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Background The association between type 2 diabetes and electrocardiographic (ECG) markers are incompletely explored and the dependence on diabetes duration is largely unknown. We aimed to investigate the electrocardiographic (ECG) changes associated with type 2 diabetes over time. Methods In this cross-sectional study, we matched people with type 2 diabetes 1:1 on sex, age, and body mass index with people without diabetes from the general population. We regressed ECG markers with the presence of diabetes and the duration of clinical diabetes, respectively, adjusted for sex, age, body mass index, smoking, heart rate, diabetes medication, renal function, hypertension, and myocardial infarction. Results We matched 988 people with type 2 diabetes (332, 34% females) with as many controls. Heart rate was 8 bpm higher (p < 0.001) in people with vs. without type 2 diabetes, but the difference declined with increasing diabetes duration. For most depolarization markers, the difference between people with and without type 2 diabetes increased progressively with diabetes duration. On average, R-wave amplitude was 6 mm lower in lead V5 (p < 0.001), P-wave duration was 5 ms shorter (p < 0.001) and QRS duration was 3 ms (p = 0.03). Among repolarization markers, T-wave amplitude (measured in V5) was lower in patients with type 2 diabetes (1 mm lower, p < 0.001) and the QRS-T angle was 10 degrees wider (p = 0.002). We observed no association between diabetes duration and repolarization markers. Conclusions Type 2 diabetes was independently associated with electrocardiographic depolarization and repolarization changes. Differences in depolarization markers, but not repolarization markers, increased with increasing diabetes duration., Background: The association between type 2 diabetes and electrocardiographic (ECG) markers are incompletely explored and the dependence on diabetes duration is largely unknown. We aimed to investigate the electrocardiographic (ECG) changes associated with type 2 diabetes over time. Methods: In this cross-sectional study, we matched people with type 2 diabetes 1:1 on sex, age, and body mass index with people without diabetes from the general population. We regressed ECG markers with the presence of diabetes and the duration of clinical diabetes, respectively, adjusted for sex, age, body mass index, smoking, heart rate, diabetes medication, renal function, hypertension, and myocardial infarction. Results: We matched 988 people with type 2 diabetes (332, 34% females) with as many controls. Heart rate was 8 bpm higher (p < 0.001) in people with vs. without type 2 diabetes, but the difference declined with increasing diabetes duration. For most depolarization markers, the difference between people with and without type 2 diabetes increased progressively with diabetes duration. On average, R-wave amplitude was 6 mm lower in lead V5 (p < 0.001), P-wave duration was 5 ms shorter (p < 0.001) and QRS duration was 3 ms (p = 0.03). Among repolarization markers, T-wave amplitude (measured in V5) was lower in patients with type 2 diabetes (1 mm lower, p < 0.001) and the QRS-T angle was 10 degrees wider (p = 0.002). We observed no association between diabetes duration and repolarization markers. Conclusions: Type 2 diabetes was independently associated with electrocardiographic depolarization and repolarization changes. Differences in depolarization markers, but not repolarization markers, increased with increasing diabetes duration.

Background The association between type 2 diabetes and electrocardiographic (ECG) markers are incompletely explored and the dependence on diabetes duration is largely unknown. We aimed to investigate the electrocardiographic (ECG) changes associated with type 2 diabetes over time. Methods In this cross-sectional study, we matched people with type 2 diabetes 1:1 on sex, age, and body mass index with people without diabetes from the general population. We regressed ECG markers with the presence of diabetes and the duration of clinical diabetes, respectively, adjusted for sex, age, body mass index, smoking, heart rate, diabetes medication, renal function, hypertension, and myocardial infarction. Results We matched 988 people with type 2 diabetes (332, 34% females) with as many controls. Heart rate was 8 bpm higher (p < 0.001) in people with vs. without type 2 diabetes, but the difference declined with increasing diabetes duration. For most depolarization markers, the difference between people with and without type 2 diabetes increased progressively with diabetes duration. On average, R-wave amplitude was 6 mm lower in lead V5 (p < 0.001), P-wave duration was 5 ms shorter (p < 0.001) and QRS duration was 3 ms (p = 0.03). Among repolarization markers, T-wave amplitude (measured in V5) was lower in patients with type 2 diabetes (1 mm lower, p < 0.001) and the QRS-T angle was 10 degrees wider (p = 0.002). We observed no association between diabetes duration and repolarization markers. Conclusions Type 2 diabetes was independently associated with electrocardiographic depolarization and repolarization changes. Differences in depolarization markers, but not repolarization markers, increased with increasing diabetes duration., Background: The association between type 2 diabetes and electrocardiographic (ECG) markers are incompletely explored and the dependence on diabetes duration is largely unknown. We aimed to investigate the electrocardiographic (ECG) changes associated with type 2 diabetes over time. Methods: In this cross-sectional study, we matched people with type 2 diabetes 1:1 on sex, age, and body mass index with people without diabetes from the general population. We regressed ECG markers with the presence of diabetes and the duration of clinical diabetes, respectively, adjusted for sex, age, body mass index, smoking, heart rate, diabetes medication, renal function, hypertension, and myocardial infarction. Results: We matched 988 people with type 2 diabetes (332, 34% females) with as many controls. Heart rate was 8 bpm higher (p < 0.001) in people with vs. without type 2 diabetes, but the difference declined with increasing diabetes duration. For most depolarization markers, the difference between people with and without type 2 diabetes increased progressively with diabetes duration. On average, R-wave amplitude was 6 mm lower in lead V5 (p < 0.001), P-wave duration was 5 ms shorter (p < 0.001) and QRS duration was 3 ms (p = 0.03). Among repolarization markers, T-wave amplitude (measured in V5) was lower in patients with type 2 diabetes (1 mm lower, p < 0.001) and the QRS-T angle was 10 degrees wider (p = 0.002). We observed no association between diabetes duration and repolarization markers. Conclusions: Type 2 diabetes was independently associated with electrocardiographic depolarization and repolarization changes. Differences in depolarization markers, but not repolarization markers, increased with increasing diabetes duration.

Aims . The European Society of Cardiology guidelines on diabetes and cardiovascular disease (CVD) recommend an electrocardiogram (ECG) in patients with diabetes and hypertension or with suspected CVD. We investigated whether ECG abnormalities can be used as a diagnostic and prognostic marker of heart failure (HF) in patients with type-2 diabetes (T2D) in secondary care diabetes-clinics. Methods . We included 722 patients with T2D in sinus rhythm. HF with preserved ejection fraction (HFpEF) was defined according to the European Society of Cardiology guidelines. Heart failure with mid-range ejection fraction (HFmrEF) was patients with dyspnoea and an LVEF 41-49%. Heart failure with reduced ejection fraction (HFrEF) or asymptomatic left ventricular systolic dysfunction (ALVSD) was defined as a LVEF ≤40%. Results . Overall, 24% patients had ECG abnormalities. A total of 15% had HF whereof 48% had ECG abnormalities. A normal ECG had a 99.3% negative predictive value (NPV) of ruling out HFrEF/ALVSD. In a sub-group with 0-1 simple clinical risk markers, the ECG ruled out both HFrEF/ALVSD, HFmrEF, and HFpEF with an NPV of 96.6%. The hazard-ratio (HR) of incident CVD or death in patients with HF and a normal ECG compared with patients without HF was 1.85 [95%CI 1.01-3.39], p = .05, while an abnormal ECG increased the HR to 3.84 [2.33-6.33], p < .001. Conclusion . HFrEF/ALVSD and HFmrEF were rare and HFpEF was frequent in this T2D population. A normal ECG ruled out HFrEF/ALVSD and in a sub-population with 0-1 simple clinical risk markers also both HFrEF/ALVSD, HFmrEF, and HFpEF.Key messages What is already known about this subject?In early studies of unselected patients from primary care with suspected chronic heart failure, the presence of a normal ECG was found be useful to rule out heart failure with reduced ejection fraction. What does this study add?This study confirms that a standard electrocardiogram when normal in 722 stable outpatients with type 2 diabetes c

Aims . The European Society of Cardiology guidelines on diabetes and cardiovascular disease (CVD) recommend an electrocardiogram (ECG) in patients with diabetes and hypertension or with suspected CVD. We investigated whether ECG abnormalities can be used as a diagnostic and prognostic marker of heart failure (HF) in patients with type-2 diabetes (T2D) in secondary care diabetes-clinics. Methods . We included 722 patients with T2D in sinus rhythm. HF with preserved ejection fraction (HFpEF) was defined according to the European Society of Cardiology guidelines. Heart failure with mid-range ejection fraction (HFmrEF) was patients with dyspnoea and an LVEF 41-49%. Heart failure with reduced ejection fraction (HFrEF) or asymptomatic left ventricular systolic dysfunction (ALVSD) was defined as a LVEF ≤40%. Results . Overall, 24% patients had ECG abnormalities. A total of 15% had HF whereof 48% had ECG abnormalities. A normal ECG had a 99.3% negative predictive value (NPV) of ruling out HFrEF/ALVSD. In a sub-group with 0-1 simple clinical risk markers, the ECG ruled out both HFrEF/ALVSD, HFmrEF, and HFpEF with an NPV of 96.6%. The hazard-ratio (HR) of incident CVD or death in patients with HF and a normal ECG compared with patients without HF was 1.85 [95%CI 1.01-3.39], p = .05, while an abnormal ECG increased the HR to 3.84 [2.33-6.33], p < .001. Conclusion . HFrEF/ALVSD and HFmrEF were rare and HFpEF was frequent in this T2D population. A normal ECG ruled out HFrEF/ALVSD and in a sub-population with 0-1 simple clinical risk markers also both HFrEF/ALVSD, HFmrEF, and HFpEF.Key messages What is already known about this subject?In early studies of unselected patients from primary care with suspected chronic heart failure, the presence of a normal ECG was found be useful to rule out heart failure with reduced ejection fraction. What does this study add?This study confirms that a standard electrocardiogram when normal in 722 stable outpatients with type 2 diabetes c

AIM: To investigate echocardiographic changes during acute hypoglycaemia followed by recovery to hyperglycaemia or euglycaemia in patients with type 1 diabetes.MATERIALS AND METHODS: In a randomized crossover study, 24 patients with type 1 diabetes took part in two experimental study days, consisting of a hyperinsulinaemic-euglycaemic phase (5.0-8.0 mmol/L) for 45 minutes followed by a hyperinsulinemic-hypoglycaemic phase (2.5 mmol/L) for 60 minutes, and a recovery phase in either hyperglycaemia (20 mmol/L) or euglycaemia (5.0-8.0 mmol/L) for 60 minutes. Cardiac function was evaluated with echocardiography during each phase.RESULTS: Acute hypoglycaemia increased all markers of left ventricular (LV) systolic function, including LV ejection fraction (LVEF), global longitudinal strain (GLS), GLS rate and peak systolic velocity of mitral annular longitudinal movement (s'; P < 0.001 for all). During the recovery phases, all markers of LV systolic function were increased during hyperglycaemia (P < 0.01 for all), and LVEF and GLS remained increased during euglycaemia (P = 0.0116 and P = 0.0092, respectively). The increment in LVEF during the recovery phase was greater during hyperglycaemia than euglycaemia (P = 0.0046).CONCLUSIONS: Hypoglycaemia, recent hypoglycaemia, and overcorrection of hypoglycaemia to rebound hyperglycaemia increased LV systolic function in type 1 diabetes and may imply consideration of plasma glucose when evaluating LV function in patients with type 1 diabetes. An increase in LV systolic function may cause increased strain on the heart and partly explain the link between hypoglycaemia, high glycaemic variability and cardiovascular disease.

Aims We aimed to evaluate the effect of acute hyperglycaemia and hypoglycaemia on cardiac function in patients with type 2 diabetes (T2D) and a control group. Materials and methods In a nonrandomized interventional study, insulin-treated patients with T2D (N = 21, mean +/- SD age 62.8 +/- 6.5 years, body mass index [BMI] 29.0 +/- 4.2 kg/m(2), glycated haemoglobin [HbA1c] 51.0 +/- 5.4 mmol/mol [6.8 +/- 0.5%]) and matched controls (N = 21, mean +/- SD age 62.2 +/- 8.3 years, BMI 29.2 +/- 3.5 kg/m(2), HbA1c 34.3 +/- 3.3 mmol/L [5.3 +/- 0.3%]) underwent one experimental day with plasma glucose (PG) clamped at three different 30-minute steady-state levels: (1) fasting plasma glucose (FPG); (2) hyperglycaemia (FPG + 10 mmol/L); and (3) hyperinsulinaemic hypoglycaemia (PG

Aims We aimed to evaluate the effect of acute hyperglycaemia and hypoglycaemia on cardiac function in patients with type 2 diabetes (T2D) and a control group. Materials and methods In a nonrandomized interventional study, insulin-treated patients with T2D (N = 21, mean +/- SD age 62.8 +/- 6.5 years, body mass index [BMI] 29.0 +/- 4.2 kg/m(2), glycated haemoglobin [HbA1c] 51.0 +/- 5.4 mmol/mol [6.8 +/- 0.5%]) and matched controls (N = 21, mean +/- SD age 62.2 +/- 8.3 years, BMI 29.2 +/- 3.5 kg/m(2), HbA1c 34.3 +/- 3.3 mmol/L [5.3 +/- 0.3%]) underwent one experimental day with plasma glucose (PG) clamped at three different 30-minute steady-state levels: (1) fasting plasma glucose (FPG); (2) hyperglycaemia (FPG + 10 mmol/L); and (3) hyperinsulinaemic hypoglycaemia (PG

Background: Diagnostic tests including echocardiography, albuminuria, electrocardiogram (ECG), high-sensitivity troponin I (hs-TnI), and N-terminal prohormone brain natriuretic peptide (NT-proBNP) have been suggested as cardiovascular (CV) risk predictors in type 2 diabetes. We studied the separate and combined prognostic yield of these risk markers. Methods: In all, 1030 patients with type 2 diabetes were recruited from specialized clinics in this prospective cohort study. Full echocardiographic evaluation was feasible in 886 patients in sinus rhythm with adequate image quality. ECG was performed in 998 patients. Albuminuria was measured in 1009 and NT-proBNP/hs-TnI in 933 patients. The end point was a composite of CV events. Results: The median follow-up was 4.7 years (interquartile range: 4.0-5.3), and 174 patients experienced a CV disease event. All considered markers, except hs-TnI, were significantly (P <.001) associated with the outcome: abnormal echocardiogram (hazard ratio 2.40 [1.70-3.39]), albuminuria 2.01 (1.47-2.76), abnormal ECG (2.27 [1.66-3.08]), high NT-proBNP (>150 pg/mL) 3.05 (2.11-4.40), and hs-TnI 1.12 (0.79-1.59). After adjusting for clinical variables, all remained significantly associated with the end point. However, after adjusting for each other, only NT-proBNP >150 pg/mL remained significantly associated with the end point (2.07 [1.28-3.34], P <.001). Measured by C-statistics, model performance was highest with log2 (NT-proBNP) (0.70 [0.65-0.75]) and similar to clinical variables alone (0.71 [0.67-0.76]). Combining all risk markers only resulted in a very limited increase in C-statistics (0.69 [0.64-0.74]). Conclusions: This study identified NT-proBNP over echocardiography, ECG, and albuminuria in risk prediction in patients with type 2 diabetes. The diagnostic yield in considering more than one risk marker was limited in this population.

Aims Colour tissue Doppler imaging (TDI) M-mode through the mitral leaflet is an easy and precise method to obtain cardiac time intervals including isovolumic contraction time (IVCT), isovolumic relaxation time (IVRT) and systolic ejection time (SET). The myocardial performance index (MPI) is defined as [(IVCT + IVRT)/SET]. Whether cardiac time intervals obtained by the TDI M-mode method can be used to predict outcome in patients with heart failure with reduced ejection fraction (HFrEF) remains unknown.Methods and results A total of 997 patients with HFrEF (mean age 67 +/- 11 years, 74% male) underwent an echocardiographic examination including TDI. During a median follow-up of 3.4 years (interquartile range 1.9-4.8 years), 165 (17%) patients died. The risk of mortality increased by 9% per 10 ms decrease in SET [per 10 ms decrease: hazard ratio (HR) 1.09, 95% confidence interval (CI) 1.06-1.13; P <0.001]. The association remained significant even after multivariable adjustment for clinical and echocardiographic parameters (per 10 ms decrease: HR 1.06, 95% CI 1.01-1.11; P = 0.030). The MPI was a significant predictor in an unadjusted model (per 0.1 increase: HR 3.06, 95% CI 1.16-8.06; P = 0.023). However, the association did not remain significant after multivariable adjustment. No significant associations between IVCT or IVRT and mortality were found in unadjusted nor adjusted models. Additionally, SET provided incremental prognostic information with regard to predicting mortality when added to established clinical predictors of mortality in patients with HFrEF.Conclusion In patients with HFrEF, SET provides independent and incremental prognostic information regarding all-cause mortality.

Background: Mid-regional pro-atrial natriuretic peptide (MR-proANP) is a useful biomarker in outpatients with type 2 diabetes (T2D) to diagnose heart failure (HF). Elevated B-type natriuretic peptides are included in the definition of HF with preserved ejection fraction (HFpEF) but little is known about the prognostic value of including A-type natriuretic peptides (MR-proANP) in the evaluation of patients with T2D. Methods: We prospectively evaluated the risk of incident cardiovascular (CV) events in outpatients with T2D (n = 806, mean ± standard deviation age 64 ± 10 years, 65% male, median [interquartile range] duration of diabetes 12 [6–17] years, 17.5% with symptomatic HFpEF) according to MR-proANP levels and stratified according to HF-status including further stratification according to a prespecified cut-off level of MR-proANP. Results: A total of 126 CV events occurred (median follow-up 4.8 [4.1–5.3] years). An elevated MR-proANP, with a cut-off of 60 pmol/l or as a continuous variable, was associated with incident CV events (p < 0.001). Compared to patients without HF, patients with HFpEF and high MR-proANP (≥ 60 pmol/l; median 124 [89–202] pmol/l) and patients with HF and reduced ejection fraction (HFrEF) had a higher risk of CV events (multivariable model; hazard ratio (HR) 2.56 [95% CI 1.64–4.00] and 3.32 [1.64–6.74], respectively). Conversely, patients with HFpEF and low MR-proANP (< 60 pmol/l; median 46 [32–56] pmol/l) did not have an increased risk (HR 2.18 [0.78–6.14]). Conclusions: Patients with T2D and HFpEF with high MR-proANP levels had an increased risk for CV events compared to patients with HFpEF without elevated MR-proANP and compared to patients without HF, supporting the use of MR-proANP in the definition of HFpEF from a prognostic point-of-view.

Background: Mid-regional pro-atrial natriuretic peptide (MR-proANP) is a useful biomarker in outpatients with type 2 diabetes (T2D) to diagnose heart failure (HF). Elevated B-type natriuretic peptides are included in the definition of HF with preserved ejection fraction (HFpEF) but little is known about the prognostic value of including A-type natriuretic peptides (MR-proANP) in the evaluation of patients with T2D. Methods: We prospectively evaluated the risk of incident cardiovascular (CV) events in outpatients with T2D (n = 806, mean ± standard deviation age 64 ± 10 years, 65% male, median [interquartile range] duration of diabetes 12 [6–17] years, 17.5% with symptomatic HFpEF) according to MR-proANP levels and stratified according to HF-status including further stratification according to a prespecified cut-off level of MR-proANP. Results: A total of 126 CV events occurred (median follow-up 4.8 [4.1–5.3] years). An elevated MR-proANP, with a cut-off of 60 pmol/l or as a continuous variable, was associated with incident CV events (p < 0.001). Compared to patients without HF, patients with HFpEF and high MR-proANP (≥ 60 pmol/l; median 124 [89–202] pmol/l) and patients with HF and reduced ejection fraction (HFrEF) had a higher risk of CV events (multivariable model; hazard ratio (HR) 2.56 [95% CI 1.64–4.00] and 3.32 [1.64–6.74], respectively). Conversely, patients with HFpEF and low MR-proANP (< 60 pmol/l; median 46 [32–56] pmol/l) did not have an increased risk (HR 2.18 [0.78–6.14]). Conclusions: Patients with T2D and HFpEF with high MR-proANP levels had an increased risk for CV events compared to patients with HFpEF without elevated MR-proANP and compared to patients without HF, supporting the use of MR-proANP in the definition of HFpEF from a prognostic point-of-view.

Hypoglycaemia remains an inevitable risk in insulin-treated type 1 diabetes and type 2 diabetes and has been associated with multiple adverse outcomes. Whether hypoglycaemia is a cause of fatal cardiac arrhythmias in diabetes, or merely a marker of vulnerability, is still unknown. Since a pivotal report in 1991, hypoglycaemia has been suspected to induce cardiac arrhythmias in patients with type 1 diabetes, the so-called 'dead-in-bed syndrome'. This suspicion has subsequently been supported by the coexistence of an increased mortality and a three-fold increase in severe hypoglycaemia in patients with type 2 diabetes receiving intensive glucose-lowering treatment in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Studies have investigated the association between hypoglycaemia-induced cardiac arrhythmias. In a rat-model, severe hypoglycaemia resulted in a specific pattern of cardiac arrhythmias including QT-prolongation, ventricular tachycardia, second- and third-degree AV block and ultimately cardiorespiratory arrest. In clinical studies of experimentally induced hypoglycaemia, QTc-prolongation, a risk factor of ventricular arrhythmias, is an almost consistent finding. The extent of QT-prolongation seems to be modified by several factors, including antecedent hypoglycaemia, diabetes duration and cardiac autonomic neuropathy. Observational studies indicate diurnal differences in the pattern of electrocardiographic alterations during hypoglycaemia with larger QTc-prolongations during daytime, whereas the risk of bradyarrhythmias may be increased during sleep. Daytime periods of hypoglycaemia are characterized by shorter duration, increased awareness and a larger increase in catecholamines. The counterregulatory response is reduced during nightly episodes of hypoglycaemia, resulting in prolonged periods of hypoglycaemia with multiple nadirs. An initial sympathetic activity at plasma glucose nadir is replaced by increased vagal activity, which re

Background: Mid-regional pro-atrial natriuretic peptide (MR-proANP) is a useful biomarker in outpatients with type 2 diabetes (T2D) to diagnose heart failure (HF). Elevated B-type natriuretic peptides are included in the definition of HF with preserved ejection fraction (HFpEF) but little is known about the prognostic value of including A-type natriuretic peptides (MR-proANP) in the evaluation of patients with T2D. Methods: We prospectively evaluated the risk of incident cardiovascular (CV) events in outpatients with T2D (n = 806, mean ± standard deviation age 64 ± 10 years, 65% male, median [interquartile range] duration of diabetes 12 [6–17] years, 17.5% with symptomatic HFpEF) according to MR-proANP levels and stratified according to HF-status including further stratification according to a prespecified cut-off level of MR-proANP. Results: A total of 126 CV events occurred (median follow-up 4.8 [4.1–5.3] years). An elevated MR-proANP, with a cut-off of 60 pmol/l or as a continuous variable, was associated with incident CV events (p < 0.001). Compared to patients without HF, patients with HFpEF and high MR-proANP (≥ 60 pmol/l; median 124 [89–202] pmol/l) and patients with HF and reduced ejection fraction (HFrEF) had a higher risk of CV events (multivariable model; hazard ratio (HR) 2.56 [95% CI 1.64–4.00] and 3.32 [1.64–6.74], respectively). Conversely, patients with HFpEF and low MR-proANP (< 60 pmol/l; median 46 [32–56] pmol/l) did not have an increased risk (HR 2.18 [0.78–6.14]). Conclusions: Patients with T2D and HFpEF with high MR-proANP levels had an increased risk for CV events compared to patients with HFpEF without elevated MR-proANP and compared to patients without HF, supporting the use of MR-proANP in the definition of HFpEF from a prognostic point-of-view.

Hypoglycaemia remains an inevitable risk in insulin-treated type 1 diabetes and type 2 diabetes and has been associated with multiple adverse outcomes. Whether hypoglycaemia is a cause of fatal cardiac arrhythmias in diabetes, or merely a marker of vulnerability, is still unknown. Since a pivotal report in 1991, hypoglycaemia has been suspected to induce cardiac arrhythmias in patients with type 1 diabetes, the so-called 'dead-in-bed syndrome'. This suspicion has subsequently been supported by the coexistence of an increased mortality and a three-fold increase in severe hypoglycaemia in patients with type 2 diabetes receiving intensive glucose-lowering treatment in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Studies have investigated the association between hypoglycaemia-induced cardiac arrhythmias. In a rat-model, severe hypoglycaemia resulted in a specific pattern of cardiac arrhythmias including QT-prolongation, ventricular tachycardia, second- and third-degree AV block and ultimately cardiorespiratory arrest. In clinical studies of experimentally induced hypoglycaemia, QTc-prolongation, a risk factor of ventricular arrhythmias, is an almost consistent finding. The extent of QT-prolongation seems to be modified by several factors, including antecedent hypoglycaemia, diabetes duration and cardiac autonomic neuropathy. Observational studies indicate diurnal differences in the pattern of electrocardiographic alterations during hypoglycaemia with larger QTc-prolongations during daytime, whereas the risk of bradyarrhythmias may be increased during sleep. Daytime periods of hypoglycaemia are characterized by shorter duration, increased awareness and a larger increase in catecholamines. The counterregulatory response is reduced during nightly episodes of hypoglycaemia, resulting in prolonged periods of hypoglycaemia with multiple nadirs. An initial sympathetic activity at plasma glucose nadir is replaced by increased vagal activity, which re

Background: Cardiac fat is a cardiovascular biomarker but its importance in patients with type 2 diabetes is not clear. The aim was to evaluate the predictive potential of epicardial (EAT), pericardial (PAT) and total cardiac (CAT) fat in type 2 diabetes and elucidate sex differences. Methods: EAT and PAT were measured by echocardiography in 1030 patients with type 2 diabetes. Follow-up was performed through national registries. The end-point was the composite of incident cardiovascular disease (CVD) and all-cause mortality. Analyses were unadjusted (model 1), adjusted for age and sex (model 2), plus systolic blood pressure, body mass index (BMI), low-density lipoprotein (LDL), smoking, diabetes duration and glycated hemoglobin (HbA1c) (model 3). Results: Median follow-up was 4.7 years and 248 patients (191 men vs. 57 women) experienced the composite end-point. Patients with high EAT (> median level) had increased risk of the composite end-point in model 1 [Hazard ratio (HR): 1.46 (1.13; 1.88), p = 0.004], model 2 [HR: 1.31 (1.01; 1.69), p = 0.038], and borderline in model 3 [HR: 1.32 (0.99; 1.77), p = 0.058]. For men, but not women, high EAT was associated with a 41% increased risk of CVD and mortality in model 3 (p = 0.041). Net reclassification index improved when high EAT was added to model 3 (19.6%, p = 0.035). PAT or CAT were not associated with the end-point. Conclusion: High levels of EAT were associated with the composite of incident CVD and mortality in patients with type 2 diabetes, particularly in men, after adjusting for CVD risk factors. EAT modestly improved risk prediction over CVD risk factors.

Background: Dyspnea is a common clinical challenge in patients with type 2 diabetes and may be a sign of heart failure (HF). We sought to evaluate the predictive value dyspnea with and without an echocardiographic substrate in patients with type 2 diabetes without known heart disease. Methods: A total of 724 patients with type 2 diabetes followed at specialized clinics participated in this prospective cohort study. Clinical evaluation, comprehensive echocardiography and follow-up through national registers were performed. An echocardiographic substrate was either left ventricular hypertrophy, increased left atrial size, E/e’ > 15, or LV ejection fraction<50%. The end-points were cardiovascular (CVD)events and all-cause mortality. Results: Median follow-up was 4.8 years [Interquartile range: 4.1, 5.3]for CVD event and 77 patients suffered a CVD event. Dyspnea was significantly associated with CVD event: Hazard ratio (HR): 1.58 (95% confidence interval: 1.01–2.48), p = 0.04. Stratifying by evidence of echocardiographic substrate revealed high risk individuals: CVD event: 0.71 (0.35–1.46), p = NS in patients with dyspnea and no echocardiographic substrate and 2.85 (1.74–4.67), p < 0.001 in patients with dyspnea with echocardiographic substrate). This pattern was similar in multivariable analyses. Also, C-statistics improved from 0.66 (0.60–0.72)to 0.69 (0.63–0.75), p < 0.001 and net reclassification index was 27.5%(5.0–50.0), p = 0.01 for CVD event. The results were similar for all-cause mortality except dyspnea was only a borderline significant predictor. Conclusion: In patients with type 2 diabetes complaining of dyspnea, identifying an echocardiographic substrate - thus indicating patients with HF - accurately stratifies patients with increased risk of CV events and all-cause mortality.

Background: Cardiac fat is a cardiovascular biomarker but its importance in patients with type 2 diabetes is not clear. The aim was to evaluate the predictive potential of epicardial (EAT), pericardial (PAT) and total cardiac (CAT) fat in type 2 diabetes and elucidate sex differences. Methods: EAT and PAT were measured by echocardiography in 1030 patients with type 2 diabetes. Follow-up was performed through national registries. The end-point was the composite of incident cardiovascular disease (CVD) and all-cause mortality. Analyses were unadjusted (model 1), adjusted for age and sex (model 2), plus systolic blood pressure, body mass index (BMI), low-density lipoprotein (LDL), smoking, diabetes duration and glycated hemoglobin (HbA1c) (model 3). Results: Median follow-up was 4.7 years and 248 patients (191 men vs. 57 women) experienced the composite end-point. Patients with high EAT (> median level) had increased risk of the composite end-point in model 1 [Hazard ratio (HR): 1.46 (1.13; 1.88), p = 0.004], model 2 [HR: 1.31 (1.01; 1.69), p = 0.038], and borderline in model 3 [HR: 1.32 (0.99; 1.77), p = 0.058]. For men, but not women, high EAT was associated with a 41% increased risk of CVD and mortality in model 3 (p = 0.041). Net reclassification index improved when high EAT was added to model 3 (19.6%, p = 0.035). PAT or CAT were not associated with the end-point. Conclusion: High levels of EAT were associated with the composite of incident CVD and mortality in patients with type 2 diabetes, particularly in men, after adjusting for CVD risk factors. EAT modestly improved risk prediction over CVD risk factors.

Background: Dyspnea is a common clinical challenge in patients with type 2 diabetes and may be a sign of heart failure (HF). We sought to evaluate the predictive value dyspnea with and without an echocardiographic substrate in patients with type 2 diabetes without known heart disease. Methods: A total of 724 patients with type 2 diabetes followed at specialized clinics participated in this prospective cohort study. Clinical evaluation, comprehensive echocardiography and follow-up through national registers were performed. An echocardiographic substrate was either left ventricular hypertrophy, increased left atrial size, E/e’ > 15, or LV ejection fraction<50%. The end-points were cardiovascular (CVD)events and all-cause mortality. Results: Median follow-up was 4.8 years [Interquartile range: 4.1, 5.3]for CVD event and 77 patients suffered a CVD event. Dyspnea was significantly associated with CVD event: Hazard ratio (HR): 1.58 (95% confidence interval: 1.01–2.48), p = 0.04. Stratifying by evidence of echocardiographic substrate revealed high risk individuals: CVD event: 0.71 (0.35–1.46), p = NS in patients with dyspnea and no echocardiographic substrate and 2.85 (1.74–4.67), p < 0.001 in patients with dyspnea with echocardiographic substrate). This pattern was similar in multivariable analyses. Also, C-statistics improved from 0.66 (0.60–0.72)to 0.69 (0.63–0.75), p < 0.001 and net reclassification index was 27.5%(5.0–50.0), p = 0.01 for CVD event. The results were similar for all-cause mortality except dyspnea was only a borderline significant predictor. Conclusion: In patients with type 2 diabetes complaining of dyspnea, identifying an echocardiographic substrate - thus indicating patients with HF - accurately stratifies patients with increased risk of CV events and all-cause mortality.

AIMS/HYPOTHESIS: Cardiovascular disease is the most common comorbidity in type 1 diabetes. However, current guidelines do not include routine assessment of myocardial function. We investigated whether echocardiography provides incremental prognostic information in individuals with type 1 diabetes without known heart disease.METHODS: A prospective cohort of individuals with type 1 diabetes without known heart disease was recruited from the outpatient clinic. Follow-up was performed through Danish national registers. The association of echocardiography with major adverse cardiovascular events (MACE) and the incremental prognostic value when added to the clinical Steno T1D Risk Engine were examined.RESULTS: A total of 1093 individuals were included: median (interquartile range) age 50.2 (39.2-60.3) years and HbA1c 65 (56-74) mmol/mol; 53% men; and mean (SD) BMI 25.5 (3.9) kg/m2 and diabetes duration 25.8 (14.6) years. During 7.5 years of follow-up, 145 (13.3%) experienced MACE. Echocardiography significantly and independently predicted MACE: left ventricular ejection fraction (LVEF) <45% (n = 18) vs ≥45% (n = 1075), HR (95% CI) 3.93 (1.91, 8.08), p < 0.001; impaired global longitudinal strain (GLS), 1.65 (1.17, 2.34) (n = 263), p = 0.005; diastolic mitral early velocity (E)/early diastolic tissue Doppler velocity (e') <8 (n = 723) vs E/e' 8-12 (n = 285), 1.59 (1.04, 2.42), p = 0.031; and E/e' <8 vs E/e' ≥12 (n = 85), 2.30 (1.33, 3.97), p = 0.003. In individuals with preserved LVEF (n = 1075), estimates for impaired GLS were 1.49 (1.04, 2.15), p = 0.032; E/e' <8 vs E/e' 8-12, 1.61 (1.04, 2.49), p = 0.033; and E/e' <8 vs E/e' ≥12, 2.49 (1.41, 4.37), p = 0.001. Adding echocardiographic variables to the Steno T1D Risk Engine significantly improved risk prediction: Harrell's C statistic, 0.791 (0.757, 0.824) vs 0.780 (0.746, 0.815), p = 0.027; and net reclassification index, 52%, p < 0.001.CONCLUSIONS/INTERPRETATION: In individua

The prevalence of heart failure (HF) in patients with type 2 diabetes (T2DM) is debatable and no data exist concerning the diagnostic value of mid-regional pro-atrial natriuretic peptide (MR-proANP). We aimed to identify HF prevalence and evaluate the diagnostic value of MR-proANP in outpatients followed in two specialized diabetes clinics. HF was pre-defined as HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). The prevalence of HFrEF and HFpEF was 2.4% and 17.5%, respectively. An MR-proANP <60 pmol/L ruled out HFrEF in the total population (n = 806) and in patients reporting dyspnea (n = 311) with a sensitivity of 94.7% and 87.5%, a negative predictive value of 99.7% and 99.0%, a specificity of 39.5% and 33.0%, and a positive predictive value of 3.6% and 3.3%, respectively. In a multivariable model including age, sex, T2DM duration, albuminuria, uncontrolled systolic blood pressure, abnormal electrocardiogram and ischaemic heart disease for diagnosis of HF in patients reporting dyspnea, adding MR-proANP increased the area under the curve from 0.69 to 0.78 (P < 0.001). In conclusion, HFrEF was rare among outpatients with T2DM. MR-proANP rules out HFrEF and contributes independent information relevant to diagnosis of HF in patients reporting dyspnea.

The aim of this study was to investigate the association of epicardial (EAT) and pericardial (PAT) adipose tissues with myocardial function in type 2 diabetes (T2D). EAT and PAT were measured by ultrasound in 770 patients with T2D and 234 age- and sex-matched non-diabetic controls. Echocardiography was performed, including tissue Doppler imaging and 2D speckle tracking. Patients with T2D versus controls had increased EAT (4.6 ± 1.8 mm vs. 3.4 ± 1.2 mm, P < 0.0001) and PAT (6.3 ± 2.8 mm vs. 5.3 ± 2.4 mm, P < 0.0001). EAT and PAT were associated with structural cardiac measures both in T2D patients and controls (all P < 0.043), but only in T2D patients with functional measures: PAT was associated with impaired global longitudinal strain [beta coefficient (SE)] [0.11% (0.04), P = 0.002], while EAT was associated with reduced diastolic function by lateral early diastolic myocardial velocity (e’lat) [−0.31 (0.05) cm/s, P = 0.001], mitral inflow velocities: peak early (E)/peak atrial (A) ratio [−0.02 (0.01), P = 0.001] and lateral E/e’lat [0.36 (0.10), P < 0.001]. However, no interaction was found between diabetes status and PAT (P = 0.75) or EAT (P = 0.45). Adipose tissue in intimate relation to the myocardium is higher in patients with T2D versus controls and is associated with functional myocardial measures in T2D.

Aims: Echocardiography is suggested in the diagnostic work-up of patients with Type 2 diabetes (T2D). We investigated which echocardiographic parameters that best predicted cardiovascular disease (CVD) and whether this was persistent in both genders in a large cohort of outpatients with T2D.Methods and results: We performed comprehensive echocardiography in 933 patients with T2D followed at specialized out-patients clinics in Copenhagen, Denmark. Follow-up was performed using national registries and included admission with future CVD events and non-CVD death as competing risk. Median follow-up was 4.8 years and 138 CVD events occurred. In univariable and multivariable analyses, a wide range of structural, diastolic, and systolic measurements predicted CVD including mean E/e' [hazard ratio (HR) 1.06, 95% confidence interval: (1.03-1.10), P < 0.001, C-statistics 0.74 (0.70-0.78)] and global longitudinal strain (GLS) [1.10 (1.01-1.20), P = 0.03, C-statistics 0.73 (0.69-0.77)]. However, this was modified by gender. In men, mean E/e' remained the strongest predictor in multivariable analyses and performed best measured by highest C-statistics [HR 1.15, 95% confidence interval: (1.08-1.21), P < 0.001, C-statistics 0.75 (0.71-0.80)] whereas in women this was GLS [1.39 (1.14-1.70), P = 0.001, C-statistics 0.79 (0.70-0.87)]. These findings persisted when excluding patients with known heart disease and when regarding all-cause mortality as a competing risk.Conclusion: A range of echocardiographic parameters predicted CVD in patients with Type 2 diabetes, however, in multivariable analyses, mean E/e' was the strongest predictor and had the highest model performance. Importantly, this study identifies a hitherto undescribed gender interaction as mean E/e' performed best in men, whereas in women this was GLS.

Background: Cardiac fat is a cardiovascular biomarker but its importance in patients with type 2 diabetes is not clear. The aim was to evaluate the predictive potential of epicardial (EAT), pericardial (PAT) and total cardiac (CAT) fat in type 2 diabetes and elucidate sex differences. Methods: EAT and PAT were measured by echocardiography in 1030 patients with type 2 diabetes. Follow-up was performed through national registries. The end-point was the composite of incident cardiovascular disease (CVD) and all-cause mortality. Analyses were unadjusted (model 1), adjusted for age and sex (model 2), plus systolic blood pressure, body mass index (BMI), low-density lipoprotein (LDL), smoking, diabetes duration and glycated hemoglobin (HbA1c) (model 3). Results: Median follow-up was 4.7 years and 248 patients (191 men vs. 57 women) experienced the composite end-point. Patients with high EAT (> median level) had increased risk of the composite end-point in model 1 [Hazard ratio (HR): 1.46 (1.13; 1.88), p = 0.004], model 2 [HR: 1.31 (1.01; 1.69), p = 0.038], and borderline in model 3 [HR: 1.32 (0.99; 1.77), p = 0.058]. For men, but not women, high EAT was associated with a 41% increased risk of CVD and mortality in model 3 (p = 0.041). Net reclassification index improved when high EAT was added to model 3 (19.6%, p = 0.035). PAT or CAT were not associated with the end-point. Conclusion: High levels of EAT were associated with the composite of incident CVD and mortality in patients with type 2 diabetes, particularly in men, after adjusting for CVD risk factors. EAT modestly improved risk prediction over CVD risk factors.

Aims: Two-dimensional speckle tracking echocardiography (2DSTE) detects early signs of left ventricular dysfunction; however, it is unknown whether layer-specific global longitudinal strain (GLS) has incremental value in diagnosis of patients with reversible ischemia assessed by single photon emission computed tomography (SPECT). Methods and Results: Eighty patients with stable angina pectoris (SAP), normal left ventricular ejection fraction (LVEF), and no history of ischemic heart disease were retrospectively identified to have been examined by 2DSTE, SPECT, and coronary angiography (CAG). Patients with a normal SPECT constituted the control group, and patients with a positive SPECT were divided into patients with or without (true- or false- positive SPECT) significant stenosis assessed by CAG. GLS was measured for two myocardial layers (endocardial and epicardial) and as well as mid-myocardial GLS. Patients with reversible ischemia had significantly lower GLS compared to the control group (GLSE ndocardial: −19.0 ± 4.4% vs −21.4 ± 3.7%, P =.011; GLSE picardial: −14.3 ± 2.9% vs −16.3 ± 2.9%, P =.004); GLSM id-myocardial: −16.5 ± 3.6% vs −18.6 ± 3.2%, P =.006. This difference was even more evident in patients with a true-positive SPECT (GLSE ndocardial: −18.0 ± 4.4% vs −21.4 ± 3.7%, P <.001; GLSE picardial: −13.6 ± 3.0% vs −16.3 ± 2.9%, P <.001); GLSM id-myocardial: −15.6 ± 3.6% vs −18.6 ± 3.2%, P <.001. Notably, no significant differences existed in patients with a false-positive SPECT. GLSE picardial was the only independent predictor of coronary artery disease. In conclusion: In patients with SAP and preserved LVEF, layer-specific GLS at rest identifies patients with reversible ischemia. This seems to be evident only in patients with a true-positive SPECT, thus, 2DSTE at rest might improve the diagnos

In patients with type 2 diabetes, both supervised exercise and treatment with the glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1RA) liraglutide may improve cardiac function. We evaluated cardiac function before and after 16 weeks of treatment with the GLP-1RA liraglutide or placebo, combined with supervised exercise, in 33 dysregulated patients with type 2 diabetes on diet and/or metformin. Early diastolic myocardial tissue velocity was improved by exercise in the placebo group (mean ± standard deviation [s.d.] -7.1 ± 1.6 to -7.7 ± 1.8 cm/s, P = .01), but not in the liraglutide group (-7.1 ± 1.4 to -7.0 ± 1.4 cm/s, P = .60; between groups, P = .02). Similarly, the mean ± s.d. ratio of early and atrial mitral annular tissue velocities improved in the placebo group (1.0 ± 0.4 to 1.2 ± 0.4, P = .003), but not in the liraglutide group (1.0 ± 0.3 to 1.0 ± 0.3, P = .87; between groups, P = .03). We found no significant differences in heart rate, left ventricular (LV) structure or function within or between the groups. In conclusion, the addition of liraglutide to exercise in sedentary patients with dysregulated type 2 diabetes may blunt the suggested beneficial effect of exercise on LV diastolic function.

BACKGROUND: Contemporary treatment of type 2 diabetes (T2D) has improved patient outcome and may also have affected myocardial structure and function. We aimed to describe the effect of T2D and T2D duration on cardiac structure and function in a large outpatient population.METHODS: We performed comprehensive echocardiography on a representative sample of 1004 persons including a representative sample of 770 patients with T2D without known heart disease and 234 age- and sex-matched controls.RESULTS: T2D was associated with increased left ventricular (LV) wall thicknesses and decreased LV internal diameter and the changes were pronounced with increasing diabetes duration (P<0.01 for all) but not with increased LV mass (P=0.74). It was also significantly associated with the prevalence of diastolic dysfunction (16.5% vs. 4.0%; P<0.001), with indices of LV relaxation and elevated filling pressures expressed as e'septal (mean: 6.9 (SD: 1.9) cm/s vs. 7.5 (2.4); P<0.001) and E/e'septal (median: 10.8 (interquartile range (IQR): 9.1-13.3) vs. 9.1 (7.2-11.1); P<0.001) and global longitudinal strain (mean: -14.1 (SD: 2.4) vs. -15.0 (2.0), P<0.001) but not with LV ejection fraction (median: 60.8 (IQR: 56.5-65.1) vs. 62.1 (57.9-65.4), P=0.28). With the exception of global longitudinal strain, this was pronounced with increasing diabetes duration for all measures including increasing diastolic dysfunction (<10years: 10.8%, 10-20years: 18.5%, >20years: 24.8%; P<0.001). The increased risk of diastolic dysfunction persisted after multivariable adjustment (P=0.013).CONCLUSIONS: In patients with T2D, LV structural and functional alterations persist and are accentuated with increasing diabetes duration despite reductions in overall risk of cardiovascular disease in this patient population.

Several clinical prediction score models have been investigated for predicting mortality in patients with cerebral infarction. However, none of these include echocardiographic measures. Our objective was to evaluate the prognostic value of tissue Doppler imaging (TDI) of the myocardium in patients with cerebral infarction. Two hundred forty-four patients with cerebral infarction and subsequent echocardiographic examination in sinus rhythm were identified. Using TDI in three apical projections, longitudinal mitral annular velocities were obtained in six segments. Cox regression models, C-statistics and reclassification analysis were performed for global and segmental e'. During a median follow-up of 3 years 42 patients died. Patients who died had significantly impaired systolic and diastolic function (determined by LVEF and E/e'). The risk of dying increased with decreasing global e', being approximately 13 times higher for patients in the lowest tertile compared to patients in the highest tertile (HR 13.4 [3.2;56.3], p < 0.001). Patients with significantly impaired global e' showed increased mortality after multivariable adjustment for: LVEF, E/e', age, gender, heart failure, chronic obstructive pulmonary disease, prior cerebral infarction, ischemic heart disease, cancer, hypertension, hypercholesterolemia, carotid stenosis, mitral regurgitation, liver disease and thromboembolisms (HR 1.9 [1.1;3.2]), per 1 cm/s decrease, p < 0.05). Similar pattern was seen in segmental analyses of the e'. In contrast to e', no conventional echocardiographic parameters remained independent predictors of mortality after multivariable adjustment. Diastolic myocardial dysfunction determined as e' by TDI is a significant predictor of mortality in patients with cerebral infarction. Applying this parameter can aid the prognostic assessment after cerebral infarction.

BACKGROUND: Though the electrocardiogram(ECG) and plasma pro-brain-natriuretic-peptide (pro-BNP) are widely used markers of subclinical cardiac injury and can be used to predict future cardiovascular disease(CVD), they could merely be markers of the same underlying pathology. We aimed to determine if ECG changes and pro-BNP are independent predictors of CVD and if the combination improves risk prediction in persons without known heart disease.METHODS: Pro-BNP and ECG were obtained on 5454 persons without known heart disease from the 4th round of the Copenhagen City Heart Study, a prospective cohort study. Median follow-up was 10.4 years. High pro-BNP was defined as above 90th percentile of age and sex adjusted levels. The end-points were all-cause mortality and the combination of admission with ischemic heart disease, heart failure or CVD death.RESULTS: ECG changes were present in 907 persons and were associated with high levels of pro-BNP. In a fully adjusted model both high pro-BNP and ECG changes remained significant predictors: all-cause mortality(high pro-BNP, no ECG changes: HR: 1.43(1.12-1.82);P=0.005, low pro-BNP, ECG changes: HR: 1.22(1.05-1.42);P=0.009, and both high pro-BNP and ECG changes: HR: 1.99(1.54-2.59);P<0.001), CVD event(high pro-BNP, no ECG changes: HR: 1.94(1.45-2.58);P<0.001, low pro-BNP, ECG changes: HR: 1.55(1.29-1.87);P<0.001, and both high pro-BNP and ECG changes: HR: 3.86(2.94-5.08);P<0.001). Adding the combination of pro-BNP and ECG changes to a fully adjusted model correctly reclassified 33.9%(26.5-41.3);P<0.001 on the continuous net reclassification scale for all-cause mortality and 49.7%(41.1-58.4);P<0.001 for CVD event.CONCLUSION: Combining ECG changes and pro-BNP improves risk prediction in persons without known heart disease.

AIMS/HYPOTHESIS: Heart failure is one of the leading causes of mortality in type 1 diabetes. Early identification is vitally important. We sought to determine the prevalence and clinical characteristics associated with subclinical impaired systolic and diastolic function in type 1 diabetes patients without known heart disease.METHODS: In this cross-sectional examination of 1,093 type 1 diabetes patients without known heart disease, randomly selected from the Steno Diabetes Center, complete clinical and echocardiographic examinations were performed and analysed in uni- and multivariable regression models.RESULTS: The mean (SD) age was 49.6 (15) years, 53% of participants were men, and the mean duration of diabetes was 25.5 (15) years. Overall, 15.5% (n = 169) of participants had grossly abnormal systolic or diastolic function, including 1.7% with left ventricular ejection fraction (LVEF) < 45% and 14.4% with evidence of long-standing diastolic dysfunction. In univariable models, clinical characteristics associated with abnormal myocardial function were: age (per 10 years), OR (95% CI) 2.1 (1.8, 2.4); diabetes duration (per 10 years), 1.7 (1.4, 1.9); systolic BP ≥ 140 mmHg, 2.7 (1.9, 3.8); diastolic BP ≥ 90 mmHg, 1.8 (1.0, 3.1); estimated (e)GFR < 60 ml min(-1) 1.73 m(-2), 3.8 (2.5, 5.9); microalbuminuria, 2.0 (1.3, 3.0); macroalbuminuria, 5.9 (3.8, 9.3); proliferative retinopathy, 3.6 (2.3, 5.8); blindness, 10.1 (3.2, 31.6); and peripheral neuropathy, 3.8 (2.7, 5.3). In multivariable models only age (2.1 [1.7, 2.5]), female sex, (1.9 [1.2, 2.8]) and macroalbuminuria (5.2 [2.9, 10.3]) remained significantly associated with subclinical grossly abnormal myocardial function.CONCLUSIONS/INTERPRETATION: Subclinical myocardial dysfunction is a common finding in type 1 diabetes patients without known heart disease. Type 1 diabetes patients with albuminuria are at greatly increased risk of having subclinical abnormal myocardial function compared

AIMS/HYPOTHESIS: Heart failure is one of the leading causes of mortality in type 1 diabetes. Early identification is vitally important. We sought to determine the prevalence and clinical characteristics associated with subclinical impaired systolic and diastolic function in type 1 diabetes patients without known heart disease.METHODS: In this cross-sectional examination of 1,093 type 1 diabetes patients without known heart disease, randomly selected from the Steno Diabetes Center, complete clinical and echocardiographic examinations were performed and analysed in uni- and multivariable regression models.RESULTS: The mean (SD) age was 49.6 (15) years, 53% of participants were men, and the mean duration of diabetes was 25.5 (15) years. Overall, 15.5% (n = 169) of participants had grossly abnormal systolic or diastolic function, including 1.7% with left ventricular ejection fraction (LVEF) < 45% and 14.4% with evidence of long-standing diastolic dysfunction. In univariable models, clinical characteristics associated with abnormal myocardial function were: age (per 10 years), OR (95% CI) 2.1 (1.8, 2.4); diabetes duration (per 10 years), 1.7 (1.4, 1.9); systolic BP ≥ 140 mmHg, 2.7 (1.9, 3.8); diastolic BP ≥ 90 mmHg, 1.8 (1.0, 3.1); estimated (e)GFR < 60 ml min(-1) 1.73 m(-2), 3.8 (2.5, 5.9); microalbuminuria, 2.0 (1.3, 3.0); macroalbuminuria, 5.9 (3.8, 9.3); proliferative retinopathy, 3.6 (2.3, 5.8); blindness, 10.1 (3.2, 31.6); and peripheral neuropathy, 3.8 (2.7, 5.3). In multivariable models only age (2.1 [1.7, 2.5]), female sex, (1.9 [1.2, 2.8]) and macroalbuminuria (5.2 [2.9, 10.3]) remained significantly associated with subclinical grossly abnormal myocardial function.CONCLUSIONS/INTERPRETATION: Subclinical myocardial dysfunction is a common finding in type 1 diabetes patients without known heart disease. Type 1 diabetes patients with albuminuria are at greatly increased risk of having subclinical abnormal myocardial function compared