33 results on '"Fraser J. Pirie"'
Search Results
2. Burden of Diabetes and First Evidence for the Utility of HbA1c for Diagnosis and Detection of Diabetes in Urban Black South Africans: The Durban Diabetes Study.
- Author
-
Thomas R Hird, Fraser J Pirie, Tonya M Esterhuizen, Brian O'Leary, Mark I McCarthy, Elizabeth H Young, Manjinder S Sandhu, and Ayesha A Motala
- Subjects
Medicine ,Science - Abstract
OBJECTIVE:Glycated haemoglobin (HbA1c) is recommended as an additional tool to glucose-based measures (fasting plasma glucose [FPG] and 2-hour plasma glucose [2PG] during oral glucose tolerance test [OGTT]) for the diagnosis of diabetes; however, its use in sub-Saharan African populations is not established. We assessed prevalence estimates and the diagnosis and detection of diabetes based on OGTT, FPG, and HbA1c in an urban black South African population. RESEARCH DESIGN AND METHODS:We conducted a population-based cross-sectional survey using multistage cluster sampling of adults aged ≥18 years in Durban (eThekwini municipality), KwaZulu-Natal. All participants had a 75-g OGTT and HbA1c measurements. Receiver operating characteristic (ROC) analysis was used to assess the overall diagnostic accuracy of HbA1c, using OGTT as the reference, and to determine optimal HbA1c cut-offs. RESULTS:Among 1190 participants (851 women, 92.6% response rate), the age-standardised prevalence of diabetes was 12.9% based on OGTT, 11.9% based on FPG, and 13.1% based on HbA1c. In participants without a previous history of diabetes (n = 1077), using OGTT as the reference, an HbA1c ≥48 mmol/mol (6.5%) detected diabetes with 70.3% sensitivity (95%CI 52.7-87.8) and 98.7% specificity (95%CI 97.9-99.4) (AUC 0.94 [95%CI 0.89-1.00]). Additional analyses suggested the optimal HbA1c cut-off for detection of diabetes in this population was 42 mmol/mol (6.0%) (sensitivity 89.2% [95%CI 78.6-99.8], specificity 92.0% [95%CI: 90.3-93.7]). CONCLUSIONS:In an urban black South African population, we found a high prevalence of diabetes and provide the first evidence for the utility of HbA1c for the diagnosis and detection of diabetes in black Africans in sub-Saharan Africa.
- Published
- 2016
- Full Text
- View/download PDF
3. Polygenic prediction of lipid traits in sub-Saharan Africans
- Author
-
Tinashe Chikowore, Marijana Vujkovic, Elizabeth Young, Ayesha A. Motala, Sounkou Toure, Abram Bunya Kamiza, Fraser J. Pirie, Christopher Kintu, Tafadzwa Machipisa, Manjinder S. Sandhu, Opeyemi S. Soremekun, Dipender Gill, Moffat J. Nyirenda, Segun Fatumo, Pontiano Kaleebu, and Manuel Corpas
- Subjects
Sub saharan ,Biology ,Demography - Abstract
Polygenic risk scores (PRS) can enhance risk stratification and are useful for precision medicine interventions. Here we show that African American Genome-wide Association Study (GWAS) derived PRS enhance prediction of lipid traits in Sub-Saharan Africans. Our PRS prediction varied greatly between South African Zulus (LDL-C, R2 = 8.49%) and Ugandans (LDL-C, R2= 0.043%), potentially attributable to environmental factors. Moreover, the PRS shown here had a higher discriminatory ability (AUC = 74.6%) than conventional risk factors (AUC= 67.8%) to identify extreme phenotypes. This work highlights the utility of PRS derived from relevant ethnic groups for identifying high-risk cases missed by conventional clinical factors.
- Published
- 2021
- Full Text
- View/download PDF
4. Polygenic prediction of type 2 diabetes in continental Africa
- Author
-
Elizabeth Young, Adebowale Adeyemo, Fraser J. Pirie, Segun Fatumo, Charles N. Rotimi, Marijana Vujkovic, Dipender Gill, Mark I. McCarthy, Ayesha Motola, Manjinder S Sandhu, Tinashe Chikowore, and Kenneth Ekoru
- Subjects
Research design ,Decile ,business.industry ,Diabetes mellitus ,Psychological intervention ,Ethnic group ,Medicine ,Genome-wide association study ,Type 2 diabetes ,business ,medicine.disease ,Genetic association ,Demography - Abstract
ObjectivePolygenic prediction of type 2 diabetes in continental Africans is adversely affected by the limited number of genome-wide association studies (GWAS) of type 2 diabetes from Africa, and the poor transferability of European derived polygenic risk scores (PRS) in diverse ethnicities. We set out to evaluate if African American or multi-ethnic derived PRSs would improve polygenic prediction in continental Africans.Research Design and MethodsUsing the PRSice software, ethnic-specific PRSs were computed with weights from the type 2 diabetes GWAS of the Million Veteran Program (MVP) study. The South African Zulu study (1602 cases and 976 controls) was used as the target data set. Replication and assessment of the best predictive PRS association with age at diagnosis was done in the Africa America Diabetes Mellitus (AADM) study (1031 cases and 738 controls).ResultsThe African American derived PRS was more predictive of type 2 diabetes compared to the European and multi-ethnic derived scores. Notably, participants in the 10th decile of this PRS had a 3.19-fold greater risk (OR 3.19; 95%CI (1.94-5.29), p = 5.33 x10-6) of developing diabetes and were diagnosed 2.6 years earlier compared to those in the first decile.ConclusionsAfrican American derived PRS enhances polygenic prediction of type 2 diabetes in continental Africans. Improved representation of non-Europeans populations (including Africans) in GWAS, promises to provide better tools for precision medicine interventions in type 2 diabetes.
- Published
- 2021
- Full Text
- View/download PDF
5. Trans-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- Author
-
Anubha Mahajan, Cassandra N Spracklen, Weihua Zhang, Maggie CY Ng, Lauren E Petty, Hidetoshi Kitajima, Grace Z Yu, Sina Rüeger, Leo Speidel, Young Jin Kim, Momoko Horikoshi, Josep M Mercader, Daniel Taliun, Sanghoon Moon, Soo-Heon Kwak, Neil R Robertson, Nigel W Rayner, Marie Loh, Bong-Jo Kim, Joshua Chiou, Irene Miguel-Escalada, Pietro della Briotta Parolo, Kuang Lin, Fiona Bragg, Michael H Preuss, Fumihiko Takeuchi, Jana Nano, Xiuqing Guo, Amel Lamri, Masahiro Nakatochi, Robert A Scott, Jung-Jin Lee, Alicia Huerta-Chagoya, Mariaelisa Graff, Jin-Fang Chai, Esteban J Parra, Jie Yao, Lawrence F Bielak, Yasuharu Tabara, Yang Hai, Valgerdur Steinthorsdottir, James P Cook, Mart Kals, Niels Grarup, Ellen M Schmidt, Ian Pan, Tamar Sofer, Matthias Wuttke, Chloe Sarnowski, Christian Gieger, Darryl Nousome, Stella Trompet, Jirong Long, Meng Sun, Lin Tong, Wei-Min Chen, Meraj Ahmad, Raymond Noordam, Victor JY Lim, Claudia HT Tam, Yoonjung Yoonie Joo, Chien-Hsiun Chen, Laura M Raffield, Cécile Lecoeur, Nisa M Maruthur, Bram Peter Prins, Aude Nicolas, Lisa R Yanek, Guanjie Chen, Richard A Jensen, Salman Tajuddin, Edmond Kabagambe, Ping An, Anny H Xiang, Hyeok Sun Choi, Brian E Cade, Jingyi Tan, Fernando Abaitua, Linda S Adair, Adebowale Adeyemo, Carlos A Aguilar-Salinas, Masato Akiyama, Sonia S Anand, Alain Bertoni, Zheng Bian, Jette Bork-Jensen, Ivan Brandslund, Jennifer A Brody, Chad M Brummett, Thomas A Buchanan, Mickaël Canouil, Juliana CN Chan, Li-Ching Chang, Miao-Li Chee, Ji Chen, Shyh-Huei Chen, Yuan-Tsong Chen, Zhengming Chen, Lee-Ming Chuang, Mary Cushman, Swapan K Das, H. Janaka de Silva, George Dedoussis, Latchezar Dimitrov, Ayo P Doumatey, Shufa Du, Qing Duan, Kai-Uwe Eckardt, Leslie S Emery, Daniel S Evans, Michele K Evans, Krista Fischer, James S Floyd, Ian Ford, Myriam Fornage, Oscar H Franco, Timothy M Frayling, Barry I Freedman, Christian Fuchsberger, Pauline Genter, Hertzel C Gerstein, Vilmantas Giedraitis, Clicerio González-Villalpando, Maria Elena González-Villalpando, Mark O Goodarzi, Penny Gordon-Larsen, David Gorkin, Myron Gross, Yu Guo, Sophie Hackinger, Sohee Han, Andrew T Hattersley, Christian Herder, Annie-Green Howard, Willa Hsueh, Mengna Huang, Wei Huang, Yi-Jen Hung, Mi Yeong Hwang, Chii-Min Hwu, Sahoko Ichihara, Mohammad Arfan Ikram, Martin Ingelsson, Md. Tariqul Islam, Masato Isono, Hye-Mi Jang, Farzana Jasmine, Guozhi Jiang, Jost B Jonas, Marit E Jørgensen, Torben Jørgensen, Yoichiro Kamatani, Fouad R Kandeel, Anuradhani Kasturiratne, Tomohiro Katsuya, Varinderpal Kaur, Takahisa Kawaguchi, Jacob M Keaton, Abel N Kho, Chiea-Chuen Khor, Muhammad G Kibriya, Duk-Hwan Kim, Katsuhiko Kohara, Jennifer Kriebel, Florian Kronenberg, Johanna Kuusisto, Kristi Läll, Leslie A Lange, Myung-Shik Lee, Nanette R Lee, Aaron Leong, Liming Li, Yun Li, Ruifang Li-Gao, Symen Ligthart, Cecilia M Lindgren, Allan Linneberg, Ching-Ti Liu, Jianjun Liu, Adam E Locke, Tin Louie, Jian’an Luan, Andrea O Luk, Xi Luo, Jun Lv, Valeriya Lyssenko, Vasiliki Mamakou, K Radha Mani, Thomas Meitinger, Andres Metspalu, Andrew D Morris, Girish N. Nadkarni, Jerry L Nadler, Michael A Nalls, Uma Nayak, Ioanna Ntalla, Yukinori Okada, Lorena Orozco, Sanjay R Patel, Mark A Pereira, Annette Peters, Fraser J Pirie, Bianca Porneala, Gauri Prasad, Sebastian Preissl, Laura J Rasmussen-Torvik, Alexander P Reiner, Michael Roden, Rebecca Rohde, Katheryn Roll, Charumathi Sabanayagam, Maike Sander, Kevin Sandow, Naveed Sattar, Sebastian Schönherr, Claudia Schurmann, Mohammad Shahriar, Jinxiu Shi, Dong Mun Shin, Daniel Shriner, Jennifer A Smith, Wing Yee So, Alena Stančáková, Adrienne M Stilp, Konstantin Strauch, Ken Suzuki, Atsushi Takahashi, Kent D Taylor, Barbara Thorand, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Brian Tomlinson, Jason M Torres, Fuu-Jen Tsai, Jaakko Tuomilehto, Teresa Tusie-Luna, Miriam S Udler, Adan Valladares-Salgado, Rob M van Dam, Jan B van Klinken, Rohit Varma, Marijana Vujkovic, Niels Wacher-Rodarte, Ellie Wheeler, Eric A Whitsel, Ananda R Wickremasinghe, Konstantin Willems van Dijk, Daniel R Witte, Chittaranjan S Yajnik, Ken Yamamoto, Toshimasa Yamauchi, Loïc Yengo, Kyungheon Yoon, Canqing Yu, Jian-Min Yuan, Salim Yusuf, Liang Zhang, Wei Zheng, null FinnGen, Leslie J Raffel, Michiya Igase, Eli Ipp, Susan Redline, Yoon Shin Cho, Lars Lind, Michael A Province, Craig L Hanis, Patricia A Peyser, Erik Ingelsson, Alan B Zonderman, Bruce M Psaty, Ya-Xing Wang, Charles N Rotimi, Diane M Becker, Fumihiko Matsuda, Yongmei Liu, Eleftheria Zeggini, Mitsuhiro Yokota, Stephen S Rich, Charles Kooperberg, James S Pankow, James C Engert, Yii-Der Ida Chen, Philippe Froguel, James G Wilson, Wayne HH Sheu, Sharon LR Kardia, Jer-Yuarn Wu, M Geoffrey Hayes, Ronald CW Ma, Tien-Yin Wong, Leif Groop, Dennis O Mook-Kanamori, Giriraj R Chandak, Francis S Collins, Dwaipayan Bharadwaj, Guillaume Paré, Michèle M Sale, Habibul Ahsan, Ayesha A Motala, Xiao-Ou Shu, Kyong-Soo Park, J Wouter Jukema, Miguel Cruz, Roberta McKean-Cowdin, Harald Grallert, Ching-Yu Cheng, Erwin P Bottinger, Abbas Dehghan, E-Shyong Tai, Josee Dupuis, Norihiro Kato, Markku Laakso, Anna Köttgen, Woon-Puay Koh, Colin NA Palmer, Simin Liu, Goncalo Abecasis, Jaspal S Kooner, Ruth JF Loos, Kari E North, Christopher A Haiman, Jose C Florez, Danish Saleheen, Torben Hansen, Oluf Pedersen, Reedik Mägi, Claudia Langenberg, Nicholas J Wareham, Shiro Maeda, Takashi Kadowaki, Juyoung Lee, Iona Y Millwood, Robin G Walters, Kari Stefansson, Simon R Myers, Jorge Ferrer, Kyle J Gaulton, James B Meigs, Karen L Mohlke, Anna L Gloyn, Donald W Bowden, Jennifer E Below, John C Chambers, Xueling Sim, Michael Boehnke, Jerome I Rotter, Mark I McCarthy, and Andrew P Morris
- Subjects
0303 health sciences ,Transferability ,Translation (biology) ,Type 2 diabetes ,Biology ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Evolutionary biology ,Global health ,medicine ,Genetic risk ,Gene ,030217 neurology & neurosurgery ,030304 developmental biology ,Genetic association - Abstract
We assembled an ancestrally diverse collection of genome-wide association studies of type 2 diabetes (T2D) in 180,834 cases and 1,159,055 controls (48.9% non-European descent). We identified 277 loci at genome-wide significance (p-8), including 237 attaining a more stringent trans-ancestry threshold (p-9), which were delineated to 338 distinct association signals. Trans-ancestry meta-regression offered substantial enhancements to fine-mapping, with 58.6% of associations more precisely localised due to population diversity, and 54.4% of signals resolved 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 foundations for functional investigations. Trans-ancestry genetic risk scores enhanced transferability across diverse populations, providing a step towards more effective clinical translation to improve global health.
- Published
- 2020
- Full Text
- View/download PDF
6. Rickets mimicker: a report of two cases of primary hyperparathyroidism in adolescence
- Author
-
Ayesha A. Motala, Imran M Paruk, and Fraser J. Pirie
- Subjects
Pediatrics ,medicine.medical_specialty ,business.industry ,Endocrinology, Diabetes and Metabolism ,Rickets ,medicine.disease ,Asymptomatic ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Internal Medicine ,medicine ,030212 general & internal medicine ,medicine.symptom ,Presentation (obstetrics) ,business ,030217 neurology & neurosurgery ,Primary hyperparathyroidism - Abstract
The presentation of primary hyperparathyroidism (PHPT) in most Western countries has evolved from the classic description of ‘stones, bones, and groans’ to becoming increasingly asymptomatic as a r...
- Published
- 2018
- Full Text
- View/download PDF
7. Characteristics and outcome of surgically treated acromegaly patients attending an endocrinology clinic at a tertiary referral centre in Durban, South Africa over a period of 10 years
- Author
-
Abdurraouf Masaud Elbueishi, Ayesha A. Motala, and Fraser J. Pirie
- Subjects
medicine.medical_specialty ,Modalities ,business.industry ,Endocrinology, Diabetes and Metabolism ,Tertiary referral centre ,General surgery ,030209 endocrinology & metabolism ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Acromegaly ,Internal Medicine ,Medicine ,Presentation (obstetrics) ,business ,030217 neurology & neurosurgery - Abstract
Background: The mode of presentation, clinical, radiologic and laboratory characteristics of patients with acromegaly and the outcome following various modalities of treatment are not well document...
- Published
- 2018
- Full Text
- View/download PDF
8. Characteristics and outcome of patients with pheochromocytoma at a tertiary endocrinology clinic in Durban, South Africa over 14 years
- Author
-
Ayesha A. Motala, Fraser J. Pirie, and Abdurraouf Esseid Zorgani
- Subjects
medicine.medical_specialty ,business.industry ,Endocrinology, Diabetes and Metabolism ,General surgery ,030209 endocrinology & metabolism ,medicine.disease ,Pheochromocytoma ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,030220 oncology & carcinogenesis ,Internal Medicine ,medicine ,business - Abstract
Objectives: To evaluate the characteristics and outcomes of treatment of patients with pheochromocytoma at Inkosi Albert Luthuli Central Hospital (ILACH) in Durban, South Africa over 14 years. Desi...
- Published
- 2018
- Full Text
- View/download PDF
9. Characteristics of subjects with diabetes mellitus diagnosed before 35 years of age presenting to a tertiary diabetes clinic in Durban, South Africa, from 2003 to 2016
- Author
-
Fraser J. Pirie, Imran M Paruk, Prevendri Govender, Tonya M. Esterhuizen, Khaled K. Elmezughi, and Ayesha A. Motala
- Subjects
Pediatrics ,medicine.medical_specialty ,Type 1 diabetes ,endocrine system diseases ,business.industry ,Endocrinology, Diabetes and Metabolism ,nutritional and metabolic diseases ,030209 endocrinology & metabolism ,Mean age ,Type 2 diabetes ,medicine.disease ,Obesity ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Diabetes clinic ,Diabetes mellitus ,Chart review ,Internal Medicine ,medicine ,030212 general & internal medicine ,business - Abstract
Background: Most patients diagnosed with diabetes mellitus
- Published
- 2018
- Full Text
- View/download PDF
10. Uganda Genome Resource Enables Insights into Population History and Genomic Discovery in Africa
- Author
-
Mary D Fortune, Fraser J. Pirie, Li Chen, Nicole Soranzo, Gershim Asiki, Eleftheria Zeggini, M. S. Sandhu, Martin O. Pollard, Konstantinos Hatzikotoulas, Louise V. Wain, David Neil Cooper, Deepti Gurdasani, Charles Kooperberg, Alexander P. Reiner, Ayesha A. Motala, Segun Fatumo, Yali Xue, Marianne K. DeGorter, Elizabeth H. Young, Iain Mathieson, David Heckerman, Federico Abascal, Javier Prado-Martinez, Dermot Maher, Stephen B. Montgomery, Guanjie Chen, Stephen Schiffels, Heather Elding, Chris Widmer, Tommy Carstensen, Pontiano Kaleebu, Janet Seeley, Charles N. Rotimi, Ioanna Tachmazidou, Carl M. Kadie, Yuan Chen, Inês Barroso, Anders Bergström, Kenneth Ekoru, Rebecca N Nsubuga, Anatoli Kamali, Graham R. S. Ritchie, Ayo P. Doumatey, Cristina Pomilla, Chris Finan, Chris S Franklin, Andrew P. Morris, Georg Ehret, Adebowale Adeyemo, Eleanor Wheeler, Marc Haber, Erik Garrison, Chris Tyler-Smith, Nora Franceschini, Heleen J. Bouman, Paul L. Auer, Alexander J. Mentzer, Wheeler, Eleanor [0000-0002-8616-6444], Fortune, Mary [0000-0002-6006-4343], Soranzo, Nicole [0000-0003-1095-3852], Barroso, Ines [0000-0001-5800-4520], Sandhu, Manjinder [0000-0002-2725-142X], and Apollo - University of Cambridge Repository
- Subjects
Male ,Population ,Black People ,Genomics ,Genome-wide association study ,Biology ,Genome ,Polymorphism, Single Nucleotide ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,Gene Frequency ,Humans ,Genetic Predisposition to Disease ,Uganda ,education ,030304 developmental biology ,ddc:616 ,0303 health sciences ,education.field_of_study ,Whole Genome Sequencing ,Genome, Human ,Heritability ,Human genetics ,Evolutionary biology ,Trait ,Female ,030217 neurology & neurosurgery ,Imputation (genetics) ,Genome-Wide Association Study - Abstract
Genomic studies in African populations provide unique opportunities to understand disease etiology, human diversity, and population history. In the largest study of its kind, comprising genome-wide data from 6,400 individuals and whole-genome sequences from 1,978 individuals from rural Uganda, we find evidence of geographically correlated fine-scale population substructure. Historically, the ancestry of modern Ugandans was best represented by a mixture of ancient East African pastoralists. We demonstrate the value of the largest sequence panel from Africa to date as an imputation resource. Examining 34 cardiometabolic traits, we show systematic differences in trait heritability between European and African populations, probably reflecting the differential impact of genes and environment. In a multi-trait pan-African GWAS of up to 14,126 individuals, we identify novel loci associated with anthropometric, hematological, lipid, and glycemic traits. We find that several functionally important signals are driven by Africa-specific variants, highlighting the value of studying diverse populations across the region.
- Published
- 2019
- Full Text
- View/download PDF
11. Genome-wide association study of type 2 diabetes in Africa
- Author
-
Ayo P. Doumatey, Cristina Pomilla, Elizabeth H. Young, Anubha Mahajan, Mark I. McCarthy, Meng Sun, Ayesha A. Motala, Fraser J. Pirie, Guanjie Chen, Eleanor Wheeler, Ji Chen, Andrew P. Morris, Adebowale Adeyemo, Inês Barroso, Tommy Carstensen, Charles N. Rotimi, Manjinder S. Sandhu, Sandhu, Manjinder [0000-0002-2725-142X], Barroso, Ines [0000-0001-5800-4520], Wheeler, Eleanor [0000-0002-8616-6444], and Apollo - University of Cambridge Repository
- Subjects
0301 basic medicine ,Genome-wide association study ,Genotyping Techniques ,Endocrinology, Diabetes and Metabolism ,Black People ,030209 endocrinology & metabolism ,Locus (genetics) ,Type 2 diabetes ,Biology ,Genetic analysis ,Polymorphism, Single Nucleotide ,Article ,White People ,03 medical and health sciences ,0302 clinical medicine ,Internal Medicine ,medicine ,Humans ,Genetic Predisposition to Disease ,Genetic association ,Genetics ,Fine-mapping ,medicine.disease ,Genetic architecture ,3. Good health ,Minor allele frequency ,030104 developmental biology ,Diabetes Mellitus, Type 2 ,Africa ,Established loci ,TCF7L2 ,Transcription Factor 7-Like 2 Protein - Abstract
Aims/hypothesis Genome-wide association studies (GWAS) for type 2 diabetes have uncovered >400 risk loci, primarily in populations of European and Asian ancestry. Here, we aimed to discover additional type 2 diabetes risk loci (including African-specific variants) and fine-map association signals by performing genetic analysis in African populations. Methods We conducted two type 2 diabetes genome-wide association studies in 4347 Africans from South Africa, Nigeria, Ghana and Kenya and meta-analysed both studies together. Likely causal variants were identified using fine-mapping approaches. Results The most significantly associated variants mapped to the widely replicated type 2 diabetes risk locus near TCF7L2 (p = 5.3 × 10−13). Fine-mapping of the TCF7L2 locus suggested one type 2 diabetes association signal shared between Europeans and Africans (indexed by rs7903146) and a distinct African-specific signal (indexed by rs17746147). We also detected one novel signal, rs73284431, near AGMO (p = 5.2 × 10−9, minor allele frequency [MAF] = 0.095; monomorphic in most non-African populations), distinct from previously reported signals in the region. In analyses focused on 100 published type 2 diabetes risk loci, we identified 21 with shared causal variants in African and non-African populations. Conclusions/interpretation These results demonstrate the value of performing GWAS in Africans, provide a resource to larger consortia for further discovery and fine-mapping and indicate that additional large-scale efforts in Africa are warranted to gain further insight in to the genetic architecture of type 2 diabetes. Electronic supplementary material The online version of this article (10.1007/s00125-019-4880-7) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
- Published
- 2019
- Full Text
- View/download PDF
12. Non-alcoholic fatty liver disease in Africa: a hidden danger
- Author
-
Ayesha A. Motala, Fraser J. Pirie, and Imran M Paruk
- Subjects
obesity ,Epidemiology ,Population ,HIV Infections ,type-2 diabetes ,Type 2 diabetes ,Disease ,03 medical and health sciences ,Health services ,0302 clinical medicine ,Cost of Illness ,Risk Factors ,Environmental health ,Diabetes mellitus ,Prevalence ,Humans ,Medicine ,030212 general & internal medicine ,education ,Ultrasonography ,Health Services Needs and Demand ,education.field_of_study ,business.industry ,Fatty liver ,Public Health, Environmental and Occupational Health ,non-alcoholic fatty liver disease ,nutritional and metabolic diseases ,Non alcoholic ,medicine.disease ,Obesity ,Diabetes Mellitus, Type 2 ,Africa ,Perspective ,030211 gastroenterology & hepatology ,Other ,non-alcoholic steatohepatitis ,Insulin Resistance ,business - Abstract
There is a dearth of data on the burden and spectrum of non-alcoholic fatty liver disease (NAFLD) in African populations. The limited available information suggests that the prevalence of NAFLD in the general population is lowest for the Africa region. However, this is likely to be an underestimate and also does not take into consideration the long-term impact of rising rates of obesity, type-2 diabetes mellitus (T2DM) and high human immunodeficiency virus infection burden in Africa. A racial disparity in the prevalence of NAFLD has been observed in some studies but remains unexplained. There is an absence of data from population-based studies in Africa and this highlights the need for such studies, to reliably define the health service needs for this region. Screening for NAFLD at a population-based level using ultrasound is perhaps the ideal method for resource-poor settings because of its relative cost-effectiveness. What is required as a priority from Africa, are well-designed epidemiologic studies that screen for NAFLD in the general population as well as high-risk groups such as patients with T2DM or obesity.
- Published
- 2019
- Full Text
- View/download PDF
13. Cardiovascular disease management in people with diabetes outside North America and Western Europe in 2006 and 2015
- Author
-
Olga K. Vikulova, Dianna J. Magliano, Andrea O.Y. Luk, A. Ramachandran, Fraser J. Pirie, Chern En Chiang, Sanjay Kalra, Juan José Gagliardino, Filip Surmont, Jorge Federico Elgart, Satheesh Krishnamoorthy, Maryam Tabesh, Jonathan E. Shaw, Stephanie K. Tanamas, Jencia Wong, Hiroshi Maegawa, Ayesha A. Motala, K. Tayeb, and Silver Bahendeka
- Subjects
Male ,Epidemiology ,Endocrinology, Diabetes and Metabolism ,Enfermedad cardiovascular ,Salud ,Type 2 diabetes ,Medicina Clínica ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Endocrinología y Metabolismo ,Western europe ,purl.org/becyt/ford/3.2 [https] ,Endocrinología ,030212 general & internal medicine ,Complicaciones de la Diabetes ,Research Articles ,Aspirin ,diabetes ,cardiovascular ,Middle Aged ,Europe ,Tolerability ,Hypertension ,Female ,purl.org/becyt/ford/3 [https] ,medicine.drug ,medicine.medical_specialty ,CIENCIAS MÉDICAS Y DE LA SALUD ,Medicina ,030209 endocrinology & metabolism ,03 medical and health sciences ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,medicine ,Humans ,Thiazide ,Antihypertensive Agents ,Aged ,Dyslipidemias ,Cholesterol ,business.industry ,Calcium channel ,medicine.disease ,Health Surveys ,North america ,Blood pressure ,chemistry ,Diabetes Mellitus, Type 2 ,Ciencias Médicas ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,business ,Diabetic Angiopathies ,Research: Epidemiology - Abstract
Aim: Optimal treatment of cardiovascular disease is essential to decrease mortality among people with diabetes, but information is limited on how actual treatment relates to guidelines. We analysed changes in therapeutic approaches to anti-hypertensive and lipid-lowering medications in people with Type 2 diabetes from 2006 and 2015. Methods: Summary data from clinical services in seven countries outside North America and Western Europe were collected for 39 684 people. Each site summarized individual-level data from outpatient medical records for 2006 and 2015. Data included: demographic information, blood pressure (BP), total cholesterol levels and percentage of people taking statins, anti-hypertensive medication (angiotensin-converting enzyme inhibitors, calcium channel blockers, angiotensin II receptor blockers, thiazide diuretics) and antiplatelet drugs. Results: From 2006 to 2015, mean cholesterol levels decreased in six of eight sites (range: −0.5 to −0.2), whereas the proportion with BP levels > 140/90 mmHg increased in seven of eight sites. Decreases in cholesterol paralleled increases in statin use (range: 3.1 to 47.0 percentage points). Overall, utilization of anti-hypertensive medication did not change. However, there was an increase in the use of angiotensin II receptor blockers and a decrease in angiotensin-converting enzyme inhibitors. The percentage of individuals receiving calcium channel blockers and aspirin remained unchanged. Conclusions: Our findings indicate that control of cholesterol levels improved and coincided with increased use of statins. The percentage of people with BP > 140/90 mmHg was higher in 2015 than in 2006. Hypertension treatment shifted from using angiotensin-converting enzyme inhibitors to angiotensin II receptor blockers. Despite the potentially greater tolerability of angiotensin II receptor blockers, there was no associated improvement in BP levels., Centro de Endocrinología Experimental y Aplicada
- Published
- 2018
14. Prevalence of low serum testosterone levels among men with type 2 diabetes mellitus attending two outpatient diabetes clinics in KwaZulu-Natal Province, South Africa
- Author
-
Imran M Paruk, Fraser J. Pirie, Ntombifikile M. Nkwanyana, and Ayesha A. Motala
- Subjects
Male ,medicine.medical_specialty ,Cross-sectional study ,Type 2 diabetes ,010501 environmental sciences ,Ambulatory Care Facilities ,01 natural sciences ,Body Mass Index ,South Africa ,03 medical and health sciences ,Sex hormone-binding globulin ,Blood serum ,Risk Factors ,Sex Hormone-Binding Globulin ,Surveys and Questionnaires ,Internal medicine ,Androgen deficiency ,Prevalence ,medicine ,Humans ,Testosterone ,Aged ,030304 developmental biology ,0105 earth and related environmental sciences ,Glycated Hemoglobin ,Metabolic Syndrome ,0303 health sciences ,biology ,business.industry ,Age Factors ,Testosterone (patch) ,General Medicine ,Luteinizing Hormone ,Middle Aged ,medicine.disease ,Lipids ,Cross-Sectional Studies ,Diabetes Mellitus, Type 2 ,Case-Control Studies ,Fructosamine ,biology.protein ,Symptom Assessment ,Waist Circumference ,Metabolic syndrome ,business ,Body mass index - Abstract
Background. The reported prevalence of low testosterone among men with type 2 diabetes mellitus (T2DM) is high. However, there is a dearth of information on the prevalence of androgen deficiency symptoms and low serum testosterone levels in men with T2DM from sub-Saharan Africa. Scanty data are available from Nigeria, Ghana and South Africa (SA). Objectives. To determine the prevalence of low serum testosterone and associated risk factors and the prevalence of androgen deficiency symptoms in men with T2DM. Methods. In a cross-sectional observational study, androgen deficiency symptoms in men with T2DM attending two outpatient diabetes clinics in Durban, KwaZulu-Natal Province, SA, were assessed using the Ageing Males’ Symptoms Scale (AMS) questionnaire and direct enquiry. Serum total testosterone (TT), sex hormone-binding globulin (SHBG), luteinising hormone (LH), fructosamine, serum lipids and glycated haemoglobin (HbA1c) were measured and free testosterone (FT) was calculated. TT, SHBG and FT levels were measured in control subjects with no history of diabetes. Results. There were 148 men with T2DM in the study group and 50 control subjects in the control group. In the study group, the majority were black Africans (58.8%); Indians (39.2%) and whites (2.0%) constituted the remainder. The mean (standard deviation (SD)) age was 57.5 (11.2) years, the mean duration of diabetes 11.4 (8.9) years and the mean HbA1c 8.6% (1.9%). Of the study group, 85.8% had metabolic syndrome. Mean TT, SHBG and FT and median LH (interquartile range) in the study group were within normal ranges. However, mean (SD) serum TT and FT were lower in the study group than in the control subjects (14.5 (5.8) v. 18.8 (7.2) nmol/L; p
- Published
- 2019
- Full Text
- View/download PDF
15. The effect of the introduction of a standard monitoring protocol on the investigations performed on the metabolic control of type 2 diabetes at Addington Hospital Medical Outpatients Department, Durban, South Africa
- Author
-
Tonya M. Esterhuizen, Andrew Ross, John Morton Gill, and Fraser J. Pirie
- Subjects
medicine.medical_specialty ,Pediatrics ,business.industry ,Public Health, Environmental and Occupational Health ,Type 2 diabetes ,medicine.disease ,Blood pressure ,Diabetes management ,Diabetes mellitus ,Metabolic control analysis ,Emergency medicine ,Medicine ,Family Practice ,business ,Glycated haemoglobin - Abstract
Background: A comprehensive approach to the control of type 2 diabetes is required to reduce mortality and morbidity. To improve diabetes management, in 2005 a protocol for the monitoring and management of type 2 diabetes, aligned to the 2003 Society for Endocrinology, Metabolism and Diabetes of South Africa (SEMDSA) guidelines, was introduced atAddington Hospital Medical Outpatients Department, Durban, South Africa.Method: Data were collected from 120 randomly selected patients with type 2 diabetes. The number of glycated haemoglobin (HbA1c) and lipid estimations, blood pressure (BP) measurements and body mass indices (BMIs) recorded in 2005 was compared with those recorded in 2008 and 2009. The mean levels of these parameters and the number of patients reaching goal in 2008 were compared with the figures for 2009.Results: In 2005, 18.8% of patients had HbA1c levels measured compared with 82.9% in 2009 (P < 0.01). The mean HbA1c was 6.9% (± 1.9) in 2008 and 6.4% (± 2.0) in 2009 (P = 0.1). BP and BMI was measured in over 93% of patients in 2005, 2008 and 2009. BP goals were attained by 21% of patients in 2008 and 30% in 2009 (P = 0.65). The mean BMI in 2008was 29.4 kg/m2 (24% achieved goal), and in 2009 it was 28.6kg/m2 (29% achieved goal; P = 0.267). Lipid estimations rose significantly from 26% in 2005 to 73% in 2009 (P < 0.01). There was no improvement in the number of patients reaching target lipid levels between 2008 and 2009.Conclusion: The monitoring protocol improved adherence to the SEMDSA 2003 guidelines from 2005 to 2009. Overall glycaemic control was within target, but attainment of most nonglycaemic goals was suboptimal and did not improve over the study period.
- Published
- 2012
- Full Text
- View/download PDF
16. High prevalence of abnormal liver enzymes in South African patients with type 2 diabetes mellitus attending a diabetes clinic
- Author
-
Babatope Kolawole, Fraser J. Pirie, Ayesha A. Motala, and Imran M Paruk
- Subjects
medicine.medical_specialty ,Past medical history ,biology ,medicine.diagnostic_test ,business.industry ,Endocrinology, Diabetes and Metabolism ,Type 2 Diabetes Mellitus ,Type 2 diabetes ,medicine.disease ,Endocrinology ,Alanine transaminase ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,medicine ,biology.protein ,Liver function ,Liver function tests ,Lipid profile ,business ,South African, type 2 diabetes, abnormal liver enzymes, prevalence - Abstract
Objective: To determine the prevalence of liver function test abnormalities in South African black and Indian adult patients with type 2 diabetes mellitus attending a tertiary diabetes clinic. iabetes clinic. Recorded data included the past medical and drug history, history of alcohol abuse, anthropometry, lipid profile and liver function tests. Results: The charts of 313 patients were reviewed. Liver function test abnormalities were found in 146 patients (46.6%). Of these,15 patients had a history of alcohol abuse, or a past medical history that might explain the abnormality, and these patients were excluded from further analysis. Elevations in serum gamma-glutamyl transferase, alkaline phosphatase and alanine transaminase were found in 25.2% (n = 79), 23.3% (n = 73) and 15.3% (n = 48), respectively. Serum total cholesterol, triglycerides and low-density lipoprotein cholesterol were higher in the group with liver function test abnormalities when compared with subjects with normal results. Mean body mass index was similar in the two groups (32.5 vs. 33.2 kg/m2). Although morbidly obese patients (n = 42) demonstrated the highest frequency of liver enzyme derangements (54.8%), this was not statistically significant. Conclusion: There is a high prevalence of liver function test abnormalities in this group of patients with type 2 diabetes, and this is particularly so in the morbidly obese subjects. This is comparable with the reported prevalence in the Western world. Lipid abnormalities were more frequent in the group with liver enzyme derangements.Keywords: South African, type 2 diabetes, abnormal liver enzymes, prevalence
- Published
- 2011
- Full Text
- View/download PDF
17. The Prevalence of Metabolic Syndrome and Determination of the Optimal Waist Circumference Cutoff Points in a Rural South African Community
- Author
-
Ayesha A. Motala, Tonya M. Esterhuizen, Mahomed A.K. Omar, and Fraser J. Pirie
- Subjects
Gerontology ,Adult ,Male ,medicine.medical_specialty ,Cardiovascular and Metabolic Risk ,Waist ,Cross-sectional study ,Endocrinology, Diabetes and Metabolism ,Concordance ,Black People ,Sex Factors ,Diabetes mellitus ,Epidemiology ,Internal Medicine ,medicine ,Humans ,National Cholesterol Education Program ,Original Research ,Aged ,Advanced and Specialized Nursing ,Metabolic Syndrome ,business.industry ,Anthropometry ,Middle Aged ,medicine.disease ,Cross-Sectional Studies ,Africa ,Female ,Metabolic syndrome ,Waist Circumference ,business ,Demography - Abstract
OBJECTIVE To determine the prevalence of metabolic syndrome and to define optimal ethnic-specific waist-circumference cutoff points in a rural South African black community. RESEARCH DESIGN AND METHODS This was a cross-sectional survey conducted by random-cluster sampling of adults aged >15 years. Participants had demographic, anthropometric, and biochemical measurements taken, including a 75-g oral glucose tolerance test. Metabolic syndrome was defined using the 2009 Joint Interim Statement (JIS) definition. RESULTS Of 947 subjects (758 women) studied, the age-adjusted prevalence of metabolic syndrome was 22.1%, with a higher prevalence in women (25.0%) than in men (10.5%). Peak prevalence was in the oldest age-group (≥65 years) in women (44.2%) and in the 45- to 54-year age-group in men (25.0%). The optimal waist circumference cutoff point to predict the presence of at least two other components of the metabolic syndrome was 86 cm for men and 92 cm for women. The crude prevalence of metabolic syndrome was higher with the JIS definition (26.5%) than with the International Diabetes Federation (IDF) (23.3%) or the modified Third Report of the National Cholesterol Education Program Adult Treatment Panel (ATPIII) (18.5%) criteria; there was very good agreement with the IDF definition (κ = 0.90 [95% CI 0.87–0.94]) and good concordance with ATPIII criteria (0.77 [0.72–0.82]). CONCLUSIONS There is a high prevalence of metabolic syndrome, especially in women, suggesting that this community, unlike other rural communities in Africa, already has entered the epidemic of metabolic syndrome. Waist circumference cutoff points differ from those currently recommended for Africans.
- Published
- 2011
18. Screening for asymptomatic coronary artery disease in type 2 diabetes mellitus
- Author
-
Ayesha A. Motala, Fraser J. Pirie, and H B Bacus
- Subjects
medicine.medical_specialty ,Framingham Risk Score ,endocrine system diseases ,Vascular disease ,business.industry ,Endocrinology, Diabetes and Metabolism ,nutritional and metabolic diseases ,Type 2 Diabetes Mellitus ,medicine.disease ,Asymptomatic ,Coronary artery disease ,Endocrinology ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,medicine ,Cardiology ,cardiovascular diseases ,medicine.symptom ,Risk factor ,business ,Stroke - Abstract
Diabetes mellitus is a known independent risk factor for coronary artery disease (CAD) and other macrovascular complications, including stroke and peripheral vascular disease.
- Published
- 2008
- Full Text
- View/download PDF
19. Diabetes and Other Disorders of Glycemia in a Rural South African Community
- Author
-
Fraser J. Pirie, Tonya M. Esterhuizen, Ayesha A. Motala, Eleanor Gouws, and Mahomed A.K. Omar
- Subjects
Gerontology ,Adult ,Blood Glucose ,Male ,Rural Population ,medicine.medical_specialty ,Aging ,Waist ,endocrine system diseases ,Adolescent ,Cross-sectional study ,Endocrinology, Diabetes and Metabolism ,Black People ,Body Mass Index ,Impaired glucose tolerance ,South Africa ,Internal medicine ,Diabetes mellitus ,Glucose Intolerance ,Internal Medicine ,medicine ,Diabetes Mellitus ,Prevalence ,Humans ,Family history ,Epidemiology/Health Services Research ,Aged ,Advanced and Specialized Nursing ,business.industry ,nutritional and metabolic diseases ,Odds ratio ,Middle Aged ,medicine.disease ,Health Surveys ,Blood pressure ,Cross-Sectional Studies ,Hyperglycemia ,Female ,business ,Body mass index - Abstract
OBJECTIVE—The purpose of this study was to determine the prevalence of diabetes, impaired glucose tolerance (IGT), impaired fasting glycemia (IFG), and associated risk factors in a rural South African black community. RESEARCH DESIGN AND METHODS—This was a cross-sectional survey conducted by random cluster sampling of adults aged >15 years. Participants had a 75-g oral glucose tolerance test using the 1998 World Health Organization criteria for disorders of glycemia. RESULTS—Of 1,300 subjects selected, 1,025 subjects (815 women) participated (response rate 78.9%). The overall age-adjusted prevalence of diabetes was 3.9%, IGT 4.8%, and IFG 1.5%. The prevalence was similar in men and women for diabetes (men 3.5%; women 3.9%) and IGT (men 4.6%; women 4.7%) but higher in men for IFG (men 4.0%; women 0.8%). The prevalence of diabetes and IGT increased with age both in men and women, with peak prevalence in the 55- to 64-year age-group for diabetes and in the ≥65-year age-group for IGT. Of the cases of diabetes, 84.8% were discovered during the survey. In multivariate analysis, the significant independent risk factors associated with diabetes included family history (odds ratio 3.5), alcohol ingestion (2.8), waist circumference (1.1), systolic blood pressure (1.0), serum triglycerides (2.3), and total cholesterol (1.8); hip circumference was protective (0.9). CONCLUSIONS—There is a moderate prevalence of diabetes and a high prevalence of total disorders of glycemia, which suggests that this community, unlike other rural communities in Africa, is well into an epidemic of glucose intolerance. There is a low proportion of known diabetes and a significant association with potentially modifiable risk factors.
- Published
- 2008
20. Burden of Diabetes and First Evidence for the Utility of HbA1c for Diagnosis and Detection of Diabetes in Urban Black South Africans: The Durban Diabetes Study
- Author
-
Mark I. McCarthy, Ayesha A. Motala, Elizabeth H. Young, Thomas R. Hird, Fraser J. Pirie, Tonya M. Esterhuizen, Manjinder S. Sandhu, Brian O’Leary, Sandhu, Manjinder [0000-0002-2725-142X], and Apollo - University of Cambridge Repository
- Subjects
Blood Glucose ,Male ,Urban Population ,endocrine system diseases ,Cross-sectional study ,Physiology ,Oral Glucose Suppression Test ,lcsh:Medicine ,Blood Pressure ,Biochemistry ,Vascular Medicine ,South Africa ,0302 clinical medicine ,Endocrinology ,Cost of Illness ,Cost of illness ,Prevalence ,Medicine and Health Sciences ,Diabetes diagnosis and management ,Public and Occupational Health ,030212 general & internal medicine ,lcsh:Science ,Multidisciplinary ,Traditional medicine ,Fasting ,Hematology ,Middle Aged ,3. Good health ,Body Fluids ,Blood ,Population Surveillance ,Female ,Anatomy ,Research Article ,Adult ,HbA1c ,Adolescent ,Endocrine Disorders ,Physical activity ,Black People ,030209 endocrinology & metabolism ,Blood Plasma ,03 medical and health sciences ,Young Adult ,Diabetes mellitus ,Environmental health ,parasitic diseases ,medicine ,Diabetes Mellitus ,Humans ,Hemoglobin ,Aged ,Glycated Hemoglobin ,Pharmacology ,Biology and life sciences ,Diabetes diagnosis ,business.industry ,lcsh:R ,Urban Health ,Proteins ,nutritional and metabolic diseases ,Physical Activity ,Glucose Tolerance Test ,medicine.disease ,Diagnostic medicine ,Pharmacologic-Based Diagnostics ,Cross-Sectional Studies ,Hird ,ROC Curve ,Metabolic Disorders ,Glucose Tolerance Tests ,lcsh:Q ,business - Abstract
OBJECTIVE: Glycated haemoglobin (HbA1c) is recommended as an additional tool to glucose-based measures (fasting plasma glucose [FPG] and 2-hour plasma glucose [2PG] during oral glucose tolerance test [OGTT]) for the diagnosis of diabetes; however, its use in sub-Saharan African populations is not established. We assessed prevalence estimates and the diagnosis and detection of diabetes based on OGTT, FPG, and HbA1c in an urban black South African population. RESEARCH DESIGN AND METHODS: We conducted a population-based cross-sectional survey using multistage cluster sampling of adults aged ≥18 years in Durban (eThekwini municipality), KwaZulu-Natal. All participants had a 75-g OGTT and HbA1c measurements. Receiver operating characteristic (ROC) analysis was used to assess the overall diagnostic accuracy of HbA1c, using OGTT as the reference, and to determine optimal HbA1c cut-offs. RESULTS: Among 1190 participants (851 women, 92.6% response rate), the age-standardised prevalence of diabetes was 12.9% based on OGTT, 11.9% based on FPG, and 13.1% based on HbA1c. In participants without a previous history of diabetes (n = 1077), using OGTT as the reference, an HbA1c ≥48 mmol/mol (6.5%) detected diabetes with 70.3% sensitivity (95%CI 52.7-87.8) and 98.7% specificity (95%CI 97.9-99.4) (AUC 0.94 [95%CI 0.89-1.00]). Additional analyses suggested the optimal HbA1c cut-off for detection of diabetes in this population was 42 mmol/mol (6.0%) (sensitivity 89.2% [95%CI 78.6-99.8], specificity 92.0% [95%CI: 90.3-93.7]). CONCLUSIONS: In an urban black South African population, we found a high prevalence of diabetes and provide the first evidence for the utility of HbA1c for the diagnosis and detection of diabetes in black Africans in sub-Saharan Africa.
- Published
- 2016
21. Studies of the Peptide YY and Neuropeptide Y2 Receptor Genes in Relation to Human Obesity and Obesity-Related Traits
- Author
-
I. Sadaf Farooqi, Chiao-Chien Connie Hung, Nicholas J. Wareham, Stephen O'Rahilly, Julia M. Keogh, Fraser J. Pirie, Giles S.H. Yeo, Jian'an Luan, Ayesha A. Motala, and Emma Lank
- Subjects
Male ,medicine.medical_specialty ,Linkage disequilibrium ,Endocrinology, Diabetes and Metabolism ,Population ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Cohort Studies ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Missense mutation ,Peptide YY ,Obesity ,Age of Onset ,Child ,education ,Genetics ,education.field_of_study ,digestive, oral, and skin physiology ,medicine.disease ,Phenotype ,Pedigree ,Receptors, Neuropeptide Y ,Postprandial ,Endocrinology ,Female - Abstract
Peptide-YY (PYY) is secreted from endocrine L-cells of the gastrointestinal tract in response to caloric ingestion and may mediate postprandial satiety through the hypothalamic neuropeptide Y2 receptor (Y2R). We examined whether variants in the genes encoding PYY and Y2R might be associated with obesity-related phenotypes in humans. Among 101 subjects with severe early-onset obesity and a history of hyperphagia, we found two rare sequence variants—L73P and IVS2 + 32delG—in PYY and three rare missense mutations—L40F, F87I, and A172T—in Y2R. Although none of these were found in 100 normal-weight white control subjects, L73P in PYY and F87I and A172T in Y2R did not segregate with obesity in family studies, and family data were unavailable for IVS2 + 32delG in PYY and L40F in Y2R. Two common single nucleotide polymorphisms (SNPs), R72T and IVS3 + 68C>T, in PYY were in tight linkage disequilibrium but showed no association with BMI in a large white population. In the Y2R, two SNPs, 585T>C and 936T>C, were found and were in tight linkage disequilibrium. Men, homozygous for the rarer variant, had significantly lower BMI (P = 0.017), waist-to-hip ratio (P = 0.013), and, surprisingly, higher nonesterified fatty acid levels (P = 0.01). In conclusion, mutations in PYY and Y2R are not commonly found in humans with severe early-onset obesity. The relationship between common variants in Y2R and obesity-related traits deserves further exploration in other populations.
- Published
- 2004
- Full Text
- View/download PDF
22. Myocardial perfusion imaging for evaluation of suspected ischemia and its relationship with glycemic control in South African subjects with diabetes mellitus
- Author
-
Datshana P Naidoo, Ayesha A. Motala, Akram Shmendi, Wilfred Pilloy, Fraser J. Pirie, and Boikhutso Tlou
- Subjects
medicine.medical_specialty ,Pathology ,Ischemia ,Coronary artery disease ,Myocardial perfusion imaging ,chemistry.chemical_compound ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,medicine ,Targets and Therapy [Diabetes, Metabolic Syndrome and Obesity] ,Glycemic ,Original Research ,Pharmacology ,medicine.diagnostic_test ,business.industry ,Odds ratio ,myocardial perfusion imaging ,medicine.disease ,chemistry ,diabetes mellitus ,Cardiology ,Glycated hemoglobin ,business ,Perfusion ,coronary artery disease ,glycated hemoglobin - Abstract
Akram Shmendi,1 Fraser Pirie,2 Datshana P Naidoo,3 Boikhutso Tlou,4 Wilfred Pilloy,5 Ayesha A Motala2 1Department of Medicine, 2Department of Diabetes and Endocrinology, 3Department of Cardiology, 4Department of Biostatistics, 5Department of Nuclear Medicine, University of KwaZulu-Natal, Durban, South Africa Background: The relationship between myocardial perfusion imaging (MPI) abnormalities, diabetes mellitus, and glucose control in South African populations is unknown. It was hypothesized that in subjects undergoing MPI for suspected coronary artery disease (CAD), those with diabetes would have more extensive perfusion defects and that diabetes control would influence MPI abnormalities. The aim of this study was to examine the relationship between the severity of CAD diagnosed with MPI in subjects with and without diabetes and to determine the relationship between diabetes control and extent of CAD.Methods: This study was a retrospective chart review of 340 subjects in whom MPI scans were performed over a 12-month period.Results: Subjects with diabetes had a higher prevalence of abnormal MPI, with more extensive ischemia, compared with subjects without diabetes (85.6% versus 68%; odds ratio 2.81, P
- Published
- 2014
23. The African Genome Variation Project shapes medical genetics in Africa
- Author
-
Gershim Asiki, Fasil Tekola-Ayele, Stephen Tollman, Dominic P. Kwiatkowski, Eleftheria Zeggini, Adebowale Adeyemo, Manjinder S. Sandhu, Luca Pagani, Ayesha A. Motala, Charles N. Rotimi, Deepti Gurdasani, Kalifa Bojang, Tommy Carstensen, Yali Xue, Elizabeth H. Young, Anatoli Kamali, Savita Karthikeyan, Tamiru Oljira, Neil Bradman, Rebecca N. Nsubuga, Katja Kivinen, Muminatou Jallow, Janet Seeley, Fatoumatta Sisay-Joof, Jennifer L. Asimit, Ephrem Mekonnen, Louise Iles, Endashaw Bekele, Graham R. S. Ritchie, Ananyo Choudhury, Pontiano Kaleebu, Rosemary Ekong, Konstantinos Hatzikotoulas, Martin O. Pollard, Fraser J. Pirie, Michèle Ramsay, Shane A. Norris, K Rockett, Ayo P. Doumatey, Cristina Pomilla, Ioanna Tachmazidou, Chris Tyler-Smith, Asimit, Jennifer [0000-0002-4857-2249], Kivinen, Katja [0000-0002-1135-7625], Sandhu, Manjinder [0000-0002-2725-142X], and Apollo - University of Cambridge Repository
- Subjects
medicine.medical_specialty ,Asia ,Genetics, Medical ,Population genetics ,Biology ,Genome variation ,Risk Factors ,Genotype ,Genetic variation ,parasitic diseases ,medicine ,Humans ,Selection, Genetic ,Africa South of the Sahara ,Genetics ,Genetic diversity ,Multidisciplinary ,Genome, Human ,Haplotype ,Genetic Variation ,Genomics ,3. Good health ,Europe ,Evolutionary biology ,Africa ,Medical genetics ,Imputation (genetics) - Abstract
Given the importance of Africa to studies of human origins and disease susceptibility, detailed characterization of African genetic diversity is needed. The African Genome Variation Project provides a resource with which to design, implement and interpret genomic studies in sub-Saharan Africa and worldwide. The African Genome Variation Project represents dense genotypes from 1,481 individuals and whole-genome sequences from 320 individuals across sub-Saharan Africa. Using this resource, we find novel evidence of complex, regionally distinct hunter-gatherer and Eurasian admixture across sub-Saharan Africa. We identify new loci under selection, including loci related to malaria susceptibility and hypertension. We show that modern imputation panels (sets of reference genotypes from which unobserved or missing genotypes in study sets can be inferred) can identify association signals at highly differentiated loci across populations in sub-Saharan Africa. Using whole-genome sequencing, we demonstrate further improvements in imputation accuracy, strengthening the case for large-scale sequencing efforts of diverse African haplotypes. Finally, we present an efficient genotype array design capturing common genetic variation in Africa.
- Published
- 2014
24. Open-source electronic data capture system offered increased accuracy and cost-effectiveness compared with paper methods in Africa
- Author
-
Stephen Rice, Fraser J. Pirie, David G. Dillon, Ayesha A. Motala, Cristina Pomilla, Elizabeth H. Young, and Manjinder S. Sandhu
- Subjects
Paper ,Open-source ,Operations research ,Electronic data capture ,Cost effectiveness ,Epidemiology ,Cost-Benefit Analysis ,Automatic identification and data capture ,Data capture ,Field (computer science) ,Surveys and Questionnaires ,Medicine ,Humans ,Electronics ,Survey ,Data collection ,Cost–benefit analysis ,Sub-Saharan Africa ,business.industry ,Data Collection ,Reproducibility of Results ,Electronic questionnaire ,3. Good health ,Risk analysis (engineering) ,General partnership ,Africa ,Original Article ,business - Abstract
ObjectivesExisting electronic data capture options are often financially unfeasible in resource-poor settings or difficult to support technically in the field. To help facilitate large-scale multicenter studies in sub-Saharan Africa, the African Partnership for Chronic Disease Research (APCDR) has developed an open-source electronic questionnaire (EQ).Study Design and SettingTo assess its relative validity, we compared the EQ against traditional pen-and-paper methods using 200 randomized interviews conducted in an ongoing type 2 diabetes case–control study in South Africa.ResultsDuring its 3-month validation, the EQ had a lower frequency of errors (EQ, 0.17 errors per 100 questions; paper, 0.73 errors per 100 questions; P-value ≤0.001), and a lower monetary cost per correctly entered question, compared with the pen-and-paper method. We found no marked difference in the average duration of the interview between methods (EQ, 5.4 minutes; paper, 5.6 minutes).ConclusionThis validation study suggests that the EQ may offer increased accuracy, similar interview duration, and increased cost-effectiveness compared with paper-based data collection methods. The APCDR EQ software is freely available (https://github.com/apcdr/questionnaire).
- Published
- 2013
25. Continuous subcutaneous insulin infusion therapy in type 1 diabetes: 2013 clinical guidelines and recommendations from the Association of Clinical Endocrinologists of South Africa (ACE-SA)
- Author
-
David Segal, Joel A. Dave, Imran M Paruk, Fraser J. Pirie, Larry A. Distiller, Michelle Carrihill, Wayne May, and Aslam Amod
- Subjects
Insulin pump ,medicine.medical_specialty ,Type 1 diabetes ,business.industry ,Endocrinology, Diabetes and Metabolism ,Insulin ,medicine.medical_treatment ,medicine.disease ,Diabetes Control and Complications Trial ,Surgery ,Subcutaneous insulin ,Endocrinology ,Infusion therapy ,Internal medicine ,Internal Medicine ,medicine ,Pump design ,business ,Normal range - Abstract
The first external insulin pump device to deliver continuous subcutaneous insulin infusion (CSII or “insulin pump”) therapy was used more than 30 years ago. Subsequently, the Diabetes Control and Complications Trial (DCCT) has convincingly demonstrated that stricter glycaemic control, using insulin delivered by multiple-dose injections (MDI) or CSII, prevents and retards the progression of microvascular complications. Technological improvements in pump design and functionality, the wider dissemination of accumulated knowledge and the desire to achieve blood glucose values as close to the normal range as possible, have resulted in a significant increase in insulin pump use throughout the world. An increasing body of evidence supports the ability of insulin pump therapy to improve glycaemic control while reducing hypoglycaemic episodes when used in appropriately selected patients with type 1 diabetes.
- Published
- 2013
26. Cost-effective management of diabetes mellitus
- Author
-
Ayesha A, Motala, Fraser J, Pirie, Sophia, Rauff, and Hajira B, Bacus
- Subjects
Diabetes Mellitus, Type 2 ,Cost-Benefit Analysis ,Disease Management ,Humans ,Hypoglycemic Agents ,Health Care Costs - Abstract
Diabetes is one of the most common noncommunicable diseases (NCD) globally and a leading cause of death in many countries; the global epidemic of type 2 diabetes will most affect the developing world. The burden of diabetes is related to its chronic complications, both the specific microvascular and the nonspecific macrovascular (atherosclerosis), making diabetes one of the leading causes of death in some countries and an enormous financial burden. The costs of diabetes care, both direct and indirect, are high. Single and multiple risk-factor intervention studies have provided evidence that targeting hyperglycemia and other nonglycemic risk factors reduces the risk of chronic complications; most national guidelines recommend intensified, multitargeted intervention of known modifiable risk factors. The aim in management is optimal control, both glycemic and non-glycemic (blood pressure, lipid and weight control). Management strategies for hyperglycemia include standard methods and individualized options. Given the complexities of the therapeutic choices (classes/agents) and regimens and on the basis of proven benefit, long familiarity, known side-effects, and reduced cost of sulfonylureas, biguanides, and insulin, one should start with standard methods. Despite the evidence for benefit of glycemic control, wide therapeutic choices and regimens and clearer targets for control, glycemic control is far from ideal. The cost-effectiveness of interventions to reduce the burden of diabetes-related complications compares favorably with that of other accepted uses of healthcare resources and provides convincing economic rationale for improving standards of care for patients with type 2 diabetes.
- Published
- 2006
27. Self-monitoring of blood glucose—problems with progress
- Author
-
Fraser J. Pirie
- Subjects
Newly diagnosed diabetes ,medicine.medical_specialty ,Endocrinology ,business.industry ,Endocrinology, Diabetes and Metabolism ,education ,Internal Medicine ,Self-monitoring ,Medicine ,business ,Adaptation (computer science) ,Intensive care medicine - Abstract
People with newly diagnosed diabetes are faced with an overwhelming amount of information about their condition, new skills to learn and adaptation to a new lifestyle.
- Published
- 2009
- Full Text
- View/download PDF
28. The adrenal gland in acute illness
- Author
-
Fraser J. Pirie
- Subjects
medicine.medical_specialty ,Adrenal gland ,business.industry ,Endocrinology, Diabetes and Metabolism ,Acute illness ,Endocrinology ,medicine.anatomical_structure ,Internal medicine ,Internal Medicine ,medicine ,business ,Glucocorticoid ,medicine.drug - Abstract
Defining normal adrenocortical responses (especially glucocorticoid responses) to various stimuli has been a topic of debate for many years in clinical endocrinology.
- Published
- 2006
- Full Text
- View/download PDF
29. JEMDSA 2009—A firm foundation for the future!
- Author
-
Fraser J. Pirie
- Subjects
Endocrinology ,Work (electrical) ,business.industry ,Endocrinology, Diabetes and Metabolism ,Internal Medicine ,Medicine ,Foundation (evidence) ,business ,Management - Abstract
As 2009 draws to a close, there is time to reflect on the new-look JEMDSA. Through the tireless work of Professor Stephen Hough, a new publisher was found and the endocrine community drew together to ensure the success of JEMDSA as the official journal of six societies (SEMDSA, DESSA, NOFSA, SASOM, LASSA, and PAEDS-SA).
- Published
- 2009
- Full Text
- View/download PDF
30. Holistic diabetes care—empowering patients and practitioners
- Author
-
Fraser J. Pirie
- Subjects
Blood pressure control ,medicine.medical_specialty ,endocrine system diseases ,business.industry ,Endocrinology, Diabetes and Metabolism ,Lower blood pressure ,medicine.disease ,humanities ,Surgery ,Endocrinology ,Diabetes mellitus ,Internal Medicine ,Medicine ,business ,Intensive care medicine ,psychological phenomena and processes ,Lipoprotein cholesterol - Abstract
A number of landmark studies have made it abundantly clear that the goals of diabetes care involve striving for optimal metabolic and blood pressure control. The message is now loud and clear: lower HbA1C, lower lowdensity lipoprotein cholesterol, and lower blood pressure.
- Published
- 2005
- Full Text
- View/download PDF
31. Macrovascular disease in type 2 diabetes
- Author
-
Fraser J. Pirie
- Subjects
Excess mortality ,Chronic hyperglycaemia ,medicine.medical_specialty ,endocrine system diseases ,business.industry ,Endocrinology, Diabetes and Metabolism ,nutritional and metabolic diseases ,Type 2 diabetes ,Disease ,medicine.disease ,medicine.disease_cause ,Gastroenterology ,Endocrinology ,Increased risk ,Internal medicine ,Internal Medicine ,medicine ,cardiovascular diseases ,Complication ,business ,Oxidative stress ,Macrovascular disease - Abstract
Type 2 diabetes is associated with a 2 - 4-fold increased risk of cardiovascular disease (CVD), and over half the excess mortality in subjects with type 2 diabetes is due to this complication. The development of macrovascular disease in type 2 diabetes is partly related to chronic hyperglycaemia, but also to other associated atherogenic factors, including dyslipidaemia, oxidative stress, endothelial damage, hypercoaguability and activation of inflammatory pathways.
- Published
- 2004
- Full Text
- View/download PDF
32. SEMDSA Congress 2004—a word from the Organising Committee
- Author
-
Fraser J. Pirie
- Subjects
Endocrinology ,business.industry ,Endocrinology, Diabetes and Metabolism ,Internal Medicine ,Medicine ,Library science ,business ,Word (computer architecture) - Abstract
The SEMDSA Congress, to be held on the Durban beachfront at the end of March 2004, promises to be an inspiring mix of international expertise and local input.
- Published
- 2004
- Full Text
- View/download PDF
33. Retinopathy in subjects with type 2 diabetes at a tertiary diabetes clinic in Durban, South Africa: Clinical, biochemical and genetic factors
- Author
-
Ayesha A. Motala, Sureka Maharaj, Fraser J. Pirie, Tonya M. Esterhuizen, and Imran M Paruk
- Subjects
medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Type 2 diabetes ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,chemistry.chemical_compound ,Endocrinology ,Diabetes clinic ,Internal medicine ,Diabetes mellitus ,Genetics ,Medicine ,Retinopathy ,Creatinine ,Proteinuria ,lcsh:RC648-665 ,business.industry ,Insulin ,Diabetic retinopathy ,medicine.disease ,Surgery ,chemistry ,Africa ,medicine.symptom ,business ,Research Paper - Abstract
Aim To determine the prevalence of clinical and laboratory variables and genetic polymorphisms in association with diabetic retinopathy (DR) in subjects with type 2 diabetes attending a tertiary referral diabetes clinic in Durban, South Africa. Methods Cross-sectional study on 292 Indian and African patients with type 2 diabetes (71.5% women). The presence of DR was determined by direct ophthalmoscopy. Clinical and laboratory data were collected and polymorphisms in the NOS3 (rs61722009, rs2070744, rs1799983) and VEGF (rs35569394, rs2010963) genes were determined. Results DR was present in 113 (39%) subjects. Those with DR were older (60.6 ± 9.6 vs. 55.4 ± 12.9 years, p = 0.005), had longer duration diabetes (18.5 ± 8.8 vs. 11.9 ± 9.2 years, p 1c (9.2 ± 1.8 vs. 8.8 ± 1.7%, p = 0.049), serum creatinine (106.3 ± 90.2 vs. 75.2 ± 33.4 μmol/l), triglycerides (2.1 ± 1.2 vs. 1.9 ± 1.6 mmol/l, p = 0.042), proteinuria (72% vs. 28%, p = 0.001), and used more insulin (78% vs. 39% p = 0.0001), anti-hypertensive (95% vs. 80%, p = 0.0003) and lipid-lowering therapy (70% vs. 56%, p = 0.023). There was no association between DR and any of the NOS3 or VEGF gene polymorphisms studied, although there were ethnic differences. After adjustment, diabetes duration (OR 1.05, 95% CI 1.01–1.08), presence of proteinuria (OR 4.15, 95% CI 1.70–10.11) and use of insulin therapy (OR 3.38, 95% CI 1.60–7.12) were associated with DR. Conclusion Hyperglycemia, duration of diabetes and proteinuria are associated with DR in Indian and African patients in South Africa, whereas NOS3 and VEGF gene polymorphisms were not associated with DR.
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.