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Saravanan, Ponnusamy
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Biography
Professor Saravanan is a Professor and Honorary Consultant Physician in Diabetes, Endocrinology & Metabolism at Warwick Medical School, University of Warwick & George Eliot Hospital, Nuneaton. He is the Lead for Diabetes division for the NIHR Clinical Research Network, West Midlands. He is the Founder-Director of international Doctoral Training Programme, which focusses on research capacity building activities in low- and middle-income countries.
He splits his time equally between clinical and research activity. For the past 17 years, Prof Saravanan’s main research focus is understanding the mechanisms and ethnic variations in ‘programming of obesity and cardiometabolic disorders’ as well as ‘precision medicine’. He has published >130 peer reviewed articles and won several national and international awards. He passionately believes in 'primordial prevention' of metabolic disorders and approaches this by focusing on the health of young women and Gestational Diabetes (GDM). To address this, he has set up early pregnancy cohorts across the world (UK – PRiDE study, n=4746; STRiDE – India, n=3070; STRiDE – Kenya, n= 4134; Malaysia – MAGIC, n=5200 and Thailand – TaRGET, n=4260).
His team won the prestigious NHS Innovation award in 2015 for individualised diabetes management for South Asians in the UK. He is instrumental in fast-track adoption of newer therapies and technologies in diabetes locally, regionally, and nationally. During the Covid-19 pandemic he was instrumental in writing the new RCOG UK screening guidelines for GDM based on his work, which was adopted widely in the UK. He co-led the BABYSTEPS trial – an innovative, combined face-face and remote intervention in post-GDM women to improve their physical activity, in collaboration with University of Leicester. He is the Editor-in-Chief for the RCP’s journal, Clinical Medicine. He reviews grants and board member for funding bodies nationally and internationally.
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Publication Open Access Cord blood adipocytokines and body composition in early childhood: a systematic review and meta-analysis(MDPI, 2021-02-16) Bagias, Christos; Sukumar, Nithya; Weldeselassie, Yonas; Oyebode, Oyinlola; Saravanan, Ponnusamy; Saravanan, Ponnusamy; Saravanan, Ponnusamy; University of Warwick; University Hospital of Ioannina, Greece; George Eliot Hospital NHS Trust, Nuneaton; Department of Diabetes, Endocrinology and Metabolism; Medical and Dental; Saravanan, Ponnusamy; Sukumar, NithyaChildhood obesity is a growing epidemic. Early identification of high-risk groups will allow for the development of prevention strategies. Cord blood adipocytokines have been previously examined as biomarkers predicting future obesity. We conducted a systematic review looking at the association between cord blood leptin and adiponectin with adiposity up to 5 years of age. A literature review was performed between January 1994 and August 2020 using two bibliographic databases (Medline/Pubmed and EMBASE) and was registered on PROSPERO (CRD42017069024). Studies using skinfold thickness and direct methods of assessing body composition in full term neonates were considered. Partial correlation and multiple regression models were used to present the results. Meta-analysis was performed, were possible, using a random effects model. Cochran's Q test was used to assess heterogeneity and I2 statistics to calculate the percentage of variation across studies. The potential for publication bias was assessed using funnel plots. Data from 22 studies were retrieved and reviewed by two independent reviewers. Cord blood leptin was positively associated with adiposity at birth (r = 0.487; 95% CI: 0.444, 0.531) but was inversely related to adiposity up to 3 years of age. The association was not sustained at 5 years. There was a weak positive association between adiponectin in cord blood and adiposity at birth (r = 0.201; 95% CI: 0.125, 0.277). No correlation was found between cord blood adiponectin in young children, but data were limited. This review supports that cord blood leptin and adiponectin are associated with adiposity at birth. The results of this study provide insight into the role of adipocytokines at birth on future metabolic health and their potential use as risk stratification tools.Publication Open Access ENDOCRINOLOGY IN THE TIME OF COVID-19: Diagnosis and management of gestational diabetes mellitus(Oxford University Press, 2020-08-01) Thangaratinam, Shakila; Cooray, Shamil D; Sukumar, Nithya; Huda, Mohammed S B; Devlieger, Roland; Benhalima, Katrien; McAuliffe, Fionnuala; Saravanan, Ponnusamy; Teede, Helena J; Saravanan, Ponnusamy; Saravanan, Ponnusamy; University of Birmingham; Birmingham Women's and Children's NHS Foundation Trust; Monash University; University of Warwick; Barts Health NHS Trust; University Hospitals Leuven; KU Leuven; University College Dublin; George Eliot Hospital; Diabetes & Metabolism; Medical and Dental; Saravanan, PonnusamyThe COVID-19 pandemic has required rapid transformation and adaptation of healthcare services. Women with gestational diabetes mellitus (GDM) are one of the largest high-risk groups accessing antenatal care. In reformulating the care offered to those with GDM, there is a need to balance the sometimes competing requirement of lowering the risk of direct viral transmission against the potential adverse impact of service changes. We suggest pragmatic options for screening of GDM in a pandemic setting based on blood tests, and risk calculators applied to underlying risk factors. Alternative models for antenatal care provision for women with GDM, including targeting high-risk groups, early lifestyle interventions and remote monitoring are provided. Testing options and their timing for postpartum screening in women who had GDM are also considered. Our suggestions are only applicable in a pandemic scenario, and usual guidelines and care pathways should be re-implemented as soon as possible and appropriate.Publication Metadata only Why do pregnant women participate in research? A patient participation investigation using Q-Methodology(Wiley, 2017-04) Meshaka, Riwa; Jeffares, Stephen; Sadrudin, Farah; Huisman, Nicole; Saravanan, Ponnusamy; Saravanan, Ponnusamy; Saravanan, Ponnusamy; University of Warwick; University of Birmingham; George Eliot Hospital; Endocrinology & Metabolism; Medical and Dental; Saravanan, PonnusamyBackground: Patient participation in study design is paramount to design studies that are acceptable to patients. Despite an increase in research involving pregnant women, relatively little is known about the motivational factors that govern their decision to be involved in a clinical trial, compared to other patient groups. Objective: To better understand the viewpoints of pregnant women who take part in clinical trials. Method: We chose to use Q-Methodology, a method of exploring the structure of opinions surrounding a topic. We developed a set of 40 statements that encompassed the reasons why pregnant women might want to take part in research and 30 research participants from the PRiDE study (an observational trial investigating the role of micronutrients in gestational diabetes) were asked to rank them in order of agreement. The finished matrices from each participant were compared and analysed to produce capturing viewpoints. Results: About 30 women aged 19-40 involved in the PRiDE study completed the questionnaire. There were two overarching motivators that emerged: a willingness to help medical research and improve our knowledge of medical science, and having a personal connection to the disease, therefore a potential fear of being affected by it. A third, less significant viewpoint, was that of a lack of inconvenience being a motivating factor. Conclusion and discussion: Understanding what motivates pregnant women to decide to take part in a research study is valuable and helps researchers maximize their uptake and retention rates when designing a trial involving pregnant women.Publication Metadata only Vitamin B12 status in women of childbearing age in the UK and its relationship with national nutrient intake guidelines: results from two National Diet and Nutrition Surveys(BMJ Publishing Group, 2016-08-12) Sukumar, Nithya; Adaikalakoteswari, Antonysunil; Venkataraman, Hema; Maheswaran, Hendramoorthy; Saravanan, Ponnusamy; Saravanan, Ponnusamy; Saravanan, Ponnusamy; University of Warwick; George Eliot Hospital, Nuneaton; General Medicine; Diabetes and Metabolism; Medical and Dental; Sukumar, Nithya; Venkataraman, Hema; Saravanan, PonnusamyObjective: To assess serum B12, folate and the associated homocysteine (Hcy) levels among women of childbearing age in the UK and examine their association with dietary intake in relation to the UK Recommended Nutrient Intakes (RNIs) for B12 and folate. Design: Cross-sectional study. Setting: Data from two publicly available National Diet and Nutrition Surveys (NDNS 2000/2001 and 2008/2012) were used. These were population-based surveys of randomly selected samples of adults which were carried out in their households. Participants: Women of childbearing age (aged 19-39 years), representative of the UK population. Those who were pregnant or breastfeeding were excluded. Outcome measures: The associations between micronutrient intakes and blood levels of B12, folate and Hcy were assessed by correlation and stepwise linear regression. B12 intake was divided into quintiles and plotted against blood B12 and Hcy concentrations to determine the threshold of any associations. Results: 299 women from the first NDNS cohort had complete intake and biomarker data. The prevalence of serum vitamin B12 (≤150 pmol/L) and serum folate (≤10 nmol/L) deficiency and hyperhomocysteinemia (≥12 µmol/L) was 12.4%, 6.4% and 21.2%, respectively, despite seemingly adequate B12 intakes (median 3.8 μg/day, 96% consumed more than the UK RNI of 1.5 μg/day). B12 concentrations increased across all quintiles of intake with serum levels in quintiles 4 and 5 (median intake 4.9 and 7.1 μg/day, respectively) significantly higher than quintile 1. However, Hcy concentrations levelled off between quintiles 4 and 5. Comparison of micronutrient intake between the two surveys found that folate intake has reduced in the more recent cohort. Conclusions: The UK RNI for B12 intake should be increased for women of childbearing age with intakes of around 5-7 μg/day likely to be associated with stable biomarker levels. B12 levels should also be measured in women preconceptionally or in early pregnancy given the high rates of deficiency.Publication Open Access Risk of dysglycemia in pregnancy amongst Kenyan women with HIV infection: a nested case-control analysis from the STRiDE study(Wiley, 2021-04-05) Pastakia, Sonak D; . Kosgei, Wycliffe K; Christoffersen-Deb, Astrid; Kiragu, Benson; Hector, John N; Anusu, Gertrude; Saravanan, Ponnusamy; Saravanan, Ponnusamy; Saravanan, Ponnusamy; Purdue University College of Pharmacy, Indianapolis, USA; Academic Model Providing Access to Healthcare, Eldoret, Kenya; Moi Teaching and Referral Hospital, AMPATH Plus-RMNCAH/FP, Kenya; University of British Columbia, Canada; University of Toronto, Canada; University of Warwick; George Eliot Hospital NHS Trust, Nuneaton; Department of Diabetes, Endocrinology and Metabolism; Medical and Dental; Saravanan, PonnusamyIntroduction. Gestational diabetes is a common complication, whose incidence is growing globally. There is a pressing need to obtain more data on GDM in low- and middle-income countries, especially amongst high-risk populations, as most of the data on GDM comes from high-income countries. With the growing awareness of the role HIV plays in the progression of noncommunicable diseases and the disproportionate HIV burden African countries like Kenya face, investigating the potential role HIV plays in increasing dysglycemia amongst pregnant women with HIV is an important area of study. Methods. The STRiDE study is one of the largest ever conducted studies of GDM in Kenya. This study enrolled pregnant women aged between 16 and 50 who were receiving care from public and private sector facilities in Eldoret, Kenya. Within this study, women received venous testing for glycosylated hemoglobin (HbA1c) and fasting glucose between 8- and 20-week gestational age. At their 24-32-week visit, they received a venous 75 g oral glucose tolerance test (OGTT). Because of the pressing need to assess the burden of GDM within the population of pregnant women with HIV, a nested case-control study design was used. Pregnant women with HIV within the larger STRiDE cohort were matched to non-HIV-infected women within the STRiDE cohort at a 1 : 3 ratio based on body mass index, parity, family history of GDM, gestational age, and family history of hypertension. The measurements of glucose from the initial visit (fasting glucose and HbA1c) and follow-up visit (OGTT) were compared between the two groups of HIV+ cases and matched HIV- controls. Results. A total of 83 pregnant women with HIV were well matched to 249 non-HIV-infected women from the STRiDE cohort with marital status being the only characteristic that was statistically significantly different between the two groups. Statistically significant differences were not observed in the proportion of women who developed GDM, the fasting glucose values, the HbA1c, or OGTT measurements between the two groups. Discussion. Significant associations were not seen between the different measures of glycemic status between pregnant women with and without HIV. While significant differences were not seen in this cohort, additional investigation is needed to better describe the association of dysglycemia with HIV, especially in Kenyan populations with a higher prevalence of GDM.Publication Open Access Experiences of using a digital type 2 diabetes prevention application designed to support women with previous gestational diabetes(BioMed Central, 2021-08-05) Ekezie, Winifred; Dallosso, Helen; Saravanan, Ponnusamy; Khunti, Kamlesh; Hadjiconstantinou, Michelle; Saravanan, Ponnusamy; Saravanan, Ponnusamy; University of Leicester; Leicester General Hospital; University of Warwick; George Eliot Hospital NHS Trust, Nuneaton; Diabetes and Endocrinology; Medical and Dental; Saravanan, PonnusamyBackground: Gestational diabetes mellitus (GDM) is diagnosed during pregnancy, and women with a history of GDM are at a higher risk of developing type 2 diabetes mellitus (T2DM). Prevention strategies focused on lifestyle modification help to reduce long-term complications. Self-management technology-based interventions can support behaviour change and diabetes control. The Baby Steps programme, a randomised controlled trial intervention offering group education and access to a mobile web application, was evaluated to explore user experience of the app and barriers and facilitators to app usability. Methods: Ten semi-structured interviews and four focus group discussions were conducted with 23 trial participants between 2018 and 2019. Interviews and focus group discussions were audiotaped, transcribed and independently analysed. The analysis was informed by thematic analysis, with the use of the Nvivo 12 software. Results: Themes identified were: (1) GDM and post-pregnancy support from healthcare services; (2) Impact of Baby Steps app on lifestyle changes; (3) Facilitators and barriers to the usability of the Baby Steps app. The Baby Steps app served as a motivator for increasing self-management activities and a tool for monitoring progress. Peer support and increased awareness of GDM and T2DM enhanced engagement with the app, while poor awareness of all the components of the app and low technical skills contributed to low usability. Conclusions: This study documents experiences from existing GDM support, user experiences from using the Baby Steps app, and the barriers and facilitators to app usability. The app was both a motivational and a monitoring tool for GDM self-management and T2DM prevention. Peer support was a key trait for enhanced engagement, while barriers were low technical skills and poor awareness of the app components. A digital app, such as the Baby Steps app, could strengthen existing face-to-face support for the prevention of T2DM. The results also have wider implications for digital support technologies for all self-management interventions. Further research on the effect of specific components of apps will be required to better understand the long term impact of apps and digital interventions on self-management behaviours and outcomes. Trial registration: ISRCTN, ISRCTN17299860 . Registered on 5 April 2017.Publication Open Access Machine learning prediction of early postpartum prediabetes in women with gestational diabetes mellitus(medRxiv, 2023-02-23) Parkhi, Durga; Periyathambi, Nishanthi; Ghebremichael-Weldeselassie, Yonas; Patel, Vinod; Sukumar, Nithya; Siddharthan, Rahul; Narlikar, Leelavati; Saravanan, Ponnusamy; Saravanan, Ponnusamy; Saravanan, Ponnusamy; University of Warwick, Coventry; George Eliot Hospital, Nuneaton; The Open University, Milton Keynes; The Institute of Mathematical Sciences, Chennai, India; Indian Institute of Science Education and Research, Pune, India; Diabetes and Endocrinology; Medical and Dental; Periyathambi, Nishanthi; Patel, Vinod; Sukumar, Nithya; Ponnusamy, SaravananBackground Early onset of type 2 diabetes and cardiovascular disease are common complications for women diagnosed with gestational diabetes. About half of the women with gestational diabetes develop postpartum prediabetes within 10 years of the index pregnancy. These women also have double the risk of developing cardiovascular disease than women without a history of gestational diabetes. Currently, there is no accurate way of knowing which women with gestational diabetes are likely to develop postpartum prediabetes. This study aims to predict the risk of postpartum prediabetes in women diagnosed with gestational diabetes. Methods We build a sparse logistic regression-based machine learning model to learn key variables significant for the prediction of postpartum prediabetes, from antenatal data with maternal anthropometric and biochemical variables as well as neonatal characteristics of 607 UK women diagnosed with gestational diabetes. We evaluate the performance of the proposed model in addition to other more advanced machine learning methods using established metrics such as the area under the receiver operating characteristic curve and specificity for pre-determined values of sensitivity. We use K-L divergence and information graphs to evaluate and compare different thresholds of classification for targeted screening options in resource-constrained settings. We also perform a decision curve analysis to study the net standardized benefit of our model compared to the universal screening approach. Results Strikingly, our sparse logistic regression approach selects only two variables as relevant but gives an area under the receiver operating characteristic curve of 0.72, outperforming all other methods. It can identify postpartum prediabetes in women with gestational diabetes using the Rule-in test with 92% specificity at an optimal probability threshold of 0.381 and using the Rule-out test with 92% sensitivity at an optimal probability threshold of 0.140. Conclusion We propose a simple logistic regression model, which needs only the antenatal fasting glucose at OGTT and HbA1c soon after the diagnosis of GDM, to predict, with remarkable accuracy, the probability of postpartum prediabetes in women with gestational diabetes. We envision this to be a practical solution, which coupled with a targeted follow-up of high-risk women, could yield better cardiometabolic outcomes in women with a history of GDM.Publication Open Access Vitamin B12 deficiency and altered one-carbon metabolites in early pregnancy is associated with maternal obesity and dyslipidaemia(Nature Research, 2020-07-06) Adaikalakoteswari, Antonysunil; Wood, Catherine; Mina, Theresia H.; Webster, Craig; Goljan, Ilona; Weldeselassie, Yonas; Reynolds, Rebecca M.; Saravanan, Ponnusamy; Saravanan, Ponnusamy; Saravanan, Ponnusamy; Nottingham Trent University; University of Warwick; George Eliot Hospital NHS Trust; University of Edinburgh; University Hospitals of Birmingham NHS Foundation Trust; Diabetes and Endocrinology; Pathology; Additional Professional Scientific and Technical Field; Medical and Dental; Wood, Catherine; Goljan, Ilona; Saravanan, Ponnusamy; Webster, CraigVitamin B12 (B12) is a micronutrient essential for one-carbon (1C) metabolism. B12 deficiency disturbs the 1C cycle and alters DNA methylation which is vital for most metabolic processes. Studies show that B12 deficiency may be associated with obesity, insulin resistance and gestational diabetes; and with obesity in child-bearing women. We therefore hypothesised that the associations between B12 deficiency, BMI and the metabolic risk could be mediated through altered 1C metabolites in early pregnancy. We explored these associations in two different early pregnancy cohorts in the UK (cohort 1; n = 244 and cohort 2; n = 60) with anthropometric data at 10-12 weeks and plasma/serum sampling at 16-18 weeks. B12, folate, total homocysteine (tHcy), methionine, MMA, metabolites of 1C metabolism (SAM, SAH) and anthropometry were measured. B12 deficiency (< 150 pmol/l) in early pregnancy was 23% in cohort 1 and 18% in cohort 2. Regression analysis after adjusting for likely confounders showed that B12 was independently and negatively associated with BMI (Cohort 1: β = - 0.260, 95% CI (- 0.440, - 0.079), p = 0.005, Cohort 2: (β = - 0.220, 95% CI (- 0.424, - 0.016), p = 0.036) and positively with HDL cholesterol (HDL-C) (β = 0.442, 95% CI (0.011,0.873), p = 0.045). We found that methionine (β = - 0.656, 95% CI (- 0.900, - 0.412), p < 0.0001) and SAH (β = 0.371, 95% CI (0.071, 0.672), p = 0.017) were independently associated with triglycerides. Low B12 status and alteration in metabolites in 1C metabolism are common in UK women in early pregnancy and are independently associated with maternal obesity and dyslipidaemia. Therefore, we suggest B12 monitoring in women during peri-conceptional period and future studies on the pathophysiological relationship between changes in 1C metabolites and its association with maternal and fetal outcomes on larger cohorts. This in turn may offer potential to reduce the metabolic risk in pregnant women and their offspring.Publication Metadata only Global burden of early pregnancy gestational diabetes mellitus (eGDM): A systematic review(Springer Verlag, 2022-03) Hannah, Wesley; Bhavadharini, Balaji; Beks, Hannah; Deepa, Mohan; Anjana, Ranjit Mohan; Uma, Ram; Martin, Erik; McNamara, Kevin; Versace, Vincent; Saravanan, Ponnusamy; Mohan, Viswanathan; Saravanan, Ponnusamy; Saravanan, Ponnusamy; Madras Diabetes Research Foundation - ICMR Center for Advanced Research on Diabetes and Dr. Mohan's Diabetes Specialities Centre, Chennai, India; Deakin University, Geelong, Australia; Women's College Hospital, Toronto, Canada; Seethapathy Clinic & Hospital, Chennai, India; University of Warwick; George Eliot Hospital NHS Trust, Nunetaon; Diabetes, Endocrinology and Metabolism; Medical and Dental; Saravanan, PonnusamyAims: Gestational diabetes mellitus (GDM) diagnosed during the first trimester of pregnancy is called 'early pregnancy Gestational Diabetes Mellitus' (eGDM). The burden of eGDM has only been studied sporadically. This review aims to understand the global burden of eGDM in terms of prevalence, risk factors, pregnancy outcomes, treatment and postpartum dysglycemia. METHODS: A review of epidemiologic studies reporting on early GDM screening as per Joanna Briggs Institute (JBI) methodology for prevalence reviews was conducted. A customized search strategy was used to search electronic databases namely, PubMed, CINAHL, EMBASE, Cochrane Library, Scopus, MEDLINE, Ovid, ScienceDirect, and Google Scholar. Three independent reviewers reviewed studies using Covidence software. Observational studies irrespective of study design and regardless of diagnostic criteria were included. Quality of evidence was appraised, and findings were synthesized. Results: Of 58 included studies, 41 reported a prevalence of eGDM, ranging from 0.7 to 36.8%. Body mass index (BMI), previous history of GDM, family history of diabetes and multiparity were reported as eGDM risk factors. Adverse pregnancy outcomes associated with eGDM were macrosomia, caesarean delivery, induction of labour, hypertension, preterm delivery, and shoulder dystocia. The incidence of postpartum dysglycemia and the need for insulin was higher in women with eGDM. The risk of bias was moderate. Heterogeneity of studies is a limitation. Meta-analysis was not performed. Conclusions: There is heterogeneity in the prevalence of eGDM and intrapartum and postpartum ill effects for the mother and the offspring. There is a need to develop a universal screening protocol for eGDM.Publication Metadata only Low maternal vitamin B12 status is associated with lower cord blood HDL cholesterol in white Caucasians living in the UK(MDPI, 2015-04-02) Adaikalakoteswari, Antonysunil; Vatish, Manu; Lawson, Alexander; Wood, Catherine; Sivakumar, Kavitha; McTernan, Philip. G; Webster, Craig; Anderson, Neil; Yajnik, Chittaranjan. S; Tripathi, Gyanendra; Saravanan, Ponnusamy; Saravanan, Ponnusamy; Saravanan, Ponnusamy; University of Warwick; University of Oxford; Heartlands Hospital, Birmingham; George Eliot Hospital NHS Trust, Nuneaton; University Hospitals Coventry and Warwickshire NHS Trust; Diabetes and Endocrinology; Medical and Dental; Wood, Catherine; Anderson, Neil; Saravanan, PonnusamyBackground and aims: Studies in South Asian population show that low maternal vitamin B12 associates with insulin resistance and small for gestational age in the offspring. Low vitamin B12 status is attributed to vegetarianism in these populations. It is not known whether low B12 status is associated with metabolic risk of the offspring in whites, where the childhood metabolic disorders are increasing rapidly. Here, we studied whether maternal B12 levels associate with metabolic risk of the offspring at birth. Methods: This is a cross-sectional study of 91 mother-infant pairs (n = 182), of white Caucasian origin living in the UK. Blood samples were collected from white pregnant women at delivery and their newborns (cord blood). Serum vitamin B12, folate, homocysteine as well as the relevant metabolic risk factors were measured. Results: The prevalence of low serum vitamin B12 (<191 ng/L) and folate (<4.6 μg/L) were 40% and 11%, respectively. Maternal B12 was inversely associated with offspring's Homeostasis Model Assessment 2-Insulin Resistance (HOMA-IR), triglycerides, homocysteine and positively with HDL-cholesterol after adjusting for age and BMI. In regression analysis, after adjusting for likely confounders, maternal B12 is independently associated with neonatal HDL-cholesterol and homocysteine but not triglycerides or HOMA-IR. Conclusions: Our study shows that low B12 status is common in white women and is independently associated with adverse cord blood cholesterol.