Early Signs of Atherosclerosis Are Associated with Insulin Resistance in Non-obese Adolescent and Young Adults with Type 1 Diabetes

Overview

Journal Cardiovasc Diabetol

Publisher Biomed Central

Specialties Cardiology & Vascular Diseases
Endocrinology

Date 2012 Nov 29

PMID 23185996

Citations 20

Authors

Bjorn Rathsman

Stefan Rosfors

Ake Sjoholm

Thomas Nystrom

Affiliations

Soon will be listed here.

Abstract

Background: Patients with type 1 diabetes have a substantial risk of developing cardiovascular complications early in life. We aimed to explore the role of insulin sensitivity (Si) as an early factor of atherosclerosis in young type 1 diabetes vs. non-diabetic subjects.

Methods: Forty adolescent and young adult individuals (20 type 1 diabetics and 20 non-diabetics), age 14-20 years, without characteristics of the metabolic syndrome, participated in this cross-sectional study. After an overnight fast, Si was measured by hyperinsulinemic euglycemic clamp (40 mU/m2) and calculated by glucose infusion rate (GIR). Carotid intima-media thickness (cIMT) was measured in the common carotid artery with high-resolution ultrasonography. Risk factors of atherosclerosis (Body mass index [BMI], waist circumference, systolic blood pressure [sBP], triglycerides, low HDL-cholesterol and HbA1c) were also investigated.

Results: cIMT was increased (0.52 ± 0.1 vs. 0.47 ± 0.1 mm, P < 0.01), whereas GIR was decreased (5.0 ± 2.1 vs. 7.1 ± 2.2 mg/kg/min, P < 0.01) in type 1 diabetics vs. non-diabetics. The differences in cIMT were negatively associated with Si (r = -0.4, P < 0.01) and positively associated with waist circumference (r = 0.34, P = 0.03), with no such associations between BMI (r = 0.15, P = 0.32), sBP (r = 0.09, P = 0.58), triglycerides (r = 0.07, P = 0.66), HDL-cholesterol (r = 0.10, P = 0.55) and HbA1c (r = 0.24, P = 0.13). In a multivariate regression model, between cIMT (dependent) and group (explanatory), only adjustment for Si affected the significance (ß = 0.08, P = 0.11) vs. (ß = 0.07, P < 0.01) for the whole model. No interaction between cIMT, groups and Si was observed.

Conclusions: cIMT is increased and associated with insulin resistance in adolescent, non-obese type 1 diabetic subjects. Although, no conclusions toward a causal relationship can be drawn from current findings, insulin resistance emerges as an important factor reflecting early signs of atherosclerosis in this small cohort.

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References

Pambianco G, Costacou T, Orchard T . The prediction of major outcomes of type 1 diabetes: a 12-year prospective evaluation of three separate definitions of the metabolic syndrome and their components and estimated glucose disposal rate: the Pittsburgh Epidemiology of Diabetes.... Diabetes Care. 2007; 30(5):1248-54. DOI: 10.2337/dc06-2053. View

Howard G, OLeary D, Zaccaro D, Haffner S, Rewers M, Hamman R . Insulin sensitivity and atherosclerosis. The Insulin Resistance Atherosclerosis Study (IRAS) Investigators. Circulation. 1996; 93(10):1809-17. DOI: 10.1161/01.cir.93.10.1809. View

Wendelhag I, Liang Q, Gustavsson T, Wikstrand J . A new automated computerized analyzing system simplifies readings and reduces the variability in ultrasound measurement of intima-media thickness. Stroke. 1997; 28(11):2195-200. DOI: 10.1161/01.str.28.11.2195. View

Krolewski A, Kosinski E, Warram J, LELAND O, Busick E, Asmal A . Magnitude and determinants of coronary artery disease in juvenile-onset, insulin-dependent diabetes mellitus. Am J Cardiol. 1987; 59(8):750-5. DOI: 10.1016/0002-9149(87)91086-1. View

Magnussen C, Koskinen J, Chen W, Thomson R, Schmidt M, Srinivasan S . Pediatric metabolic syndrome predicts adulthood metabolic syndrome, subclinical atherosclerosis, and type 2 diabetes mellitus but is no better than body mass index alone: the Bogalusa Heart Study and the Cardiovascular Risk in Young Finns Study. Circulation. 2010; 122(16):1604-11. PMC: 3388503. DOI: 10.1161/CIRCULATIONAHA.110.940809. View

Berenson G, Srinivasan S, Bao W, Newman 3rd W, Tracy R, Wattigney W . Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. The Bogalusa Heart Study. N Engl J Med. 1998; 338(23):1650-6. DOI: 10.1056/NEJM199806043382302. View

Wendelhag I, Gustavsson T, Suurkula M, Berglund G, Wikstrand J . Ultrasound measurement of wall thickness in the carotid artery: fundamental principles and description of a computerized analysing system. Clin Physiol. 1991; 11(6):565-77. DOI: 10.1111/j.1475-097x.1991.tb00676.x. View

Giannini C, Mohn A, Chiarelli F, Kelnar C . Macrovascular angiopathy in children and adolescents with type 1 diabetes. Diabetes Metab Res Rev. 2011; 27(5):436-60. DOI: 10.1002/dmrr.1195. View

. Effect of intensive diabetes treatment on carotid artery wall thickness in the epidemiology of diabetes interventions and complications. Epidemiology of Diabetes Interventions and Complications (EDIC) Research Group. Diabetes. 1999; 48(2):383-90. PMC: 2622732. DOI: 10.2337/diabetes.48.2.383. View

10.

Zimmet P, Alberti K, Kaufman F, Tajima N, Silink M, Arslanian S . The metabolic syndrome in children and adolescents - an IDF consensus report. Pediatr Diabetes. 2007; 8(5):299-306. DOI: 10.1111/j.1399-5448.2007.00271.x. View

11.

Maahs D, Nadeau K, Snell-Bergeon J, Schauer I, Bergman B, West N . Association of insulin sensitivity to lipids across the lifespan in people with Type 1 diabetes. Diabet Med. 2011; 28(2):148-55. PMC: 3395467. DOI: 10.1111/j.1464-5491.2010.03143.x. View

12.

Dengel D, Jacobs D, Steinberger J, Moran A, Sinaiko A . Gender differences in vascular function and insulin sensitivity in young adults. Clin Sci (Lond). 2010; 120(4):153-60. PMC: 5785277. DOI: 10.1042/CS20100223. View

13.

Nathan D, Genuth S, Lachin J, Cleary P, Crofford O, Davis M . The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993; 329(14):977-86. DOI: 10.1056/NEJM199309303291401. View

14.

Goldberger Z, Valle J, Dandekar V, Chan P, Ko D, Nallamothu B . Are changes in carotid intima-media thickness related to risk of nonfatal myocardial infarction? A critical review and meta-regression analysis. Am Heart J. 2010; 160(4):701-14. DOI: 10.1016/j.ahj.2010.06.029. View

15.

Palombo C, Kozakova M, Morizzo C, Gnesi L, Barsotti M, Spontoni P . Circulating endothelial progenitor cells and large artery structure and function in young subjects with uncomplicated type 1 diabetes. Cardiovasc Diabetol. 2011; 10:88. PMC: 3198903. DOI: 10.1186/1475-2840-10-88. View

16.

Watarai T, Yamasaki Y, Ikeda M, Kubota M, Kodama M, Tsujino T . Insulin resistance contributes to carotid arterial wall thickness in patients with non-insulin-dependent-diabetes mellitus. Endocr J. 2000; 46(5):629-38. DOI: 10.1507/endocrj.46.629. View

17.

Marshall W, Tanner J . Variations in pattern of pubertal changes in girls. Arch Dis Child. 1969; 44(235):291-303. PMC: 2020314. DOI: 10.1136/adc.44.235.291. View

18.

Jarvisalo M, Putto-Laurila A, Jartti L, Lehtimaki T, Solakivi T, Ronnemaa T . Carotid artery intima-media thickness in children with type 1 diabetes. Diabetes. 2002; 51(2):493-8. DOI: 10.2337/diabetes.51.2.493. View

19.

Cardellini M, Marini M, Frontoni S, Letizia Hribal M, Andreozzi F, Perticone F . Carotid artery intima-media thickness is associated with insulin-mediated glucose disposal in nondiabetic normotensive offspring of type 2 diabetic patients. Am J Physiol Endocrinol Metab. 2006; 292(1):E347-52. DOI: 10.1152/ajpendo.00291.2006. View

20.

Wohlin M, Sundstrom J, Arnlov J, Andren B, Zethelius B, Lind L . Impaired insulin sensitivity is an independent predictor of common carotid intima-media thickness in a population sample of elderly men. Atherosclerosis. 2003; 170(1):181-5. DOI: 10.1016/s0021-9150(03)00283-1. View