Tasmia Islam, M. Rahman, Nilanjana Paul, S. Akhteruzzaman, A. Sajib
{"title":"Allele-Specific Detection of SLC22A2 rs316019 Variants Associated with Metformin Disposition through the Kidney","authors":"Tasmia Islam, M. Rahman, Nilanjana Paul, S. Akhteruzzaman, A. Sajib","doi":"10.1159/000493584","DOIUrl":"https://doi.org/10.1159/000493584","url":null,"abstract":"Background: Metformin is prescribed as a first-line drug to treat type 2 diabetes. It is excreted directly and primarily through the SLC22A2 gene-encoded OCT2 transporter in the kidney. rs316019 (c.808G>T, p.270A>S) is the most common variant of SLC22A2, which affects its capacity to clear metformin from the body. Metformin increases the plasma lactate level in a concentration-dependent manner by inhibiting mitochondrial respiration and may lead to a condition known as metformin-associated lactic acidosis (MALA). MALA is a potentially life-threatening complication that can occur within the clinical doses of metformin. Therefore, dose adjustments based on the SLC22A2 rs316019 variants may be beneficial to maximize the efficacy and minimize the toxicity of metformin. Objective: This study was carried out to develop a simple and fast method to define genotype at the rs316019 locus. This method was applied to estimate the rs316019 allele frequencies in the Bangladeshi population. Methods: We designed allele-specific primers to determine genotype at the rs316019 locus using allele-specific polymerase chain reaction (AS-PCR). AS-PCR data were confirmed by targeted sequencing of randomly selected samples. Results: The DNA sequence chromatograms showed the exact genotypes predicted through the AS-PCR method. A proportion of 79.62, 18.01, and 2.37% of Bangladeshi individuals have GG, GT, and TT genotypes, respectively. Conclusion: We report here a simple and fast method to define genotypes at the rs316019 locus in diabetic patients who are under metformin regimen. Allele frequencies at the rs316019 locus in the Bangladeshi population are close to those reported in other populations.","PeriodicalId":405374,"journal":{"name":"International Journal of Diabetes and Metabolism","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116281512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Beshyah, A. Beshyah, Waleed S. Beshyah, Salim Yaghi
{"title":"Use of SGLT2 Inhibitors in Diabetic Renal Transplant Recipients: A Mixed Method Exploratory Exercise","authors":"S. Beshyah, A. Beshyah, Waleed S. Beshyah, Salim Yaghi","doi":"10.1159/000492758","DOIUrl":"https://doi.org/10.1159/000492758","url":null,"abstract":"Background: Diabetes is the leading cause of end-stage renal disease (ESRD) worldwide. Also, diabetes is prevalent in kidney transplant recipients for nondiabetic reasons. Methodology: We used a mixed method methodology, including a case report, surveys of physicians’ opinions, and a review of the literature. Results: (A) A 58-year-old retired police officer was seen at the diabetes clinic in October 2015. His care was transferred from another physician who had relocated elsewhere. The patient’s medical history included type 2 diabetes for over 25 years, hyperlipidemia, hypertension, diabetic neuropathy, diabetic nephropathy, and diabetic retinopathy in addition to vitamin D deficiency and morbid obesity. He had received a renal transplant from a nonrelated live donor 7 years previously. His medications included sitagliptin 50 mg/day, gliclazide (modified release) 60–90 mg/day, metformin (extended release) 750 mg twice daily, and dapagliflozin 10 mg/day. We focus on the off-license use of dapagliflozin in a patient with a history of ESRD and renal transplantation. The lack of published experience with sodium-glucose cotransporter 2 (SGLT2) inhibitors in renal transplant recipients was discussed with him. “But I came to no harm,” was his reply. His records on renal function, hydration status, and glycemic control all seemed unaffected over the previous 2.5 years. He remains well till the time of this report. Serum electrolytes, creatinine, plasma albumin, hemoglobin, packed cell volume, and estimated glomerular filtration rate (eGFR) were not adversely affected. Glycated hemoglobin and fasting blood glucose were stable. Urine was consistently negative for ketones but loaded with glycosuria. It was agreed to continue with the same medication, observe the patient carefully, and seek for opinions of other physicians. (B) An online survey was conducted; the responses revealed that many physicians would use SGLT2 inhibitors in renal transplant recipients provided the renal function was satisfactory with an eGFR > 60. We have learned of an ongoing trial on SGLT2 inhibitors in renal transplant recipients. (C) A case series of 10 patients treated with canagliflozin showed reassuring findings. Conclusions: Despite the lack of formal trial evidence, the index case suggested the safe use of SGLT2 inhibitors by renal transplant recipients for a remarkably extended period of 2.5 years. Physicians seem willing to use SGLT2 inhibitors in this group of patients provided renal function is satisfactory.","PeriodicalId":405374,"journal":{"name":"International Journal of Diabetes and Metabolism","volume":"201 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122757596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
G. Bhatti, S. Kaur, R. Vijayvergiya, S. Bhadada, S. Mastana, Bhupinder Singh, J. S. Bhatti
{"title":"ENPP1 K121Q Functional Variant Enhances Susceptibility to Insulin Resistance and Dyslipidemia with Metabolic Syndrome in Asian Indians","authors":"G. Bhatti, S. Kaur, R. Vijayvergiya, S. Bhadada, S. Mastana, Bhupinder Singh, J. S. Bhatti","doi":"10.1159/000492478","DOIUrl":"https://doi.org/10.1159/000492478","url":null,"abstract":"Background: Ectonucleotide pyrophosphatase/phosphodiesterase1 (ENPP1/PC-1) is a key modulator of the insulin signaling pathway, and its common variant, K121Q, increases the susceptibility to diabetes and cardiovascular diseases. Objectives: The main objective of the present study was to investigate the association of ENPP1 K121Q polymorphism with the pathophysiology of metabolic syndrome (MetS) in a north Indian population. Methods: A total of 567 participants (303 MetS subjects and 264 healthy controls) were examined for ENPP1 genotypes and various clinical parameters, including body mass index (BMI), waist circumference (WC), systolic and diastolic blood pressures (SBP/DBP), fasting blood glucose (FBG), cholesterol, triglycerides (TG), high-density lipoprotein, and insulin. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Statistical analysis of the data was done using SPSS. Results: Significant increases in BMI, WC, SBP, DBP, FBG, TG, low-density lipoprotein, insulin, and Homeostasis Model Assessment of insulin resistance (HOMA-IR) and of beta-cell function (HOMA-BF) were observed in MetS patients compared to healthy controls. Logistic regression analysis of data demonstrated a nonsignificant association of QQ and KQ+QQ genotypes with increased risk of MetS (OR [95% CI], 1.583 [0.455–5.507], p = 0.470 for QQ genotypes and 1.097 [0.784–1.540], p = 0.587 for KQ+QQ genotypes). Moreover, MetS subjects carrying Q alleles had significantly higher levels of TG, insulin, body fat percentage, and insulin resistance as evident by higher values of HOMA-IR. Conclusions: We conclude that ENPP1 K121Q functional variant enhances susceptibility to insulin resistance and dyslipidemia in MetS subjects of an Asian Indian population.","PeriodicalId":405374,"journal":{"name":"International Journal of Diabetes and Metabolism","volume":"39 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134400474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Prevalence of Adult-Onset Hypogonadism and Erectile Dysfunction in Males with Prediabetes","authors":"R. Rajput, Saurav Banerjee","doi":"10.1159/000492477","DOIUrl":"https://doi.org/10.1159/000492477","url":null,"abstract":"Background: The prevalence of prediabetes is high globally; however, few studies have investigated the prevalence of adult-onset hypogonadism (AOH) and erectile dysfunction (ED) in men with prediabetes, and there is no study from India. Aims: The aim of this study was to evaluate the prevalence of AOH and ED in men with prediabetes and to correlate the risk of testosterone deficiency with prediabetes. Methods: This cross-sectional study was performed on 100 diagnosed cases of prediabetes and 100 normoglycemic controls. Prediabetes was defined as impaired fasting glucose, impaired glucose tolerance, or both. AOH was defined as a positive response in the Androgen Deficiency in Ageing Males (ADAM) questionnaire in the setting of low testosterone. ED was assessed by the International Index of Erectile Function Questionnaire (IIEF-5) score. Results: AOH and ED were diagnosed in 34 (34%) and 79 (79%) males with prediabetes as compared to 16 (16%) and 58 (58%) males in the control population, respectively (p = 0.004 and p = 0.001). Both AOH and ED were observed in significantly more younger males with prediabetes (< 50 years) than in controls. On multivariate analysis, total testosterone remained significantly low in males with prediabetes as compared to controls after adjustment for possible confounders (odds ratio 2.5; p = 0.028). Conclusion: Males with prediabetes even in the younger age group are at an increased risk of AOH, ED, and testosterone deficiency.","PeriodicalId":405374,"journal":{"name":"International Journal of Diabetes and Metabolism","volume":"4 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122309986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"International Journal of Diabetes and Metabolism Returns","authors":"D. Abdelmannan, M. Farooqi, S. Beshyah","doi":"10.1159/000487570","DOIUrl":"https://doi.org/10.1159/000487570","url":null,"abstract":"We are delighted to announce the return of the International Journal of Diabetes and Metabolism (IJDM) having been interrupted for 2 years. The present first issue will be the first issue under the auspices of the Medical Education Center of Dubai Health Authority, Dubai, UAE. We are proud to build upon the journal’s previous track record under the United Arab Emirates University, Al Ain between 2001 and 2012. We will maintain the same name, National Library of Medicine ID number (101244770) and the ISSN for both online and print versions (print: 1606–7754 and electronic: 2073–5944) and also load up all previous issues and articles on the new website of the journal. We are pleased to have an agreement with an international publisher, Karger Publishers, which will maintain the production of the journal to the international standards of scholarly publishing. We would like to record our appreciation to the editors and advisors who have sustained the journal at any stage of its life. IJDM publishes reports of clinical and experimental research on diabetes mellitus, endocrinology, and metabolism. Original contributions on morphological, biochemical, physiological, pathophysiological and clinical aspects of research on diabetes and metabolism are all welcome. Reports are published in the form of research and review articles, case reports, discussion papers, letters to the editor, and book reviews. Review articles are normally commissioned by the editors from authors with demonstrable expertise in the field. However, unsolicited reviews may be considered if authors meet the same criteria. The International Journal of Diabetes and Metabolism also publishes abstracts of scientific meetings of reputable organizations. Topical commentaries or perspectives relating to current clinical, professional or scientific issues may either be commissioned or proposed. We are most grateful to the leadership of the Dubai Health Authority for the initiative of resurrecting the journal under its auspices and the generous financial support. We are committed to the genuine open access movement at the authors’ and readers’ end. There will be no submission, processing or publishing charges and access to all forms of published material will be free of charge. In the transition period of 2018–2020, the IJDM will be online only. Based on these pledges, we invite all colleagues in clinical practice and related biomedical sciences to reciprocate support as readers, authors, and reviewers.","PeriodicalId":405374,"journal":{"name":"International Journal of Diabetes and Metabolism","volume":"53 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126194922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Letters to Editor","authors":"R. Stevenson","doi":"10.1159/000497538","DOIUrl":"https://doi.org/10.1159/000497538","url":null,"abstract":"Dr Moneit makes two points, which we would endorse and re-emphasize. First, if infants are being discharged at or before 24 hours, then ensuring that they are seen again between 48 and 96 hours, would be prudent practice. What should be avoided is the temptation to count the discharge physical examination as the first follow-up visit of a well newborn and schedule the infant to be seen again in 2 weeks for routine care, leaving the parents with the assignment of monitoring for transitional jaundice.","PeriodicalId":405374,"journal":{"name":"International Journal of Diabetes and Metabolism","volume":"32 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1995-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122177898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}