| 1. |
- Ferrannini, Ele, et al.
(författare)
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Early Metabolic Markers of the Development of Dysglycemia and Type 2 Diabetes and Their Physiological Significance
- 2013
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 62:5, s. 1730-1737
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Tidskriftsartikel (refereegranskat)abstract
- Metabolomic screening of fasting plasma from nondiabetic subjects identified alpha-hydroxybutyrate (alpha-HB) and linoleoyl-glycerophosphocholine (L-GPC) as joint markers of insulin resistance (IR) and glucose intolerance. To test the predictivity of alpha-HB and L-GPC for incident dysglycemia, alpha-HB and L-GPC measurements were obtained in two observational cohorts, comprising 1,261 nondiabetic participants from the Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) study and 2,580 from the Botnia Prospective Study, with 3-year and 9.5-year follow-up data, respectively. In both cohorts, alpha-HB was a positive correlate and L-GPC a negative correlate of insulin sensitivity, with alpha-HB reciprocally related to indices of beta-cell function derived from the oral glucose tolerance test (OGTT). In follow-up, alpha-HB was a positive predictor (adjusted odds ratios 1.25 [95% CI 1.00-1.60] and 1.26 [1.07-1.48], respectively, for each standard deviation of predictor), and L-GPC was a negative predictor (0.64 [0.48-0.85] and 0.67 [0.54-0.84]) of dysglycemia (RISC) or type 2 diabetes (Botnia), independent of familial diabetes, sex, age, BMI, and fasting glucose. Corresponding areas under the receiver operating characteristic curve were 0.791 (RISC) and 0.783 (Botnia), similar in accuracy when substituting cc-JIB and L-GPC with 2-h OGTT glucose concentrations. When their activity was examined, alpha-JIB inhibited and L-GPC stimulated glucose-induced insulin release in INS-le cells. alpha-JIB and L-GPC are independent predictors of worsening glucose tolerance, physiologically consistent with a joint signature of IR and beta-cell dysfunction. Diabetes 62:1730-1737, 2013
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| 2. |
- Aizawa, Kunihiko, et al.
(författare)
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Type 2 diabetes exacerbates changes in blood pressure-independent arterial stiffness : cross-sectional and longitudinal evidence from the SUMMIT study
- 2024
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Ingår i: Journal of Applied Physiology. - 8750-7587. ; 136:1, s. 13-22
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Tidskriftsartikel (refereegranskat)abstract
- Greater central artery stiffness is observed in people with type 2 diabetes (T2DM). Elevated blood pressure (BP) and altered arterial wall structure/composition in T2DM are generally considered as main drivers for this alteration. However, because conventional arterial stiffness measures are BP-dependent and as such an influence of BP remains in a measure, it is unclear if greater central artery stiffness is a function of greater BP, or due to changes in the structure and composition of the arterial wall. We aimed to measure BP-independent arterial stiffness (b0) cross-sectionally and longitudinally in T2DM. We studied 753 adults with T2DM (DM þ) and 436 adults without (DM-) at baseline (Phase 1), and 310 DM þ and 210 DM- adults at 3-yr follow-up (Phase 2). We measured carotid-femoral pulse wave velocity and used it to calculate b0. In Phase 1, b0 was significantly greater in DM þ than DM- after adjusting for age and sex [27.5 (26.6–28.3) vs. 23.6 (22.4–24.8) au, P < 0.001]. Partial correlation analyses after controlling for age and sex showed that b0 was significantly associated with hemoglobin A1c (r ¼ 0.15 P < 0.001) and heart rate [(HR): r ¼ 0.23 P < 0.001)] in DM þ . In Phase 2, percentage-change in b0 was significantly greater in DM þ than DM-[19.5 (14.9–24.0) vs. 5.0 (-0.6 to 10.6) %, P < 0.001] after adjusting for age, sex, and baseline b0. b0 was greater in DM þ than DM- and increased much more in DM þ than in DM- over 3 yr. This suggests that T2DM exacerbates BP-independent arterial stiffness and may have a complemental utility to existing arterial stiffness indices. NEW & NOTEWORTHY We demonstrate in this study a greater BP-independent arterial stiffness b0 in people with type 2 diabetes (T2DM) compared to those without, and also a greater change in b0 over 3 yr in people with T2DM than those without. These findings suggest that the intrinsic properties of the arterial wall may change in a different and more detrimental way in people with T2DM and likely represents accumulation of cardiovascular risk.
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| 3. |
- Casalinuovo, Silvia, et al.
(författare)
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AuNP-coated cotton as VOC sensor for disease detection from breath
- 2023
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Ingår i: Proceedings of SIE 2022. - Cham : Springer Nature Switzerland. - 9783031260667 - 9783031260650
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Konferensbidrag (refereegranskat)abstract
- The COVID-19 pandemic outbreak, declared in March 2020, has led to several behavioral changes in the general population, such as social distancing and mask usage among others. Furthermore, the sanitary emergency has stressed health system weaknesses in terms of disease prevention, diagnosis, and cure. Thus, smart technologies allowing for early and quick detection of diseases are called for. In this framework, the development of point-of-care devices can provide new solutions for sanitary emergencies management. This work focuses on the development of useful tools for early disease diagnosis based on nanomaterials on cotton substrates, to obtain a low-cost and easy-to-use detector of breath volatiles as disease markers. Specifically, we report encouraging experimental results concerning acetone detection through impedance measurements. Such findings can pave the way to the implementation of VOCs (Volatile Organic Compounds) sensors into smart and user friendly diagnostic devices.
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| 4. |
- Chiriacò, Martina, et al.
(författare)
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Female sex and angiotensin-converting enzyme (ace) insertion/deletion polymorphism amplify the effects of adiposity on blood pressure
- 2022
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Ingår i: Hypertension. - 0194-911X. ; 79:1, s. 36-46
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Tidskriftsartikel (refereegranskat)abstract
- The pathophysiological link between adiposity and blood pressure is not completely understood, and evidence suggests an influence of sex and genetic determinants. We aimed to identify the relationship between adiposity and blood pressure, independent of a robust set of lifestyle and metabolic factors, and to examine the modulating role of sex and Angiotensin-Converting Enzyme (ACE) insertion/deletion (I/D) polymorphisms. In the Relationship Between Insulin Sensitivity and Cardiovascular Disease (RISC) study cohort, 1211 normotensive individuals, aged 30 to 60 years and followed-up after 3.3 years, were characterized for lifestyle and metabolic factors, body composition, and ACE genotype. Body mass index (BMI) and waist circumference (WC) were independently associated with mean arterial pressure, with a stronger relationship in women than men (BMI: R=0.40 versus 0.30; WC: R=0.40 versus 0.30, both P<0.01) and in individuals with the ID and II ACE genotypes in both sexes (P<0.01). The associations of BMI and WC with mean arterial pressure were independent of age, sex, lifestyle, and metabolic variables (standardized regression coefficient=0.17 and 0.18 for BMI and WC, respectively) and showed a significant interaction with the ACE genotype only in women (P=0.03). A 5 cm larger WC at baseline increased the risk of developing hypertension at follow-up only in women (odds ratio, 1.56 [95% CI, 1.15-2.10], P=0.004) and in II genotype carriers (odds ratio, 1.87 [95% CI, 1.09-3.20], P=0.023). The hypertensive effect of adiposity is more pronounced in women and in people carrying the II variant of the ACE genotype, a marker of salt sensitivity.
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| 5. |
- Edsfeldt, Andreas, et al.
(författare)
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Circulating soluble IL-6 receptor associates with plaque inflammation but not with atherosclerosis severity and cardiovascular risk
- 2023
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Ingår i: Vascular Pharmacology. - 1537-1891. ; 152
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Tidskriftsartikel (refereegranskat)abstract
- Background: The residual cardiovascular risk in subjects receiving guideline-recommended therapy is related to persistent vascular inflammation and IL-6 represents a target for its treatment. IL-6 binds to receptors on leukocytes and hepatocytes and/or by forming complexes with soluble IL-6 receptors (sIL-6R) binding to gp130 which is present on all cells. Here we aimed to estimate the associations of these two pathways with risk of cardiovascular disease (CVD). Methods: IL-6 and sIL-6R were analyzed using the proximity extension assay. Baseline plasma samples were obtained from participants in the prospective Malmö Diet and Cancer (MDC) study (n = 4661), the SUMMIT VIP study (n = 1438) and the Carotid Plaque Imaging Project (CPIP, n = 285). Incident clinical events were obtained through national registers. Plaques removed at surgery were analyzed by immunohistochemistry and biochemical methods. Results: During 23.1 ± 7.0 years follow-up, 575 subjects in the MDC cohort suffered a first myocardial infarction. Subjects in the highest tertile of IL-6 had an increased risk compared to the lowest tertile (HR and 95% CI 2.60 [2.08–3.25]). High plasma IL-6 was also associated with more atherosclerosis, increased arterial stiffness, and impaired endothelial function in SUMMIT VIP, but IL-6 was only weakly associated with plaque inflammation in CPIP. sIL-6R showed no independent association with risk of myocardial infarction, atherosclerosis severity or vascular function, but was associated with plaque inflammation. Conclusions: Our findings show that sIL-6R is a poor marker of CVD risk and associated vascular changes. However, the observation that sIL-6R reflects plaque inflammation highlights the complexity of the role of IL-6 in CVD.
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| 6. |
- Fontanella, Chiara Giulia, et al.
(författare)
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Interaction Phenomena between Dental Implants and Bone Tissue in Case of Misfit : A Pilot Study
- 2023
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Ingår i: Applied Sciences. - : MDPI. - 2076-3417. ; 13:10
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Tidskriftsartikel (refereegranskat)abstract
- The biomechanical response of cortical and trabecular bone tissues represents a fundamental aspect for the interpretation of the functional response of dental implants. In the case of misfit, the interaction phenomena occurring within the surgical and the subsequent healing phases must be interpreted primarily in the light of the response of bone tissue. This is influenced by the specific loadings induced, characterized by intensity and variable trends. The pilot study reported, which intentionally refers to a simple case of a two-implants frame, is addressed to define the method to approach the biomechanical investigation of the problem and to attest the necessity to integrate clinical competences with biomechanical analysis for interpreting different aspects of osseointegration. The action induced in cortical and trabecular bone regions depending on the implant frame conformation, the surgical procedure adopted, the varying condition at the bone-implant interface and the evolutionary trend of healing are the principal aspects to be considered to evaluate the osseointegration process. The biomechanical reliability of the specific implant frame is investigated in terms of bone-implant interaction by means of numerical models. This approach can offer valid information and support clinical practice under the fundamental condition that bone biomechanical behavior is properly characterized and represented in the model, in spite of the complex formulation to be adopted.
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| 7. |
- Genovese, Federica, et al.
(författare)
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Plasma levels of PRO-C3, a type III collagen synthesis marker, are associated with arterial stiffness and increased risk of cardiovascular death
- 2024
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Ingår i: Atherosclerosis. - 0021-9150. ; 388
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: The N-terminal propeptide of type III collagen (PRO-C3) assay measures a pro-peptide released during type III collagen synthesis, an important feature of arterial stiffening and atherogenesis. There is a clinical need for improved non-invasive, cheap and easily accessible methods for evaluating individuals at risk of cardiovascular disease (CVD). In this study, we investigate the potential of using circulating levels of PRO-C3 to mark the degree of vascular stenosis and risk of cardiovascular events. Methods: Baseline plasma levels of PRO-C3 were measured by ELISA in subjects belonging to the SUrrogate markers for Micro- and Macro-vascular hard endpoints for Innovative diabetes Tools (SUMMIT) cohort (N = 1354). Associations between PRO-C3 levels with vascular characteristics, namely stiffness and stenosis, and risk of future cardiovascular events were explored. Subjects were followed up after a median of 35 months (interquartile range 34–36 months), with recorded outcomes cardiovascular death and all-cause mortality. Results: We found a correlation between PRO-C3 levels and pulse wave velocity (rho 0.13, p = 0.000009), a measurement of arterial stiffness. Higher PRO-C3 levels were also associated with elevated blood pressure (rho 0.07, p = 0.014), as well as risk of cardiovascular mortality over a three-year follow-up period (OR 1.56, confidence interval 1.008–2.43, p = 0.046). Conclusions: Elevated circulating PRO-C3 levels are associated with arterial stiffness and future cardiovascular death, in the SUMMIT cohort, suggesting a potential value of PRO-C3 as a novel marker for declining vascular health.
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| 8. |
- Gonçalves, Isabel, et al.
(författare)
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Association between renin and atherosclerotic burden in subjects with and without type 2 diabetes
- 2016
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 16:1, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Activation of the renin-angiotensin-aldosterone-system (RAAS) has been proposed to contribute to development of vascular complications in type 2 diabetes (T2D). The aim of the present study was to determine if plasma renin levels are associated with the severity of vascular changes in subjects with and without T2D. Methods: Renin was analyzed by the Proximity Extension Assay in subjects with (n = 985) and without (n = 515) T2D participating in the SUMMIT (SUrrogate markers for Micro- and Macro-vascular hard endpoints for Innovative diabetes Tools) study and in 205 carotid endarterectomy patients. Vascular changes were assessed by determining ankle-brachial pressure index (ABPI), carotid intima-media thickness (IMT), carotid plaque area, pulse wave velocity (PWV) and the reactivity hyperemia index (RHI). Results: Plasma renin was elevated in subjects with T2D and demonstrated risk factor-independent association with prevalent cardiovascular disease both in subjects with and without T2D. Renin levels increased with age, body mass index, HbA1c and correlated inversely with HDL. Subjects with T2D had more severe carotid disease, increased arterial stiffness, and impaired endothelial function. Risk factor-independent associations between renin and APBI, bulb IMT, carotid plaque area were observed in both T2D and non-T2D subjects. These associations were independent of treatment with RAAS inhibitors. Only weak associations existed between plasma renin and the expression of pro-inflammatory and fibrous components in plaques from 205 endarterectomy patients. Conclusions: Our findings provide clinical evidence for associations between systemic RAAS activation and atherosclerotic burden and suggest that this association is of particular importance in T2D.
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| 9. |
- Goncalves, Isabel, et al.
(författare)
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Elevated Plasma Levels of MMP-12 Are Associated With Atherosclerotic Burden and Symptomatic Cardiovascular Disease in Subjects With Type 2 Diabetes.
- 2015
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1524-4636. ; 35:7, s. 1723-1731
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Tidskriftsartikel (refereegranskat)abstract
- Matrix metalloproteinases (MMPs) degrade extracellular matrix proteins and play important roles in development and tissue repair. They have also been shown to have both protective and pathogenic effects in atherosclerosis, and experimental studies have suggested that MMP-12 contributes to plaque growth and destabilization. The objective of this study was to investigate the associations between circulating MMPs, atherosclerosis burden, and incidence of cardiovascular disease with a particular focus on type 2 diabetes mellitus.
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| 10. |
- Khan, Faisel, et al.
(författare)
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Plaque characteristics and biomarkers predicting regression and progression of carotid atherosclerosis
- 2022
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Ingår i: Cell Reports Medicine. - : Elsevier BV. - 2666-3791. ; 3:7
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Tidskriftsartikel (refereegranskat)abstract
- The factors that influence the atherosclerotic disease process in high-risk individuals remain poorly understood. Here, we used a combination of vascular imaging, risk factor assessment, and biomarkers to identify factors associated with 3-year change in carotid disease severity in a cohort of high-risk subjects treated with preventive therapy (n = 865). The results show that changes in intima-media thickness (IMT) are most pronounced in the carotid bulb. Progression of bulb IMT demonstrates independent associations with baseline bulb IMT, the plaque gray scale median (GSM), and the plasma level of platelet-derived growth factor (PDGF) (standardized β-coefficients and 95% confidence interval [CI] −0.14 [−0.06 to −0.02] p = 0.001, 0.15 [0.02–0.07] p = 0.001, and 0.20 [0.03–0.07] p < 0.001, respectively). Plasma PDGF correlates with the plaque GSM (0.23 [0.15–0.29] p < 0.001). These observations provide insight into the atherosclerotic process in high-risk subjects by showing that progression primarily occurs in fibrotic plaques and is associated with increased levels of PDGF.
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