Arslanian, MD, Division of Endocrinology, Chil- revealed total R2 ϭ 0.357 (P ϭ 0.002), dren’s Hospital of Pittsburgh, 3705 Fifth Avenue at DeSoto Street, Pittsburgh, PA 15213. E-mail: HOMA-IS (R2 ϭ 0.272, P ϭ 0.011) and Received for publication 12 November 2004 and accepted in revised form 19 January 2005.
HbA1c (⌬R2 ϭ 0.085, P ϭ 0.066).
Abbreviations: aPWV, aortic pulse wave velocity; CVD, cardiovascular disease; hs-CRP, high-sensitivity
C-reactive protein; IMT, intima media thickness; HOMA-IS, homeostasis model assessment of insulin sen-sitivity.
CONCLUSIONS — In the present
A table elsewhere in this issue shows conventional and Syste`me International (SI) units and conversion 2005 by the American Diabetes Association.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. DIABETES CARE, VOLUME 28, NUMBER 5, MAY 2005 Atherosclerosis in youth
Table 1—Clinical and biochemical characteristics of study subjects
Data are means Ϯ SE. Significant post-hoc comparisons with Bonferroni adjustment, P Ͻ 0.025. *Normal weight vs. obese; †obese vs. type 2 diabetic; ‡type 2diabetic vs. normal weight.
mal-weight control subjects (P ϭ 0.006) abetic youth in our study (after adjusting suggests that obesity alone is associated obese adults in a previous study (13) and Acknowledgements — This work was sup-
ϳ40-year-old men in the Baltimore Lon- nonobese adults (13) and in obese French ported by U.S. Public Health Service Grantsgitudinal Study of Aging (6), suggestive of RO1 HD27503 (to S.A.) and K24 HD01357(to S.A.), The Pittsburgh Foundation Grant increased risk for premature aging of car- (to N.G.), Children’s Hospital of Pittsburgh diabetes. These findings may reflect early RR00084, to S.A. and N.G.), The University of Pittsburgh Obesity Nutrition Research Center (DK046204 from the National Institute of Di- tectable structural changes. With increas- abetes and Digestive and Kidney Diseases, to functional changes may progress to struc- (to N.G.), and the Renziehausen Trust Fund tural changes if left without intervention.
diabetic compared with obese subjects.
This proposal is consistent with a study in American Diabetes Association 64th Scientific Sessions, 4 – 8 June 2004 in Orlando, Florida.
endothelial activation (21). Our findings of low adiponectin level in the obese and type 2 diabetic subjects with evidence of References
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creased vascular stiffness, renders further Heart Study. Am J Cardiol 90 (10C):3L– 4. Pignoli P, Tremoli E, Poli A, Oreste P, Pa- DIABETES CARE, VOLUME 28, NUMBER 5, MAY 2005 Gungor and Associates
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tion: Markers of inflammation and cardio- O’Rourke MF, Safar M, Eds. Paris, Else- vascular disease: application to clinical 20. Montagnani M, Quon MJ: Insulin action and public health practice: a statement for 8. Kuller L, Borhani N, Furberg C, Gardin J, healthcare professionals from the Centers anisms linking insulin resistance with hy- Manolio T, O’Leary D, Psaty B, Robbins J: pertension. Diabetes Obes Metab 2:285– Prevalence of subclinical atherosclerosis the American Heart Association. Circula- tion with risk factors in the Cardiovascu- 15. O’Rourke M: Arterial stiffness, systolic lar Health Study. Am J Epidemiol 139: arterial hypertension. Hypertension 15: endothelium-dependent vasodilation. J and application of arterial stiffness in clin- 16. Taniwaki H, Kawagishi T, Emoto M, Shoji Clin Endocrinol Metab 89:765–769, 2004 ical research: focus on new methodologies and diabetes mellitus. Med Sci Monit 9: media thickness of the carotid artery and in cardiovascular disease. Am J Med 115: 10. Tanner JM: Growth and maturation dur- aortic pulse-wave velocity in patients with ing adolescence. Nutr Rev 39:43–55, 1981 type 2 diabetes: vessel wall properties in 23. Kavey RE, Daniels SR, Lauer RM, Atkins 11. Gungor N, Saad R, Janosky J, Arslanian S: type 2 diabetes. Diabetes Care 22:1851– Validation of surrogate estimates of insu- ciation guidelines for primary prevention children and adolescents. J Pediatr 144: of atherosclerotic cardiovascular disease beginning in childhood. J Pediatr 142: 12. Bacha F, Saad R, Gungor N, Arslanian S: sclerosis in youth: Pathobiological Deter- DIABETES CARE, VOLUME 28, NUMBER 5, MAY 2005


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