Therapeutic Potential of Tpl2 (Tumor Progression Locus 2) Inhibition on Diabetic Vasculopathy Through the Blockage of the Inflammasome Complex.

OBJECTIVE: Diabetic retinopathy, one of retinal vasculopathy, is characterized by retinal inflammation, vascular leakage, blood-retinal barrier breakdown, and neovascularization. However, the molecular mechanisms that contribute to diabetic retinopathy progression remain unclear. Approach and Results: Tpl2 (tumor progression locus 2) is a protein kinase implicated in inflammation and pathological vascular angiogenesis. Nε-carboxymethyllysine (CML) and inflammatory cytokines levels in human sera and in several diabetic murine models were detected by ELISA, whereas liquid chromatography-tandem mass spectrometry analysis was used for whole eye tissues. The CML and p-Tpl2 expressions on the human retinal pigment epithelium (RPE) cells were determined by immunofluorescence. Intravitreal injection of pharmacological inhibitor or NA (neutralizing antibody) was used in a diabetic rat model. Retinal leukostasis, optical coherence tomography, and H&E staining were used to observe pathological features. Sera of diabetic retinopathy patients had significantly increased CML levels that positively correlated with diabetic retinopathy severity and foveal thickness. CML and p-Tpl2 expressions also significantly increased in the RPE of both T1DM and T2DM diabetes animal models. Mechanistic studies on RPE revealed that CML-induced Tpl2 activation and NADPH oxidase, and inflammasome complex activation were all effectively attenuated by Tpl2 inhibition. Tpl2 inhibition by NA also effectively reduced inflammatory/angiogenic factors, retinal leukostasis in streptozotocin-induced diabetic rats, and RPE secretion of inflammatory cytokines. The attenuated release of angiogenic factors led to inhibited vascular abnormalities in the diabetic animal model. CONCLUSIONS: The inhibition of Tpl2 can block the inflammasome signaling pathway in RPE and has potential clinical and therapeutic implications in diabetes-associated retinal microvascular dysfunction.

Subjects with coronary artery disease and reduced ejection fraction have longer (GT)n repeats in the heme-oxygenase 1 gene promoter.

Heme oxygenase (HO)-1 is a rate-limiting enzyme for degrading heme into carbon monoxide. Longer (GT)n repeat of the HO-1 gene (HMOX1) promoter has a lower transcription rate. Subjects with longer GT repeats in the HMOX1 promoter are more likely to have coronary artery disease (CAD) and cardiovascular events. We retrospectively enrolled CAD subjects with an abnormal ejection fraction (EF) < 50% from our catheterization data (N = 670). Polymerase chain reactions were performed for amplifying the HMOX1 promoter GT repeating segment to determine the number of repeats. Two subgroups, reduced EF < 40% (N = 256), and mid-range EF 40-49% (N = 414), were compared. The distribution of genotypes of SS, SL and LL were significantly different in reduced EF (29%, 48%, 23%) vs. mid-range EF CAD (64%, 30%, 5%) (S allele: ≤ 30 repeats, L allele: > 30 repeats) (p < 0.001). The patients with reduced EF had a significantly longer average (GT)n (median 27.5 vs. 26.5, p = 0.004) than those with the mid-range EF. In multivariate analysis, the carrier of L allele (odds ratio 4.437, p < 0.001) was a significant predictor for the diagnosis of reduced vs. mid-range EF CAD. In conclusion, CAD patients with reduced EF had longer HMOX1 promoter (GT)n repeats than those with mid-range EF.

Distinct associations of self-monitoring of blood glucose with glycemic control and hypoglycemia between groups of recently diagnosed and long-term follow-up type 2 diabetes: The Taiwan Diabetes Registry.

BACKGROUND: We investigated the uses and frequency of self-monitoring of blood glucose (SMBG) with glycemic control and hypoglycemia in two groups of type 2 diabetes (T2D) (recently diagnosed and long-term follow-up) using real-world data in Taiwan (the Taiwan Diabetes Registry). METHODS: Patients with T2D recently diagnosed within 6 months (n = 3297, mean age 54.4 ± 13.9 years) and T2D patients with long-term follow-up (n = 1201, mean age 65.5 ± 12.1 years, mean diabetes duration 14.3 ± 7.8 years) from the Taiwan Diabetes Registry were analysed. All patients were interviewed by certified diabetes educators. Information about SMBG and hypoglycemia was recorded. Demography, personal history, and laboratory data were obtained from electronic medical records. Logistic regression analyses were used to examine the associations of SMBG with glycated haemoglobin (HbA1c) <7% and hypoglycemia. RESULTS: Mean HbA1c values were 8.4 ± 2.5 and 7.6 ± 1.4%, respectively, in the recently diagnosed and long-term follow-up T2D groups. The self-reported rates of hypoglycemic events within 3 months were 10.5% and 19.0%, respectively. SMBG was associated with higher odds of HbA1c <7% (OR 1.21, 95% CI 1.01-1.44) in patients with recently diagnosed T2D, but with lower odds of HbA1c <7% in T2D patients with long-term follow-up (OR 0.60, 95% CI 0.44-0.82). In both study populations, SMBG was independently associated with hypoglycemia (OR 3.90 [95% CI 2.99-5.08] and OR 3.93 [95% CI 2.73-5.66], respectively). The aforementioned findings were consistent across the strata of SMBG frequency. CONCLUSION: We reported different associations between SMBG and glycemic control in patients recently diagnosed with T2D and in T2D patients with long-term follow-up. SMBG was associated with higher detection of hypoglycemic episodes in both study populations.

Hypoglycaemic episodes increase the risk of ventricular arrhythmia and sudden cardiac arrest in patients with type 2 diabetes-A nationwide cohort study.

BACKGROUND: The impact of hypoglycaemic episode (HE) on the risk of ventricular arrhythmia (VA) and sudden cardiac arrest (SCA) remains unclear. We hypothesized that HE increases the risk of both VA and SCA and that glucose-lowering agents causing HE also increase the risk of VA/SCA in patients with type 2 diabetes (T2D). METHODS: Patients aged 20 years or older with newly diagnosed T2D were identified using the Taiwan National Health Insurance Database. HE was defined as the presentation of hypoglycaemic coma or specified/unspecified hypoglycaemia. The control group consisted of T2D patients without HE. The primary outcome was the occurrence of VA (including ventricular tachycardia and fibrillation) and SCA during the defined follow-up periods. A multivariate Cox hazards regression model was used to evaluate the hazard ratio (HR) for VA or SCA. RESULTS: A total of 54 303 patients were screened, with 1037 patients with HE assigned to the HE group and 4148 frequency-matched patients without HE constituting the control group. During a mean follow-up period of 3.3 ± 2.5 years, 29 VA/SCA events occurred. Compared with the control group, HE group had a higher incidence of VA/SCA (adjusted HR: 2.42, P = .04). Patients who had used insulin for glycaemic control showed an increased risk of VA/SCA compared with patients who did not receive insulin (adjusted HR: 3.05, P = .01). CONCLUSIONS: The HEs in patients with T2D increased the risk of VA/SCA, compared with those who did not experience HEs. Use of insulin also independently increased the risk of VA/SCA.

Subjects with microvascular angina have longer GT repeats polymorphism in the haem oxygenase-1 gene promoter.

Objective: Few studies have investigated haem oxygenase-1 gene (HMOX1) promoter polymorphism in microvascular angina (MVA).Materials and methods: HMOX1 promoter (GT)n repeats were examined in healthy controls (N = 220) and MVA subjects (N = 181).Results: The distribution of genotype of SS, SL and LL were significantly different in MVA (17%, 51%, 33%) vs. normal controls (35%, 46%, 20%) (p < 0.001, S allele: ≤30 repeats, L allele: >30 repeats). In multivariate analysis, carrier of L allele (odds ratio 2.772, p < 0.001) was a significant predictor for the diagnosis of MVA.Conclusions: Subjects with MVA had longer HMOX1 promoter (GT)n repeats than the healthy controls. Trial registration number: NCT01198730 at https://clinicaltrials.gov.

Systolic blood pressure trajectory and cardiovascular outcomes: An analysis using data in the Systolic Blood Pressure Intervention Trial.

BACKGROUND: Blood pressure changes in response to medication intensification differ over time across individuals, and could affect their cardiovascular outcomes. We aimed to investigate the relationship between systolic blood pressure (SBP) trajectory and cardiovascular outcomes using data from the Systolic Blood Pressure Intervention Trial (SPRINT). METHODS: Groups of SBP trajectory were modelled separately in the standard and intensive treatment groups. SBP at each site visit post randomisation were used for modelling by group-based trajectory with latent class growth model. We classified six SBP trajectories (on target [reference group], near target, and off target in the intensive treatment group; on target-below 130, on target-below 140, and off target in the standard treatment group). A Cox-proportional hazard model was used to analyse the effects of SBP trajectory on the primary composite outcome, death from any cause, and the composite of the primary outcome or death from any cause. RESULTS: The respective mean SBP was 119 ± 5, 128 ± 6, 141 ± 8, 124 ± 4, 136 ± 4, and 147 ± 6 mm Hg. With respect to the primary composite outcomes, the standard-on target (below 130) had the highest risk (adjusted hazard ratio [lower to upper confidence interval], 2.525 [1.865-3.420]), despite its mean SBP was the second lowest of the six groups. The standard-on target (below 140) had a higher risk (1.323 [1.056-1.657]) when compared with the intensive-on target. However, the standard-on target (below 140) had a similar risk (1.12 [0.861-1.458]) when compared with the intensive-near target, despite an 8 mm Hg difference in mean SBP (136 vs 128 mm Hg, P < .001). CONCLUSION: An SBP treatment target of <120 mm Hg was only associated with a better cardiovascular outcome compared with a treatment target of <140 mm Hg, provided that the target of <120 mm Hg was reached. TRIAL REGISTRATION: ClinicalTrials.gov NCT01206062. Registered 21 September 2010.

Effect of low-protein intake on all-cause mortality in subjects with an estimated glomerular filtration rate higher than 60 mL/min/1.73 m2 with or without albuminuria.

BACKGROUND: We aimed to investigate the effect of a low-protein intake on all-cause mortality in subjects with an estimated glomerular filtration rate (eGFR) ≧60 mL/min/1.73 m2 with or without albuminuria using data from the National Health and Nutrition Examination Survey (NHANES). METHODS: We analysed participants in the NHANES from 2003 to 2010. We excluded participants with an eGFR less than 60 mL/min/1.73 m2 from the analyses. Low-protein intake was defined as a protein intake of less than 0.8 g/kg/day. The Healthy Eating Index 2010 was used to assess diet quality. The vital status of all participants in the NHANES was determined by linking to the National Death Index through the end of 2011. The hazard ratios (HRs) for the association of low-protein intake and mortality were determined using weighted Cox proportional hazards regression models. RESULTS: A total of 7730 participants were included in the analyses. After a median follow up of 4.7 years, 462 participants died. A low-protein intake was associated with a higher risk of mortality (HRs 1.394, 95% CI 1.121-1.734, P = .004) with adjustment for diet quality and relevant risk factors. The higher risk of mortality associated with a low-protein intake was consistent in subjects with or without albuminuria (P interaction .280). CONCLUSION: A protein intake of less than 0.8 g/kg/day was associated with a higher risk of mortality in subjects with an eGFR ≧60 mL/min/1.73 m2 , irrespective of whether they had albuminuria.

Associations of fear of hypoglycemia with second-line use of insulin secretagogues or insulin and subsequent glycemic control in patients with type 2 diabetes: An analysis using data from the DISCOVER study.

BACKGROUND: Associations of fear of hypoglycemia with prescription of second-line insulin secretagogues (IS) or insulin and subsequent glycemic control in patients with type 2 diabetes were analysed using data from the DISCOVER study-a large, prospective, observational study. METHODS: Patients with type 2 diabetes initiating a second-line treatment after a first-line oral therapy were enrolled. Fear of hypoglycemia was assessed using baseline Hypoglycemia Fear Survey (HFS) worry score. Glycemic control was assessed using glycated haemoglobin (HbA1c) levels at 6-month and 1-year follow-up, and HbA1c change from baseline was analysed. To examine the association of baseline HFS worry scores with second-line use of IS or insulin, a hierarchical logistic model with country as random effect was used. RESULTS: A total of 6217 patients were analysed. The mean HFS worry score was 6.9 ± 11.4, while patients in the upper quartile had an HFS worry score ≥9. We divided patients into three groups according to their baseline HFS worry score (0, 1-8, ≥9). HFS worry score was associated with the use of first-line IS, but not the second-line treatment. Compared to treatments with no IS and insulin, a better HbA1c response to second-line IS or insulin was noted in patients with a baseline HFS worry score of 0 or 1-8, but not in patients with a baseline HFS worry score ≥9. CONCLUSION: HFS worry score was associated with the use of first-line IS and glycemic response to second-line IS or insulin in patients with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02322762. Registered 23 December 2014.

Protein-Truncating Variants at the Cholesteryl Ester Transfer Protein Gene and Risk for Coronary Heart Disease.

RATIONALE: Therapies that inhibit CETP (cholesteryl ester transfer protein) have failed to demonstrate a reduction in risk for coronary heart disease (CHD). Human DNA sequence variants that truncate the CETP gene may provide insight into the efficacy of CETP inhibition. OBJECTIVE: To test whether protein-truncating variants (PTVs) at the CETP gene were associated with plasma lipid levels and CHD. METHODS AND RESULTS: We sequenced the exons of the CETP gene in 58 469 participants from 12 case-control studies (18 817 CHD cases, 39 652 CHD-free controls). We defined PTV as those that lead to a premature stop, disrupt canonical splice sites, or lead to insertions/deletions that shift frame. We also genotyped 1 Japanese-specific PTV in 27561 participants from 3 case-control studies (14 286 CHD cases, 13 275 CHD-free controls). We tested association of CETP PTV carrier status with both plasma lipids and CHD. Among 58 469 participants with CETP gene-sequencing data available, average age was 51.5 years and 43% were women; 1 in 975 participants carried a PTV at the CETP gene. Compared with noncarriers, carriers of PTV at CETP had higher high-density lipoprotein cholesterol (effect size, 22.6 mg/dL; 95% confidence interval, 18-27; P<1.0×10-4), lower low-density lipoprotein cholesterol (-12.2 mg/dL; 95% confidence interval, -23 to -0.98; P=0.033), and lower triglycerides (-6.3%; 95% confidence interval, -12 to -0.22; P=0.043). CETP PTV carrier status was associated with reduced risk for CHD (summary odds ratio, 0.70; 95% confidence interval, 0.54-0.90; P=5.1×10-3). CONCLUSIONS: Compared with noncarriers, carriers of PTV at CETP displayed higher high-density lipoprotein cholesterol, lower low-density lipoprotein cholesterol, lower triglycerides, and lower risk for CHD.

Hospitalization in patients with type 2 diabetes mellitus in Taiwan: A nationwide population-based observational study.

BACKGROUND/PURPOSE: We investigated hospitalization rates of patients with type 2 diabetes mellitus (T2DM) and individuals without diabetes mellitus (non-DM) in a disease-specific manner from 2005 to 2014 in Taiwan. METHODS: This population-based study was conducted using data from the National Health Insurance Research Database. We analyzed the hospitalization rates of patients with and without T2DM. We collected up to five diagnostic codes given at discharge for each hospitalization, and the first one was considered the main diagnosis. Odds ratios were determined to assess the risk of hospitalization according to disease-specific classifications in patients with T2DM compared with those without T2DM. RESULTS: The hospitalization rates of non-DM patients was stable from 2005 to 2014. By contrast, the rate of hospitalization among patients with T2DM decreased from 395.4 (per 1000 person-years) in 2005 to 336.9 (per 1000 person-years) in 2014. An increase in hospitalization rates for malignancies and sepsis/infection (other than pneumonia) was observed from 2005 to 2014 in both patients with and without T2DM. Although patients with T2DM had a higher hospitalization risk for all the disease-specific classifications than non-DM patients, this difference in risk decreased from 2005 to 2014 for all diseases except pneumonia. CONCLUSION: Hospitalization rates for malignancies and sepsis/infection (other than pneumonia) continually increased from 2005 to 2014 in Taiwan. Although patients with T2DM had a greater risk of disease-specific hospitalization than those without, this difference in risk decreased from 2005 to 2014 for all diseases except for pneumonia.

Testing for HbA1c, in addition to the oral glucose tolerance test, in screening for abnormal glucose regulation helps to reveal patients with early ß-cell function impairment.

BACKGROUND: The oral glucose tolerance test (OGTT) is recommended to screen for diabetes in patients with coronary artery disease. We hypothesized that testing for glycated hemoglobin (HbA1c), in addition to the OGTT, in screening for abnormal glucose regulation may help to reveal patients with ß-cell function impairment. METHODS: Patients with no history of diabetes who were admitted for coronary angiography were recruited to undergo an OGTT and HbA1c test 2-4 weeks after hospital discharge. ß-cell function and insulin resistance were assessed using the homeostasis model assessment (HOMA-ß and HOMA-IR, respectively). For patients with normal glucose tolerance (NGT) based on the OGTT, we compared HOMA-ß between two subgroups of patients using an HbA1c cutoff of 39 mmol/mol or 42 mmol/mol. For patients with prediabetes based on an OGTT, we compared the HOMA-ß between two subgroups of patients using an HbA1c cutoff of 48 mmol/mol. RESULTS: A total of 1044 patients were analyzed. In patients with NGT by OGTT (n=432), those with an HbA1c ≥42 mmol/mol had a lower HOMA-ß compared to those with an HbA1c <42 mmol/mol (107±82 vs. 132±96, p=0.018). In patients with prediabetes by OGTT (n=423), those with an HbA1c ≥48 mmol/mol had a lower HOMA-ß compared to those with an HbA1c <48 mmol/mol (91±52 vs. 120±88, p=0.003). No significant between-group difference in HOMA-IR was noted. CONCLUSIONS: The use of HbA1c in addition to the OGTT in screening for abnormal glucose regulation helped to reveal patients with early ß-cell function impairment.

Differential expression of circulating vascular cell adhesion molecule-1 in subjects with coronary artery disease and cardiac syndrome X without known diabetes mellitus.

CONTEXT: Inflammation is one of the mechanisms underlying cardiac syndrome X (CSX). OBJECTIVES: Few studies have compared the expression of inflammatory or adhesion molecules between coronary artery disease (CAD) versus CSX. MATERIALS AND METHODS: Ninety-two CSX and 145 CAD subjects without known diabetes mellitus underwent coronary angiogram for angina. RESULTS: Vascular cell adhesion molecule (VCAM)-1 (median, 507 versus 431 ng/ml, p = 0.001) was significantly higher in the CAD group. In the binary regression, VCAM-1 was a significant differential factor for CAD versus CSX. DISCUSSION AND CONCLUSION: Adhesion molecules might be implicated in the differential expression of macro versus microvascular coronary disease. TRIAL REGISTRATION NUMBER: NCT01198730 at https://clinicaltrials.gov.

Hydroxychloroquine reduces risk of incident diabetes mellitus in lupus patients in a dose-dependent manner: a population-based cohort study.

OBJECTIVE: SLE is associated with increased risk of diabetes mellitus. Treatment for SLE requires high-dose glucocorticoids that may worsen glucose homoeostasis. HCQ can reduce diabetes risk in RA. This study aimed to investigate the association of HCQ use and diabetes mellitus risk in SLE patients. METHODS: This nationwide, population-based cohort study was conducted using the Taiwan National Health Insurance Research Database. In the period 2001-10, 8628 newly diagnosed SLE patients were identified after excluding those with a previous diagnosis of RA, psoriasis or diabetes mellitus. Incidence of diabetes mellitus was identified as a new diagnostic code using a diabetes mellitus-specific medication. RESULTS: Two hundred and twenty-one newly diagnosed diabetes mellitus patients were identified among SLE patients (6795 had taken HCQ and 1833 had never taken HCQ), with an average follow-up period of 5.6 years. Compared with patients without HCQ treatment, the hazard ratio (HR) of diabetes mellitus in patients taking HCQ at a cumulative dose ≥129 g was reduced [HR 0.26 (95% CI 0.18, 0.37), P < 0.001]. Daily glucocorticoid ≥10 mg prednisolone-equivalent dose was associated with increased risk of developing diabetes mellitus [HR 2.47 (95% CI 1.44, 4.23), P = 0.001], which was minimized by concomitant HCQ use at a cumulative dose ≥129 g. CONCLUSION: In SLE patients, the use of HCQ is associated with reduced risk of incident diabetes mellitus in a dose-dependent manner. High-dose glucocorticoids increase the risk of diabetes, which can be decreased by concomitant HCQ use.

Weight loss reduces serum monocyte chemoattractant protein-1 concentrations in association with improvements in renal injury in obese men with metabolic syndrome.

BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) is involved in obesity-related renal injury. The aim of the present study was to examine the effects of weight loss on changes in MCP-1 and markers of renal injury, specifically serum cystatin C (S-CysC) and urinary N-acetyl glucosaminidase (UNAG), in obese people. METHODS: In this prospective study, 40 obese men with metabolic syndrome (MetS) participated in a 3-month dietary and exercise intervention. Twenty-eight subjects completed the study with a ≥5% weight loss. Circulating MCP-1, S-CysC and UNAG to creatinine ratio (UNCR) were determined before and after the weight loss program. RESULTS: Obesity-associated components of MetS demonstrated significant improvements after the weight loss program. In addition, at baseline, circulating MCP-1 concentrations were positively correlated with UNCR and S-CysC levels. After weight loss, blood MCP-1 and UNCR levels were significantly decreased, but S-CysC was not affected. Using multiple linear regression analysis, there was a significant relationship between changes in UNCR and MCP-1 after adjusting for other potential confounding factors. CONCLUSIONS: Weight loss may improve renal tubular injury by ameliorating obesity-related inflammation in obese men with MetS.

Comparing HbA1c, fasting and 2-h plasma glucose for screening for abnormal glucose regulation in patients undergoing coronary angiography.

BACKGROUND: We aimed to investigate the prevalence of undiagnosed abnormal glucose regulation (AGR, including diabetes and prediabetes) in patients undergoing coronary angiography (CAG) by using both glycated hemoglobin (HbA1c) and oral glucose tolerance test (OGTT) to screen, and to compare the performance of fasting plasma glucose (FPG), 2-h plasma glucose (2hPG), and HbA1c for screening for AGR. METHODS: Eligible patients were adults without known diabetes who were admitted for CAG. Patients' glucose regulation status was defined by conducting HbA1c and OGTT 2-4 weeks after hospital discharge. The performance of FPG, 2hPG, and HbA1c for detecting AGR was evaluated using receiver operating characteristic (ROC) analysis. RESULTS: A total of 689 subjects were included. According to OGTT, the prevalence rates of diabetes and prediabetes were 19.9% and 41.7%, respectively. The corresponding values were 28.0% and 60.4%, respectively, when HbA1c was adopted as a diagnostic criterion in addition to OGTT. For detecting diabetes, the area under the ROC curve (AUC) was higher for HbA1c than for FPG (0.87 vs. 0.80, p=0.005), but was not significantly different from that for 2hPG (0.87 vs. 0.88, p=0.58). For detecting AGR, the AUC was higher for HbA1c than for either FPG (0.94 vs. 0.74, p<0.001) or 2hPG (0.94 vs. 0.83, p<0.001). CONCLUSIONS: Using HbA1c and OGTT to screen, we reported an extremely high prevalence of previously undiagnosed AGR (28.0% diabetes and 60.4% prediabetes) in patients admitted for CAG. HbA1c may be adopted as an alternative to OGTT for screening for AGR in patients undergoing CAG.

A new formula for estimation of low-density lipoprotein cholesterol in an ethnic Chinese population.

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) is an established risk factor for cardiovascular disease and is usually estimated by the Friedewald formula (FF) calculated from three parameters, namely, total cholesterol (TC), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C). We aimed to develop a new and simple formula (NF) for LDL-C estimation. METHODS: This cross-sectional study enrolled two study populations (a testing group, n=16,749, and a validation group, n=4940). Linear regression analysis was used in the testing group to investigate the association between measured LDL-C (mLDL-C) and TC concentration, and was verified in the validation group. RESULTS: The NF yielded an estimated LDL-C (eLDL-C) equal to 0.75 × total cholesterol-0.6465 (mmol/L). For the subjects with TC between 2.58 and 7.74 mmol/L, the difference between mLDL-C and eLDL-C using the NF was less than that from the FF (testing group: -0.04 to -0.20 vs. -0.28 to -0.38 mmol/L; validation group: 0.01 to -0.12 vs. -0.23 to -0.30 mmol/L; p<0.001, respectively). The predictability of the NF was not inferior to that of the FF in subjects with different triglyceride and HDL-C concentrations, and was not affected by diabetes diagnosis and statin use. However, the NF performed similar to or worse than the FF at TC concentrations <2.58 mmol/L and >7.74 mmol/L, respectively. CONCLUSIONS: In the Chinese population, the accuracy of eLDL-C measurement with the NF was better than that with the FF, especially in subjects with TC levels between 2.58 and 7.74 mmol/L. The NF is simple and may be used for screening as well as for follow-up of patients on lipid lowering agents.

Insulinoma in a young female patient with systemic lupus erythematosus: a case report.

OBJECTIVE: Fasting hypoglycemia may occur in subjects with systemic lupus erythematosus (SLE) when accompanied with insulin-binding antibodies or insulin-receptor antibodies. However, insulinoma has not been reported in SLE subjects with hypoglycemia. METHODS: We present a case report and review the relevant literature. RESULTS: A 26-year-old female with underlying SLE experienced several episodes of neuropsychiatric symptoms in a fasting state. The steroid dosage was titrated up, but in vain. Timely imaging studies showed a pancreatic tumor, and insulinoma was proven by pathology. Hypoglycemia did not recur after surgery. CONCLUSION: Physicians should distinguish insulinoma from autoimmunity-mediated hypoglycemia in SLE patients with fasting hypoglycemia.

Sex Disparity in the Association of Metabolic Syndrome with Cognitive Impairment.

Background/Objectives: Metabolic syndrome (MS) is a constellation of several cardiometabolic risk factors. We investigated sex disparity in the associations between MS and cognitive impairment using cross-sectional data from Taiwan Biobank. Methods: We determined the associations of MS and its five components with cognitive impairment (mini-mental state examination, MMSE < 24) and the five domains of MMSE using logistic regression analyses. Results: A total of 7399 men and 11,546 women were included, and MS was significantly associated with cognitive impairment only in women (adjusted OR 1.48, 95% CI 1.29-1.71, p = 0.001) (p for interaction 0.005). In women, the association with MS was significant in orientation (adjusted OR 1.21, 95% CI 1.07-1.37, p = 0.003), memory (adjusted OR 1.12, 95% CI 1.01-1.25, p = 0.034) and design copying (adjusted OR 1.41, 95% CI 1.23-1.62, p = 0.001) (p value for interaction 0.039, 0.023, and 0.093, respectively). Among the components of MS, a large waist circumference (adjusted OR 1.25, 95% CI 1.08-1.46, p = 0.003), high fasting glucose (adjusted OR 1.16, 95% CI 1.00-1.34, p = 0.046), and low HDL cholesterol (adjusted OR 1.16, 95% CI 1.00-1.34, p = 0.049) were significantly associated with cognitive impairment in women. Conclusions: Our findings suggest that sex has a significant influence on the association between MS and cognitive dysfunction, especially in orientation and memory.

Validation of a Prediction Model for Acute Kidney Injury after Cardiac Surgery in a Retrospective Asian Cohort.

Background: The incidence of postoperative acute kidney injury (AKI) is relatively high in some Asian regions. The objective of this study was to examine the performance of an AKI prediction model developed based on data from a White-dominant population in a retrospective Asian cohort of patients undergoing cardiovascular surgery. Methods: We retrospectively identified 549 patients who underwent elective major cardiovascular surgery (coronary artery bypass graft, valve surgery, and aorta surgery), and excluded those who underwent a percutaneous cardiovascular procedure. Patients with a baseline estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 were also excluded. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) definition. Performance of the prediction model for AKI was expressed as area under the receiver operating characteristic curve (AUC). Results: The prediction model had a good predictive accuracy for postoperative AKI (all AUC > 0.92). The AUC of the prediction model in subgroups of age (<65 years and ≥65 years), sex (male and female), hypertension, and diabetes were all >0.85 (all p values < 0.001). Conclusions: The model could be used to predict postoperative AKI in Asian patients undergoing cardiovascular surgery with a baseline eGFR ≥ 60 mL/min/1.73 m2.

Associations of overweight/obesity with patient-reported outcome measures after oblique lumbar interbody fusion.

Background: Oblique lateral interbody fusion (OLIF) combined with transpedicular screw fixation has been practiced for degenerative spinal diseases of elderly patients for years. However, overweight patients have been shown to have longer operative times and more complications from surgery. The effect on clinical outcome is still uncertified. The objective of this study was to determine is overweight a risk factor to clinical outcome of OLIF combined with transpedicular screw fixation technique. Material and methods: A retrospective study in patients submitted to OLIF combined with transpedicular screw fixation from January 2018 to August 2019 was conducted. VAS score, ODI score and EQ5D were measured before the operation and one year after the operation. Results: A total of 111 patients were included with 48 patients in the non-obese group and 55 patients in the overweight/obese group. There was no significant difference between the two groups in gender, age, smoking history, hypertension, chronic kidney disease and diabetes mellitus. Overweight/obese group has higher BMI (28.4 vs. 22.7, p < 0.001) than non-obese group. There was no difference between the two groups in pre-operative VAS score, ODI score and EQ5D score. However, the healthy weight group improved much more than the overweight score in VAS score, ODI score and EQ5D score. Conclusion: The overweight/obese patient group had clinical outcomes worse than the non-obese group in terms of pain relief and life functions.