Comparison of Point-of-Care and Laboratory Glycated Hemoglobin A1c and Its Relationship to Time-in-Range and Glucose Variability: A Real-World Study.

Introduction The main objective of the current study was to perform a comparison of point-of-care testing for hemoglobin A1c (POCT-HbA1c) versus the standard laboratory method (Lab HbA1c) and their relationship to time-in-range (TIR) and glucose variability (GV) among patients with diabetes mellitus (DM) presented to the outpatient diabetes clinics. Methods This single-center cross-sectional study was carried out on diabetic patients (aged ≥14 years of both genders) who undergo routine follow-up at our institution and whose physicians ordered HbA1c analysis for routine care. The included patients were those using the intermittently scanned continuous glucose monitoring (isCGM) Abbott's FreeStyle Libre system for at least three months and regular CGM users with at least 70% use. Results We included 97 diabetic patients (41 female and 56 male), with a median age of 25 years (Interquartile range= 18) and a mean DM duration of 10.33±5.48 years. The mean values of Lab-HbA1c and POCT HbA1c were 8.82%±0.85% and 8.53%±0.89%, respectively. The TIR, time below range, and time above range were 33.47±14.38 minutes (47.78%±14.32%), 5.44±2.58 minutes (8.41%±4.42%), and 28.8±8.27 minutes (43.81%±13.22%), respectively. According to the Bland-Altman plot analysis, the POCT-HbA1c values are consistent with the standard Lab-HbA1c values (SD of bias= 0.55, and 95% CI= -0.78 to 1.4). The univariate linear regression analysis showed a statistically significant relationship between laboratory HbA1c and POCT HbA1c (R2= 0.637, p <0.001), TIR (R2= 0.406, p <0.001), and GV (R2= 0.048, p= 0.032). After adjusting for age, gender, disease duration, diabetes type, and percentage of sensor data in a multivariable linear regression model, the linear associations remained significant (all p < 0.05). Conclusion The current findings show that TIR and GV can be used as endpoints and valuable parameters for the therapy of DM.

Level of Agreement and Correlation Between the Estimated Hemoglobin A1c Results Derived by Continuous or Conventional Glucose Monitoring Systems Compared with the Point-of-Care or Laboratory-Based Measurements: An Observational Study.

INTRODUCTION: Hemoglobin A1C (HbA1c) is an important marker for diabetes care management. With the increasing use of new technologies such as continuous glucose monitoring (CGM) and point-of-care testing (POCT), patients and their physicians have been able to monitor and continuously check their blood glucose levels in an efficient and timely manner. This study aimed to investigate the level of agreement between the standard laboratory test for HbA1c (Lab-HbA1c) with point-of-care testing (POCT-HbA1c) and glucose monitoring index (GMI) derived by intermittently scanned CGM (isCGM) or estimated average glucose (eAG) derived by conventional self-monitored blood glucose (SMBG) devices. METHODS: A cross-sectional study was conducted at the Diabetes Treatment Center, Prince Sultan Military Medical City, Saudi Arabia, between May and December 2020 with 81 patients with diabetes who used the isCGM system (n = 30) or conventional finger-pricking SMBG system (n = 51). At the same visit, venous and capillary blood samples were taken for routine HbA1c analysis by the standard laboratory and POCT methods, respectively. Also, for isCGM users, the GMI data for 28 days (GMI-28) and 90 days (GMI-90) were obtained, while for SMBG users, eAG data for 30 days (eAG-30) and 90 days (eAG-90) were calculated. The limits of agreement in different HbA1c measurements were evaluated using a Bland-Altman analysis. Pearson correlation and multivariate linear regression analyses were also performed. RESULTS: Based on the Bland-Altman analysis, HbA1c levels for 96.7% and 96.1% of the patients analyzed by the POCT and the standard laboratory methods were within the range of the 95% limit of agreement in both isCGM and conventional SMBG users, respectively. About 93.3% of the GMI measurements were within the 95% limit of agreement. Also, about 94.12% of the eAG-30 and 90.2% of the eAG-90 measurements were within the 95% limit of agreement. Moreover, the correlation analysis revealed a statistically significant positive correlation and linear regression among Lab-HbA1c, POCT-HbA1c, GMI, and eAG in both conventional SMBG and isCGM users (all p < 0.001). These positive results persisted significantly after adjusting for different factors (all p < 0.001). CONCLUSION: GMI derived by isCGM or eAG derived by conventional SMBG systems, as well as the POCT-HbA1c measurements, showed a high level of agreement; therefore, we recommend them as potential methods for diabetes monitoring, especially when a rapid result is needed or with patients with uncontrolled diabetes or on intensive insulin therapy.

Immunohistochemistry of IL-1ß, IL-6 and TNF-α in spleens of mice treated with gold nanoparticles.

Gold nanoparticles (AuNPs) possess considerable biocompatibility and therefore gaining more attention for their biomedical applications. Previous studies have shown the transient increase in pro-inflammatory cytokines expression in different organs of rats and mice exposed to AuNPs. Structural changes in the spleen of mice treated with AuNPs have also been reported. This investigation was aimed to study the immunostaining of IL-1ß, IL-6 and TNF-α in mice treated with different sizes of AuNPs. The animals were divided into 7 groups of 4 animals in each group. One group received saline and served as control. Two sets of three groups were treated with 5 nm, 20 nm and 50 nm diameter AuNPs. One set was sacrificed on day 1 and the other on day 7 following the AuNPs injections. Spleens were dissected out and promptly fixed in formalin for 3 days and then processed for IL-1ß, IL-6 and TNF-α immunostaining using target-specific antibodies. The immunoreactivities of IL-1ß and IL-6 were increased with the increase of AuNP size. The immunostaining of IL-1ß in spleen of 20 nm AuNP treated mice was subsequently decreased on day 7 whereas it persisted in 50 nm AuNP group. The increase in the immunoreactivity of IL-6 on day 1 was decreased on day 7 in the spleens of mice treated with 20 nm or 50 nm AuNPs. The immunostaining of TNF-α was found to be negative in all the treatment groups. In conclusion, the size of AuNPs plays an important role in the expression of proinflammatory cytokines in mouse spleen; small size (5 nm) AuNPs caused minimal effect, whereas larger (50 nm) AuNPs produced intense immunostaining.

Biomarker potential of C-peptide for screening of insulin resistance in diabetic and non-diabetic individuals.

Insulin resistance is a hallmark feature of type-2 diabetes mellitus (T2DM). We determined the homeostatic model assessment insulin resistance (HOMA-IR) and evaluated its association with C-peptide, insulin, fasting blood glucose (FBG) and glycated hemoglobin (HbA1c) in T2DM patients and non-diabetic subjects. This study comprised a total of 47 T2DM patients and 38 non-diabetic controls. Venous blood samples from all the subjects were collected and sera were analyzed for FBG, HbA1c, insulin and C-peptide using an autoanalyzer. HOMA-IR was calculated using the following equation: HOMA-IR = fasting insulin (µU/ml) × fasting glucose (mmol/L)/22.5. There was a significant increase in the levels of FBG and HbA1c in diabetic patients. Although the levels of C-peptide and insulin did not differ significantly between the two groups, a significant increase in HOMA-IR was observed in T2DM patients. Both insulin and C-peptide were significantly correlated with HOMA-IR. In conclusion, C-peptide may serve as a simple and convenient predictor of HOMA-IR.

Alterations in prothrombin time and activated partial thromboplastin time in patients with acute myocardial infarction.

Prothrombin time (PT) and activated partial thromboplastin time (aPTT) respectively measures the extrinsic and intrinsic pathways of coagulation and are used to determine the bleeding or clotting tendency of blood. We compared PT and aPTT levels in acute myocardial infarction (AMI) patients and normal subjects. There were significant increases in PT levels in patients with STEMI (15.98 ± 0.96 s), NSTEMI (16.03 ± 0.97 s) and chest pain (15.02 ± 0.54 s) as compared to control group (8.86 ± 0.08 s). The level of aPTT in control subjects was 31.35 ± 0.48 s. Patients with STEMI (40.79 ± 1.83 s), NSTEMI (41.33 ± 2.06) and chest pain (37.84 ± 1.66 s) showed significantly higher levels of aPTT. There was a significant correlation between PT and aPTT levels. Both PT and aPTT were significantly correlated with age however there was no correlation between these coagulation markers and gender or body mass index. In conclusion, both PT and aPTT are significantly increased in AMI patients on anticoagulation therapy. The elevations in PT values were more than 2.5-fold greater than aPTT suggesting a high potential of PT for predicting blood clotting tendency in patients receiving anticoagulation therapy.

Lipid profile of patients with acute myocardial infarction and its correlation with systemic inflammation.

The biomarker potential of using various lipids fractions for predicting risk of acute myocardial infarction (AMI) is controversial. We therefore compared the lipid profiles, including serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL) and triglycerides (TG), in 67 AMI patients. Patients included 28 STEMI (ST-elevated myocardial infarction) patients, 39 NSTEMI (non-ST-elevated myocardial infarction) patients and 25 patients with chest pain. Control group included 54 age- and gender-matched normal subjects. We also studied the correlation between lipid profile and systemic inflammation in these subjects. There were significant decreases in TC, LDL and HDL levels in both STEMI and NSTEMI patients as compared to normal subjects; however, patients with chest pain did not show any significant change in these lipids. Serum TG levels did not differ significantly among the study groups. There were significant increases in serum high-sensitive C-reactive protein (hs-CRP) levels in STEMI and NSTEMI patients, as compared to control group. Serum hs-CRP showed significant inverse correlation with HDL; however, hs-CRP was not correlated with TC, LDL, and TG. In conclusion, our findings suggest that reduction in serum TC does not prevent the risk of AMI, whereas a decrease in serum HDL and increase in hs-CRP strongly predisposes the risky individuals to an AMI event. We emphasize the importance of HDL and CRP measurements for the assessment of a combined lipid-inflammation risk factor that could be a useful predictor of high risk individuals, as well as a prognostic marker in AMI patients.

Blood cell counts and their correlation with creatine kinase and C-reactive protein in patients with acute myocardial infarction.

This study reports differential blood cells counts and their correlations with creatine kinase (CK) and C-reactive protein (CRP) levels in acute myocardial infarction (AMI) patients and normal subjects. Peripheral blood samples were obtained from all 39 AMI patients and 35 controls for blood cell counts and CK and CRP analyses. Total WBC, WBC fractions, RBC and platelets were measured with an automated hematology analyzer. The results showed a significant increase in total WBC (8.688 × 10(9)/L versus 6.148 × 10(9)/L), monocytes (1.271 versus 0.497 × 10(9)/L), and neutrophils (8.367 versus 3.223 × 10(9)/L) counts in AMI patients than controls. The RBC count was significantly less in AMI patients (4.638 × 10(12)/L) as compared to controls (5.105 × 10(12)/L). However, there was no significant difference in lymphocytes, eosinophils, basophils and platelet counts between AMI patients and controls. Both, serum CK (215.38 ± 43.15 versus 100.82 ± 8.86 U/L) and CRP (29.49 ± 7.61 versus 3.48 ± 0.60 mg/L) were significantly higher in AMI patients as compared to controls. Age of the subjects was neither correlated with blood cell counts nor CK indicating the validity of these markers irrespective of patient age. A significant correlation was observed between WBC counts and CK (R = 0.242, P = 0.041) as well as CRP (R = 0.416, P = 0.000). In conclusion, this study clearly showed significant increase in total and differential leukocyte counts indicating a pro-inflammatory cascade in AMI patients. A significant correlation between WBC counts and CK or CRP levels suggest a possible biomarker value of WBC for a quick prediction of both myocardial necrosis and inflammation in AMI patients.

Significant increases in monocyte counts and serum creatine kinase in acute myocardial infarction versus general infections.

BACKGROUND: Biomarkers specificity is an important factor for their reliable utilization. Known markers for acute myocardial infarction (AMI), including creatine kinase (CK), C-reactive protein (CRP), and blood cell counts are thought to be altered in other pathologic conditions, such as infections. AIM: To compare the level of these biomarkers in AMI patients and infected controls with respect to normal subjects. MATERIALS AND METHODS: We recruited 15 AMI patients, 15 patients with bacterial infections (infected control group) and 35 normal subjects. Peripheral blood samples were obtained for blood cell counts and biochemical analyses. RESULTS: Only monocytes were significantly increased in AMI patients (0.793×10(9)/L) than normal controls (0.497×10(9)/L). Infected controls showed a significant increase in total white blood cell (11.50×10(9)/L versus 6.149×10(9)/L) and neutrophil (9.360 versus 3.223×10(9)/L) counts and a significant decrease in red blood cell (3.750 versus 5.105×10(12)/L) counts as compared with normal controls. Serum CK was significantly increased in AMI patients (313.20±94.84 U/L) and decreased in infected controls (48.40±10.35 U/L) as compared with normal controls (100.82±8.86 U/L). The levels of CRP were significantly higher in infected controls (136.93±34.83 mg/L) and nonsignificantly higher in AMI patients (38.53±12.76 mg/L) than normal controls (3.48±0.59 mg/L). Monocytes were significantly correlated with both CK and CRP; however, there was no correlation between CK and CRP. CONCLUSION: Differential trends of monocytes and CK in AMI and infective controls point toward their possible application in prognosis of AMI patients.

Significant impact of pace of eating on serum ghrelin and glucose levels.

OBJECTIVES: To study the effect of normal versus slow eating on serum ghrelin, glucose, insulin, and C-peptide levels in healthy subjects from Riyadh, Saudi Arabia. DESIGN AND METHODS: The specified breakfast meal was served on two randomized occasions to 24 healthy volunteers to eat with a normal pace or at a slow rate. Venous blood samples were collected at 7 time points for biochemical analysis. RESULTS: The slow ingestion of meals resulted in a significant increase in blood glucose and ghrelin levels as compared to normal pace of eating. CONCLUSIONS: Normal eating speed appears to be beneficial for maintaining the optimal blood glucose and ghrelin levels.

Chromium chloride administration causes a substantial reduction of coronary lipid deposits, aortic lipid deposits, and serum cholesterol concentration in rabbits.

This experiment was carried out to test the null hypothesis that intramuscular trivalent chromium administration would not remove lipids from the heart and ascending aorta of the hyoercholesterolemic rabbits and would not lower their serum cholesterol levels. A novel computer-based method, previously described, was used to assess the sizes of the intracardiac and aortic lesions. Clinical chemistry and histopathology were performed through routine methods. The sizes of the lipid deposits in the coronary vasculature of the hypercholesterolemic rabbits were greatly reduced as a result of the intramuscular chromium chloride injections. Lipid deposits in the ascending aorta were similarly reduced, as well as the serum cholesterol concentrations. The terminal serum chromium concentrations in the chromium-treated group were in the range of 3,258-4,513 microg/L, whereas, in the untreated animals, the concentrations were 3.2 to 6.3 microg/L. The general condition of the chromium-treated animals was good and they were continuing to gain weight up to the time they were killed. However, it was found that their liver function tests had become abnormal even though there was no evidence of hepatic histopathological lesions specifically affecting the chromium-treated group. The kidney function tests and histopathology were normal. These findings suggest that a more aggressive approach than those tried hitherto might be useful in treating atherosclerotic human patients with chromium.

A novel computer-based method for the measurement of the lipid "load" in the coronary vessels of rabbits.

INTRODUCTION: This study reports the development of a new, accurate and reproducible method which combines histological and computer techniques for the determination of fatty load in cholesterol-fed rabbits. METHODS: New Zealand male rabbits were randomly divided into three groups. The animals in group 1 (control) received neither cholesterol nor drugs. Those in group 2 received a 2% cholesterol diet for 30 days, followed by a normal diet for 45 days. In addition during the latter period (day 31 to day 75) animals received 200 g of chopped carrots each morning. The rabbits in group 3 followed the same dietary regime as those in group 2 except that 8.36 mg of simvastatin and 1.76 g cholestyramine were mixed with their carrots. On the 76th day, the animals were sacrificed and their blood and hearts were collected. Histological sections (15 microm thick) of hearts were cut at 90 degrees to the long axis using a motorized freezing microtome. Every tenth section was mounted on a glass slide and stained with Oil Red O. A total of hundred slides prepared from each heart were scanned into a computer and the area stained by Oil Red O was measured, giving a measure of the total fatty "load" in each heart. RESULTS: There was a highly significant increase in the coronary fatty deposits in the hearts of the animals fed with cholesterol rich diet (group 2) as compared to the control rabbits in group 1. Treatment of rabbits with simvastatin plus cholestyramine (group 3) significantly reduced the coronary lipids load. DISCUSSION: The combination of histological and computer-based techniques used in this study provides an accurate and reproducible method for the quantitation of fatty deposits in rabbit coronary vessels. This report is based on the measurement of coronary lipid depositions rather than aortic lesions. It also overcomes the shortcoming of the majority of the earlier published methods which are generally limited to the measurement of fatty plaques in only few major coronary vessels, totally neglecting the many small distributive vessels which are often responsible for cardiac ischemic disease.

Homocysteine in renal transplant recipients: association with transplant duration and renal function.

BACKGROUND: Hyperhomocystinemia is an established risk factor for cardiovascular events and has been identified as an important cause of morbidity and mortality in renal transplant recipients. This investigation was aimed to determine the effect of age and transplant duration on serum total homocysteine (tHcy) levels in renal transplant recipients. METHODS: We analyzed serum levels of tHcy, albumin, alkaline phosphatase, alanine transferase, bilirubin, calcium, corrected calcium, cholesterol, creatinine, folate, phosphate, potassium, sodium, triglycerides, urea and vitamin B12 in 88 transplant patients (ages, 14-67 years; transplant duration, 1-252 months) and 60 control subjects. RESULTS: Our results showed significant hyperhomocystinemia in transplant patients (19.92 +/- 0.72) as compared to controls (9.28 +/- 0.25), while male subjects in both groups had significantly higher tHcy than females. There was no correlation between patients' age and serum tHcy, whereas the time after transplantation was significantly correlated with tHcy (r=0.318, P<0.01). A significant correlation was observed between tHcy and serum urea, creatinine, vitamin B12 and potassium in renal transplant patients. CONCLUSION: This study clearly demonstrated significant hyperhomocystinemia and renal impairment in transplant recipients. A time-course increase in serum tHcy during posttransplant duration warrants long-term monitoring of patients for effective clinical management.

Impact of gestational diabetes on lipid profiling and indices of oxidative stress in maternal and cord plasma.

OBJECTIVE: To study the effect of gestational diabetes mellitus (GDM) on indices of oxidative stress and lipid profiles in maternal and cord blood samples. METHODS: Blood samples were collected from 40 normal pregnant women and 46 women with GDM during the period 1998 through to 1999 at the Armed Forces Hospital, Riyadh, Kingdom of Saudi Arabia. The GDM patients were subdivided into 2 groups: patients receiving insulin treatment (GDM-I, N=19) and patients under control diet (GDM-D, N=27). Plasma a- and y-tocopherols were estimated by high-performance liquid chromatography, whereas malondialdehyde (MDA) was analyzed by fluorometry. Serum lipids (low density lipoprotein, high density lipoprotein, total cholesterol, triglycerides, and total lipids) were determined by enzymatic colorimetry using automated clinical analyzer. RESULTS: The results of lipid profiles in maternal serum showed no significant difference between GDM patients and controls; however, all the lipid constituents except total cholesterol were significantly reduced in the cord blood of GDM patients as compared to control subjects. a-tocopherol levels in the maternal plasma were not significantly different among the 3 groups, whereas, cord plasma a-tocopherol was significantly decreased in both GDM-D and GDM-I. Maternal y-tocopherol was found to be significantly increased in GDM-D and only insignificantly increased in GDM-I, but the cord y-tocopherol showed no appreciable changes. The level of MDA was 3-fold higher in maternal plasma as compared to cord plasma. However, neither the maternal plasma nor cord plasma showed significant differences in MDA levels between GDM patients and normal pregnant women. CONCLUSION: A significant depletion of a-tocopherol in the cord blood of GDM patients is indicative of a possible oxidative stress in their fetuses. Further studies are warranted to examine a wider range of biochemical parameters to evaluate the potential risks of oxidative damage.

Effect of age on pituitary gonadal hormonal responses of saudi male patients on hemodialysis.

The pituitary gonadal axis of men with chronic renal failure is disturbed even when there is moderate reduction of the glomerular filtration rate. This axis is also disturbed in the ageing male. The present investigation was undertaken to study the pituitary gonadal hormonal response in Saudi male patients, belonging to two different age-groups, on regular hemodialysis (HD). Male patients on HD were divided into two groups. Group one included 24 individuals under 45 years of age and group two had 50 subjects > 45 years. Age-matched healthy individuals were used as controls. Serum levels of total and free testosterone were significantly reduced in patients> 45 years of age when compared to patients < 45 years of age. Also, the levels of follicle stimulating hormone (FSH) and leutenizing hormone (LH) were significantly increased in both the groups when compared with their age-matched controls. However, the serum levels of FSH, LH and sex hormone binding globulin (SHBG) were not significantly different between patients> 45 years and those < 45 years of age. Similarly, there was no significant difference in the hemoglobin levels between the two groups. The results of this study, suggest that disturbances in the pituitary gonadal hormonal responses in men on HD and> 45 years of age may be more severe than men < 45 years of age. Further studies are warranted to understand this observation.

Biochemical detection of minor myocardial injury after elective, uncomplicated, successful percutaneous coronary intervention in patients with stable angina: clinical outcome.

BACKGROUND: Minor elevations of creatine kinase MB isoform (CK-MB) identified a population with a worse long-term prognosis after successful coronary intervention. Recent studies provide evidence that cardiac troponin I (cTnI) is more sensitive than CK-MB for the detection of minor myocardial injury after coronary intervention. The purpose of the study was to determine the prognostic value of cTnI elevation after elective uncomplicated successful percutaneous coronary intervention (PCI). METHODS: cTnI was measured in 96 patients with stable angina before and 24 h after elective uncomplicated successful percutaneous transluminal coronary angioplasty (PTCA) with or without stenting. Patients were followed up for adverse cardiac events (recurrent angina, non-fatal myocardial infarction, cardiac death, repeat PCI or coronary bypass surgery). Procedure success was achieved in all cases. RESULTS: Cardiac events were best predicted by cTnI when a cut-off value of 2.0 microg/L was used. Abnormal cTnI values at 24 h after PCI were observed in 26 patients (27%). Over a follow-up period of 24 months with no significant difference in the medication used, the incidence of recurrent angina, repeat PCI, coronary bypass surgery and cardiac death was 54%, 46%, 4% and 4%, respectively, in the cTnI-positive patients versus 27%, 16%, 4% and 0% in the cTnI-negative patients. Kaplan-Meier survival analysis showed that cTnI elevation was a significant correlate of cardiac events (P = 0.0198, by log rank analysis). CONCLUSIONS: Elevation of cTnI is not uncommon after elective uncomplicated successful PCI in patients with stable angina and this elevation might be a marker of adverse long-term outcome.

Screening for congenital hypothyroidism.

OBJECTIVE: To review the screening program for congenital hypothyroidism in the Riyadh Al-Kharj Hospital Programme, Riyadh, Kingdom of Saudi Arabia, and to investigate the clinical and biochemical characteristics of affected infants. METHODS: The study was carried out from 1985 to 2000 in the Clinical Chemistry Division, Department of Pathology, Riyadh Armed Forces Hospital, Kingdom of Saudi Arabia. Laboratory data and case notes of infants diagnosed with congenital hypothyroidism were used to supply the relevant data and information. RESULTS: One hundred and twenty-one thousand, four hundred and four infants were screened over a period of nearly 15 years. The overall incidence of congenital hypothyroidism was 1:2759 live births with a female: male ratio of 1.8:1. The incidence in a rural satellite hospital was 1:1538. No seasonal variation was observed. Apart from jaundice, signs and symptoms of congenital hypothyroidism were rarely present in the neonatal period. The neonatal and maternal parameters of affected infants did not differ significantly from those of other infants. The predominant cause of congenital hypothyroidism was athyreosis (45%), followed by thyroid ectopia (24%) and dyshormonogenesis (17%). The mean age at the start of treatment of infants diagnosed in the screening program was 10.3 days. CONCLUSION: The screening program based on initial measurement of thyroid stimulating hormone in cord blood captures 97% of infants born in the Riyadh Al-Kharj Hospital Programme. The incidence of congenital hypothyroidism was 1:2759 live births with a female:male ratio of nearly 2:1. Congenital hypothyroidism infants had similar neonatal parameters as other infants. No seasonality in the incidence of congenital hypothyroidism was observed. In general, affected infants were started on thyroxine very soon after birth.