Establishment of reference intervals for free light chains and immunoglobulins in Saudi population.

OBJECTIVES: Testing of serum-free light chains kappa (κ) and lambda (λ), along with ratio (FLCR) is essential for the diagnosis and management of monoclonal gammopathies. Accurate clinical diagnosis depends upon appropriate local population reference intervals (RIs). This study examined the Saudi population for serum-free light chains and other immunoglobulins to establish RIs and to explore variations in the test results by using the International Federation for Clinical Chemistry and Laboratory Medicine's global protocol for harmonized implementation of RI study. METHODS: A total of 180 healthy Saudi adults were recruited. All serum samples were assayed using the Freelite reagents from the Binding Site. The variation in reference values attributable to sex, age, BMI, and region was calculated by ANOVA as a standard deviation ratio (SDR). The RIs for the FLCR were derived by the parametric method and validated by using samples from patients with hypo- and hypergammaglobulinemia. RESULTS: The new RIs for free κ and FLCR were shifted to a higher side from the manufacturer-adapted RIs. Based on the SDR cutoff value (>0.4), between-sex partition RIs were not required for all analytes except IgM. Validation using patients with hypo- or hypergammaglobulinemia and without multiple myeloma, was all within the new RI. BMI, smoking, and exercise were not relevant sources of variation for any analyte. CONCLUSIONS: Locally derived RIs for free light chains and immunoglobulins analytes specific for Saudis were established after careful consideration of various factors. These RIs were more reliable than those provided as guidance by the manufacturer, or from other countries, for appropriate classification and prediction of disease progression for Saudi patients.

The assessment of liver function test and fertility hormones in Saudi athletes using anabolic androgenic steroids.

Background: A growing number of athletes are using synthetic anabolic-androgenic steroids (AAS), comprised of testosterone and other derivatives, to enhance athletic performance and muscle mass. Over the years, numerous reports elucidated the side effects of the illegal use of AAS, such as infertility, and liver disorders. The effect of AAS on the hepatic and reproductive systems in Saudi athletes has not yet been studied. Therefore, this study examined the liver function and sex hormone parameters of AAS users as compared to non-users. Methods: Fasting blood samples were collected from 16 male Saudi athletes, 10 AAS-users (cases) and 6 non-users (controls) to measure liver function tests (ALT, AST, GGT, ALP, total protein, albumin, direct and total bilirubin) and muscle enzymes (CK, LDH), Fertility hormones (LH, FSH, total testosterone, estradiol, and prolactin) were included also. Furthermore, a self-reported questionnaire was obtained to identify the type of AAS used, the dosage, and the length of the course before sample collection. Results: The results show a statistically significant increase in ALT (P < 0.001), AST (P < 0.001), CK (P < 0.05), and a significant decrease (P < 0.05) in albumin (P < 0.001) and total bilirubin levels (P < 0.01) in AAS-users. Total testosterone increased significantly among AAS (P < 0.05), along with a significant decrease in LH (P < 0.01), and FSH (P < 0.001) levels, while serum prolactin and estradiol levels were significantly increased (P < 0.05). Conclusion: AAS can enhance physical performance and appearance, its potential adverse effects on the hepatic and reproductive systems necessitate careful consideration. Our research demonstrates an increase in the liver-specific enzyme ALT in AAS users relative to non-users and the possibility that short-term AAS usage increases the risk of liver injury.

Diagnostic comparison between cord blood and filter paper for the screening of congenital hypothyroidism.

BACKGROUND: Cord-blood and heel-prick TSH levels are essential in diagnosing and preventing the serious complications of congenital hypothyroidism, which mainly include intellectual disability. The study aimed to compare between cord-blood and heel-prick TSH sensitivity and specificity in detecting congenital hypothyroidism (CH) among newborn screened babies. METHOD: The study included 21,012 newborn screened babies for congenital hypothyroidism starting from September 2013 until March 2019. Both cord-blood and heel-prick TSH were collected from each newborn. Heel prick and cord-blood TSH cutoff values of >21 µU/ml and >30 mIU/L respectively were considered positive. RESULTS: Out of the total screened newborns, 12 were confirmed for having primary congenital hypothyroidism. Nine cases were positive for cord-blood TSH (Sensitivity 75%, specificity 99.9%, and a recall rate of 0.004%), while 139 cases were positive for heel-prick blood TSH (Sensitivity of 100%, specificity of 99.3%, and a recall rate of 0.60%). CONCLUSION: For the screening of CH, heel prick is considered a superior method, but cord blood remains a practical option due to its cost-effectiveness, immediate action, and lower recall rate. Therefore, whenever recall is difficult and/or early discharge is the practice, cord blood is an alternative method to heel prick but not with cases of prematurity.

Stability and validity of intact parathyroid hormone levels in different sample types and storage conditions.

BACKGROUND: Several pre-analytical factors can affect the measurement of intact Parathyroid Hormone (IPTH). In this study, we have investigated the effects of using different types of tubes, time elapsed before separation, and storage conditions over time on the measured values of IPTH. METHOD: Blood samples from 30 subjects were collected into plain, SST, and EDTA tubes. All serum and plasma were separated immediately (first set) and after 2 hrs delay (second set). The first set of samples were aliquoted and stored at RT (25°C), at fridge (4°C), and freezer (-20°C). IPTH was measured in all the stored aliquots at 2,4, and 8 days after collection using Architect analyzer. RESULTS: Paired T test and ANOVA repeated measures showed no significant difference between IPTH levels in all tubes. The second set of serum and plasma were significantly lower (3.8% and 7.4%, p < 0.001, respectively) when compared to samples measured initially. Serum samples stored at RT were significantly lower (by 45%,59%, and 77%) on days 2,4, and 8 when compared to the initial time (p < 0.001 in all cases). Plasma samples stored at RT, were significantly lower on day 8 after collection, by 30.8% (p < 0.001). These differences would be clinically important. CONCLUSION: Plasma IPTH can be stored at RT for up to four days. Both plasma and serum IPTH are not affected by a delay in the separation of up to two h and they can be stored for up to 8 days in a fridge or freezer without any clinically significant changes in their values.

Establishment of reference intervals for immunoassay analytes of adult population in Saudi Arabia.

Background This is a second part of report on the IFCC global multicenter study conducted in Saudi Arabia to derive reference intervals (RIs) for 20 immunoassay analytes including five tumor makers, five reproductive, seven other hormones and three vitamins. Methods A total of 826 apparently healthy individuals aged ≥18 years were recruited in three clinical laboratories located in western, central and eastern Saudi Arabia using the protocol specified for the global study. All serum specimens were measured using Abbott, Architect analyzers. Multiple regression analysis (MRA) was performed to explore sources of variation of each analyte: age, body mass index (BMI), physical exercise and smoking. The magnitude of variation of reference values (RVs) attributable to sex, age and region was calculated by ANOVA as a standard deviation ratio (SDR). RIs were derived by the parametric (P) method. Results MRA revealed that region, smoking and exercise were not relevant sources of variation for any analyte. Based on SDR and actual between-sex differences in upper limits (ULs), we chose to partition RIs by sex for all analytes except for α-fetoprotein and parathyroid hormone (PTH). Age-specific RIs were required in females for ferritin, estradiol, progesterone, testosterone, follitropin, luteotropin and prolactin (PRL). With prominent BMI-related increase, RIs for insulin and C-peptide were derived after excluding individuals with BMI > 32 kg/m2. Individuals taking vitamin D supplements were excluded in deriving RIs for vitamin D and PTH. Conclusions RIs of major immunoassay analytes specific for Saudi Arabians were established in careful consideration of various biological sources of variation.

Assessing the Accuracy of Different Glucometers Based on the Laboratory Reference Method.

BACKGROUND: Self-monitoring of blood glucose using point-of-care glucometers is a critical tool in diabetic care. Recently, various glucometers have been developed. This cross-sectional study aimed to evaluate the accuracy of commonly used glucometers by comparing their readings with those of the laboratory reference method. METHODS: The five commercially available glucometers - Accu-Chek (Roche Diagnostics GmbH, Mannheim, Ger-many), OneTouch (LifeScan Inc, USA), Freestyle Optium Neo (Abbott Diabetes Care Inc, USA), Contour Next, and Contour Next One (Ascensia Diabetes Care Inc. Canada) - were utilized in our study. Participants were randomly selected for measuring fasting blood glucose levels to eliminate any factors that could affect measurements by the glucometers and glucose hexokinase method (reference method). Statistical analysis was carried out and the readings were expressed as mean and standard deviation. RESULTS: All glucometer readings correlated well with the laboratory measurements; however, the venous glucose level readings showed a slight difference, especially in case of higher blood glucose levels. Although, no significant difference was found between the mean venous blood glucose and the mean of other glucometer readings, a highly significant positive correlation was found between laboratory measurements and glucometer readings. Moreover, our study confirmed that Accu-Check, OneTouch, and FreeStyle Optium Neo meters were significantly useful predictors of venous blood glucose. Notably, Freestyle Optium Neo showed the minimal mean bias (-0.4%) in contrast to Contour Next One that showed the highest proportional bias (6.1%). CONCLUSIONS: Independent comparison of all glucometers should be carried out as the proportional bias, especially in case of high blood glucose levels, can affect patient care.

Changes in Hematological Indices and Lymphocyte Subsets in Response to Platelet Apheresis Donation.

BACKGROUND: Platelet apheresis is a technique in which whole blood is collected from a donor followed by platelet (PLT) separation. Platelet apheresis has a significant impact on some biochemical indices after donation. This study aimed to investigate the impact of platelet apheresis on complete blood count (CBC) and lymphocyte subsets over a typical interdonation interval. METHODS: Healthy male subjects (n = 10) were recruited to study changes in CBC and lymphocyte subsets before and at three intervals following platelet apheresis. Repeated measures ANOVA was used to compare quantitative variables between different visits. RESULTS: Following platelet apheresis, platelet count decreased 30% at 24 hours after donation (p < 0.001) compared to the baseline count with significant repeated ANOVA across different visits (p < 0.001, Eta = 0.558). No changes were observed in other variables of CBC. The lymphocyte subsets including CD4, CD8, and CD4/CD8 ratio were decreased at 24 hours after donation (-0.6%, -0.4% and -0.7%, respectively) but none was significant. At 24 hours, the proportion of CD19 and CD16-56 were slightly increased (1.6%, 3.3%, p > 0.05, respectively). CONCLUSIONS: The significant reduction in PLT count after 24 hours of plateletpheresis may have adverse health effects on PLT donors. Platelet apheresis has no significant effect on lymphocyte subsets of the donor.

The pre-analytical stability of 25-hydroxyvitamin D: Storage and mixing effects.

BACKGROUND: There is an increasing demand for serum 25-OH VitD testing globally, and this has led to the greater use of automated immunoassays. These may be more prone to non-specific interference, that is thought to be related to pre-analytical stability of biological samples. We have investigated the changes in serum 25-OH VitD concentrations that are caused by storage and mixing conditions, and if such changes are statistical, or clinically important. METHODS: Blood samples were collected into plain tubes from 31 healthy donors. After separation, serum samples were stored at -20°C and analysis was carried out with and without mixing (vortexing) at different time intervals of days (0, 1, 2, 3, 4, 5, 15, and 30). All samples were analyzed using a chemiluminescent immunoassay. RESULTS: Mean serum 25-OH VitD concentrations for subsequent days of storage compared with day 0 showed a significant time effect (P < .05) except for the samples on day 1 (P = .654) in non-vortexed samples and day 2 (P = .087), 5 (P = .118) and 30 (P = .118) in vortexed samples. Comparing values for vortexed and non-vortexed samples on the same day, serum 25-OH VitD showed a significant difference on days 1 (P = .003), 4 (P = .037), 5 (P = .002), and 30 (P = .025). However, the maximum change value was 8.85% which was less than the known total allowable error (TEa) and reference change value (RCV) for serum 25-OH VitD. CONCLUSION: 25-OH VitD is pre-analytically stable after long-term sample storage at -20°C and can be analyzed without vortexing. This may be beneficial for both research and diagnostic laboratories.

Diet influences levels of plasma lipopolysaccharide (LPS) and its soluble receptor (sCD14) in Saudis.

OBJECTIVE: This study aimed to investigate the association between serum levels of LPS, sCD14 and hs-CRP, and markers of obesity, and dietary composition of healthy adults residing in Jeddah, Saudi Arabia. METHODS: Apparently healthy adults, aged 18-55 years, were recruited from Jeddah population in a cross-sectional design. Anthropometric measurements, and vital signs were taken using standardized techniques. Serum glucose, cholesterol (TC), triglycerides (TG), high-density lipoprotein- cholesterol (HDL-C), hs-CPR, LPS and sCD14 were assayed, and LDL- cholesterol (LDL-C), and atherogenic index of plasma (AIP) were calculated. Means of estimated variables were compared using t-test or Mann-Whitney U-test for two groups and ANOVA for multiple groups. Chi-square, and Pearson's correlation coefficient were used to identify association and correlations between studied variables. RESULTS: Means of TG, LDL-C, and hs-CRP increased significantly in both genders with increasing BMI (p= 0.019, and 0.040 for TG, 0.049, and 0.002 for LDL-C in males and females respectively, and <0.001 for hs-CRP for both). Mean hs-CRP was significantly higher in subjects with abdominal obesity (p=0.025 for men, and 0.001 for women), identified to have metabolic syndrome (p<0.001). Mean sCD14 was significantly elevated in females consuming high quantity of bread (p= 0.033) or drinking tea (p = 0.018). LPS correlated positively with sCD14 in men (p=0.049). CONCLUSIONS: An association between dietary composition and development of bacterial endotoxaemia was found. However, no association between measures of endotoxaemia and increased adiposity and inflammation was found.

Study of Biochemical Changes after Plateletpheresis in Healthy Male Donors.

BACKGROUND: There is relatively little information about endogenous biochemical changes in a response to plateletpheresis in healthy donors. We aimed to investigate the changes in different biochemical parameters including glycemic status, insulin resistance, iron status, lipid profile, and inflammatory markers after plateletpheresis in healthy male donors with normal glycemic status. METHODS: In this study we enrolled 10 male subjects. The glycemic status in all subjects was assessed using an oral glucose tolerance test pre- and post-plateletpheresis at different time intervals (1, 8, and 22 days). Different biochemical parameters including glucose, HbA1c, insulin, lipids, uric acid, transferrin, ferritin, C-reactive protein, and insulin resistance were measured. Repeated ANOVA was utilized for the purpose of statistical comparison of means between different days. RESULTS: Fasting glucose, transferrin, cholesterol, triglycerides, HDL-C, and LDL-C were significantly altered (-3.9%, p < 0.05; -2.7%, p < 0.05; -3.9%, p < 0.05; 23.9%, p < 0.05; -5.5%, p < 0.01, and -9.2%, p < 0.05, respectively) at day 1 following plateletpheresis. There was a gradual reduction in HbA1c and ferritin levels during the time-course of the study, and by day 22, both were significantly lower (-2.0%, p < 0.01; -18.1%, p < 0.05, respectively) when compared to the pre-plateletpheresis levels. CONCLUSIONS: Post-plateletpheresis, several biochemical parameters may change significantly in healthy donors. The changes were particularly evident on day 1 and 22 after donation. The potential effects of plateletpheresis need to be considered when interpreting biochemical tests.

Protective effect of metoclopramide against organophosphate-induced apoptosis in the murine skin fibroblast L929.

This study was performed to evaluate the protective efficacy of metoclopramide (MCP) against the organophosphates paraoxon (POX)- and malathion (MLT)-induced apoptosis in the murine L929 skin fibroblasts. L929 cells were exposed to either POX (10 nm) or 1.0 µm MLT in the absence and presence of increased concentrations of MCP. The protective effect of MCP on these organophosphate-stimulated apoptotic events was evaluated by flow cytometry analysis after staining with annexin-V/propidium iodide, processing and activation of the executioner caspase-3, cleavage of the poly-ADP ribose polymerase, fragmentation of the nucleosomal DNA and disruption of the mitochondrial membrane potential (Δψ). Our results showed that increased doses of MCP alone (≥10 µm) did not induce apoptosis or activation of caspase-3. Pretreatment of the cells with MCP attenuated all the apoptotic events triggered by the organophosphate compounds in a dose-dependent manner reaching ~70-80% protection when they were preincubated at 1 and 5 µm of the drug before the addition of POX and MLT, respectively. Interestingly, MCP did not offer a significant protective effect against the cytotoxicity of tumor necrosis factor-α, cisplatinum, etoposide or paclitaxel, which stimulate apoptosis by various mechanisms, suggesting that the anti-apoptotic effect of the drug is specific to organophosphates. The strong and specific anti-apoptotic activity of subclinical doses of MCP against the cytotoxicity of organophosphate compounds suggests its potential clinical application in treating their poisoning.

Comprehensive Analysis of the Chemical Composition and In Vitro Cytotoxic Mechanisms of Pallines Spinosa Flower and Leaf Essential Oils Against Breast Cancer Cells.

BACKGROUND/AIMS: In our quest for new natural anticancer agents, we studied the cytotoxicity of the essential oils extracted from flowers and leaves of Pallines spinosa. METHODS: The essential oils were extracted by hydrodistillation and solid phase microextraction (SPME) from flowers and leaves of the plant and their composition was determined by GC/GC-MS. The cytotoxicity of the oils was evaluated against MCF-7 and MDA-MB-231 breast adenocarcinomas, and the non-cancerous MCF-10-2A cells, using a flow cytometry-based assay Apoptosis was evaluated by flow cytometry, nuclear staining, caspases activation, and Western blotting techniques, and cell cycle by measuring DNA contents. RESULTS: The hydrodistilled flower oil contained mainly sesquiterpenes (96.39%), while the leaf sample was dominated by oxygenated-sesquiterpenes (51.60%) and sesquiterpene-hydrocarbons (34.06%). In contrast, the SPME oil contained mainly monoterpene-hydrocarbons (44.09%) and sesquiterpene-hydrocarbons (34.15%) in the flower and leaf samples, respectively. The cytotoxicity of the flower oil against MCF-7 (IC50 0.25 ± 0.03 µg/mL) and MDA-MB-231 (IC50 0.21 ± 0.03 µg/mL) was much stronger than the leaf oil (IC50 2.4 ± 0.5 µg/mL and 1.5 ± 0.1 µg/mL, respectively). The toxicity of the flower oil was ∼5 to 8-times less in normal MCF-10-2A (IC50 1.3 ± 0.2 µg/mL) and blood mononuclear cells (2.80 ± 0.45 µg/mL) as compared to breast and hematological cancer cells, respectively. Both oils induced a caspase-dependent and -independent apoptosis in MCF-7 and MDA-MB-231 cells, and altered the levels of Bcl-2 and Bax proteins. In addition, the oils arrested cell cycle in both cancer cell lines at G0/G1 phase by modulating the expression of cyclin D1, CDK4 and p21 proteins. CONCLUSION: The cytotoxicity of P. spinosa oils were mediated by apoptosis and cell cycle arrest, suggesting the potential use of their bioactive compounds as natural anticancer compounds.

Changes in hematological indices and lymphocyte subsets in response to whole blood donation in healthy male donors.

Whole blood donation has immunomodulatory effects, and most of these have been observed at short intervals following blood donation. This study aimed to investigate the impact of whole blood donation on lymphocyte subsets over a typical inter-donation interval. Healthy male subjects were recruited to study changes in complete blood count (CBC) (n = 42) and lymphocyte subsets (n = 16) before and at four intervals up to 106 days following blood donation. Repeated measures ANOVA were used to compare quantitative variables between different visits. Following blood donation, changes in CBC and erythropoietin were as expected. The neutrophil count increased by 11.3% at 8 days (p < .001). Novel changes were observed in lymphocyte subsets as the CD4/CD8 ratio increased by 9.2% (p < .05) at 8 days and 13.7% (p < .05) at 22 days. CD16-56 cells decreased by 16.2% (p < .05) at 8 days. All the subsets had returned to baseline by 106 days. Regression analysis showed that the changes in CD16-56 cells and CD4/CD8 ratio were not significant (Wilk's lambda = 0.15 and 0.94, respectively) when adjusted for BMI. In conclusion, following whole blood donation, there are transient changes in lymphocyte subsets. The effect of BMI on lymphocyte subsets and the effect of this immunomodulation on the immune response merit further investigation.

Establishment of reference intervals of clinical chemistry analytes for the adult population in Saudi Arabia: a study conducted as a part of the IFCC global study on reference values.

BACKGROUND: This study is a part of the IFCC-global study to derive reference intervals (RIs) for 28 chemistry analytes in Saudis. METHOD: Healthy individuals (n=826) aged ≥18 years were recruited using the global study protocol. All specimens were measured using an Architect analyzer. RIs were derived by both parametric and non-parametric methods for comparative purpose. The need for secondary exclusion of reference values based on latent abnormal values exclusion (LAVE) method was examined. The magnitude of variation attributable to gender, ages and regions was calculated by the standard deviation ratio (SDR). Sources of variations: age, BMI, physical exercise and smoking levels were investigated by using the multiple regression analysis. RESULTS: SDRs for gender, age and regional differences were significant for 14, 8 and 2 analytes, respectively. BMI-related changes in test results were noted conspicuously for CRP. For some metabolic related parameters the ranges of RIs by non-parametric method were wider than by the parametric method and RIs derived using the LAVE method were significantly different than those without it. RIs were derived with and without gender partition (BMI, drugs and supplements were considered). CONCLUSIONS: RIs applicable to Saudis were established for the majority of chemistry analytes, whereas gender, regional and age RI partitioning was required for some analytes. The elevated upper limits of metabolic analytes reflects the existence of high prevalence of metabolic syndrome in Saudi population.

Assessment of Becton Dickinson Plain and Serum Separator Tubes in Measurement of 25-Hydroxyvitamin D3 (25OHD3) by HPLC and Immunoassay Methods.

BACKGROUND: The accuracy of 25-hydroxyvitamin D3 (25OHD3) measurement on specimens collected into serum separator tubes (SSTs) has been questioned because of possible interference by the gel. Possible interference was investigated in SSTs from Becton Dickinson (BD). DESIGN AND METHODS: Blood specimens were collected simultaneously from 50 normal subjects into plain tubes and SSTs. 25OHD3 was assayed on serum using high performance liquid chromatography (Chromsystems), and Architect (Abbott) and Liaison (Diasorin) immunoassays. RESULTS: There were no significant differences between 25OHD3 results (means ± SE, nmol/l) obtained from specimens collected into plain tubes and SSTs assayed by HPLC (39.0 ± 2.7 vs. 39.3 ± 2.7), Liaison (32.9 ± 2.2 vs. 32.8 ± 2.3), or Architect (43.1 ± 2.8 vs. 43.2 ± 2.8). In specimens collected into plain tubes and SSTs, 25OHD3 measurements by HPLC correlated significantly (P < 0.0001) with those from the Architect (r = 0.895, r = 0.908) and Liaison (r = 0.907, r = 0.913), respectively. CONCLUSIONS: The gel in SSTs (BD) does not interfere with the measurement of 25OHD3 by HPLC or common immunoassays. This important finding may enable clinical laboratories to make cost savings by using SSTs without concerns about inaccuracy.

Insulin-like growth factor-II: its role in metabolic and endocrine disease.

Insulin-like growth factor-II (IGF-II) is a widely expressed 7·5 kDa mitogenic peptide hormone. Although it is abundant in serum, understanding of its physiological role is limited compared with that of IGF-I. IGF-II regulates foetal development and differentiation, but its role in adults is less well understood. Evidence suggests roles in a number of tissues including skeletal muscle, adipose tissue, bone and ovary. Altered IGF-II expression has been observed in metabolic conditions, notably obesity, diabetes and the polycystic ovary syndrome. This article summarizes what is known about the actions of IGF-II and its dysregulation in metabolic and endocrine diseases. The possible causes and consequences of dysregulation are discussed along with the implications for diagnostic tests and future research.

Assessment of the systemic immune-inflammation index in type 2 diabetic patients with and without dry eye disease: A case-control study.

Background: The inflammation plays a role in the pathophysiology of type-2 diabetes progression, and the mechanism remains unclear. The systemic immune-inflammation index (SII) is a novel inflammatory marker for type 2 diabetes patients and integrates multiple indicators in complete blood counts and routine blood tests. Aim: Since there is no international diagnostic standard for dry eye disease (DED), this study uses low-cost inflammatory blood biomarkers to investigate the correlation between SII and DM2-DED and determine the diagnosis indices of other biomarkers in DM2-DED. Methodology: A case-control retrospective analysis of totel patients n = 293 randomly selected and categorized into four groups: DED, DM2, DM2-DED, and healthy subjects. Demographic and blood biomarker variables were classified as categorical and continuous variables. The platelet-to-lymphocyte ratio (PLR), lymphocytes-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio (NLR), and SII were calculated platelet count multiply by NLR and analyzed for their correlation for all groups. Results: Focusing on DM2-DED patients was more common in females, 59.6%, than in males, 40.2%. The mean ages were 60.7 ± 11.85 years, a statistically significant difference with all groups. In the study group DM2-DED, there was an increase in all blood markers compared to all remaining groups except PLR. Only neutrophil, hemoglobin A1c (HbA1c), and fasting blood sugar levels were statistically significant differences in DM2-DED patients (p > 0.001, p < 0.001, and p < 0.001, respectively) compared to all groups. There was a positive correlation between HbA1c and PLR, HbA1c and NLR, and HbA1c and SII (r = 0.037, p = 0.705; r = 0.031, p = 0.754; and r = 0.066, p < 0.501, respectively) in the DM2-DED group. Conclusion: This study demonstrated that elevated SII values were linked to elevated HbA1c in DM2-DED patients. The potential of SII and HbA1c as early diagnostic indicators for ocular problems associated with diabetes mellitus is highlighted by their favorable connection in diagnosing DM2-DED.

Establishment of reference interval for hemoglobin A1C and other hemoglobin subfractions for healthy Saudi adults.

BACKGROUND: The establishment of Reference Intervals (RIs) for Hemoglobin A1C and other hemoglobin subfractions (A1A, A1B, F, LA1C, A0) is of utmost importance in screening, diagnosing, and monitoring diabetes and other hemoglobin abnormalities through the application of high-pressure liquid chromatography (HPLC) technique. Because there are no locally established RIs for these parameters, it is essential to establish RIs specific to the Saudi population to accurately diagnose and monitor diabetic individuals and identify abnormal levels in hemoglobin subfractions. METHODS: As part of the IFCC global multicenter study of laboratory reference values, a cross-sectional study was conducted in Saudi Arabia. The study involved recruiting a total of 381 healthy adult subjects (>18 years, BMI 28.3 ± 6 kg/m2). Blood samples were analyzed for A1C, biochemical and other immunoassay parameters. The need for RIs based on sex, age, and BMI was determined using the standard deviation ratio (SDR) through a 3-level nested ANOVA. RESULTS: Based on the threshold of SDR≥0.4, RIs for A1C and other Hb subfractions were not partitioned by sex or BMI, but partitioned by age (<45 & ≥45 years) for A1C, LA1C, A0 and F. Spearman's correlation between glucose, insulin, and C-peptide showed a positive association with different hemoglobin subtractions of A1B, F, A1C, and LA1C. The RIs were obtained by using the parametric method and the latent abnormal values exclusion (LAVE) principle was applied on A1C. CONCLUSION: This study established RIs for A1C and other Hb subfractions for healthy adult Saudis. Age was found to be an important source of variation for most of the parameters including A1C. These findings will enhance the understanding and clinical decision-making concerning A1C and other hemoglobin subfractions. The elevated upper limit of RIs for A1C reflects the high prevalence of diabetes in the Saudi population specially in those with increased age.

Reference change values for insulin and insulin-like growth factor binding protein-1 (IGFBP-1) in individuals with varying degrees of glucose tolerance.

BACKGROUND: The reference change value (RCV) is an important parameter of biological variation used to assess the significance of differences between consecutive results obtained in a single individual. This study evaluated the RCV for insulin-like growth factor binding protein-1 (IGFBP-1) and fasting serum insulin (FSI) in individuals with different degrees of glucose tolerance. METHODS: IGFBP-1 and FSI concentrations were measured in 33 fasting subjects who had two blood samples taken 10 days apart. Subjects were distributed in the following categories: Normal glucose tolerance (NGT), n = 15, impaired fasting glucose (IFG), n = 9 and impaired glucose tolerance (IGT), n = 9. RESULTS: The RCV values for IGFBP-1 were 59.9%, 83.2% and 93.0% and for FSI were 68.5%, 79.0% and 93.4% for subjects with NGT, IFG and IGT respectively. CONCLUSIONS: The RCVs for IGFBP-1 and FSI increase with deteriorating glucose tolerance. When monitoring IGFBP-1 and FSI, changes in concentrations should be interpreted using glycaemic category-specific RCV values.

Fibroblast Growth Factor 21: A More Effective Biomarker Than Free Fatty Acids and Other Insulin Sensitivity Measures for Predicting Non-alcoholic Fatty Liver Disease in Saudi Arabian Type 2 Diabetes Patients.

Background Non-alcoholic fatty liver disease (NAFLD) is more prevalent among individuals with type 2 diabetes (T2DM), elevating their risk of cardiovascular diseases (CVDs) and premature mortality. There is a need to modify treatment strategies to prevent or delay these adverse outcomes. Currently, there are no sensitive or specific biomarkers for predicting NAFLD in Saudi T2DM patients. Therefore, we aimed to explore the possibility of using fibroblast growth factor 21 (FGF-21), free fatty acids (FFAs), homeostatic model assessment for insulin resistance (HOMA-IR), and quantitative insulin sensitivity check index (QUICKI) as possible markers. Methodology In this study, a total of 67 T2DM patients were recruited. NAFLD was detected by ultrasonography in 28 patients. Plasma glucose, FFAs, FGF-21, and serum insulin were measured in fasting blood samples. HOMA-IR and QUICKI were calculated. The means of the two groups with and without NAFLD were statistically compared. The receiver operating characteristics (ROC) curve and the area under the curve (AUC) were used to assess the ability to identify NAFLD. Results The mean levels of FGF-21 and HOMA-IR were significantly higher and that of QUICKI was significantly lower in patients with NAFLD than in those without (p < 0.001, p = 0.023, and p = 0.018, respectively). FGF-21 had the highest AUC to identify NAFLD (AUC = 0.981, 95% confidence interval = 0.954-1, P < 0.001). The AUCs for HOMA-IR, QUICKI, and FFA were <0.7. The highest sensitivity, specificity, positive likelihood ratio, and the lowest negative likelihood ratio were found when FGF-21 was used to predict NAFLD. Conclusions FGF-21 may be used as a biomarker to predict NAFLD in people with T2DM due to its high sensitivity and specificity compared to the other markers.