Systemic Immune-Inflammation Index in Relation to Diabetes Markers in Saudi Adults: A Retrospective Study.

Background and objectives: Low-grade inflammation is associated with metabolic disturbances like diabetes. The systemic immune-inflammation index (SII) has been proposed as a predictive tool to identify individuals at a greater risk of diabetes. This study aims to examine the association between SII and diabetes markers. Method and materials: We used retrospective data from a large cohort of adults (n = 3895) aged ≥18 in Saudi Arabia. The SII was calculated, and the markers of diabetes such as fasting blood glucose (FBG), insulin, and hemoglobin A1c (HbA1c) were included. Results: Across the quartiles of SII, FBG, insulin, and HbA1c were significantly higher in adults with higher compared to lower SII (p < 0.0001, p = 0.04, p < 0.0001, respectively). A two SD higher FBG was significantly associated with an SII difference of 47.7 (95% CI: (15.5, 91.9)). In subgroup analysis, this relationship prevailed in normal-weight participants and among those with normoglycemia and prediabetes but was attenuated in participants with diabetes. The association also prevailed in separate analyses for males and females but was stronger among females. Linear regression models showed no significant association between insulin, HbA1c, and SII. Conclusions: SII was associated with the markers of diabetes. The utility of SII for predicting diabetes can be confirmed with prospective cohort studies.

The clinical utility of total concentration of urinary globotriaosylsphingosine plus its analogues in the diagnosis of Fabry disease.

BACKGROUND: Fabry disease (FD) is a genetic disorder caused by defective α-galactosidase-A enzyme due to mutations in the GLA gene. A reliable diagnosis in classical FD males can be made by measuring the enzyme activity while diagnosing classical FD females and non-classical FD patients requires mutation analysis. Plasma globotriaosylsphingosine (Lyso-Gb3) has progressively gained more importance as a diagnostic biomarker for FD in recent years. Having another biomarker to complement plasma Lyso-Gb3 will increase the diagnostic accuracy in the era of mass screening, and also precision medicine. This study aims to highlight the clinical utility of the total concentration of urinary Lyso-Gb3 plus its analogues in diagnosing FD. METHOD: Random urine samples collected from 42 FD patients and 48 healthy individuals. Lyso-Gb3 and its analogues were enriched by solid phase extraction and analysed by liquid chromatography tandem mass spectrometry. RESULTS: The total concentration of Lyso-Gb3 plus its analogues in classical FD male and female patients were 1124.4 ±â€¯181.2 and 308.6 ±â€¯78.6 pmol/mmol creat., respectively. The levels in non-classical FD male and female patients were 229.2 ±â€¯169.4 and 314.4 ±â€¯156.4 pmol/mmol creat., respectively. Urinary Lyso-Gb3 and its analogues were virtually undetectable in healthy volunteers making it 100% specific for FD diagnosis. For FD male and female patients, total concentration of urinary Lyso-Gb3 plus its analogue levels ≥0.25 pmol/mmol creat. yielded a diagnostic sensitivity and specificity of 100% (AUC = 1, p < 0.00001). CONCLUSIONS: Our study findings support that the total concentration of Lyso-Gb3 plus its analogues in urine is specific to FD and may provide extra diagnostic utility for both classical and non-classical FD patients.

Fat volume measurements as a predictor of image noise in coronary computed tomography angiography.

INTRODUCTION: Image noise can negatively affect the overall quality of coronary computed tomography angiography (CCTA). OBJECTIVES: The purpose of this study was to evaluate the relationship between image noise and fat volumes in the chest wall. We also aimed to compare these with other patient-specific predictors of image noise, such as body weight (BW) and body mass index (BMI). METHODS: We undertook a cross-sectional, single-center study. A tube voltage of 100 kV was used for patients with BW <85 kg and 120 kV for BW ≥85 kg. The image noise in the aortic root, single-slice fat volume (SFV) at the level of the left main coronary artery and the total fat volume of the chest (TFV) were analyzed. RESULTS: A total of 132 consecutive patients were enrolled (mean age ±â€¯standard deviation, 51 ±â€¯11 years; 64% male). The mean image noise was 30.5 ±â€¯11 Hounsfield units (HU). We found that patients with image noise >30 HU had significantly higher SFV (75 ±â€¯33 vs. 51 ±â€¯24, p < 0.0001) and TFV (2206 ±â€¯927 vs. 1815 ±â€¯737, p < 0.01) compared with patients having noise ≤30 HU, whereas BW and BMI showed no significant difference (78 ±â€¯13 vs. 81 ±â€¯14, p < 0.34) and (28.7 ±â€¯4.7 vs. 26.8 ±â€¯3.8, p < 0.19), respectively. Linear regression analysis showed that image noise has better correlation with SFV (R = 0.399; p < 0.0001); and TFV (R = 0, p < 0.009) than BMI (R = 0.154, p < 0.039) and BW (R = -0.102, p = 0.12). CONCLUSIONS: Fat volume measurements of the chest wall can predict CCTA image noise better than other patient-specific predictors, such as BW and BMI.

Globotriaosylsphingosine (Lyso-Gb3) as a biomarker for cardiac variant (N215S) Fabry disease.

Fabry disease (FD) is a multi-systemic X-linked lysosomal disorder caused by the deficient activity of α-galactosidase-A enzyme, which leads to accumulation of glycosphingolipids in various body tissues. The N215S mutation is a known variant of FD, with a late onset cardiac phenotype. Consensus guidelines acknowledged the use of globotriaosylsphingosine (Lyso-Gb3) as a diagnostic marker for classical FD but its utility for cardiac variant FD is not clear. We aim to characterize the clinical features and evaluate the diagnostic accuracy of plasma and urinary Lyso-Gb3 levels in N215S cardiac variant FD patients. Thirty-four FD patients with the late-onset N215S cardiac variant mutation were enrolled along with 62 classical FD patients and 109 healthy controls. Plasma and urinary Lyso-Gb3 and its analogues were analyzed by LC-MS/MS. Both FD males and females with N215S mutation showed Lyso-Gb3 levels of (mean ± SEM) 9.7 ± 1.0 and 5.4 ± 0.8 nM, respectively. These levels were significantly higher than healthy control and lower than classical FD patients (p < 0.0001). Plasma Lyso-Gb3 levels equal to or higher than 2.7 nM yielded a diagnostic sensitivity and specificity of 100% (AUC = 1, p < 0.0001). Cardiac involvement was frequent with 16/34 (47%) developing left ventricular hypertrophy. Three patients who underwent renal biopsy had the characteristic sphingolipid deposition in the podocytes while 6/19 (32%) had evidence of white matter changes or infarct on brain MRI. Taken together, cardiac variant N215S mutation is rather an attenuated form of classical FD. Plasma Lyso-Gb3 is a diagnostic hallmark to differentiate N215S variant phenotype from subjects with no FD.

A Novel Rapid MALDI-TOF-MS-Based Method for Measuring Urinary Globotriaosylceramide in Fabry Patients.

Fabry disease is an X-linked lysosomal storage disorder caused by deficiency of α-galactosidase A, resulting in the accumulation of glycosphingolipids in various organs. Globotriaosylceramide (Gb3) and its isoforms and analogues have been identified and quantified as biomarkers of disease severity and treatment efficacy. The current study aimed to establish rapid methods for urinary Gb3 extraction and quantitation. Urine samples from 15 Fabry patients and 21 healthy control subjects were processed to extract Gb3 by mixing equal volumes of urine, methanol containing an internal standard, and chloroform followed by sonication and centrifugation. Thereafter, the lower phase was analyzed by MALDI-TOF MS and the relative peak areas of the internal standard and four major species of Gb3 determined. The results showed high reproducibility with intra- and inter-assay coefficients variation of 9.9% and 13.7%, respectively. The limit of detection was 0.15 ng/µL and the limit of quantitation was 0.30 ng/µL. Total urinary Gb3 levels in both genders of classic Fabry patients were significantly higher than in healthy controls (p < 0.0001). Gb3 levels in Fabry males were higher than in Fabry females (p = 0.08). We have established a novel assay for urinary total Gb3 that takes less than 15 min from start to finish. Graphical Abstract ᅟ.