Blood glucose-lowering treatment options generally target insulin action or beta-cell function. In diabetes, expression of the sodium-glucose cotransporter-2 (SGLT2) genes is up-regulated and renal threshold increased, resulting in increased glucose reabsorption from glomerular filtrate, reducing urinary glucose excretion and worsening the hyperglycemic condition. The SGLT2 inhibitors (SGLT2i) are a novel class of anti-diabetic drugs that lower blood glucose levels through the suppression of renal glucose reabsorption thereby promoting renal glucose excretion. The efficacy of SGLT2i is reduced in renal impairment because the ability of glucose-lowering is directly proportional to glomerular filtration rate. On the other hand, ongoing research suggests that SGLT2i may offer potential nephroprotection in diabetes. The SGLT2i have been shown to reduce glomerular hyperfiltration, systemic and intraglomerular pressure and the biochemical progression of chronic kidney disease. Additional mechanisms through which SGLT2i exert nephroprotection may include normalizing blood pressure and uricemia. This review explores this bidirectional relationship of the SGLT2i and the glomerulus. While SGLT2i exhibit reduced efficacy in later stages, they exhibit nephroprotective effects in early stages of renal impairment. Funding: Janssen India (Pharmaceutical division of Johnson & Johnson).

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BACKGROUND: A high prevalence of antimicrobial resistance among urinary isolates in the Garhwal region of Uttaranchal. AIMS: To identify the most appropriate antibiotic for empirical treatment of community-acquired acute cystitis on the basis of local antimicrobial sensitivity profile. SETTINGS AND DESIGN: A prospective clinico microbiological study including all clinically diagnosed patients with community acquired acute cystitis attending a tertiary care teaching hospital over a period of three years. METHODS AND MATERIAL: Clean-catch midstream urine specimens, from 524 non pregnant women with community-acquired acute cystitis, were subjected to semiquantitative culture and antibiotic susceptibility by the Kirby-Bauer disc diffusion method. A survey was also conducted on 30 randomly selected local practitioners, to know the prevalent prescribing habits in this condition. STATISTICAL ANALYSIS: The difference between the susceptibility rates of E. coli isolates to Nitrofurantoin and the other commonly prescribed antibiotics was analysed by applying the z test for proportion. RESULTS: 354 (67.5%) specimens yielded significant growth of E. coli. >35% of the urinary E.coli isolates were resistant to the fluoroquinolones, which were found to be the most commonly used empirical antibiotics in acute cystitis. Resistance was minimum against Nitrofurantoin (9.3%, 33) and Amikacin (11.0%,39). >80% of the fluoroquinolone-resistant strains were found to be sensitive to Nitrofurantoin. CONCLUSION: The best in vitro susceptibility profile in our study has been shown by Nitrofurantoin and a significantly high proportion of the urinary E. coli isolates have already developed resistance to the currently prescribed empirical antibiotics, viz. the fluoroquinolones. In view of these in vitro susceptibility patterns, a transition in empirical therapy appears imminent.

BackgroundDrug-resistant pulmonary tuberculosis (DR-TB) is a significant public health issue that considerably deters the ongoing TB control efforts in India. The purpose of this review was to investigate the prevalence of DR-TB and understand the regional variation in resistance pattern across India from 1995 to 2015, based on a large body of published epidemiological studies.MethodsA systematic review of published studies reporting prevalence of DR-TB from biomedical databases (PubMed and IndMed) was conducted. Meta-analysis was performed using random effects model and the pooled prevalence estimate (95% confidence interval [CI]) of DR-TB, multidrug resistant (MDR-) TB, pre-extensively drug-resistant (pre-XDR) TB and XDR-TB were calculated across two study periods (decade 1: 1995 to 2005; decade 2: 2006 to 2015), countrywide and in different regions. Heterogeneity in this meta-analysis was assessed using I2 statistic.ResultsA total of 75 of 635 screened studies that fulfilled the inclusion criteria were selected. Over 40% of 45,076 isolates suspected for resistance to any first-line anti-TB drugs tested positive. Comparative analysis revealed a worsening trend in DR-TB between the two study decades (decade 1: 37.7% [95% CI = 29.0; 46.4], n = 25 vs decade 2: 46.1% [95% CI = 39.0; 53.2], n = 36). The pooled estimate of MDR-TB resistance was higher in previously treated patients (decade 1: 29.8% [95% CI = 20.7; 39.0], n = 13; decade 2: 35.8% [95% CI = 29.2; 42.4], n = 24) as compared with the newly diagnosed cases (decade 1: 4.1% [95% CI = 2.7; 5.6], n = 13; decade 2: 5.6% [95% CI = 3.8; 7.4], n = 17). Overall, studies from Western states of India reported highest prevalence of DR-TB (57.8% [95% CI = 37.4; 78.2], n = 6) and MDR-TB (39.9% [95% CI = 21.7; 58.0], n = 6) during decade 2. Prevalence of pre-XDR TB was 7.9% (95% CI = 4.4; 11.4, n = 5) with resistance to fluoroquinolone (66.3% [95% CI = 58.2; 74.4], n = 5) being the highest. The prevalence of XDR-TB was 1.9% (95% CI = 1.2; 2.6, n = 14) over the 20-year period.ConclusionThe alarming increase in the trend of anti-TB drug resistance in India warrants the need for a structured nationwide surveillance to assist the National TB Control Program in strengthening treatment strategies for improved outcomes.