Priyadarshani Galappatthy

Effects of zinc supplementation on diabetes mellitus: a systematic review and meta-analysis

The number of people with diabetes and pre-diabetes are exponentially increasing. Studies on humans have shown the beneficial effects of Zinc supplementation in patients with diabetes. The present study aims to systematically evaluate the literature and meta-analyze the effects of Zinc supplementation on diabetes. A systematic review of published studies reporting the effects of Zinc supplementations on diabetes mellitus was undertaken. The literature search was conducted in the following databases; PubMed, Web of Science and SciVerse Scopus. A meta-analysis of studies examining the effects of Zinc supplementation on clinical and biochemical parameters in patients with diabetes was performed. The total number of articles included in the present review is 25, which included 3 studies on type-1 diabetes and 22 studies on type-2 diabetes. There were 12 studies comparing the effects of Zinc supplementation on fasting blood glucose in patients with type-2 diabetes. The pooled mean difference in fasting blood glucose between Zinc supplemented and placebo groups was 18.13mg/dl (95%CI:33.85,2.41; p<0.05). 2-h post-prandial blood sugar also shows a similar distinct reduction in (34.87mg/dl [95%CI:75.44; 5.69]) the Zinc treated group. The reduction in HbA1c was 0.54% (95%CI:0.86;0.21) in the Zinc treated group. There were 8 studies comparing the effects of Zinc supplementation on lipid parameters in patients with type-2 diabetes. The pooled mean difference for total cholesterol between Zinc supplemented and placebo groups was 32.37mg/dl (95%CI:57.39,7.35; p<0.05). Low-density lipoprotein cholesterol also showed a similar distinct reduction in the Zinc treated group, the pooled mean difference from random effects analysis was 11.19mg/dl (95%CI:21.14,1.25; p<0.05). Studies have also shown a significant reduction in systolic and diastolic blood pressures after Zinc supplementation. This first comprehensive systematic review and meta-analysis on the effects of Zinc supplementation in patients with diabetes demonstrates that Zinc supplementation has beneficial effects on glycaemic control and promotes healthy lipid parameters. Further studies are required to identify the exact biological mechanisms responsible for these results.

Zinc and diabetes mellitus: understanding molecular mechanisms and clinical implications

BackgroundDiabetes mellitus is a leading cause of morbidity and mortality worldwide. Studies have shown that Zinc has numerous beneficial effects in both type-1 and type-2 diabetes. We aim to evaluate the literature on the mechanisms and molecular level effects of Zinc on glycaemic control, β-cell function, pathogenesis of diabetes and its complications.MethodsA review of published studies reporting mechanisms of action of Zinc in diabetes was undertaken in PubMed and SciVerse Scopus medical databases using the following search terms in article title, abstract or keywords; (“Zinc” or “Zn”) and (“mechanism” or “mechanism of action” or “action” or “effect” or “pathogenesis” or “pathology” or “physiology” or “metabolism”) and (“diabetes” or “prediabetes” or “sugar” or “glucose” or “insulin”).ResultsThe literature search identified the following number of articles in the two databases; PubMed (n = 1799) and SciVerse Scopus (n = 1879). After removing duplicates the total number of articles included in the present review is 111. Our results show that Zinc plays an important role in β-cell function, insulin action, glucose homeostasis and the pathogenesis of diabetes and its complications.ConclusionNumerous in-vitro and in-vivo studies have shown that Zinc has beneficial effects in both type-1 and type-2 diabetes. However further randomized double-blinded placebo-controlled clinical trials conducted for an adequate duration, are required to establish therapeutic safety in humans.

Genetic variants in the cytochrome P450 2D6 gene in the Sri Lankan population

INTRODUCTION: Cytochrome P450 2D6 (CYP2D6) enzymes are involved in the metabolism of a large number of commonly prescribed drugs such as antidepressants and cardiovascular drugs. The CYP2D6 *3, *4 and *14 variants associated with the loss of enzyme function; CYP2D6 *10 and *17 variants with reduced enzyme function; and CYP2D6 *2 variant with no effect on enzyme function. Establishing the frequency of these variant alleles in Sri Lankan population would be useful for optimizing pharmacotherapy with CYP2D6-substrate drugs. OBJECTIVE: The objective of this study was to determine the prevalence of CYP2D6 *2, *3, *4, *10, *14 and *17 variants in the main ethnic groups in the Sri Lankan population. MATERIALS AND METHODS: A total of 90 deoxyribonucleic acid (DNA) samples (30 each from Sinhalese, Tamils and Moors) were selected from a DNA resource at the Human Genetic Unit, Faculty of Medicine, University of Colombo. This collection had been made for population genetic studies from a random population based volunteers. Genotyping was performed using published polymerase chain reaction/restriction fragment length polymorphism methods. RESULTS: The prevalence of the CYP2D6 variants in Sinhalese, Sri Lankan Tamils and Moors respectively were CYP2D6 *2: 37%, 41.6% and 37.9%; CYP2D6 *3: 60.3%, 45% and 30%; CYP2D6 *4: 21.6%, 6.6% and 8.3%; CYP2D6 *10: 40%, 35% and 44%. CYP2D6 *14 and *17 variants were not identified. CONCLUSION: CYP2D6*3, *4 and *10 variants, which are associated with reduced or loss of CYP2D6 enzyme function were found in our population in significant frequencies. CYP2D6*4, which is reported to be a Caucasian variant was also found in all three ethnic groups.

Zinc supplementation in prediabetes: A randomized double-blind placebo-controlled clinical trial†

This study evaluated the effects of zinc supplementation on glycemic control, other cardiometabolic and anthropometric parameters, and disease progression in prediabetes.

Management, characteristics and outcomes of patients with acute coronary syndrome in Sri Lanka

Background Ischaemic heart disease is the leading cause of in-hospital mortality in Sri Lanka. Acute Coronary Syndrome Sri Lanka Audit Project (ACSSLAP) is the first national clinical-audit project that evaluated patient characteristics, clinical outcomes and care provided by state-sector hospitals. Methods ACSSLAP prospectively evaluated acute care, in-hospital care and discharge plans provided by all state-sector hospitals managing patients with ACS. Data were collected from 30 consecutive patients from each hospital during 2–4 weeks window. Local and international recommendations were used as audit standards. Results Data from 87/98 (88.7%) hospitals recruited 2177 patients, with 2116 confirmed as having ACS. Mean age was 61.4±11.8 years (range 20–95) and 58.7% (n=1242) were males. There were 813 (38.4%) patients with unstable angina, 695 (32.8%) with non-ST-elevation myocardial infarction (NSTEMI) and 608 (28.7%) with ST-elevation myocardial infarction (STEMI). Both STEMI (69.9%) and NSTEMI (61.4%) were more in males (P<0.001). Aspirin, clopidogrel and statins were given to over 90% in acute setting and on discharge. In STEMI, 407 (66.9%) were reperfused; 384 (63.2%) were given fibrinolytics and only 23 (3.8%) underwent primary percutaneous coronary intervention (PCI). Only 42.3 % had thrombolysis in <30 min and 62.5% had PCI in <90 min. On discharge, beta-blockers and ACE inhibitors/angiotensin II receptor blockers were given to only 50.7% and 69.2%, respectively and only 17.6% had coronary interventions planned. Conclusions In patients with ACS, aspirin, clopidogrel and statin use met audit standards in acute setting and on discharge. Vast majority of patients with STEMI underwent fibrinolyisis than PCI, due to limited resources. Primary PCI, planned coronary interventions and timely thrombolysis need improvement in Sri Lanka.

Determination of in-vitro Equivalence of Paracetamol Tablets

Bioequivalence studies are the usually accepted method to determine the therapeutic equivalence of two drug products. Because in-vivo bioequivalence studies are time consuming and expensive to conduct, major regulatory authorities have introduced biowaivers for some selected medicines belonging to BCS class 1 and III drugs. Comparative dissolution tests are used in biowaiver procedure to waiver the bioequivalence requirement. We performed this study to see whether two brands of paracetamol tablets are bioequivalent using the in-vitro methodology. In the first stage of this research study, British Pharmacopeia 2012 quality tests were performed on the two selected paracetamol tablet products to determine whether they are pharmaceutically equivalent. In the second stage in-vitro equivalence of the two products was determined using the biowaiver testing procedure given by the World Health Organization. Dissolution profiles were generated at pH values, 1.2, 4.5 and 6.8. Results were compared through two model independent methods, difference factor (f1) and similarity factor (f2). The two paracetamol tablet products tested, complied with all the quality requirements of the British Pharmacopeia 2012. For the two products, the difference factor (f1) was below the 15 and similarity factor (f2) was above the 50 in all dissolution test conditions. These results confirm that the two products are pharmaceutically equivalent. The test product is also bioequivalent to the reference product in-vitro, and therefore they can be interchangeable during clinical use. This study shows that in-vivo bioequivalence testing can be waived using the in-vitro method, for some pharmaceutical products such as paracetamol tablets.

Regulatory requirements for the registration of generic medicines and format of drug dossiers: procedures in Sri Lanka in comparison with selected regulatory authorities

BackgroundThe regulatory requirements for approval of generic medicines and the format of compiling drug dossiers vary among regulatory authorities. The variation is particularly wide between High-income countries (HIC) and lower and middle-income countries (LMIC) with different regulatory frameworks. In this study, document requirements for approval of generic products, approval timelines, and consideration of bioequivalence and/or biowaiver data by Regulatory Authorities (RAs) of 10 selected jurisdictions was studied.MethodsThe guidelines and procedures from 5 purposively chosen RA of HIC and4 regional RAs relevant for Sri Lanka were compared with the Sri Lankan National Medicines Regulatory Authority (NMRA). Information available in the official websites of the selected RAs, published journal articles and via personal communication was collected in2016. Drug approval timelines achieved in Sri Lanka was obtained from data available from another study.ResultsCommon technical dossier (CTD) format of the International Council on Harmonization (ICH) for registration of pharmaceuticals (ICH:CTD) or the Association of South East Asian Nations (ASEAN) CTD format (ACTD) was used by all RAs studied except Sri Lanka which use its own dossier format. Nine out of ten RAs studied request BE data or justification for not submitting BE data for generic medicines. Sri Lanka requested BE studies only for antimicrobials, antiepileptic drugs and narrow therapeutic index drugs. Biowaivers are allowed for Biopharmaceutics Classification System (BCS)-based Class 1drugs in Singapore and India. USA, EMA, Canada and South Korea allowed biowaiver for BCS Class1and Class 3drugs but Sri Lanka does not accept BW at present. Nine NMRAs out of the ten studied reported legislated timelines for approval of generic pharmaceuticals except Sri Lanka.ConclusionsStreamlining the drug regulatory systems in LMIC such as Sri Lanka with that of HIC would facilitate an effective drug regulatory system based on reliance on decisions made by stringent regulatory authorities. Findings of this study encourage Sri Lanka to adopt a CTD format for regulatory submission of drug dossiers. Expanding the BE requirement drug list and accepting BCS-based biowaivers for BSC class 1 and 3 drugs during registration of generic drugs when it is scientifically justified is also recommended for Sri Lanka.

Translation and Validation of the Sinhalese Version of the Brief Medication Questionnaire in Patients with Diabetes Mellitus

Background Adherence to long-term therapy for diabetes remains low. Accurately measuring adherence is the primary step in improving adherence. We translated and validated the Sinhalese version of the Brief Medication Questionnaire (BMQ) in patients with diabetes. Methods The study was conducted at the National Hospital of Sri Lanka between April and December 2017, including 165 patients with diabetes. BMQ was translated into Sinhalese using the translation-back translation method. The translated questionnaire validation included evaluation of internal consistency, temporal stability, and performance in regard to a gold standard (HbA1c). Results Mean age (±SD) was 60.6 ± 11.1 years, and 46.1% were males. Mean duration of diabetes in the participants was 13.4 ± 7.8 years. Mean HbA1c was 8.3 ± 1.7%, with poor glycaemic control (HbA1c ≥ 8.5%) identified in 41.8%. Medication adherence measured by the BMQ regimen, belief, and recall screens were 39.4%, 75.8%, and 18.8%, respectively. In the analysis of temporal stability, the overall BMQ and the regimen, belief, and recall screens demonstrated good concordance between test and retest with significant gamma correlation coefficients of r = 0.85 (p < 0.001), r = 0.81 (p < 0.001), r = 0.84 (p < 0.001), and r = 0.91 (p < 0.001), respectively. The overall BMQ had a Cronbach α coefficient of 0.65 (95% CI: 0.61–0.70). The questionnaire performance with regards to the gold standards for the overall BMQ AUC was 0.73 (95% CI 0.65–0.80), while the BMQ regimen screen AUC was 0.61 (95% CI 0.53–0.70). The overall BMQ score with a cutoff value of 2 presented better equilibrium between sensitivity and specificity for the gold standard. Those with low adherence had a significantly higher percentage of poor glycaemic control (HbA1c ≥ 8.5%). Conclusion The translated questionnaire demonstrated good reliability (internal consistency), temporal stability (test-retest reliability), and validity when assessed using a gold standard for disease control. Using culturally validated tools to evaluate adherence may help clinicians to identify low adherence and institute corrective measures.

Validation of the Sinhala version of the Morisky Medication Adherence Scale to determine medication adherence in patients with bipolar affective disorder on lithium therapy

Rationale, aims and objectives: The Morisky Medication Adherence Scale (MMAS-8) is a self-reported scale used in assessing medication adherence in patients on chronic therapy. Medication adherence is a neglected area of research in Sri Lanka and in this study we have attempted to validate the Sinhala translation of the MMAS-8 to determine medication adherence among patients stabilized on lithium therapy for bipolar disorder (BD). Methods: The MMAS-8 was translated to Sinhala with standard forward and backward translations from English to Sinhala. Patients with BD on stable doses of lithium were administered the Sinhala version of the MMAS-8. During the same visit, the serum lithium concentration was measured. Criterion validity was assessed using therapeutic serum lithium concentrations as the gold standard. Internal consistency was assessed using Cronbach’s alpha and Spearman’s rank correlation was used to assess test-retest reliability. Results: From a sample of 240 patients, 82.1% were considered adherent, with serum lithium concentration >0.4 mmol/L. The mean MMAS-8 score was 6.95±1.3. According to the MMAS-8 scale, 13.3% reported low adherence while 43.3% reported medium and high adherence equally using MMAS cut offs <6, 6 to<8 and 8 respectively. The scale sensitivity to identify adherence at a cut-off score of 6 was 86.3%. The test–retest reliability value was 0.708 (p<0.001). Internal consistency was found with a Cronbach’s alpha value of 0.608 for the 8 items of the scale. Conclusion: The Sinhala version of MMAS-8 can be used as a sensitive instrument to identify medication adherence in patients with bipolar disorders.

Pregnancy outcomes and contraceptive use in patients with systemic lupus Erythematosus, rheumatoid arthritis and women without a chronic illness: a comparative study

To compare the pregnancy outcomes and contraceptive practices in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and women with no chronic illness (WNCI) in a tertiary care referral center in Colombo, Sri Lanka.