No abstract

BackgroundRenal failure in diabetes is mediated by multiple pathways. Experimental and clinical evidences suggest that renin-angiotensin-aldosterone system (RAAS) has a crucial role in diabetic kidney disease. A relationship between the RAAS genotypes and chronic renal insufficiency (CRI) among type 2 diabetes subjects has therefore been speculated. We investigated the contribution of selected RAAS gene polymorphisms to CRI among type 2 diabetic Asian Indian subjects.MethodsTwelve single nucleotide polymorphisms (SNPs) from six genes namely-renin (REN), angiotensinogen (ATG), angiotensin converting enzyme I (ACE), angiotensin II type 1 receptor (AT1) and aldosterone synthase (CYP11B2) gene from the RAAS pathway and one from chymase pathway were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and tested for their association with diabetic CRI using a case-control approach. Successive cases presenting to study centres with type 2 diabetes of ≥2 years duration and moderate CRI diagnosed by serum creatinine ≥3 mg/dl after exclusion of non-diabetic causes of CRI (n = 196) were compared with diabetes subjects with no evidence of renal disease (n = 225). Logistic regression analysis was carried out to correlate various clinical parameters with genotypes, and to study pair wise interactions between SNPs of different genes.ResultsOf the 12 SNPs genotyped, Glu53Stop in AGT and A>T (-777) in AT1 genes, were monomorphic and not included for further analysis. We observed a highly significant association of Met235Thr SNP in angiotensinogen gene with CRI (O.R. 2.68, 95%CI: 2.01–3.57 for Thr allele, O.R. 2.94, 95%CI: 1.88–4.59 for Thr/Thr genotype and O.R. 2.68, 95%CI: 1.97–3.64 for ACC haplotype). A significant allelic and genotypic association of T>C (-344) SNP in aldosterone synthase gene (O.R. 1.57, 95%CI: 1.16–2.14 and O.R. 1.81, 95%CI: 1.21–2.71 respectively), and genotypic association of GA genotype of G>A (-1903) in chymase gene (O.R. 2.06, 95%CI: 1.34–3.17) were also observed.ConclusionSNPs Met235Thr in angiotensinogen, T>C (-344) in aldosterone synthase, and G>A (-1903) in chymase genes are significantly associated with diabetic chronic renal insufficiency in Indian patients and warrant replication in larger sample sets. Use of such markers for prediction of susceptibility to diabetes specific renal disease in the ethnically Indian population appears promising.

Background:Prevalence of diabetes is on an increase in India, currently there is limited nation-wide data regarding the prevalence of chronic complications in diabetic patients at diagnosis. This information will help health-care professionals approach management more aggressively to prevent complications.Objective:To determine the prevalence of chronic complications in newly-diagnosed Type 2 diabetic (T2D) patients in India.Design and Methods:This was a cross-sectional survey of T2D patients, diagnosed within 3 months of their first visit to the centers doing the survey. Each patient was screened for diabetic complications, hypertension, dyslipidemia, and body mass index. Family history was recorded. Standard protocols were used to make the diagnosis of retinopathy, neuropathy and nephropathy. Data analysis was carried out using the standard statistical techniques.Results:Of the total 4,600 (males 67%, females 33%) newly diagnosed patients with T2D, majority were from the age group 41-50 years (40%). 13.15% of newly detected India T2D had neuropathy 6.1% had retinopathy and 1.06% had nephropathy. Risk factors of macro vascular complication such as hypertension, obesity, and dyslipidemia were observed in 23.3%, 26%, and 27% of patients respectively. Ischemic heart disease was noticed in 6%.Conclusion:High prevalence of micro vascular complications was present at diagnosis along with association of CV cardiovascular risk factors among Indian T2D. In view of this, screening must be instituted for all diabetics for complications at the time of diagnosis itself.

No abstract

OBJECTIVETo examine the safety and cardiovascular (CV) effects of saxagliptin in the predefined elderly ( ‡65 years) and very elderly ( ‡75 years) subpopulations of the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-Thrombolysis in Myocardial Infarction 53 (SAVOR-TIMI 53) trial. RESEARCH DESIGN AND METHODSIndividuals ‡40 years (n = 16,492; elderly, n = 8,561; very elderly, n = 2,330) with HbA 1c ‡6.5% (47.5 mmol/mol) and £12.0% (107.7 mmol/mol) were randomized (1:1) to saxagliptin (5 or 2.5 mg daily) or placebo in a double-blind trial for a median follow-up of 2.1 years. RESULTSThe hazard ratio (HR) for the comparison of saxagliptin versus placebo for the primary end point (composite of CV mortality, myocardial infarction, or ischemic stroke) was 0.92 for elderly patients vs. 1.15 for patients <65 years (P = 0.06) and 0.95 for very elderly patients. The HRs for the secondary composite end points in the entire cohort, elderly cohort, and very elderly cohort were similar. Although saxagliptin increased the risk of hospitalization for heart failure in the overall saxagliptin population, there was no age-based treatment interaction (P = 0.76 for elderly patients vs. those <65 years; P = 0.34 for very elderly patients vs. those <75 years). Among saxagliptin-treated individuals with baseline HbA 1c ‡7.6% (59.6 mmol/mol), the mean change from baseline HbA 1c at 2 years was 20.69%, 20.64%, 20.66%, and 20.66% for those ‡65, <65, ‡75, and <75 years old, respectively. The incidence of overall adverse events (AEs) and serious AEs was similar between saxagliptin and placebo in all cohorts; however, hypoglycemic events were higher for saxagliptin versus placebo regardless of age. CONCLUSIONSThe SAVOR-TIMI 53 trial supports the overall CV safety of saxagliptin in a robust number of elderly and very elderly participants, although the risk of heart failure hospitalization was increased irrespective of age category. AEs and serious AEs as well as glycemic efficacy of saxagliptin in elderly patients are similar to those found in younger patients.Estimates place the global prevalence of diabetes in individuals between 60 and 79 years old at ;19%, with the number of these individuals projected to almost double by 2035 (1). Despite ongoing emphasis on the importance of practicing evidencebased medicine (2), older patients have been underrepresented in type 2 diabetes

Advances in the treatment of diabetes have led to an increase in the number of injectable therapies, such as human insulin, insulin analogues, and glucagon-like peptide-1 analogues. The efficacy of injection therapy in diabetes depends on correct injection technique, among many other factors. Good injection technique is vital in achieving glycemic control and thus preventing complications of diabetes. From the patients’ and health-care providers’ perspective, it is essential to have guidelines to understand injections and injection techniques. The abridged version of the First Indian Insulin Injection technique guidelines developed by the Forum for Injection Technique (FIT) India presented here acknowledge good insulin injection techniques and provide evidence-based recommendations to assist diabetes care providers in improving their clinical practice.

A study of 140 days duration was performed to examine if human male volunteers (n = 5) respond to ovine follicle stimulating hormone (oFSH) immunization (administered adsorbed on Alugel on days 1, 20, 40 and 70) by producing antibodies capable of both binding and neutralizing bioactivity of human FSH. The kinetics of antibody production for both the immunogen (oFSH) and the cross-reactive antigen (hFSH) were essentially similar. The volunteers responded only to the first two immunizations. The boosters given on days 40 and 70 were ineffective, probably because of the presence of substantial amounts of circulating antibody to oFSH. Of the antibodies generated to oFSH, 25-45% bound hFSH with a mean binding affinity of 0.65 x 10(9) +/- 0.53 M(-1). The binding capacities at the time of high (30-80 days of immunization) and low (>110 days) titres were 346 +/- 185 and 10.5 +/- 5.8 ng hFSH/ml respectively. During the period of high titre, free serum FSH (value in normal males 1-5 ng/ml) was not monitorable. A 50 microl aliquot of the antiserum obtained from different volunteers between days 30 and 80 and on day 140 blocked binding of (125)I-labelled hFSH to its receptor by 82 +/- 9.7 and 53 +/- 12.2% respectively. The antibody produced was specific for FSH, and no significant change in the values of related glycoprotein hormones (luteinizing hormone/testosterone and thyroid stimulating hormone/thyroxine) were recorded. Seminal plasma transferrin, a marker of Sertoli cell as well as of seminiferous tubular function, showed marked reduction (30-90%) following immunization with oFSH. Considering that endogenous FSH remained neutralized for approximately one sperm cycle only (65 days), the reduction in sperm counts (30-74%) exhibited by some volunteers is encouraging. Immunization with oFSH did not result in any significant changes in haematology, serum biochemistry or hormonal profiles. There was no production of antibodies capable of interacting with non-specific tissues. It is concluded that it should be possible to obtain a sustained long-term blockade of endogenous FSH action in men by using oFSH as an immunogen. This is a prerequisite for obtaining significant reduction in the quality and quantity of spermatozoa produced, thus leading to infertility.

Objective: Despite rising incidence of diabetes in India, we currently lack country wide data on the prevalence of CKD in T2DM patients. Hence this nationwide study was planned.Methods: This was a nationwide, cross-sectional, observational, multi-centric study to assess prevalence of CKD among T2DM patients. The primary endpoint of the study was to estimate proportion of T2DM patients with CKD (glomerular filtration rate [GFR] <60 ml/min/1.73 m 2 or albumin creatinine ratio [ACR] ≥ 30 mg/g or ≥ 3 mg/mmol or both). The blood/plasma and urine samples, were collected for estimation of hemoglobin A1c, microalbuminuria, serum creatinine, urine creatinine, and routine urine analysis.Results: Of the 3043 screened subjects, 3000 eligible subjects were enrolled, out of which 46% were females. The mean age was 53.4 (± 11.9) years, with a mean body mass index of 27.3 (± 4.8) kg/m 2 . Both micro and macro vascular complications were reported. In the studied population with T2DM, 47.8% had mildly decreased, 15.1% had mild to moderately decreased, and 1.8% had severely decreased GFR respectively. As per ACR categorization, 61.3% had normal to mildly increased ACR, 25.6% with moderately increased and 7.2% with severely increased ACR were seen. We observed a significant (p<0.0001) weak negative correlation (-0.23069) between eGFR< 60 mL/ min/1.73 m² and urinary ACR in over six hundred patients. We found 48.4% prevalence of CKD in T2DM patients. The results on analysis of HbA1c goal achievement showed that the patients without CKD had a better success rate to achieve the target <7% goal of HbA1c compared to those who had CKD (29.6% vs. 23.4%). Conclusion:Study reported higher prevalence of CKD which was driven by the ACR levels and majority of the patients had reasonable eGFR. This can be a guide to select drug and dosage of diabetes drug as it depends on kidney function.