Medicine
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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty
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Item Incidence and risk factors for metabolic syndrome among urban, adult Sri Lankans: a prospective, 7-year community cohort, follow-up study.(BioMed Central, 2019) de Silva, S.T.; Niriella, M.A.; Ediriweera, D.S.; Kottahachchi, D.; Kasturiratne, A.; de Silva, A.P.; Dassanayake, A.S.; Pathmeswaran, A.; Wickremasinghe, A.R.; Kato, N.; de Silva, H.J.BACKGROUND:The metabolic syndrome (MetS) is a clustering of abdominal obesity, diabetes and prediabetes, high cholesterol and high blood pressure, that confers an increased risk of cardiovascular disease. There is limited data on incidence of MetS from South Asia. This study investigated incidence and risk factors for new onset MetS in an urban adult Sri Lankan population.METHODS:Subjects (selected by age-stratified random sampling from the Ragama Medical Officer of Health area) were screened initially in 2007 (35-64 years) and re-evaluated in 2014 (42-71 years). On both occasions they were assessed by structured interview, anthropometric measurements, liver ultrasound, and biochemical/serological tests. MetS was diagnosed on International Diabetes Federation (IDF-2006) criteria. Total body fat (TBF) and visceral fat percentage (VFP) were measured in 2014, using body impedance method. Incidence and factors at baseline, associated with new onset MetS, were investigated among those who presented for re-evaluation.RESULTS:2985 (99.1%) [1636 (54.8%) women (54.8%); median age (IQR) 53 (47-59) years] from the initial cohort in 2007 had complete data. 2148 (71.9%) [1237 (57.6%) women; median age (IQR) 60 (54-66) years] attended follow-up. 949 of them [701 (73.9%) women; median age (IQR) 60 (54-65) years] had MetS (prevalence 47.2%, 95% CI 45.0-49.4%). Of 1246 who did not have MetS in 2007, 265 [178 (67.1%) women, median age (IQR) 57 (51-64) years] had developed MetS after 7 years (annual incidence 3.5% (95% CI 2.4-4.5%). Females (OR = 4.9, 95% CI 3.4-7.4), BMI > 23 kg/m2 in 2007 (OR = 1.6 per unit increase, 95% CI 1.5-1.7), weight gain (by 2-5% OR = 2.0, 95% CI 1.1-3.5; by > 5% OR = 2.2, 95% CI 1.4-3.4), and increase in waist circumference (by 2-5% OR = 7.0, 95% CI 4.0-12.2; by > 5% OR = 13.4, 95% CI 8.3-22.4) from baseline and presence of non-alcoholic fatty liver disease (NAFLD) in 2007 (OR = 1.70, 95% CI 1.04-2.76) were associated new onset MetS. Those with MetS had abnormal VFP and TBF in 2014 [P < 0.001].CONCLUSION:In this study, annual incidence of MetS was 3.5%. Female gender, BMI > 23 kg/m2 and NAFLD in 2007 and increase in weight and waist circumference from baseline were significantly associated with new onset MetS. Obesity was the best predictor of future MetSItem Incidence and risk factors for Non-Alcoholic Fatty Liver Disease in an urban, adult Sri Lankan population – a community cohort follow-up study(Sage Publishing, 2015) Niriella, M.; Kasturiratne, A.; de Silva, S.; Perera, R.; Subasinghe, C.; Kodisinghe, K.; Priyantha, C.; Rishikeshavan, V.; Dassanayake, A.; de Silva, A.; Pathmeswaran, A.; Kato, N.; de Silva, H.J.INTRODUCTION: We previously reported a community prevalence of 33% for NAFLD in an urban, adult Sri Lankan population. We also found a significant association between patatin-like phospholipase domain containing 3 (PNPLA3) gene rs738409 polymorphism, and susceptibility to NAFLD in the same population, after testing 10 selected single nucleotide polymorphisms (SNPs) in a case control study. AIMS & METHODS: The aim of this study was to assess the incidence and risk factors for NAFLD in this population after seven years of follow-up. The study population consisted of 42-71-year-old adults, originally selected by age stratified random sampling from electoral lists from Ragama, Sri Lanka. The target population was screened initially in 2007 and subsequently invited back for re-evaluation in 2014. On both occasions they were assessed using a structured interview, clinical and anthropometric measurements, liver ultrasound, and biochemical and serological tests. NAFLD was diagnosed on established ultrasound criteria for fatty liver (two out of three criteria: increased echogenecity of the liver compared to kidney and spleen, obliteration of the vascular architecture of the liver and deep attenuation of the ultrasonic signal), safe alcohol consumption (Asian standards: 514 units/week for men, 57 units/week for females) and absence of hepatitis B and C markers. Non-NAFLD controls were defined as subjects who did not have any of the ultrasound criteria for NAFLD. We also performed an updated case-control study to investigate associations of selected genetic variants with incident NAFLD [SNPs: PNPLA3 (rs738409), LYPLAL1 (rs12137855), GCKR (rs780094), PPP1R3B (rs4240624) and NCAN (rs2228603), APOC3 (rs2854117 and rs2854116), ADIPOR2 (rs767870) and STAT3 (rs6503695 and rs9891119)]. RESULTS: Of the 2985 original study participants, 2155 (72.2%) (1244 women and 911 men; mean age 59.2 years [SD, 7.7]) participated in the follow-up assessment. 1322 [mean age 58.9 years (SD, 7.6), 483 (53.0%) men and 839 (67.4%) women] had NAFLD. Out of 795 [466 (58.6%) women] participants who did not have NAFLD in the original study, 365 [226 (61.9%) women, mean age 58.6 years (SD, 7.9)] had developed NAFLD after 7 years, giving an annual incidence rate 6.6%. On multivariate analysis, increased waist circumference [OR 1.96(1.30 – 2.97), p=0.001], BMI4 23 kg/m2 [OR 2.93(1.99 – 4.30), p50.001] and raised plasma triglycerides (TG) [OR 1.49(1.03 – 2.13), p=0.03] were independently predictive of incident NAFLD in this cohort, while raised BP and reduced HDL, were not. In the updated association study involving 1310 cases and 427 controls, we found borderline association with NAFLD at two of the 10 candidate loci: rs4240624 at PPP1R3B and rs738409 at PNPLA3 (one-tailed P=0.044 and 0.033, respectively). CONCLUSION: In this community cohort follow-up study in an urban, adult population in Sri Lanka, the annual incidence of NAFLD was 6.6%. Incident NAFLD was associated with features of the metabolic syndrome, and showed tendency of association at PNPLA3 and PPP1R3B gene polymorphisms. Disclosure of Interest: None declaredItem Genetic variants of NAFLD in an urban Sri Lankan community(Wiley Blackwell Scientific Publications, 2013) Niriella, M.A.; Kasturiratne, A.; Akiyama, K.; Takeuchi, F.; Isono, M.; Dassanayake, A.S.; de Silva, A.P.; Wickremasinghe, A.R.; Kato, N.; de Silva, H.J.OBJECTIVE: Recently, genome-wide association studies (GWAS) have successfully identified loci associated with susceptibility to non-alcoholic fatty liver disease (NAFLD) in populations of European descent. No large-scale genetic studies have been performed thus far in South Asian populations. Therefore, as part of a community-based cohort study in an urban adult population of Sri Lankans, we investigated associations of genetic variants with NAFLD, diagnosed on established ultrasound criteria, and its related phenotypes. METHODS: We selected 10 single nucleotide polymorphisms (SNPs), all previously reported to be associated with NAFLD in populations of European and/or South Asian ancestry, for a case-control replication study. They included loci derived from GWAS [PNPLA3 (rs738409), LYPLAL1 (rs12137855), GCKR (rs780094), PPP1R3B (rs4240624) and NCAN (rs2228603)] plus those from candidate gene studies [APOC3 (rs2854117 and rs2854116), ADIPOR2 (rs767870) and STAT3 (rs6503695 and rs9891119)]. Genotype data of 2988 participants were used for the analysis. RESULTS: A significant NAFLD association was observed for PNPLA3 (rs738409) [OR = 1.25, 95% CI 1.08–1.44, P = 0.003)]; rs738409 was also associated with a trend towards lower serum triglycerides APOC3 variants were significantly (P = 7.3–7.5 × 10–8) associated with higher triglycerides, but not with NAFLD (OR = 0.86). Apart from SNP–lipid associations previously reported at the GCKR, PPP1R3B and NCAN loci, there were no other prominent associations. CONCLUSION: Our data confirm that the PNPLA3 gene variant is significantly associated with NAFLD in the general Sri Lankan population but could not replicate previously reported disease associations at other loci, reinforcing the importance of further large-scale study on genetic variants in diverse populations to better understand the pathophysiology of NAFLD.Item Prevalence and risk factors for metabolic syndrome among aging adults in an urban Sri Lankan population(Sri Lanka Medical Association, 2015) Kasturiratne, K.T.A.A.; Niriella, M.A.; de Silva, S.T.; Perera, K.R.; Subasinghe, S.K.C.E.; Kodisinghe, S.K.; Piyaratna, T.A.C.L.; Vithiya, K.; Kottachchi, D.; Ranawaka, U.K.; Jayasinghe, C.; Rajindrajith, S.; Dassanayake, A.S.; de Silva, A.P.; Pathmeswaran, A.; de Silva, H.J.INTRODUCTION AND OBJECTIVES: Metabolic syndrome (MetS) is assumed to be of high prevalence in the Asian region. However, its community prevalence and risk factors in South Asia is poorly studied. We determined the prevalence and risk factors for MetS among adults in an urban Sri Lankan population. METHOD: The study population consisted of 42-71 year old adults, selected by stratified random sampling from the Ragama Medical Officer of Health area. MetS was defined by the International Diabetic Federation criteria with ethnic specific cutoffs. Anthropometric measurements, blood pressure (BP) and body fat distribution estimates were made. Glycosylated hemoglobin, fasting serum lipids, serum alanine aminotransferase (ALT) and serum creatinine (SCr) with estimated glomerular filtration rate (eGFR) were determined. CKD was defined as GFR<60ml/min/1.72m2 (KDIGO/KDOQI classification), USS abdomen was performed to detect fatty liver and non-alcoholic fatty liver disease (NAFLD) was diagnosed on safe alcohol consumption (< 14 units/week for men, < 7 units/week for females) and absence of hepatitis B and C markers. RESULTS: 2155 (1244 [57.7%] women, mean age 59.2 years [SD, 7.7]) participated. 1014 (47.1%) [mean age 59.2 years (SD, 7.7), 256 (28.1%) men; 758 (60.9%) women] had MetS. On multivariate analysis female gender, abnormal total body fat and abnormal visceral fat level (>10%) and presence of NAFLD were independently associated with MetS. Age 65 or more, raised ALT and CKD were not associated with MetS. CONCLUSION: The prevalence of MetS among adults in this aging urban Sri Lankan community was high and is independently associated with female gender, abnormal body fat distribution and presence NAFLD.Item Alanine Transaminase (ALT) levels in normal adult Sri Lankans(American Gastroenterological Association(AGA) Institute, Published by Elsevier Inc., 2009) Niriella, M.A.; Dassanayake, A.S.; Kalubowila, K.; Kalubowila, U.; de Silva, A.P.; Wickremasinghe, A.R.; Kato, N.; Makaya, M.; de Silva, H.J.BACKGROUND : Alanine transaminase (ALT) levels are widely used in screening for liver disease.The upper limit of normal (ULN) of ALT (males 30 IU/l, females 19 IU/l) have been definedfor western populations. Normal levels have not been established for Asian populations. OBJECTIVES: To establish levels of ALT for a normal, adult Sri Lankan population METHODS: This study was part of a community based investigation - Ragama Health Study (RHS). The study population consisted of 35-64 year old adults, selected using stratified random sampling. Consenting adults were screened by a structured interview, liver ultrasound and collection of 10 ml venous blood. The “normal” population was defined as those not using potentially hepatotoxic drugs, safe alcohol consumption (14 units/week for males, 7 units/week for females), absence of fatty liver, and being HBsAg and anti-HCVab negative. ALT levels were estimated by a kit using the Bergmeyer method. The 95th percentile of the ALT levels was taken as the ULN. RESULTS: 3012 subjects participated in the study. The ALT level (U/l) among 831 normal males (mean 36, median 30, SD 20, ULN 68) was significantly higher than that of the 885 normal females (mean 29, median 25, SD 13, ULN 53) (p<0.001,Student's t-test ). CONCLUSION: The ULN for ALT levels of a “normal” Sri Lankan population was higher than observed in western populations. The levels were higher in males. ULN for ALT may need to be redefined for different population groups.Item Prevalence of non-alcoholic fatty liver disease and its risk factors in an urban adolescent cohort in Sri Lanka(Sri Lanka Medical Association, 2015) Jayasinghe, Y.C.; Rajindrajith, S.; Kasturiratne, A.; de Silva, S.T.; Niriella, M.A.; Perera, K.R.; Subasinghe, S.K.C.E.; Kodisinghe, S.K.; Priyantha, T.A.C.L.; Vithiya, K.; Pathmeswaran, A.; de Silva, H.J.INTRODUCTION AND OBJECTIVES: High prevalence of non-alcoholic fatty liver disease (NAFLD) is reported among adults in Sri Lanka. Although limited data on childhood obesity is available, community prevalence of NAFLD and its risk factors among adolescents is unknown. We investigated the prevalence and risk factors for NAFLD in an urban adolescent birth cohort in Sri Lanka. METHODS: The study population consisted 14 year-olds, belonging to the birth cohort born in 2000, residing in the Ragama Medical Officer of Health area. NAFLD was diagnosed based on established ultrasound criteria. Anthropometric measurements, blood pressure (BP) and total body fat distribution (TBF) estimates were made. Fasting blood sugar, serum insulin, fasting serum lipid and serum alanine aminotransferase (ALT) levels were measured. Independent predictors of NAFLD were determined by multivariate analysis. RESULTS: 508 adolescents [263 (51.8%) girls] participated in the study. Overall 44 (8.7%) had NAFLD [22 (8.4%) girls]. 46 (18.8%) boys and 54 (20.5%) girls had a BMI above the equivalent of 23 kgm2in adults. 44 (17.1%) boys and 77 (29.3%) girls had elevated TBF. On multivariate analysis, having an elevated BMI [OR=10.1 (95% confidence interval: 3.9-29.2) and elevated TBF [OR=4.4 (95% confidence interval: 1.5-12.8)] were independently associated with NAFLD. CONCLUSION: The prevalence of NAFLD among adolescents in this urban Sri Lankan community is high, and is strongly associated with obesity and abnormal TBF. Despite elevated TBF being commoner in girls, we found no gender differences in prevalence of NAFLD among adolescents in this urban Sri Lankan community is strongly associated with obesity and abnormal TBF. Our findings emphasize the needs to access these risk factors through preventive and screening programs.