Steno type 1 risk engine and preclinical atherosclerosis in Mediterranean individuals with type 1 diabetes

Abstract Background 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. Purpose 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. Methods 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. Results 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. Conclusion 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. Acknowledgement/Funding None

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Utility of Insulin Resistance in Estimating Cardiovascular Risk in Subjects with Type 1 Diabetes According to the Scores of the Steno Type 1 Risk Engine

Journal of Clinical Medicine ◽

10.3390/jcm9072192 ◽

2020 ◽

Vol 9 (7) ◽

pp. 2192 ◽

Cited By ~ 1

Author(s):

Albert Cano ◽

Gemma Llauradó ◽

Lara Albert ◽

Isabel Mazarico ◽

Brenno Astiarraga ◽

...

Keyword(s):

Insulin Resistance ◽

Type 1 Diabetes ◽

Clinical Practice ◽

Insulin Sensitivity ◽

High Risk ◽

Cvd Risk ◽

C Statistic ◽

Potential Applicability ◽

Risk Engine

Background: We sought to assess the potential of insulin resistance (IR) for estimating cardiovascular disease (CVD) risk in adults with type 1 diabetes (T1DM) according to the scores of the Steno Type 1 Risk Engine (ST1RE). Methods: A total of 179 adults with T1DM (50.8% men, age 41.2 ± 13.1 years, duration of T1DM 16 (12–23) years) without established CVD were evaluated. IR was assessed by the estimation of insulin sensitivity (eIS) using two validated prediction equations: the estimated insulin sensitivity developed from the Pittsburgh Epidemiology of Diabetes Complications Study (eIS-EDC) and the estimated insulin sensitivity developed from Coronary Artery Calcification in T1DM Study (eIS-CACTI) ST1RE was used to estimate 10-year CVD risk and to classify subjects into three groups according to their risk: low (<10%; n = 105), moderate (10–20%; n = 53), and high (≥20%; n = 21). Results: Both eIS-EDC and eIS-CACTI correlated negatively with ST1RE scores (eIS-EDC: r = −0.636, p < 0.001; eIS-CACTI: r = −0.291, p < 0.001). The C-statistic for predicting moderate/high risk and high risk was 0.816 (95% confidence interval (CI): 0.754–0.878) and 0.843 (95% CI: 0.772–0.913), respectively, for the eIS-EDC equation, and was 0.686 (95% CI: 0.609–0.763) and 0.646 (95% CI: 0.513–0.778), respectively, for the eIS-CACTI equation. The eIS-EDC equation had a significantly higher C-statistic both for moderate-/high-risk (p = 0.001) and high-risk (p = 0.007) subjects. Two cut-off points of eIS-EDC were identified for detecting moderate/high risk (8.52 mg·kg−1·min−1; sensitivity 74% and specificity 76%) and high risk (8.08 mg·kg−1·min−1; sensitivity 65% and specificity 95%) with potential applicability in clinical practice. Conclusions: eIS negatively correlates with the score of CVD risk in the ST1RE. Two cut-off points of eIS are reported with potential utility in clinical practice for detecting adults with T1DM with the highest CVD risk.

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P2487Echocardiography and NT-ProBNP both provide independent and improved prediction of prognosis in a type 1 diabetes population without heart disease and with preserved ejection fraction

European Heart Journal ◽

10.1093/eurheartj/ehz748.0817 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

R Roerth ◽

P G Jorgensen ◽

H U Andersen ◽

J P Goetze ◽

P Rossing ◽

...

Keyword(s):

Type 1 Diabetes ◽

Heart Disease ◽

Ejection Fraction ◽

Risk Prediction ◽

Cardiovascular Events ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Risk Engine

Abstract Background Cardiovascular disease is the most common comorbidity in type 1 diabetes (T1D). Current guidelines, however, do not include routine echocardiography or cardiac biomarkers in T1D. Objectives To investigate if echocardiography and NT-proBNP provide incremental prognostic information in individuals with T1D without heart disease and with preserved left ventricular ejection fraction (LVEF). Methods A prospective cohort of individuals with T1D without heart disease and with preserved LVEF (≥45%) from the outpatient clinic were included. Follow-up was performed through Danish national registers. The association between E/e', a marker of diastolic function, from echocardiography and NT-proBNP with major adverse cardiovascular events (MACE) was tested. MACE was defined as death from all-causes, acute coronary syndromes, cardiac revascularization, incident heart failure, or stroke. Additionally, the incremental prognostic value when adding E/e' and NT-proBNP to the clinical Steno T1D Risk Engine score (including age, sex, duration of diabetes, systolic blood pressure, LDL, HbA1c, presence of albuminuria (micro-or macroalbuminuria), eGFR, smoking status, and physical activity [low, medium, high]), was examined. Follow-up was 100% complete. Results Of 964 individuals (mean (SD)) age 49.7 (14.5) years, 51% men, HbA1c 66 (14) mmol/mol, BMI 25.6 (4.0) kg/m2, and diabetes duration 26.1 (14.5) years), 121 (12.6%) experienced MACE during 7.5 years of follow-up. In the full multivariable model, E/e' significantly and independently predicted MACE: (HR (95%)) E/'e <8 (n=639) vs. 8–12 (n=248): 2.00 (1.23; 3.25), p=0.005, E/'e <8 vs E/e'≥12 (n=77): 3.36 (1.8; 6.1), p<0.001. Also, NT-proBNP significantly predicted outcome: NT-proBNP <150 pg/ml (n=435) vs. 150–450 pg/ml (n=386): 1.52 (0.9; 2.5), p=0.11, NT-proBNP <150 pg/ml vs NT-proBNP >450 pg/ml (n=143): 2.78 (1.6; 4.9), p<0.001. Adding both (log)E/e' and (log)NT-proBNP to the Steno T1D Risk Engine score significantly and incrementally improved risk prediction: Harrell's C-index: Steno T1D Risk Engine (AUC 0.783 (0.747; 0.818)) vs. Steno T1D Risk Engine + (log)E/e' (AUC 0.805 (0.773; 0.837)): p<0.001 and Steno T1D Risk Engine + (log)E/e' + (log) NT-proBNP (AUC 0.816 (0.783; 0.848)): p=0.002. The risk of MACE by groups of E/e' and NT-proBNP is shown in the figure. Figure 1 Conclusion In individuals with T1D without heart disease and with preserved LVEF, E/e' and NT-proBNP significantly improved risk prediction of cardiovascular events beyond clinical risk factors alone. Echocardiography and NT-proBNP could have a role in clinical care.

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Novel glycoproteins identify preclinical atherosclerosis among women with previous preeclampsia regardless of type 1 diabetes status

Nutrition Metabolism and Cardiovascular Diseases ◽

10.1016/j.numecd.2021.08.041 ◽

2021 ◽

Author(s):

Antonio J. Amor ◽

Irene Vinagre ◽

Maite Valverde ◽

Nuria Alonso ◽

Xavier Urquizu ◽

...

Keyword(s):

Type 1 Diabetes ◽

Diabetes Status ◽

Preclinical Atherosclerosis

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Nuclear magnetic resonance-based metabolomic analysis in the assessment of preclinical atherosclerosis in type 1 diabetes and preeclampsia

Diabetes Research and Clinical Practice ◽

10.1016/j.diabres.2020.108548 ◽

2021 ◽

Vol 171 ◽

pp. 108548

Author(s):

Antonio J. Amor ◽

Irene Vinagre ◽

Maite Valverde ◽

Xavier Urquizu ◽

Eva Meler ◽

...

Keyword(s):

Nuclear Magnetic Resonance ◽

Type 1 Diabetes ◽

Magnetic Resonance ◽

Metabolomic Analysis ◽

Preclinical Atherosclerosis ◽

Nuclear Magnetic

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Preclinical atherosclerosis is associated with insulin resistance in type 1 diabetes women

Atherosclerosis ◽

10.1016/j.atherosclerosis.2017.06.184 ◽

2017 ◽

Vol 263 ◽

pp. e54

Author(s):

Pavlina Pithova ◽

Jan Pitha ◽

Katerina Stechova ◽

Milan Kvapil

Keyword(s):

Insulin Resistance ◽

Type 1 Diabetes ◽

Preclinical Atherosclerosis

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Preeclampsia Is Associated With Increased Preclinical Carotid Atherosclerosis in Women With Type 1 Diabetes

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgz031 ◽

2019 ◽

Vol 105 (1) ◽

pp. 85-95 ◽

Cited By ~ 4

Author(s):

Antonio J Amor ◽

Irene Vinagre ◽

Maite Valverde ◽

Adriana Pané ◽

Xavier Urquizu ◽

...

Keyword(s):

Type 1 Diabetes ◽

Carotid Atherosclerosis ◽

Intima Media Thickness ◽

Carotid Intima Media Thickness ◽

Statin Treatment ◽

Multivariate Models ◽

Carotid Imt ◽

Established Cardiovascular Risk Factor ◽

Preclinical Atherosclerosis

Abstract Purpose Although preeclampsia (PE) is a well-established cardiovascular risk factor (CVRF) in the general population, its role in type 1 diabetes (T1D) has been scarcely studied. We assessed the association between PE and preclinical atherosclerosis in T1D. Methods We recruited 112 women without cardiovascular disease and last pregnancy ≥5 years before: (1) T1D and previous PE (T1D+/PE+; n = 28); (2) T1D without preeclampsia (T1D+/PE–; n = 28); (3) previous PE without T1D (T1D–/PE+; n = 28); and (4) controls (without T1D or PE; T1D–/PE–; n = 28). Groups were matched by age, several CVRFs, and diabetes duration and retinopathy (in T1D participants). Carotid intima-media thickness (IMT) and the presence of plaque (IMT ≥ 1.5 mm) were assessed by standardized ultrasonography protocol. Results Mean age of the participants was 44.9 ± 7.8 years (14.3% hypertension and 21.4% active smokers). Groups including T1D (T1D+/PE+ and T1D+/PE–) more frequently presented hypertension and statin treatment (23.2% vs 5.4% and 37.5% vs 8.9%; respectively; P < 0.01), without differences in other CVRFs. Carotid plaques were observed in 20.5%. In multivariate models adjusted for age, CVRF, and statins, both T1D and PE showed a similar impact on the presence of plaque, with odds ratios (95% confidence interval), 5.45 (1.36–21.9) and 4.24 (1.04–17.3), respectively. Both entities showed an additive effect when combined, both in common carotid-IMT (T1D+/PE– or T1D–/PE+, β = 0.198; T1D+/PE+, β = 0.297) and in the presence of plaque (8.53 [1.07–68.2] and 28.1 [2.67–296.4], respectively). Conclusions Previous PE was independently associated with preclinical atherosclerosis in T1D. Further studies are needed to ascertain its usefulness for stratifying risk in T1D women.

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