# Echocardiography and inflammatory biomarkers for predicting mortality and major adverse cardiovascular events in type 1 diabetes

## TL;DR

Combining echocardiography and inflammatory biomarkers improves risk prediction for mortality and heart events in people with type 1 diabetes.

## Contribution

This study shows that combining subclinical heart dysfunction and inflammation markers improves risk prediction beyond existing tools in type 1 diabetes.

## Key findings

- Elevated E/e’ with IL-6 or suPAR, but not hsCRP, was independently linked to higher mortality risk.
- Adding E/e’ and IL-6 or suPAR to existing risk models improved predictive accuracy (C-statistic increased to 0.887 and 0.868).
- Similar results were observed when using global longitudinal strain and when analyzing major adverse cardiovascular events.

## Abstract

Current clinical risk tools in type 1 diabetes do not include left ventricular dysfunction or inflammation, potentially limiting early risk detection. We aimed to evaluate the associations and predictive value of combining echocardiography with inflammatory biomarkers for mortality and major adverse cardiovascular events (MACE).

In a prospective cohort of individuals with type 1 diabetes without known cardiovascular disease, we evaluated whether subclinical left ventricular dysfunction, defined by an elevated ratio of early mitral inflow velocity to early diastolic mitral annular velocity (E/e′) or impaired global longitudinal strain (GLS), combined with elevated levels of an inflammatory biomarker (interleukin-6 [IL-6], soluble urokinase-plasminogen-activator-receptor [suPAR], or high-sensitivity C-reactive-protein [hsCRP]), was associated with all-cause mortality and MACE. Cox models were adjusted for all 10 variables included in the Steno T1 Risk Engine variables: age, sex, systolic blood pressure, duration of diabetes, HbA1c, low-density lipoprotein, estimated glomerular filtration rate, albuminuria status, smoking, and physical activity. C-statistics and net reclassification improvement were assessed.

Among 876 participants (51% male, median age 50 years), 114 deaths occurred over 14.5 years of follow-up. Elevated E/e’ combined with IL-6 or suPAR, but not hsCRP, was independently associated with mortality. Compared with individuals with E/e’ <8 and non-elevated IL-6, the hazard ratio (HR) for E/e’ 8–13 with elevated IL-6 was 2.5 (95% CI 1.4 to 4.6, P < 0.01), and for E/e′ ≥13 with elevated IL-6 was 3.4 (1.5–7.6; P < 0.01). Corresponding HRs for suPAR were 2.4 (1.2 to 4.7, P < 0.01) and 3.9 (1.8 to 8.5, P < 0.01). Adding E/e′ and an inflammatory biomarker increased the C-statistic from 0.839 (Steno T1 Risk Engine alone) to 0.887 (E/e’ and IL6) and 0.868 (E/e’ and suPAR). Findings were similar for GLS and with MACE as the outcome.

Echocardiography combined with inflammatory biomarkers synergistically identifies individuals with type 1 diabetes, without known cardiovascular disease, who are at high risk of mortality and MACE.

The online version contains supplementary material available at 10.1186/s12933-025-03071-2.