Diabetes and related complications are associated with long-term damage and failure of various organ systems. The line of demarcation between the pathogenic mechanisms of microvascular and macrovascular complications of diabetes and differing responses to therapeutic interventions is blurred. Diabetes induces changes in the microvasculature, causing extracellular matrix protein synthesis, and capillary basement membrane thickening which are the pathognomic features of diabetic microangiopathy. These changes in conjunction with advanced glycation end products, oxidative stress, low grade inflammation, and neovascularization of vasa vasorum can lead to macrovascular complications. Hyperglycemia is the principal cause of microvasculopathy but also appears to play an important role in causation of macrovasculopathy. There is thought to be an intersection between micro and macro vascular complications, but the two disorders seem to be strongly interconnected, with micro vascular diseases promoting atherosclerosis through processes such as hypoxia and changes in vasa vasorum. It is thus imperative to understand whether microvascular complications distinctly precede macrovascular complications or do both of them progress simultaneously as a continuum. This will allow re-focusing on the clinical issues with a unifying perspective which can improve type 2 diabetes mellitus outcomes.

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In general, infectious diseases are more frequent and/or serious in patients with diabetes mellitus, which potentially increases their morbimortality. The greater frequency of infections in diabetic patients is caused by the hyperglycemic environment that favors immune dysfunction (e.g., damage to the neutrophil function, depression of the antioxidant system, and humoral immunity), micro- and macro-angiopathies, neuropathy, decrease in the antibacterial activity of urine, gastrointestinal and urinary dysmotility, and greater number of medical interventions in these patients. The infections affect all organs and systems. Some of these problems are seen mostly in diabetic people, such as foot infections, malignant external otitis, rhinocerebral mucormycosis, and gangrenous cholecystitis. In addition to the increased morbidity, infectious processes may be the first manifestation of diabetes mellitus or the precipitating factors for complications inherent to the disease, such as diabetic ketoacidosis and hypoglycemia. Immunization with anti-pneumococcal and influenza vaccines is recommended to reduce hospitalizations, deaths, and medical expenses.

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Insulin resistance is one pretty troublesome entity which very commonly aggravates metabolic syndrome. Many methods and indices are available for the estimation of insulin resistance. It is essential to test and validate their reliability before they can be used as an investigation in patients. At present, hyperinsulinemic euglycemic clamp and intravenous glucose tolerance test are the most reliable methods available for estimating insulin resistance and are being used as a reference standard. Some simple methods, from which indices can be derived, have been validated e.g. homeostasis model assessment (HOMA), quantitative insulin sensitivity check index (QUICKI). For the clinical uses HOMA-insulin resistance, QUIKI, and Matsuda are suitable, while HES, McAuley, Belfiore, Cederholm, Avignon and Stumvoll index are suitable for epidemiological/research purposes. With increasing number of these available indices of IR, it may be difficult for clinicians to select the most appropriate index for their studies. This review provides guidelines that must be considered before performing such studies.

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There are several interactions between thyroid and kidney functions in each other organ's disease states. Thyroid hormones affect renal development and physiology. Thyroid hormones have pre-renal and intrinsic renal effects by which they increase the renal blood flow and the glomerular filtration rate (GFR). Hypothyroidism is associated with reduced GFR and hyperthyroidism results in increased GFR as well as increased renin - angiotensin - aldosterone activation. Chronic kidney disease (CKD) is characterized by a low T3 syndrome which is now considered a part of an atypical nonthyroidal illness. CKD patients also have increased incidence of primary hypothyroidism and subclinical hypothyroidism. The physiological benefits of a hypothyroid state in CKD, and the risk of CKD progression with hyperthyroidism emphasize on a conservative approach in the treatment of thyroid hormone abnormalities in CKD. Thyroid dysfunction is also associated with glomerulonephritis often by a common autoimmune etiology. Several drugs could affect both thyroid and kidney functions. There are few described interactions between thyroid and renal malignancies. A detailed knowledge of all these interactions is important for both the nephrologists and endocrinologists for optimal management of the patient.

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In the modern environment one is exposed to various stressful conditions. Stress can lead to changes in the serum level of many hormones including glucocorticoids, catecholamines, growth hormone and prolactin. Some of these changes are necessary for the fight or flight response to protect oneself. Some of these stressful responses can lead to endocrine disorders like Graves' disease, gonadal dysfunction, psychosexual dwarfism and obesity. Stress can also alter the clinical status of many preexisting endocrine disorders such as precipitation of adrenal crisis and thyroid storm.

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Hypoglycemia is an important complication of glucose-lowering therapy in patients with diabetes mellitus. Attempts made at intensive glycemic control invariably increases the risk of hypoglycemia. A six-fold increase in deaths due to diabetes has been attributed to patients experiencing severe hypoglycemia in comparison to those not experiencing severe hypoglycemia Repeated episodes of hypoglycemia can lead to impairment of the counter-regulatory system with the potential for development of hypoglycemia unawareness. The short- and long-term complications of diabetes related hypoglycemia include precipitation of acute cerebrovascular disease, myocardial infarction, neurocognitive dysfunction, retinal cell death and loss of vision in addition to health-related quality of life issues pertaining to sleep, driving, employment, recreational activities involving exercise and travel. There is an urgent need to examine the clinical spectrum and burden of hypoglycemia so that adequate control measures can be implemented against this neglected life-threatening complication. Early recognition of hypoglycemia risk factors, self-monitoring of blood glucose, selection of appropriate treatment regimens with minimal or no risk of hypoglycemia and appropriate educational programs for healthcare professionals and patients with diabetes are the major ways forward to maintain good glycemic control, minimize the risk of hypoglycemia and thereby prevent long-term complications.

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Thyroid diseases are common worldwide. In India too, there is a significant burden of thyroid diseases. According to a projection from various studies on thyroid disease, it has been estimated that about 42 million people in India suffer from thyroid diseases. This review will focus on the epidemiology of five common thyroid diseases in India: (1) hypothyroidism, (2) hyperthyroidism, (3) goiter and iodine deficiency disorders, (4) Hashimoto's thyroiditis, and (5) thyroid cancer. This review will also briefly cover the exciting work that is in progress to ascertain the normal reference range of thyroid hormones in India, especially in pregnancy and children.

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Metabolic syndrome is a clustering of several cardiovascular risk factors. Contrary to earlier thoughts, metabolic syndrome is no longer rare in Africa. The prevalence is increasing, and it tends to increase with age. This increase in the prevalence of metabolic syndrome in the continent is thought to be due to departure from traditional African to western lifestyles. In Africa, it is not limited to adults but is also becoming common among the young ones. Obesity and dyslipidemia seem to be the most common occurring components. While obesity appears more common in females, hypertension tends to be more predominant in males. Insulin resistance has remained the key underlying pathophysiology. Though pharmacologic agents are available to treat the different components of the syndrome, prevention is still possible by reverting back to the traditional African way of life.

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Diabetes Mellitus is a metabolic cum vascular syndrome with resultant abnormalities in both micro- and macrovasculature. The adverse long-term effects of diabetes mellitus have been described to involve many organ systems. Apart from hyperglycemia, abnormalities of angiogenesis may cause or contribute toward many of the clinical manifestations of diabetes. These are implicated in the pathogenesis of vascular abnormalities of the retina, kidneys, and fetus, impaired wound healing, increased risk of rejection of transplanted organs, and impaired formation of coronary collaterals. A perplexing feature of the aberrant angiogenesis is that excessive and insufficient angiogenesis can occur in different organs in the same individual. The current article hereby reviews the molecular mechanisms including abnormalities in growth factors, cytokines, and metabolic derangements, clinical implications, and therapeutic options of dealing with abnormal angiogenesis in diabetes.

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Bone is a dynamic tissue which undergoes constant remodeling throughout the life span. Bone turnover is balanced with coupling of bone formation and resorption at various rates leading to continuous remodeling of bone. A study of bone turnover markers (BTMs) provides an insight of the dynamics of bone turnover in many metabolic bone disorders. An increase in bone turnover seen with aging and pathological states such as osteoporosis leads to deterioration of bone microarchitecture and thus contributes to an increase in the risk of fracture independent of low bone mineral density (BMD). These microarchitectural alterations affecting the bone quality can be assessed by BTMs and thus may serve as a complementary tool to BMD in the assessment of fracture risk. A systematic search of literature regarding BTMs was carried out using the PubMed database for the purpose of this review. Various reliable, rapid, and cost-effective automated assays of BTMs with good sensitivity are available for the management of osteoporosis. However, BTMs are subjected to various preanalytical and analytical variations necessitating strict sample collection and assays methods along with utilizing ethnicity-based reference standards for different populations. Estimation of fracture risk and monitoring the adherence and response to therapy, which is a challenge in a chronic, asymptomatic disease such as osteoporosis, are the most important applications of measuring BTMs. This review describes the physiology of bone remodeling, various conventional and novel BTMs, and BTM assays and their role in the assessment of fracture risk and monitoring response to treatment with antiresorptive or anabolic agents.

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Statins or 3-hydroxy-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors not only prevents the synthesis of cholesterol biosynthesis but also inhibits the synthesis of essential isoprenoid intermediates such as farnesyl pyrophosphate, geranylgeranyl pyrophosphate, isopentanyl adenosine, dolichols and polyisoprenoid side chains of ubiquinone, heme A, and nuclear lamins. These isoprenoid intermediates are required for activation of various intracellular/signaling proteins- small guanosine triphosphate bound protein Ras and Ras-like proteins like Rho, Rab, Rac, Ral, or Rap which plays an indispensible role in multiple cellular processes. Reduction of circulating isoprenoids intermediates as a result of HMG CoA reductase inhibition by statins prevents activation of these signalling proteins. Hence, the multiple effects of statins such as antiinflammatory effects, antioxidant effects, antiproliferative and immunomodulatory effects, plaque stability, normalization of sympathetic outflow, and prevention of platelet aggregation are due to reduction of circulating isoprenoids and hence inactivation of signalling proteins. These multiple lipid-independent effects of statins termed as statin pleiotropy would potentially open floodgates for research in multiple treatment domains catching attentions of researchers and clinician across the globe.

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Bone remodeling is a cyclic and continuous physiological process, which ensures the conservation and renewal of the bone matrix. Osteosynthesis of the bone matrix is achieved by osteoblasts and coordinated within this complex machinery of bone remodeling with resorption of extracellular bone matrix performed by osteoclasts. The mismatch between the activities of osteoblasts and osteoclasts has immunopathologic implications associated with either a decrease or increase of bone mass mineral density. The balance of the trimolecular control factor complex composed of osteoprotegerin (OPG), RANKL (osteoprotegerin ligand) and RANK maintains physiologic bone remodeling. This trimolecular complex functions as receptors and ligands and belongs to the superfamily of tumor necrosis factor (TNF). This mini review highlights the complex interplay of the RANKL-RANK/OPG axis and their immunopathologic implications in clinical medicine.

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Glucocorticoid-induced myopathy is the most common type of drug-induced myopathy. Nearly 60% of patients with Cushing's syndrome have muscle weakness. Glucocorticoid-induced muscle atrophy affects mainly fast-twitch glycolytic muscle fibers (type IIb fibers). This brief review will discuss the pathophysiology behind glucocorticoid-induced myopathy, along with diagnostic features and treatment.

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Background: Hypothyroidism is believed to be a common health issue in India, as it is worldwide. However, there is a paucity of data on the prevalence of hypothyroidism in adult population of India. Materials and Methods: A cross-sectional, multi-centre, epidemiological study was conducted in eight major cities (Bangalore, Chennai, Delhi, Goa, Mumbai, Hyderabad, Ahmedabad and Kolkata) of India to study the prevalence of hypothyroidism among adult population. Thyroid abnormalities were diagnosed on the basis of laboratory results (serum FT3, FT4 and Thyroid Stimulating Hormone [TSH]). Patients with history of hypothyroidism and receiving levothyroxine therapy or those with serum free T4 <0.89 ng/dl and TSH >5.50 μU/ml, were categorized as hypothyroid. The prevalence of self reported and undetected hypothyroidism, and anti-thyroid peroxidase (anti-TPO) antibody positivity was assessed. Results: A total of 5376 adult male or non-pregnant female participants ΃18 years of age were enrolled, of which 5360 (mean age: 46 ± 14.68 years; 53.70% females) were evaluated. The overall prevalence of hypothyroidism was 10.95% (n = 587, 95% CI, 10.11-11.78) of which 7.48% (n = 401) patients self reported the condition, whereas 3.47% (n = 186) were previously undetected. Inland cities showed a higher prevalence of hypothyroidism as compared to coastal cities. A significantly higher ( P < 0.05) proportion of females vs. males (15.86% vs 5.02%) and older vs. younger (13.11% vs 7.53%), adults were diagnosed with hypothyroidism. Additionally, 8.02% (n = 430) patients were diagnosed to have subclinical hypothyroidism (normal serum free T4 and TSH >5.50 μIU/ml). Anti - TPO antibodies suggesting autoimmunity were detected in 21.85% (n = 1171) patients. Conclusion: The prevalence of hypothyroidism was high, affecting approximately one in 10 adults in the study population. Female gender and older age were found to have significant association with hypothyroidism. Subclinical hypothyroidism and anti-TPO antibody positivity were the other common observations.

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Background: Obesity is an important risk factor for non-alcoholic fatty liver disease (NAFLD); however, NAFLD does occur in lean subjects. This study was aimed to evaluate the magnitude, clinical, pathological, and metabolic profiles of NAFLD in normal body mass index (BMI) subjects (defined as lean NAFLD) in comparison to overweight or obese NAFLD and lean healthy control. Materials and Methods: 336 subjects (205 consecutive NAFLD, and 131 healthy controls) were studied. Results: Among 205 NAFLD patients, 27 (13.2%) were lean, while 141 (68.8%) and 37 (18%) patients were obese and overweight, respectively. The lean NAFLD compared to obese NAFLD had significantly lesser degree of fasting hyperinsulinemia ( P < 0.001), homeostasis model assessment insulin resistance (HOMA-IR, P < 0.001), and lower prevalence of diabetes mellitus ( P = 0.01) and metabolic syndrome ( P < 0.001). The profiles of serum lipids were similar between all 3 BMI categories, and 89% of lean NAFLD were dyslipidemic. Compared to obese subjects, patients with lean NAFLD had less hepatic necro-inflammation ( P = 0.05) and fibrosis ( P < 0.001). However, the proportion of steatohepatitis and advanced fibrosis were similar between all BMI categories. The profiles of overweight NAFLD were similar to those of lean NAFLD, except for higher HOMA-IR, uric acids and male gender in overweight group. Despite being lean, the mean BMI of lean NAFLD were still higher than unselected lean healthy controls ( P = 0.02). Conclusions: Lean NAFLD patients have less severe disease, minor, or no insulin resistance, but are frequently dyslipidemic and have BMI higher than lean healthy control.

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The first description of patients with clustering of various metabolic abnormalities was as early as 1923 but it was more than five decades later, in 1988, that Reaven coined the term 'syndrome X' for this entity. The last two decades have brought forth a number of definitions and criteria to identify this condition. Various studies have demonstrated disparities in these definitions and a few researchers have questioned the utility of these criteria and even the existence of such a syndrome. A few important definitions are reviewed in this paper and, at the end, a simplified clinical definition is given and a simple parameter - lipid accumulation product - is been described that can be used to identify this condition.

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Glucose homeostasis is closely regulated not only by insulin, but also by leptin. Both hormones act centrally, regulating food intake and adiposity in humans. Leptin has several effects on the glucose-insulin homeostasis, some of which are independent of body weight and adiposity. Those effects of leptin are determined centrally in the hypothalamus and peripherally in the pancreas, muscles and liver. Leptin has beneficial effects on the glucose-insulin metabolism, by decreasing glycemia, insulinemia and insulin resistance. The understanding of the effects of leptin on the glucose-insulin homeostasis will lead to the development of leptin-based therapies against diabetes and other insulin resistance syndromes. In these review, we summarize the interactions between leptin and insulin, and their effects on the glucose metabolism.

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Abnormalities of the incretin axis have been implicated in the pathogenesis of type 2 diabetes mellitus. Glucagon-like peptide-1 (GLP-1) and gastroinhibitory intestinal peptide constitutes >90% of all the incretin function. Augmentation of GLP-1 results in improvement of beta cell health in a glucose-dependant manner (post-prandial hyperglycemia) and suppression of glucagon (fasting hyperglycemia), amongst other beneficial pleiotropic effects. Native GLP-1 has a very short plasma half-life and novel methods have been developed to augment its half life, such that its anti-hyperglycemic effects can be exploited. They can be broadly classified as exendin-based therapies (exenatide, exenatide once weekly), DPP-4-resistant analogues (lixisenatide, albiglutide), and analogues of human GLP-1 (liraglutide, taspoglutide). Currently, commercially available analogues are exenatide, exenatide once weekly, and liraglutide. This review aims to provide an overview of most GLP-1 analogues.

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South Asia is home to one of the largest population of people with metabolic syndrome (MetS). The prevalence of MetS in South Asians varies according to region, extent of urbanization, lifestyle patterns, and socioeconomic/cultural factors. Recent data show that about one-third of the urban population in large cities in India has the MetS. All classical risk factors comprising the MetS are prevalent in Asian Indians residing in India. The higher risk in this ethnic population necessitated a lowering of the cut-off values of the risk factors to identify and intervene for the MetS to prevent diabetes and cardiovascular disease. Some pharmacological and nonpharmacological interventions are underway in MetS to assess the efficacy in preventing the diabetes and cardiovascular disease in this ethnic population.

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Osteoporosis is common disorder of elderly population all over the world as well as in India. The presence of osteoporosis predicts fracture risk. Fragility fracture has marked morbidity as well as mortality. Thus, osteoporosis has marked therapeutic and economic implications. Osteoporosis is defined by low bone mineral density (BMD). The gold-standard method to assess BMD is dual X-ray absorptiometry (DXA). In India, hologic and lunar machines are most commonly used to measure BMD; these machines have their own normative data from which patients BMD is compared and results are generated. As per recommendations, all postmenopausal women and men above 70 years need BMD estimation other than quite a few other specific indications as well. With increasing life expectancy, increased awareness of osteoporosis, and availability of DXA machines, there is flooding of requests for BMD estimation. In view of all this, it becomes imperative on part of physicians, orthopedicians, rheumatologists, and endocrinologists alike to be fully aware about pitfalls in BMD assessment by DXA and interpretation of BMD reports.

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Growth chart committee of Indian Academy of Pediatrics (IAP) has revised growth charts for 5-18-year-old Indian children in Jan 2015. The last IAP growth charts (2007) were based on data collected in 1989-92 which is now >2 decades old. India is in an economic and nutrition transition and hence growth pattern of Indian children has changed over last few years. Thus, it was necessary to produce contemporary, updated growth references for Indian children. The new IAP charts were prepared by collating data from nine groups who had published studies in indexed journals on growth from India in the last decade. Growth charts were constructed from a total of 87022 middle and upper socioeconomic class children (m 54086, f 32936) from all five zones of India. Data from middle and upper socioeconomic class children are likely to have higher prevalence of overweight and obesity and hence growth charts produced on such populations are likely to "normalize" obesity. To remove such unhealthy weights form the data, method suggested by World Health Organization was used to produce weight charts. Thus, the new IAP weight charts are much lower than the recently published studies on affluent Indian children. Since Indian's are at a higher risk of obesity-related cardiometabolic complications at lower body mass index (BMI), BMI charts adjusted for 23, and 27 adult equivalent cut-offs as per International obesity task force guidelines were constructed. IAP now recommends use of these new charts to replace the 2007 IAP charts.

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Background: Representative data on knowledge and awareness about diabetes is scarce in India and is extremely important to plan public health policies aimed at preventing and controlling diabetes. Aim: The aim of the following study is to assess awareness and knowledge about diabetes in the general population, as well as in individuals with diabetes in four selected regions of India. Materials and Methods: The study subjects were drawn from a representative sample of four geographical regions of India, Chandigarh, Tamil Nadu, Jharkhand and Maharashtra representing North, South, East and West and covering a population of 213 million. A total of 16,607 individuals (5112 urban and 11,495 rural) aged ≥20 years were selected from 188 urban and 175 rural areas. Awareness of diabetes and knowledge of causative factors and complications of diabetes were assessed using an interviewer administered structured questionnaire in 14,274 individuals (response rate, 86.0%), which included 480 self-reported diabetic subjects. Results: Only 43.2% (6160/14,274) of the overall study population had heard about a condition called diabetes. Overall urban residents had higher awareness rates (58.4%) compared to rural residents (36.8%) (P < 0.001). About 46.7% of males and 39.6% of females reported that they knew about a condition called diabetes (P < 0.001). Of the general population, 41.5% (5726/13,794) knew about a condition called diabetes. Among them, 80.7% (4620/5726) knew that the prevalence of diabetes was increasing, whereas among diabetic subjects, it was 93.0% (448/480). Among the general and diabetic population, 56.3% and 63.4% respectively, were aware that diabetes could be prevented. Regarding complications, 51.5% of the general population and 72.7% diabetic population knew that diabetes could affect other organs. Based on a composite knowledge score to assess knowledge among the general population, Tamil Nadu had the highest (31.7) and Jharkhand the lowest score (16.3). However among self-reported diabetic subjects, Maharashtra had the highest (70.1) and Tamil Nadu, the lowest score (56.5). Conclusion: Knowledge and awareness about diabetes in India, particularly in rural areas, is poor. This underscores the need for conducting large scale diabetes awareness and education programs.

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Statins are an established class of drugs with proven efficacy in cardiovascular risk reduction. The concern over statin safety was first raised with the revelation of myopathy and rhabdomyolysis with the use of now withdrawn cerivastatin. Enhanced understanding of the mechanisms behind adverse effects of statins including an insight into the pharmacokinetic properties have minimised fear of statin use among clinicians. Studies reveal that occurrence of myopathy and rhabdomyolysis are rare 1/100000 patient-years. The risk of myopathy/rhabdomyolysis varies between statins due to varying pharmacokinetic profiles. This explains the differing abilities of statins to adverse effects and drug interaction potentials that precipitate adverse effects. Higher dose of rosuvastatin (80 mg/day) was associated with proteinuria and hematuria while lower doses were devoid of such effects. Awareness of drugs interacting with statins and knowledge of certain combinations such as statin and fibrates together with monitoring of altered creatine kinase activity may greatly minimise associated adverse effects. Statins also asymptomatically raise levels of hepatic transaminases but are not correlated with hepatotoxicity. Statins are safe and well tolerated including more recent potent statins such as, rosuvastatin. The benefits of intensive statin use in cardiovascular risk reduction greatly outweigh risks. The present review discusses underlying causes of statin-associated adverse effects including management in high risk groups.

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Since their introduction in clinical practice in the 1950's, Sulfonylureas (SUs) have remained the main-stay of pharmacotherapy in the management of type 2 diabetes. Despite their well-established benefits, their place in therapy is inappropriately being overshadowed by newer therapies. Many of the clinical issues associated with the use of SUs are agent-specific, and do not pertain to the class as such. Modern SUs (glimepiride, gliclazide MR) are backed by a large body of evidence, experience, and most importantly, outcome data, which supports their role in managing patients with diabetes. Person-centred care, i.e., careful choice of SU, appropriate dosage, timing of administration, and adequate patient counseling, will ensure that deserving patients are not deprived of the advantages of this well-established class of anti-diabetic agents. Considering their efficacy, safety, pleiotropic benefits, and low cost of therapy, SUs should be considered as recommended therapy for the treatment of diabetes in South Asia. This initiative by SAFES aims to encourage rational, safe and smart prescription of SUs, and includes appropriate medication counseling.

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