LAUSR

Peripheral neuropathy (PN) is a highly prevalent and feared microvascular complication in patients with type 1 diabetes (T1D). Cardiovascular disease (CVD) is the most common cause of mortality in patients with T1D. PN may act as an early indicator of CVD and can potentially contribute to the propagation of atherosclerosis and cause the disease to remain clinically silent into advanced stages. Therefore, identification of T1D patients at risk of CVD is important in assuring timely prevention and treatment. The purpose of this study was to evaluate the risk of major adverse cardiovascular events (MACE) associated with measures of PN and diastolic function (DF) in patients with T1D and no known heart disease. Furthermore, we tested the additional prognostic value of including PN and DF both alone and in combination, in the validated Steno T1D Risk Engine. Patients with T1D without known heart disease were included from the Steno Diabetes Center Copenhagen. Echocardiography and quantitative testing for PN using biothesiometry to determine sensory vibration threshold were performed. The patients were divided into three categories according to sensory threshold: <20mV, 20–49 mV, and ≥50mV. DF was divided into three categories of E/e': <8, 8–12, and >12. Endpoints was first occurring MACE. Using multivariable Cox regression models adjusting for age, sex, blood pressure, BMI, HbA1c, smoking, alcohol consumption, family history of CVD, eGFR, albuminuria, and duration of diabetes, the association between PN and/or DF and the risk of MACE was analysed. Improvement in prediction of prognosis was assessed with Harrell's C-statistics and compared to Steno T1D Risk Engine. A total of 946 patients (51.5% males) with T1D were included. Mean age was 48.4 (SD 14.4) years and mean duration of diabetes was 25 (SD 14.3) years. In the adjusted analysis, which was mutually adjusted for measures of PN and DF, both PN and DF were associated with increased risk of MACE: Sensory threshold ≥50mV vs. <20mV: Hazard Ratio (HR) 2.18 (95% confidence interval [CI]: 1.02–4.64, p=0.044). Threshold 20–49mV vs. <20mV: HR 1.33 (95% CI: 0.77–2.30, p=0.31). Diastolic measurement E/e' >12 vs. E/e' <8: HR 2.31 (95% CI: 1.16–4.59, p=0.017), and E/e' 8–12 vs. E/e' <8: HR 1.70 (95% CI: 1.03–2.82, p=0.038). In combination, a threshold ≥50mV and E/e' >12 vs. <20mV and E7e' <8 was associated with a marked increased risk of MACE: HR 8.59 (95% CI: 2.60–28.4, p<0.001). The addition of E/e' to the Steno T1D Risk Engine improved the prediction of outcome: C-statistic 0.797, (95% CI: 0.758–0.835) vs. 0.785 (95% CI: 0.744–0.825), p<0.001. In patients with T1D without known heart disease and with preserved ejection fraction, PN and DF are independently associated with an increased risk of MACE. However, only measures of DF improved the prediction of prognosis when added to clinical risk factors. None