| 1. |
- Fortin, Elena, et al.
(author)
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Empagliflozin improves insulin sensitivity in patients with recent acute coronary syndrome and newly detected dysglycaemia : Experiences from the randomized, controlled SOCOGAMI trial
- 2023
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In: Cardiovascular Diabetology. - : Springer Nature. - 1475-2840. ; 22:1, s. 208-
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Journal article (peer-reviewed)abstract
- BACKGROUND: Empagliflozin reduces the risk of cardiovascular disease (CVD) in patients with type 2 diabetes (T2DM) and high cardiovascular risk via mechanisms which have not been fully explained. The mechanisms of such benefit have not been fully understood, and whether empagliflozin can be safely administered as first-line treatment in patients with CVD at the initial stages of glycaemic perturbations remains to be established. We investigated the effects of empagliflozin on insulin resistance, insulin sensitivity and β-cell function indexes in patients with a recent acute coronary event and newly detected dysglycaemia, i.e., impaired glucose tolerance (IGT) or T2DM. METHODS: Forty-two patients (mean age 67.5 years, 19% females) with a recent myocardial infarction (n = 36) or unstable angina (n = 6) and newly detected dysglycaemia were randomized to either empagliflozin 25 mg daily (n = 20) or placebo (n = 22). Patients were investigated with stress-perfusion cardiac magnetic resonance imaging before randomization, 7 months after the start of study drug and 3 months following its cessation. Indexes of insulin resistance, sensitivity and β-cell function were calculated based on glucose and insulin values from 2-hour oral glucose tolerance tests (OGTT) and fasting C-peptide. The differences in glucose, insulin, C-peptide, mannose levels and indexes between the two groups were computed by repeated measures ANOVA including an interaction term between the treatment allocation and the time of visit. RESULTS: After 7 months, empagliflozin significantly decreased glucose and insulin values during the OGTT, whereas C-peptide, mannose and HbA1c did not differ. Empagliflozin significantly improved insulin sensitivity indexes but did not impact insulin resistance and β-cell function. After cessation of the drug, all indexes returned to initial levels. Insulin sensitivity indexes were inversely correlated with left ventricular mass at baseline. CONCLUSIONS: Empagliflozin improved insulin sensitivity indexes in patients with a recent coronary event and drug naïve dysglycaemia. These findings support the safe use of empagliflozin as first-line glucose-lowering treatment in patients at very high cardiovascular risk with newly diagnosed dysglycaemia. TRIAL REGISTRATION NUMBER: EudraCT number 2015-004571-73.
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| 2. |
- Fortin, Elena, et al.
(author)
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Plasma mannose as a novel marker of myocardial infarction across different glycaemic states : A case control study
- 2022
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In: Cardiovascular Diabetology. - : Springer Nature. - 1475-2840. ; 21:1
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Journal article (peer-reviewed)abstract
- Background Plasma mannose, an emerging novel biomarker of insulin resistance, is associated with both diabetes mellitus and coronary atherosclerosis, but the relationship between mannose concentrations and myocardial infarction (MI) across different glycaemic states remains to be elucidated. The aim of this study was to investigate the independent association between mannose and a first MI in a group of subjects characterized according to their glycaemic state. Methods Fasting plasma mannose concentrations were analysed in 777 patients 6-10 weeks after a first myocardial infarction and in 770 matched controls by means of high-performance liquid chromatography coupled to tandem mass spectrometry. Participants without known diabetes mellitus were categorized by an oral glucose tolerance test (OGTT) as having normal glucose tolerance (NGT, n = 1045), impaired glucose tolerance (IGT, n = 246) or newly detected type 2 diabetes (T2DM, n = 112). The association between mannose and MI was investigated across these glycaemic states by logistic regression. Results Mannose levels increased across the glycaemic states (p < 0.0001) and were significantly associated with a first MI in the whole study population (odds ratio, OR: 2.2; 95% CI 1.4 to - 3.5). Considering the different subgroups separately, the association persisted only in subjects with NGT (adjusted OR: 2.0; 95% CI 1.2-3.6), but not in subgroups with glucose perturbations (adjusted OR: 1.8, 95% CI 0.8-3.7). Conclusions Mannose concentrations increased across worsening levels of glucose perturbations but were independently associated with a first MI only in NGT individuals. Thus, mannose might be a novel, independent risk marker for MI, possibly targeted for the early management of previously unidentified patients at high cardiovascular risk.
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| 3. |
- Lundin, Magnus, et al.
(author)
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SOdium-glucose CO-transporter inhibition in patients with newly detected Glucose Abnormalities and a recent Myocardial Infarction (SOCOGAMI)
- 2022
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In: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227 .- 1872-8227. ; 193, s. 110141-
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Journal article (peer-reviewed)abstract
- Aims/hypothesis: Established dysglycaemia (impaired glucose tolerance [IGT] or type 2 diabetes [T2DM]) is a risk factor for further cardiovascular events in patients with coronary artery disease. Sodium-glucose cotransporter 2 inhibitors reduce this risk. The aim of the present investigation was to test the hypothesis that empagliflozin exerts beneficial effects on myocardial function in patients with a recent acute coronary syndrome and newly detected dysglycaemia. Methods: Forty-two patients (mean age 67.5 years, 81 % male) with recent myocardial infarction (n = 36) or unstable angina (n = 6) and newly detected IGT (n = 27) or T2DM (n = 15) were randomised to 25 mg of empagliflozin daily (n = 20) or placebo (n = 22) on top of ongoing therapy. They were investigated with oral glucose tolerance tests, stress-perfusion cardiac magnetic resonance imaging (CMR) and echocardiography at three occasions: before randomisation, after seven months on study drug and three months following cessation of such drug. Primary outcome was a change in left ventricular (LV) end-diastolic volume (LVEDV) and secondary outcomes were a change in a) systolic and diastolic LV function; b) coronary flow reserve; c) myocardial extracellular volume (ECV) in non-infarcted myocardium; d) aortic pulse wave velocity. Results: Empagliflozin induced a significant decrease in fasting and post load glucose (p < 0.05) and body weight (p < 0.01). Empagliflozin did not influence LVEDV, LV systolic or mass indexes, coronary flow reserve, ECV or aortic pulse wave velocity. Echocardiographic indices of LV diastolic function (E/e' and mitral E/A ratio) were not influenced. No safety concerns were identified. Conclusions/interpretation: Empagliflozin had predicted effects on the dysglycaemia but did not influence vari-ables expressing LV function, coronary flow reserve and ECV. An explanation may be that the LV function of the patients was within the normal range.
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| 4. |
- Meziani, Sara, et al.
(author)
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Mannose-binding lectin does not explain the dismal prognosis after an acute coronary event in dysglycaemic patients : A report from the GAMI cohort
- 2022
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In: Cardiovascular Diabetology. - : Springer Nature. - 1475-2840. ; 21:1
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Journal article (peer-reviewed)abstract
- Background Mannose binding lectin (MBL) has been suggested to be associated with an impaired cardiovascular prognosis in dysglycaemic conditions, but results are still contrasting. Our aims are (i) to examine whether MBL levels differ between patients with an acute myocardial infarction (MI) and healthy controls and between subgroups with different glucose tolerance status, and (ii) to investigate the relation between MBL and future cardiovascular events. Methods MBL levels were assessed at discharge and after 3 months in 161 AMI patients without any previously known glucose perturbations and in 183 age- and gender-matched controls from the Glucose metabolism in patients with Acute Myocardial Infarction (GAMI) study. Participants were classified as having dysglycaemia, i.e. type 2 diabetes or impaired glucose tolerance, or not by an oral glucose tolerance test. The primary outcome was a composite of cardiovascular events comprising cardiovascular death, AMI, stroke or severe heart failure during 11 years of follow-up. Total and cardiovascular mortality served as secondary outcomes. Results At hospital discharge patients had higher MBL levels (median 1246 mu g/L) than three months later (median 575 mu g/L; p < 0.01), the latter did not significantly differ from those in the controls (801 mu g/L; p = 0.47). MBL levels were not affected by dysglycaemia either in patients or controls. Independent of glycaemic state, increasing MBL levels did not predict any of the studied outcomes in patients. In unadjusted analyses increasing MBL levels predicted cardiovascular events (hazard ratio HR: 1.67, 95% confidence interval CI 1.06-2.64) and total mortality (HR 1.53, 95% CI 1.12-2.10) in the control group. However, this did not remain in adjusted analyses. Conclusions Patients had higher MBL levels than controls during the hospital phase of AMI, supporting the assumption that elevated MBL reflects acute stress. MBL was not found to be independently associated with cardiovascular prognosis in patients with AMI regardless of glucose state.
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| 5. |
- Riccio, Alessia, et al.
(author)
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Sex differences in the association between insulin resistance and non-fatal myocardial infarction across glycaemic states
- 2024
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In: Cardiovascular Diabetology. - : Springer Nature. - 1475-2840. ; 23:1
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Journal article (peer-reviewed)abstract
- Background: Females are generally less prone to cardiovascular (CV) events than males, but this protection is trumped by diabetes. The mechanism behind the increased relative risk in females with diabetes is not fully understood. Insulin resistance (IR) is suggested to be a more important contributor to CV morbidity in females than in males. We aim to investigate differences in the association between IR indexes (Homeostatic Model Assessment of IR - HOMA-IR, visceral adiposity index – VAI, and triglycerides/high-density lipoprotein-cholesterol - TG/HDL-C index), and a first non-fatal myocardial infarction (MI) across different glycaemic states. Methods: IR indexes were calculated in a population with (n = 696) and without (n = 707) a first non-fatal MI, free from known diabetes. MI cases were investigated at least six weeks after the event. All participants were categorized by an oral glucose tolerance test as having normal glucose tolerance, impaired fasting glucose, impaired glucose tolerance, or newly diagnosed diabetes. Comparison of proportion of glycaemic states by sex was tested by chi-square test. The associations between sex, a first non-fatal MI, IR indexes, and traditional CV risk factors were analysed by multivariate logistic regression models. Continuous variables were logarithmically transformed. Results: Of the total population 19% were females and 81% males, out of whom 47% and 50% had a first non-fatal MI, respectively. Compared with males, females were older, less often smokers, with lower body mass index and higher total cholesterol and high-density lipoprotein cholesterol levels. The proportion of glycaemic states did not differ between the sexes (p = 0.06). Females were less insulin resistant than males, especially among cases and with normal glucose tolerance. In logistic regression models adjusted for major CV risk factors including sex, the associations between VAI and TG/HDL-C index and a first non-fatal MI remained significant only in females (odds ratios and 95% confidence intervals: 1.7, 1.0-2.9, and 1.9, 1.1–3.4 respectively). Conclusions: These results support the assumption that IR indexes based on anthropometrics and lipid panel, i.e., VAI and TG/HDL-C, could be a better measure of IR and CV-predictor for non-fatal MI in females, even without glycaemic perturbations.
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| 6. |
- Wang, Anne, et al.
(author)
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Androgen receptor polymorphism, testosterone levels, and prognosis in patients with acute myocardial infarction
- 2021
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In: European Heart Journal Open. - : Oxford University Press (OUP). - 2752-4191. ; 1:2
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Journal article (peer-reviewed)abstract
- Aims Low testosterone has been associated with cardiovascular disease in men but with contradictory findings. Testosterone bind to the androgen receptor and polymorphisms of the receptor gene such as CAG repeat length may affect transcriptional activity, possibly mitigating testosterone effects. The aims were to study the CAG repeat length and testosterone levels at four time points following a myocardial infarction (MI) and to analyse possible relationships between CAG repeat length and cardiovascular prognosis. Methods and results Male patients admitted for acute MI (n = 122) from the Glucose in Acute Myocardial Infarction study were included. Blood samples were drawn at four time points (day after admission, at discharge, and at 3 and 12 months post-infarction) for assessment of testosterone levels. Patients were followed for a median of 11.6 years. Cox regression analyses were performed for CAG repeat length by one unit increment and by > vs. <_median for cardiovascular events and all-cause mortality. Median CAG repeat length was 20. There was no difference in testosterone levels at each time point when dividing the cohort into <_ vs. >CAG repeat median (=20). There was no association between CAG repeat length either as a continuous or categorical variable in unadjusted and age-adjusted Cox analyses for cardiovascular events. While CAG >20 was associated with all-cause mortality in unadjusted analyses (hazard ratio 2.19, 95% confidence interval 1.13–4.22; P = 0.02), it did not remain significant following adjustment for age. Conclusion CAG repeat length was not associated with testosterone levels or prognosis in men with acute MI.
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| 7. |
- Wang, Anne, et al.
(author)
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Dynamics of testosterone levels in patients with newly detected glucose abnormalities and acute myocardial infarction
- 2018
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In: Diabetes & Vascular Disease Research. - : Sage Publications. - 1479-1641 .- 1752-8984. ; 15:6, s. 511-518
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Journal article (peer-reviewed)abstract
- Objective: Low testosterone has been associated with increased cardiovascular risk and glucose abnormalities. This study explored the prevalence of low testosterone, dynamics over time and prognostic implications in acute myocardial infarction patients with or without glucose abnormalities. Methods: Male acute myocardial infarction patients (n = 123) and healthy controls (n = 124) were categorised as having normal or abnormal glucose tolerance (impaired glucose tolerance or diabetes) by oral glucose tolerance testing. Testosterone was measured at hospital admission, discharge, 3 and 12 months thereafter in patients. Patients and controls were followed for 11 years for major cardiovascular events (cardiovascular death/acute myocardial infarction/stroke/severe heart failure). Results: At hospital admission, more patients had low testosterone (<= 300 ng/dl) and lower median levels than controls (64 vs 28%; p < 0.001 and 243 vs 380 ng/dl; p < 0.01). At the subsequent time points, testosterone had increased to 311, 345 and 357 ng/dl. Patients with abnormal glucose tolerance had the highest prevalence (75%) of low levels. In adjusted Cox regression models, neither total nor free testosterone predicted major cardiovascular events. Conclusion: Low testosterone levels were common in male acute myocardial infarction patients in the acute phase, especially in the presence of abnormal glucose tolerance, but increased over time indicating that testosterone measured in close proximity to acute myocardial infarction should be interpreted with caution.
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