Medicine
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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 Non-alcoholic fatty liver disease and its associations among adolescents in an urban, Sri Lankan community(BioMed Central, 2017) Rajindrajith, S.; Pathmeswaran, A.; Jayasinghe, C.; Kottahachchi, D.; Kasturiratne, A.; de Silva, S.T.; Niriella, M.A.; Dassanayake, A.S.; de Silva, A.P.; de Silva, H.J.BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a common problem across the world. We aimed to determine the prevalence of NAFLD and its associations in Sri Lankan adolescents living in an urban Sri Lankan community. METHOD: The study population consisted of the birth cohort of the year 2000, residing in the Ragama Medical Officer of Health area. Socio-demographic and anthropometric data [anthropometric measurements, blood pressure and total body fat distribution] of these adolescents were collected by trained data collectors. Fasting blood sugar, serum insulin, fasting serum lipids and serum alanine aminotransferase (ALT) levels were measured and an abdominal ultrasound was performed. NAFLD was diagnosed on established ultrasound criteria for fatty liver and absent alcohol consumption. RESULTS: The study sample consisted of 499 adolescents [263 (51.8%) girls]. Forty two (8.4%) had NAFLD. NAFLD was significantly associated with being breast fed for less than 4 months (33.3% vs. 17.1 in controls, p = 0.02), higher waist circumference (prevalence risk ratio 83.3/20.3, 4.1, p < 0.0001), higher body mass index (prevalence risk ratio 40.5/4.8, 8.4, p < 0/0001),higher HOMA-IR (3.7 vs. 1.9, p < 0.0001) and high triglycerides (prevalence risk ratio 14.3/5.8, 2.5, p = 0.033). Adolescents with NAFLD also had a higher amount of total body fat (p < 0.001) and subcutaneous fat (p < 0.001) than those without NAFLD. The number of children with metabolic derangements was higher among adolescents with NAFLD than those without (85.8 vs 26.3 in controls, p < 0.0001), but a family history of hypertension, diabetes, myocardial infarction or dyslipidaemia were not. CONCLUSION: Prevalence of NAFLD was high in Sri Lankan adolescents, and was associated with metabolic derangements, especially obesity, insulin resistance and early cessation of breast feeding.Item Incidence, prevalence and demographic and life style risk factors for obesity among urban, adult Sri Lankans: a community cohort follow-up study(Sri Lanka Medical Association, 2017) Niriella, M.A.; de Silva, S.T.; Kasturiratne, A.; Kottachchi, D.; Ranasinghe, R.M.A.G.; Dassanayake, A.S.; de Silva, A.P.; Pathmeswaran, A.; Wickremasinghe, A.R.; Kato, N.; de Silva, H.J.INTRODUCTION & OBJECTIVES: Obesity is a global problem. Data from the South Asian region is limited. METHODS: In a cohort follow-up study we investigated obesity among urban, adult, Sri Lankans (35-64y; selected by age-stratified random sampling from Ragama-MOH area; initial screening 2007; re-evaluation 2014). On both occasions structured interview, anthropometry, liver ultrasound, biochemical and serological tests were performed. Total body fat (TBF) and visceral fat percentage (VFP) were assessed by impedance in 2014. General-obesity (GO) was BMI>25kg/m2. Central-obesity (CO) was waist circumference (WC)>90cm males and WC>80cm females. Multinomial logistic regression was fitted to assess associations. RESULTS: In 2007 (n=2967), 614 (20.7%) were overweight [51.9%-women], 1161(39.1%) had GO [65.9%-women] and 1584(53.4%) had CO [71%-women]. Females (p<0.001), raised-TG (p<0.001), low-HDL (p<0.001), diabetes (p<0.001), hypertension (p<0.001), NAFLD (p<0.001), and low household income (p<0.001) were significantly associated with prevalent GO and CO respectively. Additionally, increased-age (p=0.05), low-educational level (p<0.001) and unhealthy eating (p<0.001) were associated with prevalent CO. Inadequate physical activity was not associated with either. 2137 (72%) attended follow-up in 2014. Of those who were initially non-obese who attended follow-up, 189/1270 (14.9%) [64% women] had developed GO (annual-incidence 2.13%) and 206/947 (21.9%) [56.3% women] had developed CO (annual incidence 3.12%) after 7 years. TBF and VFP significantly correlated with incident GO and CO (p<0.001). Female gender (OR-1.78, p<0.001; 2.81, p<0.001) and NAFLD (OR-2.93, p<0.001; OR-2.27, p<0.001) independently predicted incident GO and CO respectively. CONCLUSION: The prevalence and incidence of GO and CO were high in this cohort. Both incident GO and CO were strongly associated with female gender and NAFLD.Item Incidence and risk factors for non-alcoholic fatty liver disease in an urban, adult Sri Lankan population – a community cohort follow-up study(Sri Lanka Medical Association, 2016) Niriella, M.A.; Kasturiratne, A.; de Silva, S.T.; Perera, K.R.; Subasinghe, S.K.C.E.; Kodisinghe, S.K.; Piyarathna, T.A.C.L.; Vithiya, K.; Dassanayake, A.S.; de Silva, A.P.INTRODUCTION: In 2007, we reported a 33% prevalence of non-alcoholic fatty liver disease (NAFLD) and its association with PNPLA3(rs738409) gene polymorphism in an urban, adult Sri Lankan population. OBJECTIVES: This study investigated incidence and risk factors for NAFLD after seven years follow-up. METHOD: The study population (42-71-year-olds, selected by age-stratified random sampling from the Ragama MOH area) was screened initially in 2007 and re-evaluated in 2014. On both occasions they were assessed by structured interview, anthropometric measurements, liver ultrasound, biochemical and serological tests. NAFLD was diagnosed on established ultrasound criteria, safe alcohol consumption and absence of hepatitis B/C markers. Non-NAFLD controls did not have any ultrasound criteria for NAFLD. An updated case-control genetic association study for 10 selected genetic variants and incident NAFLD was also performed. RESULTS: 2155/2985 (72.2%) of the original cohort attended follow-up [1244-women, 911-men; mean-age 59.2(SD, 7.7) years]. 1322 [839 women; mean-age 58.9 (SD, 7.6) years] had NAFLD. Out of 795 [466 women] who initially did not have NAFLD, 365 [226 women, mean-age 58.6(SD,7.9) years] had developed NAFLD after 7 years (annual incidence-6.6%). Increased waist circumference [p=0.001], BMI>23kg/m2 [p<0.001] and raised plasma triglycerides [p<0.05] independently predicted incident NAFLD. The updated genetic association study (1310 cases, 427 controls) showed borderline association with NAFLD at 2/10 candidate loci: PPP1R3B(rs4240624), PNPLA3(rs738409) (one-tailed p=0.044 and 0.033, respectively). CONCLUSIONS: In this community cohort follow-up study, the annual incidence of NAFLD was 6.6%. Incident NAFLD was associated with features of metabolic syndrome, and showed tendency of association with PNPLA3 and PPP1R3B gene polymorphisms.Item Incidence and risk factors for non-alcoholic fatty liver disease: A 7-year follow-up study among urban, adult Sri Lankans(Blackwell Munksgaard, 2017) Niriella, M.A.; Pathmeswaran, A.; de Silva, S.T.; Kasturiratne, A.; Perera, R.; Subasinghe, C.E.; Kodisinghe, K.; Piyaratna, C.; Rishikesawan, V.; Dassanayake, A.S.; de Silva, A.P.; Wickremasinghe, R.; Takeuchi, F.; Kato, N.; de Silva, H.J.BACKGROUND: This study investigated incidence and risk factors for NAFLD among an adult cohort with 7-year follow-up. METHODS: The study population (age-stratified random sampling, Ragama MOH area) was screened initially in 2007 (aged 35-64 years) and re-evaluated in 2014 (aged 42-71 years). On both occasions assessed by structured interview, anthropometric measurements, liver ultrasound, biochemical and serological tests. NAFLD was diagnosed on ultrasound criteria, safe alcohol consumption and absence of hepatitis B/C markers. Non-NAFLD controls did not have any ultrasound criteria for NAFLD. An updated case-control genetic association study for 10 selected genetic variants and NAFLD was also performed. RESULTS: Out of 2985 of the original cohort, 2148 (72.0%) attended follow-up (1238 [57.6%] women; mean-age 59.2 [SD-7.6] years) in 2014, when 1320 (61.5%) were deemed NAFLD subjects. Out of 778 who initially did not have NAFLD and were not heavy drinkers throughout follow-up, 338 (43.4%) (221 [65.4%] women, mean-age 57.8 [SD-8.0] years) had developed NAFLD after 7-years (annual incidence-6.2%). Central obesity (OR=3.82 [95%-CI 2.09-6.99]), waist increase >5% (OR=2.46 [95%-CI 1.20-5.05]) overweight (OR=3.26 [95%-CI 1.90-5.60]), weight gain 5%-10% (OR=5.70 [95%-CI 2.61-12.47]), weight gain >10% (OR=16.94 [95%-CI 6.88-41.73]), raised plasma triglycerides (OR=1.96 [95%-CI 1.16-3.29]) and diabetes (OR=2.14 [95%-CI 1.13-4.06]), independently predicted the development of incident NAFLD in multivariate analysis. The updated genetic association study (1362-cases, 392-controls) showed replicated association (P=.045, 1-tailed) with NAFLD at a candidate locus: PNPLA3 (rs738409). CONCLUSIONS: In this community cohort study, the annual incidence of NAFLD was 6.2%. Incident NAFLD was associated with general and central obesity, raised triglycerides and diabetes, and showed a tendency of association with PNPLA3 gene polymorphisms.Item 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.