Elevated Serum Gamma-glutamyl Transferase Research Articles

Association between Gamma-Glutamyl Transferase Levels and Pancreatobiliary Cancer Risk in Patients with Diabetes: Evidence from the National Health Insurance Cooperation Health Checkup 2009 to 2012.

Elevated gamma-glutamyl transferase (GGT) levels indicate hepatic dysfunction and have been linked to an increased risk of pancreatobiliary cancers. However, this association, particularly in individuals with diabetes mellitus (DM), requires elucidation. We aimed to examine the association between elevated serum GGT levels and pancreatobiliary cancer risk in patients with diabetes. Our study included data from the National Health Insurance Service (NHIS) database for 2,459,966 adults aged >20 years diagnosed with DM between 2009 and 2012. We examined the association between serum GGT levels and pancreatobiliary cancer risk, considering DM-related factors. Serum GGT levels were categorized into quartiles, and Cox proportional hazards analysis was performed to evaluate the association between serum GGT levels and pancreatobiliary cancer risk. Over a median follow-up period of 7.2 years, 21,795 patients (0.89%) were newly diagnosed with pancreatobiliary cancer. The adjusted hazard ratio for pancreatobiliary cancer in quartiles 2-4 compared with that in quartile 1 was 1.091, 1.223, and 1.554, respectively, demonstrating a significant upward trend (p<0.001). This association remained consistent across all cancer types and was independent of the DM duration or treatment regimen. Elevated serum GGT levels were independently associated with an increased risk of pancreatobiliary cancer, regardless of the duration of DM or the use of oral hypoglycemic agents and insulin. While these findings suggest the potential utility of serum GGT as a biomarker for identifying individuals at higher risk of pancreatobiliary cancer within the diabetic population, further research is needed to validate its clinical applicability.

Study of serum gamma glutamyl transferase in acute stroke - a single centre experience

Background: Gamma-glutamyl transferase (GGT) is an enzyme involved in oxidative stress and inflammation, which are key mechanisms in the pathogenesis of stroke. Recent evidence suggests serum GGT levels may be associated with the risk and prognosis of acute ischemic stroke. This study aimed to investigate serum GGT levels in patients with acute stroke at a single center in India. Methods: This case-control study included 100 patients (50 with acute stroke and 50 age and sex-matched controls). Patients aged 40 to 80 years and diagnosed with acute stroke (encompassing first-time occurrences of intracerebral hemorrhage, ischemic stroke, and subarachnoid hemorrhage) were included in the study. Serum GGT levels were compared between stroke patients and controls. The association of GGT with various risk factors was also analyzed among cases. Results: The mean age of cases is 60.2±10.07 years. Hemorrhagic stroke was most common and found in 52% of cases. Mean serum GGT levels were significantly higher in stroke patients (55.2540±40.8909 U/l). Higher serum GGT levels were associated with male gender, presence of diabetes, hypertension, dyslipidemia and smoking and were found to be statistically significant (p&lt;0.005). Age and stroke type were found to be not significantly associated with GGT levels. Conclusions: In conclusion, our study findings indicate that elevated serum GGT levels are associated with an increased risk of stroke, particularly in male patients and those with hypertension, dyslipidemia, and diabetes. Further prospective studies are needed to establish the predictive value of GGT for stroke.

Maralixibat (Livmarli)

CADTH recommends that Livmarli should be reimbursed by public drug plans for the treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS) if certain conditions are met. Livmarli should only be covered to treat patients aged 12 months and older with a diagnosis of ALGS and who have impaired bile flow demonstrated by at least 1 of the following: elevated serum bile acids (sBAs), conjugated bilirubin, or gamma-glutamyl transferase; fat-soluble vitamin deficiency; and/or intractable itch. Patients must experience moderate to severe itch symptoms and must be currently or have been previously treated with systemic medication for itch. Livmarli should only be reimbursed if it is prescribed under the care of a specialist with experience in managing ALGS, if patients experience an improvement in their itching after using Livmarli for 6 months, and if the cost of Livmarli is reduced. Livmarli should be stopped if the patient receives a liver transplant or biliary diversion surgery.

Pretreatment gamma-glutamyl transferase predicts mortality in patients with chronic hepatitis B treated with nucleotide/nucleoside analogs.

Elevated serum gamma-glutamyl transferase (GGT) levels are associated with chronic hepatitis B (CHB)-related hepatocellular carcinoma. However, their role in predicting mortality in patients with CHB treated with nucleotide/nucleoside analogs (NAs) remains elusive. Altogether, 2843 patients with CHB treated with NAs were recruited from a multinational cohort. Serum GGT levels before and 6 months (Month-6) after initiating NAs were measured to explore their association with all-cause, liver-related, and non-liver-related mortality. The annual incidence of all-cause mortality was 0.9/100 person-years over a follow-up period of 17,436.3 person-years. Compared with patients who survived, those who died had a significantly higher pretreatment (89.3 vs. 67.4 U/L, p = 0.002) and Month-6-GGT levels (62.1 vs. 38.4 U/L, p < 0.001). The factors associated with all-cause mortality included cirrhosis (hazard ratio [HR]/95% confidence interval [CI]: 2.66/1.92-3.70, p < 0.001), pretreatment GGT levels (HR/CI: 1.004/1.003-1.006, p < 0.001), alanine aminotransferase level (HR/CI: 0.996/0.994-0.998, p = 0.001), and age (HR/CI: 1.06/1.04-1.07, p < 0.001). Regarding liver-related mortality, the independent factors included cirrhosis (HR/CI: 4.36/2.79-6.89, p < 0.001), pretreatment GGT levels (HR/CI: 1.006/1.004-1.008, p < 0.001), alanine aminotransferase level (HR/CI: 0.993/0.990-0.997, p = 0.001), age (HR/CI: 1.03/1.01-1.05, p < 0.001), and fatty liver disease (HR/CI: 0.30/0.15-0.59, p = 0.001). Pretreatment GGT levels were also independently predictive of non-liver-related mortality (HR/CI: 1.003/1.000-1.005, p = 0.03). The results remained consistent after excluding the patients with a history of alcohol use. A dose-dependent manner of <25, 25-75, and >75 percentile of pretreatment GGT levels was observed with respect to the all-cause mortality (trend p < 0.001). Pretreatment serum GGT levels predicted all-cause, liver-related, and non-liver-related mortality in patients with CHB treated with NAs.

Serum alkaline phosphatase can be elevated in patients with hypophosphatasia due to liver disease

BackgroundHypophosphatasia (HPP) is a rare inherited disorder caused by pathogenic loss-of-function variants in the ALPL gene, encoding the tissue-nonspecific isoenzym of alkaline phosphatase (ALP; TNSALP). Low serum ALP is the biochemical hallmark of HPP, but it is unknown whether ALP levels can increase due to concurring liver disease, which may lead to a missed diagnose of HPP. We present a patient with genetically confirmed HPP, who showed a transient increase of serum ALP levels due to alcohol-induced hepatitis. Clinical reportA 71-year old man was seen at our Bone Center for surveillance of HPP. Serum ALP was always low (23 U/L; reference value: <115 U/L). During follow-up, his serum ALP increased (156 U/L, further rising to 204 U/L), with concomitantly elevated serum gamma-glutamyl transferase and transaminases, and a rise in bone specific ALP (18.7 μg/L; reference value: 5.7–32.9 μg/L). This was attributed to alcohol-induced hepatitis. After refraining from alcohol intake, both serum ALP and bone specific ALP levels returned to initial low levels (30 U/L and 4.3 μg/L respectively). ConclusionsWe demonstrated the history of a 71-year old patient with HPP, presenting during routine follow-up with an elevated serum ALP level up to 204 U/L due to alcohol-induced hepatitis. This case illustrates that the diagnosis of HPP can potentially be missed when ALP levels are normal or elevated due to a concomitant liver disease.

Association between Asia–Pacific body mass index classification and serum liver enzymes: alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase in healthy individuals

BackgroundElevated levels of serum liver transaminases are good indicators of liver cell damage, and elevated serum gamma-glutamyl transferase (GGT) level is a good indicator of both bile duct and hepatocellular damage. At early stages, elevated serum levels of these liver enzymes can be mostly prevailed as an asymptomatic condition and therefore in an undiagnosed state. This may be resulted in a number of complications and may lead to chronic hepatic damage that will be more severe and difficult to care. Serum liver enzyme levels are affected by age, gender, body mass index (BMI), ethnicity, drugs and viruses. Obesity has been an epidemic in nearly every country in the world. BMI is the best parameter to assess the magnitude of obesity. Having this background, the present study was designed to investigate the correlation between the levels of serum liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST) and GGT and Asia–Pacific cut-off points of BMI in healthy individuals.MethodsA descriptive cross-sectional study was conducted using 120 Sinhala, Buddhist subjects which belonged to 18–32 years. BMI was calculated according to the standard protocol. The serum ALT and AST concentrations were measured by UV assay according to the IFCC method without pyridoxal phosphate activation, and the serum GGT concentration was measured by UV assay according to Szasz method, using the Mindray BS-240 Full Automatic Biochemistry Analyser.ResultsSerum levels of liver enzymes were significantly higher in males than females. In females, serum levels of ALT (r = 0.312, p < 0.001), AST (r = 0.138, p = 0.071) and GGT (r = 0.212, p = 0.047) positively correlated with BMI. In males too, serum levels of ALT (r = 0.431, p < 0.001), AST (r = 0.324, p = 0.013) and GGT (r = 0.314, p = 0.031) were positively correlated with BMI. The minimum values of serum ALT, AST and GGT levels were observed in underweight group, while the maximum values were observed in obese group in both genders.ConclusionsALT had the strongest correlation with BMI in both females and males. Therefore, ALT can be suggested as the best liver enzyme that can be used in screening purposes by concerning BMI.

270 The Liberal Use of Magnetic Resonance Cholangiopancreatography (MRCP) can be switched over to its Selective use to detect choledocholithiasis

Abstract Background Gallstone disease is known in 10-15% of adults in Western populations. Cholangiopancreatography is the investigation of choice for choledocholithiasis; however, its use is varied, and guidelines are not well-defined. The NICE guidelines recommend MRCP be done when common bile duct dilatation ≥ 8mm or liver function tests) are abnormal but do not quantify this further. The liberal use of MRCP is gaining popularity as a roadmap prior to cholecystectomy, aiming to assess primarily for the presence of migrated gallstones within the cystic duct or common bile duct, as well as providing information regarding the anatomical features of the extrahepatic biliary tree on an individualized basis. Due to these reasons, MRCP is at times done unnecessarily which creates an economic burden and restricts access to patients in real need of imaging slots. Method It is a hospital-based retrospective observational study. The time frame was July 2021 to July 2022. The sample size was 230 patients. Result Our Study showed that isolated elevated Alanine Aminotransferase levels should not be a reason to evaluate patients for Choledocholithiasis. It concluded that elevated serum bilirubin levels, Alkaline Phosphatase, and Gamma Glutamyl Transferase are the strongest predictors of CBD stones in patients with gallstone disease and hence can be used to triage patients for undergoing MRCP. Conclusions To conclude elevated serum bilirubin levels, ALP and GGT are the strongest predictors of CBD stones in patients with gallstone disease and hence can be used to triage patients for undergoing MRCP. Isolated elevated ALT should not be a reason to evaluate patients for CBD stones.

Serum gamma glutamyl transferase levels in metabolic syndrome in obese south Indian population

Background: Increased waist circumference in metabolic syndrome (MS), which reflects central obesity is associated with an increased risk of type 2 diabetes, dyslipidemia, hypertension and coronary vascular disease. Generation of free radicals in central obesity depletes intracellular glutathione, thereby induces release of gamma glutamyl transferase (GGT) into circulation. Elevated GGT levels could be a marker of high oxidative stress which is known to be associated with central obesity and metabolic syndrome. Hence the aim of this study was to determine the association of GGT levels with components of metabolic syndrome in obese South Indian population. Materials and methods: In this case control study conducted at Master Health Check (MHC) Department, Sri Ramachandra Medical College, study population included 60 obese subjects with metabolic syndrome (cases) and 60 non obese subjects (controls) of South Indian population who were non-smokers and non-alcoholics, between the ages of 30-50 years. Components of metabolic syndrome such as waist circumference, blood pressure, fasting plasma glucose, lipid profiles and GGT measured in both the groups. Data between cases and controls compared with unpaired student t-test. Pearson’s correlation was performed to find the association of GGT levels with other variables in Metabolic syndrome. Results: Serum GGT levels were significantly higher in metabolic syndrome patients (cases) than controls with p &lt; 0.0001. High levels of serum GGT were also associated with increase in BP and atherogenic lipid levels and ratios. Conclusion: Elevated serum GGT levels were significantly associated with components of metabolic syndrome in obese South Indian population.

Association of gamma-glutamyl transferase concentrations with all-cause and cause-specific mortality in Chinese adults with type 2 diabetes.

Evidence links gamma-glutamyl transferase (GGT) to mortality in the general population. However, the relationship of GGT with all-cause and cause-specific mortality risk has been little explored in type 2 diabetes mellitus (T2DM) patients. We recruited 20 340 community-dwelling T2DM patients between 2013 and 2014 in Jiangsu, China. Cox regression models were used to assess associations of GGT with all-cause and specific-cause mortality. Restricted cubic splines were used to analyze dose-response relationships between GGT and mortality. Stratified analysis was conducted to examine potential interaction effects by age, sex, smoking status, body mass index (BMI), diabetes duration, and dyslipidemia. During a median follow-up period of 7.04 years (interquartile range: 6.98-7.08), 2728 deaths occurred, including 902 (33.09%) due to cardiovascular disease (CVD), and 754 (27.58%) due to cancer. GGT concentrations were positively associated with all-cause, CVD, and cancer mortality. Multivariable hazard ratios (HRs) for the highest (Q5) vs. the lowest quintile (Q1) were 1.63 (95% confidence intervals [CI]: 1.44-1.84) for all-cause mortality, 1.87 (95% CI: 1.49-2.35) for CVD mortality, and 1.43 (95% CI: 1.13-1.81) for cancer mortality. Effect modification by BMI and dyslipidemia was observed for all-cause mortality (both p for interaction <.05), and HRs were stronger in the BMI <25 kg/m2 group and those without dyslipidemia. Our findings suggest that, in Chinese T2DM patients, elevated serum GGT concentrations were associated with mortality for all-cause, CVD, and cancer, and further research is needed to elucidate the role of obesity, nonalcoholic fatty liver disease, and lipids in this association.

Diabetes mellitus in patients with type 1 autoimmune pancreatitis at diagnosis and after corticosteroid therapy

BackgroundA high prevalence of diabetes mellitus (DM) coexisting with autoimmune pancreatitis (AIP) is observed. However, evidence on the circumstances under which corticosteroid therapy (CST) for AIP improves or worsens DM is scarce. This study aimed to demonstrate and identify predictors of DM control under the influence of CST. MethodsPatients diagnosed with type 1 AIP were enrolled from a prospectively maintained cohort and were classified into three groups according to the chronology in which AIP and DM were diagnosed: pre-existing DM (pDM), concurrent DM (cDM), and non-DM (nDM). The responses of DM to CST were assessed when corticosteroid was ceased or tapered to a maintenance dose and classified as ‘improvement’ and ‘non-improvement’ (including ‘no change’ and ‘exacerbation’). ResultsAmong 101 patients with type 1 AIP, 52 (51.5%) patients were complicated with DM at the time of AIP diagnosis, with 36 patients in the cDM group and 16 patients in the pDM group. The incidences of diffuse pancreatic swelling (72.2%) and pancreatic body/tail involvement (91.7%) were significantly higher in the cDM group than in both the pDM and nDM groups. Of the 52 patients with DM, CST was administered in 48 cases. Multivariate logistic analysis identified that elevated serum gamma-glutamyl transferase (GGT) level at AIP diagnosis [odds ratio (OR) = 0.032, 95% confidence interval (CI): 0.003-0.412, P = 0.008] and pancreatic atrophy after CST (OR = 0.027, 95% CI: 0.003-0.295, P = 0.003) were negatively associated with DM control improvement. ConclusionsPatients with diffuse pancreatic swelling and pancreatic body/tail involvement in pancreatitis tended to be complicated with cDM at AIP diagnosis. CST exerted a beneficial effect on the clinical course of DM in nearly half of the AIP patients complicated with DM at diagnosis, particularly in those without elevated serum GGT levels at diagnosis and who did not experience pancreatic atrophy after CST.

The Preclinical Benefit of Glutamine in bisphenol A-induced Hepatotoxicity in Wistar Rats

Background: Oxidative stress may be a causative factor for bisphenol A (BPA) -induced hepatotoxicity. Glutamine (GM) is an amino acid with the ability to inhibit oxidative stress. Objective: This study evaluated the ability of GM to prevent BPA-induced hepatotoxicity in rats. Methods: Adult Wistar rats of both sexes (n=30) were used. The rats were randomly grouped into six of five rats each. Groups A (Control), B, and C were treated with normal saline (0.2 mL), GM (80 mg/kg), and BPA (50 mg/kg), respectively for 60 days. Groups D-F were treated with GM (20 mg/kg)+BPA (50 mg/kg), GM (40 mg/kg)+BPA (50 mg/kg), and GM (80 mg/kg)+BPA (50 mg/kg), respectively for 60 days. After treatment, blood and liver samples were obtained for biochemical and histological assessments, respectively. Results: Significantly (P&lt;0.01) decreased body weight and significantly (P&lt;0.01) increased liver weight occurred in the BPA-administered group when compared to the control group. The BPA-administered group showed significantly (P&lt;0.001) elevated serum total bilirubin, lactate dehydrogenase, aminotransferases, conjugated bilirubin, gamma-glutamyl transferase, alkaline phosphatase, and liver malondialdehyde concentrations when compared to the control group. Significantly (P&lt;0.001) decreased liver superoxide dismutase, glutathione peroxidase, catalase, and glutathione levels occurred in the PBA-administered group when compared to the control group. BPA caused hepatocyte necrosis, sinusoids, and central vein congestion. BPA-induced hepatotoxicity was reversed by GM; 20 mg/kg (P&lt;0.05), 40 mg/kg (P&lt;0.01), and 80 mg/kg (P&lt;0.001) in a dose-related fashion when compared to BPA. Conclusion: GM may be effective against BPA-associated hepatotoxicity.

The liberal use of magnetic resonance cholangiopancreatography can be switched over to its selective use to detect choledocholithiasis

Background: Gallstone disease is known in 10-15% of adults in Western populations. Magnetic resonance cholangiopancreatography (MRCP) is the investigation of choice for choledocholithiasis; however, its use is varied, and guidelines are not well defined. The National Institute for Health and Care (NICE) guidelines recommends MRCP to be done when common bile duct (CBD) dilatation ≥8 mm or liver function tests (LFTs) are abnormal but do not quantify this further. The liberal use of MRCP is gaining popularity as a roadmap prior to cholecystectomy, aiming to assess primarily for the presence of migrated gallstones within the cystic duct or common bile duct, as well as providing information regarding the anatomical features of the extrahepatic biliary tree on an individualised basis. Due to these reasons MRCP at times is done unnecessarily which creates economic burden and restricts access to patients in real need of imaging slots. Methods: It is hospital based retrospective observational study. Time frame was July 2021 to July 2022 and sample size was 230 patients. Results: Our study showed that isolated elevated alanine aminotransferase (ALT) level should not be reason to evaluate patients for choledocholithiasis. It concluded that elevated serum bilirubin levels, alkaline phosphatase (ALP) and gamma glutamyl transferase (GGT) are the strongest predictors of CBD stones in patients with gallstone disease and hence can be used to triage patients for undergoing MRCP. Conclusions: To conclude elevated serum bilirubin levels, ALP and GGT are the strongest predictors of CBD stones in patients with gallstone disease and hence can be used to triage patients for undergoing MRCP. Isolated elevated ALT should not be a reason to evaluate patients for CBD stones.

Chemical Composition of Tagetes patula Flowers Essential Oil and Hepato-Therapeutic Effect against Carbon Tetrachloride-Induced Toxicity (In-Vivo)

The liver is a crucial organ among body organs due to its wide functions, in particular, detoxification and metabolism. Exposure to detrimental chemicals or viral infections may provoke liver dysfunction and ultimately induce liver tissue damage. Finding natural substances for liver disease treatment to overcome the conventional treatments' side effects has attracted the attention of researchers worldwide. Our current work was conducted to investigate the hepato-therapeutic activities of essential oil (EO) isolated from Tagetes patula flowers. EO was extracted using the hydro-distillation (HD) technique and its chemical composition was identified by GC/MS. Then, the hepatic treatment potential of extracted EO was evaluated in vivo against CCL4 in rats. HD of T. patula flowers yielded highly chemical constituents of EO along with significant antioxidant potential. A coherent molecular network was fashioned via the Global Natural Products Social Molecular Networking (GNPS) to visualize the essential components and revealed that the sesquiterpene (E)-β-caryophyllene was the most predominant volatile constituent which accounted for 24.1%. The treatment of CCL4 led to significant induced oxidative stress markers malonaldehyde, total protein, and non-protein sulfhydryl, as well as elevated serum aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, and bilirubin. In addition, it disrupted the level of lipid profile. The post-treatment using T. patula EO succeeded in relieving all toxic effects of CCl4 and recuperating the histopathological signs induced by CCL4. Silymarin was used as a standard hepatoprotective agent. The obtained results demonstrated that the extracted EO exerted high protective activities against the toxicity of CCL4. Moreover, the T. patula flowers EO can be used as a natural remedy to relieve many contemporary liver diseases related to oxidative stress.

Clinicopathologic and immunophenotypic features in dogs with presumptive large granular lymphocyte leukaemia.

Large granular lymphocytic leukaemia (LGLL) has been described in a range of species but has been most commonly reported in humans and dogs. In both species, this neoplasia exhibits diversity in both phenotype and biological behaviour with phenotype only partially predicting behaviour. There is currently little knowledge of concurrent haematological and serum biochemistry features or concurrent occurrence of distinct neoplasia in canine LGLL cases. This study presents a canine case series and defines haematological parameters, novel serum biochemistry findings and phenotype of the large granular lymphocytes in an Australian case series. Neutrophilia was the most common haematological abnormality, identified in 43% of dogs, and 84% of dogs with biochemistry data available had elevated serum gamma-glutamyl transferase. Five of the 40 dogs in this study exhibited concurrent neoplasia during the period of the study, demonstrating this is a relatively common clinical outcome in canine LGLL cases. In agreement with previous canine and human studies, the most common LGLL phenotype in dogs is CD3+, CD4- and CD8+. Further work is needed to define the variables predictive of the biological behaviour of LGLL in dogs.

Gamma-glutamyl-transferase may predict COVID-19 outcomes in hospitalised patients.

AimIn this study, we aimed to define the predictive role of liver function tests at admission to the hospital in outcomes of hospitalised patients with COVID‐19.Material and MethodIn this multicentric retrospective study, a total of 269 adult patients (≥18 years of age) with confirmed COVID‐19 who were hospitalised for the treatment were enrolled. Demographic features, complete medical history and laboratory findings of the study participants at admission were obtained from the medical records. Patients were grouped regarding their intensive care unit (ICU) requirements during their hospitalisation periods.ResultsAmong all 269 participants, 106 were hospitalised in the ICU and 66 died. The patients hospitalised in ICU were older than patients hospitalised in wards (P = .001) and expired patients were older than alive patients (P = .001). Age, elevated serum D‐dimer, creatinine and gamma‐glutamyl transferase (GGT) levels at admission were independent factors predicting ICU hospitalisation and mortality in COVID‐19 patients.ConclusionIn conclusion, in hospitalised patients with COVID‐19, laboratory data on admission, including serum, creatinine, GGT and d‐dimer levels have an important predictive role for the ICU requirement and mortality. Since these tests are readily available in all hospitals and inexpensive, some predictive formulas may be calculated with these parameters at admission, to define the patients requiring intensive care.

Serum Gamma-Glutamyltransferase Levels Predict the Development of Cerebral Infarction in the Korean Population.

PurposeThis study examined the relationship between serum gamma-glutamyltransferase concentration and the risk of cerebral infarction in the Koreans.Materials and MethodsA total of 209,481 out of 223,551 participants in the National Health Information Database who received medical checkups in 2009 were included in the final analysis. The diagnosis code ICD I63 was used for identifying cerebral infarction cases and tracked the development of cerebral infarction by 2013. Cox proportional hazards model was used to calculate hazard ratios (HRs) for cerebral infarction and their confidence interval (CI).ResultsDuring a follow-up period of 915,387.5 person-years, 2403 incident cases of cerebral infarction developed between 2009 and 2013. After adjusting for multiple covariates, the hazard ratios (95% confidence interval) for incident cerebral infarction, comparing the second, third, and fourth quartile of serum gamma-glutamyltransferase levels with the first quartile, were 1.11 (0.98–1.27), 1.39 (1.22–1.58), and 1.49 (1.29–1.71), respectively (P for trend <0.001).ConclusionElevated serum gamma-glutamyltransferase levels were independently associated with the future development of cerebral infarction in Koreans.

Exploration of the Underlying Nutritional, Inflammatory and Oxidative Stress Pathological Mechanisms in Preeclampsia using Principal Component Analysis

Normal pregnancy is characterized by a mild systemic inflammatory response and progressive increase in serum inflammatory cytokines that peak in the third trimester. During pregnancy pre-existing inflammatory conditions, acquired oxidative stress arising from the placenta malfunction and nutritional deficiencies can trigger intense systemic responses that lead to endothelial activation, dysfunction and preeclampsia. We investigated the principal nutritional, oxidative and inflammatory pathways that trigger the clinical manifestation of preeclampsia.&#x0D; This case-control study included 250 women with preeclampsia and 150 normotensive pregnant women. Urinary Iodine concentration (IUC) and serum levels of Ferritin, Thyroid-stimulating Hormone (TSH), selenium, Nitric Oxide (NO) gamma glutamyl transferase (GGT), Rheumatoid factor, and high sense C-reactive protein (hs-CRP) of cases and controls were compared using the student’s t and the Mann-Whitney U tests. Principal component analysis was carried out to delineate the patterns of association between nutritional, inflammatory and oxidative markers and preeclampsia.&#x0D; The main pathophysiological pathways identified were the interactions between selenium/iodine deficiency and elevated serum TSH (endothelial dysfunction); serum ferritin, GGT, CRP and low urinary iodine concentration (inflammatory oxidative stress); elevated serum hs-CRP and Rheumatoid factor subclinical inflammation and immune cell activation) and high T3/T4 ratio (acute TSH stimulation of thyroid with low thyroid iodine stores)&#x0D; Combined selenium and iodine deficiency resulting into elevated TSH, low NO and preferential T3 secretion; acute inflammatory conditions associated with elevated serum GGT, CRP, and Ferritin; and subclinical inflammatory conditions characterized by autoimmunity are some of the major oxidant and inflammatory pathways associated with increased risk of preeclampsia.

Enhanced Susceptibility to Breast Cancer in Korean Women With Elevated Serum Gamma-Glutamyltransferase Levels: A Nationwide Population-Based Cohort Study.

BackgroundThe incidence of breast cancer has been gradually increasing in Korea. Recently, the elevated level of serum gamma-glutamyltransferase (GGT) has emerged to be associated with the development and progression of some malignancies. This study aimed to determine the effect of serum GGT levels on the risk of developing breast cancer in Korean women.MethodsWe used National Health Insurance Service Health Checkup data to examine the association between serum GGT levels and breast cancer development in Korean women. Women aged 40 years or older who participated in the Korean National Health Screening Examination between January 2009 and December 2009 and who did not develop any cancer within 1-year post examination were included in this analysis (n = 3,109,506). Cox proportional hazard regression analysis was conducted to calculate hazard ratios (HRs) with 95% confidence intervals (CIs).ResultsOverall, an elevated serum GGT level was associated with the increased risk of developing breast cancer; compared to the Q1 group, the Q4 group showed a significantly increased breast cancer risk (HR: 1.120,95% CI: 1.08–1.162). Such a relationship was stronger in post-menopausal women than pre-menopausal women (HR: 1.173, 95% CI: 1.107–1.243; HR: 1.070, 95% CI:1.019–1.124). Women with a high GGT level (Q4) were also at an increased risk of developing carcinoma in situ (CIS) (HR: 1.114, 95% CI: 1.04–1.192). In post-menopausal women, the Q4 group also exhibited higher CIS risk (HR: 1.266, 95% CI: 1.132–1.416). However, no significant difference in the risk of developing CIS was observed between the Q1 and Q4 groups in pre-menopausal women. Further analysis revealed that obese, post-menopausal women with a high GGT level (Q4) were associated with an increased risk of developing breast cancer (HR: 1.214, 95% CI: 1.125–1.31) and CIS (HR: 1.348, 95% CI: 1.159–1.569).ConclusionsOur study results demonstrate that increased serum GGT level is a risk factor for developing breast cancer. The post-menopausal women group with obesity and elevated serum GGT level showed the highest incidence of breast cancer. Thus, serum GGT concentration could be a novel and potential risk factor for breast cancer. Further validation in different ethnic groups would be warranted.

Risk of gastrointestinal cancer in patients with an elevated level of gamma-glutamyltransferase: A nationwide population-based study.

Emerging evidence that an elevated serum gamma-glutamyltransferase (GGT) level is associated with an increased risk of gastrointestinal cancer, but still controversial. The aim of this study to assess the relationship between GGT level and risk of gastrointestinal cancer, and the contribution of the interaction of hyperglycemia with elevated GGT level to the incidence of gastrointestinal cancer by the stratified analysis. A total of 8,120,665 Koreans who received medical checkups in 2009 were included. Subjects were classified according to the quartile of GGT level for women and men. The incidence rates of gastrointestinal cancer for each group were analyzed using Cox proportional hazards models. During follow-up, 129,853 cases of gastrointestinal cancer newly occurred (esophagus, 3,792; stomach, 57,932; and colorectal, 68,789 cases). The highest GGT quartile group showed an increased risk of gastrointestinal cancer (esophagus, hazard ratio = 2.408 [95% confidence interval, 2.184-2.654]; stomach, 1.121 [1.093-1.149]; and colorectal, 1.185 [1.158-1.211]). The risk increased significantly with the rise in GGT quartile level, regardless of the site of cancer. The stratified analysis according to glycemic status showed that the effect of elevated GGT was predominant in the risk of esophageal cancer. The effect of elevated GGT further increased the risk of stomach and colorectal cancers in diabetic patients. An elevated level of GGT was associated with an increased risk of gastrointestinal cancer, regardless of the site of cancer. The effect of the increase in GGT level on the risk of gastrointestinal cancer depended on the type of cancer and glycemic status.

Determining the association between repeatedly elevated serum gamma-glutamyltransferase levels and risk of respiratory cancer: A nationwide population-based cohort study.

BackgroundAlthough elevated serum gamma‐glutamyltransferase (GGT) is a known indicator of increased risk of several cancers, the clinical value of repeated measurements of GGT has not been determined. Therefore, we aimed to investigate whether repeatedly elevated serum GGT levels are associated with the risk of respiratory cancer incidence.MethodsWe included participants who had undergone the Korean Health screening four times during 2009–2012 and had previously undergone four consecutive examinations. Those who were diagnosed with respiratory cancer before the date of examination were excluded. The participants obtained one GGT point if their GGT levels were in the highest quartile (the quartile 4 group). We analyzed the association between GGT points and respiratory cancer incidence by Cox proportional hazard models.ResultsDuring mean follow‐up of 6.39 ± 1.2 years, 3,559,109 participants were enrolled. Of them, 8,944 (0.34%) men and 1,484 (0.14%) women were newly diagnosed with respiratory cancer. In multivariate analysis adjusted for confounding factors, male participants with 4 GGT points had a significantly higher hazards of developing respiratory cancer than those with 0 GGT points (hazard ratio [HR]: 1.39; 95% confidence interval [CI]: 1.31–1.48). Among female, participants with the highest points of GGT also had sixfold increased risk of developing laryngeal cancer. However, no significant association was observed between GGT points and lung cancer incidence among women (HR: 0.95; 95% CI: 0.81–1.11).ConclusionRepeatedly elevated serum levels of GGT were associated with a higher risk of respiratory cancer incidence, especially in men. This finding suggests that physicians can identify a person with a higher risk of respiratory cancer through a simple repeated measurement of GGT.