Journal/Magazine Articles

Permanent URI for this collectionhttp://repository.kln.ac.lk/handle/123456789/13

This collection contains original research articles, review articles and case reports published in local and international peer reviewed journals by the staff members of the Faculty of Medicine

Browse

Filters

2021 - 20223

Settings

Author: search.filters.author.Loh, M.Subject: search.filters.subject.Diabetes

Search Results

Now showing 1 - 3 of 3
  • No Thumbnail Available
    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.
  • Thumbnail Image
    Item
    Identification of genetic effects underlying type 2 diabetes in South Asian and European populations
    (Nature Publishing Group UK, 2022) Loh, M.; Zhang, W.; Ng, H.K.; Schmid, K.; Lamri, A.; Tong, L.; Ahmad, M.; Lee, J.J.; Ng, M.C.Y.; Petty, L.E.; Spracklen, C.N.; Takeuchi, F.; Islam, M.T.; Jasmine, F.; Kasturiratne, A.; Kibriya, M.; Mohlke, K.L.; Paré, G.; Prasad, G.; Shahriar, M.; Chee, M.L.; de Silva, H.J.; Engert, J.C.; Gerstein, H.C.; Mani, K.R.; Sabanayagam, C.; Vujkovic, M.; Wickremasinghe, A.R.; Wong, T.Y.; Yajnik, C.S.; Yusuf, S.; Ahsan, H.; Bharadwaj, D.; Anand, S.S.; Below, J.E.; Boehnke, M.; Bowden, D.W.; Chandak, G.R.; Cheng, C.Y.; Kato, N.; Mahajan, A.; Sim, X.; McCarthy, M.I.; Morris, A.P.; Kooner, J.S.; Saleheen, D.; Chambers, J.C.
    South Asians are at high risk of developing type 2 diabetes (T2D). We carried out a genome-wide association meta-analysis with South Asian T2D cases (n = 16,677) and controls (n = 33,856), followed by combined analyses with Europeans (neff = 231,420). We identify 21 novel genetic loci for significant association with T2D (P = 4.7 × 10-8 to 5.2 × 10-12), to the best of our knowledge at the point of analysis. The loci are enriched for regulatory features, including DNA methylation and gene expression in relevant tissues, and highlight CHMP4B, PDHB, LRIG1 and other genes linked to adiposity and glucose metabolism. A polygenic risk score based on South Asian-derived summary statistics shows ~4-fold higher risk for T2D between the top and bottom quartile. Our results provide further insights into the genetic mechanisms underlying T2D, and highlight the opportunities for discovery from joint analysis of data from across ancestral populations.
  • Thumbnail Image
    Item
    The iHealth-T2D study, prevention of type 2 diabetes amongst South Asians with central obesity and prediabetes: study protocol for a randomised controlled trial
    (BioMed Central, London, 2021) Kasturiratne, A.; Khawaja, K.I.; Ahmad, S.; Siddiqui, S.; Shahzad, K.; Athauda, L.K.; Jayawardena, R.; Mahmood, S.; Muilwijk, M.; Batool, T.; Burney, S.; Glover, M.; Palaniswamy, S.; Bamunuarachchi, V.; Panda, M.; Madawanarachchi, S.; Rai, B.; Sattar, I.; Silva, W.; Waghdhare, S.; Jarvelin, M.R.; Rannan-Eliya, R.P.; Gage, H.M.; van Valkengoed, I.G.M.; Valabhji, J.; Frost, G.S.; Loh, M.; Wickremasinghe, A.R.; Kooner, J.S.; Katulanda, P.; Jha, S.; Chambers, J.C.
    Background: People from South Asia are at increased risk of type 2 diabetes (T2D). There is an urgent need to develop approaches for the prevention of T2D in South Asians that are cost-effective, generalisable and scalable across settings.Hypothesis: Compared to usual care, the risk of T2D can be reduced amongst South Asians with central obesity or raised HbA1c, through a 12-month lifestyle modification programme delivered by community health workers.Design: Cluster randomised clinical trial (1:1 allocation to intervention or usual care), carried out in India, Pakistan, Sri Lanka and the UK, with 30 sites per country (120 sites total). Target recruitment 3600 (30 participants per site) with annual follow-up for 3 years.Entry criteria: South Asian, men or women, age 40-70 years with (i) central obesity (waist circumference ≥ 100 cm in India and Pakistan; ≥90 cm in Sri Lanka) and/or (ii) prediabetes (HbA1c 6.0-6.4% inclusive).Exclusion criteria: known type 1 or 2 diabetes, normal or underweight (body mass index < 22 kg/m2); pregnant or planning pregnancy; unstable residence or planning to leave the area; and serious illness.Endpoints: The primary endpoint is new-onset T2D at 3 years, defined as (i) HbA1c ≥ 6.5% or (ii) physician diagnosis and on treatment for T2D. Secondary endpoints at 1 and 3 years are the following: (i) physical measures: waist circumference, weight and blood pressure; (ii) lifestyle measures: smoking status, alcohol intake, physical activity and dietary intake; (iii) biochemical measures: fasting glucose, insulin and lipids (total and HDL cholesterol, triglycerides); and (iv) treatment compliance. Intervention: Lifestyle intervention (60 sites) or usual care (60 sites). Lifestyle intervention was delivered by a trained community health worker over 12 months (5 one-one sessions, 4 group sessions, 13 telephone sessions) with the goal of the participants achieving a 7% reduction in body mass index and a 10-cm reduction in waist circumference through (i) improved diet and (ii) increased physical activity. Usual care comprised a single 30-min session of lifestyle modification advice from the community health worker. Results: We screened 33,212 people for inclusion into the study. We identified 10,930 people who met study entry criteria, amongst whom 3682 agreed to take part in the intervention. Study participants are 49.2% female and aged 52.8 (SD 8.2) years. Clinical characteristics are well balanced between intervention and usual care sites. More than 90% of follow-up visits are scheduled to be complete in December 2020. Based on the follow-up to end 2019, the observed incidence of T2D in the study population is in line with expectations (6.1% per annum). Conclusion: The iHealth-T2D study will advance understanding of strategies for the prevention of diabetes amongst South Asians, use approaches for screening and intervention that are adapted for low-resource settings. Our study will thus inform the implementation of strategies for improving the health and well-being of this major global ethnic group.