scholarly journals Apolipoprotein C‐III predicts cardiovascular events and mortality in individuals with type 1 diabetes and albuminuria

2021 ◽  
Author(s):  
Fanny Jansson Sigfrids ◽  
Lars Stechemesser ◽  
Emma H. Dahlström ◽  
Carol M. Forsblom ◽  
Valma Harjutsalo ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Cardiovascular Events ◽  
Apolipoprotein C

Serum Apolipoprotein C-III and Cardiovascular Events in Type 1 Diabetes

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 188-LB
Author(s):  
ARPITA BASU ◽  
IONUT BEBU ◽  
ALICIA JENKINS ◽  
JULIE STONER ◽  
YING ZHANG ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Cardiovascular Events ◽  
Apolipoprotein C

Insulin resistance and risk of vascular events, interventions and mortality in type 1 diabetes

2021 ◽  
Author(s):  
Marga A.g. Helmink ◽  
Marieke de Vries ◽  
Frank L.j. Visseren ◽  
Wendela L. de Ranitz ◽  
Harold W. de Valk ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Cardiovascular Disease ◽  
Type 1 Diabetes ◽  
Insulin Sensitivity ◽  
Lower Risk ◽  
Cardiovascular Events ◽  
Additional Risk Factor ◽  
Vascular Events ◽  
All Cause Mortality

Objective: To identify determinants associated with insulin resistance and to assess the association between insulin resistance and cardiovascular events, vascular interventions and mortality in people with type 1 diabetes at high risk of cardiovascular disease . Design: Prospective cohort study. Methods: 195 people with type 1 diabetes from the Secondary Manifestations of ARTerial disease (SMART) cohort were included. Insulin resistance was quantified by the estimated glucose disposal rate (eGDR) with higher eGDR levels indicating higher insulin sensitivity (i.e. lower eGDR levels indicating higher insulin resistance). Linear regression models were used to evaluate determinants associated with eGDR. The effect of eGDR on cardiovascular events, cardiovascular events or vascular interventions (combined endpoint) and on all-cause mortality was analysed using Cox proportional hazards models adjusted for confounders. Results: In 195 individuals (median follow-up 12.9 years, IQR 6.7-17.0), a total of 25 cardiovascular events, 26 vascular interventions and 27 deaths were observed. High eGDR as a marker for preserved insulin sensitivity was independently associated with a lower risk of cardiovascular events (HR 0.75; 95%CI 0.61-0.91), a lower risk of cardiovascular events and vascular interventions (HR 0.74; 95%CI 0.63-0.87), and a lower risk of all-cause mortality (HR 0.81; 95%CI 0.67-0.98). Conclusions: Insulin resistance as measured by eGDR is an additional risk factor for cardiovascular disease in individuals with type 1 diabetes. Modification of insulin resistance by lifestyle interventions or pharmacological treatment could be a viable therapeutic target to lower the risk of cardiovascular disease.

scholarly journals Early Trajectory of Estimated Glomerular Filtration Rate and Long-term Advanced Kidney and Cardiovascular Complications in Type 1 Diabetes

Diabetes Care ◽  
2022 ◽  
Author(s):  
Bruce A. Perkins ◽  
Ionut Bebu ◽  
Xiaoyu Gao ◽  
Amy B. Karger ◽  
Irl B. Hirsch ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Glomerular Filtration Rate ◽  
Cardiovascular Events ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Cardiovascular Complications ◽  
Egfr Slope

OBJECTIVE Rapid loss of estimated glomerular filtration rate (eGFR) within its normal range has been proposed as a strong predictor of future kidney disease. We investigated this association of eGFR slope early in the course of type 1 diabetes with long-term incidence of kidney and cardiovascular complications. RESEARCH DESIGN AND METHODS The annual percentage change in eGFR (slope) was calculated during the Diabetes Control and Complications Trial (DCCT) for each of 1,441 participants over a mean of 6.5 years and dichotomized by the presence or absence of early rapid eGFR loss (slope ≤−3% per year) as the exposure of interest. Outcomes were incident reduced eGFR (eGFR <60 mL/min/1.73 m2), composite cardiovascular events, or major adverse cardiovascular events (MACE) during the subsequent 24 years post-DCCT closeout follow-up. RESULTS At DCCT closeout (the baseline for this analysis), diabetes duration was 12 ± 4.8 years, most participants (85.9%) had normoalbuminuria, mean eGFR was 117.0 ± 13.4 mL/min/1.73 m2, and 149 (10.4%) had experienced early rapid eGFR loss over the preceding trial phase. Over the 24-year subsequent follow-up, there were 187 reduced eGFR (6.3 per 1,000 person-years) and 113 MACE (3.6 per 1,000 person-years) events. Early rapid eGFR loss was associated with risk of reduced eGFR (hazard ratio [HR] 1.81, 95% CI 1.18–2.79, P = 0.0064), but not after adjustment for baseline eGFR level (HR 0.94, 95% CI 0.53–1.66, P = 0.84). There was no association with composite cardiovascular events or MACE. CONCLUSIONS In people with type 1 diabetes primarily with normal eGFR and normoalbuminuria, the preceding slope of eGFR confers no additional association with kidney or cardiovascular outcomes beyond knowledge of an individual’s current level.

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

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.

Circulating Tissue Factor Procoagulant Activity (TF-PCA) Is Elevated in Type 1 Diabetes Mellitus: Differential Regulation of TF-PCA in Type 1 and Type 2 Diabetes

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 540-540
Author(s):  
Anamika Singh ◽  
Guenther Boden ◽  
Carol Homko ◽  
Jay Gunawardana ◽  
A. Koneti Rao
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Tissue Factor ◽  
Plasma Glucose ◽  
Cardiovascular Events ◽  
Plasma Adiponectin ◽  
Control Subjects

Abstract Abstract 540 Background: Type 1 diabetes mellitus (T1DM) is a hypercoagulable state associated with increased acute cardiovascular events. Potential risk factors for this include alterations in coagulation and fibrinolytic systems. Tissue factor (TF) is the principal initiator of blood coagulation. Several studies show that there is a circulating pool of TF in blood, which is thrombogenic, and elevated in thrombotic states. We have shown (J Clin Endo Metab 2007, 92:4352-8) that circulating TF procoagulant activity (TF-PCA) is elevated in patients with Type 2 DM (T2DM) and increases further with acute combined hyperglycemia-hyperinsulinemia and selective hyperinsulinemia. There is currently no information on circulating TF-PCA levels and TF responses to hyperglycemia and/or hyperinsulinemia in patients with T1DM who are at comparable risk for cardiovascular events as T2DM patients. Objective: To investigate circulating TF-PCA and other coagulation factors under basal conditions and in response to acute selective hyperglycemia, selective hyperinsulinemia and combined hyperglycemia and hyperinsulinemia in T1DM. Methods: Three study protocols were used: 1) acute correction of hyperglycemia (with IV insulin) followed by 24 h of hyperglycemia, 2) 24 h of selective hyperinsulinemia and 3) 24 h of combined hyperinsulinemia and hyperglycemia. Studies were performed in 9 T1DM patients and 7 non-diabetic subjects. T1DM patients were on a basal/bolus insulin regimen (insulin glargine, 15–70 units at night) or Novolog 70/30 mix twice daily (45-50 units). Circulating membrane bound TF-PCA was measured in whole blood lysates by a two-stage clotting assay (Key et al, Blood; 1998:91). Results: Basal TF-PCA (64.7 ± 6.0 vs. 24.6 ± 1.2 U/ml, p < 0.001) and plasma factor VIIa (104 ± 24 vs. 38 ± 8 mU/ml, p < 0.03), the activated form of factor VII, were higher in T1DM (n=9) than in non-diabetic controls (n= 7) indicating a chronic procoagulant state. Plasma FVIIc, FVIII, thrombin-antithrombin complexes (TAT) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were not significantly different between patients and controls. When control subjects and T1DM patients were combined, HbA1C correlated with TF-PCA (r=0.71, p=0.0001, n=23). Plasma adiponectin was elevated in T1DM patients compared to control subjects (12.4 ± 1.9 vs 6.7 ± 2.0 μg/ml, p < 0.05). Acutely normalizing hyperglycemia in T1DM patients over 3–15 h did not decrease TF-PCA. There were also no changes in plasma FVIIc and FVIII. To explore effects of acutely raising plasma glucose, glucose was raised from 103 ± 8 to ∼ 300 mg/dl by infusion of 20% dextrose and maintained for 24 hours. Insulin concentrations were kept at basal concentrations (6 and 13 μU/ml) by IV infusion. In our previous studies in non-diabetic subjects (Diabetes 2006, 55,202-8) and in T2DM patients (J Clin Endo Metab 2007, 92,4352-8), raising glucose and insulin together produced a marked increase in circulating TF-PCA. We therefore raised glucose to ∼ 250 mg/dl and insulin to ∼ 100 μU/ml together in 8 T1DM patients. Raising glucose levels alone or in combination with insulin decreased circulating TF-PCA by 26% (p < 0.02) and 37% (p < 0.01), respectively, which is in striking contrast to the elevations noted in non-diabetic controls and T2DM patients. To explore effects of selective hyperinsulinemia, plasma insulin levels were raised in 3 T1DM patients by IV infusion of regular insulin from 15 ± 0.2 to ∼ 75 μU/ml and maintained for 24 hours while plasma glucose was kept at ∼ 100 mg by infusion of 20% dextrose. Again, in contrast to our studies in T2DM patients and healthy subjects we found no increase in TF-PCA Conclusions: Circulating TF-PCA and FVIIa levels are elevated in T1DM patients indicating a potential prothrombotic state. The studies on acutely induced hyperinsulinemia and hyperglycemia indicate that the regulation of TF expression is different in T1DM and T2DM. This may be due to multiple mechanisms, including a differential effect of insulin on monocytes TF expression in T1DM and T2DM, and due to differences in plasma adiponectin, which has been shown to inhibit TF expression and is elevated in T1DM. Additional studies are needed to obtain insights into the mechanisms regulating the differential expression of TF in the two forms of diabetes. Disclosures: No relevant conflicts of interest to declare.

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