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Prognostic and Therapeutic Role of Vitamin D in COVID-19: Systematic Review and Meta-analysis.
Dissanayake, HA, de Silva, NL, Sumanatilleke, M, de Silva, SDN, Gamage, KKK, Dematapitiya, C, Kuruppu, DC, Ranasinghe, P, Pathmanathan, S, Katulanda, P
The Journal of clinical endocrinology and metabolism. 2022;107(5):1484-1502
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Vitamin D is implicated in optimum function of the immune system. Its deficiency has been linked to susceptibility to respiratory infections. It is postulated that vitamin D deficiency/insufficiency is also associated with COVID-19. The aim of this study was to determine the association between vitamin D deficiency/insufficiency and susceptibility to COVID-19, its severity, mortality and role of vitamin D in its treatment. This study is a systematic review and meta-analysis of seventy-six publications. Results show increased odds of developing COVID-19, progression to severe COVID-19 and death in people with vitamin D deficiency/insufficiency. In fact, people who developed COVID-19, severe COVID-19 and fatal disease had lower 25-hydroxy vitamin D concentration compared to people without COVID-19 or non-severe COVID-19 or non-fatal COVID-19 respectively. Authors conclude that Vitamin D deficiency/insufficiency may increase the risk of developing COVID-19 infection and susceptibility to more severe disease.
Abstract
PURPOSE Vitamin D deficiency/insufficiency may increase the susceptibility to coronavirus disease 2019 (COVID-19). We aimed to determine the association between vitamin D deficiency/insufficiency and susceptibility to COVID-19, its severity, mortality, and role of vitamin D in its treatment. METHODS We searched CINAHL, Cochrane library, EMBASE, PubMED, Scopus, and Web of Science up to May 30, 2021, for observational studies on association between vitamin D deficiency/insufficiency and susceptibility to COVID-19, severe disease, and death among adults, and, randomized controlled trials (RCTs) comparing vitamin D treatment against standard care or placebo, in improving severity or mortality among adults with COVID-19. Risk of bias was assessed using Newcastle-Ottawa scale for observational studies and AUB-KQ1 Cochrane tool for RCTs. Study-level data were analyzed using RevMan 5.3 and R (v4.1.0). Heterogeneity was determined by I2 and sources were explored through prespecified sensitivity analyses, subgroup analyses, and meta-regressions. RESULTS Of 1877 search results, 76 studies satisfying eligibility criteria were included. Seventy-two observational studies were included in the meta-analysis (n = 1 976 099). Vitamin D deficiency/insufficiency increased the odds of developing COVID-19 (odds ratio [OR] 1.46; 95% CI, 1.28-1.65; P < 0.0001; I2 = 92%), severe disease (OR 1.90; 95% CI, 1.52-2.38; P < 0.0001; I2 = 81%), and death (OR 2.07; 95% CI, 1.28-3.35; P = 0.003; I2 = 73%). The 25-hydroxy vitamin D concentrations were lower in individuals with COVID-19 compared with controls (mean difference [MD] -3.85 ng/mL; 95% CI, -5.44 to -2.26; P ≤ 0.0001), in patients with severe COVID-19 compared with controls with nonsevere COVID-19 (MD -4.84 ng/mL; 95% CI, -7.32 to -2.35; P = 0.0001) and in nonsurvivors compared with survivors (MD -4.80 ng/mL; 95% CI, -7.89 to -1.71; P = 0.002). The association between vitamin D deficiency/insufficiency and death was insignificant when studies with high risk of bias or studies reporting unadjusted effect estimates were excluded. Risk of bias and heterogeneity were high across all analyses. Discrepancies in timing of vitamin D testing, definitions of severe COVID-19, and vitamin D deficiency/insufficiency partly explained the heterogeneity. Four RCTs were widely heterogeneous precluding meta-analysis. CONCLUSION Multiple observational studies involving nearly 2 million adults suggest vitamin D deficiency/insufficiency increases susceptibility to COVID-19 and severe COVID-19, although with a high risk of bias and heterogeneity. Association with mortality was less robust. Heterogeneity in RCTs precluded their meta-analysis.
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Glycemic and cardiometabolic effects of exercise in South Asian Sri Lankans with type 2 diabetes mellitus: A randomized controlled trial Sri Lanka diabetes aerobic and resistance training study (SL-DARTS).
Ranasinghe, C, Devage, S, Constantine, GR, Katulanda, P, Hills, AP, King, NA
Diabetes & metabolic syndrome. 2021;(1):77-85
Abstract
BACKGROUND AND AIMS To examine the effects of aerobic training (AT) and resistance training (RT) compared to standard care on glycemic control in South Asian Sri Lankan adults with Type 2 Diabetes Mellitus (T2DM). METHODS Randomized controlled trial (RCT) with parallel-group design recruited 86 sedentary Sri Lankans (aged 35-65 years) with T2DM into aerobic training (AT, n = 28), resistance training (RT, n = 28) and control (CN, n = 30) groups. Supervised progressive exercise training consisting of 75 min per session, 2 days per week for 12 weeks was conducted. The primary outcome was pre- and post-intervention absolute change in hemoglobin A1c (HBA1c). Secondary outcomes were serum lipids, liver enzymes, chronic inflammatory status, anthropometry, body composition and blood pressure. RESULTS The absolute change in HbA1c of RT vs. CN was -0.08% (95% CI, 0.8% to -0.7%, p = 0.8) and AT vs. CN was -0.22% (95% CI, 0.95% to -0.5%). Subgroup analysis (n = 49) with a high baseline HbA1c (>7.5%), absolute reduction in HbA1c in exercise groups were statistically significant (RT vs. CN was -0.37%; 95% CI 1.3% to -0.6%, p = 0.04 and AT vs. CN was -0.57%; 95% CI 1.7% to -0.6%, p = 0.03). The effect sizes (total and subgroup HbA1c >7.5%) ranged from 0.7 to 1.0 in AT, 0.4 to 1.1 in RT compared to 0.35 to 0.6 for the CN. Secondary outcomes did not significantly differ among groups. CONCLUSIONS Exercise training 2 days/week improved glycemic control in Sri Lankan adults with T2DM and the effects were significant in high baseline HbA1c (>7.5%) groups (RT > AT).
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Effects of a lifestyle intervention programme after 1 year of follow-up among South Asians at high risk of type 2 diabetes: a cluster randomised controlled trial.
Muilwijk, M, Loh, M, Siddiqui, S, Mahmood, S, Palaniswamy, S, Shahzad, K, Athauda, LK, Jayawardena, R, Batool, T, Burney, S, et al
BMJ global health. 2021;(11)
Abstract
INTRODUCTION South Asians are at high risk of type 2 diabetes (T2D). We assessed whether intensive family-based lifestyle intervention leads to significant weight loss, improved glycaemia and blood pressure in adults at elevated risk for T2D. METHODS This cluster randomised controlled trial (iHealth-T2D) was conducted at 120 locations across India, Pakistan, Sri Lanka and the UK. We included 3684 South Asian men and women, aged 40-70 years, without T2D but with raised haemoglobin A1c (HbA1c) and/or waist circumference. Participants were randomly allocated either to the family-based lifestyle intervention or control group by location clusters. Participants in the intervention received 9 visits and 13 telephone contacts by community health workers over 1-year period, and the control group received usual care. Reductions in weight (aim >7% reduction), waist circumference (aim ≥5 cm reduction), blood pressure and HbA1C at 12 months of follow-up were assessed. Our linear mixed-effects regression analysis was based on intention-to-treat principle and adjusted for age, sex and baseline values. RESULTS There were 1846 participants in the control and 1838 in the intervention group. Between baseline and 12 months, mean weight of participants in the intervention group reduced by 1.8 kg compared with 0.4 kg in the control group (adjusted mean difference -1.10 kg (95% CI -1.70 to -1.06), p<0.001). The adjusted mean difference for waist circumference was -1.9 cm (95% CI -2.5; to 1.3), p<0.001). No overall difference was observed for blood pressure or HbA1c. People who attended multiple intervention sessions had a dose-dependent effect on waist circumference, blood pressure and HbA1c, but not on weight. CONCLUSION An intensive family-based lifestyle intervention adopting low-resource strategies led to effective reduction in weight and waist circumference at 12 months, which has potential long-term benefits for preventing T2D. A higher number of attended sessions increased the effect on waist circumference, blood pressure and HbA1c. TRIAL REGISTRATION NUMBER EudraCT: 2016-001350-18; ClinicalTrials.gov: NCT02949739.
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The iHealth-T2D study, prevention of type 2 diabetes amongst South Asians with central obesity and prediabetes: study protocol for a randomised controlled trial.
Kasturiratne, A, Khawaja, KI, Ahmad, S, Siddiqui, S, Shahzad, K, Athauda, LK, Jayawardena, R, Mahmood, S, Muilwijk, M, Batool, T, et al
Trials. 2021;(1):928
Abstract
BACKGROUND People from South Asia are at increased risk of type 2 diabetes (T2D). There is an urgent need to develop approaches for the prevention of T2D in South Asians that are cost-effective, generalisable and scalable across settings. HYPOTHESIS Compared to usual care, the risk of T2D can be reduced amongst South Asians with central obesity or raised HbA1c, through a 12-month lifestyle modification programme delivered by community health workers. DESIGN Cluster randomised clinical trial (1:1 allocation to intervention or usual care), carried out in India, Pakistan, Sri Lanka and the UK, with 30 sites per country (120 sites total). Target recruitment 3600 (30 participants per site) with annual follow-up for 3 years. ENTRY CRITERIA South Asian, men or women, age 40-70 years with (i) central obesity (waist circumference ≥ 100 cm in India and Pakistan; ≥90 cm in Sri Lanka) and/or (ii) prediabetes (HbA1c 6.0-6.4% inclusive). EXCLUSION CRITERIA known type 1 or 2 diabetes, normal or underweight (body mass index < 22 kg/m2); pregnant or planning pregnancy; unstable residence or planning to leave the area; and serious illness. ENDPOINTS The primary endpoint is new-onset T2D at 3 years, defined as (i) HbA1c ≥ 6.5% or (ii) physician diagnosis and on treatment for T2D. Secondary endpoints at 1 and 3 years are the following: (i) physical measures: waist circumference, weight and blood pressure; (ii) lifestyle measures: smoking status, alcohol intake, physical activity and dietary intake; (iii) biochemical measures: fasting glucose, insulin and lipids (total and HDL cholesterol, triglycerides); and (iv) treatment compliance. INTERVENTION Lifestyle intervention (60 sites) or usual care (60 sites). Lifestyle intervention was delivered by a trained community health worker over 12 months (5 one-one sessions, 4 group sessions, 13 telephone sessions) with the goal of the participants achieving a 7% reduction in body mass index and a 10-cm reduction in waist circumference through (i) improved diet and (ii) increased physical activity. Usual care comprised a single 30-min session of lifestyle modification advice from the community health worker. RESULTS We screened 33,212 people for inclusion into the study. We identified 10,930 people who met study entry criteria, amongst whom 3682 agreed to take part in the intervention. Study participants are 49.2% female and aged 52.8 (SD 8.2) years. Clinical characteristics are well balanced between intervention and usual care sites. More than 90% of follow-up visits are scheduled to be complete in December 2020. Based on the follow-up to end 2019, the observed incidence of T2D in the study population is in line with expectations (6.1% per annum). CONCLUSION The iHealth-T2D study will advance understanding of strategies for the prevention of diabetes amongst South Asians, use approaches for screening and intervention that are adapted for low-resource settings. Our study will thus inform the implementation of strategies for improving the health and well-being of this major global ethnic group. IRB APPROVAL 16/WM/0171 TRIAL REGISTRATION EudraCT 2016-001350-18 . Registered on 14 April 2016. ClinicalTrials.gov NCT02949739 . Registered on 31 October 2016, First posted on 31/10/2016.
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The Impact of SARS-Cov-2 Virus Infection on the Endocrine System.
Somasundaram, NP, Ranathunga, I, Ratnasamy, V, Wijewickrama, PSA, Dissanayake, HA, Yogendranathan, N, Gamage, KKK, de Silva, NL, Sumanatilleke, M, Katulanda, P, et al
Journal of the Endocrine Society. 2020;(8):bvaa082
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has spread across the globe rapidly causing an unprecedented pandemic. Because of the novelty of the disease, the possible impact on the endocrine system is not clear. To compile a mini-review describing possible endocrine consequences of SARS-CoV-2 infection, we performed a literature survey using the key words Covid-19, Coronavirus, SARS CoV-1, SARS Cov-2, Endocrine, and related terms in medical databases including PubMed, Google Scholar, and MedARXiv from the year 2000. Additional references were identified through manual screening of bibliographies and via citations in the selected articles. The literature review is current until April 28, 2020. In light of the literature, we discuss SARS-CoV-2 and explore the endocrine consequences based on the experience with structurally-similar SARS-CoV-1. Studies from the SARS -CoV-1 epidemic have reported variable changes in the endocrine organs. SARS-CoV-2 attaches to the ACE2 system in the pancreas causing perturbation of insulin production resulting in hyperglycemic emergencies. In patients with preexisting endocrine disorders who develop COVID-19, several factors warrant management decisions. Hydrocortisone dose adjustments are required in patients with adrenal insufficiency. Identification and management of critical illness-related corticosteroid insufficiency is crucial. Patients with Cushing syndrome may have poorer outcomes because of the associated immunodeficiency and coagulopathy. Vitamin D deficiency appears to be associated with increased susceptibility or severity to SARS-CoV-2 infection, and replacement may improve outcomes. Robust strategies required for the optimal management of endocrinopathies in COVID-19 are discussed extensively in this mini-review.
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The impact of propranolol on nitric oxide and total antioxidant capacity in patients with resistant hypertension-evidence from the APPROPRIATE trial.
Ranasinghe, HN, Fernando, N, Handunnetti, S, Weeratunga, PN, Katulanda, P, Rajapakse, S, Galappatthy, P, Constantine, GR
BMC research notes. 2020;(1):228
Abstract
OBJECTIVES The objective was to assess the effect of propranolol on oxidative stress and anti-oxidant potential in patients with resistant hypertension as a secondary analysis of the APPROPRIATE trial. This randomized double blinded clinical trial recruited patients with resistant hypertension and allocated forty patients to propranolol and placebo in 1:1 ratio. The pro-oxidant state (nitrate and nitrite) was assessed using modified Griess assay. The total anti-oxidant capacity was measured using ABTS assay. RESULTS Analysis was performed for 18 patients from the propranolol group and 15 from the placebo group. A decline in end point ambulatory blood pressure (p = 0.031) and greater mean reduction in office SBP (29.7 ± 13.0 mmHg, p = 0.021) was noted in the propranolol arm. Nitrate and nitrite levels were lower at the end of a 90 day follow up period in both arms, with a greater mean reduction with propranolol. A significant increase in the AOC was noted in both arms with higher incremental value with Propranolol. The findings of this study do not demonstrate a statistically significant effect of propranolol on the oxidative stress/antioxidant balance in patients with resistant hypertension. The observed trends merit further evaluation.
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mHealth nutrition and lifestyle intervention (mHENAL) to reduce cardiovascular disease risk in a middle-aged, overweight and obese population in Sri Lanka: Study protocol for a randomized controlled trial.
Senarath, U, Katulanda, P, Fernando, DN, Kalupahana, NS, Partheepan, K, Jayawardena, R, Katulanda, G, Dibley, MJ
Contemporary clinical trials communications. 2019;:100453
Abstract
Mobile phone-based health interventions (mHealth) are viewed as an attractive approach to foster behaviour change, and found to be effective in promoting physical activity and healthy diets. The present study aims to investigate whether mHealth with advice for dietary and lifestyle modifications would reduce 10-year cardio vascular disease (CVD) risk among overweight or obese adults aged 35-64 years in Sri Lanka. A two-group parallel-arm randomized controlled trial (RCT) was conducted in Colombo district, recruiting 1200 individuals aged 35-64 years with a body mass index (BMI) of ≥25 kgm-2. Participants were randomly assigned either to mHealth package (intervention arm, n = 600) or usual care (control arm, n = 600). The intervention package contains a series of dietary and lifestyle improvement messages, a mobile application to register participants, and a web application to deliver these messages. Participants in the intervention arm receive 2 voice and 2 text messages per week to their mobile phones for a period of 12 months. The primary outcome (10-year CVD risk) will be assessed according to sex, age, smoking status, blood pressure, serum cholesterol and glycaemic status. Data are collected at enrollment and after 12 months of intervention on: dietary practices, physical activity, smoking, anthropometry, body composition, blood pressure, fasting plasma glucose, HbA1c and lipid profile. Analysis of effect will be performed by intention-to-treat principle, comparing the outcomes between intervention and control arms. The study resulted in a comprehensive mHealth nutrition and lifestyle package (mHENAL) and successfully completed recruitment and baseline assessment of participants. The message delivery is in progress.
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Among young Sri Lankan patients with diabetes, how do lipid profiles differ between those with and without metabolic syndrome?
Katulanda, GW, Dissanayake, HA, Katulanda, P, Matthews, DR, Shine, B
Diabetes & metabolic syndrome. 2019;(5):3057-3063
Abstract
AIMS: Metabolic syndrome (MetS) is a risk factor for cardiovascular disease (CVD). Apolipoproteins are emerging as powerful predictors of CVD. We aimed to study associations of metabolic syndrome and apoB, apoAI, apoB/AI ratio in young Sri Lankans with type 2 diabetes. MATERIALS & METHODS Blood samples were available from 690 patients with type 2 diabetes in Sri Lanka Young Diabetes Study, and were analysed for apoB, apoAI, total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), triglycerides (TG) and glycated haemoglobin (HbA1c). Their associations with MetS as perNCEP/ATPIII criteria were studied. RESULTS MetS was present in 60.9% of subjects. Of those with MetS, 76.0% were women. Those with MetS had higher apoB (1.27 V s 1.19 mmol/L; p = 0.001), apoB/AI (0.80 V s 0.75; p = 0.001), non-HDL cholesterol (NHDLC) (4.15 V s 3.98 mmol/L; p = 0.002),and triglycerides (1.51 V s 1.31 mmol/L; p < 0.001) and lower apoAI (1.58 V s 1.60 mmol/L; p = 0.03) and HDLC (1.02 V s 1.16 mmol/L, p < 0.001). ApoB and apoB/AIlevels increased significantly as the number of MetS components increased. ApoB and apoB:AI ratio were independently associated with MetS and components. CONCLUSION MetS showed a high prevalence among young Sri Lankans with diabetes. Elevated apoB is commonly clustered with other risk indicators in MetS.
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Study protocol: a randomised controlled trial of supervised resistance training versus aerobic training in Sri Lankan adults with type 2 diabetes mellitus: SL-DART study.
Ranasinghe, C, Hills, AP, Constantine, GR, Finlayson, G, Katulanda, P, King, NA
BMC public health. 2018;(1):176
Abstract
BACKGROUND The prevalence of type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD) is rising globally. T2DM is particularly problematic in South Asia with an estimated 10-15% of Sri Lankans diagnosed with the disease. Exercise is known to improve blood glucose, lipid profiles, blood pressure and adiposity, key goals in the management of T2DM. However, much of the evidence to date has been gained from white Caucasians who have a different body composition and disease profile compared to South Asians. Similarly, the recreational exercise culture is new to Sri Lankans and the effects of exercise on T2DM has not been studied in this population. METHODS The Sri Lanka Diabetes Aerobic and Resistance Training (SL-DART) Study will be comprised of 2 components. Component 1 is a 12-week randomized controlled trial (RCT) to compare the effects of a supervised progressive resistance exercise program (RT) and aerobic exercise program (AT) with standard treatment/control (CN). Sedentary Sri Lankan adults with T2DM (aged 35-65 years) and with no contraindications to exercise will be randomized into one of 3 groups (AT, RT, CN). Exercise sessions will be conducted 2 days/week for 3 months. Baseline and post-intervention biochemical (glycemic control, lipid and liver profiles, inflammatory markers), anthropometric (height, weight, body circumferences), body composition, physical fitness, food preference (liking and wanting food) and quality of life parameters will be measured and compared between groups. Component 2 will be a qualitative study conducted immediately post-intervention via in-depth interviews to assess the barriers and facilitators for adherence to each exercise program. DISCUSSION SL-DART Study represents one of the first adequately powered methodologically sound RCTs conducted in South Asia to assess the effects of resistance and aerobic exercise in participants with T2DM. Triangulation of quantitative and qualitative outcomes will enable the design of a culturally appropriate therapeutic physical activity intervention for Sri Lankans with T2DM, and the initiation of a professionally driven and specialized clinical exercise prescription service. TRIAL REGISTRATION Sri Lanka Clinical Trials Registry; SLCTR/2016/017 . Date registered 17.06.2016. Universal trial number U1111-1181-7561.
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Hypoglycaemia in diabetes: do we think enough of the cause? An observational study on prevalence and causes of hypoglycaemia among patients with type 2 diabetes in an out-patient setting in Sri Lanka.
Dissanayake, HA, Keerthisena, GSP, Gamage, KKK, Liyanage, JH, Ihalagama, IRHS, Wijetunga, WMUA, Tillekaratne, TAD, Katulanda, GW, Katulanda, P
BMC endocrine disorders. 2018;(1):35
Abstract
BACKGROUND Hypoglycaemia is a feared experience for people with diabetes. We aimed to study the prevalence and causes of hypoglycaemia among Sri Lankans with diabetes. METHODS One thousand patients with diabetes attending a private sector diabetic clinic were interviewed using a structured questionnaire. Hypoglycaemic episodes within the preceding month were inquired and severity was graded according to clinical features and/or capillary blood glucose levels. RESULTS Mean age 55.0 years (± 12.5), 58.6% were males, mean diabetes duration 10.6 years (± 8.1), mean FPG 7.48 mmol/l (± 2.79) and mean HbA1c 7.82% (± 1.71) (62 mmol/mol). Of them, 26.1%. (mild 20.7%, moderate 3.9%, and severe 1.5%) experienced symptomatic hypoglycaemia. Sudden change diet (46.7%), unaccustomed exercise (15.7%) and increase in antihyperglycaemic therapy dosage (14.9%) were the recognized causes. Cause was not recognized by 16.3%. Non-prescribed native food items accounted for hypoglycaemia in 16.9% of patients (Momordica charantia 54.5%, Costus speciosus 52.3%, Salacia prinoides 11.4%, Coccinia grandis 6.8%, Adenanthera pavonina 4.5%). Severity of hypoglycaemia was positively correlated to age and duration of diabetes but not to HbA1C. CONCLUSION Hypoglycaemia is common among patients with diabetes. Patients need advice on regular diet and exercise. Consumption of non-prescribed native foods should be considered as a possible cause.