Association Between Triglyceride-Glucose Index and Homeostasis Model Assessment for Insulin Resistance with Estimated Glucose Disposal Rate.

This cross-sectional study was aimed to compare insulin resistance, Triglyceride- Glucose (TyG) index, fatty liver index (FLI) and hepatic steatosis index (HSI), glycaemic and lipids among groups/quartiles based upon estimated Glucose Disposal Rate (eGDR) from August 2022 to December 2022 among 249 male participants. The eGDR results in (mg/kg/min) were divided into four quartiles as: Group-I: {<6.88, n = 62}, Group-II: {<6.88-9.45, n = 63}, Group-III: {9.46-10.39, n = 62}, and Group-IV: {>10.39, n = 62}. Fasting plasma glucose (FPG), HbA1c, low density lipoprotein (LDL), homeostasis model assessment for insulin-resistance (HOMAIR), and TyG index demonstrated significant worsening increase from high to low eGDR groups. Receiver operating curve (ROC) analysis to calculate area under curve (AUC) for diagnostic efficiency candidate indices for eGDR demonstrated highest AUC for FLI as AUC: 0.736 (95% CI: 0.669-0.803), p < 0.001, followed by FPG: AUC: 0.682 (95% CI: 0.606-0.757), HOMAIR: AUC: 0.670 (95% CI: 0.602-0.739), HSI: AUC: 0.660 (95% CI: 0.589-0.731), TyG index: 0.658 (95% CI: 0.583-0.732), and HbA1c: 0.639 (95% CI: 0.583-0.732). Glycaemic measures, lipid indices, insulin resistance and TyG index deteriorated with declining eGDR. Diagnostic performance as evaluated by AUC for eGDR was highest for FLI, followed by FPG, HOMAIR, HSI, TyG index, HbA1c, and triglycerides. Key Words: Triglyceride, Insulin, Glucose, Diabetes.

Differences Between Conventional and Newer Anthropometric Measures Among Individuals with and without Fatty Liver Disease.

A cross-sectional analysis was conducted to compare conventional and emerging anthropometric measures among male participants with and without fatty liver disease (FLD). The objective was to assess differences and diagnostic efficiency of anthropometric-parameters using receiver operating curve (ROC) analysis at Combined Military Hospital Multan, NUMS from April to October 2022. Comparison for anthropometric measurements between non-FLD (n=164) vs. FLD (n=85) indicated significant differences in weight (74.01 + 11.96 vs. 85.91 + 14.07 kg, p<0.001), waist circumference (9.38 + 9.82 vs. 101.35 + 10.74 cm, p<0.001), BMI (24.81 + 4.0 vs. 29.21 + 4.38 kg/m2, p<0.001), waist-to-hip ratio (WHpR) (0.924 + 0.054 vs. 0.971 + 0.054, p<0.001), waist-to-height ratio (WHtR) (0.508 + 0.054 vs. 0.578 + 0.062, p<0.001), and abdominal volume index (AVI) (16.17 + 3.56 vs. 20.77 + 4.61, p<0.001). Fatty liver index (FLI) also showed significant difference between non-FLD vs. FLD groups (38.35 + 27.12 vs. 72.01 + 21.31, p<0.001). AUCs for various significant anthropometric measurements from highest to lowest as 0.821 (95% CI: 0.767-0.874) for FLI, 0.815 (95% CI: 0.761-0.869) for WHtR, 0.809 (95% CI: 0.754-0.863) for AVI, and 0.808 (95% CI: 0.754-0.863) for waist circumference with lowest recorded AUC for height as 0.422 (95% CI: 0.347-0.497). Key Words: Fatty liver disease (FLD), Body mass index (BMI), A body shape index (ABSI), C-index, Abdominal volume index (AVI), Body roundness index (BRI).

Role of δ-tocotrienol and resveratrol supplementation in the regulation of micro RNAs in patients with metabolic syndrome: A randomized controlled trial.

OBJECTIVE: To determine the effect of δ-tocotrienol and resveratrol mixture (TRM) supplementation in comparison to placebo for 24 weeks, on the relative expression of miRNAs (miRNA-130b-5p, miRNA-221-5p, miR-15b-5p, miRNA-122-5p, and miRNA-376b-5p) in patients with Metabolic syndrome (MetS). DESIGN: This randomized placebo-controlled trial was conducted at the tertiary care institute of the NUMS, Rawalpindi, Pakistan. A total of 82 adult MetS patients were enrolled and randomly grouped into the TRM group (n = 41) and the Placebo group (n = 41). Patients in the TRM group were given 400 mg capsules (δ-tocotrienol 250 mg; Resveratrol 150 mg) and placebo received (cellulose 400 mg capsule) twice daily for 24 weeks. RESULTS: The TRM supplementation revealed a significant (p < 0.001) upregulation of 3.05-fold in miRNA-130b-5p and 2.45-fold in miRNA-221-5p while miRNA-122-5p was downregulated by 2.22-fold as compared to placebo. No significant difference was observed in miRNA-15b-5p and miRNA-376b-5p. Moreover, TRM group participants with reverted MetS had significantly (p < 0.05) upregulated miRNA-130b-5p, miRNA-221-5p, and downregulated miRNA-122-5p relative to non-reverted patients with MetS. CONCLUSION: Daily TRM supplementation may improve metabolic syndrome by upregulated miR-130b-5p, which is involved in central obesity and inflammation, as well as miR-221-5p, which is involved in insulin resistance. Additionally, TRM downregulate of miRNA 122, which improved dyslipidemia.

Trace metal profiling in patients with depression in Pakistani population.

OBJECTIVE: To determine level of trace metals in patients with depression in order to explore any association between the two. METHODS: The case-control study was conducted at the Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology and Armed Forces Institute of Mental Health, Rawalpindi, Pakistan, from January to December 2017, and comprised diagnosed cases of depression with equal number of age- and gender-matched controls. Depression was diagnosed by a consultant psychiatrist as per the International Classification of Diseases version 10 / Diagnostic and Statistical Manual of Mental Disorders -IV criteria and a self-reported depression screening through Siddiqui-Shah Depression Scale. Blood samples were collected from each subject for the measurement of metals like zinc, chromium and copper. Data was analysed using SPSS 24. RESULTS: Of the 370 subjects, there were 185(50%) in each of the two groups. There were 82(44.3%) males and 103(55.7%) females among the cases with an overall mean age of 37.75±11.49 years, and 65(35.1%) males and 120(64.9%) females with an overall mean age of 39.38±12.56 years among the controls. Mean levels of zinc and copper were significantly different between the groups (p<0.05), while the difference was non-significant for chromium (p>0.05). Equivocal prevalence of depression was present between males and females (p=0.04) without any significant age group association (p=1.92). CONCLUSIONS: Blood level of serum zinc and copper were found to be associated with depression.

Evaluation of blood lead levels by atomic absorption spectrometry in school going children of northern areas of Pakistan.

OBJECTIVE: To evaluate blood lead levels and assess their correlation with academic performance in school children. METHODS: The cross-sectional study was conducted at the Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from January to December, 2017, and comprised school children in Rawalpindi, Pakistan, and Hajira, Azad Jammu and Kashmir. About 5 ml of venous blood was collected in potassium-ethylenediaminetetraacetic acid tubes for lead levels, haemoglobin and plasma ferritin. The preceding three years' academic performance, rated as excellent, good, fair and poor, of the subjects was categorised on a specifically-designed proforma. Data was analysed using SPSS 24. RESULTS: Of the 400 subjects, 205 (50.25%) were females. The overall mean age was 9.15±2.8 years. Mean level of lead was 4.3±2.6 µg/dL, and difference in values was significant between children of Hajira and Rawalpindi (p<0.05). Mean haemoglobin was 12.9±0.919g/dL and mean ferritin was 49.17±16.0ng/ml. Of the total, 85(21.3%) showed excellent school performance, 162(40.5%) good, 113(28.3%) fair and 40(10%) showed poor performance. Significant negative association was found between school performance and mean blood lead level (p>0.05). No significant difference was found in terms of gender and age with school performance of both regions. CONCLUSIONS: Majority of school going children in northern Pakistan were found to have lead levels ≤ 5µg/dL which is a level of concern as it is inversely related to academic performance.

Diagnosis of inherited metabolic disorders by selective metabolite testing: three years' experience at a tertiary care center in Rawalpindi.

OBJECTIVE: To determine the pattern of various inherited metabolic disorders specifically through plasma amino acid and urine organic acid testing in high-risk paediatric population.. METHODS: The cross-sectional retrospective study was conducted at the Armed Forces Institute of Pathology, Rawalpindi, Pakistan, and comprised data from April 2015 to March 2018 of children referred to the Department of Chemical Pathology and Endocrinology for work-up of suspected inherited metabolic disorders. Complete clinical history, baseline biochemical investigations, plasma amino acid and urine organic acid profiles, where indicated, were collected. Quantitative plasma amino acid and analysis was carried out by Ion Exchange Chromatography on Biochrome 30+ amino acid analyser, and urine organic acid analysis by Gas Chromatography-Mass Spectrometry. Findings were linked to the identified disorders. SPSS 21 was used for data analysis. RESULTS: Of the 805 cases reviewed, 49(6%) had an inherited metabolic disorder. Male:Female ratio of the cases was 1.5:1, and the median age was 240 days (interquartile range: 1-15695 days). The most common presenting symptom was seizures 316(39.3%) followed by lethargy 283(35.2%). Of the diagnosed cases, aminoacidopathies were 28(57%) and in them, non-ketotic hyperglycaemia accounted for 7(25%.). There were 12(24.5%) cases of organic acidurias followed by 9(18.4%) that were other than the two diagnoses. CONCLUSIONS: The cases of inherited metabolic disorder detected indicated significant prevalence. Non-ketotic hyperglycinemia was the commonest disorder diagnosed.

Diagnostic accuracy of cannabinoid testing by liquid chromatography-tandem mass spectrometry in human hair.

OBJECTIVE: To determine the diagnostic accuracy of Cannabinoids testing by LC-MS/MS in human hair and compare it with urine in civil heavy vehicle drivers. METHODS: Current study was a diagnostic accuracy study done in "Armed Forces Institute of Pathology Rawalpindi, Pakistan" from February to November 2017. Urine and hair samples were collected by non-probability convenient sampling technique from 151 heavy vehicle drivers from Punjab. Hair and urine samples were collected from each subject. Separation of compounds was performed on Agilent Poroshell and analyzed using 6460 Triple Quadrapole LC-MS along-with software Mass hunter ©. RESULTS: Study population (151 civil heavy vehicle drivers) was divided into three main divisions There were 69 (46%) truck drivers,43 (28.5%) twenty-wheeler drivers and 39 (26%) bus drivers. Mean age of study participants was 36±10.82 years. Paired t-test was applied to check mean difference between the two tests' concentration (i.e urine and hair analysis for cannabis) which showed significant difference at p<0.001. Among the different factors of diagnostic accuracy in hair and urine specimens were: Sensitivity (96% and 62%), Specificity (93% and 95%) Positive Predictive Value (88% and 87%), Negative Predictive Value (97% and 82%) respectively. Overall diagnostic accuracy of Cannabinoids detection in hair was 94% while in urine it was 83%. ROC curve showed area under curve of 0.79 and 0.96 for urine and hair samples respectively. CONCLUSIONS: Current study signified hair as a substitute matrix owing to its non-invasive specimen collection, better diagnostic yield and wider detection period compared to urine.

Dyskinesia in a Child: A Concern for a Rare Neuro-Metabolic Disorder.

A 3-year child is discussed who presented with dyskinesia, large head size, developmental delay, and recurrent infections necessitating multiple hospital admissions. The diagnosis was not made at initial presentation or even after multiple hospital admissions. An organic acidemia was suspected, based on raised ammonia and lactate levels and metabolic acidosis and the diagnosis of glutaric aciduria Type 1 was established by finding markedly elevated levels of glutaric acid and its specific metabolites on urine organic acids analysis by gas chromatography-mass spectrometry, in the setting of specific clinical features. Further supporting evidence was provided by CT scan brain showing subdural hygroma along left cerebral hemisphere causing gyral flattening and widening of sylvian fissure.

A Novel Clinico-Biochemical Score for Screening of Inherited Metabolic Diseases in Children.

OBJECTIVE: To evaluate a novel clinico-biochemical score for screening of inherited metabolic diseases (IMDs) in children in our setup. STUDY DESIGN: Descriptive analytical study. PLACE AND DURATION OF STUDY: Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, from August 2016 to August 2017. METHODOLOGY: Clinical data, preliminary biochemical investigations, plasma amino acid (PAA) and organic acid profiles (where indicated) of 354 children, aged <1 year to 12 years, referred to the study place for evaluation of suspected inherited metabolic diseases, was collected and evaluated. A clinico-biochemical score card named Rawalpindi Inherited Metabolic Diseases Score (RISc) was devised, on a scale from 1 to 10, incorporating 5 clinical and 5 important biochemical findings, and each variable was assigned a score, based on its relative frequency/risk. Each case was then assigned the RISc score and evaluated for presence or absence of any inherited metabolic disease, based on the score. This score was validated keeping plasma amino acids and organic acid profiles (in selected cases) as reference standard. RESULTS: Patients were divided into three groups, based on RISc score as low RISc (0.5-2.5), medium RISc (3.0-5.5) and high RISc (6-10). A total of 354 cases reported in 2016 and 2017 and 33 (9.3%) were diagnosed to be having IMDs. One (3.0%) patient from low RISc, four (12.1%) from medium RISc, and 28 (84.8%) from high RISc group were found to test positive for any one IMD. High RISc group had a statistically significant higher IMD rate than the other two groups (p<0.001). Specificity, sensitivity, positive likelihood ratio, negative likelihood ratio, positive predictive value, negative predictive value and accuracy were 93%, 85%, 11.8, 0.16, 55%, 98% and 90%, respectively. CONCLUSION: The cost effective RISc, based on clinical data and preliminary biochemical investigations, is highly accurate in diagnosing IMDs in cost restrained setups. It is strongly suggested that the initial screening for suspected IMDs and decision for advanced laboratory testing be carried out, based on the RISc card presented in the study.

Bilirubin Interference in Plasma Amino Acid Analysis by Ion Exchange Chromatography.

OBJECTIVE: To evaluate the effect of bilirubin interference on plasma amino acid analysis by Ion Exchange Chromatography (IEC). STUDY DESIGN: Cross-sectional (method validation) study. PLACE AND DURATION OF STUDY: Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi from August 2016 to July 2017. METHODOLOGY: Twenty non-icteric samples from paediatric patients were collected in lithium heparin tubes and analysed for amino acids on IEC-based Biochrome® 30+ Analyzer (Harvard Biosciences UK). Baseline bilirubin levels were noted. Samples were spiked with neonatal bilirubin standard with concentration of 488.4 mol/L (Spinreact®-Spain) at final concentrations of 50, 150 and 230 mol/L and re-analysed for amino acids at these three concentrations. RESULTS: Among the 20 selected patients with normal amino acid profiles, 12 (60%) were males. Majority (55%) were in age group of 1-5 years. Significant difference was observed for Arginine (p = 0.01), Histidine (p = 0.001), Isoleucine (p = 0.01), Leucine (p = 0.007), Lysine (p = 0.005), Ornithine (p = 0.03) and Phenylalanine (p = 0.02). Mean rank of these amino acids showed decreasing trend with the increase of bilirubin concentration, and pronounced interference was identified at bilirubin level of 50 mol/L. No difference was observed for alanine, citrulline, glutamic acid, glycine, methionine, proline, threonine, tyrosine, asparagine, aspartic acid, cystine, valine and tryptophan. CONCLUSION: Bilirubin significantly interferes with certain amino acid levels when analysis is carried out by ion exchange chromatography. A close follow-up of such patients with other biochemical tests and a repeat amino acid analysis, after jaundice is settled, is recommended to confidently rule out any possible inherited metabolic disorder in these patients.

Cost-effectiveness of Screening and Confirmatory Tests for Multiple Myeloma in Pakistani Population: An Audit Report.

OBJECTIVE: To find out the use of screening and confirmatory tests for diagnosis of multiple myeloma as ordered by clinicians. STUDY DESIGN: An Audit. PLACE AND DURATION OF STUDY: Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, from January 2012 to January 2017. METHODOLOGY: Data retrieved from Laboratory Information Management system (LIMs) by selecting serum protein electrophoresis (SPE) as screening test and immunoelectophoresis (IE) and immunofixation (IF) as confirmatory tests. RESULTS: There were 3,108 tests of serum protein electrophoesis and 1,329 tests of immunoelectophoresis had been performed in last five year. Cost-effective clinical audit of SPE tests showed that only 17.1% tests of SPE were either used for proper diagnosis of multiple myeloma (totally justified tests 13%) or useful for diagnosis of other important diseases whose early diagnosis were helpful for patients management (partially justified tests 4.1%). The cost related to these tests were justified while 82.8% tests of SPE were either normal (total unjustified tests 24.4%), or diagnosed irrevalent and nonspecific diseases (partially unjustified 58.4%). IE and IF audit revealed that only 26.6% tests were properly utilised for diagnosis and differentiation of multiple myeloma and its subtypes and cost attributable to these tests were justified while 73.4% of these confirmatory tests were normal and cost related to them was not justified. CONCLUSION: Overutilisation of laboratory tests for diagnosis of multiple myeloma can be minimised by proper clinical scrutiny of request forms.

Classical Homocystinuria in a Juvenile Patient.

Classical homocystinuria, also known as cystathionine beta synthase deficiency, is a rare disorder of methionine metabolism, leading to an abnormal accumulation of homocysteine and its metabolites in blood and urine. A young child with homocystinuria is discussed, who presented with behavioral abnormalities, involuntary movement, mental retardation, and decreased vision since birth. The diagnosis of homocystinuria was not made at initial presentation. Subtle phenotypic features with developmental delay and MRI brain finding of bilateral medially dislocated lens, eventually provided the first indication at five years of age. Laboratory screening with plasma amino acid profile by ion exchange chromatography (IEC) showed elevated homocystine and methionine, and low cystine in plasma in the absence of vitamin B12, and folate deficiency; giving the diagnosis of classical homocysteinuria.

Prevalence of selected pharmaceuticals in surface water receiving untreated sewage in northwest Pakistan.

This study investigated the occurrence of four non-steroidal anti-inflammatory drugs (NSAIDs) and four benzodiazepines/anti-depressants (ADs) in municipal wastewater in Mardan city, Pakistan, and in River Kabul and River Indus receiving untreated sewage. Liquid chromatography with a triple quadrupole tandem mass spectrometry (LC-MS/MS) was used for the analysis of paracetamol, diclofenac, ibuprofen, and codeine (NSAIDs) and diazepam, bromazepam, lorazepam, and temazepam (ADs). Except codeine and lorazepam, all the target compounds were observed in sewage and surface water in various concentrations. In sewage, paracetamol was found at the higher end (32.4 µg/L) of the reported ranges in literature for other countries. Results of river samples showed that the target compounds were usually lower in concentration than the respective EC50 values for aquatic organisms. However, the levels for paracetamol and ibuprofen were critical depicting the consequence of untreated disposal. Environmental risk assessment by estimating the risk quotient (RQ) as the ratio of measured environmental concentration and predicted no-effect concentration showed medium to high (RQ > 1 and 0.1 < RQ < 1) risk from paracetamol and ibuprofen to aquatic organisms in River Kabul and Kalpani stream, Pakistan.