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Backgrounds and aims: Preclinical studies suggest that a triglyceride (TG)-independent proinflammatory action of apolipoprotein C-III (apoCIII) exists. We aimed to investigate the relationship between circulating apoCIII levels and subclinical inflammation markers across different cohorts with distinctive inflammatory patterns: patients with metabolic disorders (MDs), patients with rheumatoid arthritis (RA), and controls. Specifically, we assessed the associations of apoCIII with acute inflammation biomarkers (e.g., high sensitivity C-reactive protein (hsCRP)) and novel systemic inflammation biomarkers (e.g., glycosylated proteins: Glyc-A, Glyc-B, Glyc-F), aiming to understand the role of apoCIII beyond its traditional function in TG metabolism. Methods: This cross-sectional study involved 1242 participants: 906 patients with MD (metabolic syndrome, type 2 diabetes (T2DM) and/or obesity), 192 patients with RA, and 144 controls. ApoCIII and hsCRP levels were measured via immunoturbidimetric assays, and glycosylated proteins were quantified via 1 H-NMR spectroscopy. Correlation and multivariate linear regression analyses were conducted. Results: ApoCIII levels were significantly and positively associated with Glyc-A, Glyc-B, and Glyc-F levels across all cohorts. Most of these associations remained significant in the MD group after adjusting for TG levels. Conversely, negative associations were detected between apoCIII and hsCRP patients with MD and RA, which were maintained after including TG in the models. Conclusion: In patients with MD and RA, circulating apoCIII levels were positively associated with glycoproteins and negatively with hsCRP, in a TG-independent manner. Our results suggest that apoCIII is associated with the low-grade inflammatory profile represented by glycoproteins, independent of triglyceride levels. Additionally, we observed a negative association with hsCRP, which, while seemingly paradoxical, has been reported in previous studies. [ABSTRACT FROM AUTHOR]

Background: Apolipoprotein (apo) C-III is involved in several processes that increase triglyceride levels, inflammation, and insulin resistance. Four of its proteoforms have been the focus of several studies and have shown differential associations with cardiovascular risk biomarkers, mostly lipids. However, there are other proteoforms of apoC-III that have not yet been investigated in detail. The aim of this study was to evaluate the associations of seven apoC-III proteoforms with a comprehensive set of biomarkers, including lipid metabolism, inflammation, and glucose homeostasis. Methods: Seven apoC-III proteoforms (apoC-III0a, apoC-III0b, apoC-III1, apoC-III1d, apoC-III2, apoC-III2d, and apoC-III0f) were measured using a mass spectrometry immunoassay in 875 participants from the cross-sectional study of the Di@bet.es cohort. The complete lipoprotein profile was obtained via the Liposcale test, and the proton nuclear magnetic resonance (1H-NMR)-assessed glycoprotein signals were also obtained as biomarkers of inflammation. Results: Three proteoform ratios (apoC-III2d, apoC-III2, and apoC-III0f normalized to apoC-III1) showed protective associations with most of the cardiovascular risk biomarkers in comparison with total apoC-III in linear regression models and were negatively associated with triglycerides (β=-0.173, p < 0.001; β=-0.297, p < 0.001; β=-0.223, p = 0.002), very low-density (VLDL) particle concentration (β=-0.133, p < 0.001; β=-0.265, p < 0.001; β=-0.203, p < 0.001), GlycA (β=-0.148, p < 0.001; β=-0.263, p < 0.001; β=-0.211, p < 0.001) and homeostatic model assessment of insulin resistance (HOMA-IR) (β=-0.096, p = 0.003; β=-0.199, p < 0.001; β=-0.114, p = 0.002). These associations were partly independent of total apoC-III concentrations. Participants with high levels of these proteoforms had a lower prevalence of cardiometabolic disorders, such as type 2 diabetes (p = 0.022), obesity (p = 0.001), and metabolic syndrome (p = 0.013). Conclusions: While apoC-III is positively associated with biomarkers of cardiometabolic risk, the proportions of three apoC-III proteoforms show opposite associations, independent of total apoC-III concentrations. Measuring not only apoC-III but also the proportions of apoC-III proteoforms can provide valuable information since individuals with similar levels of total apoC-III could display opposite lipid profiles depending on the proportion of apoC-III proteoforms. [ABSTRACT FROM AUTHOR]

Background: Obesity is a complex, diverse and multifactorial disease that has become a major public health concern in the last decades. The current classification systems relies on anthropometric measurements, such as BMI, that are unable to capture the physiopathological diversity of this disease. The aim of this study was to redefine the classification of obesity based on the different H-NMR metabolomics profiles found in individuals with obesity to better assess the risk of future development of cardiometabolic disease. Materials and methods: Serum samples of a subset of the Di@bet.es cohort consisting of 1387 individuals with obesity were analyzed by H-NMR. A K-means algorithm was deployed to define different H-NMR metabolomics-based clusters. Then, the association of these clusters with future development of cardiometabolic disease was evaluated using different univariate and multivariate statistical approaches. Moreover, machine learning-based models were built to predict the development of future cardiometabolic disease using BMI and waist-to-hip circumference ratio measures in combination with H-NMR metabolomics. Results: Three clusters with no differences in BMI nor in waist-to-hip circumference ratio but with very different metabolomics profiles were obtained. The first cluster showed a metabolically healthy profile, whereas atherogenic dyslipidemia and hypercholesterolemia were predominant in the second and third clusters, respectively. Individuals within the cluster of atherogenic dyslipidemia were found to be at a higher risk of developing type 2 DM in a 8 years follow-up. On the other hand, individuals within the cluster of hypercholesterolemia showed a higher risk of suffering a cardiovascular event in the follow-up. The individuals with a metabolically healthy profile displayed a lower association with future cardiometabolic disease, even though some association with future development of type 2 DM was still observed. In addition, H-NMR metabolomics improved the prediction of future cardiometabolic disease in comparison with models relying on just anthropometric measures. Conclusions: This study demonstrated the benefits of using precision techniques like H-NMR to better assess the risk of obesity-derived cardiometabolic disease. [ABSTRACT FROM AUTHOR]

Background: Typical bone proteins, such as sclerostin and periostin, have been associated with cardiovascular disease (CVD). Simultaneously, several risk scores have been developed to predict CVD in the general population. Therefore, we aimed to evaluate the association of these bone proteins related to CVD, with the main vascular risk scales: Framingham Risk Score (FRS), REGICOR and SCORE2-Diabetes, in patients with type 2 diabetes. We focus in particular on the SCORE2-Diabetes algorithm, which predicts 10-year CVD risk and is specific to the study population. Methods: This was a cross-sectional study including 104 patients with type 2 diabetes (62 ± 6 years, 60% males). Clinical data, biochemical measurements, and serum bioactive sclerostin and periostin levels were collected, and different risk scales were calculated. The association between bioactive sclerostin or periostin with the risk scales was analyzed. Results: A positive correlation was observed between circulating levels of bioactive sclerostin (p < 0.001) and periostin (p < 0.001) with SCORE2-Diabetes values. However, no correlation was found with FRS or REGICOR scales. Both serum bioactive sclerostin and periostin levels were significantly elevated in patients at high-very high risk of CVD (score ≥ 10%) than in the low-moderate risk group (score < 10%) (p < 0.001 for both). Moreover, analyzing these proteins to identify patients with type 2 diabetes at high-very high vascular risk using ROC curves, we observed significant AUC values for bioactive sclerostin (AUC = 0.696; p = 0.001), periostin (AUC = 0.749; p < 0.001), and the model combining both (AUC = 0.795; p < 0.001). For diagnosing high-very high vascular risk, serum bioactive sclerostin levels > 131 pmol/L showed 51.6% sensitivity and 78.6% specificity. Similarly, serum periostin levels > 1144 pmol/L had 64.5% sensitivity and 76.2% specificity. Conclusions: Sclerostin and periostin are associated with vascular risk in the SCORE2-Diabetes algorithm, opening a new line of investigation to identify novel biomarkers of cardiovascular risk in the type 2 diabetes population. [ABSTRACT FROM AUTHOR]

Background: In this study, we evaluated the lipidome alterations caused by type 1 diabetes (T1D) and type 2 diabetes (T2D), by determining lipids significantly associated with diabetes overall and in both sexes, and lipids associated with the glycaemic state. Methods: An untargeted lipidomic analysis was performed to measure the lipid profiles of 360 subjects (91 T1D, 91 T2D, 74 with prediabetes and 104 controls (CT)) without cardiovascular and/or chronic kidney disease. Ultra-high performance liquid chromatography-electrospray ionization mass spectrometry (UHPLC-ESI-MS) was conducted in two ion modes (positive and negative). We used multiple linear regression models to (1) assess the association between each lipid feature and each condition, (2) determine sex-specific differences related to diabetes, and (3) identify lipids associated with the glycaemic state by considering the prediabetes stage. The models were adjusted by sex, age, hypertension, dyslipidaemia, body mass index, glucose, smoking, systolic blood pressure, triglycerides, HDL cholesterol, LDL cholesterol, alternate Mediterranean diet score (aMED) and estimated glomerular filtration rate (eGFR); diabetes duration and glycated haemoglobin (HbA1c) were also included in the comparison between T1D and T2D. Results: A total of 54 unique lipid subspecies from 15 unique lipid classes were annotated. Lysophosphatidylcholines (LPC) and ceramides (Cer) showed opposite effects in subjects with T1D and subjects with T2D, LPCs being mainly up-regulated in T1D and down-regulated in T2D, and Cer being up-regulated in T2D and down-regulated in T1D. Also, Phosphatidylcholines were clearly down-regulated in subjects with T1D. Regarding sex-specific differences, ceramides and phosphatidylcholines exhibited important diabetes-associated differences due to sex. Concerning the glycaemic state, we found a gradual increase of a panel of 1-deoxyceramides from normoglycemia to prediabetes to T2D. Conclusions: Our findings revealed an extensive disruption of lipid metabolism in both T1D and T2D. Additionally, we found sex-specific lipidome changes associated with diabetes, and lipids associated with the glycaemic state that can be linked to previously described molecular mechanisms in diabetes. [ABSTRACT FROM AUTHOR]

Background: The diabetogenic effect of statins has been well established by clinical trials, Mendelian randomisation studies and meta-analyses. According to large clinical trials, PCSK9 inhibitors (PCSK9i) have no deleterious impact on glucose metabolism. However, few real-life studies have yet evaluated the long-term effects of these drugs on glucose homeostasis and their impact on new-onset diabetes (NODM). Methods: We studied 218 patients treated with either alirocumab or evolocumab (70% with familial hypercholesterolemia) for at least three years (PCSK9iG). We studied the NODM rate in the nondiabetic group at baseline (168) and overall glucose metabolism control in the whole group. Incidental DM was compared with two groups. The first was a propensity score matching (PSM)-selected group (n = 168) from the database of patients attending the Reus lipid unit (Metbank, n = 745) who were not on PCSK9i (PSMG). The second was a subgroup with a similar age range (n = 563) of the Di@bet.es study (Spanish prospective study on diabetes development n = 5072) (D@G). The incidence was reported as the percentage of NODM cases per year. Results: The fasting glucose (FG) level of the subjects with normoglycaemia at baseline increased from 91 (86-95.5) to 93 (87–101) mg/dL (p = 0.014). There were 14 NODM cases in the PCSK9i group (2.6%/y), all among people with prediabetes at baseline. The incidence of NODM in PSMG and D@G was 1.8%/y (p = 0.69 compared with the PCSK9iG). The incidence among the subjects with prediabetes was 5.1%/y in the PCSK9iG, 4.8%/y in the PSMG and 3.9%/y in the D@G (p = 0.922 and p = 0.682, respectively). In the multivariate analysis, only the FG level was associated with the development of NODM in the PCSK9iG (OR 1.1; 95% CI: 1.0-1.3; p = 0.027). Neither FG nor A1c levels changed significantly in patients with DM at baseline. Conclusion: A nonsignificant increase in NODM occurred in the PCSK9iG, particularly in patients with prediabetes, compared with the PSMG and D@G groups. Baseline FG levels were the main variable associated with the development of DM. In the subjects who had DM at baseline, glucose control did not change. The impact of PCSK9i on glucose metabolism should not be of concern when prescribing these therapies. [ABSTRACT FROM AUTHOR]

Background: The impact of Type 2 Diabetes (T2D) on the outcomes of heart transplantation (HT) has not yet been clearly established. The objectives of this study were to examine the trends in the prevalence of T2D among individuals who underwent a HT in Spain from 2002 to 2021, and to compare the clinical characteristics and hospitalization outcomes between HT recipients with and without T2D. Methods: We used the national hospital discharge database to select HT recipients aged 35 and older. The International Classification of Diseases, Ninth and Tenth Revisions (ICD-9 and ICD-10) were used to identify patients with and without T2D. We also recorded comorbidities, complications of HT, and procedures. Propensity score matching (PSM) and Cox regression were used to analyze the effect of T2D on in-hospital mortality (IHM). Results: Between 2002 and 2021, a total of 4429 HTs (T2D, 19.14%) were performed in Spain. The number of HTs in patients with T2D decreased from 2002 to 2005 (n = 171) to 2014–2017 (n = 154), then rose during 2018–2021 (n = 186). Complications of HT increased in patients with and without T2D over the study period (26.9% and 31.31% in 2002–2005 vs. 42.47% and 45.01% in 2018–2021, respectively). The results of the PSM showed that pneumonia and Gram-negative bacterial infections were less frequent in patients with T2D and that these patients less frequently required hemodialysis, extracorporeal membrane oxygenation (ECMO), and tracheostomy. They also had a shorter hospital stay and lower IHM than patients without diabetes. The variables associated with IHM in patients with T2D were hemodialysis and ECMO. IHM decreased over time in people with and without T2D. The Cox regression analysis showed that T2D was associated with lower IHM (HR 0.77; 95% CI 0.63–0.98). Conclusions: The number of HTs increased in the period 2018–2021 compared with 2002–2005 in patients with and without T2D. Over time, complications of HT increased in both groups studied, whereas IHM decreased. The presence of T2D is associated with lower IHM. [ABSTRACT FROM AUTHOR]

Background: Diagnosing fatty liver and identifying disease status are important for fatty liver related-diseases prevention. The fatty liver index (FLI), which can be easily available in clinical practice, can be very useful for managing fatty liver and preventing related diseases. No large-scale and long-term follow-up prospective studies have investigated the relationship between FLI and incident type 2 diabetes (T2DM) independent of baseline insulin resistance status. Therefore, this study aimed to evaluate the association between FLI and incident T2DM and to determine whether FLI could be used as an indicator of T2DM using a large-sample, community-based Korean cohort over 12 years. Methods: Among the 10,030 total participants, 7,777 (3,676 men and 4,101 women) without diabetes were selected from the Korean Genome and Epidemiology Study (KoGES). FLI grade, which ranged from 0 to 100, was categorized into three groups: low, FLI (< 30); intermediate, FLI (30–59); and high, FLI (≥ 60). The hazard ratios (HRs) with 95% confidence intervals (CIs) for incident T2DM were calculated using multivariate Cox proportional hazards regression models after adjusting for potentially confounding variables. Results: In total, 1,490 individuals (19.2%) developed T2DM during follow-up. Compared to the reference FLI (< 30), the HRs of incident T2DM for the FLI (30–59), and FLI (≥ 60) increased after adjusting for potentially confounding variables, including the HOMA-IR marker. Conclusions: FLI grade at baseline could be a future indicator of T2DM even when prior glucose or insulin (HOMA-IR) levels are normal. [ABSTRACT FROM AUTHOR]

Background: We examined trends in incidence (2001–2019), clinical characteristics, and in-hospital outcomes following major and minor lower extremity amputations (LEAs) among type 1 diabetes mellitus (T1DM) patients in Spain and attempted to identify sex differences. Methods: Retrospective cohort study using data from the Spanish National Hospital Discharge Database. We estimated the incidence of the LEA procedure stratified by type of LEA. Joinpoint regression was used to estimate incidence trends, and logistic regression was used to estimate factors associated with in-hospital mortality (IHM). Results: LEA was coded in 6011 patients with T1DM (66.4% minor and 33.6% major). The incidence of minor LEA decreased by 9.55% per year from 2001 to 2009 and then increased by 1.50% per year, although not significantly, through 2019. The incidence of major LEA decreased by 13.39% per year from 2001 to 2010 and then remained stable through 2019. However, incidence increased in men (26.53% per year), although not significantly, from 2017 to 2019. The adjusted incidence of minor and major LEA was higher in men than in women (IRR 3.01 [95% CI 2.64–3.36] and IRR 1.85 [95% CI 1.31–2.38], respectively). Over the entire period, for those who underwent a minor LEA, the IHM was 1.58% (2.28% for females and 1.36% for males; p = 0.045) and for a major LEA the IHM was 8.57% (10.52% for females and 7.59% for males; p = 0.025). IHM after minor and major LEA increased with age and the presence of comorbid conditions such as peripheral arterial disease, ischemic heart disease or chronic kidney disease. Female sex was associated with a higher IHM after major LEA (OR 1.37 [95% CI 1.01–1.84]). Conclusions: Our data show a decrease in incidence rates for minor and major LEA in men and women with T1DM and a slight, albeit insignificant, increase in major LEA in men with T1DM in the last two years of the study. The incidence of minor and major LEA was higher in men than in women. Female sex is a predictor of IHM in patients with T1DM following major LEA. [ABSTRACT FROM AUTHOR]

Background: To analyze incidence, use of therapeutic procedures, and in-hospital outcomes in patients with ST elevation myocardial infarction (STEMI) and non-ST elevation myocardial infarction (NSTEMI) according to the presence of type 2 diabetes (T2DM) in Spain (2016–2018) and to investigate sex differences. Methods: Using the Spanish National Hospital Discharge Database, we estimated the incidence of myocardial infarctions (MI) in men and women with and without T2DM aged ≥ 40 years. We analyzed comorbidity, procedures, and outcomes. We matched each man and woman with T2DM with a non-T2DM man and woman of identical age, MI code, and year of hospitalization. Propensity score matching was used to compare men and women with T2DM. Results: MI was coded in 109,759 men and 44,589 women (30.47% with T2DM). The adjusted incidence of STEMI (IRR 2.32; 95% CI 2.28–2.36) and NSTEMI (IRR 2.91; 95% CI 2.88–2.94) was higher in T2DM than non-T2DM patients, with higher IRRs for NSTEMI in both sexes. The incidence of STEMI and NSTEMI was higher in men with T2DM than in women with T2DM. After matching, percutaneous coronary intervention (PCI) was less frequent among T2DM men than non-T2DM men who had STEMI and NSTEMI. Women with T2DM and STEMI less frequently had a code for PCI that matched that of non-T2DM women. In-hospital mortality (IHM) was higher among T2DM women with STEMI and NSTEMI than in matched non-T2DM women. In men, IHM was higher only for NSTEMI. Propensity score matching showed higher use of PCI and coronary artery bypass graft and lower IHM among men with T2DM than women with T2DM for both STEMI and NSTEMI. Conclusions: T2DM is associated with a higher incidence of STEMI and NSTEMI in both sexes. Men with T2DM had higher incidence rates of STEMI and NSTEMI than women with T2DM. Having T2DM increased the risk of IHM after STEMI and NSTEMI among women and among men only for NSTEMI. PCI appears to be less frequently used in T2DM patients After STEMI and NSTEMI, women with T2DM less frequently undergo revascularization procedures and have a higher mortality risk than T2DM men. [ABSTRACT FROM AUTHOR]

Background: We aimed to investigate the hazard of hospitalization for heart failure (hHF) according to the transitions in metabolic health and obesity status. Methods: The Korean National Health Insurance Service datasets from 2002 to 2017 were used for this nationwide, longitudinal, population-based study. The hazard of hHF was analyzed according to the eight groups stratified by stability in metabolic health and transition in obesity status among initially metabolically healthy adults who underwent two cycles of health examinations in 2009–2010 and 2013–2014 (N = 7,148,763). Results: During two examinations, 48.43% of the initially metabolically healthy obese (MHO) individuals and 20.94% of the initially metabolically healthy non-obese (MHNO) individuals showed changes in their metabolic health and obesity status. During a mean follow-up of 3.70 years, 3151 individuals were hospitalized for HF. When stable MHNO individuals were set as the reference, transition to metabolically unhealthy phenotype was associated with an increased hazard of hHF; the hazard ratio (HR) and 95% confidence interval (CI) in the individuals who transformed from MHO to metabolically unhealthy non-obese was 2.033 (1.579–2.616). The constant MHO group had a 17.3% increased hazard of hHF compared with the stable MHNO group [HR (95% CI) 1.173 (1.039–1.325)]. Individuals who shifted from MHO to MHNO showed a 34.3% lower hazard of hHF compared with those who maintained the MHO category [HR (95% CI) 0.657 (0.508–0.849)]. Conclusion: Dynamic changes in metabolic health and obesity status were observed during a relatively short interval of 3–5 years. Loss of metabolic health was significantly associated with an increased hazard of hHF. Even if metabolic health was maintained, persistent obesity remained as a risk factor for hHF, and transition from MHO to MHNO had a protective effect against hHF. Therefore, the prevention and control of obesity while maintaining metabolic health would be crucial in preventing hHF. [ABSTRACT FROM AUTHOR]

Background: Risk of type 2 diabetes mellitus (T2DM) is increased in metabolically obese but normal-weight people. However, we have limited knowledge of how to prevent T2DM in normal-weight people. We aimed to evaluate the association between triglyceride glucose (TyG) index and incident T2DM among normal-weight people in rural China. Methods: We included data from 5706 people with normal body mass index (BMI) (18.5-23.9 kg/m2) without baseline T2DM in a rural Chinese cohort followed for a median of 6.0 years. A Cox proportional-hazard model was used to assess the risk of incident T2DM by quartiles of TyG index and difference in TyG index between follow-up and baseline (TyG-D), estimating hazard ratios (HRs) and 95% confidence intervals (CIs). A generalized additive plot was used to show the nonparametric smoothed exposure-response association between risk of T2DM and TyG index as a continuous variable. TyG was calculated as ln [fasting triglyceride level (mg/dl) × fasting plasma glucose level (mg/dl)/2]. Results: Risk of incident T2DM was increased with quartiles 2, 3 and 4 versus quartile 1 of TyG index (adjusted HR [aHR] 2.48 [95% CI 1.20-5.11], 3.77 [1.83-7.79], and 5.30 [2.21-12.71], Ptrend < 0.001 across quartiles of TyG index). Risk of incident T2DM was increased with quartile 4 versus quartile 1 of TyG-D (aHR 3.91 [2.22-6.87]). The results were consistent when analyses were restricted to participants without baseline metabolic syndrome and impaired fasting glucose level. The generalized additive plot showed cumulative increased risk of T2DM with increasing TyG index. Conclusions: Risk of incident T2DM is increased with increasing TyG index among rural Chinese people, so the index might be an important indicator for identifying people at high risk of T2DM. [ABSTRACT FROM AUTHOR]

Background: We aimed to determine the association between nonalcoholic fatty liver disease (NAFLD) and diabetes risk among body size phenotypes which was based on cross-classification of body mass index (BMI) categories (normal or overweight/obesity) and metabolic status (metabolically health or metabolically at-risk). Methods: We conducted a cross-sectional analysis using a cohort of 10,761 apparently healthy Chinese adults who underwent comprehensive health checkups including abdominal ultrasonography. Subjects were classified as metabolically at-risk by having any two of the following, consistent with the Adult Treatment Panel-III metabolic syndrome definition: (1) systolic/diastolic blood pressure ≥130/85 mmHg, (2) triglycerides ≥1.7 mmol/L, (3) fasting blood glucose ≥5.6 mmol/L, (4) HDL-cholesterol ≥1.0/1.3 mmol/L for men/women. Results: Among participants without metabolically at-risk, multivariate-adjusted odds ratios (ORs) for diabetes from NAFLD compared with those without NAFLD in the normal-weight (BMI <23 kg/m2) and overweight/obese (BMI ≥23 kg/m2) group were 2.10 (1.85–3.93) and 1.85 (1.35–2.53), respectively. Among participants with metabolically at-risk, the significant association between NAFLD and diabetes was lost, regardless of obesity status. There were only 27.1 % subjects with the presence of the three factors (overweight/obesity, NAFLD, and metabolically at-risk) occurring together, while the three factors occurring together was common (56.16 %) in diabetic individuals. The multivariate-adjusted ORs for diabetes were 1.1 (0.61–1.98) for overweight/obesity, 2.23 (1.05–5.14) for NAFLD, and 8.04 (5.0–12.09) for metabolically at-risk. The OR for the presence of all the three factors occurring together was 23.22 (13.96–38.63). Conclusions: NAFLD was associated with diabetes risk among participants without metabolically at-risk. The clustering of overweight/obesity, NAFLD, and metabolically at-risk is common in diabetic subjects and strikingly and markedly increases the diabetes risk. [ABSTRACT FROM AUTHOR]

Background: This study aims to describe trends in the rate of abdominal aortic aneurysm (AAA) and use of open surgery repair (OSR) and endovascular aneurysm repair (EVAR) in elderly patients with and without type 2 diabetes in Spain, 2003–2012. Methods: We select all patients with a discharge of AAA using national hospital discharge data. Discharges were grouped by diabetes status: type 2 diabetes and no diabetes. In both groups OSR and EVAR were identified. The incidence of discharges attributed to AAA were calculated overall and stratified by diabetes status and year. We calculated length of stay (LOHS) and in-hospital mortality (IHM). Use of OSR and EVAR were calculated stratified by diabetes status. Multivariate analysis was adjusted by age, sex, year, smoking habit and comorbidity. Results: From 2003 to 2012, 115,020 discharges with AAA were identified. The mean age was 74.91 years and 16.7% suffered type 2 diabetes. Rates of discharges due to AAA increased significantly in diabetic patients (50.09 in 2003 to 78.23 cases per 100,000 in 2012) and non diabetic subjects (69.24 to 78.66). The incidences were higher among those without than those with diabetes in all the years studied. The proportion of patients that underwent EVAR increased for both groups of patients and the open repair decreased. After multivariate analysis we found that LOHS and IHM have improved over the study period and diabetic patients had lower IHM than those without diabetes (OR 0.81; 95%CI 0.76-0.85). Conclusions: Incidence rates were higher in non-diabetic patients. For diabetic and non diabetic patients the use of EVAR has increased and open repair seems to be decreasing. IHM and LOHS have improved from 2003 to 2012. Patients with diabetes had significantly lower mortality. [ABSTRACT FROM AUTHOR]

Background: Uncoupling protein 2 (UCP2) gene polymorphisms have been reported as genetic risk factors for obesity and type 2 diabetes mellitus (T2DM). We examined the association of commonly observed UCP2 G(?866)A (rs659366) and Ala55Val (C>T) (rs660339) single nucleotide polymorphisms (SNPs) with obesity, high fasting plasma glucose, and serum lipids in a Balinese population. Methods: A total of 603 participants (278 urban and 325 rural subjects) were recruited from Bali Island, Indonesia. Fasting plasma glucose (FPG), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) were measured. Obesity was determined based on WHO classifications for adult Asians. Participants were genotyped for G(?866)A and Ala55Val polymorphisms of the UCP2 gene. Results: Obesity prevalence was higher in urban subjects (51%) as compared to rural subjects (23%). The genotype, minor allele (MAF), and heterozygosity frequencies were similar between urban and rural subjects for both SNPs. All genotype frequencies were in Hardy-Weinberg equilibrium. A combined analysis of genotypes and environment revealed that the urban subjects carrying the A/A genotype of the G(?866)A SNP have higher BMI than the rural subjects with the same genotype. Since the two SNPs showed strong linkage disequilibrium (D' = 0.946, r2 = 0.657), a haplotype analysis was performed. We found that the AT haplotype was associated with high BMI only when the urban environment was taken into account. Conclusions: We have demonstrated the importance of environmental settings in studying the influence of the common UCP2 gene polymorphisms in the development of obesity in a Balinese population. [ABSTRACT FROM AUTHOR]

Context: Obesity is a multifactorial disorder, that is, a disease determined by the combined effect of genes and environment. In this context, polygenic approaches are needed. Objective: To investigate the possibility of the existence of a crosstalk between the CALPAIN 10 homologue CALPAIN 5 and nuclear receptors of the peroxisome proliferator-activated receptors family. Design: Cross-sectional, genetic association study and gene-gene interaction analysis. Subjects: The study sample comprise 1953 individuals, 725 obese (defined as body mass index ≥ 30) and 1228 non obese subjects. Results: In the monogenic analysis, only the peroxisome proliferator-activated receptor delta (PPARD) gene was associated with obesity (OR = 1.43 [1.04-1.97], p = 0.027). In addition, we have found a significant interaction between CAPN5 and PPARD genes (p = 0.038) that reduces the risk for obesity in a 55%. Conclusion: Our results suggest that CAPN5 and PPARD gene products may also interact in vivo. [ABSTRACT FROM AUTHOR]

Background: The main aims of this study were to describe trends and outcomes during admission for infective endocarditis (IE) in people ≥ 40 years old with or without type 2 diabetes distributed in five time-periods (2001–2003; 2004–2006; 2007–2009; 2010–2012 and 2013–2015), using Spanish national hospital discharge data. Methods: We estimated admission rates by diabetes status. We analyzed comorbidity, therapeutic procedures, and outcomes. We built Poisson regression models to compare the adjusted time-trends in admission rates. Type 2 diabetes cases were matched with controls using propensity score matching (PSM). We tested in-hospital mortality (IHM) in logistic regression analyses. Results: We identified 16,626 hospitalizations in patients aged ≥ 40 years for IE in Spain, 2001–2015. The incidence of IE increased significantly from 6.0/100,000 per year to 13.1/100,000 per year (p < 0.001) in the population with type 2 diabetes, and from 3.9/100,000 per year to 5.5/100,000 per year (p < 0.001) in the population without diabetes, over the study period. The adjusted incidence of IE was 2.2-times higher among patients with diabetes than among those without diabetes (IRR = 2.2; 95% CI 2.1–2.3). People with type 2 diabetes less often underwent heart valve surgery than people without diabetes (13.9% vs. 17.3%; p < 0.001). Although IHM decreased significantly in both groups over time, it represented 20.8% of IE cases among diabetes patients and 19.9% among PSM matched controls (p = 0.337). Type 2 diabetes was not associated with a higher IHM in people admitted to the hospital for IE (OR = 1.1; 95% CI 0.9–1.2). Conclusion: Incidence rates of IE in Spain, among those with and without T2DM, have increased during the period 2001–2015 with significantly higher incidence rates in the T2DM population. In our population based study and after PSM we found that T2DM was not a predictor of IHM in IE. [ABSTRACT FROM AUTHOR]

Background: The aims of this study were to examine trends in the incidence and in-hospital outcomes of SAVR among T2DM patients from 2001 to 2015, to compare clinical variables among T2DM patients and matched non-T2DM patients hospitalized for SAVR and to identify factors associated with in-hospital mortality (IHM) among T2DM patients. Methods: We performed a retrospective study using the Spanish National Hospital Discharge Database, 2001–2015. We included patients who had SAVR as the procedure in their discharge report. For each T2DM patient, we selected a sex-, age-, implanted valve type- and year-matched nondiabetic patient. Results: We identified 78,223 patients who underwent SAVR (23.49% with T2DM). The prevalence of T2DM increased significantly (p < 0.001) from 16.7% in 2001–2003 to 23.5% in 2012–2015. The incidence of SAVR increased significantly from 28.99 cases in 2001 to 65.79 cases in 2015 per 100,000 individuals in the T2DM population. Using Poisson regression models, we found that the incidence of SAVR was 2.60 times higher among patients with T2DM than among those without diabetes (IRR 2.60; 95% CI 2.56–2.65). The incidence of mechanical SAVR among T2DM patients remained stable from 2001 to 2015, and bioprosthetic SAVR rose from 8.29 to 41.74 cases per 100,000 individuals in the T2DM patient population (p < 0.001). We matched 8835 and 9543 patients who underwent mechanical and bioprosthetic SAVR, respectively. IHM decreased over time in T2DM patients and non-T2DM patients (from 8.89% and 7.81% to 3.88% and 5.07%, respectively). IHM was significantly lower in T2DM patients than in nondiabetic subjects who underwent bioprosthetic SAVR (4.77% vs. 6.04%, p < 0.001), with similar results obtained for mechanical valves (7.11% and 7.77%). Conclusions: The incidence of SAVR was higher in T2DM patients, and the incidence of bioprosthetic SAVR increased significantly among T2DM subjects. IHM decreased over time, regardless of the existence or absence of T2DM and the valve type. IHM was significantly lower in T2DM patients than in nondiabetic patients who underwent bioprosthetic SAVR. [ABSTRACT FROM AUTHOR]

Patients with diabetes type 2 have an increased risk for cardiovascular disease and commonly use combination therapy consisting of the anti-diabetic drug metformin and a cholesterol-lowering statin. However, both drugs act on glucose and lipid metabolism which could lead to adverse effects when used in combination as compared to monotherapy. In this review, the proposed molecular mechanisms of action of statin and metformin therapy in patients with diabetes and dyslipidemia are critically assessed, and a hypothesis for mechanisms underlying interactions between these drugs in combination therapy is developed. [ABSTRACT FROM AUTHOR]