Impact of metabolic indices on central artery stiffness: independent association of insulin resistance and glucose with aortic pulse wave velocity

Abstract

Aims/hypothesis Non-invasive measures of aortic stiffness reflect vascular senescence and predict outcome in diabetes. Glucose-mediated elastic artery sclerosis may play an integral role in the development of macrovascular complications. We used carotid-femoral pulse wave velocity ( cf PWV) to quantify independent associations of fasting glucose, post-challenge glucose and derived insulin resistance (HOMA-IR) with aortic stiffness. Methods cf PWV was measured using a 4 MHz continuous wave Doppler ultrasound probe within groups with newly identified age-and sex-matched normal glucose metabolism (NGM), impaired glucose regulation (IGR) and diabetes mellitus populations (n=570, mean age 59.1, 56% male). Results After multivariate adjustment, IGR and diabetes were associated with significant aortic stiffening compared with NGM (adjusted cf PWV±SE: NGM, 9.15±0.12 m/s; IGR 9.76±0.11 m/s, p<0.001; diabetes, 9.89±0.12 m/s, p< 0.001). IGR stratification indicated that impaired fasting glucose (IFG; 9.71±0.12 m/s) and post-challenge (impaired glucose tolerance; 9.82±0.24 m/s) categories had similar cf PWV (p=0.83). Modelled predictors of cf PWV were used to assess independent metabolic associations with arterial stiffness. Fasting glucose concentration (β=0.10; 95% CI 0.05, 0.18; p=0.003), 2 h post-challenge glucose (β=0.14; 95% CI 0.02, 0.23; p<0.001) and HOMA-IR (β=0.20, 95% CI 0.05, 0.53; p<0.001) were independently related to cf PWV after adjustment for age, sex, mean arterial pressure, heart rate, body mass index, renal function and antihypertensive medication. Conclusions/interpretation IGR characterised by fasting or post-challenge hyperglycaemia is associated with significant vascular stiffening. Post-challenge glucose and HOMA-IR are the most powerful metabolic predictors of arterial stiffness, implying hyperglycaemic excursion and insulin resistance play important roles in the pathogenesis of arteriosclerosis.

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“…However, this may be a paradoxical effect whereby meal-induced elevations in insulin are acutely beneficial, but sustained hyperinsulinemia (resulting in insulin resistance and related conditions) is associated with arterial stiffness (41)(42)(43)(44)(45). Given that these postprandial reductions can be maintained hours after a meal, they also may be due in part to increased blood flow to digestive organs, with compensatory reductions in flow to other organs (46).…”

Predictive markers of abdominal aortic stiffness measured by echo-tracking in subjects with varying insulin sensitivity

“…There exists strong evidence that diabetes is associated with increased arterial stiffness 5 . Associations have also been described between arterial stiffness and prediabetic states such as insulin resistance and impaired glucose tolerance 6,19,20 . In a study of 41 subjects a correlation between fasting glucose levels and local aortic distensibility was shown using a local invasive method 21 .…”

“…Markers of an impaired glucose metabolism are linked to an increased arterial stiffness measured by c-f PWV 6 as well as brachial PP progression 7 .…”

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“…2). At the level of conduit arteries, an extensive body of data indicates that metabolic insulin resistance, as seen in obesity, metabolic syndrome, and type 1 and type 2 diabetes, is accompanied by dysfunction that is manifested by increased vascular stiffness and/or impaired NO-mediated vasodilation (95,102,112,114). In addition, the responsiveness of these vessels to insulin is impaired (114).…”