Insulin resistance in adolescents with type 1 diabetes and its relationship to cardiovascular function

Abstract

Context: Cardiovascular disease is the major cause of death in adults with diabetes, yet little is specifically known about the effects of type 1 diabetes (T1D) on cardiovascular outcomes in youth. Although insulin resistance (IR) likely contributes to exercise and cardiovascular dysfunction in T2D, IR is not typically considered a contributor in T1D.

Objective: We hypothesized that cardiopulmonary fitness would be reduced in T1D youth in association with IR and cardiovascular dysfunction.

Design and participants: This cross-sectional study at an academic hospital included 12 T1D adolescents compared with 12 nondiabetic controls, similar in age, pubertal stage, activity level, and body mass index.

Outcome measures: Cardiopulmonary fitness was measured by peak oxygen consumption (VO(2)peak) and oxygen uptake kinetics (VO(2)kinetics), IR by hyperinsulinemic clamp, cardiac function by echocardiography, vascular function by venous occlusion plethysmography, intramyocellular lipid by magnetic resonance spectroscopy, and body composition by dual-energy x-ray absorptiometry.

Results: T1D adolescents had significantly decreased VO(2)peak, peak work rate, and insulin sensitivity compared with nondiabetic adolescents. T1D youth also had reduced vascular reactivity and evidence of diastolic dysfunction and left ventricular hypertrophy. Despite their IR and reduced cardiovascular fitness, T1D youth had paradoxically normal intramyocellular lipid, waist to hip ratio, and serum lipids and high adiponectin levels. In multivariate analysis, IR primarily, and forearm blood flow secondarily, independently predicted VO(2)peak.

Conclusions: T1D youth demonstrated IR, impaired functional exercise capacity and cardiovascular dysfunction. The phenotype of IR in T1D youth was unique, suggesting a pathophysiology that is different from T2D, yet may adversely affect long-term cardiovascular outcomes.

Figures

Figure 1

A, Correlation between maximal exercise capacity (VO2peak) expressed in milliliters per kilogram per minute and glucose disposal rate from the hyperinsulinemic-euglycemic clamp, expressed in milligrams per kilogram per minute; ○, control subjects; •, T1D subjects. B, Correlation between maximal exercise capacity (VO2peak) expressed in milliliters per kilogram per minute and peak hyperemic forearm blood flow from venous plethysmography, expressed in milliliters per 100 ml per minute; ○, control subjects; •, T1D subjects.

Figure 2

Insulin sensitivity expressed as the glucose disposal rate in milligrams per kilogram per minute. Data from control (white bar), T1D (gray bar), obese (black bar), and type 2 diabetic (hatched bar) adolescents are displayed. ^ and #, P values compared with control adolescents; *, P values compared with obese adolescents.