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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty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 Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation(Nature Publishing Company, New York, 2022) Mahajan, A.; Spracklen, C.N.; Zhang, W.; Ng, M.C.Y.; Petty, L.E.; Kitajima, H.; Yu, G.Z.; Rüeger, S.; Speidel, L.; Kim, Y.J.; Horikoshi, M.; Mercader, J.M .; Taliun, D.; Moon, S.; Kwak, S.H.; Robertson, N.R.; Rayner, N.W.; Loh, M.; Kim, B.; Chiou, J.; Miguel-Escalada, I.; Parolo, P.D.B.; Lin, K.; Bragg, F.; Preuss, M.H.; Takeuchi, F.; Nano, J.; Guo, X.; Lamri, A.; Nakatoch, M.; Scott, R.A.; Lee, J.J.; Huerta-Chagoya, A.; Graff, M.; Chai, J.F.; Parra, E. J.; Yao, J.; Bielak, L.F.; Tabara, Y.; Hai, Y.; Steinthorsdottir, V.; Cook, J.P.; Kals, M.; Grarup, N.; Schmidt, E.M.; Pan, I.; Sofer, T.; Wuttke, M.; Sarnowski, C.; Gieger, C.; Nousome, D.; Trompet, S.; Long, J.; Sun, M.; Tong, L.; Chen, W.M.; Ahmad, M.; Noordam, R.; Lim, V.J.Y.; Tam, C.H.T.; Joo, Y.Y.; Chen, C.H.; Raffield, L.M.; Lecoeur, C.; Prins, B.P.; Nicolas, A.; Yanek, L.R.; Chen, G.; Jensen, R.A.; Tajuddin, S.; Kabagambe, E.K.; An, P.; Xiang, A.H.; Choi, H.S.; Cade, B.E.; Tan, J.; Flanagan, J.; Abaitua, F.; Adair, L.S.; Adeyemo, A.; Aguilar-Salinas, C.A.; Akiyama, M.; Anand, S.S.; Bertoni, A.; Bian, Z.; Bork-Jensen, J.; Brandslund, I.; Brody, J.A.; Brummett, C.M.; Buchanan, T.A.; Canouil, M.; Chan, J.C.N.; Chang, L.C.; Chee, M.L.; Chen, J.; Chen, S.H.; Chen, Y.T.; Chen, Z.; Chuang, L.M.; Cushman, M.; Das, S.K.; de Silva, H.J.; Dedoussis, G.; Dimitrov, L.; Doumatey, A.P.; Du, S.; Duan, Q.; Eckardt, K.U.; Emery, L.S.; Evans, D.S.; Evans, M.K.; Fischer, K.; Floyd, J.S.; Ford, I.; Fornage, M.; Franco, O.H.; Frayling, T.M.; Freedman, B.I.; Fuchsberger, C.; Genter, P.; Gerstein, H.C.; Giedraitis, V.; Villalpando, C.G.; Villalpando, M.E.G.; Goodarzi, M.O.; Larsen, P.G.; Gorkin, D.; Gross, M.; Guo, Y.; Hackinger, S.; Han, S.; Hattersley, A.T.; Herder, C.; Howard, A.G.; Hsueh, W.; Huang, M.; Huang, W.; Hung, Y.; Hwang, M.Y.; Hwu, C.; Ichihara, S.; Ikram, M.A.; Ingelsson, M.; Islam, M.T.; Isono, M.; Jang, H.M.; Jasmine, F.; Jiang, G.; Jonas, J.B.; Jørgensen, M.E.; Jørgensen, T.; Kamatani, Y.; Kandeel, F.R.; Kasturiratne, A.; Katsuya, T.; Kaur, V.; Kawaguchi, T.; Keaton, J.M.; Kho, A.N.; Khor, C.C.; Kibriya, M.G.; Kim, D.H.; Kohara, K.; Kriebel, J.; Kronenberg, F.; Kuusisto, J.; Läll, K.; Lange, L.A.; Lee, M.; Lee, N.R.; Leong, A.; Li, L.; Li, Y.; Li-Gao, R.; Ligthart, S.; Lindgren, C.M.; Linneberg, A.; Liu, C.; Liu, J.; Locke, A.E.; Louie, T.; Luan, J.; Luk, A.O.; Luo, X.; Lv, J.; Lyssenko, V.; Mamakou, V.; Mani, K.R.; Meitinger, T.; Metspalu, A.; Morris, A.D.; Nadkarni, G.N.; Nadler, J.L.; Nalls, M.A.; Nayak, U.; Nongmaithem, S.S.; Ntalla, I.; Okada, Y.; Orozco, L.; Patel, S.R.; Pereira, M.A.; Peters, A.; Pirie, F.J.; Porneala, B.; Prasad, G.; Preissl, S.; Rasmussen-Torvik, L.J.; Reiner, A.P.; Roden, M.; Rohde, R.; Roll, K.; Sabanayagam, C.; Sander, M.; Sandow, K.; Sattar, N.; Schönherr, S.; Schurmann, C.; Shahriar, M.; Shi, J.; Shin, D.M.; Shriner, D.; Smith, J.A.; So, W.Y.; Stančáková, A.; Stilp, A.M.; Strauch, K.; Suzuki, K.; Takahashi, A.; Taylor, K.D.; Thorand, B.; Thorleifsson, G.; Thorsteinsdottir, U.; Tomlinson, B.; Torres, J.M.; Tsai, F.; Tuomilehto, J.; Tusie-Luna, T.; Udler, M.S.; Salgado, A.V.; Dam, R.M.; Klinken, J.B.; Varma, R.; Vujkovic, M.; Wacher-Rodarte, N.; Wheeler, E.; Whitsel, E.A.; Wickremasinghe, A.R.; Dijk, K.W.; Witte, D.R.; Yajnik, C.S; Yamamoto, K.; Yamauchi, T.; Yengo, L.; Yoon, K.; Yu, C.; Yuan, J.M.; Yusuf, S.; Zhang, L.; Zheng, W.; FinnGen; eMERGE Consortium; Leslie J Raffel; Igase, M.; Ipp, E.; Redline, S.; Cho, Y.S.; Lind, L.; Province, M.A.; Hanis, C.L.; Peyser, P.A.; Ingelsson, E.; Zonderman, A.B.; Psaty, B.M.; Wang, Y.; Rotimi, C.N.; Becker, D.M.; Matsuda, F.; Liu, Y.; Zeggini, E.; Yokota, M.; Rich, S.S.; Kooperberg, C.; Pankow, J.S.; Engert, J.C.; Chen, Y.I.; Froguel, P.; Wilson, J.G.; Sheu, W.H.H.; Kardia, S.L.R.; Wu, J.Y.; Hayes, M.G.; Ma, R.C.W.; Wong, T.Y.; Groop, L.; Mook-Kanamori, D.O.; Chandak, G.R.; Collins, F.S.; Bharadwaj, D.; Paré, G.; Sale, M.M.; Ahsan, H.; Motala, A.A.; Shu, X.O.; Park, K.S.; Jukema, J.W.; Cruz, M.; Cowdin, R.M.; Grallert, H.; Cheng, C.Y.; Bottinger, E.P.; Dehghan, A.; Tai, E.S.; Dupuis, J.; Kato, N.; Laakso, M.; Köttgen, A.; Koh, W.P.; Palmer, C.N.A.; Liu, S.; Abecasis, G.; Kooner, J.S.; Loos, R.J.F.; North, K.E.; Haiman, C.A.; Florez, J.C.; Saleheen, D.; Hansen, T.; Pedersen, O.; Mägi, R.; Langenberg, C.; Wareham, N.J.; Maeda, S.; Kadowaki, T.; Lee, J.; Millwood, I.Y.; Walters, R.G.; Stefansson, K.; Myers, S.R.; Ferrer, J.; Gaulton, K.J.; Meigs, J.B.; Mohlke, K.L.; Gloyn, A.L.; Bowden, D.W.; Below, J.E.; Chambers, J.C.; Sim, X.; Boehnke, M.; Rotter, J.I.; McCarthy, M.I.; Morris, A.P.We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 × 10-9), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background.Item Effects of alirocumab on cardiovascular and metabolic outcomes after acute coronary syndrome in patients with or without diabetes: a prespecified analysis of the ODYSSEY OUTCOMES randomised controlled trial.(The Lancet. Diabetes & Endocrinology., 2019) Ray, K.K.; Colhoun, H.M.; Szarek, M.; Baccara-Dinet, M.; Bhatt, D.L.; Bittner, V.A.; Budaj, A.J.; Diaz, R.; Goodman, S.G.; Hanotin, C.; Harrington, R.A.; Jukema, J.W.; Loizeau, V.; Lopes, R.D.; Moryusef, A.; Murin, J.; Pordy, R.; Ristic, A.D.; Roe, M.T.; Tuñón, J.; White, H.D.; Zeiher, A.M.; Schwartz, G.G.; Steg, P.G.; de Silva, H.A.ODYSSEY OUTCOMES Committees and Investigators.BACKGROUND: After acute coronary syndrome, diabetes conveys an excess risk of ischaemic cardiovascular events. A reduction in mean LDL cholesterol to 1·4-1·8 mmol/L with ezetimibe or statins reduces cardiovascular events in patients with an acute coronary syndrome and diabetes. However, the efficacy and safety of further reduction in LDL cholesterol with an inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) after acute coronary syndrome is unknown. We aimed to explore this issue in a prespecified analysis of the ODYSSEY OUTCOMES trial of the PCSK9 inhibitor alirocumab, assessing its effects on cardiovascular outcomes by baseline glycaemic status, while also assessing its effects on glycaemic measures including risk of new-onset diabetes. METHODS: ODYSSEY OUTCOMES was a randomised, double-blind, placebo-controlled trial, done at 1315 sites in 57 countries, that compared alirocumab with placebo in patients who had been admitted to hospital with an acute coronary syndrome (myocardial infarction or unstable angina) 1-12 months before randomisation and who had raised concentrations of atherogenic lipoproteins despite use of high-intensity statins. Patients were randomly assigned (1:1) to receive alirocumab or placebo every 2 weeks; randomisation was stratified by country and was done centrally with an interactive voice-response or web-response system. Alirocumab was titrated to target LDL cholesterol concentrations of 0·65-1·30 mmol/L. In this prespecified analysis, we investigated the effect of alirocumab on cardiovascular events by glycaemic status at baseline (diabetes, prediabetes, or normoglycaemia)-defined on the basis of patient history, review of medical records, or baseline HbA1c or fasting serum glucose-and risk of new-onset diabetes among those without diabetes at baseline. The primary endpoint was a composite of death from coronary heart disease, non-fatal myocardial infarction, fatal or non-fatal ischaemic stroke, or unstable angina requiring hospital admission. ODYSSEY OUTCOMES is registered with ClinicalTrials.gov, number NCT01663402. FINDINGS: At study baseline, 5444 patients (28·8%) had diabetes, 8246 (43·6%) had prediabetes, and 5234 (27·7%) had normoglycaemia. There were no significant differences across glycaemic categories in median LDL cholesterol at baseline (2·20-2·28 mmol/L), after 4 months' treatment with alirocumab (0·80 mmol/L), or after 4 months' treatment with placebo (2·25-2·28 mmol/L). In the placebo group, the incidence of the primary endpoint over a median of 2·8 years was greater in patients with diabetes (16·4%) than in those with prediabetes (9·2%) or normoglycaemia (8·5%); hazard ratio (HR) for diabetes versus normoglycaemia 2·09 (95% CI 1·78-2·46, p<0·0001) and for diabetes versus prediabetes 1·90 (1·65-2·17, p<0·0001). Alirocumab resulted in similar relative reductions in the incidence of the primary endpoint in each glycaemic category, but a greater absolute reduction in the incidence of the primary endpoint in patients with diabetes (2·3%, 95% CI 0·4 to 4·2) than in those with prediabetes (1·2%, 0·0 to 2·4) or normoglycaemia (1·2%, -0·3 to 2·7; absolute risk reduction pinteraction=0·0019). Among patients without diabetes at baseline, 676 (10·1%) developed diabetes in the placebo group, compared with 648 (9·6%) in the alirocumab group; alirocumab did not increase the risk of new-onset diabetes (HR 1·00, 95% CI 0·89-1·11). HRs were 0·97 (95% CI 0·87-1·09) for patients with prediabetes and 1·30 (95% CI 0·93-1·81) for those with normoglycaemia (pinteraction=0·11). INTERPRETATION: After a recent acute coronary syndrome, alirocumab treatment targeting an LDL cholesterol concentration of 0·65-1·30 mmol/L produced about twice the absolute reduction in cardiovascular events among patients with diabetes as in those without diabetes. Alirocumab treatment did not increase the risk of new-onset diabetes.Item The Influence of the smart glucose manager mobile application on Diabetes management(Sage Publications, 2019) Gunawardena, K.C.; Jackson, R.; Robinett, I.; Dhaniska, L.; Jayamanne, S.; Kalpani, S.; Muthukuda, D.BACKGROUND: Smartphone use is rapidly growing in developing countries, providing opportunity for development of new health-based mobile applications. The present study investigated the efficacy of a newly designed mobile application, Smart Glucose Manager (SGM), in Sri Lankan patients with diabetes. METHODS: A total of 67 patients with access to Android smartphones were randomized into an SGM (n = 27) and a control group (n = 25). Glycosylated hemoglobin (A1c) levels were measured at baseline and every 3 months afterward. The SGM group utilized the application daily, while control-group patients were instructed to continue their standard methods of diabetes management. Independent t-tests were utilized to assess A1c differences at 3 and 6 months postrandomization. A1c improvement, defined as A1c at 6 months minus baseline, was compared with SGM usage to assess effectiveness of diabetic management. RESULTS: At the 6-month follow up, the SGM group had significant lower A1c levels than the control group (7.2% vs 8.17%, P < .0001). For both groups, A1c values decreased from baseline to the 3 months (SGM: 9.52% to 8.16%, P < .0001; control: 9.44% to 8.31%, P < .0001). From 3 months to 6 months, the SGM group showed further improvement of A1c (-0.96% P < .0001), whereas the control group did not ( P = 0.19). A1c improvement was positively correlated with SGM usage ( R = .81, P < .001). CONCLUSION: The SGM, a mobile application specifically designed to support self-management of diabetes, appeared to show long-term improvement of A1c levels in patients with diabetes residing in Sri Lanka.Item Incidence and predictors of metabolic syndrome among urban, adult Sri Lankans: a community cohort, 7-year follow-up study(European Association for the Study of Diabetes, 2017) de Silva, S.T.; Niriella, M.A.; Kasturiratne, A.; Kottahachchi, D.; Ranawaka, U.K.; Dassanayake, A.; de Silva, A.P.; Pathmeswaran, P.; Wickremasinghe, R.; Kato, N.; de Silva, H.J.BACKGROUND AND AIMS In 2007, we reported a 38.9% prevalence of metabolic syndrome (MetS) in an urban, adult population. Published data on incident MetS from South Asia is lacking. This study investigated the incidence and risk factors for MetS after a 7-year follow-up of the initial cohort. MATERIALS AND METHODS: The study population (selected by age-stratified random sampling from the Ragama MOH area) was screened in 2007 (aged 35-64 years) and re-evaluated in 2014 (aged 42-71 years). On both occasions, structured interview, anthropometric measurements, liver ultrasound, biochemical and serological tests were performed. MetS was diagnosed on established International Diabetes Federation (IDF 2012) criteria. Total body fat (TBF) and visceral fat percentage (VFP) were measured in 2014, using impedance. Abnormal TBF was defined as >32% for females and >25% for males. Abnormal VFP was defined as >10% for both sexes. Non-alcoholic fatty liver disease (NAFLD) was diagnosed on established ultrasound criteria, safe alcohol consumption (Asian standards: <14 units/week for men, <7 units/week for women) and absence of hepatitis B and C markers. RESULTS: 2137/2967 (72.0%) of the initial cohort attended follow-up [1229 (57.5%) women; mean-age 52.4 (SD-7.7) years]. 1000/2137 [548 (54.8%) women; mean age 57.5 years (SD-7.74)] had MetS (prevalence-46.8%). Out of 1246 individuals who initially did not have MetS in 2007, 318 [225 (70.8%) women; mean age 57.5 (SD 7.7) years] had developed incident MetS after 7 years (annual incidence-2.13%). Comparison of incident MetS with those with no MetS in 2014 is shown in Table 1. On logistic regression, female sex (OR 3.6, p<0.001), central obesity [OR 4.58, p<0.001], BMI >23kg/m2 [OR 4.84, p<0.001], increase in weight 2%-5% [OR 2.02, p<0.001], increase in weight >5% [OR 5.3, p<0.001), increase in waist circumference (WC) 5-10-cm [OR 3.68, p<0.001], increase in WC >10cm [OR 10.34, p<0.001] and NAFLD (OR 2.44, p<0.001) in 2007 were independently predictive of incident MetS in 2014. Abnormal VFP [OR 4.23, p<0.001] and abnormal TBF [OR 5.25, p<0.001] were also associated with incident MetS. CONCLUSION: In this prospective community study, the annual incidence of MetS was 2.13%. Female gender, increase in weight and WC from baseline and the presence of NAFLD predicted the development of incident MetS. Obesity at baseline was the only defining individual component of MetS that predicted future MetS.Item The role of pharmacist counselling in the control of diabetes(Sri Lanka Medical Association, 2017) Mamunuwa, A.M.V.G.N.; Jayamanne, S.F.; Coombes, J.; de Silva, A.; Lynch, C.B.; Wickramasinghe, N.D.D.INTRODUCTION & OBJECTIVES: Diabetes is a global health burden. Data in international literature prove the success of involving pharmacists to achieve glycaemic control. This is the first study in Sri Lanka on the impact of pharmacist counselling among outpatients with diabetes. The objective was to assess the impact of pharmacist counselling on glycaemic control of outpatients with diabetes. METHODS: A total of 400 consecutive patients with diabetes mellitus attending the outpatient diabetes clinics at Base Hospital, Dambadeniya, were randomized into either the intervention group (IG) or the control group (CG). IG received pharmacist counselling (verbal and written) for four consecutive monthly visits in addition to the standard care at the clinic, while the CG received standard care only. Glycaemic control was assessed for both groups with HbA1c measured at the end of the four monthly visits.RESULTS: Mean age of participants was 57.14±10.15 years and 67.5% were females. Non parametric tests were performed as data did not follow the normal distribution. On analysis of HbA1c data, the IG had a median of 7.2% (IQR: 8.2%-6.5%) whereas the CG had a median of 7.7% (IQR: 8.8%-6.9%). The IG patients had statistically lower HbA1c levels compared to the CG patients, according to the Mann-Whitney U test (p<0.05). HbA1c levels <8.00% indicate good/fair glycaemic control. 73.9% of the IG, but only 58% of the CG subjects had levels <8.00%. However, 9.1% of the IG and 10% of the CG had very poor glycaemic control (HbA1c level >10.00%). CONCLUSION: Pharmacist counselling in the outpatient clinics can improve the glycaemic control of patients with diabetes.