Insulin Sensitivity is Inversely Associated with Cardiovascular Disease Risk Factors in Adolescents with and without Type 1 Diabetes

Brian J. Specht1, B.A.; R. Paul Wadwa2, M.D.; Janet K. Snell-Bergeon2, Ph.D.; Franziska K. Bishop2, M.S.; David M. Maahs2, M.D. Ph.D. 1University of Colorado School of Medicine, Aurora, CO; 2Barbara Davis Center for Childhood Diabetes, Aurora, CO

Objective

The ISS for adolescents ages 12-20 years with T1D (n=292; age 15.4 ± 2.1 years; duration 8.8 ± 3.0 years) and non-DM controls (n=89; age 15.4 ± 2.1 years) was determined using the SEARCH ISS model: logeIS = 4.64725 – 0.02032(waist, cm) – 0.09779(HbA1c, %) – 0.00235(TG, mg/dl).

The ISS for the T1D adolescents was then divided into tertiles (ISS ≤ 6.83, ISS 6.83 – 8.59, and ISS ≥ 8.59); CVD risk factors were compared between all non-DM controls and by ISS tertile in T1D subjects. Comparisons were then stratified by sex and adjusted for race-ethnicity and Tanner Stage of puberty, both known to influence insulin sensitivity.

To compare the relationship between insulin sensitivity and CVD risk factors in adolescents. We tested two hypotheses: 1) Adolescents with T1D have increased CVD risk factors as compared to non-DM controls and 2) CVD risk factors are inversely associated with ISS in adolescents with T1D.

ConclusionsT1D adolescents have increased CVD risk factors as compared to non-DM controls, including decreased estimated insulin sensitivity score indicating reduced insulin sensitivity.

Additionally, CVD risk factors are inversely associated with estimated insulin sensitivity in T1D adolescents.

Adolescence is a crucial period in the understanding and prevention of CVD risk factors in T1D and insulin sensitivity may be an important therapeutic target.

Background

Methods

Cardiovascular disease (CVD) is the primary cause of death in type 1 diabetes (T1D) with many risk factors beginning in early adolescence.

Insulin sensitivity is decreased in T1D as compared to non-diabetic (non-DM) controls and is already present in adolescents. An insulin sensitivity score (ISS) developed in the SEARCH for Diabetes in Youth Study can be used to estimate insulin sensitivity (lower ISS = less insulin sensitive).

This project was supported by the following:

NIDDK Medical Student Research Program, Grant 3T32DK063687-09S1

NIDDK DK075630 for Dr. Maahs

JDRF Early Career Award (11-2007-694) for Dr. Wadwa

NIH/NCRR Colorado CTSI Grant Number UL1 RR025780. Its contents are the authors’ sole responsibility and do not necessarily represent official NIH views.

CVD risk factors were more atherogenic for T1D adolescents as compared to non-DM controls (p<0.05) for body-mass index (BMI), total cholesterol, HDL-cholesterol, LDL-cholesterol, systolic blood pressure (SBP), diastolic blood pressure (DBP) and C-reactive protein (CRP). The ISS was also significantly different between the two groups (non-DM ISS 11.5 2.9, T1D ISS 7.8 2.4; p<0.0001), and hemoglobin A1c (HbA1c) was significantly different by diabetes status, as expected.

When ISS was divided into tertiles in T1D subjects, CVD risk factors were progressively more atherogenic as insulin sensitivity decreased and as compared to non-DM controls. When the data were adjusted for race-ethnicity and Tanner Stage and stratified by sex, similar differences were seen in both males and females.

Results

Acknowledgments